Follow–up of Sustained Virological Responders With Hepatitis C and Advanced Liver Disease After Interferon/Ribavirin–free Treatment

Karin Kozbial; Stephan Moser; Ramona Al-Zoairy; Remy Schwarzer; Christian Datz; Rudolf Stauber; Hermann Laferl; Michael Strasser; Sandra Beinhardt; Albert F. Stättermayer; Michael Gschwantler; Heinz Zoller; Andreas Maieron; Ivo Graziadei; Michael Trauner; Petra Steindl-Munda; Harald Hofer; Peter Ferenci


Liver International. 2018;38(6):1028-1035. 

In This Article

Abstract and Introduction


Background: The introduction of direct–acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long–term durability of viral eradication after successful DAA therapy are scarce.

Aim: To evaluate the long–term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs.

Methods: Five hundred and fifty–one patients with advanced fibrosis (n = 158) or cirrhosis (CPS–A:317, CPS–B/C:76) and SVR after interferon and ribavirin–free DAA therapy treated between October 2013 and April 2016 were studied with a median follow–up of 65.6 (13.0–155.3) weeks. Only patients without hepatocellular carcinoma (HCC) at baseline and without liver transplantation were included.

Results: Twelve patients (2.2%) died during follow–up: the mortality rate was 0.6% in F3, 2.2% in CPS–A and 5.3% in CPS–B/C patients (P = .08). During follow–up 36 patients with cirrhosis (9.1%) developed a liver related event, including 16 with de–novo HCC (4.1%). Seven patients were transplanted at a median of 9.7 (range 3.8–21.7) months after EOT. History of decompensation was significantly associated with liver related events during follow–up (HR 7.9; 95% CI 2.7–22.6; P < .001), and with mortality (HR 5.5; 95% CI 1.5–20.2, P = .01).

Conclusions: Eradication of HCV by DAA therapy was durable irrespective of the DAA combination used. Most of the cured patients had an excellent long–term clinical prognosis. Nevertheless, the risk of new occurrence of HCC remains worrisome and thus regular surveillance is obligatory even after clinical stabilization and improvement of the patient.


The introduction of direct acting antivirals (DAA) has revolutionized the therapy of chronic hepatitis C (CHC) in so far as even patients with advanced liver disease achieve high rates of sustained virological response (SVR) irrespective of genotype or therapy experience. Long–term follow–up studies in patients treated by peginterferon/ribavirin (PEG/RBV) alone or in combination with telaprevir or boceprevir have shown that Hepatitis C Virus (HCV) eradication was durable after follow up periods of more than 20 years.[1–5] Furthermore SVR has been shown to prevent progression to end stage liver disease, liver related death and reduce the incidence of hepatocellular carcinoma (HCC).[6–8] Even cases of reversal of cirrhosis were documented many years after achieving SVR.[9] With the availability of new DAAs the treatment of CHC has made an unprecedented progress. Early analysis of patients with SVR showed associated improvement in liver function measured by MELD or Child–Pugh score (CPS) in some cases resulting in being delisted from the liver transplant waiting list.[10–12] A recent controversial Cochrane review challenged the long–term benefit of DAA therapy.[13] This misleading opinion reflects the paucity of data supporting an effect of DAAs on HCV–related morbidity and all–cause mortality, since DAAs were available in the USA for less than 4 years.[14]

So far, little data on the long–term outcome of patients with SVR following PEG/RBV–free DAA combination therapy have been reported. In Austria, many physicians preferred not to use ribavirin because of its side effects and limited additional efficacy.[15,16] Data on DAA treated patients were collected in the AUstrian Ribavirin/Interferon (RBV/IFN)–free Cohort (AURIC,, NCT02628717). The aim of this study was to report the results of the long–term follow–up after successful CHC eradication within the AURIC.