Introduction

Antibiotic resistance is the main factor that determines the efficacy of treatments to eradicate Helicobacter pylori infection.

Aims & Methods

To evaluate the effectiveness of first-line and rescue treatment against H. pylori in Europe according to the resistance to different antibiotics.
Prospective, multicenter, international, non-interventionist registry on the management of H. pylori (Hp-EuReg) by European gastroenterologists. All infected and culture-diagnosed adult patients registered in AEG-REDCap e-CRD were included. The analysis of therapeutic effectiveness was performed per-protocol according to the presence or absence of bacterial resistance to the different antibiotics. Optimal therapeutic effectiveness was considered when the eradication rate was ≥ 90%. Data was subject to quality control.

Results

A total of 2,852 naïve patients with culture results were analysed. Resistance to clarithromycin, metronidazole and quinolones was 22%, 27% and 18%, respectively. The most effective treatment, regardless of resistance, was the three-in-one single capsule with bismuth, metronidazole and tetracycline, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin (93%) or metronidazole (91%). Triple schedules with clarithromycin plus amoxicillin, metronidazole plus amoxicillin or the sequential quadruple therapy with metronidazole did not achieve optimal results (Table). A total of 1,118 non-naïve patients were analysed. Resistance to clarithromycin, metronidazole and quinolones was 49%, 41% and 24%, respectively. None of the rescue treatments achieved optimal eradication rates; however, the highest effectiveness was reported with the triple therapy with amoxicillin and levofloxacin (87%, 345/397) followed by the three-in-one single capsule (86%, 206/244).

Conclusion

In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the three-in-one single capsule, the bismuth quadruple therapy and the concomitant treatment with tinidazole were the best options in naïve patients. In non-naïve patients, the three-in-one single capsule and the triple therapy with levofloxacin provided encouraging results.

Disclosure

Olga P. Nyssen received research funding from Mayoly and Allergan.
Javier P. Gisbert served as speaker, consultant, and advisory member for or received research funding from Mayoly, Allergan, Diasorin, Gebro Pharma, and Richen.

Introduction

​Non-alcoholic fatty liver disease (NAFLD) is associated with unhealthy lifestyle habits and diet. However, there is limited prospective evidence on the combined association of those factors and NAFLD, with no data regarding insulin resistance (IR), fibrosis, and steatohepatitis markers.

Aims & Methods

We aimed to test the association between a combination of lifestyle components, expressed as a healthy lifestyle index (HLI), with the incidence of NAFLD, IR, fibrosis, and steatohepatitis.
​A prospective cohort study among volunteers who participated in a metabolic and hepatic screening survey, and follow-up evaluation at Tel-Aviv Medical Center. NAFLD was evaluated by ultrasonography or controlled attenuation parameter (CAP) at two-time points to evaluate incidence, persistence or remission, and IR was evaluated by homeostasis model assessment. Presumed fibrosis and non-alcoholic steatohepatitis were evaluated non-invasively by FibroMax serum biomarkers. HLI was calculated as the sum of four lifestyle components (ranging from 0 to 4 points): lifetime non-smoking, healthy weight, healthy dietary pattern, and routine performance of physical activity.

Results

​The final sample included 315 subjects, 40-70 years old, 56.8% men, and 18.3% with incident NAFLD. The mean follow-up was 6.66±0.73 years. In multivariable analyses, a favorable lifestyle (≥3 healthy lifestyle components) was independently associated with a lower risk for incident NAFLD (OR=0.42; 95%CI 0.19-0.90; P=0.026). Similarly, a favorable lifestyle was associated with lower odds of new-onset/persistence (versus never or remission) of NAFLD and IR, respectively (OR=0.49; 95%CI 0.30-0.80; P=0.004; OR=0.40; 95%CI 0.24-0.66; P<0.001), with a dose-response association in univariate analysis (P for trend <0.001 for NAFLD, and P<0.001 for IR), and similar trend in multivariable analysis. In addition, a favorable lifestyle was associated with a lower risk for incident steatohepatitis on its own or combined with significant fibrosis (≥F2), respectively (OR=0.50; 95%CI 0.27-0.95; P=0.035; OR=0.45; 95%CI 0.24-0.85; P=0.014).

Conclusion

​Adherence to a healthy lifestyle is associated with reduced risk of NAFLD, markers of significant fibrosis and steatohepatitis, and IR. A holistic approach taking into consideration the combination of lifestyle behaviors may be more useful for preventing NAFLD and related liver damage.

Introduction

The ongoing phase 3 ESSENCE trial (NCT04822181) reported positive results for histological and non-invasive test (NIT) endpoints in an interim analysis of the first 800 randomised participants with biopsy-defined metabolic dysfunction-associated steatohepatitis (MASH) and F2/F3 fibrosis receiving once-weekly subcutaneous semaglutide 2.4 mg vs placebo. Participants receiving semaglutide achieved a mean weight loss of 10.5% vs 2.0% with placebo. In this post hoc analysis, we assessed the weight dependency of the effects of semaglutide 2.4 mg on study endpoints (NITs and histology) after 72 weeks of treatment, using weight loss-independent and weight loss-dependent pathways as covariates.

Aims & Methods

NITs and biopsies were assessed at baseline and week 72. MASH-related NIT responder endpoints were change in alanine aminotransferase (ALT; ≥17-unit reduction) and FibroScan-aspartate aminotransferase (FAST) score (≥0.22 reduction). Fibrosis-related NIT responder endpoints were change in vibration-controlled transient elastography (VCTE) liver stiffness measurement (30% reduction) and Enhanced Liver Fibrosis (ELF) score (≥0.5-unit reduction). Histological endpoints included resolution of MASH and improvement in fibrosis. All endpoints were assessed using logistic regression at week 72 with treatment as exposure, percentage weight loss from baseline to week 72 as mediator, and baseline type 2 diabetes status, fibrosis stage and body weight as covariates. The total and weight loss-independent and weight loss-dependent effect sizes were calculated as odds ratios (ORs), and missing data were omitted. All data are based on the full analysis set from the on-treatment observation period.

Results

For MASH-related endpoints, the total effect (OR [95% confidence interval (CI)]) for ALT, FAST score and resolution of MASH without worsening of fibrosis was 4.7 (3.3, 6.6), 6.9 (4.3, 10.9) and 3.9 (2.8, 5.5), respectively. ORs (95% CI) for the weight loss-independent effect were 3.0 (2.0, 4.6), 2.8 (1.7, 4.7) and 2.0 (1.4, 3.0), respectively; for the weight loss-dependent effect, ORs (95% CI) were 1.5 (1.2, 2.0), 2.5 (1.8, 3.4) and 1.9 (1.6, 2.4), respectively. Overall, 71.9%, 53.3% and 51.9% of the total effect for ALT, FAST score and resolution of MASH, respectively, were not mediated by weight loss. For the fibrosis-related endpoints, the total effect (OR [95% CI]) for VCTE, ELF score and improvement in fibrosis without worsening of MASH were 3.0 (2.0, 4.4), 4.5 (3.1, 6.4) and 2.1 (1.5, 3.1), respectively. ORs (95% CI) for the weight loss-independent effect were 1.7 (1.1, 2.7), 2.4 (1.6, 3.7) and 1.5 (1.0, 2.4), respectively; for the weight loss-dependent effect, ORs (95% CI) were 1.7 (1.4, 2.2), 1.9 (1.5, 2.3) and 1.4 (1.1, 1.8), respectively. This shows that 48.9%, 58.5% and 55.5% of the total effect for VCTE, ELF score and fibrosis improvement, respectively, were not mediated by weight loss.

Conclusion

Semaglutide 2.4 mg improved MASH-related histological and NIT endpoints and fibrosis-related NIT endpoints through equal contributions of weight loss-independent and weight loss-dependent metabolic mechanisms, with effects beyond weight loss.

Disclosure

Philip N. Newsome reports grants from Novo Nordisk, and has received consulting fees from Boehringer Ingelheim, Madrigal and Novo Nordisk. PNN also reports honoraria as a speaker from AiCME, Echosens and Novo Nordisk; support for attending meetings for Novo Nordisk; and participation on an advisory board for Boehringer Ingelheim, GSK, Madrigal, Novo Nordisk and Sagimet.
Elisabetta Bugianesi served as a consultant or advisory board member for Boehringer Ingelheim, Gilead, Intercept, Merck, Novo Nordisk, Pfizer and ProSciento, and as a speaker for Gilead, Intercept, Merck, Novo Nordisk and Pfizer. EB has also received a research grant from Gilead for fatty liver research.
Vlad Ratziu received consulting fees from Boehringer Ingelheim, GSK, Madrigal, Novo Nordisk, ProSciento and Sagimet, and research grants (to institution) from MSD.
Mary E. Rinella consults for 89bio, Akero, Boehringer Ingelheim, CytoDyn, GSK, HistoIndex, Intercept, Madrigal, NGM Bio, Novo Nordisk, Sagimet and Sonic Incytes. MER has received fees for consulting or participation in advisory boards for Boehringer Ingelheim, Echosens, Eli Lilly and Novo Nordisk. MER also reports honoraria as a speaker for CME events sponsored by Boehringer Ingelheim, Madrigal and Novo Nordisk.
Michael Roden received lecture fees or served on advisory boards for AstraZeneca, Echosens, Eli Lilly, Madrigal, Merck-MSD, Novo Nordisk and Target RWE, and performed investigator-initiated research with support from Boehringer Ingelheim, Novo Nordisk and Nutricia/Danone to the German Diabetes Center.
Arun J. Sanyal consults for and advises AstraZeneca and Avant Santé. AJS also consults for and has received grants from Akero, BMS, Eli Lilly, Intercept, Madrigal and Novo Nordisk. AJS consults for and owns stock in Rivus, and consults for 89bio, AGED Diagnostics, Albireo, Alnylam, Altimmune, Boehringer Ingelheim, Echosens, Genentech, Gilead, GSK, HistoIndex, Mallinckrodt, Merck, NGM Bio, Novartis, PathAI, Pfizer, Poxel, Regeneron Pharmaceuticals, Inc., Salix, Siemens, Surrozen, Takeda, Terns and Zydus. AJS owns stock in Durect, Exalenz, Genfit, Indalo, Inversago and Tiziana, and has received royalties from Elsevier and Wolters Kluwer.
Adel Belloum, Niels Krarup, Anna Cali, Mohamed Tawfik and Thea Vestergaard are employees and stockholders of Novo Nordisk A/S.
Jörn M. Schattenberg declares consultant honoraria from 89bio, Alentis, Alexion, Altimmune, AstraZeneca, Bionorica, Boehringer Ingelheim, Gilead Sciences, GSK, Inventiva Pharma, Ipsen, Eli Lilly, Madrigal Pharmaceuticals, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi and Siemens Healthineers; speaker honoraria from AbbVie, Academic Medical Education, Boehringer Ingelheim, Echosens, Forum für Medizinische Fortbildung, Gilead Sciences, Madrigal Pharmaceuticals, MedicalTribune, MedPublico GmbH, MedScape and Novo Nordisk; and stockholder options in AGED Diagnostics and Hepta Bio.
Matthew J. Armstrong reports investigator fees from Novo Nordisk.
Anja Geerts reports no conflicts of interest.
Jacob George is supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia Program Grant (APP1053206), Project, Ideas and Investigator grants (APP2001692, APP1107178, APP1108422, APP1196492) and a Cancer Institute, NSW grant (2021/ATRG2028). He serves on advisory boards for AbbVie, AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Roche.
Chun-Jen Liu reports no conflicts of interest.
Ewa Janczewska was involved in clinical trials and lectures with Novo Nordisk, was involved in clinical trials with Inventiva Pharma, MSD, Galectin, Dr Falk and Sanofi and reports travel grants from Novo Nordisk and Eli Lilly.
Håvard Midgard is involved in lectures with Novo Nordisk, AbbVie and Gilead, and reports ad boards for Boeringer Ingelheim, AbbVie and Gilead.
Igor Bakulin reports involvement in clinical trials for Novo Nordisk and Eli Lilly and lectures for AbbVie and Johnson & Johnson.