Reply
Authors: Anthony Cousien, Sylvie Deuffic‐Burban, Yazdan Yazdanpanah
Journal: Hepatology (2016)

Potential conflict of interest: Sylvie Deuffic‐Burban consults and has received grants from Janssen and MSD. She consults for AbbVie, Bristol‐Myers Squibb, Gilead, HEVA, and PHE. Yazdan Yazdanpanah consults and has received grants from Abbott, Bristol‐Myers Squibb, Gilead, Pfizer, Tibotec, and ViiV. He consults for MSD and Roche. We carefully read the letter from Dahari et al. regarding our modeling study on hepatitis C virus (HCV) in people who inject drugs (PWID) in the Paris area.1 Dahari et al. were surprised that, in citing their article,2 we assumed no reduction in cirrhosis complications after sustained virological response (SVR) in patients with cirrhosis. We cited their article to support the possibility of cirrhosis complication occurrence despite a SVR. The absence of reduction in the risk of cirrhosis complications was an assumption we made. As proposed by Dahari et al., we conducted new analyses assessing the impact on our results of marked reduction in the risk of cirrhosis complications after SVR. We simulated the seven scenarios of improvement in the cascade of care of chronic hepatitis C of our article with the following relative risks (RR) of complication after SVR: compensated cirrhosis to decompensation = 0.07 and compensated cirrhosis to hepatocellular carcinoma = 0.19.2 Figure 1 presents the results (data not presented in the original article). Regarding HCV incidence and prevalence at 10 years, the results remained almost unchanged, as expected. Regarding the number of cirrhosis complications avoided compared with the current situation (scenario S1), the trend in results of this sensitivity analysis remained unchanged compared with the main analysis. Improved testing (S2) had almost no impact. The number of complications decreased after improving linkage to care (S3), testing and linkage to care (S4), or adherence to treatment (S5) (between 9% and 21% after 40 years versus between 12% and 13% in the main analysis). Treating at F0 (versus F2) (S6) led to a moderate decrease (6% after 40 years versus 7% in the main analysis). Improvements in the entire cascade of care of hepatitis C (S7) was the most effective scenario (−35% of complications after 40 years versus −29% in the main analysis). Compared with the main analysis, we can notice the impact of scenarios S4, S5, and S7 was twice as high after 10 years. The decrease in the risk of cirrhosis complications occurrence after SVR avoid or delay complications in treated patients, explaining these results. However, overall conclusions of the main analysis remain valid and were robust to these sensitivity analyses.Figure 1: Boxplots and barplots of the outcomes of the model according to the different scenarios. (A) Prevalence at 10 years. (B) Incidence at 10 years. (C, D) Average percentage of cirrhosis complications avoided over 10 years (C) and over 40 years (D) for each scenario, compared with scenario 1. Black lines represent the median; boxes represent the interquartile range. For the boxplots, the maximum distance of the whiskders is 1.5 times the interquartile range. The scenarios are: S1, current cascade of care (reference); S2, improvement of HCV testing; S3, improvement of linkage to care; S4, improvement of testing and linkage to care; S5, improvement of adherence to treatment; S6, treatment initiated from F0; S7, improvement of the entire cascade of care (combination of scenarios S4, S5, and S6). See Cousien et al.1 for details of the model structure and scenarios.To conclude, we would like to highlight the absence of estimations of the RR of cirrhosis complications after SVR versus non‐SVR among people who inject drugs; in this population, risk factors for liver fibrosis progression as alcohol consumption and comorbidities may accelerate complications occurrence. For example, a study among HCV‐positive drug users initiating an antiviral treatment between 2002 and 2005 in France recorded an alcohol consumption rate of >20 g/day for 37% of the active drug users group.3 In 2011, a survey recruiting in high and low threshold structures for drug users found similar results: 28% of the participants reported daily alcohol consumption.4 Although SVR reduces the risk of cirrhosis complications, severe alcohol consumption would potentially increase the risk of liver failure (RR = 2.20) or hepatocellular carcinoma (RR = 2.57).2 Thus, our initial assumption of no reduction in cirrhosis complications after SVR in people who inject drugs, although conservative, is probably realistic.