Enhanced liver fibrosis score stratifies HCC risk in CHB patients after HBsAg seroclearance | Multidisciplinary

After functional cure with HBsAg SC, male patients or those ≥50 years of age at HBsAg seroclearance (ageSC ≥50) are still at risk of HCC, highlighting the need of robust markers for risk stratification. [Gastroenterology 2008;135:1192-1199; J Hepatol 2017;67:902-908] ELF test, a serological biomarker panel that includes aminoterminal propeptide of type III collagen, hyaluronic acid and tissue inhibitor of matrix metalloproteinase type 1, is a noninvasive tool for diagnosing fibrosis in chronic liver diseases, such as nonalcoholic fatty liver disease and alcoholic liver disease. [Ann Clin Biochem 2020;57:36-43; J Gastroenterol Hepatol 2021;36:1788-1802] “However, the use of ELF [score] for risk stratification of HCC after HBsAg SC remains unknown,” wrote the researchers.

The current retrospective study included 337 patients (median age, 51.6 years; male, 69.1 percent; diabetes, 22.6 percent) with spontaneous HBsAg SC between April 1996 and October 2012 who were followed up biannually in the Queen Mary Hospital. All patients showed no signs of liver cirrhosis on ultrasonography at the time of HBsAg SC. During the follow-up period (median, 12.7 years), HCC cases were confirmed by CT scan. After analysis of patients’ blood samples collected at a median interval of 3.4 years before HBsAg SC, the ELF score cut-off was derived by statistical methods. [Clin Infect Dis 2022;doi:10.1093/cid/ciac387]

At a median of 6.6 years after HBsAg SC, nine patients (median ageSC, 65.4 years) were diagnosed with HCC (median age at HCC diagnosis, 69.3 years) (annual rate, 0.21 percent). Of these, the median ELF score was 11.5, which was significantly higher than patients without HCC (9.5; p<0.001).

Multivariate analysis showed that HCC development after HBsAg SC was associated with ageSC (hazard ratio [HR], 1.134; 95 percent confidence interval [CI], 1.038–1.240; p=0.006) and ELF score (HR, 2.588; 95 percent CI, 1.305–5.131; p=0.006). In subgroup analysis, both ageSC and ELF score were significant predictive factors of HCC in male patients (ageSC, p=0.018; ELF score, p=0.033), but not in female patients (ageSC, p=0.093; ELF score, p=0.175).

Among patients with ageSC ≥50, the best cut-off for ELF score was 10.8 (sensitivity, 87.5 percent; specificity, 85.2 percent; positive predictive value, 14.0 percent; negative predictive value, 99.6 percent). Of note, ELF score <10.8 was associated with >97 percent reduction in HCC risk (HR, 0.027; 95 percent CI, 0.003–0.219).

Notably, patients with ageSC ≥50 and ELF score ≥10.8 had cumulative risk of HCC of 9.02 percent at 5 years and 23.45 percent at 10 years. For those with ageSC ≥50 and ELF score <10.8, the cumulative risk of HCC was 0.67 percent at 5 years and 10 years.

“Our cohort included radiologically noncirrhotic patients who achieved spontaneous HBsAg SC, representing the very end of the entire spectrum of CHB natural history [with low risk of HCC],” the researchers wrote. “Our present study demonstrated that the use of ELF [score], a blood-based liver fibrosis marker, can potentially aid in identifying patients with ageSC ≥50 at low risk of HCC.”

“If a patient with CHB achieves functional cure, there is a biomarker [ie, ELF score] that predicts the uncommon occurrence of liver cancer,” commented corresponding author Professor Walter Seto of the Department of Medicine, HKU.