Changes of liver function parameters and estimated fibrosis after HCV eradication with IFN-free therapy in cirrhotic HIV co-infected patients

Abstract

Objectives: laboratory parameters improve in cirrhotic HCV mono-infected patients after sustained virological response (SVR24) with all-oral direct-acting antivirals (DAA). We analyzed biochemical tests of liver function, liver stiffness (LS) and clinical events in HIV/HCV co-infected patients with cirrhosis after HCV eradication with DAA.

Methods: HIV/HCV patients included in the cohort “VIH-DOC” were eligible if treated with DAA between 9th January 2015 and 31st August 2016, presented LS≥14.6 kPa or unequivocal clinical data of cirrhosis before treatment, and confirmed SVR24. Serum albumin, total bilirubin, platelet count, serum creatinine and International Normalized Ratio (INR) values were collected at baseline, week 4, end of therapy (EOT) and SVR24. The Model for End-stage Liver Disease (MELD) score was calculated at baseline, EOT and SRV24, excluding patients with oral anticoagulation and/or atazanavir as treatment. LS was evaluated and FIB-4 calculated at baseline and SVR24. Means were compared with T-Student tests or repeated measures ANOVA tests.

Results: There were 129 patients with LS≥14.6 kPa and one patient with lower LS but clinical evidence of cirrhosis. SVR24 was confirmed in 119 (91.5%) Table 1

Age: mean (years) (SD) 51.0 (5.1) Gender: n (%) Male / Female 87 (73.1) / 32 (26.9) Transmission mechanism: n (%) People who inject(ed) drugs / Heterosexual / Men who have sex with men 108 (90.8) / 10 (8.4) / 1 (0.8) Time since HCV infection or diagnosis: median (years) (IQR) 29.4 (24.7 - 33.4) Basal HCV-RNA: median (UI/mL) (IQR) 1765728 (351886 - 4193546) Basal liver stiffness estimated by transient elastography: median (kPa) (IQR) 25.7 (18.0 - 35.3) Basal Fibrosis-4 (FIB4) score: median (IQR) 4.24 (2.70 - 6.13) Previous diagnosis of hepatocellular carcinoma: n (%) 4 (3.4) Previous clinical liver decompensation event: n (%) 26 (21.8) Previous liver transplant with HCV relapse on the liver graft: n (%) 1 (0.8) [Table 1: Baseline characteristics]

shows baseline characteristics. At SVR24 vs. baseline, there were higher albumin (4.55 g/dL vs. 4.25 g/dL, p< 0.001) and platelet count (135800/mcL vs. 118700/mcL, p< 0.001); and lower bilirubin (0.91 mg/dL vs. 1.21 mg/dL, p< 0.001) and MELD score (7.96 vs. 8.39, p=0.045). When comparing baseline vs. SVR24, LS mean decrease was 6.27 kPa (95%CI: 3.71-8.83, p< 0.001) and FIB-4 mean decrease was 1.79 (95%CI: 1.44-2.14, p< 0.001).

Two and eight patients developed liver decompensation during or after treatment, respectively. Three deaths occurred in the follow-up (2.5%): two of them due to malignant neoplasms; the third because of a spontaneous intracranial hemorrhage.

Conclusion: SVR24 associates improvement in liver function and fibrosis tests of HIV/HCV co-infected patients with cirrhosis. Nevertheless, clinical events still happen.