The consecution of sustained virological response (SVR) is associated with a reduction in the risk of liver-related events, including hepatocellular carcinoma (HCC), and liver-related mortality in HIV/HCV-coinfected patients. However, HIV/HCV-coinfected patients who achieve SVR are still at risk of developing HCC. It is not known if the risk of developing HCC after SVR has been modified with the arrival of all-oral direct antiviral agents (DAA) interferon (IFN)-free regimens. Our objective was to assess the proportion of HCC cases diagnosed after SVR in HIV/HCV-coinfected patients and its evolution over time.
The GEHEP-002 multicentric cohort (ClinicalTrials.gov ID: NCT02785835) recruits HCC cases diagnosed in HIV-infected patients from 32 centers from Spain. The proportion of HCC cases after SVR and the evolution of this proportion over time were analyzed. For this purpose, we define 4 periods of time according to the changes of treatment strategies for hepatitis C in Spain: 1) Period 1 (≤ 2001): non-pegylated IFN; 2) Period 2 (2002-2011): pegylated IFN plus ribavirin; 3) Period 3 (2011-October 2014): DAA in combination with IFN and 4) Period 4 (October 2014-September 2016): DAA IFN-free regimens.
295 HCC cases diagnosed in HIV/HCV-coinfected patients have been included in the GEHEP-002 cohort. The median (Q1-Q3) age was 49 (46-52) years and 265 (90%) were male. HCV genotype distribution was: Gt 1, 114 (48%); Gt 2: 3 (1%); Gt 3, 85 (36%) and Gt 4, 35 (15%). Since 1999, when the first HCC case was recorded, 34 (11.5%) cases have occurred in patients with previous SVR. The proportion of HCC cases in patients with previous SVR was 16.7% (1 out of 6), 10.9% (15 out of 137) and 7.9% (10 out of 126) in period 1, 2 and 3, respectively (Figure 1). By contrast, this proportion increased to 30.8% (8 out of 26) in the DAA IFN-free period (p<0.01 for the comparison between period 1-3 vs 4) (Figure 1). Twenty-one patients with previously treated HCC received subsequent therapy with DAA IFN-free regimens. HCC recurred in 1 (4.7%) of them.
The proportion of HCC cases diagnosed in HIV/HCV-coinfected patients with previous SVR has significantly increased parallel to the arrival of DAA IFN-free strategies. This finding may be, at least partially, explained by the fact that DAA have allowed treating patients at advanced stages of liver disease in which the protective effect of SVR on the risk of HCC could be less marked.