Liver biopsies, the “gold standard” for reaching treatment decisions for people coinfected with HIV and hepatitis C (HCV) may be unnecessary in the majority of cases as tests on biochemical markers can, in most cases, give an indication of liver damage according to two recent studies. In addition, an editorial comment in the 28th March 2003 edition of the journal AIDS suggests that recent diagnostic and therapeutic advances mean that liver biopsy is not needed in most HIV/HCV coinfected patients.
Liver biopsies, despite their utility as a diagnostic tool, are painful, can cause bleeding, infection and other complications, and in rare cases, death.
In a study published in AIDS French investigators looked at the utility of an index of five biochemical and virological markers at predicting HCV-related liver fibrosis in 130 HIV/HCV patients, treated at the Hopital La Pitie-Salpetriere, Paris between 1995 and 2000.
The markers assessed were age, sex, total bilirubin, gamma-glutamyltranspeptidase (GGT), alpha2-macroglobulin, apolipoprotein A1 and haptoglobin. These markers had been used to accurately determine the degree of fibrosis and risk of further HCV disease progression in HIV-negative, HCV patients. CD4 count and HIV viral load were also recorded.
Investigators found a significant relationship between the stage of fibrosis and alpha2-macroglobin and apolipoprotein. Predictors of septal fibrosis were alpha2-macroglobulin, apolipoprotein A1 and male sex, with GGT of borderline significance.
Investigators argued that it would have been possible to restrict biopsies to patients with scores of borderline significance, therefore “preventing liver biopsies in 55% of patients while maintaining 89% accuracy.” Adding, “as in HIV-negative patients, our non-invasive index of biochemical markers accurately predicts fibrosis in HIV/HCV co-infected individuals.” Indeed, the investigators suggest that not only are non-invasive tests easier to conduct, but they may be more accurate than liver biopsy.
Although lower CD4 counts were found to be associated with septal fibrosis in univariate analysis, this was not the case under multivariate analysis. They suggest that “this probably relates to the strong association between the biochemical markers...and the stage of fibrosis.” No association was found between HIV viral load and the stage of fibrosis.
The investigators conclude, “if independent, prospective studies confirm these findings, this index may substantially reduce the need for liver biopsy and thereby improve the management of coinfected patients.”
In addition, a small Spanish study which was presented to ICAAC in 2002, found that GGT level along with alcohol abuse, duration of HCV infection, age at HCV infection, HCV genotype, HCV viral load, and having an AIDS diagnosis were all predictive of fibrosis in HIV/HCV coinfected patients. Indeed, only 6% of patients with a high GGT level did not have fibrosis.
Recent advances in HCV therapy also make liver biopsy unnecessary, according to an editorial comment in AIDS. The editorial suggests that most HIV/HCV coinfected patients should be considered as candidates for anti-HCV therapy regardless of fibrosis stage, particularly given the greater efficacy of anti-HCV therapy since the introduction of ribavirin and pegylated interferon, and the ability to predict the likely outcome of therapy as early as twelve weeks after starting anti-HCV treatment. The editorial concludes, “given the more aggressive course of HCV infection in HIV-positive individuals, treatment should be considered for all co-infected patients, irrespective of histological findings and based mainly on two particular issues, the CD4 cell count”, as patients with lower CD4 counts have a poorer response to therapy and are more likely to develop side-effects, "and the choice of drug regimen". Use of ddI and AZT should be avoided if anti-HCV therapy is started using ribavirin due to the increased risk of pancreatitis and anaemia if ribavirin is used alongside either drug.
Further information on this website
Hepatitis C - Overview
Liver function tests - Overview
Hepatitis C - Factsheet
The Liver - Factsheet
Draft BHIVA guidelines for management of HIV/HCV coinfection
HIV and hepatitis - Booklet in the information series for HIV-positive people series
Myers RP et al. Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients. AIDS 17: 721-725, 2003.
Quereda C et al. Features and biochemical markers of histological severity in HIV-HCV coinfected patients. 42nd ICAAC, San Diego, abstract H-1722, 2002.
Soriano V et al. Treatment of chronic hepatitis C infection: we must target the virus or liver fibrosis? AIDS 17: 751-753, 2003.