No abstract

HAART regimens including nevirapine are associated with faster liver fibrosis progression in HIV-infected patients with chronic hepatitis C. In contrast, patients on PI as the backbone of potent antiretroviral therapy are more likely to show less liver fibrosis.

Background: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/ HCV coinfected patients. Aim: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. Patients: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. Methods: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results: The models performed better when liver biopsies >15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27-34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. Conclusions: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.

IL28B gene variations independently predict SVR in HIV/HCV-coinfected patients with HCV genotype 1 and non-genotype 1 HCV infection. The association between rs12979860 and plasma low-density lipoprotein cholesterol suggests that the system low-density lipoprotein ligand/receptor might be involved in the effect of this genotype.

Liver toxicity is one of the most relevant adverse effects of antiretroviral therapy. Within the non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz can be considered a safer drug for the liver than nevirapine. In fact, the frequency of severe increased liver enzymes in patients on efavirenz ranges from 1 to 8%, whereas in patients treated with nevirapine, it ranges from 4 to 18%. Likewise, nevirapine is more commonly associated than efavirenz with early acute hepatitis, which is produced by a hypersensitivity mechanism and has a defined risk profile that often makes it avoidable. Despite the fact that most cases of NNRTI-induced liver toxicity are asymptomatic, the rates of symptomatic events in patients treated with nevirapine are greater than in subjects on efavirenz. In any case, it is unusual for an NNRTI to be suspended due to liver toxicity.