Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial

Fast Fibrosis Progression Between Repeated Liver Biopsies in Patients Coinfected with Human Immunodeficiency Virus/Hepatitis C Virus†

“…The distribution of individual antiretroviral drugs and of treatment regimens prescribed during the follow-up is represented in the Table 2. The median (Q1-Q3) length of the initial biopsy was 17 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) with a range of 12-30 mm. The median (Q1-Q3) length of the second biopsy was 18 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25) with a range of 15-30 mm.…”

“…Regression of liver fibrosis has been observed in HIV-infected and uninfected subjects with chronic hepatitis C who achieve SVR 20,21 and in HCV-monoinfected patients treated with pegylated interferon plus ribavirin without SVR. 22 Suppression of HIV replication through HAART was associated with a slower estimated fibrosis progression rate in a single liver biopsy study. 9 However, paired liver biopsy studies in coinfected patients have not found any relation between HAART and fibrosis progression.…”

Impact of High-Dose Peginterferon Alfa-2A on Virological Response Rates in Patients with Hepatitis C Genotype 1: a Randomized Controlled Trial† ‡

“…Patient exclusion criteria included: infection with HCV genotype other than genotype 1 (genotype non-1), hepatitis B virus, and/or human immunodeficiency virus; history of decompensated liver disease; evidence of hepatocellular carcinoma; causes of chronic liver disease other than HCV; therapy with any systemic antiviral, antineoplastic, or immunomodulatory agent within 6 months prior to first receiving study drug; pregnancy or breast feeding, or male partners of women who were pregnant; neutrophil count Ͻ1500 cells/mm 3 ; platelet count Ͻ90,000 cells/mm 3 ; hemoglobin concentration Ͻ120 g/L in women or Ͻ130 g/L in men; serum creatinine level Ͼ1.5 times the upper limit of normal at screening; active severe psychiatric disease; history of immunologically mediated disease or any severe chronic or uncontrolled disease; current or recent drug or alcohol abuse; and unwillingness to provide informed consent. Patients with cirrhosis were also excluded due to the potential enhanced toxicity of induction therapy.…”

“…In patients receiving standard dose PEG-IFN␣-2a, the decremental adjustment in the weekly dose was from 180 g to 135 g, 90 g, and 45 g; in patients who were receiving 360 g of PEG-IFN␣-2a, the decremental adjustment was from 360 g to 270 g, 180 g, 135 g, 90 g, and 45 g, depending on the severity of adverse events. Specific guidelines for PEG-IFN␣-2a dose adjustment for neutropenia included dose reduction to 135 g for patients with fewer than 750 cells/mm 3 , and for those with fewer than 500 cells/mm 3 to suspend therapy until counts rose above 1000 cells/mm 3 . When required, adjustments to the daily dose of ribavirin were performed in gradual stepwise decrements of 200 mg.…”

Host genetic determinants in hepatitis C virus infection

“…Newer regimens such as pegylated interferon-a in combination with ribavirin result in viral eradication in approximately 50% of individuals with genotype-1 infections and 70% of those with non-1 type infections. 13,14 In addition to viral (ie, viral genotypes) and environmental/behavioural factors (ie, coinfections or excessive alcohol intake), host genetic factors are believed to exert an impact on the outcome of HCV infection. Studies among monozygotic twins suggest that host genetic factors may account for 50% or more of the variability in the major outcomes in infectious diseases.…”