Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort

Abstract

ObjectiveTo assess the current frequency of ART-associated grade 3–4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART.Patients and MethodsA total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study.ResultsForty-one (21.4%) subjects had been naïve to ART, median (IQR) follow-up was 11.6 (5.6–12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53%-9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417–37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3–4 TE.ConclusionsCurrently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern.

Liver damage in patients living with HIV on antiretroviral treatment with normal baseline liver function and without HBV/HCV infection: an 11-year retrospective cohort study in Guangxi, China

“…This retrospective cohort study was conducted on HIV-positive individuals with an initially normal hepatic function and without HBV/HCV infection. We found that liver damage (grade II–IV LEE/TBE) occurred in all patients at different period of ART, indicating that hepatic damage always exists among HIV/AIDS patients receiving ART, which has been shown in a few previous studies,4 5 although the incidence rate of LEE/TBE in our study was quite stable and low in the longer ART during times. Our study showed that the liver damage prevalence was 12.41% (263/2119) (figure 1), which is lower than those (14%–23%) in several previous studies conducted on HIV/AIDS patients 21 22.…”

“…Hepatitis viral infections, either hepatitis B virus (HBV) or hepatitis C virus (HCV), have been reported to lead to hepatotoxicity 12 13. Elevated hepatotoxicity was observed to be associated with ART in HIV/AIDS patients co-infected with HBV or HCV 4 12. ART-related hepatotoxicity was also reported in quite a few previous studies 6 11 13.…”

“…An earlier study showed that the prevalence of liver transaminase elevation among HIV-positive individuals on ART ranged from 14% to 20% 5. Consistently, some researchers have found the incidence of hepatic injury in ART-treated patients was increased 4. However, quite a few other studies indicated that the approved antiretroviral agents have low liver toxicity and generally are considered to be well tolerated 6 7…”

“…With the implementation of ART, the life expectancy of HIV-infected individuals is now approaching that of the general population 3. However, ART has some adverse effects, especially hepatic damage, which comes along with the treatment 4. An earlier study showed that the prevalence of liver transaminase elevation among HIV-positive individuals on ART ranged from 14% to 20% 5.…”

“…Although there are many studies focusing on relationship of ART and liver function among HIV-1 infected patients, after extended exposure to antiretroviral therapy, whether the association between ART and hepatic dysfunction remains true is unclear. Moreover, even though most of the previous studies were controlled for baseline liver enzymes level,5 7–9 there were still some studies had no initial liver function15 or co-infection with viral hepatitis4 6 12 reported. Since ART generally lasts for many years and even lifelong, the effect of long-term ART on liver function needs to be elucidated, which is crucial to ascertain whether the risks of hepatic impairment are self-limiting, and to help to make better clinical decision and monitoring.…”