Severe transaminitis after interferon–ribavirin therapy in HIV/HCV‐coinfected patients: influence of a sustained HCV response

Abstract

Chronic hepatitis C is an independent risk factor for severe drug hepatotoxicity. Successful treatment of chronic hepatitis C may modulate drug hepatotoxicity, as it is associated with a decline in hepatic enzyme release and halts fibrosis progression in HIV/HCV-coinfected patients. The aim of this study was to determine biological and/or clinical determinants of alanine aminotransferase and/or aspartate aminotransferase elevation (>five-fold above the upper limit of normal in patients with normal baseline levels or >3.5-fold increase from baseline in those with increased baseline levels) in a large prospective cohort of HIV/HCV-coinfected patients on HAART who had previously been treated for HCV infection. Median follow-up exceeded five years. Cox proportional hazards models were used. At baseline, 248 patients had been receiving antiretroviral therapy for a mean of 6.3 (± 3.2) years. Seventy-one patients (29%) had a sustained HCV viral response (SVR). During follow-up, 66 patients (26.6%) received a second course of HCV therapy and 29 (44%) of them had an SVR. Severe transaminitis occurred in 64 patients (26%). In multivariate analysis, no SVR (HR 33.33, 95% CI 4.54-222, P = 0.001) and stavudine-based therapy (HR 2.11, 95% CI 1.12-3.99, P = 0.018) remained significantly associated with severe transaminitis. A SVR to anti-HCV therapy is thus associated with a markedly reduced risk of severe transaminitis during antiretroviral therapy. Treatment of HCV infection should therefore be a priority in HIV-coinfected patients. Stavudine is associated with an increased risk of severe transaminitis.

Risk of diabetes in HIV‐infected patients is associated with cirrhosis but not with chronic HCV coinfection in a French nationwide HIV cohort

“…Several studies have assessed the impact of interferon therapy on DM, either as a protective factor or as a risk factor . SVR in HCV infected patients has been associated with both regression of severe transaminitis, steatosis, IR and the prevention of DM development . In a Spanish cohort of 1625 HIV/HCV coinfected patients treated with IFN and ribavirin, SVR (n = 592) after a median 5‐year follow‐up was associated with a significant decrease in the hazard ratio for DM (sHR 0.57 [95% CI, 0.35‐0.93] P = 0.024) .…”

“…34 SVR in HCV infected patients has been associated with both regression of severe transaminitis, steatosis, IR and the prevention of DM development. 14,18,19,[34][35][36] In a Spanish cohort of 1625 HIV/HCV coinfected patients treated with IFN and ribavirin, SVR (n = 592) after a median 5-year follow-up was associated with a significant decrease in the hazard ratio for DM (sHR 0.57 [95% CI, 0.35-0.93] P = 0.024). 19 In a Swiss cohort, HCV-treated patients without SVR (n = 281) had a 4-fold higher risk of DM compared to those with SVR (n = 345).…”

Correlates of HIV sustained viral suppression in HIV/hepatitis C virus coinfected patients

“…Indeed, it is well established that HCV SVR markedly lessens the risk of severe transaminitis during antiretroviral therapy and reduces the risk of developing severe endstage liver disease [7,16]. One possible reason for this could be a better tolerance of antiretroviral drugs, which in turn leads to a higher rate of HIV SVS.…”

“…Early HAART initiation is associated with less severe liver disease [2,6]. However, chronic hepatitis C is an independent risk factor for severe antiretroviral hepatotoxicity, with a three-fold higher risk of grade 3 or 4 transaminitis [7][8][9]. Despite the higher risk of HAART hepatotoxicity in this population, most studies have not shown a negative impact of HCV infection on HIV virologic control [10,11].…”