Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population
Bruno S, Di Marco V, Iavarone M, Roffi L, Crosignani A, Calvaruso V et al.
J Hepatol. 2016 Jun;64(6):1217-23.
Abstract :
Background & Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to
be measured.
Methods:
The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population.
Results:
Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1–25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3–94.8) and 62.9% (95% CI, 45.9–75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72–1.35), with an SMR for non-SVR patients of 3.85 (95% CI, 3.43–4.30), for untreated of 3.01 (95% CI, 2.64–3.42) and for decompensated of 6.70 (95% CI, 5.39–8.22).
Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable.
Expert's Commentary
«This important study is the first to demonstrate that patients with compensated HCV cirrhosis who achieve sustained virologic response will have a life expectancy similar to that of the sex- and age-matched general population. Authors included prospective surveillance data from 181 patients of three cohorts of Italian patients with compensated HCV cirrhosis who achieved sustained virological response (SVR) on an interferon-based (IFN) regimen were compared to simultaneously observed non-SVR, untreated and decompensated patients. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3–94.8) and 62.9% (95% CI, 45.9–75.9), respectively. The number of expected deaths in the corresponding age- and sex-matched general population was 28.1, corresponding to a standardized mortality ratio (SMR ) of 1.00 (95% CI, 0.72–1.35) for patients with SVR, and a SMR for non-SVR patients of 3.85( 95% CI, 3.43–4.30). The study has two relevant advantages. Firstly, only patients with definite diagnosis of cirrhosis were included, while those with advanced fibrosis were exclude,d avoiding the main limitation of a previous study in patients with F3 and F4. Secondly, the long-term follow-up allowed to generate data on long-term (10- and 20-year) survival rates in cirrhotic patients achieving SVR, similar to those of non-cirrhotic patients previously reported with a shorter observation period [van der Meer AJ. JAMA 2014;312:1927–8.]. A major issue is the fact that the eligibility criteria to receive IFN may originate from an under-representation of comorbidities otherwise prevalent in the age-matched general population. This is an important reason to perform long term survival studies including patients with cirrhosis and comorbidities who had achieved a SVR with direct antiviral agents to show the impact of SVR in survival in a more heterogeneous population. During the study, 20 patients developed HCC (16 in Child-Pugh A5 and 4 in Child-Pugh A6). The 10- and 20-year cumulative incidence of HCC was 10.3% and 23.7% (14.4–37.6) respectively. This observation confirms that antiviral treatment should be administered as early as possible thus avoiding the occurrence of cirrhosis, which is the main determinant of HCC development. The main limitation of study is the multicenter historical cohort studies with baseline characteristics slightly differ between centers. In addition, patients were enrolled at different time periods, distinguished by different treatment protocols or patients management guidelines. In summary, eradicative treatment of patients with compensated HCV cirrhosis is strongly justified since the achievement of SVR leads to a major survival benefit, with a life expectancy similar to the general population. »
Pr Maria Butti,
Hospital General Universitari Valle Hebron, Barcelona
