Introduction

Helicobacter pylori (H. pylori) infection remains a major public health problem. Given the high resistance to antibiotics, different treatment strategies must be validated in each specific country. The recurrence rates of H. pylori infection and its predictors remain unclear.

Aims & Methods

To determine the independent factors predicting recurrence after successful eradication with a first-line treatment for H. pylori infection.
All patients were submitted to eradication treatment with five quadruple therapies (A-Concomitant with metronidazole 500mg tid, 14 days; B-Concomitant with metronidazole 500mg bid, 14 days; C-Quadruple with bismuth, 10 days; D-Sequential, 14 days; E-Hybrid, 14 days)) in a blind, randomized trial. Esomeprazole was the proton-pump inhibitor of choice. Efficacy rate at 1-2 months and recurrence rate at 12 months using ¹³C-urea breath test were evaluated. Sociodemographic data, personal/family history, health status and biochemical parameters were assessed using univariate and multivariate analyses.

Results

A total of 126 patients (42.9% males; mean age: 57.4±16.7 years) concluded the treatment protocol (A-25; B-21; C-27; D-24; E-29). Overall efficacy rate of quadruple therapy regimens was 98.4%(n=124): Group A-100%; Group B-100.0%; Group C-100.0%; Group D-100.0%; Group E-93.1% (p=0.147). Overall recurrence rate of quadruple therapy regimens was 4.1%(n=5/123): Group A-12.0%; Group B-9.5%; Group C-0.0%; Group D-0.0%; Group E-0.0% (p=0.009). After univariate/multivariate analysis, high LDL-cholesterol level (OR 1.032, p=0.042), non-bismuth concomitant H. pylori eradication regimen (OR 8.904, p=0.064) and alcoholism (OR 8.333, p=0.035) were independent risk factors for H. pylori reinfection.

Conclusion

In this South-European country, all quadruple therapy regimens with or without bismuth are very effective for H. pylori eradication. The 12-months recurrence rate of H. pylori infection after successful eradication is <5%. High LDL-cholesterol, non-bismuth concomitant H. pylori eradication regimen and alcoholism are independent predictors for H. pylori reinfection. A close surveillance on infectious state in high-risk patients is crucial to prevent long-term H. pylori-associated complications.

References

1. Zamani, M., Ebrahimtabar, F., Zamani, V., et al. (2018) Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 47(7), 868-876.
2. Malfertheiner, P., Megraud, F., O’Morain, C.A., et al. (2017) Management of Helicobacter pylori infection – the Maastricht V/Florence Consensus Report. Gut 66(1), 6-30.
3. Savoldi, A., Carrara, E., Graham, D.Y., et al. (2018) Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in World Health Organization Regions. Gastroenterology 155(5), 1372-1382.
4. Lopo, I., Libânio, D., Pita, I., et al. (2018) Helicobacter pylori antibiotic resistance in Portugal: Systematic review and metaanalysis. Helicobacter 23(4), e12493.
5. Hu, Y., Wan, J.H., Li, X.Y., et al. Systematic review with meta-analysis: the global recurrence rate of Helicobacter pylori. Aliment Pharmacol Ther. 2017;46(9):773-779.
6. Zhao, H., Yan, P., Zhang, N., et al. The recurrence rate of Helicobacter pylori in recent 10 years: A systematic review and meta-analysis. Helicobacter. 2021;26(6):e12852.

Disclosure

None of the authors have anything to declare with regard to personal or financial interests in carrying out this work.

Introduction

Inappropriate proton pump inhibitor (PPI) use is a growing concern, with estimates of up to 70% of long-term use lacking a valid indication (1,2).

Aims & Methods

This study investigates the feasibility of PPI deprescribing in a primary care setting and evaluates its impact on gastrointestinal symptoms and blood values. General practitioners (GPs) recruited long-term, chronic PPI users without strict indication. Demographics, PPI duration/dosage, medical history, and GP-estimated success probability were registered at baseline (Visit 0). Patients on healing-dose PPIs at baseline were down-titrated to maintenance dose for 1 month before deprescription at Visit 1. At Visit 1, all patients were instructed to deprescribe their PPI within one month. After this period, patients returned for Visit 2, where the PPI was stopped completely if feasible. One month later, during Visit 3, patients entered a one-year follow-up period. Patients returned after 6 and 12 months for Visit 4 and 5, respectively, with online questionnaires at 3 and 9 months. Gastrointestinal symptoms (nausea, fullness, bloating, upper abdominal pain, lower abdominal pain, heartburn) were assessed using the PAGI-SYM questionnaire. Successful deprescription was defined as ≤3 PPI doses/month. Optional blood samples at baseline and end of study measured gastrin, magnesium, calcium, iron, and vitamin B12 levels. Results are shown as median(IQR).

Results

Sixty GPs included a total of 640 patients (62(50-70) years, 60% female, BMI 27(25-31) kg/m²). Down-titration from healing to maintenance dose (n=128) before PPI deprescription was successful in 92% of the patients.
One month after deprescribing, 76% of patients (n=444/582) had successfully interrupted their PPI intake. Of these, 78% maintained success, resulting in a sustained success rate of 61% (n=264/432). Success rates did not differ by initial PPI indication (dyspepsia, low-grade GERD, NERD, non-gastric indications), demographics or initial PPI dose. However, GP-estimated success probability at baseline was associated with successful deprescribing at 6 months (p=0.0075, OR = 2.6, 95%CI: 1.3–5.2).
Patients who successfully reduced PPI intake reported a transient increase in heartburn (p<0.0001) after deprescribing (visit1), returning to baseline during follow-up. Interestingly, bloating and postprandial fullness decreased significantly during follow-up (visits 2-4) compared to baseline (both p<0.0001).
A significant difference in delta magnesium (+0.01 vs -0.03 mmol/l, p=0.004) and gastrin levels (-57 vs. -19 pg/mL, p=0.002 ) was observed between successfully (n=105) and unsuccessfully (n=41) deprescribed patients.

Conclusion

PPI deprescription is highly feasible in primary care, with a sustained success rate of 61% after 6 months. While heartburn may transiently increase, bloating and postprandial fullness improved. In patients who successfully reduced PPI intake. Magnesium levels increased while gastrin levels decreased.

References

1. Boghossian TA et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev. 2017 Mar 16;3(3).
2. Heidelbaugh JJ, Kim AH, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5(4):219–32.

Disclosure

All authors have declared no conflict of interest.

Clinical Case Summary

Materials and methods: 24-year-old man with an episode of nausea, anorexia and loss of 4-5 kg in a week, which resolved spontaneously without drugs. During the episode had hyperchromic urine, yellowing of skin and eyes.After 1 month small increase of serum transaminases x 1.5. Regular bowel function. No clinical signs. US regular. Anti-HbsAg and HCV-Ab negative. After another month he had highly increase of serum transaminases with AST x 27 and ALT x50 GGT x3, Total bilirubin 2.85. Negative ANA, AMA, LKM, IgA anti TTG, anti EBV, anti CMV, alpha1 anti trypsian slight increase. He performed a new serum analysis with increase of anti-TTG IgA. He subsequently performed genetics for celiac disease and confirmed homozygous DQ2.Performs EGDS for suspected celiac disease which documents nodularity in bulb and DII scalloping. Histological examination shows Marsh 3B.After 150 g gluten daily intake had IgA anti TTG x 4. A diagnosis of celiac disease is made and he started GFD with serum transaminases x 2After 2 months with good adherence to GFD has AST x20 and ALT x 50. He denies alcohol abuse.Negative hemochromatosis mutations. Stable weight, Regular bowel function. We perform liver biopsy. The histological examination documents Histological Activity index acc. Knodell modified by Ishak: 7 Grading.
Results: Diagnosis is moderately active chronic autoimmune hepatitis.Therapy is started with prednisone 40 mg daily. With AST x10 and ALT x 20After 15 days of therapy AST x 5 and ALT x9, therefore values halving and normal bilirubin. Currently under follow-up in our Hospital
Conclusions: Although the history is still unknown and the histological exam is compatible but not certain, the good response to steroid therapy is a positive factor that proves the correctness of the diagnosis. This diagnostic difficulty leads us to always evaluate the autoimmune cause in a young patient without risk factors with a small increase in transaminases.

References

University of Salerno