Change in Fibrosis 4 Index as Predictor of High Risk of Incident Hepatocellular Carcinoma After Eradication of Hepatitis C Virus

Abstract

Background: It is unclear whether the fibrosis 4 index (FIB-4), a marker of liver fibrosis, at baseline and change in FIB-4 after sustained virological response (SVR) is associated with incident hepatocellular carcinoma (HCC) risk. In this study, we examined the association of incident HCC risk with baseline FIB-4 and sustained high FIB-4 (>3.25) at any time point after SVR.

Methods: A total of 3823 patients who received direct-acting antiviral treatment and achieved SVR were enrolled. The FIB-4 was measured 24 weeks after the end of direct-acting antiviral treatment and achievement of SVR (SVR24), and 1, 2, and 3 years after SVR24, after which subsequent HCC development was investigated.

Results: In patients with an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years after SVR24, subsequent HCC development was significantly higher than in those with an FIB-4 ≤3.25 at each point. The rates of HCC development 1, 2, 3, and 4 years after SVR24 were significantly higher in patients with sustained FIB-4 >3.25 than in those whose FIB-4 decreased to ≤3.25 (5.4%, 9.2%, 11.7%, and 16.0%, respectively, vs 2.2%, 3.1%, 3.7%, and 4.4%; P < .001). The adjusted hazard ratios (95% confidence intervals) for an FIB-4 >3.25 at SVR24 and 1, 2, and 3 years later were 3.38 (2.4-4.8), 2.95 (1.9-4.7), 2.62 (1.3-5.1), and 3.37 (1.4-9.8), respectively.

Conclusions: The FIB-4 could be used to assess HCC development risk at any time after SVR, and changes in FIB-4 were associated with changes in the HCC development risk. Repeated assessments of FIB-4 could serve as a prognostic indicator of a high-risk HCC cohort that may require more intensive HCC surveillance strategy.

Keywords: DAA; FIB-4; SVR; hepatocellular carcinoma.

Figure 1.

Flowchart of patient selection. Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HIV, human immunodeficiency virus; SVR, sustained virological response.

Figure 2.

Change in proportion of high-risk patients (fibrosis 4 index [FIB-4] >3.25) over time. Abbreviation: SVR24, 24 weeks after achievement of sustained virological response.

Figure 3.

Cumulative rates of hepatocellular carcinoma development after sustained virological response (SVR) stratified by fibrosis 4 index (FIB-4). Patients were classified into 2 groups according to FIB-4 at 24 weeks after achievement of SVR (SVR24) (A) and 1 (B), 2 (C), and 3 (D) years after SVR24.

Figure 4.

Cumulative incidence of hepatocellular carcinoma (HCC) development after sustained virological response (SVR) stratified by change in fibrosis 4 index (FIB-4). In patients with FIB-4 >3.25 at 24 weeks after achievement of SVR (SVR24), patients were categorized into 2 groups according to changes in FIB-4. Patients with FIB-4 ≤3.25 at last follow-up or at the time of HCC development were classified in the improvement group, and those with FIB-4 >3.25 at last follow-up or at the time of HCC development were classified in the nonimprovement group.