HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.
Background
Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA).
Methods
In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication—hepatic decompensation or hepatocellular carcinoma (HCC)—or requiring liver transplant after SVR.
Results
During a median (Q1–Q3) follow-up of 31.6 (22.7–36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28–9.12]), pretreatment CPT class B or C (62.5 [3.08–1246.42]) and MELD scores (1.37 [1.03–1.82]), CPT class B or C at SVR (10.71 [1.32–87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49–13.15]), FIB-4 index at SVR (1.39 [1.13–1.70]), and LS at SVR (1.05 [1.02–1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant.
Conclusions
LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.
Background
In the setting of HCV active infection, liver stiffness (LS)-based strategies identify patients with low risk of developing esophageal variceal bleeding (VB) episodes, in whom unnecessary upper esophagogastroduodenoscopy (UGE) screening can safely avoided. However, after sustained virological response (SVR), data on the accuracy of the criteria predictingthis outcomein HCV-infected patients with cirrhosis, with or without HIV-coinfection, are very limited.
Methods
Multicenter prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if: 1) SVR with DAA-based therapy; 2) LS ≥9.5 kPa previous to treatment; 3) LS measurement at the SVR time-point≥ 14kPa. Diagnostic accuracy of HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria, at the time of SVR, wasevaluated. Missed VB episodes, negative predictive values (NPV), and number of spared UGEs were specifically assessed.
Results
435patients were included, 284 (65%) coinfected with HIV. Seven(1.6%) patients developed a firstepisode of VB after SVR. In patients without a previous VB episode, HEPAVIR, expanded Baveno VI and HIV cirrhosis criteria achieved NPV for first VB episode after SVR of 99.5% (97.1%-100%), 100% (97.8%-100%) and 100% (98%-100%) while sparing 45%, 39% and 44% of UGEs, respectively. When considering HIV-coinfection, the performance of the three criteria was similar, both in HCV-monoinfected and HIV/HCV-coinfected individuals.
Conclusions
After SVR, predictive LS-based strategies accurately identify HCV-infected patients, HIV-coinfected or not, with low risk of developing VB during follow-up. In these specific patients, using HIV cirrhosis criteria maximize the number of spared UGEs while missing no VB episode.
Interleukin-7 receptor subunit alpha (IL7RA) rs6897932 polymorphism is related to CD4+ recovery after combination antiretroviral therapy (cART), but no studies so far have analyzed its potential impact in patients with very low CD4+ T-cells count. We aimed to analyze the association between IL7RA rs6897932 polymorphism and CD4+ T-cells count restoration in HIV-infected patients starting combination antiretroviral therapy (cART) with CD4+ T-cells count <200 cells/mm3. We performed a retrospective study in 411 patients followed for 24 months with a DNA sample available for genotyping. The change in CD4+ T-cells count during the follow-up was considered as the primary outcome. The rs6897932 polymorphism had a minimum allele frequency (MAF) >20% and was in Hardy–Weinberg equilibrium (p = 0.550). Of 411 patients, 256 carried the CC genotype, while 155 had the CT/TT genotype. The CT/TT genotype was associated with a higher slope of CD4+ T-cells recovery (arithmetic mean ratio; AMR = 1.16; p = 0.016), higher CD4+ T-cells increase (AMR = 1.19; p = 0.004), and higher CD4+ T-cells count at the end of follow-up (AMR = 1.13; p = 0.006). Besides, rs6897932 CT/TT was related to a higher odds of having a value of CD4+ T-cells at the end of follow-up ≥500 CD4+ cells/mm3 (OR = 2.44; p = 0.006). After multiple testing correction (Benjamini–Hochberg), only the increase of ≥ 400 CD4+ cells/mm3 lost statistical significance (p = 0.052). IL7RA rs6897932 CT/TT genotype was related to a better CD4+ T-cells recovery and it could be used to improve the management of HIV-infected patients starting cART with CD4+ T-cells count <200 cells/mm3.
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