Interferon-based 
                Therapy Less Effective for Hepatitis C Patients with Advanced 
                Liver Fibrosis or Cirrhosis
              
              
                
                 
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                        | SUMMARY: 
                          People with chronic genotype 1 hepatitis C virus (HCV) 
                          infection who have developed advanced liver fibrosis 
                          or cirrhosis are not as likely as those with less severe 
                          disease to achieve sustained virological response to 
                          pegylated interferon plus ribavirin, according to a 
                          report in the February 
                          2010 issue of Hepatology. Sustained response 
                          rates were similar, however, for people with good early 
                          viral suppression. |  |  |  | 
                 
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              By 
                Liz Highleyman
                
                Over years or decades, chronic hepatitis C can progress to severe 
                liver disease including advanced fibrosis 
                affecting large areas of the liver, cirrhosis, 
                and hepatocellular 
                carcinoma (liver cancer).
              
              Savino 
                Bruno and colleagues from Italy conducted a study to assess the 
                safety and efficacy of pegylated 
                interferon alfa-2a (Pegasys) plus ribavirin in people with 
                advanced fibrosis enrolled in 3 international randomized clinical 
                trials.
                
                The analysis included data from 341 chronic hepatitis C patients 
                with hard-to-treat HCV 
                genotypes 1 or 4 patients (99 of whom had bridging fibrosis 
                or cirrhosis) and 1547 patients with genotype 
                2 or 3 (380 of whom had advanced fibrosis or cirrhosis). Genotype 
                1 or 4 patients were treated 48 weeks, while those with genotypes 
                2 or 3 were treated for either 16 or 24 weeks.
                
                The researchers looked at early virological response after starting 
                treatment and sustained virological 
                response (SVR), defined as continued undetectable HCV RNA 
                viral load 24 weeks after completion of therapy.
                
                Results 
                  
              
                 
                  |  | SVR 
                    rates progressively decreased as degree of liver damage increased: | 
                 
                  |  | 
                       
                        |  | Genotype 
                          1 or 4 patients: |   
                        |  | 
                             
                              |  | 60% 
                                SVR without advanced fibrosis; |   
                              |  | 51% 
                                SVR with bridging fibrosis; |   
                              |  | 33% 
                                SVR with cirrhosis (P = 0.0028 for trend). |  |  | 
                 
                  |  | 
                       
                        |  | Genotype 
                          2 or 3 treated for 24 weeks: |   
                        |  | 
                             
                              |  | 76% 
                                SVR without advanced fibrosis; |   
                              |  | 61% 
                                SVR with bridging fibrosis; |   
                              |  | 57% 
                                SVR with cirrhosis (P < 0.0001 for trend). |  |  | 
                 
                  |  | Regardless 
                    of genotype, participants without advanced fibrosis were more 
                    likely to experience early response to treatment. | 
                 
                  |  | Earlier 
                    treatment response was associated with higher SVR rates and 
                    lower relapse rates during post-treatment follow-up. | 
                 
                  |  | Patients 
                    with similar responses during the first 12 weeks of treatment 
                    had similar SVR and relapse rates, regardless of degree of 
                    fibrosis/cirrhosis. | 
              
              Based 
                on these findings, the study authors concluded, "Compared 
                with patients with less severe disease, SVR rates are significantly 
                lower in patients with advanced fibrosis."
                
                However, they added, "irrespective of genotype and degree 
                of fibrosis, the time to become hepatitis C virus (HCV) RNA undetectable 
                was the strongest predictor of SVR."
                
                AO Fatebenefratelli e Oftalmico, Milan, Italy; Virginia Commonwealth 
                University Medical Center, Blacksburg, VA; The Alfred Hospital, 
                Melbourne, Australia; Auckland Clinical Studies, Auckland, New 
                Zealand; IST, Mannheim, Germany; Henry Dunant Hospital, Athens, 
                Greece; Service d'Hepatologie and Centre de Recherches Biologiques 
                Bichat Beaujon (Inserm CRB3), Hôpital Beaujon, Clichy, France.
                
                4/9/10
              Reference
                S 
                Bruno, ML Shiffman, SK Roberts, and others. Efficacy and safety 
                of peginterferon alfa-2a (40KD) plus ribavirin in hepatitis C 
                patients with advanced fibrosis and cirrhosis. Hepatology 
                51(2): 388-397 (Abstract). 
                February 2010.