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

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    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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Real-Time Polymerase Chain Reaction: Feed Two Birds with One Seed?

Yoon Jin Choi

Center for Gastric Cancer, National Cancer Center, Goyang, Korea

Correspondence to: Yoon Jin Choi
ORCID https://orcid.org/0000-0002-1922-9388
E-mail erica0007@gmail.com

See “Real-Time Polymerase Chain Reaction for the Detection of Helicobacter pylori and Clarithromycin Resistance” by Jin Hee Noh, et al. on page 375, Vol. 17, No. 3, 2023

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 2023;17(3):345-346. https://doi.org/10.5009/gnl230158

Published online May 15, 2023, Published date May 15, 2023

Copyright © Gut and Liver.

After Barry Marshall proved Helicobacter pylori as a pathogen of gastritis and peptic ulcers, antibiotic therapy is the most effective treatment for H. pylori infection. However, due to the increase in the antibiotic resistant H. pylori strains, eradicating H. pylori has been more challenging.1

The accurate diagnosis of H. pylori infection and detection of resistant strains is essential for improving the rate of H. pylori eradication. Although culture and antibiotic susceptibility tests based on culture are considered as reference methods for diagnosing infection and evaluating drug resistance, respectively, culturing H. pylori is technically demanding; it requires microaerophilic atmosphere and prolonged incubation time.2 Culture-based method takes approximately 2 weeks to decide H. pylori-negative. There are different success rates for culture depending on the laboratories. On the contrary, molecular techniques which mostly use polymerase chain reaction (PCR) have advantages over the conventional culture; the increase of sensitivity in detection (over 95%) and simultaneous detection of H. pylori and its resistances to clarithromycin and levofloxacin in a short time (<4 hours).

In a recently published Korean study using dual priming oligonucleotide-based multiplex PCR, per protocol eradication rate for 7 days of tailored treatment with either bismuth quadruple therapy or standard triple therapy was 92.7% compared to 76.5% of the 7-day empirical standard triple therapy group.3 In terms of medical cost within Korea, the cost of tailored treatment was almost same as that of 14-day empirical standard triple therapy, and was not inferior in cost-effectiveness.4 However, while tailored treatment as a first-line based on clarithromycin resistance reported consistently a higher eradication rate than empirical triple therapy, it did not show superiority in treatment success in a rescue setting or compared to the bismuth quadruple therapy.5-7 In this context, the Korean College of Helicobacter and Upper Gastrointestinal Research recommends performing clarithromycin resistance test through PCR methods when selecting standard 7-day triple therapy as first-line treatment.8

Noh et al.9 showed real-time (RT)-PCR method (SeaSun Biomaterials) detection of H. pylori infection more efficiently 97.1% (68/70) compared to rapid urease test (82.9%, 58/70) using leftover specimens. RT-PCR also detected that 84.6% (11/13) of point mutations in 23S rRNA. The authors said RT-PCR-based assay is a simple and accurate method for detecting H. pylori and clarithromycin resistance using a small formalin-fixed or paraffin-embedded specimen. However, the failure to find point mutations in the two culture-proven resistant strains implies the RT-PCR method has limitations in detecting only specific mutations like dual priming oligonucleotide PCR.

In real practice, resistance or susceptibility tests are often required for patients who have failed the preceding eradication therapy, aside from the issue of the effectiveness of tailored therapy as a secondary treatment. The necessity of re-acquisition of gastric mucosa under endoscopy is the biggest hurdle to use resistant tests. Sensitive molecular methods using non-invasive specimens such as saliva can be a good alternative modality in the current circumstance where insurance coverage is the same as the indication for eradication.

For now, PCR cannot completely replace the rapid urease test and the conventional culture method. The development of more diverse methods for identifying H. pylori and resistance and vigorous research on their clinical usefulness are required.

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

  1. Thung I, Aramin H, Vavinskaya V, et al. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016;43:514-533.
    Pubmed KoreaMed CrossRef
  2. Wang YK, Kuo FC, Liu CJ, et al. Diagnosis of Helicobacter pylori infection: current options and developments. World J Gastroenterol 2015;21:11221-11235.
    Pubmed KoreaMed CrossRef
  3. Cho JH, Jeon SR, Kim HG, Jin SY, Park S. Cost-effectiveness of a tailored Helicobacter pylori eradication strategy based on the presence of a 23S ribosomal RNA point mutation that causes clarithromycin resistance in Korean patients. J Gastroenterol Hepatol 2019;34:700-706.
    Pubmed CrossRef
  4. Gweon TG, Kim JS, Kim BW. An economic modeling study of Helicobacter pylori eradication: comparison of dual priming oligonucleotide-based multiplex polymerase chain reaction and empirical treatment. Gut Liver 2018;12:648-654.
    Pubmed KoreaMed CrossRef
  5. Liou JM, Chen PY, Luo JC, et al. Efficacies of genotypic resistance-guided vs empirical therapy for refractory Helicobacter pylori infection. Gastroenterology 2018;155:1109-1119.
    Pubmed CrossRef
  6. Kwon YH, Kim N, Lee JY, et al. Comparison of the efficacy of culture-based tailored therapy for Helicobacter pylori eradication with that of the traditional second-line rescue therapy in Korean patients: a prospective single tertiary center study. Scand J Gastroenterol 2016;51:270-276.
    Pubmed CrossRef
  7. Choi YI, Chung JW, Park DK, et al. Tailored eradication vs empirical bismuth-containing quadruple therapy for first-line Helicobacter pylori eradication: a comparative, open trial. World J Gastroenterol 2019;25:6743-6751.
    Pubmed KoreaMed CrossRef
  8. Jung HK, Kang SJ, Lee YC, et al. Evidence-based guidelines for the treatment of Helicobacter pylori infection in Korea: 2020 revised edition. Korean J Helicobacter Up Gastrointest Res 2020;20:261-287.
    CrossRef
  9. Noh JH, Ahn JY, Choi J, et al. Real-time polymerase chain reaction for the detection of Helicobacter pylori and clarithromycin resistance. Gut Liver 2023;17:375-381.
    Pubmed CrossRef

Article

Editorial

Gut and Liver 2023; 17(3): 345-346

Published online May 15, 2023 https://doi.org/10.5009/gnl230158

Copyright © Gut and Liver.

Real-Time Polymerase Chain Reaction: Feed Two Birds with One Seed?

Yoon Jin Choi

Center for Gastric Cancer, National Cancer Center, Goyang, Korea

Correspondence to:Yoon Jin Choi
ORCID https://orcid.org/0000-0002-1922-9388
E-mail erica0007@gmail.com

See “Real-Time Polymerase Chain Reaction for the Detection of Helicobacter pylori and Clarithromycin Resistance” by Jin Hee Noh, et al. on page 375, Vol. 17, No. 3, 2023

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

After Barry Marshall proved Helicobacter pylori as a pathogen of gastritis and peptic ulcers, antibiotic therapy is the most effective treatment for H. pylori infection. However, due to the increase in the antibiotic resistant H. pylori strains, eradicating H. pylori has been more challenging.1

The accurate diagnosis of H. pylori infection and detection of resistant strains is essential for improving the rate of H. pylori eradication. Although culture and antibiotic susceptibility tests based on culture are considered as reference methods for diagnosing infection and evaluating drug resistance, respectively, culturing H. pylori is technically demanding; it requires microaerophilic atmosphere and prolonged incubation time.2 Culture-based method takes approximately 2 weeks to decide H. pylori-negative. There are different success rates for culture depending on the laboratories. On the contrary, molecular techniques which mostly use polymerase chain reaction (PCR) have advantages over the conventional culture; the increase of sensitivity in detection (over 95%) and simultaneous detection of H. pylori and its resistances to clarithromycin and levofloxacin in a short time (<4 hours).

In a recently published Korean study using dual priming oligonucleotide-based multiplex PCR, per protocol eradication rate for 7 days of tailored treatment with either bismuth quadruple therapy or standard triple therapy was 92.7% compared to 76.5% of the 7-day empirical standard triple therapy group.3 In terms of medical cost within Korea, the cost of tailored treatment was almost same as that of 14-day empirical standard triple therapy, and was not inferior in cost-effectiveness.4 However, while tailored treatment as a first-line based on clarithromycin resistance reported consistently a higher eradication rate than empirical triple therapy, it did not show superiority in treatment success in a rescue setting or compared to the bismuth quadruple therapy.5-7 In this context, the Korean College of Helicobacter and Upper Gastrointestinal Research recommends performing clarithromycin resistance test through PCR methods when selecting standard 7-day triple therapy as first-line treatment.8

Noh et al.9 showed real-time (RT)-PCR method (SeaSun Biomaterials) detection of H. pylori infection more efficiently 97.1% (68/70) compared to rapid urease test (82.9%, 58/70) using leftover specimens. RT-PCR also detected that 84.6% (11/13) of point mutations in 23S rRNA. The authors said RT-PCR-based assay is a simple and accurate method for detecting H. pylori and clarithromycin resistance using a small formalin-fixed or paraffin-embedded specimen. However, the failure to find point mutations in the two culture-proven resistant strains implies the RT-PCR method has limitations in detecting only specific mutations like dual priming oligonucleotide PCR.

In real practice, resistance or susceptibility tests are often required for patients who have failed the preceding eradication therapy, aside from the issue of the effectiveness of tailored therapy as a secondary treatment. The necessity of re-acquisition of gastric mucosa under endoscopy is the biggest hurdle to use resistant tests. Sensitive molecular methods using non-invasive specimens such as saliva can be a good alternative modality in the current circumstance where insurance coverage is the same as the indication for eradication.

For now, PCR cannot completely replace the rapid urease test and the conventional culture method. The development of more diverse methods for identifying H. pylori and resistance and vigorous research on their clinical usefulness are required.

CONFLICTS OF INTEREST

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

References

  1. Thung I, Aramin H, Vavinskaya V, et al. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther 2016;43:514-533.
    Pubmed KoreaMed CrossRef
  2. Wang YK, Kuo FC, Liu CJ, et al. Diagnosis of Helicobacter pylori infection: current options and developments. World J Gastroenterol 2015;21:11221-11235.
    Pubmed KoreaMed CrossRef
  3. Cho JH, Jeon SR, Kim HG, Jin SY, Park S. Cost-effectiveness of a tailored Helicobacter pylori eradication strategy based on the presence of a 23S ribosomal RNA point mutation that causes clarithromycin resistance in Korean patients. J Gastroenterol Hepatol 2019;34:700-706.
    Pubmed CrossRef
  4. Gweon TG, Kim JS, Kim BW. An economic modeling study of Helicobacter pylori eradication: comparison of dual priming oligonucleotide-based multiplex polymerase chain reaction and empirical treatment. Gut Liver 2018;12:648-654.
    Pubmed KoreaMed CrossRef
  5. Liou JM, Chen PY, Luo JC, et al. Efficacies of genotypic resistance-guided vs empirical therapy for refractory Helicobacter pylori infection. Gastroenterology 2018;155:1109-1119.
    Pubmed CrossRef
  6. Kwon YH, Kim N, Lee JY, et al. Comparison of the efficacy of culture-based tailored therapy for Helicobacter pylori eradication with that of the traditional second-line rescue therapy in Korean patients: a prospective single tertiary center study. Scand J Gastroenterol 2016;51:270-276.
    Pubmed CrossRef
  7. Choi YI, Chung JW, Park DK, et al. Tailored eradication vs empirical bismuth-containing quadruple therapy for first-line Helicobacter pylori eradication: a comparative, open trial. World J Gastroenterol 2019;25:6743-6751.
    Pubmed KoreaMed CrossRef
  8. Jung HK, Kang SJ, Lee YC, et al. Evidence-based guidelines for the treatment of Helicobacter pylori infection in Korea: 2020 revised edition. Korean J Helicobacter Up Gastrointest Res 2020;20:261-287.
    CrossRef
  9. Noh JH, Ahn JY, Choi J, et al. Real-time polymerase chain reaction for the detection of Helicobacter pylori and clarithromycin resistance. Gut Liver 2023;17:375-381.
    Pubmed CrossRef
Gut and Liver

Vol.18 No.4
July, 2024

pISSN 1976-2283
eISSN 2005-1212

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