Liver and Cardiovascular Mortality After Hepatitis C Virus Eradication by DAA

Data From RESIST-HCV Cohort

Vincenza Calvaruso; Salvatore Petta; Irene Cacciola; Giuseppe Cabibbo; Fabio Cartabellotta; Marco Distefano; Gaetano Scifo; Maria Antonietta Di Rosolini; Maurizio Russello; Tullio Prestileo; Salvatore Madonia; Giuseppe Malizia; Arturo Montineri; Antonio Digiacomo; Anna Licata; Francesco Benanti; Gaetano Bertino; Marco Enea; Salvatore Battaglia; Giovanni Squadrito; Giovanni Raimondo; Calogero Cammà; Antonio Craxì; Vito Di Marco


J Viral Hepat. 2021;28(8):1190-1199. 

In This Article

Abstract and Introduction


Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio, HR0.09, beta −2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta −1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.


Globally, 71 million people live with chronic hepatitis C virus (HCV) infection[1] and a significant proportion of these are at risk of developing cirrhosis.[2] Patients with HCV cirrhosis have a risk of 2 to 5% and 3 to 6% per year to develop hepatocellular carcinoma (HCC) and liver decompensation, respectively.[3–5] Liver decompensation increases the risk of death to 15–20% per year.[6,7] Patients with HCV infection, especially those with diabetes, are also at increased risk of death due to cardiovascular disease.[8–11]

HCV infection can be eliminated through the use of direct-acting antiviral (DAA) drugs,[12,13] a treatment indicated for all patients, even those with decompensated cirrhosis.[14–16] Several real-world studies have demonstrated that patients with chronic HCV achieving a sustained virologic response (SVR) with interferon-based or DAA treatment are at lower risk of developing liver complications.[17–23] However, these studies failed to offer clear conclusions about the effects of SVR on clinical end points such as liver transplantation and mortality.[24,25] In this rapidly evolving scenario, it is necessary to demonstrate that treatment provides benefit for individual patients as well as general utility at the population level[26] to justify expansion of treatment and efforts for global elimination of HCV infection.[27]

Here, we report the results of a large prospective observational real-world cohort study, in order to assess the rate of disease outcomes and overall survival in patients with chronic HCV disease treated with DAAs, to analyse the rate of liver-related (LR) and cardiovascular (CV) deaths, and to identify risk factors associated with mortality, thereby stratifying patients according to their stage of liver disease.