Interferon treatment for chronic hepatitis C infection in hemophiliacs-- influence of virus load, genotype, and liver pathology on response

Abstract

In this study, we assessed the effectiveness of interferon treatment in 31 hemophiliacs with chronic hepatitis C virus (HCV) infection. Interferon alfa-2a (3 MU three times weekly) was administered for 6 months. Response was assessed by both serial alanine transaminase (ALT) and HCV RNA levels measured by a sensitive semiquantitative polymerase chain reaction (PCR) method. HCV genotype was determined by restriction fragment length polymorphism (RFLP), and evidence of changing genotypes during interferon therapy was sought. Severity of liver disease was assessed by both noninvasive and invasive methods, including laparoscopic liver inspection and biopsy. Sustained normalization of ALT levels occurred in eight patients (28%), and seven (24%) became nonviremic as assessed by PCR (<80 HCV/mL). Responders universally cleared HCV RNA within 2 months of starting interferon. Genotype 3a was associated with a favorable response to interferon. No evidence was found for a change in circulating genotype in patients who failed to respond to interferon or who relapsed. This study confirms that response rates to interferon are low in hemophiliacs as compared with other groups with chronic HCV infection. We have also demonstrated that virus load measurement over the first 8 to 12 weeks of treatment is an extremely useful method to identify responders at an early stage.

Hepatitis C infection and outcomes in the Scottish haemophilia population

“…The natural clearance rate of 17.4% is similar to that observed in non-haemophilia cohorts, the slightly lower level possibly reflects the preponderance of males in our study [4]. Previous data report lower rates of SVR for monotherapy in PWH compared with other HCV-infected groups [16][17][18][19] and our SVR (14.5%) is consistent with this. Combination therapy with interferon-alpha and ribavirin produces higher SVR in the non-haemophilia population with levels of 55% using pegylated interferon-alpha and ribavirin [20].…”

Hepatitis C virus infection and interferon therapy in patients with Down syndrome

“…Absence of cirrhosis, young age, and low serum HCV-RNA levels and genotypes 2 and 3 are the factors that are associated with a favorable response to IFN. 27 The present data show that none of the patients with DS cleared viremia on IFN therapy whereas six of the 12 controls had SVR. Demographic factors including sex, age, baseline ALT levels, distribution of HCV genotype, and viral load were not different between the two groups.…”

Hepatitis C virus genotypes in multi‐transfused individuals

“…Although the results of a number of trials indicate that genotype influences response to interferon [12, 48, 501, other factors associated with better response include absence of cirrhosis, young age, early treatment and presence of lobular hepatitis [47, [51][52][53][54]. Initial interferon trials in haemophiliacs tend t o suggest that overall response rates are lower in this group than in other HCV-infected patients although, as seen with other risk groups, patients infected with type 3 do seem to show a better response [55]. Repeated exposure to multiple HCV variants may be an important factor determining the overall poor response seen in haemophiliacs and if genotypes do show different sensitivities to interferon, a shift in the distribution of genotypes following treatment can be anticipated in these multiple-exposed individuals.…”