The absence of warfarin treatment and situs inversus are associated with the occurrence of hepatocellular carcinoma after Fontan surgery

Background Hepatocellular carcinoma (HCC) is a long-term complication of Fontan-associated liver disease (FALD). However, risk factors for HCC in patients with FALD remain unclear. This study aimed to identify factors associated with HCC development post-Fontan procedure. Methods We retrospectively examined 103 post-Fontan patients who underwent hepatic imaging at our institution. HCC incidence and patient characteristics were analyzed. A Cox proportional hazards model was used to identify risk factors for HCC. Results The median interval between Fontan surgery and final hepatic imaging was 19.6 (1.0-37.7) years. Among 103 patients, nine developed HCC. The cumulative incidence rates of HCC at 10, 20, and 30 years postoperatively were 0%, 7%, and 13%, respectively. In the univariate analysis, age at Fontan surgery, situs inversus, and warfarin absence were associated with HCC occurrence. The multivariate analysis identified the warfarin absence (adjusted hazard ratio [aHR], 22.71; 95% confidence interval: 3.29-507.1; p = 0.0005) and situs inversus (aHR, 14.36; 95% confidence interval: 2.75-105.5; p = 0.002) as risk factors. The prevalence of situs inversus and the warfarin absence was 12% and 50%, respectively. The 20- and 30-year incidence rates of HCC among patients who received warfarin were 0% and 7%, respectively, while those among patients who did not receive warfarin were 14% and 21%, respectively. HCC incidence was significantly higher in the non-warfarin group than in the warfarin group (p = 0.006) and among patients with situs inversus than among those with situs solitus (p = 0.004). Conclusions Warfarin absence and situs inversus were associated with HCC development post-Fontan procedure.

Automated summary

This study found that warfarin absence and situs inversus are associated with the development of HCC after Fontan procedure. Warfarin absence and situs inversus are potential risk factors for HCC occurrence.