Persistent Risk of Hepatocellular Carcinoma Despite Improvement of Liver Stiffness in Patients with Chronic HBV with Advanced Fibrosis

Background & Aims: Patients with chronic HBV (CHB) with advanced fibrosis are at high risk for hepatocellular carcinoma (HCC). Liver stiffness measurement (LSM) correlates with fibrosis in untreated patients, and is used to monitor changes in severity of liver disease. However, the association between on-treatment LSM and HCC risk is controversial. Methods: We conducted an international multicenter retrospective cohort study of patients with CHB with advanced fibrosis and assessed the association between on-treatment LSM, HCC development, and decompensation events. Results: We analyzed 562 patients (62.8% F4 LSM measurement, 69.2% Asian). During antiviral therapy, the on-treatment LSM decreased to <6 kPa in 209 (37.2%), to 6–9 kPa in 174 (31.0%), and remained >9 kPa in 179 (31.9%) patients. During a median follow-up of 6.8 years after the on-treatment LSM, 56 patients developed HCC and 18 (32.2%) had an on-treatment LSM <6 kPa. The 5-year cumulative HCC incidence was comparable across on-treatment LSM strata; 4.4% for <6 kPa, 5.5% for 6–9 kPa, and 5.8% for >9 kPa (p = 0.300). In multivariable analysis, older age (adjusted hazard ratio (aHR) 1.058, 95% CI 1.026–1.091, p <0.001) and lower platelet count (aHR 0.992, 95% CI 0.992–0.998, p = 0.005) were associated with HCC development, whereas on-treatment LSM was not (aHR 0.974, p = 0.974). By contrast, patients with an LSM decrease to ≤9 kPa had a negligible risk of decompensation (0% vs. 1.8% at 5 years, p = 0.017). Conclusions: Most patients with CHB with advanced fibrosis experienced a decrease in LSM during antiviral therapy. Although a decrease in liver stiffness was associated with a lower risk of decompensation, an improvement in liver stiffness was not associated with a reduction in HCC risk. Impact and implications: The majority of CHB patients with advanced fibrosis have a decrease in LSM during antiviral therapy. Although a decrease in LSM was associated with a lower risk of subsequent hepatic decompensation, an improvement in LSM was not associated with a reduction in HCC risk. HCC surveillance should therefore be continued in patients with advanced fibrosis at baseline regardless of LSM values obtained during therapy.