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    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

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Efficacy and Safety of Surgical Resection in Elderly Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Jin-Soo Lee1 , Dong Ah Park2 , Seungeun Ryoo2 , Jungeun Park2 , Gi Hong Choi3 , Jeong-Ju Yoo1

1Department of Internal Medicine, Soonchunhyang University School of Medicine, Asan, Korea; 2Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea; 3Department of General Surgery, Yonsei University School of Medicine, Seoul, Korea

Correspondence to: Dong Ah Park
ORCID https://orcid.org/0000-0001-7225-3152
E-mail pda124@neca.re.kr

Jeong-Ju Yoo
ORCID https://orcid.org/0000-0002-7802-0381
E-mail puby17@naver.com

Jin-Soo Lee and Dong Ah Park contributed equally to this work as first authors.

Received: November 22, 2023; Revised: January 17, 2024; Accepted: January 29, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver.

Published online May 7, 2024

Copyright © Gut and Liver.

Background/Aims: With increased life expectancy, the management of elderly hepatocellular carcinoma (HCC) patients became a crucial issue, yet it is still challenging due to comorbidities and high surgical risks. While surgical resection is considered as primary treatment for eligible HCC patients, systematic evidence on its outcomes in elderly patients remains scarce. In this review, we aimed to analyze the efficacy and safety outcomes of surgical resection in elderly HCC patients.
Methods: The studies included in this meta-analysis were selected from Ovid-MEDLINE, Ovid-Embase, CENTRAL, KoreaMed, KMbase, and KISS databases following a predefined protocol. Efficacy outcomes included overall survival and disease-free survival, while the safety outcomes included postoperative mortality and complications.
Results: Patients in the elderly group (≥65 years) who underwent surgery exhibited non-inferior overall survival (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.92 to 1.74) and disease-free survival (HR, 1.03; 95% CI, 0.99 to 1.08) compared to the non-elderly group. Overall postoperative mortality exhibited no statistical difference (odds ratio [OR], 1.07; 95% CI, 0.87 to 1.31), but 30-day, 90-day, and in-hospital mortality were higher in the elderly group. The incidence of overall complications was higher in the elderly group (OR, 1.44; 95% CI, 1.22 to 1.69). Sensitivity analysis for the super elderly group (≥80 years) showed significantly higher in-hospital mortality compared to the non-super elderly group (OR, 2.51; 95% CI, 1.16 to 5.45).
Conclusions: The efficacy outcome of surgical resection in the elderly HCC patients was not worse than that in the non-elderly HCC patients, while in-hospital mortality and complications rates were higher. Therefore, surgical resection should be purposefully considered in the elderly population, with careful candidate selection.

Keywords: Hepatocellular carcinoma, Aged, Surgery, Treatment

According to the World Health Organization, hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide, in 2020, with an annual estimate of 830,000 deaths.1 Deaths caused by HCC are particularly frequent in Asia, where HCC is the second cause of cancer-related death.2 Due to the increase in life expectancy and advancements in medical technology, the number of elderly patients with HCC has been rising and the treatment selection for elderly HCC patients has become increasingly important.3,4

Surgical resection is considered the gold standard for curative treatment of early to intermediate-stage HCC patients.5 Owing to recent advances in surgical techniques and perioperative management, recent studies have shown that surgical resection shows better outcomes than other treatment options such as radiofrequency ablation, transarterial chemoembolization, and systemic chemotherapy.6,7 However, recommending surgical resection as a primary treatment for elderly HCC patients (≥65 years) is significantly challenged by their higher comorbidity rates, increased surgical risks, and the lack of objective data.8,9 Moreover, most patients aged 80 and above are typically excluded from research designs, further exacerbating the scarcity of data for this specific age group. Here arises a demand for guidelines addressing the safety and feasibility of surgical resection in this specific patient age range, necessitating large-scale studies comparing the efficacy and safety outcomes of surgical resection between elderly and non-elderly patients.10

The objective of this study was to provide systematic evidence that supports the decision for surgical resection in elderly patients with HCC. There have been several studies comparing the outcomes of surgical resection between elderly and non-elderly patients, but most of them were limited to single institution,11 or had a small number,12 or were restricted to the domestic population.13 Therefore, we conducted a systematic review and meta-analysis on outcomes of surgical resection, including the super elderly population.

This article was registered at the International Prospective Register of Systematic Reviews (CRD42023469975) for adequate protocol. Systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-analysis of Observational Studies in Epidemiology checklists. Ethics approval was waived from the Institutional Review Board of the National Evidence-based Healthcare Collaborating Agency and the current study conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki.

1. Study selection and subgroup design

The study selection algorithm is characterized in Fig. 1. Articles were mainly identified and searched from databases and registers in 2021 and an updated search was conducted in 2022. Ovid-MEDLINE, Ovid-Embase, and CENTRAL were the international databases used, and KoreaMed, KMbase, and KISS were the domestic databases. In primary study screening, title-based selection and exclusion were conducted and 9,601 studies were excluded. Furthermore, abstract-based screening was done, and 2,511 studies were excluded. A total of 225 studies were selected for full-text review. After considering the relevance to our study design, a final set of 56 studies was selected for systemic analysis (Fig. 1). Since all the studies included in the meta-analysis were retrospective design, they are inherently more susceptible to selection bias and confounding factors. To address this limitation, we conducted subgroup analyses based on various classification such as age cutoff, publication year, country, and methodological index for non-randomized studies (MINORS) score. Additionally, sensitivity analysis was performed specifically for the super elderly population. The primary meta-analysis of our study focused on comparing the elderly group, defined as individuals aged 65 and above, with the non-elderly group, defined as those under 65, and presenting the analysis results. However, considering the increasing prevalence of very elderly patients in clinical practice, we conducted an additional sensitivity analysis specifically for the super elderly group, defined as individuals aged 80 and above, in studies where this age category was separately classified.

Figure 1.Selection flowchart of the studies included in meta-analysis.

2. Study outcome

The purpose of the study was to compare efficacy and safety outcomes between elderly and non-elderly patients with HCC. Efficacy-related outcomes included overall survival (OS) and disease-free survival (DFS), while safety-related outcomes included postoperative mortality and postoperative complications.

3. Methodological quality and risk of bias assessment

The assessment of bias risk was conducted independently by two researchers, and consensus was reached through discussion with a third party. For randomized controlled trials, the Cochrane Risk of Bias 1.0 tool was used whereas the MINORS (a valid instrument designed to assess the methodological quality of non-randomized surgical studies, consisting of 12 questions with a total of 24 points14 was used for non-randomized controlled trials (Supplementary Fig. 1).

4. Statistical analysis

Efficacy-related outcomes, OS and DFS, were evaluated using median value, interquartile range (IQR), and range. Meta-analysis was primarily done with a random effects model, using the following methods: (1) inverse variance method for survival and consecutive data and (2) Mantel-Haenszel method for binary data. The binary outcomes were presented as odds ratio (OR), and for survival outcomes, hazard ratio (HR) with a 95% confidence interval (CI). Statistical inter-study heterogeneity of meta-analysis was primarily assessed by Forest plot and Cochrane Q statistics (p<0.10) with I2 statistics (≥50%). Moreover, subgroup analysis was conducted to find factors contributing to heterogeneity and those factors included age threshold, disease stage, country of study, publication year, quality assessment scores, and the number of adjusted variables. Also, sensitivity analysis was conducted on super elderly patients, independently (≥80 years). Publication bias was assessed using funnel plots and Egger’s test (Supplementary Fig. 2). Meta-analysis was conducted using RevMan 5.3, and statistical significance for differences between groups was assessed at a significance level of 5%.

1. Characteristics of studies included in the systemic review

As mentioned above, a total of 56 articles were included in the final analysis. The baseline characteristics of the enrolled studies including baseline liver function and cancer status are presented in Table 1.11-13,15-62 When classified by continent, the majority of studies, 47 (83.9%), were from Asia, while nine studies (16.0%) were from Europe. Forty-six studies (82.1%) were conducted by a single institution, and 10 studies (17.8%) involved multi-institutions. All 56 studies were retrospective cohort studies. An age threshold of 70 years for elderly patients was used in 24 studies (42.8%), followed by 75 years in 14 studies (25%), and 65 years in five studies (8.9%).

Table 1. Demographics and Characteristics of Studies Included in the Systematic Review: Elderly versus Non-Elderly

Study (year)CountryInstitutionRecruitment
period
MatchingObjectiveAge
cutoff, yr
No. of
elderly
No. of
non-elderly
Baseline liver function, %Tumor size, mm
Elderly
Child A/B
Non-elderly
Child A/B
ElderlyNon-elderly
Fujio (2022)12JapanSingle2012–2016NRHR for HCC75223995/587/1353.652
Pu (2022)15ChinaMulticenter2007–2019PSMR0 HR for HCC7014014094/694/6NANA
Harada (2021)11JapanSingle2001–2012PSMHR for HCC7023423497/395/53031
Liu (2021)16TaiwanRegistry2007–2017NRHR for HCC7596908NANA41.5NA
Tan (2021)17SingaporeSingle2000–2018NRHR for HCC7027876494/695/54538
Chen (2020)13ChinaMulticenter2006–2016NRHR for HCC659273891/989/11105108
Shin (2020)18KoreaSingle2012–2018NRHR for HCC7049184NANANANA
Shimada (2020)19JapanSingle2000–2017NRHR for HCC65363384NANA5761
Yasuda (2020)20JapanSingle2000–2013NRMajor HR for HCC702318100/0100/05478
Xing (2020)21ChinaMulticenter2003–2016NRHR for HCC702591,87596/490/10NANA
Famularo (2019)22ItalyMulticenter2005–2015PSMHR for HCC75929292/896/43541
Jiang (2019)23ChinaRegistry2004–2015NRHR for HCC659561,392NANANANA
Kaibori (2019)24JapanRegistry2000–2007NRHR for HCC752,02010,56792/890/1038NA
Okamura (2018)25JapanSingle2002–2014PSMHR for HCC75727299/199/1NANA
Chen (2018)26ChinaSingle2010–2016NRHR for HCC6525688691/982/18NA84
Goh (2018)27SingaporeSingle2007–2016PSMLMH for HCC704094NANA3025
Hsu (2018)28TaiwanSingle2003–2014NRHR for large HCC (>5 cm)707917892/889/118690
Wang (2018)29ChinaSingle2011–2016NRHR for HCC704897NANANANA
Yu (2018)30ChinaSingle2003–2013NRHR for HCC70235883/1791/94737
Santambrogio (2017)31ItalySingle1998–2015NRHR for HCC7553115100/0100/0NANA
Bauschke (2016)32GermaySingle1995–2014NRHR for HCC70638187/1377/23NANA
Cucchetti (2016)33ItalySingle1997–2013NRHR for HCC with LC70229690NANANANA
Harimoto (2016)34JapanSingle2004–2013NRHR for HCC7013915794/696/44040
Kim (2015)35KoreaSingle2006–2010NRHR for HCC7060219NANA4949
Kishida (2015)36JapanSingle2005–2010NRHR for HCC75228291/999/13530
Motoyama (2015)37JapanSingle1990–2013NRHR for HCC7511349995/594/63330
Nozawa (2015)38JapanSingle2000–2010NRHR for HCC7019223986/1485/15NA30
Sato (2015)39JapanSingle2000–2010NRHR for HCC753419574/2683/174954
Faber (2014)40GermanySingle2000–2010NRHR for HCC with LC706378NANA5050
Liu (2014)41TaiwanSingle2002–2013PSMHR for HCC7511811893/793/7NANA
Mori (2014)42JapanSingle2000–2012NRHR for HCC with PHT706413178/2271/294133
Ueno (2014)43JapanSingle2001–2010NRHR for HCC756618691/991/95040
Wang (2014)44ChinaSingle2007–2012NRHR for HBV related HCC652071,336NANANANA
Wang (2014)45ChinaSingle2007–2012Paired
matched
Major hepatectomy for HCC with LC705615286/1480/207589
Hirokawa (2013)46JapanSingle2000–2011NRHR for HCC7010012088/1282/183530
Ide (2013)47JapanSingle2000–2010NRHR for HCC756419289/1188/124949
Murillo (2013)48SpainSingle2000–2011NRHR for HCC702214NANA3847
Nishikawa (2013)49JapanSingle2004–2012NRHR for HCC759220698/296/44648
Taniai (2013)50JapanSingle1990–2010NRHR for HCC756335389/1175/24/1NANA
Lee (2012)51KoreaSingle2000–2010NRHR for HCC706190NANA4543
Nanashima (2011)52JapanSingle1994–2009NRHR for HCC706911993/789/11NANA
Portolani (2011)53ItalySingle1992–2009NRHR for HCC7017527692/893/74849
Mirici-Cappa (2010)54ItalyMulticenter1987–2004PSMHR for HCC70323293/782/133441
Tan (2021)17*SingaporeSingle2000–2018NRHR for HCC80501,04292/894/680NA
Sanyal (2020)55EnglandSingle2005–2015NRHR for HCC8019181NANANANA
Shimada (2020)19JapanSingle2000–2017NRHR for HCC8049757NANA64NA
Inoue (2019)56JapanSingle2001–2017PSMHR for HCC8045485100/093/74132
Lee (2019)57TaiwanSingle1986–2015NRHR for HCC80773,30996/496/45942
Wu (2019)58TaiwanSingle1992–2016NRHR for HCC85311,85887/10/387/11/25665
Chen (2018)26ChinaSingle2010–2016NRHR for HCC80321,11094/684/1669NA
Hamaoka (2017)59JapanSingle2004–2013NRHR for HCC806056593/793/73327
Nozawa (2015)38JapanSingle2000–2010NRHR for HCC802041195/585/1541NA
Katsuta (2014)60§JapanSingle2000–2012NRHR for HCC802945783/1791/9NANA
Tsujita (2012)61JapanMulticenter1995–2008NRHR for HCC8023385NANANANA
Yamada (2012)62JapanMulticenter1992–2009NRHR for HCC801126782/1892/85248
Nanashima (2011)52JapanSingle1994–2009NRHR for HCC8012167100/090/10NANA

NR, not reported; PSM, propensity score matching; HR, hepatic resection; HCC, hepatocellular carcinoma; LC, liver cirrhosis; LMH, laparoscopic minor hepatectomy; PHT, portal hypertension; HBV, hepatitis B virus; NA, not applicable.

Definition of elderly: *<70/70–79/≥80 yr; <65/65–79/≥80; <70/70–80/≥81 yr; §<50/50–79/≥80; <50/50–69/70–79/≥80 yr.



2. Overall survival

Forty-eight articles reported the results of the OS. In the elderly group meta-analysis, at the 3-year postoperative point, the median OS of the elderly group was 70.0% (IQR, 62.7% to 75.1%) and 74.3% (IQR, 66.8% to 77.9%) in the non-elderly group. The median survival periods were similar between the two groups: the elderly group had a median of 69 months (IQR, 52.5 to 77.0 months), while the non-elderly group had a median of 73.3 months (IQR, 60.0 to 89.7 months). In the analysis of the super elderly group (≥80 years), the 3-year median OS rates were 67.7% (IQR, 53.3% to 79.3%) for the super elderly and 70.9% (IQR, 46.0% to 76.8%) for the non-super elderly, respectively. Similar to the elderly group analysis, median survival periods were similar between the super elderly and non-super elderly; 64.8 months in super elderly and 79.4 months in non-super elderly (Supplementary Table 1).

We conducted a meta-analysis on OS between elderly and non-elderly groups. Univariate analysis showed that the OS of the elderly group was worse than that of the non-elderly group (HR, 1.18; 95% CI, 1.09 to 1.27; I2=67%) (Fig. 2A), whereas, in multivariate analysis, there was no significant difference between the two groups (HR, 1.26; 95% CI, 0.92 to 1.74; I2=71%). In subgroup analysis, studies that used 75 years as the age threshold for the elderly showed lower heterogeneity, and the overall mortality of the elderly group was higher than that of the non-elderly group (HR, 1.29; 95% CI, 1.17 to 1.42; I2=23%) (Table 2).

Figure 2.Forest plots. (A) Overall mortality between elderly versus non-elderly. (B) Disease-free survival between elderly versus non-elderly. (C) Postoperative mortality between elderly versus non-elderly. (D) Post operative mortality between super elderly versus non-super elderly. (E) Postoperative complication between elderly versus non-elderly. (F) Postoperative complication between super elderly versus non-super elderly. SE, standard error; IV, inverse variance; CI, confidence interval; M-H, Mantel-Haenszel.

Table 2. Meta-Analysis on Overall Survival: Elderly versus Non-Elderly

VariableUnivariate analysisMultivariate analysis
No. of studiesRandom, IV HR (95% CI)I2, %No. of studiesRandom, IV HR (95% CI)I2, %
Overall mortality321.18 (1.09–1.27)6741.26 (0.92–1.74)71
Using dataNA
Calculated data231.13 (1.04–1.22)52NA
Reported data91.26 (1.07–1.49)79NA
Age cutoff
65–70 yr181.09 (1.00–1.19)6611.08 (0.49–2.36)NA
75 yr141.29 (1.17–1.42)2321.39 (0.69–2.81)89
Publication year
2016–2022201.19 (1.08–1.31)7041.26 (0.92–1.74)71
2010–2015131.19 (1.02–1.40)610--
Country
Asia261.15 (1.07–1.24)6521.23 (0.90–1.69)0
Non-Asia61.46 (0.96–2.20)7721.39 (0.69–2.81)89
MINORS score
Over median value (20)151.32 (1.15–1.50)7021.39 (0.69–2.81)89
Under median value (20)171.10 (0.99–1.22)6721.23 (0.90–1.69)0

IV HR, inverse variance hazard ratio; CI, confidence interval; NA, not applicable; MINORS, methodological index for non-randomized studies.



Sensitivity analysis between the super elderly (≥80 years) and the non-super elderly group showed higher overall mortality in the super elderly group (HR, 1.32; 95% CI, 1.04 to 1.67; I2=79%), but had higher heterogeneity between studies. In subgroup analysis, studies published between 2010 and 2015 showed lower heterogeneity and the risk of death for the super elderly group was higher than that for the non-super elderly group (HR, 1.59; 95% CI, 1.00 to 2.53; I2=0%). Furthermore, in studies with high MINORS score, there was no statistical heterogeneity, and the overall mortality for the super elderly group was also higher (HR, 1.22; 95% CI, 1.03 to 1.44; I2=0%) (Supplementary Table 2).

3. Disease-free survival

DFS was reported in 34 studies. In the elderly group analysis, at the 3-year postoperative point, the median DFS rate for the elderly group was 40.6% (IQR, 36.0% to 50.9%), while the non-elderly group showed a rate of 44.9% (IQR, 35.7% to 54.5%). Five-year median DFS rate was 33.0% in both elderly and non-elderly groups (IQR, 25.6% to 36.9% and IQR, 25.6% to 39.8%, respectively). The median DFS periods were similar between the two groups, with the elderly group having 27.8 months (IQR 20.3 to 35.8 months) and the non-elderly group having 33.4 months (IQR, 18.6 to 42.6 months) (Supplementary Table 1). According to the univariate analysis for DFS, there was no statistically significant difference between elderly and non-elderly groups (HR, 1.03; 95% CI, 0.99 to 1.08; I2=0%) (Table 3, Fig. 2B).

Table 3. Meta-Analysis on Disease-Free Survival: Elderly versus Non-Elderly

VariableUnivariate analysis
No. of studiesRandom, IV HR (95% CI)I2, %
Overall estimate211.03 (0.99–1.08)0
Using data
Calculated data151.04 (0.96–1.13)17
Reported data61.03 (0.97–1.10)0
Age cutoff
65–70 yr101.05 (0.97–1.14)0
75 yr111.02 (0.96–1.08)0
Publication year
2016–2022131.04 (0.99–1.09)0
2010–201581.17 (0.92–1.49)34
Country
Asia181.02 (0.98–1.07)0
Non-Asia31.43 (1.02–2.01)0
MINORS score
Over median value (20)101.06 (0.91–1.24)33
Under median value (20)111.04 (0.99–1.10)0

IV HR, inverse variance hazard ratio; CI, confidence interval; MINORS, methodological index for non-randomized studies.



In sensitivity analysis for the super elderly group (≥80 years), 3-year median DFS were 38.1% (IQR, 34.1% to 46.2%) and 46.3% (IQR, 38.8% to 47.9%) for super elderly and non-super elderly respectively. 5-year median DFS rates were 35.1% (IQR, 19.4% to 40.2%) and 32.3% (IQR, 28.7% to 35.2%) respectively. Median DFS periods were 26.3 months (IQR, 24.0 to 31.3 months) in super elderly and 28.4 months (IQR, 20.5 to 33.2 months) in non-super elderly (Supplementary Table 1).

4. Postoperative mortality

Overall postoperative mortality, 30 days postoperative mortality, 90 days postoperative mortality, in-hospital mortality, and mortality related to hepatic failure were analyzed (Table 4). Fourteen studies reported overall postoperative mortality and there was no significant difference between elderly and non-elderly groups (OR, 1.07; 95% CI, 0.87 to 1.31; I2=51%) (Fig. 2C). Whereas the elderly group showed significantly higher 30 days, 90 days mortality, and in-hospital mortality rates compared to the non-elderly group with OR of 2.13, 1.65, and 1.78, respectively. However, hepatic failure-related mortality showed no significant difference between the two groups (OR, 1.28; 95% CI, 0.76 to 2.16; I2=0%). Within the super elderly (≥80 years) group versus non-super elderly group analysis, the super elderly group showed significantly higher in-hospital mortality (OR, 2.51; 95% CI, 1.16 to 5.45). However, there were no significant differences in overall postoperative mortality (OR, 0.91; 95% CI, 0.33 to 2.50) (Fig. 2D), 30 days, and 90 days mortality between the two groups (Table 4).

Table 4. Postoperative Mortality: Elderly versus Non-Elderly, Super Elderly versus Non-Super Elderly

Outcome variableNo. of
studies
ElderlyNon-elderlyRandom, M-H
pooled OR
95% CII2, %
No. of participantsEventsNo. of participantsEvents
Elderly vs non-elderly
Overall mortality rate141,8137344,5252,0571.070.87–1.3151
30-Day mortality rate101,740245,921582.131.28–3.540
90-Day mortality rate131,738475,8411151.651.09–2.498
In-hospital mortality rate101,055313,175471.781.03–3.0914
Hepatic failure-related mortality rate111,463282,976451.280.76–2.160
Super elderly vs non-super elderly
Overall mortality rate4137392,3049290.910.33–2.5075
30-Day mortality rate628766,954922.270.99–5.180
90-Day mortality rate414933,828552.050.76–5.570
In-hospital mortality rate514364,5481022.511.16–5.450
Hepatic failure-related mortality rate0----

M-H, Mantel-Haenszel; OR, odds ratio; CI, confidence interval.



5. Postoperative complications

The overall postoperative complication was reported in 26 studies (Table 5). The elderly group had a higher incidence of postoperative complications than that of the non-elderly group (OR, 1.44; 95% CI, 1.22 to 1.69; I2=51%) (Fig. 2E). The elderly group also had a higher incidence of major postoperative complications (OR, 1.30; 95% CI, 1.11 to 1.53; I2=26%), whereas no significant difference in postoperative hepatic failure was observed between the two groups (OR, 1.20; 95% CI, 0.79 to 1.82; I2=0%). In sensitivity analysis, the super elderly group had a higher incidence of complications than the non-super elderly group (OR, 2.02; 95% CI, 1.35 to 3.02; I2=65%) (Fig. 2F) whereas major postoperative complications and postoperative hepatic failure did not show a statistical difference between groups.

Table 5. Postoperative Complications: Elderly versus Non-Elderly, Super Elderly versus Non-Super Elderly

Outcome variableNo. of
studies
ElderlyNon-elderlyRandom, M-H
pooled OR
95% CII2, %
No. of participantsEventsNo. of participantsEvents
Elderly vs non-elderly
Overall postoperative complications262,9431,1848,6292,7621.441.22–1.6951
Major postoperative complications242,4764118,3601,0411.301.11–1.5326
Postoperative hepatic failure131,154333,9141001.200.79–1.820
Super elderly vs non-super elderly
Overall postoperative complications93591719,4572,9402.021.35–3.0265
Major postoperative complications7197283,5163281.250.66–2.3947
Postoperative hepatic failure819755,147832.250.96–5.270

M-H, Mantel-Haenszel; OR, odds ratio; CI, confidence interval.


Through this meta-analysis, several meaningful results regarding the efficacy and safety of surgery in elderly HCC patients were obtained. These results can be of great help to clinicians in decision-making in a recent trend where the number of elderly HCC patients is increasing.

The first finding of our study was that there was no statistically significant difference in the efficacy outcomes, namely OS and DFS, between the elderly and non-elderly groups (Tables 2 and 3). Univariate analysis for OS showed a difference between the elderly and non-elderly groups (HR, 1.18; 95% CI, 1.09 to 1.27). However, in multivariate analysis, no statistically significant difference was observed between the two groups (HR, 1.26; 95% CI, 0.92 to 1.74). Therefore, it is suggested that factors other than surgery might have had a greater influence on the difference in OS between the elderly and non-elderly groups.24,63 One possible interpretation of this result may be that relative to the past, the overall health status has improved owing to recent advancements in medical technology, which led to an increase in average lifespan and improved performance among the elderly population.64 Another speculation is that the likelihood of undergoing surgery in selected patients, particularly those with good performance status, is higher in actual clinical practice. Patients with poor performance status often undergo other procedures such as radiofrequency ablation rather than surgery.65 Therefore, the patients analyzed in this study might have had similar initial pre-operative conditions compared to the non-elderly group. The last hypothesis is that the overall advancement in surgical techniques and postoperative management might have contributed to improved surgical outcomes in elderly HCC patients.66 To investigate this hypothesis further, subgroup analyses were conducted according to the year of publication which indicated no significant differences in results across different study periods (Table 2).

The second finding is that in the Asian region, the difference in OS and DFS between elderly and non-elderly groups had a less pronounced trend compared to the non-Asian regions, although not statistically significant (Tables 2 and 3). This is thought to be due to the differences in HCC etiology and surgical methods between Asia and non-Asian countries. In Asia, the proportion of HCC due to viral hepatitis such as hepatitis B virus or hepatitis C virus is significantly higher compared to the predominance of nonalcoholic fatty liver disease-associated HCC in the West.2,67-69 It is known that the average age of nonalcoholic fatty liver disease-associated HCC patients is about 5 to 10 years older than that of viral hepatitis-associated HCC patients.70-72 Therefore, it is assumed that the median age of Asia's HCC is lower than that of the West, potentially resulting in improved postoperative survival. Moreover, the incidence of HCC is higher in Asia compared to non-Asian countries, and the difference in surgical experience and techniques due to the higher incidence in Asia may have contributed to better surgical outcomes in elderly Asian HCC patients compared to non-Asian patients.69,73

The third finding of our study revealed a higher postoperative mortality in the elderly group compared to the non-elderly group, with a particularly high in-hospital mortality noted in the super elderly group (≥80 years). While it was somewhat predictable that postoperative mortality would be higher in the elderly, our study was able to objectively quantify this.74 Therefore, it is essential to consider longer in-hospital monitoring periods for elderly HCC patients, especially for the super elderly after surgery. Additionally, both the elderly and super elderly groups exhibited higher rates of postoperative complications, with a notably increased risk of major postoperative complications observed in the elderly group. This highlights the need for greater attention to postoperative management in elderly patients.31 Although there were no significant differences in hepatic failure-related deaths, it is important to note that this could be due to the inclusion of patients with remaining liver reserve functions suitable for surgery, emphasizing the need for careful interpretation of the results.

Our study has several limitations. First, the individual comorbidities were not considered. This study conducted a meta-analysis of the entire cohort without adjusting for comorbidities. However, the reported comorbidities varied across studies, and studies with objectively quantifiable measures suitable for meta-analysis, such as the Charlson comorbidity index score, were limited. Therefore, adjusting for comorbidities to derive conclusive results proved challenging. The comorbidities frequently mentioned and adjusted from several studies were as follows: hypertension, diabetes, hyperlipidemia, chronic kidney disease, cerebrovascular disease, cerebrovascular accident, pulmonary disease, and Charlson comorbidity index score. To make up for this shortcoming, a multivariate analysis adjusting for other variables was conducted in regard to the OS, but it still had some limitations. Second, in our meta-analysis, we did not perform sub-analyses according to baseline liver function or cancer status. However, considering that the majority of surgical candidates were likely to be Child-Pugh class A with stage I patients, we believe there may have been some level of homogeneity between the two groups. Furthermore, the included studies were all retrospective design and focused only on patients who underwent surgery, which may have resulted in selection bias. Fourth, in sensitivity analysis for the super elderly group (≥80 years), the efficacy outcomes did not demonstrate consistent results compared to those of elderly versus non-elderly analysis. Due to the small number of studies and patients, as well as high heterogeneity among the literature, accurate evaluation was restricted, hence further detailed research is required for the super elderly patient population.17,19,38,52,55-59,61,62,75 Fifth, our study did not differentiate between different surgical methods (open surgery vs laparoscopic surgery), which could influence both efficacy and safety outcomes. Lastly, while our study evaluated OS and DFS, it lacks a comprehensive analysis of other relevant outcomes such as quality of life, postoperative functional status, and patient-reported outcomes. These factors are crucial for an assessment of the impact of surgical resection on elderly patients and further research should consider these aspects of efficacy outcome.

In conclusion, through careful and multidisciplinary patient selection for surgical candidates among elderly HCC patients, both OS and DFS would not be worse than those of the non-elderly group. Thus, it is imperative to actively consider surgical treatment in the selected elderly HCC patients. Future studies that adjust for differences in comorbidity and surgical method might be crucial to determine the respective weights of variables affecting efficacy and safety outcomes. Ultimately, deriving a scoring system or a guideline to assist the decision-making process for surgical treatment in elderly HCC patients is required in the clinical setting. In our meta-analysis results, factors that could be included in the scoring system may consist of age 65 and above, age 80 and above, geographic location (Asia vs non-Asia). Further research should consider incorporating additional factors such as sex, cancer stage, cancer size, CTP score, performance status, comorbidities, surgical method, and hospital size into the scoring system.76,77

This study was supported by the National Evidence-based Healthcare Collaborating Agency (NECA) (NA21-008; NA22-006) and the Soonchunhyang University Research Fund.

Study concept and design: D.A.P., G.H.C. Data acquisition: D.A.P., S.R., J.P. Data analysis and interpretation: D.A.P., J.J.Y. Drafting of the manuscript: J.S.L., J.J.Y. Critical revision of the manuscript for important intellectual content: J.J.Y., D.A.P. Statistical analysis: J.J.Y., D.A.P. Approval of final manuscript: all authors.

  1. Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 2022;77:1598-1606.
    Pubmed KoreaMed CrossRef
  2. Zhang CH, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int 2022;42:2029-2041.
    Pubmed CrossRef
  3. Nishikawa H, Kimura T, Kita R, Osaki Y. Treatment for hepatocellular carcinoma in elderly patients: a literature review. J Cancer 2013;4:635-643.
    Pubmed KoreaMed CrossRef
  4. Jang W, Lee HW, Lee JS, et al. Clinical characteristics and prognosis of Korean patients with hepatocellular carcinoma with respect to etiology. J Liver Cancer 2022;22:158-166.
    Pubmed KoreaMed CrossRef
  5. Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. J Liver Cancer 2023;23:1-120.
    Pubmed KoreaMed CrossRef
  6. Shin SW, Ahn KS, Kim SW, Kim TS, Kim YH, Kang KJ. Liver resection versus local ablation therapies for hepatocellular carcinoma within the Milan criteria: a systematic review and meta-analysis. Ann Surg 2021;273:656-666.
    Pubmed CrossRef
  7. Lee HA, Lee YS, Kim BK, et al. Change in the recurrence pattern and predictors over time after complete cure of hepatocellular carcinoma. Gut Liver 2021;15:420-429.
    Pubmed KoreaMed CrossRef
  8. Devalapalli AP, Kashiwagi DT. Perioperative care of geriatric patients. Hosp Pract (1995) 2020;48(sup1):26-36.
    Pubmed CrossRef
  9. Jang JY, Jung J, Lee D, et al. Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: a retrospective observational study. J Liver Cancer 2022;22:136-145.
    Pubmed KoreaMed CrossRef
  10. Jo SJ, Rhu J, Kim JM, Choi GS, Joh JW. Indications for open hepatectomy in the era of laparoscopic liver resection: a high volume single institutional study. J Liver Cancer 2022;22:146-157.
    Pubmed KoreaMed CrossRef
  11. Harada M, Aramaki O, Midorikawa Y, et al. Impact of patient age on outcome after resection for hepatocellular carcinoma. Biosci Trends 2021;15:33-40.
    Pubmed CrossRef
  12. Fujio A, Usuda M, Hara Y, et al. Usefulness of preoperative controlling nutritional status in predicting prolonged hospitalization and incidence of postoperative delirium for elderly hepatectomy with hepatocellular carcinoma. Tohoku J Exp Med 2022;256:43-52.
    Pubmed CrossRef
  13. Chen ZL, Zhang CW, Liang L, et al. Major hepatectomy in elderly patients with large hepatocellular carcinoma: a multicenter retrospective observational study. Cancer Manag Res 2020;12:5607-5618.
    Pubmed KoreaMed CrossRef
  14. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg 2003;73:712-716.
    Pubmed CrossRef
  15. Pu JL, Chen Z, Yao LQ, et al. Long-term oncological prognosis after curative-intent liver resection for hepatocellular carcinoma in the young versus the elderly: multicentre propensity score-matching study. BJS Open 2022;6:zrab145.
    Pubmed KoreaMed CrossRef
  16. Liu YW, Yong CC, Lin CC, et al. Liver resection in elderly patients with hepatocellular carcinoma: age does matter. Updates Surg 2021;73:1371-1380.
    Pubmed CrossRef
  17. Tan LL, Chew VT, Syn N, et al. Effect of age on the short- and long-term outcomes of patients undergoing curative liver resection for HCC. Eur J Surg Oncol 2022;48:1339-1347.
    Pubmed CrossRef
  18. Shin IS, Kim DG, Cha SW, et al. Hepatocellular carcinoma in old age: are there any benefits of liver resection in old age?. Ann Surg Treat Res 2020;99:65-71.
    Pubmed KoreaMed CrossRef
  19. Shimada S, Kamiyama T, Orimo T, et al. Prognoses, outcomes, and clinicopathological characteristics of very elderly patients with hepatocellular carcinoma who underwent hepatectomy. World J Surg Oncol 2020;18:122.
    Pubmed KoreaMed CrossRef
  20. Yasuda S, Nomi T, Hokuto D, Yoshikawa T, Matsuo Y, Sho M. Liver regeneration after major liver resection for hepatocellular carcinoma in the elderly. J Invest Surg 2020;33:332-338.
    Pubmed CrossRef
  21. Xing H, Liang L, Wang H, et al. Multicenter analysis of long-term oncologic outcomes of hepatectomy for elderly patients with hepatocellular carcinoma. HPB (Oxford) 2020;22:1314-1323.
    Pubmed CrossRef
  22. Famularo S, Di Sandro S, Giani A, et al. The impact of age and ageing on hepatocarcinoma surgery: short- and long-term outcomes in a multicentre propensity-matched cohort. Liver Int 2019;39:894-904.
    Pubmed CrossRef
  23. Jiang YQ, Wang ZX, Deng YN, Yang Y, Wang GY, Chen GH. Efficacy of hepatic resection vs. radiofrequency ablation for patients with very-early-stage or early-stage hepatocellular carcinoma: a population-based study with stratification by age and tumor size. Front Oncol 2019;9:113.
    Pubmed KoreaMed CrossRef
  24. Kaibori M, Yoshii K, Yokota I, et al. Impact of advanced age on survival in patients undergoing resection of hepatocellular carcinoma: report of a Japanese nationwide survey. Ann Surg 2019;269:692-699.
    Pubmed CrossRef
  25. Okamura Y, Sugiura T, Ito T, Yamamoto Y, Ashida R, Uesaka K. The short- and long-term outcomes in elderly patients with hepatocellular carcinoma after curative surgery: a case-controlled study with propensity score matching. Eur Surg Res 2018;59:380-390.
    Pubmed CrossRef
  26. Chen Y, Wang J, Wang W, Zhou B, Yang N, Yang G. Feasibility of hepatectomy in elderly patients with hepatocellular carcinoma. Int J Clin Exp Med 2018;11:7038-7046.
  27. Goh BK, Chua D, Syn N, et al. Perioperative outcomes of laparoscopic minor hepatectomy for hepatocellular carcinoma in the elderly. World J Surg 2018;42:4063-4069.
    Pubmed CrossRef
  28. Hsu KF, Yu JC, Yang CW, et al. Long-term outcomes in elderly patients with resectable large hepatocellular carcinoma undergoing hepatectomy. Surg Oncol 2018;27:595-601.
    Pubmed CrossRef
  29. Wang W, Huang Z, Guo B, Liu S, Xiao W, Liang J. Short- and long-term outcomes of laparoscopic hepatectomy in elderly patients with hepatocellular carcinoma. J BUON 2018;23:971-978.
  30. Yu X, Yan YC, Chen G, Yu H. The efficacy and safety of totally laparoscopic hepatectomy for non-cirrhotic hepatocellular carcinoma in the elderly. BMC Surg 2018;18:118.
    Pubmed KoreaMed CrossRef
  31. Santambrogio R, Barabino M, Scifo G, Costa M, Giovenzana M, Opocher E. Effect of age (over 75 years) on postoperative complications and survival in patients undergoing hepatic resection for hepatocellular carcinoma. J Gastrointest Surg 2017;21:657-665.
    Pubmed CrossRef
  32. Bauschke A, Altendorf-Hofmann A, Mothes H, Rauchfuß F, Settmacher U. Partial liver resection results in a significantly better long-term survival than locally ablative procedures even in elderly patients. J Cancer Res Clin Oncol 2016;142:1099-1108.
    Pubmed CrossRef
  33. Cucchetti A, Sposito C, Pinna AD, et al. Effect of age on survival in patients undergoing resection of hepatocellular carcinoma. Br J Surg 2016;103:e93-e99.
    Pubmed CrossRef
  34. Harimoto N, Yoshizumi T, Shimokawa M, et al. Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma. Hepatol Res 2016;46:1247-1255.
    Pubmed CrossRef
  35. Kim JM, Cho BI, Kwon CH, et al. Hepatectomy is a reasonable option for older patients with hepatocellular carcinoma. Am J Surg 2015;209:391-397.
    Pubmed CrossRef
  36. Kishida N, Hibi T, Itano O, et al. Validation of hepatectomy for elderly patients with hepatocellular carcinoma. Ann Surg Oncol 2015;22:3094-3101.
    Pubmed CrossRef
  37. Motoyama H, Kobayashi A, Yokoyama T, et al. Impact of advanced age on the short- and long-term outcomes in patients undergoing hepatectomy for hepatocellular carcinoma: a single-center analysis over a 20-year period. Am J Surg 2015;209:733-741.
    Pubmed CrossRef
  38. Nozawa A, Kubo S, Takemura S, et al. Hepatic resection for hepatocellular carcinoma in super-elderly patients aged 80 years and older in the first decade of the 21st century. Surg Today 2015;45:851-857.
    Pubmed CrossRef
  39. Sato S, Tanaka K, Nojiri K, et al. Hepatic resection for hepatocellular carcinoma in the elderly: selecting hepatectomy procedures based on patient age. Anticancer Res 2015;35:6855-6860.
    Pubmed
  40. Faber W, Stockmann M, Schirmer C, et al. Significant impact of patient age on outcome after liver resection for HCC in cirrhosis. Eur J Surg Oncol 2014;40:208-213.
    Pubmed CrossRef
  41. Liu PH, Hsu CY, Lee YH, et al. Uncompromised treatment efficacy in elderly patients with hepatocellular carcinoma: a propensity score analysis. Medicine (Baltimore) 2014;93:e264.
    Pubmed KoreaMed CrossRef
  42. Mori S, Kita J, Shimizu T, Kato M, Shimoda M, Kubota K. Outcome of hepatectomy for hepatocellular carcinoma in elderly patients with portal hypertension. Int Surg 2014;99:153-160.
    Pubmed KoreaMed CrossRef
  43. Ueno M, Hayami S, Tani M, Kawai M, Hirono S, Yamaue H. Recent trends in hepatectomy for elderly patients with hepatocellular carcinoma. Surg Today 2014;44:1651-1659.
    Pubmed CrossRef
  44. Wang HQ, Yang J, Yan LN, Zhang XW, Yang JY. Liver resection in hepatitis B related-hepatocellular carcinoma: clinical outcomes and safety in elderly patients. World J Gastroenterol 2014;20:6620-6625.
    Pubmed KoreaMed CrossRef
  45. Wang WL, Zhu Y, Cheng JW, et al. Major hepatectomy is safe for hepatocellular carcinoma in elderly patients with cirrhosis. Eur J Gastroenterol Hepatol 2014;26:444-451.
    Pubmed CrossRef
  46. Hirokawa F, Hayashi M, Miyamoto Y, et al. Surgical outcomes and clinical characteristics of elderly patients undergoing curative hepatectomy for hepatocellular carcinoma. J Gastrointest Surg 2013;17:1929-1937.
    Pubmed CrossRef
  47. Ide T, Miyoshi A, Kitahara K, Noshiro H. Prediction of postoperative complications in elderly patients with hepatocellular carcinoma. J Surg Res 2013;185:614-619.
    Pubmed CrossRef
  48. Murillo A, Artigas V, González JA, et al. Hepatic resection in hepatocarcinoma: a comparative study between patients under and over 70 years-old. Cir Esp 2013;91:224-230.
    Pubmed CrossRef
  49. Nishikawa H, Arimoto A, Wakasa T, Kita R, Kimura T, Osaki Y. Surgical resection for hepatocellular carcinoma: clinical outcomes and safety in elderly patients. Eur J Gastroenterol Hepatol 2013;25:912-919.
    Pubmed CrossRef
  50. Taniai N, Yoshida H, Yoshioka M, Kawano Y, Uchida E. Surgical outcomes and prognostic factors in elderly patients (75 years or older) with hepatocellular carcinoma who underwent hepatectomy. J Nippon Med Sch 2013;80:426-432.
    Pubmed CrossRef
  51. Lee CR, Lim JH, Kim SH, et al. A comparative analysis of hepatocellular carcinoma after hepatic resection in young versus elderly patients. J Gastrointest Surg 2012;16:1736-1743.
    Pubmed CrossRef
  52. Nanashima A, Abo T, Nonaka T, et al. Prognosis of patients with hepatocellular carcinoma after hepatic resection: are elderly patients suitable for surgery?. J Surg Oncol 2011;104:284-291.
    Pubmed CrossRef
  53. Portolani N, Baiocchi GL, Coniglio A, et al. Limited liver resection: a good indication for the treatment of hepatocellular carcinoma in elderly patients. Jpn J Clin Oncol 2011;41:1358-1365.
    Pubmed CrossRef
  54. Mirici-Cappa F, Gramenzi A, Santi V, et al. Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience. Gut 2010;59:387-396.
    Pubmed CrossRef
  55. Sanyal S, Kron P, Wylie N, Hildalgo E, Toogood GJ, Lodge P. Outcomes of liver resection for hepatocellular carcinoma in octogenarians. HPB (Oxford) 2020;22:1324-1329.
    Pubmed CrossRef
  56. Inoue Y, Tanaka R, Fujii K, et al. Surgical outcome and hepatic regeneration after hepatic resection for hepatocellular carcinoma in elderly patients. Dig Surg 2019;36:289-301.
    Pubmed CrossRef
  57. Lee CW, Chan KM, Tsai HI, et al. Hepatic resection for hepatocellular carcinoma in the octogenarian: is it justified?. Aging (Albany NY) 2019;11:1537-1550.
    Pubmed KoreaMed CrossRef
  58. Wu FH, Shen CH, Luo SC, et al. Liver resection for hepatocellular carcinoma in oldest old patients. World J Surg Oncol 2019;17:1.
    Pubmed KoreaMed CrossRef
  59. Hamaoka M, Kobayashi T, Ishiyama K, et al. Evaluation of the risk factors and prognostic factors of hepatectomy for hepatocellular carcinoma in patients aged 80 years or more. J Hepatobiliary Pancreat Sci 2017;24:58-64.
    Pubmed CrossRef
  60. Katsuta E, Tanaka S, Mogushi K, et al. Age-related clinicopathologic and molecular features of patients receiving curative hepatectomy for hepatocellular carcinoma. Am J Surg 2014;208:450-456.
    Pubmed CrossRef
  61. Tsujita E, Utsunomiya T, Yamashita Y, et al. Outcome of hepatectomy in hepatocellular carcinoma patients aged 80 years and older. Hepatogastroenterology 2012;59:1553-1555.
    Pubmed CrossRef
  62. Yamada S, Shimada M, Miyake H, et al. Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma. Hepatol Res 2012;42:454-458.
    Pubmed CrossRef
  63. Lurje G, Bednarsch J, Czigany Z, et al. Prognostic factors of disease-free and overall survival in patients with hepatocellular carcinoma undergoing partial hepatectomy in curative intent. Langenbecks Arch Surg 2018;403:851-861.
    Pubmed CrossRef
  64. Lee HA, Lee S, Lee HL, et al. The efficacy of treatment for hepatocellular carcinoma in elderly patients. J Liver Cancer 2023;23:362-376.
    Pubmed KoreaMed CrossRef
  65. Nishikawa H, Kimura T, Kita R, Osaki Y. Radiofrequency ablation for hepatocellular carcinoma. Int J Hyperthermia 2013;29:558-568.
    Pubmed CrossRef
  66. Gunasekaran G, Bekki Y, Lourdusamy V, Schwartz M. Surgical treatments of hepatobiliary cancers. Hepatology 2021;73 Suppl 1:128-136.
    Pubmed CrossRef
  67. Younossi ZM, Wong G, Anstee QM, Henry L. The global burden of liver disease. Clin Gastroenterol Hepatol 2023;21:1978-1991.
    Pubmed CrossRef
  68. Lee VH, Seong J, Yoon SM, et al. Contrasting some differences in managing advanced unresectable hepatocellular carcinoma between the east and the west. Clin Oncol (R Coll Radiol) 2019;31:560-569.
    Pubmed CrossRef
  69. Choo SP, Tan WL, Goh BK, Tai WM, Zhu AX. Comparison of hepatocellular carcinoma in Eastern versus Western populations. Cancer 2016;122:3430-3446.
    Pubmed CrossRef
  70. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2021;18:223-238.
    Pubmed KoreaMed CrossRef
  71. Younossi ZM, Otgonsuren M, Henry L, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015;62:1723-1730.
    Pubmed CrossRef
  72. Lin BZ, Lin TJ, Lin CL, et al. Differentiation of clinical patterns and survival outcomes of hepatocellular carcinoma on hepatitis B and nonalcoholic fatty liver disease. J Chin Med Assoc 2021;84:606-613.
    Pubmed CrossRef
  73. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.
    Pubmed CrossRef
  74. Elfrink AK, Kok NF, den Dulk M, et al. Short-term postoperative outcomes after liver resection in the elderly patient: a nationwide population-based study. HPB (Oxford) 2021;23:1506-1517.
    Pubmed CrossRef
  75. Chen Y, Yu L, Quan C. Laparoscopic versus open hepatectomy for elderly patients with hepatocellular carcinoma. J BUON 2020;25:1404-1412.
    Pubmed
  76. Teng PC, Huang DQ, Lin TY, Noureddin M, Yang JD. Diabetes and risk of hepatocellular carcinoma in cirrhosis patients with nonalcoholic fatty liver disease. Gut Liver 2023;17:24-33.
    Pubmed KoreaMed CrossRef
  77. Shin SK, Yim HJ, Kim JH, et al. Partial virological response after 2 years of entecavir therapy increases the risk of hepatocellular carcinoma in patients with hepatitis B virus-associated cirrhosis. Gut Liver 2021;15:430-439.
    Pubmed KoreaMed CrossRef

Article

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Gut and Liver

Published online May 7, 2024

Copyright © Gut and Liver.

Efficacy and Safety of Surgical Resection in Elderly Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Jin-Soo Lee1 , Dong Ah Park2 , Seungeun Ryoo2 , Jungeun Park2 , Gi Hong Choi3 , Jeong-Ju Yoo1

1Department of Internal Medicine, Soonchunhyang University School of Medicine, Asan, Korea; 2Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea; 3Department of General Surgery, Yonsei University School of Medicine, Seoul, Korea

Correspondence to:Dong Ah Park
ORCID https://orcid.org/0000-0001-7225-3152
E-mail pda124@neca.re.kr

Jeong-Ju Yoo
ORCID https://orcid.org/0000-0002-7802-0381
E-mail puby17@naver.com

Jin-Soo Lee and Dong Ah Park contributed equally to this work as first authors.

Received: November 22, 2023; Revised: January 17, 2024; Accepted: January 29, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims: With increased life expectancy, the management of elderly hepatocellular carcinoma (HCC) patients became a crucial issue, yet it is still challenging due to comorbidities and high surgical risks. While surgical resection is considered as primary treatment for eligible HCC patients, systematic evidence on its outcomes in elderly patients remains scarce. In this review, we aimed to analyze the efficacy and safety outcomes of surgical resection in elderly HCC patients.
Methods: The studies included in this meta-analysis were selected from Ovid-MEDLINE, Ovid-Embase, CENTRAL, KoreaMed, KMbase, and KISS databases following a predefined protocol. Efficacy outcomes included overall survival and disease-free survival, while the safety outcomes included postoperative mortality and complications.
Results: Patients in the elderly group (≥65 years) who underwent surgery exhibited non-inferior overall survival (hazard ratio [HR], 1.26; 95% confidence interval [CI], 0.92 to 1.74) and disease-free survival (HR, 1.03; 95% CI, 0.99 to 1.08) compared to the non-elderly group. Overall postoperative mortality exhibited no statistical difference (odds ratio [OR], 1.07; 95% CI, 0.87 to 1.31), but 30-day, 90-day, and in-hospital mortality were higher in the elderly group. The incidence of overall complications was higher in the elderly group (OR, 1.44; 95% CI, 1.22 to 1.69). Sensitivity analysis for the super elderly group (≥80 years) showed significantly higher in-hospital mortality compared to the non-super elderly group (OR, 2.51; 95% CI, 1.16 to 5.45).
Conclusions: The efficacy outcome of surgical resection in the elderly HCC patients was not worse than that in the non-elderly HCC patients, while in-hospital mortality and complications rates were higher. Therefore, surgical resection should be purposefully considered in the elderly population, with careful candidate selection.

Keywords: Hepatocellular carcinoma, Aged, Surgery, Treatment

INTRODUCTION

According to the World Health Organization, hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide, in 2020, with an annual estimate of 830,000 deaths.1 Deaths caused by HCC are particularly frequent in Asia, where HCC is the second cause of cancer-related death.2 Due to the increase in life expectancy and advancements in medical technology, the number of elderly patients with HCC has been rising and the treatment selection for elderly HCC patients has become increasingly important.3,4

Surgical resection is considered the gold standard for curative treatment of early to intermediate-stage HCC patients.5 Owing to recent advances in surgical techniques and perioperative management, recent studies have shown that surgical resection shows better outcomes than other treatment options such as radiofrequency ablation, transarterial chemoembolization, and systemic chemotherapy.6,7 However, recommending surgical resection as a primary treatment for elderly HCC patients (≥65 years) is significantly challenged by their higher comorbidity rates, increased surgical risks, and the lack of objective data.8,9 Moreover, most patients aged 80 and above are typically excluded from research designs, further exacerbating the scarcity of data for this specific age group. Here arises a demand for guidelines addressing the safety and feasibility of surgical resection in this specific patient age range, necessitating large-scale studies comparing the efficacy and safety outcomes of surgical resection between elderly and non-elderly patients.10

The objective of this study was to provide systematic evidence that supports the decision for surgical resection in elderly patients with HCC. There have been several studies comparing the outcomes of surgical resection between elderly and non-elderly patients, but most of them were limited to single institution,11 or had a small number,12 or were restricted to the domestic population.13 Therefore, we conducted a systematic review and meta-analysis on outcomes of surgical resection, including the super elderly population.

MATERIALS AND METHODS

This article was registered at the International Prospective Register of Systematic Reviews (CRD42023469975) for adequate protocol. Systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-analysis of Observational Studies in Epidemiology checklists. Ethics approval was waived from the Institutional Review Board of the National Evidence-based Healthcare Collaborating Agency and the current study conformed to the ethical guidelines of the World Medical Association Declaration of Helsinki.

1. Study selection and subgroup design

The study selection algorithm is characterized in Fig. 1. Articles were mainly identified and searched from databases and registers in 2021 and an updated search was conducted in 2022. Ovid-MEDLINE, Ovid-Embase, and CENTRAL were the international databases used, and KoreaMed, KMbase, and KISS were the domestic databases. In primary study screening, title-based selection and exclusion were conducted and 9,601 studies were excluded. Furthermore, abstract-based screening was done, and 2,511 studies were excluded. A total of 225 studies were selected for full-text review. After considering the relevance to our study design, a final set of 56 studies was selected for systemic analysis (Fig. 1). Since all the studies included in the meta-analysis were retrospective design, they are inherently more susceptible to selection bias and confounding factors. To address this limitation, we conducted subgroup analyses based on various classification such as age cutoff, publication year, country, and methodological index for non-randomized studies (MINORS) score. Additionally, sensitivity analysis was performed specifically for the super elderly population. The primary meta-analysis of our study focused on comparing the elderly group, defined as individuals aged 65 and above, with the non-elderly group, defined as those under 65, and presenting the analysis results. However, considering the increasing prevalence of very elderly patients in clinical practice, we conducted an additional sensitivity analysis specifically for the super elderly group, defined as individuals aged 80 and above, in studies where this age category was separately classified.

Figure 1. Selection flowchart of the studies included in meta-analysis.

2. Study outcome

The purpose of the study was to compare efficacy and safety outcomes between elderly and non-elderly patients with HCC. Efficacy-related outcomes included overall survival (OS) and disease-free survival (DFS), while safety-related outcomes included postoperative mortality and postoperative complications.

3. Methodological quality and risk of bias assessment

The assessment of bias risk was conducted independently by two researchers, and consensus was reached through discussion with a third party. For randomized controlled trials, the Cochrane Risk of Bias 1.0 tool was used whereas the MINORS (a valid instrument designed to assess the methodological quality of non-randomized surgical studies, consisting of 12 questions with a total of 24 points14 was used for non-randomized controlled trials (Supplementary Fig. 1).

4. Statistical analysis

Efficacy-related outcomes, OS and DFS, were evaluated using median value, interquartile range (IQR), and range. Meta-analysis was primarily done with a random effects model, using the following methods: (1) inverse variance method for survival and consecutive data and (2) Mantel-Haenszel method for binary data. The binary outcomes were presented as odds ratio (OR), and for survival outcomes, hazard ratio (HR) with a 95% confidence interval (CI). Statistical inter-study heterogeneity of meta-analysis was primarily assessed by Forest plot and Cochrane Q statistics (p<0.10) with I2 statistics (≥50%). Moreover, subgroup analysis was conducted to find factors contributing to heterogeneity and those factors included age threshold, disease stage, country of study, publication year, quality assessment scores, and the number of adjusted variables. Also, sensitivity analysis was conducted on super elderly patients, independently (≥80 years). Publication bias was assessed using funnel plots and Egger’s test (Supplementary Fig. 2). Meta-analysis was conducted using RevMan 5.3, and statistical significance for differences between groups was assessed at a significance level of 5%.

RESULTS

1. Characteristics of studies included in the systemic review

As mentioned above, a total of 56 articles were included in the final analysis. The baseline characteristics of the enrolled studies including baseline liver function and cancer status are presented in Table 1.11-13,15-62 When classified by continent, the majority of studies, 47 (83.9%), were from Asia, while nine studies (16.0%) were from Europe. Forty-six studies (82.1%) were conducted by a single institution, and 10 studies (17.8%) involved multi-institutions. All 56 studies were retrospective cohort studies. An age threshold of 70 years for elderly patients was used in 24 studies (42.8%), followed by 75 years in 14 studies (25%), and 65 years in five studies (8.9%).

Table 1 . Demographics and Characteristics of Studies Included in the Systematic Review: Elderly versus Non-Elderly.

Study (year)CountryInstitutionRecruitment
period
MatchingObjectiveAge
cutoff, yr
No. of
elderly
No. of
non-elderly
Baseline liver function, %Tumor size, mm
Elderly
Child A/B
Non-elderly
Child A/B
ElderlyNon-elderly
Fujio (2022)12JapanSingle2012–2016NRHR for HCC75223995/587/1353.652
Pu (2022)15ChinaMulticenter2007–2019PSMR0 HR for HCC7014014094/694/6NANA
Harada (2021)11JapanSingle2001–2012PSMHR for HCC7023423497/395/53031
Liu (2021)16TaiwanRegistry2007–2017NRHR for HCC7596908NANA41.5NA
Tan (2021)17SingaporeSingle2000–2018NRHR for HCC7027876494/695/54538
Chen (2020)13ChinaMulticenter2006–2016NRHR for HCC659273891/989/11105108
Shin (2020)18KoreaSingle2012–2018NRHR for HCC7049184NANANANA
Shimada (2020)19JapanSingle2000–2017NRHR for HCC65363384NANA5761
Yasuda (2020)20JapanSingle2000–2013NRMajor HR for HCC702318100/0100/05478
Xing (2020)21ChinaMulticenter2003–2016NRHR for HCC702591,87596/490/10NANA
Famularo (2019)22ItalyMulticenter2005–2015PSMHR for HCC75929292/896/43541
Jiang (2019)23ChinaRegistry2004–2015NRHR for HCC659561,392NANANANA
Kaibori (2019)24JapanRegistry2000–2007NRHR for HCC752,02010,56792/890/1038NA
Okamura (2018)25JapanSingle2002–2014PSMHR for HCC75727299/199/1NANA
Chen (2018)26ChinaSingle2010–2016NRHR for HCC6525688691/982/18NA84
Goh (2018)27SingaporeSingle2007–2016PSMLMH for HCC704094NANA3025
Hsu (2018)28TaiwanSingle2003–2014NRHR for large HCC (>5 cm)707917892/889/118690
Wang (2018)29ChinaSingle2011–2016NRHR for HCC704897NANANANA
Yu (2018)30ChinaSingle2003–2013NRHR for HCC70235883/1791/94737
Santambrogio (2017)31ItalySingle1998–2015NRHR for HCC7553115100/0100/0NANA
Bauschke (2016)32GermaySingle1995–2014NRHR for HCC70638187/1377/23NANA
Cucchetti (2016)33ItalySingle1997–2013NRHR for HCC with LC70229690NANANANA
Harimoto (2016)34JapanSingle2004–2013NRHR for HCC7013915794/696/44040
Kim (2015)35KoreaSingle2006–2010NRHR for HCC7060219NANA4949
Kishida (2015)36JapanSingle2005–2010NRHR for HCC75228291/999/13530
Motoyama (2015)37JapanSingle1990–2013NRHR for HCC7511349995/594/63330
Nozawa (2015)38JapanSingle2000–2010NRHR for HCC7019223986/1485/15NA30
Sato (2015)39JapanSingle2000–2010NRHR for HCC753419574/2683/174954
Faber (2014)40GermanySingle2000–2010NRHR for HCC with LC706378NANA5050
Liu (2014)41TaiwanSingle2002–2013PSMHR for HCC7511811893/793/7NANA
Mori (2014)42JapanSingle2000–2012NRHR for HCC with PHT706413178/2271/294133
Ueno (2014)43JapanSingle2001–2010NRHR for HCC756618691/991/95040
Wang (2014)44ChinaSingle2007–2012NRHR for HBV related HCC652071,336NANANANA
Wang (2014)45ChinaSingle2007–2012Paired
matched
Major hepatectomy for HCC with LC705615286/1480/207589
Hirokawa (2013)46JapanSingle2000–2011NRHR for HCC7010012088/1282/183530
Ide (2013)47JapanSingle2000–2010NRHR for HCC756419289/1188/124949
Murillo (2013)48SpainSingle2000–2011NRHR for HCC702214NANA3847
Nishikawa (2013)49JapanSingle2004–2012NRHR for HCC759220698/296/44648
Taniai (2013)50JapanSingle1990–2010NRHR for HCC756335389/1175/24/1NANA
Lee (2012)51KoreaSingle2000–2010NRHR for HCC706190NANA4543
Nanashima (2011)52JapanSingle1994–2009NRHR for HCC706911993/789/11NANA
Portolani (2011)53ItalySingle1992–2009NRHR for HCC7017527692/893/74849
Mirici-Cappa (2010)54ItalyMulticenter1987–2004PSMHR for HCC70323293/782/133441
Tan (2021)17*SingaporeSingle2000–2018NRHR for HCC80501,04292/894/680NA
Sanyal (2020)55EnglandSingle2005–2015NRHR for HCC8019181NANANANA
Shimada (2020)19JapanSingle2000–2017NRHR for HCC8049757NANA64NA
Inoue (2019)56JapanSingle2001–2017PSMHR for HCC8045485100/093/74132
Lee (2019)57TaiwanSingle1986–2015NRHR for HCC80773,30996/496/45942
Wu (2019)58TaiwanSingle1992–2016NRHR for HCC85311,85887/10/387/11/25665
Chen (2018)26ChinaSingle2010–2016NRHR for HCC80321,11094/684/1669NA
Hamaoka (2017)59JapanSingle2004–2013NRHR for HCC806056593/793/73327
Nozawa (2015)38JapanSingle2000–2010NRHR for HCC802041195/585/1541NA
Katsuta (2014)60§JapanSingle2000–2012NRHR for HCC802945783/1791/9NANA
Tsujita (2012)61JapanMulticenter1995–2008NRHR for HCC8023385NANANANA
Yamada (2012)62JapanMulticenter1992–2009NRHR for HCC801126782/1892/85248
Nanashima (2011)52JapanSingle1994–2009NRHR for HCC8012167100/090/10NANA

NR, not reported; PSM, propensity score matching; HR, hepatic resection; HCC, hepatocellular carcinoma; LC, liver cirrhosis; LMH, laparoscopic minor hepatectomy; PHT, portal hypertension; HBV, hepatitis B virus; NA, not applicable..

Definition of elderly: *<70/70–79/≥80 yr; <65/65–79/≥80; <70/70–80/≥81 yr; §<50/50–79/≥80; <50/50–69/70–79/≥80 yr..



2. Overall survival

Forty-eight articles reported the results of the OS. In the elderly group meta-analysis, at the 3-year postoperative point, the median OS of the elderly group was 70.0% (IQR, 62.7% to 75.1%) and 74.3% (IQR, 66.8% to 77.9%) in the non-elderly group. The median survival periods were similar between the two groups: the elderly group had a median of 69 months (IQR, 52.5 to 77.0 months), while the non-elderly group had a median of 73.3 months (IQR, 60.0 to 89.7 months). In the analysis of the super elderly group (≥80 years), the 3-year median OS rates were 67.7% (IQR, 53.3% to 79.3%) for the super elderly and 70.9% (IQR, 46.0% to 76.8%) for the non-super elderly, respectively. Similar to the elderly group analysis, median survival periods were similar between the super elderly and non-super elderly; 64.8 months in super elderly and 79.4 months in non-super elderly (Supplementary Table 1).

We conducted a meta-analysis on OS between elderly and non-elderly groups. Univariate analysis showed that the OS of the elderly group was worse than that of the non-elderly group (HR, 1.18; 95% CI, 1.09 to 1.27; I2=67%) (Fig. 2A), whereas, in multivariate analysis, there was no significant difference between the two groups (HR, 1.26; 95% CI, 0.92 to 1.74; I2=71%). In subgroup analysis, studies that used 75 years as the age threshold for the elderly showed lower heterogeneity, and the overall mortality of the elderly group was higher than that of the non-elderly group (HR, 1.29; 95% CI, 1.17 to 1.42; I2=23%) (Table 2).

Figure 2. Forest plots. (A) Overall mortality between elderly versus non-elderly. (B) Disease-free survival between elderly versus non-elderly. (C) Postoperative mortality between elderly versus non-elderly. (D) Post operative mortality between super elderly versus non-super elderly. (E) Postoperative complication between elderly versus non-elderly. (F) Postoperative complication between super elderly versus non-super elderly. SE, standard error; IV, inverse variance; CI, confidence interval; M-H, Mantel-Haenszel.

Table 2 . Meta-Analysis on Overall Survival: Elderly versus Non-Elderly.

VariableUnivariate analysisMultivariate analysis
No. of studiesRandom, IV HR (95% CI)I2, %No. of studiesRandom, IV HR (95% CI)I2, %
Overall mortality321.18 (1.09–1.27)6741.26 (0.92–1.74)71
Using dataNA
Calculated data231.13 (1.04–1.22)52NA
Reported data91.26 (1.07–1.49)79NA
Age cutoff
65–70 yr181.09 (1.00–1.19)6611.08 (0.49–2.36)NA
75 yr141.29 (1.17–1.42)2321.39 (0.69–2.81)89
Publication year
2016–2022201.19 (1.08–1.31)7041.26 (0.92–1.74)71
2010–2015131.19 (1.02–1.40)610--
Country
Asia261.15 (1.07–1.24)6521.23 (0.90–1.69)0
Non-Asia61.46 (0.96–2.20)7721.39 (0.69–2.81)89
MINORS score
Over median value (20)151.32 (1.15–1.50)7021.39 (0.69–2.81)89
Under median value (20)171.10 (0.99–1.22)6721.23 (0.90–1.69)0

IV HR, inverse variance hazard ratio; CI, confidence interval; NA, not applicable; MINORS, methodological index for non-randomized studies..



Sensitivity analysis between the super elderly (≥80 years) and the non-super elderly group showed higher overall mortality in the super elderly group (HR, 1.32; 95% CI, 1.04 to 1.67; I2=79%), but had higher heterogeneity between studies. In subgroup analysis, studies published between 2010 and 2015 showed lower heterogeneity and the risk of death for the super elderly group was higher than that for the non-super elderly group (HR, 1.59; 95% CI, 1.00 to 2.53; I2=0%). Furthermore, in studies with high MINORS score, there was no statistical heterogeneity, and the overall mortality for the super elderly group was also higher (HR, 1.22; 95% CI, 1.03 to 1.44; I2=0%) (Supplementary Table 2).

3. Disease-free survival

DFS was reported in 34 studies. In the elderly group analysis, at the 3-year postoperative point, the median DFS rate for the elderly group was 40.6% (IQR, 36.0% to 50.9%), while the non-elderly group showed a rate of 44.9% (IQR, 35.7% to 54.5%). Five-year median DFS rate was 33.0% in both elderly and non-elderly groups (IQR, 25.6% to 36.9% and IQR, 25.6% to 39.8%, respectively). The median DFS periods were similar between the two groups, with the elderly group having 27.8 months (IQR 20.3 to 35.8 months) and the non-elderly group having 33.4 months (IQR, 18.6 to 42.6 months) (Supplementary Table 1). According to the univariate analysis for DFS, there was no statistically significant difference between elderly and non-elderly groups (HR, 1.03; 95% CI, 0.99 to 1.08; I2=0%) (Table 3, Fig. 2B).

Table 3 . Meta-Analysis on Disease-Free Survival: Elderly versus Non-Elderly.

VariableUnivariate analysis
No. of studiesRandom, IV HR (95% CI)I2, %
Overall estimate211.03 (0.99–1.08)0
Using data
Calculated data151.04 (0.96–1.13)17
Reported data61.03 (0.97–1.10)0
Age cutoff
65–70 yr101.05 (0.97–1.14)0
75 yr111.02 (0.96–1.08)0
Publication year
2016–2022131.04 (0.99–1.09)0
2010–201581.17 (0.92–1.49)34
Country
Asia181.02 (0.98–1.07)0
Non-Asia31.43 (1.02–2.01)0
MINORS score
Over median value (20)101.06 (0.91–1.24)33
Under median value (20)111.04 (0.99–1.10)0

IV HR, inverse variance hazard ratio; CI, confidence interval; MINORS, methodological index for non-randomized studies..



In sensitivity analysis for the super elderly group (≥80 years), 3-year median DFS were 38.1% (IQR, 34.1% to 46.2%) and 46.3% (IQR, 38.8% to 47.9%) for super elderly and non-super elderly respectively. 5-year median DFS rates were 35.1% (IQR, 19.4% to 40.2%) and 32.3% (IQR, 28.7% to 35.2%) respectively. Median DFS periods were 26.3 months (IQR, 24.0 to 31.3 months) in super elderly and 28.4 months (IQR, 20.5 to 33.2 months) in non-super elderly (Supplementary Table 1).

4. Postoperative mortality

Overall postoperative mortality, 30 days postoperative mortality, 90 days postoperative mortality, in-hospital mortality, and mortality related to hepatic failure were analyzed (Table 4). Fourteen studies reported overall postoperative mortality and there was no significant difference between elderly and non-elderly groups (OR, 1.07; 95% CI, 0.87 to 1.31; I2=51%) (Fig. 2C). Whereas the elderly group showed significantly higher 30 days, 90 days mortality, and in-hospital mortality rates compared to the non-elderly group with OR of 2.13, 1.65, and 1.78, respectively. However, hepatic failure-related mortality showed no significant difference between the two groups (OR, 1.28; 95% CI, 0.76 to 2.16; I2=0%). Within the super elderly (≥80 years) group versus non-super elderly group analysis, the super elderly group showed significantly higher in-hospital mortality (OR, 2.51; 95% CI, 1.16 to 5.45). However, there were no significant differences in overall postoperative mortality (OR, 0.91; 95% CI, 0.33 to 2.50) (Fig. 2D), 30 days, and 90 days mortality between the two groups (Table 4).

Table 4 . Postoperative Mortality: Elderly versus Non-Elderly, Super Elderly versus Non-Super Elderly.

Outcome variableNo. of
studies
ElderlyNon-elderlyRandom, M-H
pooled OR
95% CII2, %
No. of participantsEventsNo. of participantsEvents
Elderly vs non-elderly
Overall mortality rate141,8137344,5252,0571.070.87–1.3151
30-Day mortality rate101,740245,921582.131.28–3.540
90-Day mortality rate131,738475,8411151.651.09–2.498
In-hospital mortality rate101,055313,175471.781.03–3.0914
Hepatic failure-related mortality rate111,463282,976451.280.76–2.160
Super elderly vs non-super elderly
Overall mortality rate4137392,3049290.910.33–2.5075
30-Day mortality rate628766,954922.270.99–5.180
90-Day mortality rate414933,828552.050.76–5.570
In-hospital mortality rate514364,5481022.511.16–5.450
Hepatic failure-related mortality rate0----

M-H, Mantel-Haenszel; OR, odds ratio; CI, confidence interval..



5. Postoperative complications

The overall postoperative complication was reported in 26 studies (Table 5). The elderly group had a higher incidence of postoperative complications than that of the non-elderly group (OR, 1.44; 95% CI, 1.22 to 1.69; I2=51%) (Fig. 2E). The elderly group also had a higher incidence of major postoperative complications (OR, 1.30; 95% CI, 1.11 to 1.53; I2=26%), whereas no significant difference in postoperative hepatic failure was observed between the two groups (OR, 1.20; 95% CI, 0.79 to 1.82; I2=0%). In sensitivity analysis, the super elderly group had a higher incidence of complications than the non-super elderly group (OR, 2.02; 95% CI, 1.35 to 3.02; I2=65%) (Fig. 2F) whereas major postoperative complications and postoperative hepatic failure did not show a statistical difference between groups.

Table 5 . Postoperative Complications: Elderly versus Non-Elderly, Super Elderly versus Non-Super Elderly.

Outcome variableNo. of
studies
ElderlyNon-elderlyRandom, M-H
pooled OR
95% CII2, %
No. of participantsEventsNo. of participantsEvents
Elderly vs non-elderly
Overall postoperative complications262,9431,1848,6292,7621.441.22–1.6951
Major postoperative complications242,4764118,3601,0411.301.11–1.5326
Postoperative hepatic failure131,154333,9141001.200.79–1.820
Super elderly vs non-super elderly
Overall postoperative complications93591719,4572,9402.021.35–3.0265
Major postoperative complications7197283,5163281.250.66–2.3947
Postoperative hepatic failure819755,147832.250.96–5.270

M-H, Mantel-Haenszel; OR, odds ratio; CI, confidence interval..


DISCUSSION

Through this meta-analysis, several meaningful results regarding the efficacy and safety of surgery in elderly HCC patients were obtained. These results can be of great help to clinicians in decision-making in a recent trend where the number of elderly HCC patients is increasing.

The first finding of our study was that there was no statistically significant difference in the efficacy outcomes, namely OS and DFS, between the elderly and non-elderly groups (Tables 2 and 3). Univariate analysis for OS showed a difference between the elderly and non-elderly groups (HR, 1.18; 95% CI, 1.09 to 1.27). However, in multivariate analysis, no statistically significant difference was observed between the two groups (HR, 1.26; 95% CI, 0.92 to 1.74). Therefore, it is suggested that factors other than surgery might have had a greater influence on the difference in OS between the elderly and non-elderly groups.24,63 One possible interpretation of this result may be that relative to the past, the overall health status has improved owing to recent advancements in medical technology, which led to an increase in average lifespan and improved performance among the elderly population.64 Another speculation is that the likelihood of undergoing surgery in selected patients, particularly those with good performance status, is higher in actual clinical practice. Patients with poor performance status often undergo other procedures such as radiofrequency ablation rather than surgery.65 Therefore, the patients analyzed in this study might have had similar initial pre-operative conditions compared to the non-elderly group. The last hypothesis is that the overall advancement in surgical techniques and postoperative management might have contributed to improved surgical outcomes in elderly HCC patients.66 To investigate this hypothesis further, subgroup analyses were conducted according to the year of publication which indicated no significant differences in results across different study periods (Table 2).

The second finding is that in the Asian region, the difference in OS and DFS between elderly and non-elderly groups had a less pronounced trend compared to the non-Asian regions, although not statistically significant (Tables 2 and 3). This is thought to be due to the differences in HCC etiology and surgical methods between Asia and non-Asian countries. In Asia, the proportion of HCC due to viral hepatitis such as hepatitis B virus or hepatitis C virus is significantly higher compared to the predominance of nonalcoholic fatty liver disease-associated HCC in the West.2,67-69 It is known that the average age of nonalcoholic fatty liver disease-associated HCC patients is about 5 to 10 years older than that of viral hepatitis-associated HCC patients.70-72 Therefore, it is assumed that the median age of Asia's HCC is lower than that of the West, potentially resulting in improved postoperative survival. Moreover, the incidence of HCC is higher in Asia compared to non-Asian countries, and the difference in surgical experience and techniques due to the higher incidence in Asia may have contributed to better surgical outcomes in elderly Asian HCC patients compared to non-Asian patients.69,73

The third finding of our study revealed a higher postoperative mortality in the elderly group compared to the non-elderly group, with a particularly high in-hospital mortality noted in the super elderly group (≥80 years). While it was somewhat predictable that postoperative mortality would be higher in the elderly, our study was able to objectively quantify this.74 Therefore, it is essential to consider longer in-hospital monitoring periods for elderly HCC patients, especially for the super elderly after surgery. Additionally, both the elderly and super elderly groups exhibited higher rates of postoperative complications, with a notably increased risk of major postoperative complications observed in the elderly group. This highlights the need for greater attention to postoperative management in elderly patients.31 Although there were no significant differences in hepatic failure-related deaths, it is important to note that this could be due to the inclusion of patients with remaining liver reserve functions suitable for surgery, emphasizing the need for careful interpretation of the results.

Our study has several limitations. First, the individual comorbidities were not considered. This study conducted a meta-analysis of the entire cohort without adjusting for comorbidities. However, the reported comorbidities varied across studies, and studies with objectively quantifiable measures suitable for meta-analysis, such as the Charlson comorbidity index score, were limited. Therefore, adjusting for comorbidities to derive conclusive results proved challenging. The comorbidities frequently mentioned and adjusted from several studies were as follows: hypertension, diabetes, hyperlipidemia, chronic kidney disease, cerebrovascular disease, cerebrovascular accident, pulmonary disease, and Charlson comorbidity index score. To make up for this shortcoming, a multivariate analysis adjusting for other variables was conducted in regard to the OS, but it still had some limitations. Second, in our meta-analysis, we did not perform sub-analyses according to baseline liver function or cancer status. However, considering that the majority of surgical candidates were likely to be Child-Pugh class A with stage I patients, we believe there may have been some level of homogeneity between the two groups. Furthermore, the included studies were all retrospective design and focused only on patients who underwent surgery, which may have resulted in selection bias. Fourth, in sensitivity analysis for the super elderly group (≥80 years), the efficacy outcomes did not demonstrate consistent results compared to those of elderly versus non-elderly analysis. Due to the small number of studies and patients, as well as high heterogeneity among the literature, accurate evaluation was restricted, hence further detailed research is required for the super elderly patient population.17,19,38,52,55-59,61,62,75 Fifth, our study did not differentiate between different surgical methods (open surgery vs laparoscopic surgery), which could influence both efficacy and safety outcomes. Lastly, while our study evaluated OS and DFS, it lacks a comprehensive analysis of other relevant outcomes such as quality of life, postoperative functional status, and patient-reported outcomes. These factors are crucial for an assessment of the impact of surgical resection on elderly patients and further research should consider these aspects of efficacy outcome.

In conclusion, through careful and multidisciplinary patient selection for surgical candidates among elderly HCC patients, both OS and DFS would not be worse than those of the non-elderly group. Thus, it is imperative to actively consider surgical treatment in the selected elderly HCC patients. Future studies that adjust for differences in comorbidity and surgical method might be crucial to determine the respective weights of variables affecting efficacy and safety outcomes. Ultimately, deriving a scoring system or a guideline to assist the decision-making process for surgical treatment in elderly HCC patients is required in the clinical setting. In our meta-analysis results, factors that could be included in the scoring system may consist of age 65 and above, age 80 and above, geographic location (Asia vs non-Asia). Further research should consider incorporating additional factors such as sex, cancer stage, cancer size, CTP score, performance status, comorbidities, surgical method, and hospital size into the scoring system.76,77

ACKNOWLEDGEMENTS

This study was supported by the National Evidence-based Healthcare Collaborating Agency (NECA) (NA21-008; NA22-006) and the Soonchunhyang University Research Fund.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

AUTHOR CONTRIBUTIONS

Study concept and design: D.A.P., G.H.C. Data acquisition: D.A.P., S.R., J.P. Data analysis and interpretation: D.A.P., J.J.Y. Drafting of the manuscript: J.S.L., J.J.Y. Critical revision of the manuscript for important intellectual content: J.J.Y., D.A.P. Statistical analysis: J.J.Y., D.A.P. Approval of final manuscript: all authors.

SUPPLEMENTARY MATERIALS

Supplementary materials can be accessed at https://doi.org/10.5009/gnl230485.

Fig 1.

Figure 1.Selection flowchart of the studies included in meta-analysis.
Gut and Liver 2024; :

Fig 2.

Figure 2.Forest plots. (A) Overall mortality between elderly versus non-elderly. (B) Disease-free survival between elderly versus non-elderly. (C) Postoperative mortality between elderly versus non-elderly. (D) Post operative mortality between super elderly versus non-super elderly. (E) Postoperative complication between elderly versus non-elderly. (F) Postoperative complication between super elderly versus non-super elderly. SE, standard error; IV, inverse variance; CI, confidence interval; M-H, Mantel-Haenszel.
Gut and Liver 2024; :

Table 1 Demographics and Characteristics of Studies Included in the Systematic Review: Elderly versus Non-Elderly

Study (year)CountryInstitutionRecruitment
period
MatchingObjectiveAge
cutoff, yr
No. of
elderly
No. of
non-elderly
Baseline liver function, %Tumor size, mm
Elderly
Child A/B
Non-elderly
Child A/B
ElderlyNon-elderly
Fujio (2022)12JapanSingle2012–2016NRHR for HCC75223995/587/1353.652
Pu (2022)15ChinaMulticenter2007–2019PSMR0 HR for HCC7014014094/694/6NANA
Harada (2021)11JapanSingle2001–2012PSMHR for HCC7023423497/395/53031
Liu (2021)16TaiwanRegistry2007–2017NRHR for HCC7596908NANA41.5NA
Tan (2021)17SingaporeSingle2000–2018NRHR for HCC7027876494/695/54538
Chen (2020)13ChinaMulticenter2006–2016NRHR for HCC659273891/989/11105108
Shin (2020)18KoreaSingle2012–2018NRHR for HCC7049184NANANANA
Shimada (2020)19JapanSingle2000–2017NRHR for HCC65363384NANA5761
Yasuda (2020)20JapanSingle2000–2013NRMajor HR for HCC702318100/0100/05478
Xing (2020)21ChinaMulticenter2003–2016NRHR for HCC702591,87596/490/10NANA
Famularo (2019)22ItalyMulticenter2005–2015PSMHR for HCC75929292/896/43541
Jiang (2019)23ChinaRegistry2004–2015NRHR for HCC659561,392NANANANA
Kaibori (2019)24JapanRegistry2000–2007NRHR for HCC752,02010,56792/890/1038NA
Okamura (2018)25JapanSingle2002–2014PSMHR for HCC75727299/199/1NANA
Chen (2018)26ChinaSingle2010–2016NRHR for HCC6525688691/982/18NA84
Goh (2018)27SingaporeSingle2007–2016PSMLMH for HCC704094NANA3025
Hsu (2018)28TaiwanSingle2003–2014NRHR for large HCC (>5 cm)707917892/889/118690
Wang (2018)29ChinaSingle2011–2016NRHR for HCC704897NANANANA
Yu (2018)30ChinaSingle2003–2013NRHR for HCC70235883/1791/94737
Santambrogio (2017)31ItalySingle1998–2015NRHR for HCC7553115100/0100/0NANA
Bauschke (2016)32GermaySingle1995–2014NRHR for HCC70638187/1377/23NANA
Cucchetti (2016)33ItalySingle1997–2013NRHR for HCC with LC70229690NANANANA
Harimoto (2016)34JapanSingle2004–2013NRHR for HCC7013915794/696/44040
Kim (2015)35KoreaSingle2006–2010NRHR for HCC7060219NANA4949
Kishida (2015)36JapanSingle2005–2010NRHR for HCC75228291/999/13530
Motoyama (2015)37JapanSingle1990–2013NRHR for HCC7511349995/594/63330
Nozawa (2015)38JapanSingle2000–2010NRHR for HCC7019223986/1485/15NA30
Sato (2015)39JapanSingle2000–2010NRHR for HCC753419574/2683/174954
Faber (2014)40GermanySingle2000–2010NRHR for HCC with LC706378NANA5050
Liu (2014)41TaiwanSingle2002–2013PSMHR for HCC7511811893/793/7NANA
Mori (2014)42JapanSingle2000–2012NRHR for HCC with PHT706413178/2271/294133
Ueno (2014)43JapanSingle2001–2010NRHR for HCC756618691/991/95040
Wang (2014)44ChinaSingle2007–2012NRHR for HBV related HCC652071,336NANANANA
Wang (2014)45ChinaSingle2007–2012Paired
matched
Major hepatectomy for HCC with LC705615286/1480/207589
Hirokawa (2013)46JapanSingle2000–2011NRHR for HCC7010012088/1282/183530
Ide (2013)47JapanSingle2000–2010NRHR for HCC756419289/1188/124949
Murillo (2013)48SpainSingle2000–2011NRHR for HCC702214NANA3847
Nishikawa (2013)49JapanSingle2004–2012NRHR for HCC759220698/296/44648
Taniai (2013)50JapanSingle1990–2010NRHR for HCC756335389/1175/24/1NANA
Lee (2012)51KoreaSingle2000–2010NRHR for HCC706190NANA4543
Nanashima (2011)52JapanSingle1994–2009NRHR for HCC706911993/789/11NANA
Portolani (2011)53ItalySingle1992–2009NRHR for HCC7017527692/893/74849
Mirici-Cappa (2010)54ItalyMulticenter1987–2004PSMHR for HCC70323293/782/133441
Tan (2021)17*SingaporeSingle2000–2018NRHR for HCC80501,04292/894/680NA
Sanyal (2020)55EnglandSingle2005–2015NRHR for HCC8019181NANANANA
Shimada (2020)19JapanSingle2000–2017NRHR for HCC8049757NANA64NA
Inoue (2019)56JapanSingle2001–2017PSMHR for HCC8045485100/093/74132
Lee (2019)57TaiwanSingle1986–2015NRHR for HCC80773,30996/496/45942
Wu (2019)58TaiwanSingle1992–2016NRHR for HCC85311,85887/10/387/11/25665
Chen (2018)26ChinaSingle2010–2016NRHR for HCC80321,11094/684/1669NA
Hamaoka (2017)59JapanSingle2004–2013NRHR for HCC806056593/793/73327
Nozawa (2015)38JapanSingle2000–2010NRHR for HCC802041195/585/1541NA
Katsuta (2014)60§JapanSingle2000–2012NRHR for HCC802945783/1791/9NANA
Tsujita (2012)61JapanMulticenter1995–2008NRHR for HCC8023385NANANANA
Yamada (2012)62JapanMulticenter1992–2009NRHR for HCC801126782/1892/85248
Nanashima (2011)52JapanSingle1994–2009NRHR for HCC8012167100/090/10NANA

NR, not reported; PSM, propensity score matching; HR, hepatic resection; HCC, hepatocellular carcinoma; LC, liver cirrhosis; LMH, laparoscopic minor hepatectomy; PHT, portal hypertension; HBV, hepatitis B virus; NA, not applicable.

Definition of elderly: *<70/70–79/≥80 yr; <65/65–79/≥80; <70/70–80/≥81 yr; §<50/50–79/≥80; <50/50–69/70–79/≥80 yr.


Table 2 Meta-Analysis on Overall Survival: Elderly versus Non-Elderly

VariableUnivariate analysisMultivariate analysis
No. of studiesRandom, IV HR (95% CI)I2, %No. of studiesRandom, IV HR (95% CI)I2, %
Overall mortality321.18 (1.09–1.27)6741.26 (0.92–1.74)71
Using dataNA
Calculated data231.13 (1.04–1.22)52NA
Reported data91.26 (1.07–1.49)79NA
Age cutoff
65–70 yr181.09 (1.00–1.19)6611.08 (0.49–2.36)NA
75 yr141.29 (1.17–1.42)2321.39 (0.69–2.81)89
Publication year
2016–2022201.19 (1.08–1.31)7041.26 (0.92–1.74)71
2010–2015131.19 (1.02–1.40)610--
Country
Asia261.15 (1.07–1.24)6521.23 (0.90–1.69)0
Non-Asia61.46 (0.96–2.20)7721.39 (0.69–2.81)89
MINORS score
Over median value (20)151.32 (1.15–1.50)7021.39 (0.69–2.81)89
Under median value (20)171.10 (0.99–1.22)6721.23 (0.90–1.69)0

IV HR, inverse variance hazard ratio; CI, confidence interval; NA, not applicable; MINORS, methodological index for non-randomized studies.


Table 3 Meta-Analysis on Disease-Free Survival: Elderly versus Non-Elderly

VariableUnivariate analysis
No. of studiesRandom, IV HR (95% CI)I2, %
Overall estimate211.03 (0.99–1.08)0
Using data
Calculated data151.04 (0.96–1.13)17
Reported data61.03 (0.97–1.10)0
Age cutoff
65–70 yr101.05 (0.97–1.14)0
75 yr111.02 (0.96–1.08)0
Publication year
2016–2022131.04 (0.99–1.09)0
2010–201581.17 (0.92–1.49)34
Country
Asia181.02 (0.98–1.07)0
Non-Asia31.43 (1.02–2.01)0
MINORS score
Over median value (20)101.06 (0.91–1.24)33
Under median value (20)111.04 (0.99–1.10)0

IV HR, inverse variance hazard ratio; CI, confidence interval; MINORS, methodological index for non-randomized studies.


Table 4 Postoperative Mortality: Elderly versus Non-Elderly, Super Elderly versus Non-Super Elderly

Outcome variableNo. of
studies
ElderlyNon-elderlyRandom, M-H
pooled OR
95% CII2, %
No. of participantsEventsNo. of participantsEvents
Elderly vs non-elderly
Overall mortality rate141,8137344,5252,0571.070.87–1.3151
30-Day mortality rate101,740245,921582.131.28–3.540
90-Day mortality rate131,738475,8411151.651.09–2.498
In-hospital mortality rate101,055313,175471.781.03–3.0914
Hepatic failure-related mortality rate111,463282,976451.280.76–2.160
Super elderly vs non-super elderly
Overall mortality rate4137392,3049290.910.33–2.5075
30-Day mortality rate628766,954922.270.99–5.180
90-Day mortality rate414933,828552.050.76–5.570
In-hospital mortality rate514364,5481022.511.16–5.450
Hepatic failure-related mortality rate0----

M-H, Mantel-Haenszel; OR, odds ratio; CI, confidence interval.


Table 5 Postoperative Complications: Elderly versus Non-Elderly, Super Elderly versus Non-Super Elderly

Outcome variableNo. of
studies
ElderlyNon-elderlyRandom, M-H
pooled OR
95% CII2, %
No. of participantsEventsNo. of participantsEvents
Elderly vs non-elderly
Overall postoperative complications262,9431,1848,6292,7621.441.22–1.6951
Major postoperative complications242,4764118,3601,0411.301.11–1.5326
Postoperative hepatic failure131,154333,9141001.200.79–1.820
Super elderly vs non-super elderly
Overall postoperative complications93591719,4572,9402.021.35–3.0265
Major postoperative complications7197283,5163281.250.66–2.3947
Postoperative hepatic failure819755,147832.250.96–5.270

M-H, Mantel-Haenszel; OR, odds ratio; CI, confidence interval.


References

  1. Rumgay H, Arnold M, Ferlay J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 2022;77:1598-1606.
    Pubmed KoreaMed CrossRef
  2. Zhang CH, Cheng Y, Zhang S, Fan J, Gao Q. Changing epidemiology of hepatocellular carcinoma in Asia. Liver Int 2022;42:2029-2041.
    Pubmed CrossRef
  3. Nishikawa H, Kimura T, Kita R, Osaki Y. Treatment for hepatocellular carcinoma in elderly patients: a literature review. J Cancer 2013;4:635-643.
    Pubmed KoreaMed CrossRef
  4. Jang W, Lee HW, Lee JS, et al. Clinical characteristics and prognosis of Korean patients with hepatocellular carcinoma with respect to etiology. J Liver Cancer 2022;22:158-166.
    Pubmed KoreaMed CrossRef
  5. Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea. 2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. J Liver Cancer 2023;23:1-120.
    Pubmed KoreaMed CrossRef
  6. Shin SW, Ahn KS, Kim SW, Kim TS, Kim YH, Kang KJ. Liver resection versus local ablation therapies for hepatocellular carcinoma within the Milan criteria: a systematic review and meta-analysis. Ann Surg 2021;273:656-666.
    Pubmed CrossRef
  7. Lee HA, Lee YS, Kim BK, et al. Change in the recurrence pattern and predictors over time after complete cure of hepatocellular carcinoma. Gut Liver 2021;15:420-429.
    Pubmed KoreaMed CrossRef
  8. Devalapalli AP, Kashiwagi DT. Perioperative care of geriatric patients. Hosp Pract (1995) 2020;48(sup1):26-36.
    Pubmed CrossRef
  9. Jang JY, Jung J, Lee D, et al. Stereotactic body radiation therapy for elderly patients with small hepatocellular carcinoma: a retrospective observational study. J Liver Cancer 2022;22:136-145.
    Pubmed KoreaMed CrossRef
  10. Jo SJ, Rhu J, Kim JM, Choi GS, Joh JW. Indications for open hepatectomy in the era of laparoscopic liver resection: a high volume single institutional study. J Liver Cancer 2022;22:146-157.
    Pubmed KoreaMed CrossRef
  11. Harada M, Aramaki O, Midorikawa Y, et al. Impact of patient age on outcome after resection for hepatocellular carcinoma. Biosci Trends 2021;15:33-40.
    Pubmed CrossRef
  12. Fujio A, Usuda M, Hara Y, et al. Usefulness of preoperative controlling nutritional status in predicting prolonged hospitalization and incidence of postoperative delirium for elderly hepatectomy with hepatocellular carcinoma. Tohoku J Exp Med 2022;256:43-52.
    Pubmed CrossRef
  13. Chen ZL, Zhang CW, Liang L, et al. Major hepatectomy in elderly patients with large hepatocellular carcinoma: a multicenter retrospective observational study. Cancer Manag Res 2020;12:5607-5618.
    Pubmed KoreaMed CrossRef
  14. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg 2003;73:712-716.
    Pubmed CrossRef
  15. Pu JL, Chen Z, Yao LQ, et al. Long-term oncological prognosis after curative-intent liver resection for hepatocellular carcinoma in the young versus the elderly: multicentre propensity score-matching study. BJS Open 2022;6:zrab145.
    Pubmed KoreaMed CrossRef
  16. Liu YW, Yong CC, Lin CC, et al. Liver resection in elderly patients with hepatocellular carcinoma: age does matter. Updates Surg 2021;73:1371-1380.
    Pubmed CrossRef
  17. Tan LL, Chew VT, Syn N, et al. Effect of age on the short- and long-term outcomes of patients undergoing curative liver resection for HCC. Eur J Surg Oncol 2022;48:1339-1347.
    Pubmed CrossRef
  18. Shin IS, Kim DG, Cha SW, et al. Hepatocellular carcinoma in old age: are there any benefits of liver resection in old age?. Ann Surg Treat Res 2020;99:65-71.
    Pubmed KoreaMed CrossRef
  19. Shimada S, Kamiyama T, Orimo T, et al. Prognoses, outcomes, and clinicopathological characteristics of very elderly patients with hepatocellular carcinoma who underwent hepatectomy. World J Surg Oncol 2020;18:122.
    Pubmed KoreaMed CrossRef
  20. Yasuda S, Nomi T, Hokuto D, Yoshikawa T, Matsuo Y, Sho M. Liver regeneration after major liver resection for hepatocellular carcinoma in the elderly. J Invest Surg 2020;33:332-338.
    Pubmed CrossRef
  21. Xing H, Liang L, Wang H, et al. Multicenter analysis of long-term oncologic outcomes of hepatectomy for elderly patients with hepatocellular carcinoma. HPB (Oxford) 2020;22:1314-1323.
    Pubmed CrossRef
  22. Famularo S, Di Sandro S, Giani A, et al. The impact of age and ageing on hepatocarcinoma surgery: short- and long-term outcomes in a multicentre propensity-matched cohort. Liver Int 2019;39:894-904.
    Pubmed CrossRef
  23. Jiang YQ, Wang ZX, Deng YN, Yang Y, Wang GY, Chen GH. Efficacy of hepatic resection vs. radiofrequency ablation for patients with very-early-stage or early-stage hepatocellular carcinoma: a population-based study with stratification by age and tumor size. Front Oncol 2019;9:113.
    Pubmed KoreaMed CrossRef
  24. Kaibori M, Yoshii K, Yokota I, et al. Impact of advanced age on survival in patients undergoing resection of hepatocellular carcinoma: report of a Japanese nationwide survey. Ann Surg 2019;269:692-699.
    Pubmed CrossRef
  25. Okamura Y, Sugiura T, Ito T, Yamamoto Y, Ashida R, Uesaka K. The short- and long-term outcomes in elderly patients with hepatocellular carcinoma after curative surgery: a case-controlled study with propensity score matching. Eur Surg Res 2018;59:380-390.
    Pubmed CrossRef
  26. Chen Y, Wang J, Wang W, Zhou B, Yang N, Yang G. Feasibility of hepatectomy in elderly patients with hepatocellular carcinoma. Int J Clin Exp Med 2018;11:7038-7046.
  27. Goh BK, Chua D, Syn N, et al. Perioperative outcomes of laparoscopic minor hepatectomy for hepatocellular carcinoma in the elderly. World J Surg 2018;42:4063-4069.
    Pubmed CrossRef
  28. Hsu KF, Yu JC, Yang CW, et al. Long-term outcomes in elderly patients with resectable large hepatocellular carcinoma undergoing hepatectomy. Surg Oncol 2018;27:595-601.
    Pubmed CrossRef
  29. Wang W, Huang Z, Guo B, Liu S, Xiao W, Liang J. Short- and long-term outcomes of laparoscopic hepatectomy in elderly patients with hepatocellular carcinoma. J BUON 2018;23:971-978.
  30. Yu X, Yan YC, Chen G, Yu H. The efficacy and safety of totally laparoscopic hepatectomy for non-cirrhotic hepatocellular carcinoma in the elderly. BMC Surg 2018;18:118.
    Pubmed KoreaMed CrossRef
  31. Santambrogio R, Barabino M, Scifo G, Costa M, Giovenzana M, Opocher E. Effect of age (over 75 years) on postoperative complications and survival in patients undergoing hepatic resection for hepatocellular carcinoma. J Gastrointest Surg 2017;21:657-665.
    Pubmed CrossRef
  32. Bauschke A, Altendorf-Hofmann A, Mothes H, Rauchfuß F, Settmacher U. Partial liver resection results in a significantly better long-term survival than locally ablative procedures even in elderly patients. J Cancer Res Clin Oncol 2016;142:1099-1108.
    Pubmed CrossRef
  33. Cucchetti A, Sposito C, Pinna AD, et al. Effect of age on survival in patients undergoing resection of hepatocellular carcinoma. Br J Surg 2016;103:e93-e99.
    Pubmed CrossRef
  34. Harimoto N, Yoshizumi T, Shimokawa M, et al. Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma. Hepatol Res 2016;46:1247-1255.
    Pubmed CrossRef
  35. Kim JM, Cho BI, Kwon CH, et al. Hepatectomy is a reasonable option for older patients with hepatocellular carcinoma. Am J Surg 2015;209:391-397.
    Pubmed CrossRef
  36. Kishida N, Hibi T, Itano O, et al. Validation of hepatectomy for elderly patients with hepatocellular carcinoma. Ann Surg Oncol 2015;22:3094-3101.
    Pubmed CrossRef
  37. Motoyama H, Kobayashi A, Yokoyama T, et al. Impact of advanced age on the short- and long-term outcomes in patients undergoing hepatectomy for hepatocellular carcinoma: a single-center analysis over a 20-year period. Am J Surg 2015;209:733-741.
    Pubmed CrossRef
  38. Nozawa A, Kubo S, Takemura S, et al. Hepatic resection for hepatocellular carcinoma in super-elderly patients aged 80 years and older in the first decade of the 21st century. Surg Today 2015;45:851-857.
    Pubmed CrossRef
  39. Sato S, Tanaka K, Nojiri K, et al. Hepatic resection for hepatocellular carcinoma in the elderly: selecting hepatectomy procedures based on patient age. Anticancer Res 2015;35:6855-6860.
    Pubmed
  40. Faber W, Stockmann M, Schirmer C, et al. Significant impact of patient age on outcome after liver resection for HCC in cirrhosis. Eur J Surg Oncol 2014;40:208-213.
    Pubmed CrossRef
  41. Liu PH, Hsu CY, Lee YH, et al. Uncompromised treatment efficacy in elderly patients with hepatocellular carcinoma: a propensity score analysis. Medicine (Baltimore) 2014;93:e264.
    Pubmed KoreaMed CrossRef
  42. Mori S, Kita J, Shimizu T, Kato M, Shimoda M, Kubota K. Outcome of hepatectomy for hepatocellular carcinoma in elderly patients with portal hypertension. Int Surg 2014;99:153-160.
    Pubmed KoreaMed CrossRef
  43. Ueno M, Hayami S, Tani M, Kawai M, Hirono S, Yamaue H. Recent trends in hepatectomy for elderly patients with hepatocellular carcinoma. Surg Today 2014;44:1651-1659.
    Pubmed CrossRef
  44. Wang HQ, Yang J, Yan LN, Zhang XW, Yang JY. Liver resection in hepatitis B related-hepatocellular carcinoma: clinical outcomes and safety in elderly patients. World J Gastroenterol 2014;20:6620-6625.
    Pubmed KoreaMed CrossRef
  45. Wang WL, Zhu Y, Cheng JW, et al. Major hepatectomy is safe for hepatocellular carcinoma in elderly patients with cirrhosis. Eur J Gastroenterol Hepatol 2014;26:444-451.
    Pubmed CrossRef
  46. Hirokawa F, Hayashi M, Miyamoto Y, et al. Surgical outcomes and clinical characteristics of elderly patients undergoing curative hepatectomy for hepatocellular carcinoma. J Gastrointest Surg 2013;17:1929-1937.
    Pubmed CrossRef
  47. Ide T, Miyoshi A, Kitahara K, Noshiro H. Prediction of postoperative complications in elderly patients with hepatocellular carcinoma. J Surg Res 2013;185:614-619.
    Pubmed CrossRef
  48. Murillo A, Artigas V, González JA, et al. Hepatic resection in hepatocarcinoma: a comparative study between patients under and over 70 years-old. Cir Esp 2013;91:224-230.
    Pubmed CrossRef
  49. Nishikawa H, Arimoto A, Wakasa T, Kita R, Kimura T, Osaki Y. Surgical resection for hepatocellular carcinoma: clinical outcomes and safety in elderly patients. Eur J Gastroenterol Hepatol 2013;25:912-919.
    Pubmed CrossRef
  50. Taniai N, Yoshida H, Yoshioka M, Kawano Y, Uchida E. Surgical outcomes and prognostic factors in elderly patients (75 years or older) with hepatocellular carcinoma who underwent hepatectomy. J Nippon Med Sch 2013;80:426-432.
    Pubmed CrossRef
  51. Lee CR, Lim JH, Kim SH, et al. A comparative analysis of hepatocellular carcinoma after hepatic resection in young versus elderly patients. J Gastrointest Surg 2012;16:1736-1743.
    Pubmed CrossRef
  52. Nanashima A, Abo T, Nonaka T, et al. Prognosis of patients with hepatocellular carcinoma after hepatic resection: are elderly patients suitable for surgery?. J Surg Oncol 2011;104:284-291.
    Pubmed CrossRef
  53. Portolani N, Baiocchi GL, Coniglio A, et al. Limited liver resection: a good indication for the treatment of hepatocellular carcinoma in elderly patients. Jpn J Clin Oncol 2011;41:1358-1365.
    Pubmed CrossRef
  54. Mirici-Cappa F, Gramenzi A, Santi V, et al. Treatments for hepatocellular carcinoma in elderly patients are as effective as in younger patients: a 20-year multicentre experience. Gut 2010;59:387-396.
    Pubmed CrossRef
  55. Sanyal S, Kron P, Wylie N, Hildalgo E, Toogood GJ, Lodge P. Outcomes of liver resection for hepatocellular carcinoma in octogenarians. HPB (Oxford) 2020;22:1324-1329.
    Pubmed CrossRef
  56. Inoue Y, Tanaka R, Fujii K, et al. Surgical outcome and hepatic regeneration after hepatic resection for hepatocellular carcinoma in elderly patients. Dig Surg 2019;36:289-301.
    Pubmed CrossRef
  57. Lee CW, Chan KM, Tsai HI, et al. Hepatic resection for hepatocellular carcinoma in the octogenarian: is it justified?. Aging (Albany NY) 2019;11:1537-1550.
    Pubmed KoreaMed CrossRef
  58. Wu FH, Shen CH, Luo SC, et al. Liver resection for hepatocellular carcinoma in oldest old patients. World J Surg Oncol 2019;17:1.
    Pubmed KoreaMed CrossRef
  59. Hamaoka M, Kobayashi T, Ishiyama K, et al. Evaluation of the risk factors and prognostic factors of hepatectomy for hepatocellular carcinoma in patients aged 80 years or more. J Hepatobiliary Pancreat Sci 2017;24:58-64.
    Pubmed CrossRef
  60. Katsuta E, Tanaka S, Mogushi K, et al. Age-related clinicopathologic and molecular features of patients receiving curative hepatectomy for hepatocellular carcinoma. Am J Surg 2014;208:450-456.
    Pubmed CrossRef
  61. Tsujita E, Utsunomiya T, Yamashita Y, et al. Outcome of hepatectomy in hepatocellular carcinoma patients aged 80 years and older. Hepatogastroenterology 2012;59:1553-1555.
    Pubmed CrossRef
  62. Yamada S, Shimada M, Miyake H, et al. Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma. Hepatol Res 2012;42:454-458.
    Pubmed CrossRef
  63. Lurje G, Bednarsch J, Czigany Z, et al. Prognostic factors of disease-free and overall survival in patients with hepatocellular carcinoma undergoing partial hepatectomy in curative intent. Langenbecks Arch Surg 2018;403:851-861.
    Pubmed CrossRef
  64. Lee HA, Lee S, Lee HL, et al. The efficacy of treatment for hepatocellular carcinoma in elderly patients. J Liver Cancer 2023;23:362-376.
    Pubmed KoreaMed CrossRef
  65. Nishikawa H, Kimura T, Kita R, Osaki Y. Radiofrequency ablation for hepatocellular carcinoma. Int J Hyperthermia 2013;29:558-568.
    Pubmed CrossRef
  66. Gunasekaran G, Bekki Y, Lourdusamy V, Schwartz M. Surgical treatments of hepatobiliary cancers. Hepatology 2021;73 Suppl 1:128-136.
    Pubmed CrossRef
  67. Younossi ZM, Wong G, Anstee QM, Henry L. The global burden of liver disease. Clin Gastroenterol Hepatol 2023;21:1978-1991.
    Pubmed CrossRef
  68. Lee VH, Seong J, Yoon SM, et al. Contrasting some differences in managing advanced unresectable hepatocellular carcinoma between the east and the west. Clin Oncol (R Coll Radiol) 2019;31:560-569.
    Pubmed CrossRef
  69. Choo SP, Tan WL, Goh BK, Tai WM, Zhu AX. Comparison of hepatocellular carcinoma in Eastern versus Western populations. Cancer 2016;122:3430-3446.
    Pubmed CrossRef
  70. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 2021;18:223-238.
    Pubmed KoreaMed CrossRef
  71. Younossi ZM, Otgonsuren M, Henry L, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015;62:1723-1730.
    Pubmed CrossRef
  72. Lin BZ, Lin TJ, Lin CL, et al. Differentiation of clinical patterns and survival outcomes of hepatocellular carcinoma on hepatitis B and nonalcoholic fatty liver disease. J Chin Med Assoc 2021;84:606-613.
    Pubmed CrossRef
  73. Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7:6.
    Pubmed CrossRef
  74. Elfrink AK, Kok NF, den Dulk M, et al. Short-term postoperative outcomes after liver resection in the elderly patient: a nationwide population-based study. HPB (Oxford) 2021;23:1506-1517.
    Pubmed CrossRef
  75. Chen Y, Yu L, Quan C. Laparoscopic versus open hepatectomy for elderly patients with hepatocellular carcinoma. J BUON 2020;25:1404-1412.
    Pubmed
  76. Teng PC, Huang DQ, Lin TY, Noureddin M, Yang JD. Diabetes and risk of hepatocellular carcinoma in cirrhosis patients with nonalcoholic fatty liver disease. Gut Liver 2023;17:24-33.
    Pubmed KoreaMed CrossRef
  77. Shin SK, Yim HJ, Kim JH, et al. Partial virological response after 2 years of entecavir therapy increases the risk of hepatocellular carcinoma in patients with hepatitis B virus-associated cirrhosis. Gut Liver 2021;15:430-439.
    Pubmed KoreaMed CrossRef
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Vol.18 No.3
May, 2024

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