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  • 1. Aims and Scope

    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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    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

    Deputy Editor

    Deputy Editor
    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
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Letter to the Editor

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Endoscopic Mucosal Healing as a Treatment Target in Ulcerative Colitis: Does It Have the Same Role in Asian Patients?

Suk-Kyun Yang , Sang Hyoung Park , and Byong Duk Ye

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to:Suk-Kyun Yang
ORCID https://orcid.org/0000-0003-2772-2575
E-mail sky@amc.seoul.kr

Received: May 22, 2021; Revised: May 31, 2021; Accepted: June 14, 2021

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 and Liver 2021; 15(6): 942-943

Published online November 15, 2021 https://doi.org/10.5009/gnl210230

Copyright © Gut and Liver.

To the Editor:

We read with great interest the article by Shin et al.,1 which compared the outcomes of 131 ulcerative colitis (UC) patients in clinical remission according to the endoscopic mucosal healing status and the distribution pattern of mucosal inflammation. The authors reported that poor outcome-free survival was significantly higher in patients with endoscopic remission or only nonrectal inflammation than in those with rectal inflammation (p=0.003). Poor outcome-free survival in patients with only nonrectal inflammation was comparable to that in patients with endoscopic remission (p=0.647). In multivariable Cox regression analysis, rectal inflammation (hazard ratio, 5.76; p=0.027) was the only predictor of poor outcome. Therefore, the authors suggested that treatment escalation may be selectively required in consideration of the distribution pattern of residual mucosal inflammation in UC patients in clinical remission.

Mucosal healing has emerged as a key prognostic factor in the management of UC.2 Previous studies have demonstrated that mucosal healing in UC is associated with prolonged clinical remission and lower risks of hospitalization, colectomy, and colorectal cancer.3-6 However, these studies evaluated only the grade of residual mucosal inflammation and did not consider the distribution pattern of residual mucosal inflammation. Moreover, most of these studies were conducted in Caucasian populations3-6 and only a few small-scale studies were conducted in Asian populations.7,8 The study by Shin et al.1 was the first to evaluate the distribution pattern of residual mucosal inflammation in UC patients in clinical remission and to compare disease outcomes according to the distribution patterns. In addition, this was the largest study to evaluate the prognostic role of mucosal healing in Asian patients with UC. Their results may provide a basis for minimizing unnecessary treatment escalation that potentially increases the risk of adverse effects.

However, before applying these results to clinical practice, we would like to address some concerns. First, although the definition of poor outcome in this study was step-up therapy, hospitalization, and colectomy, none of the 131 patients included in the study was hospitalized or underwent colectomy during the median follow-up of approximately 5 years. Consequently, outcome was assessed by the presence of step-up therapy alone. This is in contrast with previous Western studies, in which outcome was assessed by clinical relapse, hospitalization, and colectomy.3-6 Physicians may decide to adopt medication escalation earlier and more frequently in patients with residual rectal inflammation than in those with only nonrectal inflammation, even when the symptom status is similar between the two groups, because rectal inflammation is generally considered to evoke symptoms more frequently than nonrectal inflammation. In this regard, medication escalation may be a less objective outcome parameter than the others. Second, the finding of no hospitalization or colectomy during the median follow-up of approximately 5 years may indicate that the prognosis of Korean UC patients is better than that of Western UC patients. The genotypes and phenotypes of UC in Asia, where the incidence and prevalence rates of UC are still low but rapidly increasing,9-11 differ from those in Western countries.12 Notably, compared with the colectomy rate in Western UC patients, the rate in Asian UC patients is very low.13,14 Therefore, it is uncertain whether the result of this study showing the same risk of step-up therapy between patients with residual nonrectal inflammation and those with endoscopic remission can be generalized to Western UC patients who have a worse prognosis than Asian patients. Third, even if future studies confirm that nonrectal residual inflammation in UC patients in clinical remission is not associated with poor outcomes in terms of hospitalization and colectomy, this inflammation may still be associated with an increased risk of colorectal cancer in the long term.15

Therefore, further studies with longer follow-up durations and larger sample sizes are needed to assess the risks and benefits of treatment escalation for nonrectal residual inflammation in UC patients in clinical remission. We expect that the prospective observational cohort of Moderate-to-Severe Ulcerative Colitis in Korea (MOSAIK) will provide answers to this question.16 Although final conclusions still need to be made, the results of this study may still be useful for consulting patients and making treatment decisions. We can safely withhold treatment escalation in asymptomatic UC patients with residual nonrectal inflammation if they have a high risk of adverse events or are reluctant to undergo step-up therapy.


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

  1. Shin J, Kong SM, Kim TJ, et al. Clinical significance of residual nonrectal inflammation in ulcerative colitis patients in clinical remission. Gut Liver 2021;15:401-409.
    Pubmed KoreaMed CrossRef
  2. Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut 2012;61:1619-1635.
    Pubmed CrossRef
  3. Reinink AR, Lee TC, Higgins PD. Endoscopic mucosal healing predicts favorable clinical outcomes in inflammatory bowel disease: a meta-analysis. Inflamm Bowel Dis 2016;22:1859-1869.
    Pubmed CrossRef
  4. Frøslie KF, Jahnsen J, Moum BA, Vatn MH; IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007;133:412-422.
    Pubmed CrossRef
  5. Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 2011;141:1194-1201.
    Pubmed CrossRef
  6. Ponte A, Pinho R, Fernandes S, et al. Impact of histological and endoscopic remissions on clinical recurrence and recurrence-free time in ulcerative colitis. Inflamm Bowel Dis 2017;23:2238-2244.
    Pubmed CrossRef
  7. Saigusa K, Matsuoka K, Sugimoto S, et al. Ulcerative colitis endoscopic index of severity is associated with long-term prognosis in ulcerative colitis patients treated with infliximab. Dig Endosc 2016;28:665-670.
    Pubmed CrossRef
  8. Yokoyama K, Kobayashi K, Mukae M, Sada M, Koizumi W. Clinical study of the relation between mucosal healing and long-term outcomes in ulcerative colitis. Gastroenterol Res Pract 2013;2013:192794.
    Pubmed KoreaMed CrossRef
  9. Park SH, Kim YJ, Rhee KH, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong district of Seoul, Korea in 1986-2015. J Crohns Colitis 2019;13:1410-1417.
    Pubmed CrossRef
  10. Yen HH, Weng MT, Tung CC, et al. Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide populationbased study. Intest Res 2019;17:54-62.
    Pubmed KoreaMed CrossRef
  11. Ng SC, Leung WK, Shi HY, et al. Epidemiology of inflammatory bowel disease from 1981 to 2014: results from a territory-wide population-based registry in Hong Kong. Inflamm Bowel Dis 2016;22:1954-1960.
    Pubmed CrossRef
  12. Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 2008;103:3167-3182.
    Pubmed CrossRef
  13. Cha JM, Park SH, Rhee KH, et al. Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Gut 2020;69:1432-1440.
    Pubmed CrossRef
  14. Aniwan S, Limsrivilai J, Pongprasobchai S, et al. Temporal trend in the natural history of ulcerative colitis in a country with a low incidence of ulcerative colitis from 2000 through 2018. Intest Res 2021;19:186-193.
    Pubmed KoreaMed CrossRef
  15. Gupta RB, Harpaz N, Itzkowitz S, et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007;133:1099-1105.
    Pubmed KoreaMed CrossRef
  16. Lee CK, Lee KM, Park DI, et al. A new opportunity for innovative inflammatory bowel disease research: the Moderate-to-Severe Ulcerative Colitis in Korea (MOSAIK) cohort study. Intest Res 2019;17:1-5.
    Pubmed KoreaMed CrossRef

Article

Letter to the Editor

Gut and Liver 2021; 15(6): 942-943

Published online November 15, 2021 https://doi.org/10.5009/gnl210230

Copyright © Gut and Liver.

Endoscopic Mucosal Healing as a Treatment Target in Ulcerative Colitis: Does It Have the Same Role in Asian Patients?

Suk-Kyun Yang , Sang Hyoung Park , and Byong Duk Ye

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to:Suk-Kyun Yang
ORCID https://orcid.org/0000-0003-2772-2575
E-mail sky@amc.seoul.kr

Received: May 22, 2021; Revised: May 31, 2021; Accepted: June 14, 2021

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.

Body

To the Editor:

We read with great interest the article by Shin et al.,1 which compared the outcomes of 131 ulcerative colitis (UC) patients in clinical remission according to the endoscopic mucosal healing status and the distribution pattern of mucosal inflammation. The authors reported that poor outcome-free survival was significantly higher in patients with endoscopic remission or only nonrectal inflammation than in those with rectal inflammation (p=0.003). Poor outcome-free survival in patients with only nonrectal inflammation was comparable to that in patients with endoscopic remission (p=0.647). In multivariable Cox regression analysis, rectal inflammation (hazard ratio, 5.76; p=0.027) was the only predictor of poor outcome. Therefore, the authors suggested that treatment escalation may be selectively required in consideration of the distribution pattern of residual mucosal inflammation in UC patients in clinical remission.

Mucosal healing has emerged as a key prognostic factor in the management of UC.2 Previous studies have demonstrated that mucosal healing in UC is associated with prolonged clinical remission and lower risks of hospitalization, colectomy, and colorectal cancer.3-6 However, these studies evaluated only the grade of residual mucosal inflammation and did not consider the distribution pattern of residual mucosal inflammation. Moreover, most of these studies were conducted in Caucasian populations3-6 and only a few small-scale studies were conducted in Asian populations.7,8 The study by Shin et al.1 was the first to evaluate the distribution pattern of residual mucosal inflammation in UC patients in clinical remission and to compare disease outcomes according to the distribution patterns. In addition, this was the largest study to evaluate the prognostic role of mucosal healing in Asian patients with UC. Their results may provide a basis for minimizing unnecessary treatment escalation that potentially increases the risk of adverse effects.

However, before applying these results to clinical practice, we would like to address some concerns. First, although the definition of poor outcome in this study was step-up therapy, hospitalization, and colectomy, none of the 131 patients included in the study was hospitalized or underwent colectomy during the median follow-up of approximately 5 years. Consequently, outcome was assessed by the presence of step-up therapy alone. This is in contrast with previous Western studies, in which outcome was assessed by clinical relapse, hospitalization, and colectomy.3-6 Physicians may decide to adopt medication escalation earlier and more frequently in patients with residual rectal inflammation than in those with only nonrectal inflammation, even when the symptom status is similar between the two groups, because rectal inflammation is generally considered to evoke symptoms more frequently than nonrectal inflammation. In this regard, medication escalation may be a less objective outcome parameter than the others. Second, the finding of no hospitalization or colectomy during the median follow-up of approximately 5 years may indicate that the prognosis of Korean UC patients is better than that of Western UC patients. The genotypes and phenotypes of UC in Asia, where the incidence and prevalence rates of UC are still low but rapidly increasing,9-11 differ from those in Western countries.12 Notably, compared with the colectomy rate in Western UC patients, the rate in Asian UC patients is very low.13,14 Therefore, it is uncertain whether the result of this study showing the same risk of step-up therapy between patients with residual nonrectal inflammation and those with endoscopic remission can be generalized to Western UC patients who have a worse prognosis than Asian patients. Third, even if future studies confirm that nonrectal residual inflammation in UC patients in clinical remission is not associated with poor outcomes in terms of hospitalization and colectomy, this inflammation may still be associated with an increased risk of colorectal cancer in the long term.15

Therefore, further studies with longer follow-up durations and larger sample sizes are needed to assess the risks and benefits of treatment escalation for nonrectal residual inflammation in UC patients in clinical remission. We expect that the prospective observational cohort of Moderate-to-Severe Ulcerative Colitis in Korea (MOSAIK) will provide answers to this question.16 Although final conclusions still need to be made, the results of this study may still be useful for consulting patients and making treatment decisions. We can safely withhold treatment escalation in asymptomatic UC patients with residual nonrectal inflammation if they have a high risk of adverse events or are reluctant to undergo step-up therapy.

CONFLICTS OF INTEREST


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

References

  1. Shin J, Kong SM, Kim TJ, et al. Clinical significance of residual nonrectal inflammation in ulcerative colitis patients in clinical remission. Gut Liver 2021;15:401-409.
    Pubmed KoreaMed CrossRef
  2. Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut 2012;61:1619-1635.
    Pubmed CrossRef
  3. Reinink AR, Lee TC, Higgins PD. Endoscopic mucosal healing predicts favorable clinical outcomes in inflammatory bowel disease: a meta-analysis. Inflamm Bowel Dis 2016;22:1859-1869.
    Pubmed CrossRef
  4. Frøslie KF, Jahnsen J, Moum BA, Vatn MH; IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007;133:412-422.
    Pubmed CrossRef
  5. Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology 2011;141:1194-1201.
    Pubmed CrossRef
  6. Ponte A, Pinho R, Fernandes S, et al. Impact of histological and endoscopic remissions on clinical recurrence and recurrence-free time in ulcerative colitis. Inflamm Bowel Dis 2017;23:2238-2244.
    Pubmed CrossRef
  7. Saigusa K, Matsuoka K, Sugimoto S, et al. Ulcerative colitis endoscopic index of severity is associated with long-term prognosis in ulcerative colitis patients treated with infliximab. Dig Endosc 2016;28:665-670.
    Pubmed CrossRef
  8. Yokoyama K, Kobayashi K, Mukae M, Sada M, Koizumi W. Clinical study of the relation between mucosal healing and long-term outcomes in ulcerative colitis. Gastroenterol Res Pract 2013;2013:192794.
    Pubmed KoreaMed CrossRef
  9. Park SH, Kim YJ, Rhee KH, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong district of Seoul, Korea in 1986-2015. J Crohns Colitis 2019;13:1410-1417.
    Pubmed CrossRef
  10. Yen HH, Weng MT, Tung CC, et al. Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide populationbased study. Intest Res 2019;17:54-62.
    Pubmed KoreaMed CrossRef
  11. Ng SC, Leung WK, Shi HY, et al. Epidemiology of inflammatory bowel disease from 1981 to 2014: results from a territory-wide population-based registry in Hong Kong. Inflamm Bowel Dis 2016;22:1954-1960.
    Pubmed CrossRef
  12. Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 2008;103:3167-3182.
    Pubmed CrossRef
  13. Cha JM, Park SH, Rhee KH, et al. Long-term prognosis of ulcerative colitis and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea. Gut 2020;69:1432-1440.
    Pubmed CrossRef
  14. Aniwan S, Limsrivilai J, Pongprasobchai S, et al. Temporal trend in the natural history of ulcerative colitis in a country with a low incidence of ulcerative colitis from 2000 through 2018. Intest Res 2021;19:186-193.
    Pubmed KoreaMed CrossRef
  15. Gupta RB, Harpaz N, Itzkowitz S, et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007;133:1099-1105.
    Pubmed KoreaMed CrossRef
  16. Lee CK, Lee KM, Park DI, et al. A new opportunity for innovative inflammatory bowel disease research: the Moderate-to-Severe Ulcerative Colitis in Korea (MOSAIK) cohort study. Intest Res 2019;17:1-5.
    Pubmed KoreaMed CrossRef
Gut and Liver

Vol.15 No.6
November, 2021

pISSN 1976-2283
eISSN 2005-1212

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