Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis.

Background & Aims: Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from >8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for >4 years.

Methods: Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system.

Reading Communities and Hippocratism in Hellenistic Medicine.

The sect of ancient Greek physicians who believed that medical knowledge came from personal experience also read the Hippocratic Corpus intensively. While previous scholarship has concentrated on the contributions of individual physicians to ancient scholarship on Hippocrates, this article seeks to identify those characteristics of Empiricist reading methodology that drove an entire medical community to credit Hippocrates with medical authority. To explain why these physicians appealed to Hippocrates' authority, I deploy surviving testimonia and fragments to describe the skills, practices, and ideologies of the reading community of ancient Empiricist physicians over the one-hundred year period 175 to 75 BCE.

All-oral therapy with nucleotide inhibitors sofosbuvir and GS-0938 for 14 days in treatment-naive genotype 1 hepatitis C (nuclear).

Sofosbuvir and GS-0938 are distinct nucleotide analogues with activity against hepatitis C virus (HCV) in vitro. We evaluated the antiviral activity and safety of sofosbuvir and GS-0938 alone and in combination in HCV genotype 1 patients. In this double-blind study, 40 treatment-naïve patients were randomly assigned to 4 treatment cohorts: (i) GS-0938 for 14 days, (ii) GS-0938 for 7 days followed by GS-0938 plus sofosbuvir for 7 days, (iii) sofosbuvir for 7 days followed by GS-0938 plus sofosbuvir for 7 days and (iv) GS-0938 plus sofosbuvir for 14 days.

Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial.

Background: The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus (HCV) NS5B polymerase. We assessed the safety and efficacy of sofosbuvir in combination with pegylated interferon alfa-2a (peginterferon) and ribavirin in non-cirrhotic treatment-naive, patients with HCV.

Methods: For this open-label, randomised phase 2 trial, we recruited patients from 42 centres in the USA and Puerto Rico between March 23, 2011, and Sept 21, 2011.

Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial.

Background: Protease inhibitors have improved treatment of infection with hepatitis C virus (HCV), but dosing, a low barrier to resistance, drug interactions, and side-effects restrict their use. We assessed the safety and efficacy of sofosbuvir, a uridine nucleotide analogue, in treatment-naive patients with genotype 1-3 HCV infection.

Methods: In this two-cohort, phase 2 trial, we recruited treatment-naive patients with HCV genotypes 1-3 from 22 centres in the USA.