Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis.

BACKGROUND & AIMS: Primary biliary cholangitis (PBC) is an autoimmune disease characterized by bile duct destruction that can progress to cirrhosis. A liver biopsy substudy was conducted in the PBC obeticholic acid (OCA) International Study of Efficacy (POISE) to determine the long-term effects of OCA on liver damage and fibrosis in patients with PBC. POISE is a phase 3, double-blind, placebo-controlled, randomized trial with a 5-year open-label extension that evaluated 5 to 10 mg OCA daily in patients who were intolerant or unresponsive to ursodeoxycholic acid. METHODS: Liver biopsy specimens were collected from 17 patients at time of enrollment in the double-blind phase and after 3 years of OCA treatment. Histologic evaluations were performed by 2 pathologists in a blinded, randomized fashion to determine the effects of OCA on fibrosis and other histologic parameters. Collagen morphometry assessments were performed by automated second harmonic generation and 2-photon excitation microscopy to observe quantitative measures of fibrosis. RESULTS: From the time of enrollment until 3 years of treatment, most patients had improvements or stabilization in fibrosis (71%), bile duct loss (76%), ductopenia (82%), ductular reaction (82%), interface hepatitis (100%), and lobular hepatitis (94%). Over the 3-year period, we found significant reductions in collagen area ratio (median, -2.1; first quartile, -4.6, third quartile, -0.3; P = .013), collagen fiber density (median, -0.8; first quartile, -2.5; third quartile, 0; P = .021), collagen reticulation index (median, -0.1; first quartile, -0.3; third quartile, 0; P = .008), and fibrosis composite score (median, -1.0; first quartile, -2.5; third quartile, -0.5; P = .002). CONCLUSIONS: A subanalysis of data from the POISE study showed that long-term OCA treatment in patients with PBC is associated with improvements or stabilization of disease features, including ductular injury, fibrosis, and collagen morphometry features (ClinicalTrials.gov no: NCT01473524 and EudraCT no: 2011-004728-36).

Cost effectiveness of entecavir versus lamivudine with adefovir salvage in HBeAg-positive chronic hepatitis B.

OBJECTIVE: To evaluate the cost effectiveness of treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with entecavir compared with lamivudine with adefovir salvage, based primarily on the results of a recent 2-year, randomised, multicentre, clinical trial (n = 709). Previous economic analyses have been limited by the lack of comparative clinical data for entecavir and lamivudine beyond 1-year duration and for salvage therapy. METHODS: We conducted a cost-utility analysis using a Markov model from a US-payer perspective over a lifetime time horizon. The hypothetical cohort was 35-year-old patients with HBeAg-positive CHB. We evaluated 2 years of treatment with entecavir 0.5mg/day versus lamivudine 100mg/day, plus addition of adefovir 10mg/day for patients who developed virologic breakthrough due to resistance to either drug. In a scenario analysis, we considered adefovir plus lamivudine combination therapy for treatment-naive patients. Clinical and economic inputs ($US, year 2006 values) were derived from publicly available data, and probabilistic sensitivity analyses were conducted to evaluate uncertainty in the results. RESULTS: The estimated 10-year cumulative incidence of cirrhosis for patients initiated on entecavir was 2.3% lower than for those on lamivudine (20.5% vs 22.8%). The discounted incremental cost per QALY gained was $US7600 in the base-case analysis, and the 95% central range from probabilistic sensitivity analysis was $US2500-$US19 100. Combination therapy for treatment-naive patients led to an increase in costs without improvement in patient outcomes compared with entecavir monotherapy. CONCLUSIONS: Our analysis suggests entecavir improves health outcomes in a cost-effective manner compared with lamivudine with adefovir salvage or combination therapy, and highlights the importance of using evidence-based effectiveness estimates in economic studies of CHB therapies.