1-7 Many of these trials showed only a reduction in inflammation with no change in fibrosis, and most evaluated histology within 6 months of the last dose of therapy. However, long-term histologic improvement, including improvement in fibrosis and loss of detectable intrahepatic HCV RNA, has been demonstrated in patients with

chronic hepatitis C (CHC) who have had a sustained virologic response (SVR) to interferon alfa therapy.5 Although histologic response is correlated Maraviroc cell line with SVR, improvements in liver histology have been observed in non-SVR treatment-naïve HCV-monoinfected patients.8-11 Histologic response has also been observed in non-SVR patients who are coinfected with HCV/human immunodeficiency virus (HIV),1, 4, 6, 7 patients with advanced fibrosis or compensated cirrhosis,2, 3 and hemodialyzed patients with CHC.12 Some

of these Everolimus in vitro studies also suggested that histologic improvements occurred in patients who became HCV RNA detectable following initial viral clearance (patients with relapse and breakthrough).2, 4 However, the number of patients with paired-biopsies in these individual studies was small. It is also important to note that there were no improvements in fibrosis stage or progression after long-term maintenance therapy with pegylated interferons or in posttransplant patients who failed to achieve SVR with HCV therapy.13, 14 The objective of this analysis was to assess the histologic response to interferon-based therapies, based on changes in the METAVIR necroinflammatory (NIF) activity and fibrosis scores in a Tryptophan synthase large group of patients with varying degrees of virologic

response, time to HCV RNA undetectability, and duration of viral suppression. APRICOT, AIDS Pegasys Ribavirin International Coinfection Trial; cEVR, complete early virologic response; CHC, chronic hepatitis C; HALT-C, Hepatitis C Antiviral Long-term Treatment Against Cirrhosis; HCV, hepatitis C virus; HIV, human immunodeficiency virus; NIF, necroinflammatory; RVR, rapid viral response; SD, standard deviation; SVR, sustained virologic response. Patients (HCV genotypes 1-6) who had both baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based clinical trials were pooled and included in the analysis.15-22 Four of the eight studies were open-label, randomized, multicenter, phase 2/3 studies comparing different dose regimens of peginterferon alfa-2a monotherapy with interferon alfa-2a monotherapy in interferon-naïve patients with CHC.15-17, 20 Two of the studies were phase 4 trials of peginterferon alfa-2a/ribavirin combination therapy, which evaluated patients with adverse prognostic factors, including African Americans and Latinos.18, 22 The remaining two studies were randomized, multicenter, phase 3 studies of interferon-naïve patients; the first study compared peginterferon alfa-2a monotherapy, peginterferon alfa-2a/ribavirin combination therapy, and interferon alfa-2b/ribavirin combination therapy.