Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.

BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P CONCLUSIONS In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone

Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection

Background Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. Results A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P<0.001) or peginterferon alfa-2a alone (56 percent vs. 29 percent, P<0.001). The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent, 36 percent, and 21 percent, respectively, for the three regimens. Among patients with HCV genotype 1 and high base-line levels of HCV RNA, the proportions of those with sustained virologic responses were 41 percent, 33 percent, and 13 percent, respectively. The overall safety profiles of the three treatment regimens were similar; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin. Conclusions In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

<p>Abstract</p> <p>Background</p> <p>In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.</p> <p>Conclusion</p> <p>The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.</p

Hépatite chronique C à transaminases normales de façon répétée

Environ un quart des malades atteints d’hépatite chronique C ont des transaminases normales de façon répétée. Le pronostic est dans l’ensemble bon. La vitesse de progression de la fibrose est lente et l’évolution vers la cirrhose est rare dans cette population. En raison d’une faible efficacité des traitements disponibles, l’attitude thérapeutique recommandée était jusqu’à présent l’abstention. Avec l’arrivée de la bithérapie interféron pégylé-ribavirine, beaucoup plus efficace, l’opportunité de traiter ces malades doit être rediscutée, en particulier chez ceux qui ont une forte probabilité de réponse prolongée

Hepatitis C Virus Quasispecies Variability Modulates Nonstructural Protein 5A Transcriptional Activation, Pointing to Cellular Compartmentalization of Virus-Host Interactions

Hepatitis C virus (HCV) behaves in infected patients as a complex mixture of genetically distinct but closely related variants referred to as a “quasispecies.” By using quasispecies analysis strategies, we showed that HCV nonstructural protein 5A (NS5A) has a quasispecies distribution in infected humans and that NS5A quasispecies undergo significant genetic evolution over time, as a result of random accumulation of nucleotide mutations during replication. Genetic evolution of the NS5A quasispecies results in sporadic amino acid changes in the protein sequence. By using the functional in vitro model of HCV NS5A transcriptional activation in Saccharomyces cerevisiae, we showed that natural NS5A quasispecies variants induce different levels of transcriptional activation, according to the charge of the residues (and possibly minor conformational changes) in the quasispecies variant sequence. These findings show that the accumulation of mutations on HCV genomes during replication randomly generates variant proteins with quantitatively different functional properties. The fact that each new variant protein is initially produced in a single infected hepatocyte and may or may not subsequently spread throughout the liver (depending on the replication capacities of the variant virus) points to cellular compartmentalization of virus-host interactions during chronic infection. This feature of quasispecies-distributed viruses could play an important role in various aspects of the viral life cycle and related disease

Chronic Hepatitis C Virus and Gastric MALT Lymphoma Congenital Erythropoietin-Dependent Erythrocytosis Responsive to Theophylline Treatment

Cases of lymphocytic monoclonal B-cell proliferation such as non-Hodgkin&apos;s lymphomas have been reported in chronically hepatitis C virus (HCV)-infected patients. Lymphomas of the mucosa-associated lymphoid tissue (MALT) type are due to monoclonal proliferation of B cells showing characteristic histopathological features of MALT. Luppi et al 1 recently reported an unexpectedly high prevalence of HCV infection in a series of patients with low-grade lymphomas of the MALT type in various body sites. This study showed the presence of both anti-HCV antibodies and HCV-RNA in the serum of 8 of 16 MALT lymphoma patients (50%). 1 In another study, Pioltelli et al 2 also observed a high prevalence of HCV infection in low-grade lymphomas of the MALT type (36.4%), although they did not mention the number of cases examined. The aim of the present study was to assess the prevalence of HCV infection in a well-characterized series of 46 patients with gastric MALT lymphoma. Of the 46 patients, 25 had a low-grade lymphoma (14 women, 11 men, mean age 54.2 years, range 30 to 75) and 21 had a high-grade lymphoma (8 women, 13 men, mean age 56.3 years, range 23 to 85). Helicobacter pylori infection was demonstrated by serological and/or histological tests in 37 of 46 patients (80.4%). One hundred sixty-five patients with gastroduodenal disease were recruited to compose the control group. There were 84 patients with duodenal ulcer, 43 with gastric ulcer, and 38 with dyspepsia. The two groups were comparable in terms of the sex ratio, age, prevalence of H pylori, risk factors for HCV infection (previous parenteral exposure to blood products, intravenous drug misuse, nosocomial exposure), and geographical origin. Diagnosis of gastric MALT lymphoma was based on gastric biopsy specimens evaluated according to Isaacson&apos;s classification 3 and by immunophenotypic analysis of surface T-and B-lymphocyte markers. Anti-HCV antibodies were determined by third-generation enzymelinked immunosorbent assay and confirmed by third-generation recombinant immunoblot assay (RIBA) in all patients (Ortho Clinical Systems, Raritan, NJ). There was no significant difference between the prevalence of HCV infection in the MALT lymphoma group and the control group: among the patients with gastric MALT lymphoma, only 1 had anti-HCV antibodies (2.2%), compared with 4 in the control group (2.4%) (not significant). The only MALT patient who tested anti-HCV Ab-positive was also positive for H pylori and belonged to the low-grade MALT lymphoma group. Thus, we found no higher prevalence of HCV infection among patients with gastric MALT lymphoma than in a control group composed of subjects with a gastroduodenal disease similarly related to H pylori infection, with the same risk factors for hepatitis C and deriving from the same geographical region. Our data contrast with those of the Italian teams 1,2 and are more in keeping with those of the American and British teams, 4,5 who did not specifically study gastric MALT lymphoma but found no evidence of a relationship between HCV infection and non-Hodgkin&apos;s lymphoma. To our knowledge, this is the first study to evaluate the prevalence of HCV infection in a large, well-characterized series of patients with gastric lymphomas of the MALT type. Our results indicate that there is no link between HCV infection and gastric MALT lymphoma in France