Risk Factors for Grade 3–4 Liver Enzyme Elevation in HIV and Hepatitis C Coinfected Patients on Combination Antiretroviral Therapy

Abstract

Although coinfection with hepatitis C (HCV) is an established risk factor for hepatotoxicity in HIV-positive patients receiving combination antiretroviral therapy (cART), specific variables that may be predictive of severe hepatotoxicity among co-infected patients receiving cART remain poorly defined. A retrospective cohort study of HIV/HCV coinfected adults from two HIV treatment centers covering the period between December 1998 and December 2003 was conducted to address this question. The primary endpoint of the study was the occurrence of grade 3 or 4 elevation of serum alanine aminotransferase (ALT) during follow-up and the primary predictors of interest were specific antiretrovirals. One hundred five coinfected patients receiving cART for a median of 70 months (interquartile range [IQR], 37, 83) were included in the analysis. Twenty-three (22%) patients developed a grade 3 or 4 increase in serum ALT at least once in follow-up. In univariate analysis, current receipt of lopinavir/ritonavir (LPV/r) (odds ratio [OR] 3.09, 95% confidence interval [CI] 1.14-8.34, p = 0.03), baseline ALT (OR 1.01, 95% CI 1.00-1.02, p = 0.004), and current use of boosting ritonavir (OR 2.84, 95% CI 1.16-7.00, p = 0.02) were significantly associated with a grade 3 or 4 increase in serum ALT, although most patients receiving boosting ritonavir were on lopinavir/ritonavir based regimens. Patients receiving LPV/r had been previously exposed to significantly more antiretrovirals (p < 0.0001), protease inhibitors (p < 0.0001), and nucleoside analogues (p = 0.0009) compared to the rest of the cohort. Further research to better clarify risk factors for hepatotoxicity in coinfected patients is warranted given the challenges in treating this population.

A case series of COVID‐19 patients with chronic hepatitis B virus infection

“…Lopinavir/ritonavir treatment was associated with substantial clinical benefit among severe acute respiratory syndrome coronavirus (SARS‐CoV) infected patients 14,15 . However, previous study reported that lopinavir/ritonavir may have hepatotoxicity in HIV patients 12,16 . A total of 9.1% of HIV antiretroviral‐experienced patients who received lopinavir/ritonavir treatment developed liver enzyme elevation 12 .…”

Liver Toxicity of Antiretroviral Drugs

“…They significantly increase an individual's risk of DILI using antiretrovirals. 11,14, [39][40][41][42][43] Elevated liver enzymes with thrombocytopenia reflecting underlying advanced liver disease with portal hypertension and increased serum creatinine leading to decreased clear-ance of hepatotoxic agents have also been associated with HAART-related DILI. 42 Ethnicity may impact on HAART-associated hepatic toxicity.…”

Incidence and Predictors of Severe Liver Fibrosis in HIV-Infected Patients with Chronic Hepatitis C in Brazil

“…Liver biopsy has traditionally been considered the gold standard method for assessing hepatic fibrosis. It allows staging of HCV hepatic damage and may also inform about comorbidities (antiretroviral toxicity, 31 hemochromatosis, alcohol-related steatosis, nonalcoholic steatosis, autoimmune hepatitis, etc. ).…”