Randomized Trial of Peginterferon alfa-2b and Ribavirin for 48 or 72 Weeks in Patients with Hepatitis C Virus Genotype 1 and Slow Virologic Response

Liver Unit, Valle d'Hebron (Ciberehd) University Hospital, and Biomedical Research Center Network in the Area of Hepatic and Digestive Disorders of the Carlos III Health Institute, Barcelona, Spain.
Hepatology (Impact Factor: 11.06). 10/2010; 52(4):1201-7. DOI: 10.1002/hep.23816
Source: PubMed


The benefit of extending treatment duration with peginterferon (PEG-IFN) and ribavirin (RBV) from 48 weeks to 72 weeks for patients with chronic hepatitis C genotype 1 infection has not been well established. In this prospective, international, open-label, randomized, multicenter study, 1,428 treatment-naïve patients from 133 centers were treated with PEG-IFN alfa-2b (1.5 μg/kg/week) plus RBV (800-1,400 mg/day). Patients with detectable hepatitis C virus (HCV) RNA and a ≥2-log(10) drop in HCV RNA levels at week 12 (slow responders) were randomized 1:1 to receive 48 weeks (n = 86) or 72 weeks (n = 73) of treatment. Sustained virologic response (SVR) rates were 43% in slow responders treated for 48 weeks and 48% in slow responders treated for 72 weeks (P = 0.644). Relapse rates were similar in slow responders treated for 48 or 72 weeks (47% versus 33%, P = 0.169). The safety profile was similar in both treatment arms; serious adverse events leading to discontinuation of treatment were observed in 3.5% of slow responders treated for 48 weeks and 8.2% of those treated for 72 weeks. Among slow responders with a <2-log drop in HCV RNA at week 8, SVR was 39% in the 72-week arm and 19% in the 48-week arm. CONCLUSION: These data suggest that 48 weeks of therapy with PEG-IFN alfa-2b plus RBV (800-1,400 mg/day) should remain a standard-of-care treatment for treatment-naïve G1 slow responders.

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    • "In CHC patients with higher initial level of HCV RNA, irrespectively of the development of RVR, and in patients with EVR, standard 48-week therapy course should be used (Zeuzem et al., 2006, Mangia et al., 2008, Moreno et al., 2010). Studies performed by Berg T., Ferenci P., and others have demonstrated the necessity and advisability of extended 72-week treatment course in case of slow virologic response to AVT (Berg et al., 2006, Ferenci et al., 2010, Buti et al., 2010). Zeuzem S, Shiffman M. et al. recommended reduced 14-16-week AVT for patients infected with HCV genotypes 2 and 3 RNA, in case of low initial viremia (from 400,000 to 800,000 IU/ml) and RVR development (Zeuzem et al., 2004, Shiffman et al., 2007). "

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    • "Treatment response is determined by the sustained virologic response (SVR), which is defined as a negative HCV-PCR result, six months after the end of treatment (7, 8, 14, 15). The SVR is predicted by multiple factors other than the HCV, including; the patient’s gender, viral load and rapid virologic response (RVR), which is defined as either a negative HCV-PCR result after four weeks of treatment or a 2 log reduction in HCV-PCR from the baseline value after four weeks of therapy (7, 8, 16, 18). Alternative treatment options are available for those patients who exhibit a partial response (defined as a greater than 2 log drop in HCV-PCR at week 12, but with detectable HCV-RNA at weeks 12 and 24), null response, or a non-response defined respectively as (less than 2 log decrease in HCV RNA level from baseline at 12 weeks of therapy, and failure to clear HCV RNA from serum after 24 weeks of therapy) (7, 8, 14, 19). "
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    ABSTRACT: Chronic hepatitis C (CHC) is a global infection. In Saudi Arabia, the prevalence of CHC is declining due to the implementation of a blood screening program. However, CHC still remains a leading cause of liver cirrhosis and hepatocellular carcinoma. This is a retrospective study of CHC patients at the King Abdul Aziz University Hospital, Jeddah, Saudi Arabia. Out of a total of 291 CHC patients from the hepatology clinic at King Abdul Aziz University hospital, Jeddah, 279 patients were included in the present study. They were primarily male (152, 54.5%), with a mean age of 50.41 ± 1.72 years. The majority of patients were either Saudi (108, 38.7%) or Egyptian (60, 21.5%). A total of 61 patients received combination treatment with pegylated interferon and ribavirin, and one patient with sickle-cell anemia received pegylated INF monotherapy. Demographic, clinical and laboratory features of the CHC patients, and their responses to treatment were studied. Decompensated cirrhosis was documented in 60 patients (21.5%), and hepatocellular carcinoma in 14 (5%). The mean level of serum alanine aminotransferase was 83.6 ± 231 u/L. The predominant genotype among the 70 patients tested, was genotype 4, followed by genotype 1 (39 and 18 patients, respectively). The sustained viral response (SVR) rate was 82.99%. The main predictive factors for SVR were baseline HCV viral load and rapid virologic response (RVR). The mean duration of follow-up was 4.2 ± .85 years. There were 24 patients who had liver disease-related mortality. our data showed that 22% of CHC patients progress to cirrhosis and another 22% had treatment. Liver related mortality was more common in patients with advanced cirrhosis.
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    • "In patients infected with genotype 2 or 3 who have a low baseline HCV RNA level and who experience an RVR, 16 weeks of therapy could be sufficient [41]. Patients who achieve an EVR require 48 weeks of therapy, whereas patients with a DVR appear to benefit from 72 weeks of treatment [42] [43] [44]. Patients with less than a 2 Log 10 decline in HCV RNA at week 12 are unlikely to achieve SVR and should stop therapy [33]. "
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    ABSTRACT: The multiple steps of the HCV lifecycle have been recently unravelled, thanks to the development of a number of cell-free or cell culture-based model systems. The HCV lifecycle offers a very large number of potential targets of intervention for specific anti-HCV drugs, including direct-acting antiviral drugs and host-targeted agents. HCV virological tools include enzyme immunoassays (EIAs) that detect anti-HCV antibodies and detect/quantify HCV core antigen, and molecular biology-based assays that are used to detect and quantify HCV RNA and to determine the HCV genotype. Recently, point-of-care tests and alternatives to laboratory tests that require whole-blood samples have been developed to improve access to screening, diagnosis and care. Virological tools are used in clinical practice to diagnose acute and chronic HCV infection, to decide who should be treated, to select the optimal therapy and to monitor treatment responses in order to tailor treatment duration.
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