Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Abstract

Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p < 0.0001), liver-related mortality (HR 0.40, 95% CI 0.17–0.96, p = 0.04), non-liver-related mortality (HR 0.17, 95% CI 0.06–0.49, p = 0.001), liver transplantation (HR 0.17, 95% CI 0.05–0.54, p = 0.003), and hepatocellular carcinoma (HR 0.52, 95% CI 0.29–0.93, p = 0.03). Conclusion Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis. Trial registration: ClinicalTrials.gov registry number: NCT01953458.

Results of interferon-free treatment for HCV-infected patients with decompensated cirrhosis from a Brazilian real-life cohort

“…Genotype 1 (84%) was the most common (G1a 42%; G1b 27%; G1 without subgenotype 15%). The median MELD score was 12 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), and 79% were Child-Pugh B. Two patients had a history of hepatocellular carcinoma before treatment.…”

“…Recently, it was demonstrated that an SVR of 85% was achieved in the French HEPATHER cohort. [ 19 ] It comprised 559 patients, most Child-Pugh A, with past liver-disease decompensation and 37% Child-Pug score B. Overall, 55 patients (6%) presented with The associated infection episodes resulted in 66% or MELD score > 20.…”

“…[6][7][8] Some further real-life also confirmed these encouraging results. [9][10][11][12][13][14][15][16][17][18][19] Nevertheless, most studies on this topic were randomized controlled trials, with scarce data on real-life cohorts. [10,12,13,19] Also, this population is prone to the development of complications of cirrhosis, which was explicitly a significant issue in patients treated with interferon-based [20] and simeprevir-containing regimens.…”

“…Despite this, there is a paucity of data regarding the frequency and clinical relevance of complications of cirrhosis in decompensated patients treated with DAAs in real-life cohorts, mostly related to hepatocellular carcinoma and liver transplantation. [11,19] Since data from Brazilian patients are scarce, our study aimed to investigate the effectiveness and safety of sofosbuvir-containing regimens for HCV in a real-life cohort of patients with decompensated cirrhosis.…”

“…Despite this, there is a paucity of data regarding the frequency and clinical relevance of complications of cirrhosis in decompensated patients treated with DAAs in real-life cohorts, mostly related to hepatocellular carcinoma and liver transplantation. [ 11 , 19 ]…”