Viral and host factors in the prediction of response to interferon‐α therapy in chronic hepatitis C after long‐term follow‐up

Abstract

Acute infection with hepatitis C virus (HCV) develops into a chronic hepatitis in about 50-70% of patients. Treatment of these patients with interferon-alpha (IFN-alpha) results in a sustained long-term response in only 15-20% but causes numerous unwanted side-effects in a higher percentage of patients. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior to the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow-up, 18 patients (21%) showed a sustained response to IFN-alpha therapy (normalization of serum transaminases and loss of viral RNA from serum) for up to 7 years after therapy had ceased. By univariate and multivariate analyses, no host factors were found to be predictive of response to therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obtained before treatment nor immunogenetic factors (major histocompatibility complex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters showed a strong association with response to therapy. HCV genotype 3 was found significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. However, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or viral genotype. The best association with response to therapy was found to be clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.001). In conclusion, determination of pretreatment viral factors, but not host factors, was significantly correlated with treatment response but did not give an accurate prediction for patients, whereas clearance of HCV RNA from serum after 3 months of therapy was predictive of response to therapy.

Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients

“…Among the host factors, cytokines, which are crucially involved in the regulation of antiviral immune responses, are likely candidates to affect the response to antiviral therapy. [19][20][21][22] For instance, the production of in- appropriate levels of tumor necrosis factor alpha and interleukin-10 have been reported to contribute to viral persistence and to affect response to treatment. [24][25][26] Here, we analyzed the effect of the IL-6 C174G polymorphism on response to HCV-specific treatment in patients with HIV coinfection.…”

“…18 However, the effect of the IL-6 polymorphism on response to HCV-specific treatment has not yet been addressed. Regarding the potentially pivotal role of host genetic factors for the outcome of anti-HCV treatment, [19][20][21][22] the current study was designed to analyze the effect of IL-6 genotypes on response to HCVspecific treatment in both HCV/HIV coinfected and HCV monoinfected patients.…”

Association of human leukocyte antigen-DRB1 alleles with chronic hepatitis B virus infection in the Han Chinese of Northeast China

“…Previous research has shown that the HLA-I genes are in linkage disequilibrium with CHB and the polymorphisms of HLA-II alleles are associated with susceptibility to CHB (7). However, the association is racially and geographically dependent (6,(8)(9)(10).…”

“…Previous research has shown that the HLA-I genes are in linkage disequilibrium with CHB and the polymorphisms of HLA-II alleles are associated with susceptibility to CHB (7). However, the association is racially and geographically dependent (6,(8)(9)(10).The prevalence of HBV infection is extremely high in China and many people with HBV infections develop CHB and some progress to the onset of cirrhosis (11). A follow-up study (1-18.4 years) revealed that 23 and 4.4% of CHB patients with hepatitis B early antigen (HBeAg)-negative serological status progress to the deve lopment of cirrhosis and HCC, respectively (12,13).…”

The Association of HLA Class II Alleles with the Response to Alfa-Interferon/Ribavirin Therapy in Chronic Hepatitis C Patients

“…Meanwhile, other studies found no difference in distribution of HLA alleles between responders and non responders to antiviral therapy, for instance, in German, Knolle et al (1998) have reported that, in patients suffering from chronic hepatitis C and treated with IFN-, the pretreatment viral factors, not host factors, were significantly correlated with treatment response. Romero-Gomez et al (2003) reported that in Spanish population, HLA class II showed no effect on response to interferon treatment.…”