Results
diarrhoea, abdominal pain, a decrease in hepatic lobular inflammation, liver fibrosis, reduction in hepatic lobular inflammation, fibrosis, vomiting, liver fibrosis stage, infections, Non-Alcoholic Steatohepatitis, abdominal distension, deaths, a decrease, trauma
HYPERTRIGLYCERIDAEMIA, ADVERSE EVENTS, LIVER FIBROSIS, FIBROSIS, INFECTIONS, SECONDARY, ADVERSE EVENT, REGRESSION, EVENTS, GASTROINTESTINAL DISORDERS
Between March 23, 2015, and Nov 10, 2021, we screened 1886 consecutive patients with a history of excessive alcohol consumption and identified 413 eligible for inclusion (Trial profile*Threshold for liver biopsy according to transient elastography was increased during the study period due to increasing knowledge of cutoffs for ruling out clinically significant liver fibrosis. We excluded liver fibrosis in 398 patients using transient elastography cutoff of 6 kPa.At baseline, demographics and clinical characteristics between the rifaximin-α group and the placebo group were similar (Demographic and baseline clinical characteristicsData are median (IQR) or n (%). The sum of percentages might deviate from 100 due to rounding.Hypertriglyceridaemia defined as triglycerides ≥1·7 mmol/L.Low HDL cholesterol defined as low if <1·03 mmol/L for men and <1·29 mmol/L for women.In the per-protocol population, the proportion of patients with a decrease in liver fibrosis stage was similar in both groups (14 [26%] of 54 patients in the rifaximin-α group Forest plot of histological endpoints in the per-protocol populationLiver biopsies were scored according to the scoring system designed by the Pathology Committee of the Non-Alcoholic Steatohepatitis Clinical Research Network.In the per-protocol population, the proportion of patients with an increase in liver fibrosis stage was significantly lower in the rifaximin-α group compared to the placebo group (13 [24%] patients in the rifaximin-α group In the per-protocol population, there was no significant difference between the groups in the proportion of patients with a decrease in hepatic lobular inflammation; however, there was a larger number of patients in the rifaximin-α group than in the placebo group who had a reduction in hepatic lobular inflammation (Changes in non-invasive markers between baseline and 18 months of follow-up in the per-protocol population are shown in Changes in non-invasive fibrosis markers, liver enzymes, and self-reported alcohol consumption for the per-protocol population(A) Forest plot of effect sizes and corresponding 95 % CIs for changes in non-invasive secondary endpoints between baseline and 18 months. (B) Median gamma-glutamyltransferase concentrations over time. C) Median alanine aminotransferase concentrations over time. D) Median self-reported daily alcohol consumption over time. *Data from 91 patients (rifaximin-α n=46; placebo n=45). CAP=controlled attenuation parameter. PRO-C3=N-terminal propeptide of type III collagen. PRO-C4=internal epitope in the 7S domain of type IV collagen. PRO-C8=C-terminal of type VIII collagen.The most common reported adverse events were gastrointestinal disorders (including diarrhoea, abdominal pain, abdominal distension, and vomiting), infections, and trauma (Selected adverse eventsData are number of patients with events (%).The most common adverse events with an incidence above 5% are reported here. Additional information on adverse events is in the A serious adverse event occurred in 14 (21%) of 68 patients in the rifaximin-α group and 12 (18%) of 68 patients in the placebo group (Three patients died during the trial (all in the rifaximin-α group), but none of the deaths were considered related to the study drug (In a per-protocol sensitivity analysis excluding patients who could not experience regression (F0 at baseline), the number of patients who had a decrease in liver fibrosis stage was 14 (27%) of 51 patients in the rifaximin-α group and 15 (30%) of 50 in the placebo group (OR 1·11 [95% CI 0·46–2·73]; p=0·80). In a per-protocol sensitivity analysis excluding patients who could not experience progression (F4 at baseline) the number of patients who had an increase in liver fibrosis stage was 13 (26%) of 50 patients in the rifaximin-α group and 23 (44%) of 52 in the placebo group (0·43 [0·18–1·01]; p=0·053). The results were robust when adjusted for age and sex (