Introduction

A 10-14 day non-bismuth quadruple "concomitant" therapy is currently the preferred first-line regimen for Helicobacter pylori (HP) eradication in Greece ^1,2. In this country, bismuth salts have recently become commercially available; however, lack of tetracycline still precludes use of bismuth quadruple therapy. Adding bismuth to the current concomitant therapy (ie; a quintuple regimen) could be an alternative; however, it has never been explored previously.

Aims & Methods

The present study aimed to assess a quintuple 10-day bismuth-enhanced concomitant regimen as first-line treatment for HP eradication in Greece. Prospective, open-label, multicenter pilot study including treatment-naïve patients diagnosed with HP infection via histology and/or rapid urease test. Exclusion criteria included recent use of PPIs, antibiotics, NSAIDs, bismuth, serious comorbidities, prior gastrectomy, pregnancy or lactation, allergy to any study drug, and refusal to participate. All patients received a 10-day regimen consisting of esomeprazole 40 mg BID, amoxicillin 1000 mg BID, clarithromycin 500 mg BID, metronidazole 500 mg BID, and bismuth subcitrate 240 mg BID. A specific probiotic supplement containing Lactobacillus acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii was also administered in all patients. Efficacy was evaluated by intention-to-treat (ITT), per-protocol (PP), and modified ITT (mITT) analyses. Successful eradication was defined as a negative histology or urea breath test at least 8 weeks post-treatment.

Results

A total of 52 patients were analyzed (mean age 48.6 ± 18.7 years, 50% male, peptic ulcer disease: 7/52, non-ulcer dyspepsia: 29/52). Eradication rates were: i) ITT: 47/52 (90.4%, 95% CI: 79.4–95.8), ii) PP: 46/49 (93.9%, 95% CI: 83.5–97.9), iii) mITT: 47/51 (92.2%, 95% CI: 81.5–96.9). Adverse events were reported by 29.4% (15/51) of patients, with taste disturbances being the most frequent (39.1%); no serious adverse events occurred. Compliance was excellent with 49/51 (96.1%) patients taking >90% of the prescribed therapy.

Conclusion

A quintuple 10-day bismuth-enhanced concomitant regimen appears to be an effective (93.9% PP), safe and well tolerated treatment option for first-line HP eradication in a country with high clarithromycin and metronidazole resistance, without negatively affecting patient compliance.

References

1. Rokkas T, et al. Assessment of first-line eradication treatment in Greece: data from the European Registry on Helicobacter pylori management (Hp-EuReg). Ann Gastroenterol 2022;35:42-7.
2. Georgopoulos SD, et al. Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas. Antibiotics 2024;13:280.

Introduction

Helicobacter pylori (H. pylori) remains a significant global pathogen, implicated in chronic gastritis, peptic ulcer disease, and gastric cancer. Over the past two decades, escalating resistance to key antibiotics—particularly clarithromycin, levofloxacin, and metronidazole—has reduced the effectiveness of standard triple therapies, with eradication rates falling below 70%. Refractory H. pylori infection, defined in this study as persistent infection after three or more failed eradication regimens, presents a growing therapeutic challenge. The absence of standardised rescue protocols and limited access to antibiotic susceptibility testing in many regions further complicates treatment. Innovative empirical strategies, especially those using agents with low resistance profiles, are urgently needed.

Aims & Methods

This real-world, prospective observational study aimed to evaluate the efficacy of a Modified Concomitant Therapy (MCT) regimen for the eradication of refractory H. pylori. Adults aged ≥18 years with confirmed H. pylori infection persisting after at least three previous treatment attempts were recruited from a gastroenterology centre in Bogotá, Colombia, between January and November 2023.

The MCT protocol included:

• Esomeprazole 40 mg, twice daily (before breakfast and dinner)
• Furazolidone 100 mg, every 8 hours
• Amoxicillin 875 mg every 8 hours (in patients <70 kg) or 1 g every 8 hours (in ≥70 kg)
• Tetracycline 500 mg, every 6 hours

Patients were counselled about the therapeutic difficulty and potential adverse effects. The treatment duration was 14 days. Eradication was assessed 6–8 weeks post-therapy using histological evaluation with haematoxylin-eosin and Giemsa staining. This choice was based on prior discordance between breath test results (often negative) and biopsy (positive). Effectiveness was analysed both by modified intention-to-treat (mITT) and per-protocol (PP) methods.

Results

A total of 30 patients were enrolled (mean age: 45 ± 6 years; range: 28–63).

• mITT eradication rate: 27/30 (90%, 95% CI: 72.3–97.4)
• PP eradication rate: 25/27 (92.5%, 95% CI: 76.3–97.9)

Adverse events were reported in 8 patients:

• Nausea (30%)
• Headache (33%)
• Diarrhoea (16%)
• Constipation (10%)

Three patients discontinued treatment prematurely between days 10 and 12. No severe adverse events or hospitalisations occurred. The major limiting factor for broader enrolment was intermittent availability of tetracycline.

Conclusion

This study demonstrates that Modified Concomitant Therapy represents a promising and effective option for the eradication of refractory H. pylori infection in real-world settings. With an eradication rate exceeding 90% and manageable adverse effects, MCT using furazolidone, amoxicillin, tetracycline, and high-dose PPI constitutes a rational empirical rescue strategy in regions where antibiotic resistance testing is unavailable and first-line therapies have failed. Further multicentre studies with larger cohorts are warranted to confirm these findings and assess long-term outcomes. The development of accessible tetracycline formulations would enhance implementation.

References

1. Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022 Jan;71(1):172–95. doi:10.1136/gutjnl-2021-325210.
2. Graham DY, Lee YC, Wu MS. Rational Helicobacter pylori therapy: evidence-based medicine rather than medicine-based evidence. Clin Gastroenterol Hepatol. 2014 Feb;12(2):177–86.e3. doi:10.1016/j.cgh.2013.06.020.
3. Liou JM, Chen CC, Chang CY, Chen MJ, Fang YJ, Lee JY, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013 Feb 16;381(9862):205–13. doi:10.1016/S0140-6736(12)61455-0.

Introduction

Hepatitis E virus (HEV) infection in Europe is predominantly due to zoonotic genotype 3, transmitted via undercooked pork, game or shellfish (1,2). In the Helsinki and Uusimaa Hospital District (HUS), 70 laboratory-confirmed cases occurred from 2020–2024, with a pronounced peak in early 2024 (3). Seroprevalence in high-income countries ranges from ~6 % to > 50 %, increasing with age and swine exposure (1,2). While most infections are asymptomatic or mild, patients with underlying liver diseases may have more severe outcomes. Diagnosis relies on anti-HEV IgM/IgG serology and PCR detection of viral RNA (4).

Aims & Methods

Objective of this study is to investigate the epidemiology of hepatitis E virus (HEV), its clinical manifestations, and factors associated with hospitalization in the Helsinki University Hospital (HUS) area between 2020 and 2024. We conducted a retrospective registry study including all patients diagnosed with hepatitis E in the HUS area from January 2020 to December 2024. Data were collected from the electronic health record system, the laboratory database, and the shared contact-tracing software of the HUS Epidemiology Unit and Uusimaa welfare regions. Variables analyzed comprised demographic data, symptoms at presentation, key laboratory parameters (ALT, bilirubin, C-reactive protein), probable sources of infection, and details of hospitalization episodes.

Results

Study population: 70 patients (median age 58 years [IQR 45–67]; 58.6 % male).
Clinical manifestations: 92.2 % were symptomatic. The most frequent symptoms were fatigue (55.9 %), abdominal pain (47.5 %), nausea (45.8 %), and jaundice (42.6 %).
Laboratory findings: Median peak ALT was 1 153 U/L (IQR 544–1 538); median peak bilirubin 39 μmol/L (IQR 17–79); median peak CRP 22 mg/L (IQR 11–32).
Genotypes: Of 19 genotyped cases, 3c (21.1 %), 3e (21.1 %), and 3f (57.9 %), with genotype 3f predominant.
Infection sources: Cold-smoked sausages (e.g., mettwurst) were implicated in most domestic cases (69.6 % of identified sources), especially during the early 2024 outbreak. Other identified sources were unspecified meat products (6.5 %), berries (6.5 %), contact with wild animals (e.g., hunting, 4.3 %), blood transfusion (4.3 %), pork meat (4.3%), and game meat (4.3%).
Hospitalization: 50.7 % required ≥1 night of inpatient care. Hospitalized patients were older, had higher ALT, bilirubin, and CRP values, and more comorbidities than outpatients.
Predictors of hospital stay: In a multivariable zero-inflated negative binomial model, higher peak CRP was independently associated with longer hospital stay (β = 0.02; p = 0.005).

Conclusion

The early-2024 surge of HEV cases in the HUS area represents an internationally rare, large genotype 3 outbreak. Cold-smoked meat products were identified as the principal transmission route, although infections linked to blood transfusions, consumption of raw berries, and wildlife contact also occurred. Cases were disproportionately concentrated in men over 50 years of age. Among hospitalized patients, peak CRP emerged as the strongest predictor of inpatient care, and both mortality and incidence of hepatic insufficiency were relatively high given high sanitation standards in Finland. Further multicenter, inter-regional studies are needed to establish statistically robust risk factors for severe outcomes and to guide clinical and public health interventions.

References

1. Luo Q, Chen J, Zhang Y, Xu W, Liu Y, Xie C, ym. Viral hepatitis E: Clinical manifestations, treatment, and prevention. Liver Res. maaliskuuta 2024;8(1):11–21.
2. Hartl J, Otto B, Madden RG, Webb G, Woolson KL, Kriston L, ym. Hepatitis E Seroprevalence in Europe: A Meta-Analysis. Viruses. 6. elokuuta 2016;8(8):211.
3. THL. Terveyden ja hyvinvoinnin laitos. 2024 [referenced: 13. lokakuuta 2024]. Hepatiitti E-tapausten esiintyvyys Suomessa – THL. Available: https://thl.fi/aiheet/infektiotaudit-ja-rokotukset/taudit-ja-torjunta/taudit-ja-taudinaiheuttajat-a-o/hepatiitti-e/hepatiitti-e-tapausten-esiintyvyys-suomessa
4. Dalton HR, Kamar N, Baylis SA, Moradpour D, Wedemeyer H, Negro F. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol. kesäkuuta 2018;68(6):1256–71.