Management of hepatitis C in HIV infected and other immunocompromised individuals.

ABSTRACT

Host immunity is important in determining the natural history of HCV infection. Patients with ineffective polyclonal HCV specific CD4+ response are persistently infected and loss of HCV-specific CD4+ T cells is associated with relapse of viraemia. Weak HCV-specific CD4+ response early in the course of chronic hepatitis C correlates with higher rates of fibrosis during subsequent course of the disease. In HIV co-infected patients, the HCV load is higher by an average of 0.5-1 log than the mono-infected patients. Based on the evidence from randomized control trials, the therapy for chronic hepatitis C in HIV co-infected patients is pegylated interferon and ribavirin for 48 weeks irrespective of genotype. In patients with CD4 counts < 200 cells/l and/or plasma HIV RNA above 100,000 copies/ml, it is recommended to administer HAART before HCV therapy. The sustained viral response rate achieved in the HCV/HIV co-infected patients is lower than that for mono-infected patients. Pre-treatment HCV RNA level and the genotype are the best predictors of sustained viral response. Treatment may be discontinued at 12 weeks if there is no early viral response as the likelihood of sustained viral response in this sub-group is only 2%. Biochemical response may not be relevant in HIV/HCV co-infected patients as a third of them have normal pretreatment ALT and normalization of ALT does not correlate with virological clearance. Histological response may not also correlate with virological response as up to 43% of subjects without sustained viral response may show histological improvement at the end of 48 weeks treatment. Liver disease due to HCV in patients with end stage renal disease on maintenance dialysis, is a significant cause of morbidity. The value of aminotransferases in patients on haemodialysis is lower than in the non-uraemic population and the level may not rise above the 'normal' range despite active liver disease. HCV RNA may be required to diagnose HCV infection, as anti-HCV may not be detectable, in such patients. Weekly pegylated interferon may be effective in them. In renal allograft recipients, paired biopsies may show rapid progression of liver disease in the absence of fibrosing cholestatic hepatitis. Interferon is contraindicated in this population due to increased risk of graft rejection. Following liver transplantation, recurrence of HCV is universal and histological evidence of recurrent infection may occur as early as 1 to 8 weeks after transplantation. Combination therapy with pegylated interferon and ribavirin may be effective in them.