Cost‐Effectiveness of Antiviral Therapy in Patients With High Viremic Indeterminate Phase Chronic Hepatitis B

ABSTRACT Background & Aims Growing evidence suggests that chronic hepatitis B (CHB) patients with high viremia are at a high risk of developing hepatocellular carcinoma (HCC) even with normal alanine transaminase (ALT) levels. This study aimed to evaluate the cost‐effectiveness of initiating antiviral therapy in patients in an indeterminate phase of CHB, defined as those who do not clearly fit into the established four phases categorised by serum HBV DNA and ALT levels. Methods A cost‐utility analysis was conducted using a Markov model to compare the incremental cost‐effectiveness ratio (ICER) of initiating antiviral therapy at the indeterminate phase (‘treat‐Indet’) versus delaying treatment until chronic hepatitis (‘untreated‐Indet’). A hypothetical cohort of 10 000 patients in the indeterminate phase (60% male, HBV DNA 4–8 log 10 IU/mL, ALT < 40 IU/L, 50% HBeAg‐positivity) was simulated over a 10‐year horizon. Input parameters were obtained from a Korean multicentre historical cohort. Results From a healthcare system perspective, the ICER of the treat‐Indet strategy was US$12050/quality‐adjusted life‐year (QALY), indicating cost‐effectiveness under the local willingness‐to‐pay threshold of US$25000/QALY. From a societal perspective, the ICER was less than 0, indicating lower costs. A U‐shaped association was identified between baseline HBV DNA levels and the ICER, as HBV DNA levels of 6–7 log 10 IU/mL were associated with the lowest ICER (US$2018/QALY), followed by 5–6 (US$7233/QALY), 7–8 (US$19677/QALY) and 4–5 log 10 IU/mL (US$24570/QALY), following the order of HCC risk. Conclusions Initiating antiviral therapy in high‐viremic indeterminate phase CHB patients with normal ALT levels was cost‐effective compared with delaying treatment until chronic hepatitis.