Risk and Risk Score Performance of Hepatocellular Carcinoma Development in Patients With Hepatitis B Surface Antigen Seroclearance

Abstract

INTRODUCTION: Hepatocellular carcinoma (HCC) can develop among chronic hepatitis B patients after hepatitis B surface antigen (HBsAg) seroclearance. However, whether HCC risk after HBsAg seroclearance differs between antiviral therapy (AVT)-induced or spontaneous seroclearance cases and ways to identify at-risk populations remain unclear. METHODS: A retrospective cohort of 1,200 adult chronic hepatitis B patients who achieved HBsAg seroclearance (median age: 56 years; 824 men; 165 with cirrhosis; 216 AVT-induced cases) were analyzed. The risk of HCC after HBsAg seroclearance and the performance of 6 HCC prediction models were assessed. RESULTS: During a median of 4.8 years of follow-up (range: 0.5–17.8 years), HCC developed in 23 patients (1.9%). The HCC incidence rate was higher in the AVT-induced cases than that in the spontaneous cases (3.9% vs 0.9% at 5 years). AVT and cirrhosis were independent factors associated with HCC, with HCC incidence rates of 0.5%, 1.2%, 4.0%, and 10.5% at 5 years for spontaneous/no-cirrhosis, AVT-induced/no-cirrhosis, spontaneous/cirrhosis, and AVT-induced/cirrhosis patients, respectively. Among the 6 predictive HCC models tested, Chinese University-HCC score (0.82) showed the highest C-statistics, which was followed by guide with age, gender, HBV DNA, core promoter mutations and cirrhosis (0.81). DISCUSSION: AVT-induced HBsAg seroclearance was associated with higher HCC risk, especially for patients with cirrhosis, indicating that they need careful monitoring for HCC risk. The HCC risk models were able to stratify the HCC risk in patients with HBsAg seroclearance.

KASL clinical practice guidelines for management of chronic hepatitis B

“…HBsAg seroclearance is also achieved in a few patients on antiviral treatment, and the long-term clinical outcome compared with that of spontaneous HBsAg seroclearance is unclear [ 45 , 46 ]. Two studies showed no difference in HCC incidence between patients who achieved treatment-induced and spontaneous HBsAg seroclearance [ 47 , 48 ], yet another study reported a 5-year cumulative incidence of HCC of 0.9% and 3.9% in spontaneous and treatment-induced HBsAg seroclearance patients, respectively [ 49 ].…”

Systematic review with meta‐analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B

“…The baseline characteristics are provided in Table 1. Among the 57 studies, 2 were prospective population‐based studies, 11,12 22 were prospective 8,9,13‐32 and 33 were retrospective cohort studies 7,33‐64 . Overall, there were a total of 258 744 HBsAg positive patients of whom 63 270 (24.4%) lost HBsAg.…”

External validation of hepatocellular carcinoma risk scores in patients with chronic hepatitis B virus infection in China

“…7 Though the risk has been significantly lowered by effective antiviral therapy, it cannot be eliminated. [3][4][5]18 Even, the incidence of HCC in these patients is still higher than that in inactive-stage CHB patients. 19,20 In our study, the 36-month cumulative incidence of HCC was 1.4% in CHB patients on antiviral therapies, 0.5% in chronic carriers and 1.0% in total.…”

“…patients with more than 5 years of effective entecavir treatment 3 or with hepatitis B surface antigen (HBsAg) loss. 4,5 Thus, all the guidelines recommend HCC surveillance in chronic HBV-infected patients routinely and regularly. 2,[6][7][8][9] The Asian Pacific Association for the Study of the Liver (APASL) even suggests regular surveillance in patients who lost HBsAg.…”