Mortality Due to Chronic Viral Liver Disease among Patients Infected with Human Immunodeficiency Virus

SIR—Chronic infection with hepatitis C virus (HCV) seems to adopt a more aggressive course among HIV-infected individuals, increasing the 20% twenty-year risk for cirrhosis observed among HIV-negative persons. Moreover, the severity of liver disease increases as the immunodeficiency progresses [1]. In this way, HCV may be considered an opportunistic process [2]. Accordingly, the US Public Health Service added progressive chronic HCV infection to its list of AIDS-defining events in 1999. It is not surprising that the impact of end-stage liver disease on the life expectancy of HIV-infected persons is currently of growing concern, because more and more reports in the literature show an increase in the number of deaths due to liver failure among persons infected with HIV [3–7]. For this reason, the recent report by Cacoub et al. [8] in Clinical Infectious Diseases was somewhat unexpected. The authors stated that, to date, there is no evidence for an increase in mortality due to HCV-related liver failure among persons infected with HIV in France. If HCV-related liver disease is, in fact, not a problem among HIV-infected persons, then anti-HCV treatment is not an urgent need for patients coinfected with HIV and HCV. This question needs to be answered because, although new therapies for chronic hepatitis C (e.g., pegylated IFN alone or in combination with ribavirin) provide a cure for nearly one-half of all patients who receive such treatment, they are expensive and are associated with a significant number of side effects. Several factors may help to explain the unexpected findings of Cacoub et al. [8]. First, the authors obtained their data by examining deaths due to cirrhosis or hepatocellular carcinoma among a large number of HIV-infected subjects who were included in cross-sectional surveys conducted in departments of internal medicine and infectious diseases. A more appropriate estimation of the real impact of HCV-related liver failure on mortality among HIV-positive persons might have been obtained by determining, among HIV-infected patients, the proportion of deaths that were, in fact, due to liver failure. When this is done, the mortality rate for this population approaches that reported in other countries (table 1). These findings support the observation that there is an increase in mortality due to end-stage liver disease among HIV-infected patients. If that correction is made, the mortality due to liver failure in France increased ~5-fold from 1995 to 1997, a finding similar to the increase observed in other places [3–7]. Mortality due to end-stage liver disease among HIV-infected individuals before and after the introduction of highly active antiretroviral therapy (HAART). One important limitation of the French study is that HIV-positive patients who died of liver complications in hepatology/gastroenterology departments were not recorded. In our experience, it is quite common for patients to die in hepatology/gastroenterology departments when they patients are hospitalized because of encephalopathy, gastrointestinal bleeding, and/or ascites [5]. On the other hand, Cacoub et al. [8] noted that the prevalence of HCV seropositivity in their population was ~17%. This rate is much lower than that observed in many other places. For instance, the overall rate observed in the EuroSIDA study was 33% [9], but the rate was >50% in Italy and Spain, where injection drug users are the largest proportion of HIV-infected patients. A further point that merits attention is that the interval between the 2 surveys conducted in France was too short (2 years; the surveys were conducted in 1995 and 1997) and does not adequately represent the changes between the era before the introduction of highly active antiretroviral therapy (HAART) and the years after the introduction of HAART. In 1995, the benefit of new drugs and dual nucleoside combination therapy was already appreciated, but in 1997, the benefit of triple-drug therapy with regard to patient survival still had not been realized. A recent report from Italy shows that, although liver failure had only a minor impact on mortality until 1997, it has become the leading cause of death among HIV-infected persons since 1998 [7]. Taking all these facts into account, a more cautious interpretation of the French data does not disagree with the findings of other reports, which show that HCV-related liver disease is an increasing cause of death among HIV-infected patients. We would like to stress that. Because both decompensated cirrhosis and hepatocellular carcinoma appear at a younger age among persons coinfected with HIV and HCV [10], anti-HCV therapy must be considered a priority for patients in that population.