Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study

Abstract

Objectives: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use. Methods: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested. Results: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively (p < 0.001), after SVR, whereas there was no evidence for a change in HDL-C (p = 0.45) and triglycerides (p = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction-p value = 0.002). Conclusions: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.

Neuropsychiatric and Laboratory Outcomes of Hepatitis C Treatment in an Early-Treated HIV Cohort in Thailand

“…In line with the results of prior studies that included HCV-monoinfected [24][25][26] and HIV/HCV-coinfected participants [27], we noted elevations in total cholesterol, triglyceride, and LDL levels after SVR. HCV is hypothesized to induce hypolipidemia by stimulating LDL receptor expression and modulating proteins involved in liver steatosis [27,28]. HCV eradication may therefore reverse these processes, leading to paradoxical increases in serum lipid levels.…”

“…Thirty-four (68%) denied any prior IVDU, while 41 (82%) contracted other sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia, during follow-up (Table 1). The median durations between HCV seroconversion and pre-DAA assessment and between DAA completion and post-DAA assessment were 15 [IQR 9,29] and [27][28][29][30][31][32][33][34][35][36][37][38] weeks, respectively. The predominant DAA regimens used were sofosbuvir/ledipasvir (52%) and sofosbuvir/velpatasvir (36%).…”

Effects of direct‐acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real‐life Italian experience

“…34 In fact, HCV infection is related to "viral" steatosis and hypolipidemia (low TCOL and LDL-C with near normal TG and HDL-C), which were shown to rapidly reverse after SVR with both IFN and DAAs. 31 On the other hand, HCV clearance is associated with a worsening lipid profile, 35,36 but it is not clearly understood if this change could be associated with an increased risk of atherogenesis. 37 To date, the CV risk in subjects with HCV after therapy with DAAs is still debated, and the evidence among the subgroup of patients with T2DM is even more scarce or quite absent.…”

Immunological and Clinical Impact of DAA-Mediated HCV Eradication in a Cohort of HIV/HCV Coinfected Patients: Monocentric Italian Experience

“…HCV infection has been described as a contributor to poor immunological recovery in PLWH. However, a recent study in the context of the ICONA and HEPA-ICONA observational cohorts showed that HCV eradication following DAA treatment does not have an impact on CD4+ T cell recovery in PLWHIV [ 26 ].…”

“…It is known that HCV alters lipid pathways to enhance its replication. HCV infection could cause hypocholesterolemia; therefore, successful treatment may lead to elevation of cholesterol, including LDL-cholesterol [ 26 ]. Indeed, several studies reported pro-atherogenic lipid changes in patients with SVR [ 29 , 30 ].…”