The efficacy and safety of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin, was evaluated in a phase 2b, open-label study of patients with genotype 1, chronic hepatitis C. In all, 458 IFN-alfa treatment-naïve patients were randomized to 48-week treatment with peginterferon alfa (PEG-IFN␣)-2a 180 g one time per week (qwk), or alb-IFN 900 or 1,200 g once every two weeks (q2wk), or 1,200 g once every four weeks (q4wk), administered subcutaneously, plus weight-based oral ribavirin 1,000 or 1,200 mg/day. Hepatitis C virus RNA was measured by real-time polymerase chain reaction (limit of detection: 10 IU/mL). The primary efficacy endpoint was sustained virologic response (hepatitis C virus RNA <10 IU/mL 24 weeks after the end of treatment). By intentionto-treat analysis, sustained virologic response rates were 58.5% (69/118) with alb-IFN 900 g q2wk, 55.5% (61/110) with 1,200 g q2wk, and 50.9% (59/116) with 1,200 g q4wk, and 57.9% (66/114) with PEG-IFN␣-2a (P ‫؍‬ 0.64 for overall test). Discontinuation rates due to adverse events were 9.3% with alb-IFN 900 g q2wk, 18.2% with 1,200 g q2wk and 12.1% with 1,200 g q4wk, and 6.1% with PEG-IFN␣-2a (P ‫؍‬ 0.04). Hematologic reductions were lowest in the q4wk group and comparable across other groups. At week 12, mean treatmentassociated missed workdays were significantly lower with alb-IFN 900 g q2wk versus PEG-IFN␣-2a (1.1 versus 4.3 days; P ‫؍‬ 0.006). Conclusion: Alb-IFN administered q2wk or q4wk may offer comparable efficacy, with an improved dosing schedule, compared with PEG-IFN␣-2a. (HEPATOLOGY 2008;48:407-417.) Abbreviations: AE, adverse event; ANC, absolute neutrophil count; CHC, chronic hepatitis C; CI, confidence interval; EVR12, early virologic response at week 12; HCV, hepatitis C virus; HRQOL, IFN␣, interferon alfa; LOD, limit of detection; LOQ, limit of quantitation; peginterferon alfa; qwk, one time per week; q2wk, once every two weeks; q4wk, once every four weeks; RBV, ribavirin; RVR4, rapid virologic response at week 4; SVR, sustained virologic response; ULN, upper limit of normal. From the 1 J.W. Frankfurt, Germany; 2 University of British Columbia, Vancouver, Canada; Paris, France; 4 Monash University Medical School, Victoria, Australia;5 University of Alberta, Edmonton, Canada; 6 Hadassah University, Jerusalem, Israel;7 Medical University of Bialystok, Poland; Romania; Prague, Czech Republic;10 University of Manitoba, Winnipeg, Canada; 11 Human Genome Sciences Inc., Rockville, MD;and 12 Division of Gastroenterology, Duke Clinical Research Institute, Durham, NC. Received February 21, 2008; accepted April 25, 2008. Supported by Human Genome Sciences Inc., Rockville, MD, and Novartis Pharma AG, Basel, Switzerland (S.Z., E.M.Y., Y.B., S.P., V.G.B., D.S., R.F., V.R., M.G., K.K., J.G.M. Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail: zeuzem@em.uni-frankfurt.de; fax: 49-(0)69-6301-6448. Copyright © 2008 [3][4][5][6][7][8] Approximately 70% ...

Since its discovery in 1988, the hepatitis C virus (HCV) has become a hot topic of research by many groups around the world. This globally spread infectious agent is responsible for a large proportion of chronic viral hepatitides. The clue to halting the hepatitis C pandemic may be the detailed understanding of the virus structure, its replication mechanism, and the exact functions of the various proteins. Such understanding could enable the development of new antivirals targeted against hepatitis C virus and possibly an effective vaccine. This review recaps the current knowledge about the HCV genome 15 years after its discovery. The structure and function of particular viral structural (core, E1, E2) and nonstructural (NS2, NS3, NS4, NS5) proteins and noncoding regions known to date are described. With respect to frequent conflicting reports from different research groups, results reproducibly demonstrated by independent investigators are emphasized. Owing to many obstacles and limitations inherent in doing research on this noteworthy virus, the current knowledge is incomplete and the answers to many important questions are to be expected in the future.

The recent surge in injection drug use (IDU) in Prague, Czech Republic, provided an opportunity to compare the distribution of hepatitis C virus (HCV) genotypes among recent injection drug users and nonusers. We provide evidence that the most common HCV subtype, 1b, has been circulating in Prague longer than the other subtypes but that IDU practice has magnified its recent prevalence, and that the primary drug of choice among IDU subjects appears to influence the prevalence of a particular HCV subtype.

Aim: To determine the prevalence of, and factors associated with, hepatitis C virus (HCV) infection in the population of Czech injecting drug users (IDUs). Design: Multicentric cross-sectional study. Setting: A convenience sample of injecting drug users was recruited using the snowball sampling method. Participants: Sample of 760 IDUs from 9 different Czech regions. Measurement: We used one-drop instant blood tests to determine the anti-HCV antibodies status; a structured questionnaire was completed during the interview with the researcher. We calculated the ratio of positive findings and performed univariate analyses of correlations between predictors and independent variables. Finally, we created a logistic regression model that controlled for age, region of residence, reported sharing of injection paraphernalia, and length of injection drug use and for the interaction between length of injection use and imprisonmentin order to assess the predictive value of imprisonment in an individual’s history. Findings: 226 participants (29.74% of the tested sample) were found to be anti-HCV positive. After adjusting for the sensitivity of the test, the ‘true proportion’ was 34.97% (95% CI: 31.56–38.35). Many correlated independent variables were found in the univariate analyses. In our logistic regression model, we have found that imprisonment increases the odds of being anti-HCV positive by a factor of 4.3. Conclusion: Anti-HCV seroprevalence remains relatively low in the Czech IDUs population compared to similar populations in the developed countries. Regional differences exist in anti-HCV prevalence within the Czech Republic. The strong association of anti-HCV prevalence with imprisonment history when controlled for other potentially clinically important factors suggests the need for more effective preventive measures in Czech prisons.

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