FIB-4 score and hepatocellular carcinoma risk after hepatitis C virus cure: time to revise surveillance?

Abstract

approximately ~20% of them had liver cirrhosis and 60% were treated by DAA. Iannou et al. showed that baseline FIB-4 ≥3.25 is an independent risk factor for HCC (Table 1). In patients with pre-treatment cirrhosis, HCC risk is more than 2-fold higher when baseline FIB-4 is ≥3.25. In patients without cirrhosis, HCC risk is higher than 1%/year in patients with baseline FIB-4 ≥3.25 with an adjusted risk 3 to 5 times higher compared to non-cirrhotic patients with baseline FIB-4 <3.25. During 10-year follow-up, the HCC risk in IFN-treated cirrhotic patients did not significantly decrease over time in patients with baseline FIB-4 ≥3.25 while remained lower than 1% in patients with baseline FIB-4 <3.25. The same findings, showing stability of HCC risk overtime in patients with FIB-4 ≥3.25 and FIB-4 <3.25, were observed in the non-cirrhotic group. Data from the DAA-treated patients showed a reduction of HCC risk over time after SVR but the short follow-up (only 4 years) cannot allow to draw any firm conclusion. Changes in HCC risk following FIB-4 drop or increase after SVR were also calculated (Table 1). Cirrhotic patients with baseline high FIB-4 which dropped below 3.25 following SVR halved the HCC risk but this was still higher than 1.9%/year. Cirrhotic patients with FIB-4 <3.25 which became ≥3.25 after SVR, increased their risk of 2-3 times which ranges to 1.35% to 2.75%/year. Non-cirrhotic patients with baseline FIB-4 ≥3.25 who dropped to a FIB-4 <3.25 after SVR also halved their risk to ~1%/year. Non-cirrhotic patients with baseline FIB-4 <3.25 who increased to a FIB-4 ≥3.25 after treatment increased their HCC risk from 2 to 5 times but the HCC incidence was still lower to 1%/year. The current international recommendations for HCC surveillance are based on cost-effectiveness analysis considering the costs per quality-adjusted life year (QALY) gained with the intervention. When the traditional cost-effectiveness benchmark of $50,000/QALY is used, HCC surveillance in HCV patients is cost-effective in population with an HCC risk ≥1.5%/year. Using exclusively the presence of cirrhosis as discriminating factor, HCC surveillance in HCV could be strongly recommended only in cirrhotic patients. The data from Ioannou et al. suggest, however, that using FIB-4, it may be possible to stratify cirrhotic and non-cirrhotic patients into different groups of HCC risk to personalize post-SVR follow-up (Figure 1). Surveillance could be recommended for cirrhotic patients with FIB-4 ≥3.25 (any time before and after SVR) and non-cirrhotic patients with FIB-4 ≥3.25 that do not drop to <3.25 at 1-year post-SVR. Non-cirrhotic patients with baseline FIB-4 <3.25 and cirrhotic patients with FIB-4 constantly <3.25 could avoid surveillance. With the actual cost-effectiveness benchmark, this approach would change the follow-up of approximately 27% of cirrhotic patients (no surveillance recommended) and 4% of non-cirrhotic patients (surveillance recommended) in the cohort of Ioannou and colleagues.