A study published in the January 1st edition of Clinical Infectious Diseases has found that patients who are coinfected with HIV and hepatitis C virus (HCV) are at increased risk of developing severe liver fibrosis if they are male, older than 35 years of age, have CD4 cell count below 500 cells/mm3 or drink alcohol. The study also found that the use of HAART neither protects patients from the development of fibrosis, nor worsens fibrosis.
The investigators also warn that the number of HIV/HCV coinfected patients presenting with end stage liver liver disease has not yet peaked and will continue to rise. They also argue that anti-HCV therapy consisting of ribavirin and pegylated interferon should be initiated in HIV/HCV coinfected individuals at "the earliest possible stage."
Investigators from ten European HIV treatment centres in four countries collaborated in a retrospective study which included 914 HIV/HCV coinfected patients who had both abnormal liver functions test and liver biopsy information available.
Patients’ demographic data were gathered, including sex, age, HIV/HCV risk group, and history of alcohol consumption (above 50mg per day for a year was considered high alcohol consumption). HIV viral load and CD4 cell count at the time of liver biopsy, and the use if anti-HIV therapy were recorded. Information on duration of HCV infection, HCV genotype and HCV viral load were also collected.
The severity of liver fibrosis was assessed on the five point METAVIR scale, with stage F0 indicating no fibrosis, and stage F4 cirrhosis.
Most of the patients were male (75%), and former injecting drug users (83%). A quarter of individuals were assessed as having a history of high alcohol intake. The median age of individuals was 37 years, and the estimated median duration of HCV infection was 16 years.
HCV genotype 1 was most prevalent (56%), followed by genotype 3 (32%). A HCV viral load above 800,000 copies/mL was present in 58% of patients at the time of liver biopsy, at which point the median CD4 cell count was 480 cells/mm3, with only 9% of individuals having severe immune suppression and a CD4 cell count below 200 cells/mm3.
At the time of liver biopsy, 55% of patients were taking HAART, and a further 15% were taking either dual or mono antiretroviral therapy. An undetectable HIV viral load (below 200 copies/mL) was present in 54% of individuals.
Severe fibrosis (stages F3 or F4) was present in 47% of individuals.
In univariate analysis, the investigators found that male sex (p=0.0017), alcohol consumption above 50mg a day (p<0.001), age over 35 years (p<0.001), 15 years or more of hcv infection (p<0.001), a cd4 cell count below 500 cells/mm3 (p=0.05), and the use of HAART were associated with an increased risk of severe fibrosis.
However, in multivariate analysis, only age above 35 years (p<0.001), high alcohol consumption (p=0.01), and a cd4 cell count below 500 cells/mm3 (p=0.02) remained significantly associated with severe liver fibrosis. Because most patients receiving HAART were aged over 35, use of HAART was found to be a confounding factor of age and ceased to have a significant association with the risk of fibrosis. The investigators comment that neither did they find any protective effect from the use of HAART, despite the fact that HIV accelerates the course of HCV infection. “In summary, HAART may have neither a protective nor a deleterious impact on HCV-related liver fibrosis in HIV-infected patients”, comment the investigators.
The investigators suggest that their findings have clinical implications. First, given the association between the severity of fibrosis and age, the investigators state that the number of HIV/HCV coinfected patients “with end stage liver disease has not yet peaked and will be on the rise.” Second, strategies aimed at preventing infection with HCV are needed. Third, given the association between severe fibrosis and lower CD4 cell count, anti-HCV therapy, comprising of pegylated interferon and ribavirin, should be initiated at “the earliest possible stage.”
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Martin-Carbenero L et al. Incidence and predictors of severe liver fibrosis in HIV infected patients with hepatitis C: a European collaborative study. Clinical Infectious Diseases 38: 128 – 133, 2004.