Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.

BACKGROUND: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis. METHODS: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan® <9.5 kPa and Fibrotest®  < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12). FINDINGS: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan® , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24. INTERPRETATION: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks.

Recalibrated MELD and hepatic encephalopathy are prognostic factors in cirrhotic patients with acute variceal bleeding.

BACKGROUND & AIMS: Early TIPS placement must be considered in patients with Child-Pugh B and active bleeding at endoscopy or in patients with Child-Pugh C 10-13 and variceal bleeding. However, active bleeding at endoscopy is a subjective criterion. Moreover, a previous study has shown that a MELD-based score accurately predicted 6-week mortality and helped to stratify patients. Using a prospective series of patients included in a multicentre study before the era of early TIPS, we aimed (i) to identify factors associated with 6-week mortality, focusing on the prognostic value of active bleeding; and (ii) to assess whether a recalibrated MELD-based score accurately predicted 6-week mortality. METHODS: Ancillary study of the prospective multicentre Baveno IV study, including patients with acute variceal bleeding. RESULTS: Two hundred and nineteen patients were analysed (Child-Pugh A/B/C = 18/45/37%). The overall actuarial likelihood of survival on day 42 was 84%. The variability for the diagnosis of active bleeding at endoscopy was high (range, 41.4% to 84.6% among the centres). Active bleeding at endoscopy was not associated with 6-week mortality in the entire population or in Child-Pugh B patients. In a multivariate analysis, independent factors associated with mortality were liver function, infection, HE and HCC. The recalibrated MELD-based score was accurate in predicting 6-week mortality (AUROC = 0.787). The recalibrated MELD-based score demonstrated better performance compared to the MELD score. CONCLUSION: The recalibrated MELD-based score accurately predicted mortality in our prospective cohort. Active bleeding at endoscopy had no prognostic value in cirrhotic patients presenting with acute variceal bleeding. Standardizing active bleeding assessment at endoscopy is warranted.

Infliximab therapy for rheumatic diseases in patients with chronic hepatitis B or C.

OBJECTIVE: To describe the safety of tumor necrosis factor-a blockade in 2 patients with inflammatory rheumatic disease with chronic hepatitis B and C. METHODS: We used infliximab therapy in 2 patients with chronic inflammatory joint disease and chronic hepatitis B or C. We describe the clinical and laboratory test data obtained in these patients during the first year of treatment. Disease activity, liver function tests, and HCV and HBV status were evaluated before infliximab therapy was started and were reevaluated before each infusion. Liver biopsy was performed in both patients before infliximab therapy. RESULT: After more than one year of treatment, no worsening in liver function or virological status was observed, while a dramatic clinical improvement of joint disease was observed in both patients. CONCLUSION: These cases suggest that infliximab therapy may be safe in some quiescent or controlled chronic HBV or HCV infection.