Tag Archives: Helicobacter pylori

Synergistic Dangers: Helicobacter Pylori and Cancer Genes

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Y Usui et al. NEJM 2023; 388: 1181-1190. Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer

Background: Gastric cancer is the fifth most common neoplasm and the fourth leading cause of death from cancer worldwide.1 Helicobacter pylori has been classified as a group I carcinogen and is an environmental risk factor for gastric cancer.2 Although H. pylori infection affects more than half the world population

Methods: This study evaluated the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in a sample of 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. This retrospective study also assessed the combined effect of pathogenic variants and H. pylori infection status on the risk of gastric cancer and calculated the cumulative risk in 1433 patients with gastric cancer and 5997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC).

Key findings:

  • Germline pathogenic variants in nine genes: (APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2) were associated with the risk of gastric cancer.
  • At 85 years of age, persons with H. pylori infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with H. pylori (45.5% vs. 14.4%).
  • Limitation: The study population was from East Asia and thus, the findings may be different in other populations.

My take: H. pylori infection has a synergistic effect in increasing the risk of gastric cancer in individuals with germline pathogenic variants in homologous-recombination genes. To minimize the risk of gastric cancer, H pylori eradication is important; however, it is especially in those with cancer-predisposing variants.

From NEJM Twitter Feed

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Brief Updates: H pylori Resistance Rates, VEDOKIDS, Increasing Bariatric Surgery in Kids

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F Megraud et al. AJG 2022; doi: 10.14309/ajg.0000000000002045 Open Access: Rates of Antimicrobial Resistance in Helicobacter pylori Isolates From Clinical Trial Patients Across the US and Europe. Resistance rates were established in isolates from 907 participants. Overall, 22.2% were resistant to clarithromycin, 1.2% to amoxicillin, and 69.2% to metronidazole.

O Atia et al. Lancet Gastroenterol Hepatol 2022; DOI:https://doi.org/10.1016/S2468-1253(22)00307-7. Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study

Methods: VEDOKIDS was a paediatric, multicentre, prospective cohort study done in 17 centres in six countries. We report the 14-week outcomes as the first analyses of the planned 3-year follow-up of the VEDOKIDS cohort

Key findings:

  • 32 (42%) of 77 children with ulcerative colitis and 21 (32%) of 65 children with Crohn’s disease were in steroid-free and exclusive enteral nutrition-free remission at 14 weeks.
  •  In children who weighed less than 30 kg, the optimal drug concentration associated with steroid-free and exclusive enteral nutrition-free clinical remission was 7 μg/mL at week 14, corresponding to a dose of 200 mg/m2 body surface area or 10 mg/kg

USAToday 11/14/22: More teens are getting weight loss surgery but some experts think more needs to be done

And of course, an important story from The Onion: Arsonist Worried He Forgot To Turn Stove On Before Leaving House

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Favorite Posts 2022

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Thank you to those who have helped me this past year with this blog –colleagues, friends and family. Wishing all of you a good 2023. Here are some of my favorite posts from this past year:

GI:

Nutrition:

Liver:

Endoscopy:

Health Policy:

Humor:

Understanding FDA Approval of Vonoprazan-Based Therapies for Helicobacter Pylori

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Pharmacy Times (5/4/22): FDA Approves Pair of Vonoprazan Treatments for Helicobacter Pylori Infection

“The (FDA) has approved 2 vonoprazan-based medications for the treatment of Helicobacter pylori (H. pylori) infection.

Phathom Pharmaceuticals announced the approvals of both the Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) based on positive safety and efficacy data from the phase 3 PHALCON-HP trial.”

WD Chey et al. Gastroenterol 2022; 163: 608-619. Open Access! Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial

Key findings from this randomized, controlled trial with treatment-naive 1046 adults:

  • In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5% (both superior)
  • In patients with clarithromycin resistance, vonoprazan triple therapy was effective in 65.8%, dual therapy in 69.6%, vs lansoprazole triple therapy 31.9% (both superior)
  • Vonoprazan increases intragastric pH rapidly “and maintains it to a greater degree than PPI; this has been associated with higher H pylori eradication rates” (in prior studies as well)

The associated editorial: CA Fallone (Open Access!) The Current Role of Vonoprazan in Helicobacter pylori Treatment

Based on this new information, the author proposes the treatment algorithm below and notes that “the role of increased acid suppression by PPI substitution with vonoprazan should be examined in other H pylori regimens.” The author favors bismuth quadruple therapy in those with clarithromycin resistance as non-bismuth quadruple therapy utilizes an unnecessary antibiotic (clarithromycin).

Other points:

  • Metronidazole resistance is fairly common, but bismuth quadruple therapy can overcome much of the metronidazole resistance
  • Levofloxacin resistance is quite high in certain regions and should only be used with caution, given recent warnings from the US Food and Drug Administration of aortic rupture in susceptible individuals
  • Rifabutin can cause some bone marrow suppression

My take: With the more widespread availability of susceptiblity testing (beyond clarithromycin), I anticipate more targeted treatments. At the same time, vonoprazan-based treatments are likely to be important in increasing eradication rates.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Position Paper for Pediatric Breath Testing

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IJ Broekaert et al. JPGN 2022; 74: 123-127. Open access: An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology

This is a good article which provides pediatric dosing of breath testing agents and important considerations in methodology and interpretation. In addition, there are 22 graded recommendations (see below) –some may be surprising. For example, the breath testing is NOT recommended for diagnosis of H pylori but is recommended for determination of eradication therapy.

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How To Achieve Helicobacter Pylori Cure Rates of >95%

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Related to yesterday’s blog, here is an SNL commercial for the “Koohl” toilet (also with Benedict Cumberbatch) in 2016: SNL Koohl Toilet

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DY Graham, SF Moss. Am J Gastroenterol 2022. 117: 524-528. Antimicrobial Susceptibility Testing for Helicobacter pylori Is Now Widely Available: When, How, Why

Key points:

  • Susceptibility testing for H pylori is widely available in the U.S. and should help optimize treatments to get success rates >95%. Testing is now available for the most common treatment antibiotics: amoxicillin, metronidazole, tetracycline, levofloxacin, clarithromycin, and rifabutin.
  • Handling/shipping specimens properly is important with susceptibility testing
  • The authors recommend a PPI which is minimally-affected by CYP2C19 metabolism, namely rabeprazole or esomeprazole.
  • Provide careful instructions to patient/family regarding treatment

Susceptibility Testing Labs (see Table 1):

  • Quest: Our Quest representative indicated code: 36994 (H. pylori culture with reflex to susceptibility). Preferred Specimen: 3 mm Gastric/Antral or Duodenal biopsy collected in Brucella broth or Trypticase Soy Broth (TSB) with 10-20% glycerol
  • LabCorp: Helicobacter pylori Culture Test Code Test Code 180885
  • ARUP: Helicobacter pylori Culture Test Code 2006686
  • Culture (Catalog HELIS) or Stool PCR testing (Catalog HPFRP) can be done by Mayo Clinic
  • Reflex stool testing as well as PCR gastric testing from formalin is available through by American Molecular laboratories

A treatment algorithm is listed:

  • In the absence of highly effective empiric treatment or after treatment failure, the authors recommend susceptibility testing.
  • If clarithromycin susceptible, then a 14-day clarithromycin triple therapy course is recommended
  • If clarithromycin resistant but metronidazole susceptible, then 14-day metronidazole triple therapy
  • If resistant to both clarithromycin and metronidazole, then either a 14-day bismuth quadruple therapy, or a rifabutin triple therapy are preferred. However, if H pylori organisms are levofloxacin susceptible, then 14-day levofloxacin triple therapy may be a good option.
  • The authors recommend quinolone therapy only in the setting of susceptibility testing due to the FDA warnings about long-term adverse effects.

My take: Perhaps H pylori susceptibility testing availability needs to be a quality metric for hospitals and endoscopy centers.


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Next-Generation Treatment for H Pylori

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KG Hulten, et al. Gastroenterol 2021; 11: 1433-1442. Open Access: Comparison of Culture With Antibiogram to Next-Generation Sequencing Using Bacterial Isolates and Formalin-Fixed, Paraffin-Embedded Gastric Biopsies

Background: “The general unavailability of culture-based susceptibility testing for H pylori has resulted in the almost universal reliance on hopeful (empiric) therapy and a high proportion of treatment failures.” Besides the lack of availability of culture-based susceptibility testing, the global increase in prevalence of antimicrobial resistance contributes to the poor cure rates obtained with empiric use of the currently most popular triple therapies for H pylori infection.

Methods: H pylori isolates (n=170) (clinical isolates and formalin-fixed, paraffin-embedded) were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics.

Key findings:

  • Agreement between agar dilution and NGS from culture isolates was very good for clarithromycin (κ = 0.90012), good for levofloxacin (κ = 0.78161) and fair for metronidazole (κ = 0.55880), and amoxicillin (κ = 0.21400)
  • Comparison of NGS from tissue blocks and agar dilution from isolates from the same stomachs demonstrated good accuracy to predict resistance for clarithromycin (94.1%), amoxicillin (95.9%), metronidazole (77%), levofloxacin (87.7%), and tetracycline (98.2%)

Associated editorial: F Megraud et al. Gastroenterol 2021; 11: 1367-1369. Open Access: Molecular Diagnosis for Helicobacter pylori . . . at Last

Excerpts from editorial:

  • “By targeting all of the genes responsible for antibiotic resistance, it is possible to obtain genotypic susceptibility data for all of the antibiotics of potential use, without the need to perform” culture and antibiotic susceptibility testing
  • “Hulten et al show not only that they obtained comparable results with the reference method (phenotypic) for most of the antibiotics, but also that NGS can also be performed on both culture isolates and stored histologic preparations. This result is important because it avoids the need for extra biopsies and culture”
  • “NGS could also be applied on stools. In this particular environment where H pylori DNA is found in a low amount, excellent DNA extraction methods are mandatory and progress is being made in this field”

My take: NGS can bring H pylori treatment to a new era (like almost all other infections). “Molecular methods can potentially augment or even replace the current in vitro methods for susceptibility testing, which are cumbersome, technically challenging, and time-consuming.”

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Lots of Room to Improve with H pylori Treatment

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Briefly noted: A recent survey study (N Du et al. JPGN Reports: 2021; 2: p e033. doi: 10.1097/PG9.0000000000000033. Full Text: Assessment of Community Pediatric Providers’ Approach to Children With Helicobacter pylori) found that pediatric providers had poor knowledge and/or adherence to pediatric H pylori guidelines.

Key findings:

  • Over a third of the respondents reported incorrectly testing patients for H. pylori while they were taking proton pump inhibitors.
  • 17% (n=17) incorrectly preferred blood serology as testing modality
  • 63% (n=64) relied on symptom resolution as indication of cure

My take: It would be interesting to compare pediatric gastroenterology provider responses to general pediatric providers. It is likely that a much higher percentage would be following established guidelines. One area of the guidelines that I think should be changed would be encouraging increased use of quadruple therapy in children, especially if resistance testing is not performed; this change would better align with adult guidelines. In adults, quadruple therapy has been associated with increased cure rates.

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Rifabutin-based Triple Therapy for H pylori

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From NEJM Journal Watch (5/8/20): A New First-Line Treatment Regimen for H. pylori Infection

In this industry-funded, phase III trial conducted in the U.S., 455 H. pylori-treatment–naive patients with dyspepsia and a confirmed H. pylori diagnosis were randomized to treatment with capsules containing rifabutin, amoxicillin, and omeprazole or capsules containing amoxicillin and omeprazole for 14 days. Participants took 4 capsules every 8 hours. The eradication rate in the rifabutin-based therapy group was significantly higher (84%) compared with the comparison group (58%). In patients with confirmed adherence to treatment, the eradication rates were 90% versus 65%, respectively. No H. pylori resistance to rifabutin was detected, and side effects were similar between groups.

My take: More treatment options are needed due to drug resistance.  Also, “further studies are needed to compare this new triple therapy with current quadruple therapies.”

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Treating Helicobacter Pylori Lowers The Risk of Gastric Cancer

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