Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals

Abstract

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 These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics

“…Degasperi et al [ 102 ] showed similar results in a retrospective study on 505 cirrhotic patients DAAs treated, demonstrating that a baseline LS > 30 kPa was an independent predictor of de novo HCC, being that the 3-year estimated incidence of de novo HCC was 20% in patients with LSM > 30 kPa versus 5% in patients with LSM ≤ 30 kPa ( p = 0.0003). Recently, in a population of 640 HIV/HCV co-infected patients followed for a median period of 31.6 months post-SVR by DAAs, with the aim of verifying the incidence of HCC, it was shown that none of the 374 patients with LS < 14 kPa at baseline developed HCC [ 103 ]. The authors suggest that the LS measurement may be helpful in selecting patients who may not be subjected to a tight surveillance program.…”

Noninvasive Risk Stratification After HCV Eradication in Patients With Advanced Chronic Liver Disease

“…LSM, which has already found its way into the recommendations for the management of PH in 2015, ( 10 ) has been used to predict liver‐related events following SVR in two recent studies. Corma‐Gomez et al ( 30 ) reported an independent association of LSM with a composite endpoint of hepatic decompensation, HCC, OLT, and mortality in patients co‐infected with HIV/HCV who achieved HCV cure. However, although such a composite endpoint increases statistical power, it negatively affects the granularity of results, as the dynamics of PH do not necessarily relate to HCC risk after HCV cure.…”

Influence of Genetic Variants on Disease Regression and Outcomes in HCV-Related Advanced Chronic Liver Disease after SVR

“…Secondly, to mitigate the risk of type II error due to the limited number of patients undergoing paired invasive HVPG measurements, we evaluated the effect of the presumably most impactful variant (i.e., PNPLA3 ) on changes in well-validated surrogates of portal hypertension [ 13 ]. Importantly, these markers may confer prognostic information, even beyond their association with HVPG [ 33 , 34 ], and post-treatment LSM and VITRO have previously been shown to predict direct endpoints after SVR, such as the development of hepatic decompensation and HCC [ 14 , 35 , 36 ]. We observed a clear association between the PNPLA3 rs738409 G -allele carriage and pre-treatment severity of hepatic dysfunction and portal hypertension, which is in line with the previous literature [ 20 ].…”