Monday, August 22, 2011

Hepatitis C in HIV-infected Patients With Compensated Liver Cirrhosis

From Journal of Viral Hepatitis
Treatment of Chronic Hepatitis C in HIV-infected Patients With Compensated Liver Cirrhosis
L. Martín-Carbonero; P. Tuma, E. Vispo; J. Medrano, P. Labarga; J. González-Lahoz; P. Barreiro; V. Soriano
Authors and Disclosures
Posted: 08/22/2011; J Viral Hepat. 2011;18(8):542-548. © 2011 Blackwell Publishing

Abstract and Introduction
Patients and Methods

Treatment of chronic hepatitis C has often been declined in HIV–HCV-coinfected patients, mainly because of concerns about poor tolerability of peginterferon–ribavirin and relatively low treatment responses. Moreover, alcohol and/or intravenous drug abuse, neuropsychiatric conditions and poor social environment have all contributed to the low implementation of HCV therapy in this population.[23,24] Given that HCV-related liver fibrosis progress faster in HIV-positive individuals,[11] a growing number of coinfected patients currently present with liver cirrhosis. Current estimates suggest that half of patients older than 50 years who acquired HIV and HCV more than 25 years earlier will show cirrhosis.[25,26] Information on the efficacy and safety of peginterferon–ribavirin in this subset of patients is scarce. This information is important because the risk of liver failure is higher in cirrhotic patients with HIV infection[27,28] and clearance of HCV as a result of successful therapy is the best way to prevent liver decompensation in these patients.[12,15] In this regard, it is encouraging that our study conducted in HIV–HCV-coinfected patients showed a similar rate of SVR and side effects in 41 compensated cirrhotics compared to 190 noncirrhotics, all of whom had been treated with peginterferon–ribavirin. This is in contrast with prior reports, which have reported lower SVR rates and poorer tolerability in patients with advanced fibrosis and cirrhosis. However, this information was mainly drawn from retrospective analysis of the relatively small subset of cirrhotic individuals enrolled in trials conducted either in HCV-monoinfected[16,17,29] or coinfected individuals.[18,19,30] In fact, although the presence of bridging fibrosis and cirrhosis was a predictor of non-SVR in the univariate analysis in some of these studies, only in one of them remained associated with nonresponse in the multivariate analysis.[16] In this respect, a more recent study that compared HCV treatment outcomes in patients with cirrhosis and noncirrhotic monoinfected patients,[31] greater SVR rates were seen in noncirrhotic patients, but cirrhotics were significantly older and had higher body mass index, which most likely explained the results. In fact, in the multivariate analysis only infection with HCV genotypes 1–4 and high-baseline serum HCV-RNA remained as independent predictors of nonresponse.
Even in the face of potential low response rates and poorer tolerability, the benefits of curing hepatitis C in patients with cirrhosis have to be highlighted.[32] HCV clearance following successful treatment is associated with a halt and even reversion of liver fibrosis,[12,33] a reduced risk of liver decompensation events[13–15,34] and most likely a diminished chance of developing hepatocellular carcinoma.[15,34] In this regard, our results demonstrating a similar performance of peginterferon–ribavirin in patients with cirrhosis and noncirrhotics should encourage the consideration of HCV treatment in all HIV–HCV-coinfected patients with cirrhosis in the absence of any serious contraindication for HCV medications.

Liver decompensation may be precipitated following the initiation of peginterferon–ribavirin therapy in subjects with advanced fibrosis, especially in the setting of HIV infection and concomitant antiretroviral therapy.[35] In our study, only one of 41 patients with cirrhosis experienced a liver decompensation event after initiating HCV therapy. It is now clear that avoidance of potentially deleterious drug interactions and careful monitoring of liver function may significantly reduce clinical hepatic events during HCV therapy. Accordingly, none of the 389 coinfected patients enrolled in a recent HIV–HCV therapeutic trial developed liver decompensation, despite 27% of them having baseline F3–F4 Metavir fibrosis scores.[18]
It should be noticed that patients infected with HCV genotypes 1 and 4 showed a relatively low SVR rate (≤35%), regardless of being cirrhotics or not. In contrast, in patients infected with HCV genotypes 2 or 3, SVR rates tended to be higher in noncirrhotic than in individuals with cirrhosis (68%vs 50%, respectively), most likely reflecting a slightly poorer tolerability of the HCV medication in the latest group. In agreement with other trials,[36] in our study, cytopenias and specially thrombocytopenia were the most common treatment limiting side effect and mainly were seen in cirrhotics, forcing drug dose reductions and occasionally treatment withdrawal. Thus, close monitoring of platelet counts and consideration of strategies to prevent and manage thrombocytopenia (e.g., using eltrombopag) should be examined in this population.

Assessment of liver fibrosis before prescription of HCV therapy is increasingly being made using noninvasive tools and replacing liver biopsy. Information on treatment outcomes in the subset of patients with cirrhosis in older studies was mainly derived from fibrosis staging using liver biopsy.[16,17,19,29,30] In our study, elastometry was used to differentiate subjects with liver cirrhosis from the rest. This new method has shown to accurately predict cirrhosis when compared with other approaches, as liver biopsy or serum fibrosis indexes.[21,22,37–41] A wide use of noninvasive tools for assessing liver fibrosis will facilitate the recognition of the subset of chronic hepatitis C patients with advanced fibrosis in whom HCV treatment consideration is warranted. Unfortunately, therapeutic considerations so far often have been based on liver enzyme elevations, which do not reflect liver damage, especially in the HIV setting.[42,43]
Our study has some limitations. As this is a retrospective study, some data as HCV treatment dose reduction or heavy alcohol intake could not be properly recorded. The former information would have been important in terms of SVR. Baseline characteristics had also some differences, patients with cirrhosis had lower CD4 cell counts and were more often on HAART. We believe that does not reflect longer duration of HCV or HIV infection in this population, as the rest of epidemiological characteristics (median age, route of infection, etc) were similar between groups. Even more, the worst HIV characteristics among patients with cirrhosis will bias them towards lower SVR rates, which was not the case.

In summary, our results proving that treatment outcomes in HIV–HCV-coinfected patients with cirrhosis are similar to those obtained in noncirrhotic individuals support that HCV treatment should be offered to all patients with compensated liver disease as long as no serious contraindications for using HCV medications are acknowledged. However, closer monitoring of cytopenias, mainly platelet counts, may be warranted in the subset of patients with liver cirrhosis undergoing HCV therapy.

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