Markers of liver damage due to hepatitis C infection that can be measured from blood samples are as effective in patients with and without HIV, according to the results of a study presented in the 15th December edition of The Journal of Acquired Immune Deficiency Syndromes. This suggests that non-invasive markers of liver damage could be used in HIV / hepatitis C co-infected patients in place of liver biopsies.
The current ‘gold standard’ for measuring the degree of liver damage or ‘fibrosis’ in patients with hepatitis C is to take a biopsy - a small sample of liver tissue - for analysis under the microscope. This procedure is expensive, risky and subject to errors caused by the sampling procedure, as well as human error by the person analysing the sample. It is also not feasible to carry out repeated biopsies on one patient to monitor liver disease or treatment.
A number of markers of liver fibrosis that can be measured in blood samples have been developed, but most have not been assessed in HIV-positive patients. Since HIV or its treatment could affect the levels of these markers, investigators wished to determine their effectiveness in HIV / hepatitis C co-infected patients.
The researchers, from Boston Medical Center, evaluated the fibrosis markers in 97 patients from the CHARM cohort, which consists of hepatitis C-infected injection drug users. Forty of the participants were co-infected with HIV and 57 were HIV-negative. Thirty-three of the HIV-positive patients were taking antiretroviral therapy.
All of the patients had a liver biopsy as part of their medical evaluation. The tissue samples were analysed by a single expert and graded on the ‘Ishak scale’. This scale runs from zero to six, with higher numbers signifying more severe liver damage.
Blood samples were taken within six months of the biopsy. The investigators then measured a range of markers that have been evaluated in HIV-negative patients, before comparing them to the biopsy results for each patient.
The markers included the international normalised ratio (INR), platelet count, ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT), AST platelet ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid and YKL-40.
The researchers found that the correlations between the markers and the degree of fibrosis were similar in the HIV-positive and –negative patients. For example, the AST / ALT ratio did not predict the stage of fibrosis in either the HIV-positive patients (p = 0.11) or those without HIV (p = 0.17). In contrast, the Forns index, which is calculated from a range of biochemical measurements, was significantly linked to the stage of fibrosis in both groups (p = 0.001 and 0.003, respectively).
The investigators saw a trend for the markers to provide slightly better information on fibrosis stage in the HIV-co-infected patients. However, this may be due to the small sample size.
They also found that the markers were more useful in predicting the presence of severe liver damage or ‘cirrhosis’ than less serious damage. This difference was even more marked for the HIV co-infected patients. “Levels of almost all the markers tended to be more abnormal in the hepatitis C virus / HIV-co-infected group at the later stages of fibrosis,” the investigators write.
“We have shown that a variety of non-specific markers and markers of extracellular matrix metabolism perform similarly in HIV-positive and –negative populations and are probably valid in co-infected populations,” the investigators conclude.
“These tests may be of value for the clinical evaluation of hepatitis C virus / HIV-co-infected patients and warrant further study,” they add.