Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV–HIV International Panel

Abstract

Introduction Chronic hepatitis C (HCV) infection is currently one of the most clinically relevant comorbidities in the HIV population; overall, it affects one third of HIV-positive individuals [1]. Progression to end-stage liver disease occurs faster in coinfected patients [2–4] and decompensated cirrhosis is one of the main causes of hospitalization and death in this population [5–8]. However, the risk of hepatotoxicity using antiretroviral drugs is increased in subjects with underlying HCV infection [9,10]. Therefore, the optimal management of chronic HCV in HIV-positive patients is currently a priority. Several guidelines for caring for HCV infection in HIV-positive individuals have been released [11–15]. Because new and relevant information has recently appeared, it is convenient to update them. Eleven areas have been identified in which new recommendations are particularly needed: management of patients with persistently normal aminotransferases liver fibrosis assessment: when and how predictors of response to anti-HCV therapy in coinfected patients optimal dosages of pegylated interferon (pegIFN) and ribavirin (RBV) optimal duration of anti-HCV therapy treatment of non-responders and/or relapsers care of patients with end-stage liver disease treatment of acute HCV infection in HIV-infected individuals management of patients with multiple hepatitis viruses interactions between HCV medications and antiretroviral drugs hepatotoxicity of antiretroviral drugs. Patients with persistently normal aminotransferases The exact definition of persistently normal aminotransferases is not well established in patients with chronic HCV infection. Fluctuations in aspartate/alanine aminotransferases (AST/ALT) are frequent in HCV-related liver disease and differences in the prevalence of persistently normal ALT may reflect the length of follow-up and/or the number of biochemical determinations made [16–18]. We propose a definition requiring the demonstration of normal ALT in at least three consecutive tests made at least 2 months apart each, over a period of 12 months. One third of individuals who initially meet these criteria, however, may show ALT elevations as the period of observation extends [19–22]. Therefore, the characterization of patients with normal ALT should not be based on sporadic determinations of liver enzymes, and the term ‘asymptomatic’ or ‘healthy’ HCV carrier is inappropriate [22]. A further consideration is that the so-called ‘normal’ limit of aminotransferases has to be revisited, since recent studies have shown that aminotransferase levels in subjects without any liver injury [23] or in persons free of liver-related death on follow-up [24] are definitely lower than those accepted as normal in the past. The degree of aminotransferase elevation generally reflects the extent of liver inflammation. Around 25% of HCV-monoinfected patients show persistently normal ALT [19–22,25] and liver disease is generally less severe in this group [25–28]. Women tend to show more frequently persistently normal ALT than men [28], as well as subjects infected with HCV genotype 4 [29–31]. In contrast, patients with HCV genotype 3 show normal ALT less frequently [31]. As expected considering the immune-mediated nature of HCV-related liver disease, there is little correlation between serum HCV RNA and aminotransferases [32]. Few studies have been conducted so far in coinfected patients with normal ALT. Only 7–9% of this population show persistently normal liver enzymes [31,33]. Exposure to antiretroviral drugs, alcohol abuse and other conditions explain, on the one hand, the lower rate of normal ALT in HIV-positive patients with chronic HCV infection. On the other hand, significant liver fibrosis has been reported in up to 25–40% of coinfected patients with normal ALT [31,33], a prevalence higher than the 10–30% reported in HCV-monoinfected individuals [28,34]. In two recent studies, 12–14% of coinfected patients with normal ALT had cirrhosis on liver biopsy [33,35]. Since less than 15% of HCV-monoinfected individuals with minimal or absent liver fibrosis progress to cirrhosis within 15 years [36], and most patients with normal ALT have mild liver disease [37], these individuals have formerly not been considered for HCV therapy. Moreover, flares in ALT activity and lower treatment responses were reported in the past in patients with normal ALT exposed to IFN, which further discouraged their treatment. However, recent studies in HCV-monoinfected patients have alerted clinicians to the higher liver fibrosis progression in initially mild chronic HCV infection [38] and similar responses to pegIFN plus ribavirin RBV have been obtained in patients with normal than with elevated aminotransferases [39]. Recommendation Given that the prevalence of and progression to advanced liver fibrosis in patients with normal ALT is higher in HIV-positive patients [31,33], these patients should be considered for anti-HCV therapy. Treatment sh