Response-guided pegylated interferon (peg-IFN) plus ribavirin (P/R) therapy trials on genotype (G)1 and G2/G3 hepatitis C virus-infected patients provide contradictory results. We conducted meta-analyses of randomized, controlled trials to address (1) the benefit of a 72-week extended-duration therapy in G1-slow responders and (2) adequate shortened duration therapy in G1 and G2/G3-rapid responders. Seventeen trials were selected, including 624 G1 rapid responders, 570 G1 slow responders, and 2,062 G2/G3 rapid responders. Virologic outcomes and treatment discontinuation data were collected from published articles and by asking investigators. Pooled estimates of sustained virologic response (SVR), relapse, and dropouts were calculated using the random effects model, considering the variability of shortened duration, ribavirin dose, genotype, and baseline viral load. In G1 slow responders, a 72-week extended duration increased SVR (110.7%; 95% CI [confidence interval]: 14.4% to 1 17.1%), decreased relapse (212.3%; 95% CI: 225.4% to 0%), and did not significantly increase drop-out rates (14.5%; 95% CI: 20.6% to 1 9.6%). The benefit of extended duration was lower when using a weight-based ribavirin regimen (18.7%; 95% CI: 11.7% to 1 15.8%). In G1 rapid responders, a 24-week shortened duration decreased SVR (212.5%; 95% CI: 219.2% to 25.8%) and increased relapse rates (18.8%; 95% CI: 12.9% to 1 14.8%). Such differences were not significant in patients with baseline viral load <400,000 UL/mL (24.4%; 95% CI: 29.8% to 1 1%). In G2/G3 rapid responders, SVR was more common for standard 24-week duration than for shortened durations (14.1%; 95% CI: 10.1% to 1 8.5), but this benefit was not significant when ribavirin was weight-adjusted and the short duration was 16 weeks (21.7%; 95% CI: 26.1% to 1 2.7%) and for G2 patients (11.6%; 95% CI: 20.2% to 1 5.5%). Conclusion: Long durations of P/R therapy improve SVR, regardless of genotype. This effect is nonetheless negligible in rapid responders, with the most favorable conditions for SVR (G2, G1 with low viral load, and G3 with weight-adjusted ribavirin regimen). (HEPATOLOGY 2011;54:789-800) T he standard of care for chronic hepatitis C is the combination of peg-interferon plus ribavirin that leads to hepatitis C virus (HCV) eradication in 60% of cases, with variations depending on the characteristics of host and virus and, in particular, viral genotype. 1,2 Patients infected with genotype 1Abbreviations: 95% CI, 95% confidence interval; cEVR, complete early virologic response; G1, genotype 1; G2/G3, genotype 2 and 3; HCV, hepatitis C virus; IFN, Interferon; IL-28B, interleukin-28B; ITT, intention-to-treat method LVL, low viral load; PCR, polymerase chain reaction; peg-IFN, pegylated interferon; P/ R, peg-interferon plus ribavirin; RCTs, randomized, controlled clinical trials; RVR, rapid virologic response; SRs, slow responders; SVR, sustained virologic response.From the

SummaryBackgroundObeticholic acid (OCA) and fibrates are second‐line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA).AimTo know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult‐to‐treat PBC.MethodsPBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second‐line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed‐effect model.ResultsAmong 58 patients included, half received OCA as second‐line and fibrates as third‐line therapy (Group OCA‐Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate‐OCA). The mean duration of triple therapy was 11 months (range 3‐26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%‐31%), an effect that was stronger in OCA‐Fibrate than in Fibrate‐OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4‐8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma‐glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris‐2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8‐16.7) and 9.2 (95% CI 3.4‐25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA‐Fibrate but not in Fibrate‐OCA group.ConclusionsTriple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult‐to‐treat PBC.

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BackgroundThe prognosis of cirrhotic patients admitted to the ICU is considered to be poor but has been mainly reported in liver ICU. We aimed to describe the prognosis of cirrhotic patients admitted to a general ICU, to assess the predictors of mortality in this population, and, finally, to identify a subgroup of patients in whom intensive care escalation might be discussed.ResultsWe performed a retrospective monocentric study of all cirrhotic patients consecutively admitted between 2002 and 2014 in a general ICU in a regional university hospital. Two hundred and eighteen cirrhotic patients were admitted to the ICU. The 28-day and 6-month mortality rates were 53 and 74 %, respectively. Among the 115 patients who were discharged from ICU, only eight patients underwent liver transplantation, whereas 48 had no clear contraindication. Multivariable analyses on 28-day mortality identified three independent variables, incorporated into a new three-variable prognostic model as follows: SOFA ≥ 12 (OR 4.2 [2.2–8.0]; 2 points), INR ≥ 2.6 (OR 2.5 [1.3–4.8]; 1 point), and renal replacement therapy (OR 2.3 [1.1–5.1]; 1 point). For a value of the score at 4 (16 % of patients), 28-day and 3-month mortality rates were 91 and 100 %, respectively. An external validation of the score among 149 critically ill cirrhotic patients showed a good accuracy for predicting in-ICU mortality.ConclusionsMortality of cirrhotic patients admitted to a general ICU was comparable to that of other studies. A pragmatic score integrating the SOFA score, INR, and the need for extrarenal epuration was strongly associated with mortality. Among the 16 % of patients presenting with score 4 at ICU admission, 100 % died in the 3-month follow-up period. The prognostic evaluation on day 3 remains essential for the majority of patients. However, this score calculable at ICU admission might identify patients in whom the benefit of intensive care escalation should be discussed, in particular when liver transplantation is contraindicated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0194-9) contains supplementary material, which is available to authorized users.

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These results suggest that in celiac disease, gluten-driven T-cell activation is not restricted to the proximal part of the intestine but is present on the whole intestinal length. Assessment of the effectiveness of a gluten-free diet through rectal biopsies warrants investigation, as it could lessen discomfort for patients and prove more cost-effective.