The progression of fibrosis and other HCV-associated histopathologic changes may also be related to coagulationcascade activity and hepatic accumulation of iron, which have been associated with mutations in factor V and hemochromatosis genes, respectively. The HIV-HCV coinfection is a particularly challenging situation. The severity of liver disease must be routinely assessed in these patients in order to initiate treatment before progression of liver disease. An important number of coinfected patients are referred to hepatology clinics only when they have hepatic decompensation, at which time the HCV treatment options are limited.
Drug-induced liver injuries (DILI) following antiretroviral therapy pose significant problems in HIV/HCV co-infection, especially in persons with advanced liver disease and cirrhosis. Dose modifications or even avoidance of liver-metabolized antiretroviral drugs may be required in patients with CP class B and C disease. Overall, in the absence of clinically significant fibrosis, it seems worthwhile to defer treatment. However, it is equally important to apply the results of the clinical studies on a case by case basis, weighing the treatment response rate and the long-term outcomes.
Outlook
Nucleic acid testing, genotyping and assessment of the level of hepatic fibrosis are invaluable tools in the diagnosis of HCV infection, treatment guidance and monitoring. Although LB is still considered the gold standard for the progression of hepatic fibrosis in chronic hepatitis C, a series of non-invasive radiological and serum-based markers are being investigated for their diagnostic accuracy. New real-time PCR tests are faster and more cost-effective methods for the assessment viral kinetics. Virological end points are surrogate references for assessing the efficiency of HCV treatments, but many randomized trials on similar drug classes have established their value in correctly evaluating the clinical outcome. However, biochemical and histological improvements can be attained even in patients who fail to eradicate HCV infection. Obtaining data on the long-term clinical outcomes in patients included in previous treatment trials is logistically difficult, due to relatively high dropout rates and to interferences of retreatment regimens. Cumulative meta-analysis may be relevant for the planning of future clinical trials.