Background: Pre-resection biopsy (PRB) of large non-pedunculated colorectal polyps (LNPCPs, ≥  20 mm) is often performed before referral for endoscopic mucosal resection (EMR). How this affects the EMR procedure is unknown.
Methods: This was a retrospective analysis of a prospectively collected cohort of patients with LNPCPs referred for EMR between 2013 to 2016 at an Australian tertiary center. Outcomes were differences between PRB and EMR histology, and effects of PRB on the EMR procedure.
Results: Among 586 LNPCPs, lesions that underwent PRB were larger (median 35 vs. 30 mm; p  <  0.007), and more commonly morphologically flat or slightly elevated (p  =  0.01) compared with lesions without PRB. PRB histology was upstaged in 26.1 %, downstaged in 13.8 %, and unchanged in 60.1 % after EMR. Sensitivity of PRB was 77.2 % (95 % confidence interval [CI]: 71.1−82.4) for low-grade dysplasia (LGD) and 21.2 % (95 % CI: 11.5−35.1) for high-grade dysplasia (HGD). Where EMR specimen showed HGD, PRB had detected LGD in 76.9 %. Where EMR specimen showed cancer, PRB had detected dysplasia only. PRB was associated with more submucosal fibrosis (p  =  0.001) and intraprocedural bleeding (p  =  0.03). EMR success or recurrence was not affected.

Conclusions: Routine pre-resection biopsy (PRB) of large non-pedunculated colorectal polyps (LNPCPs) did not reliably detect advanced histology and may have affected endoscopic mucosal resection complexity. PRB should be utilized with caution in guiding endoscopic management of LNPCPs.

Prof. Dr. M.J. Bourke, Department of Gastroenterology and Hepatology, Westmead Hospital, Westmead, Sydney, NSW, Australia,

E-Mail: michael@citywestgastro.com.au

DOI: 10.1055/a-1896-9798

Importance: Screening colonoscopy to prevent and early detect colorectal cancer is recommended to be repeated in 10-year intervals, which goes along with high demands of capacities and costs. Evidence of findings at screening colonoscopies conducted 10 or more years after a negative colonoscopy result is sparse, and it remains unclear whether screening colonoscopy intervals could possibly be prolonged.
Objective: To assess the prevalence of advanced colorectal neoplasms (ADNs) at least 10 years after a negative screening colonoscopy in a very large cohort of repeated screening colonoscopy participants in Germany.
Design, setting, and participants: This registry-based cross-sectional study on screening colonoscopy findings reported to the German screening colonoscopy registry during January 2013 to December 2019 included data on screening colonoscopies that were offered to the German general population 55 years or older since 2002; virtually all screening colonoscopies among individuals covered by Statutory Health Insurance (approx. 90% of eligible adults) are reported to the national registry. A total of 120,298 repeat screening colonoscopy participants 65 years or older were identified who had a previous negative screening colonoscopy at least 10 years prior. The findings were compared with all screening colonoscopies conducted at 65 years or older during the same period (1.25 million). The data were analyzed from March to July 2022.
Main outcomes and measures: Prevalence of colorectal cancers and ADNs (advanced adenomas and cancers).
Results: Of 120,298 participants, 72,349 (60.1%) were women. Prevalence of ADN was 3.6% and 5.2% among women and men 10 years after a negative screening colonoscopy and gradually increased to 4.9% and 6.6%, respectively, among those who had a negative colonoscopy 14 years or longer prior compared with 7.1% and 11.6% among all screening colonoscopies. Sex-specific and age-specific prevalence of ADNs at repeated colonoscopies conducted 10 or more years after a negative colonoscopy were consistently at least 40% lower among women than among men, lower at younger versus older ages, and much lower than among all screening colonoscopies (standardized prevalence ratios for cancers = 0.22−0.38 among women, 0.15−0.24 among men; standardized prevalence ratios for ADNs = 0.49−0.62 among women, 0.50−0.56 among men).

Conclusions and relevance: The results of this cross-sectional study suggest that the prevalence of advanced colorectal neoplasms at screening colonoscopies conducted 10 or more years after a negative screening colonoscopy is low. Extension of the currently recommended 10-year screening intervals may be warranted, especially for female and younger participants without gastrointestinal symptoms.

T. Heisser, Abteilung klinische Epidemiologie und Alternsforschung, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany,

E-Mail: t.heisser@dkfz.de

DOI: 10.1001/jamainternmed.2022.6215

Background: The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination.
Methods: In 2020, using a questionnaire, the authors collected empirical, systematic, modelled, or surveyed data – reported by World Health Organization (WHO) country and WHO regional offices – on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data.
Findings: WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. It was estimated that in 2019, globally, 295.9 million (3.8%) people were living with chronic hepatitis B virus (HBV) infection and 57.8 million (0.8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3.0 million new infections with HBV and HCV and more than 1.1 million deaths due to the viruses in 2019. In 2019, 30.4 million (95% confidence interval [CI]: 24.3–38.0) individuals living with hepatitis B knew their infection status and 6.6 million (95% CI: 5.3–8.3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15.2 million (95% CI: 12.1–19.0) had been diagnosed between 2015 and 2019, and 9.4 million (95% CI: 7.5–11.7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019.

Interpretation: There has been notable global progress towards hepatitis elimination. In 2019, 30.4 million (10.3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22.0 million; 9.0%), and 6.6 million (22.7%) of those diagnosed with hepatitis B received treatment, compared with 1.7 million (8.0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in hepatitis C virus (HCV) treatment 10 times that of the strategy baseline. However, an estimated 89.7% of hepatitis B virus infections and 78.6% of HCV infections remain undiagnosed. A new global strategy for 2022–2030, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis.

Dr. D. Low-Beer, Department of Global HIV, Hepatitis and Sexually Transmitted Infections Programs, WHO Headquarters, Geneva, Switzerland,

E-Mail: lowbeerd@who.int

DOI: 10.1016/s2468-1253(22)00386-7

Background: Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. The authors investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis.
Methods: This double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centers in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) ≥ 27 kg/m2 were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2.4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary end point was the proportion of patients with an improvement in liver fibrosis of ≥ 1 stage without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least 1 dose of study drug.
Findings: 71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 patients (69%) were female and 22 (31%) were male. Patients had a mean age of 59.5 years (SD 8.0) and mean BMI of 34.9 kg/m2 (SD 5.9); 53 patients (75%) had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the 2 groups in the proportion of patients with an improvement in liver fibrosis of ≥ 1 stage without worsening of NASH (5/47 patients [11%] in the semaglutide group vs. 7/24 [29%] in the placebo group; odds ratio = 0.28, 95% confidence interval: 0.06–1.24; p = 0.087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p = 0.29). Similar proportions of patients in each group reported adverse events (42 patients [89%] in the semaglutide group vs. 19 [79%] in the placebo group) and serious adverse events (6 [13%] vs. 2 [8%]). The most common adverse events were nausea (21 [45%] vs. 4 [17%]), diarrhea (9 [19%] vs. 2 [8%]), and vomiting (8 [17%] vs. 0). Hepatic and renal function remained stable. There were no decompensating events or deaths.

Interpretation: In patients with non-alcoholic steatohepatitis (NASH) and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised.

R. Loomba, M.D., Professor of Medicine, NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, CA, USA,

E-Mail: roloomba@ucsd.edu

DOI: 10.1016/s2468-1253(23)00068-7

Background and aim: Alcohol-associated hepatitis (AAH) is an acute, inflammatory liver disease with severe short-term and long-term morbidity and mortality. AAH can lead to severe complications including hepatic failure, gastrointestinal bleeding, sepsis, and the development or decompensation of cirrhosis. Rifaximin is an antibiotic that reduces bacterial overgrowth and gut translocation, and it may have a role in decreasing systemic inflammation and infection in patients with AAH. Therefore, the authors conducted a systematic review and meta-analysis to evaluate the role of rifaximin in the management of AAH.
Methods: A comprehensive search strategy was used to identify studies that met the inclusion criteria in Embase, Medline (PubMed), Cochrane Library, Web of Science Core Collection, and Google Scholar. Outcomes of interest included rates of infection, 90-day mortality, and overall mortality between the rifaximin versus non-rifaximin group. Open Meta Analyst software was used to compute the results.
Results: Three studies with a total of 162 patients were included in the final meta-analysis. Of the 3 studies, 2 were randomized control trials, and 1 was a case-control study. There was a significantly lower rate of infection in the rifaximin group versus the non-rifaximin group (risk ratio [RR] = 0.331, 95% confidence interval [CI]: 0.159–0.689, I2 = 0%, p = 0.003). There was no significant difference in 90-day mortality in the rifaximin versus non-rifaximin group (RR = 0.743, 95% CI: 0.298–1.850, I2 = 24%, p = 0.523), nor was there a significant difference in overall mortality (RR = 0.624, 95% CI: 0.299–1.3, I2 = 7.1%, p = 0.208).

Conclusions: The use of rifaximin in alcohol-associated hepatitis (AAH) is associated with a lower rate of infection rate than the non-rifaximin group. Additional research is needed to determine whether this effect is more pronounced in patients concurrently being treated with prednisolone. Differences in 90-day or overall mortality did not reach statistical significance. Further studies, particularly large randomized controlled trials, are needed to establish the role of rifaximin in AAH, especially as an adjunct therapy with prednisolone.

Z. Ahmed, M.D., Department of Internal Medicine, University of Toledo Medical Center, Toledo, USA,

E-Mail: zohaib.ahmed@utoledo.edu

DOI: 10.1111/jgh.16179

Introduction: No study has investigated the efficacy and safety of vonoprazan-amoxicillin dual therapy compared with bismuth quadruple therapy (B-quadruple). This study aimed to evaluate the efficacy and safety of 10-day vonoprazan-amoxicillin dual therapy as a first-line treatment of Helicobacter pylori infection compared with B-quadruple and to explore the optimal dosage of amoxicillin in the dual therapy.
Methods: A total of 375 treatment-naive, H. pylori-infected subjects were randomly assigned in a 1:1:1 ratio into 3 regimen groups including VHA-dual (vonoprazan 20 mg twice/day + amoxicillin 750 mg 4 times/day), VA-dual (vonoprazan 20 mg + amoxicillin 1000 mg twice/day), and B-quadruple (esomeprazole 20 mg + bismuth 200 mg + amoxicillin 1000 mg + clarithromycin 500 mg twice/day). Eradication rates, adverse events (AEs), and compliance were compared between 3 groups.
Results: The eradication rates of B-quadruple, VHA-dual, and VA-dual were 90.9%, 93.4%, and 85.1%, respectively, by per-protocol analysis; 89.4%, 92.7%, and 84.4%, respectively, by modified intention-to-treat analysis; 88.0%, 91.2%, and 82.4%, respectively, by intention-to-treat analysis. The efficacy of the VHA-dual group was not inferior to the B-quadruple group (p < 0.001), but VA-dual did not reach a non-inferiority margin of -10%. The AE rates of the B-quadruple group were significantly higher than those of the VHA-dual (p = 0.012) and VA-dual (p = 0.001) groups. There was no significant difference in medication compliance among 3 treatment groups (p = 0.995).

Conclusions: The 10-day VHA-dual therapy provided satisfactory eradication rates of > 90%, lower adverse event rates, and similar adherence compared with B-quadruple therapy as a first-line therapy for Helicobacter pylori infection. However, the efficacy of VA-dual therapy was not acceptable.

Dr. G.-X. Zhang or Dr. X. Li, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China,

E-Mail: guoxinz@njmu.edu.cn

E-Mail: lixuan20091225@163.com

DOI: 10.14309/ajg.0000000000002086

Purpose: This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma.
Methods: The authors assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1000 mg/m2) or gemcitabine alone to one 30−40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety.
Results: 287 of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cut-off (December 31, 2018; median follow-up, 38.5 [interquartile range {IQR}, 33.8−43] months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR] = 0.88; 95% confidence interval [CI]: 0.729−1.063; p = 0.18). The median investigator-assessed DFS was 16.6 (IQR, 8.4−47.0) and 13.7 (IQR, 8.3−44.1) months, respectively (HR = 0.82; 95% CI: 0.694−0.965; p = 0.02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7−53.3) months, respectively (HR = 0.82; 95% CI: 0.680−0.996; p = 0.045). At a 16-month follow-up (cut-off, April 3, 2020; median follow-up, 51.4 [IQR, 47.0−57.0] months), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR = 0.82; 95% CI: 0.687−0.973; p = 0.0232). At the 5-year follow-up (cut-off, April 9, 2021; median follow-up, 63.2 [IQR, 60.1−68.7] months), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR = 0.80; 95% CI: 0.678−0.947; p = 0.0091). 86% (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events.

Conclusion: The primary end point (independently assessed disease-free survival) was not met despite favorable overall survival seen with nab-paclitaxel + gemcitabine.

M.A. Tempero, M.D., Professor of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA,

E-Mail: mtempero@medicine.ucsf.edu

DOI: 10.1200/jco.22.01134