Hepatitis B clinical practice guidelines revised in Korea

Treatment recommendations expanded to include patients with moderate viremia

New evidence supports earlier management…discussions needed on revising the reimbursement criteria

The Korean Association for the Study of the Liver (KASL) has recently revised its hepatitis B clinical practice guidelines, signaling a potential shift in the treatment paradigm for chronic hepatitis B in Korea.

The key change in the revised guidelines is a reorganization of the treatment framework away from the traditional alanine aminotransferase (ALT)-based approach toward expanding treatment eligibility based on disease risk assessment that uses HBV DNA levels.

In particular, attention is rising on early intervention strategies for liver cancer prevention, as treatment recommendations have been strengthened for so-called ‘gray-zone’ patients who previously required treatment but often did not receive appropriate intervention under existing criteria.

On the 16th, Gilead Sciences Korea hosted the ‘2026 Hepatitis Academy,’ where experts discussed the significance and clinical evidence behind KASL’s revised hepatitis B treatment guidelines.

From the left: Young-suk Lim (Gastroenterology, Asan Medical Center), Gi-Ae Kim (Gastroenterology, Kyunghee University Hospital)

The most significant change in the revised guidelines is the reclassification of the natural history of chronic hepatitis B based primarily on hepatitis B virus (HBV) DNA levels.

Previous Korean guidelines recommended antiviral treatment for patients with ALT levels persistently exceeding twice the upper limit of normal or in cases where liver fibrosis had been confirmed. Under the guidelines, patients with high HBV DNA levels but normal ALT levels were often excluded from treatment, creating a persistent unmet need in clinical practice.

According to Korean studies, 64% of all liver cancer cases occurred outside the current National Health Insurance reimbursement criteria. Also, patients with moderate viremia, defined as HBV DNA levels of 4–8 log10 IU/mL, were reported to have the highest risk of developing liver cancer.

Reflecting these findings, KASL reclassified the natural history of chronic hepatitis B into four categories: ▲high viremia (HBV DNA >8 log10, ▲HBeAg-positive moderate viremia, ▲low viremia (HBV DNA <2000 IU/mL), and ▲HBeAg-negative moderate viremia.

In particular, the treatment recommendations were expanded to include antiviral therapy for patients with moderate viremia regardless of ALT levels.

ATTENTION study provides evidence for a previously underserved treatment population

The revised guideline was largely supported by findings from the ATTENTION study, led by Korean investigators.

The ATTENTION study was a multicenter, randomized, clinical trial involving 734 chronic hepatitis B patients without cirrhosis and with HBV DNA levels of 4–8 log10 IU/mL. Patients were assigned either to treatment with Vemlidy (tenofovir alafenamide, TAF) or to an untreated observation group.

Professor Young-suk Lim (Gastroenterology, Asan Medical Center)

After a median follow-up of 17.7 months, major clinical events, such as hepatocellular carcinoma (HCC), liver function deterioration, liver transplantation, and death, occurred in 2 patients in the TAF group (both HCC), 9 patients in the observation group (7 HCC, 1 liver function deterioration, and 1 death).

Treatment benefits were also confirmed across secondary endpoints. The proportion of patients achieving HBV DNA suppression below 10 IU/mL was 91% in the TAF group and 31% in the observation group. ALT normalization rates were 80% in the TAF group and 62% in the observation group. Among patients who had elevated ALT levels at baseline, ALT normalization rates were 73% in the TAF group and 50% in the observation group.

Professor Young-suk Lim of the Department of Gastroenterology at Asan Medical Center (President of KASL) stated, “Liver cancer is one of the leading causes of cancer-related death in Korea, and a substantial proportion of cases are associated with chronic hepatitis B. Although liver cancer risk is closely linked to HBV DNA levels, which reflect the degree of viral replication, previous treatment criteria have relied heavily on whether ALT levels were elevated.”

Professor Lim added, “The ATTENTION study provides evidence supporting the clinical value of early antiviral treatment in patients who were previously left in a treatment blind spot. We expect these findings to play an important role in shaping future clinical guidelines and treatment practices.

Professor Gi-Ae Kim (Gastroenterology, Kyunghee University Hospital)

Experts emphasized that this revision is not merely an adjustment of criteria, but a shift in the treatment paradigm, while also noting that further discussion on improving reimbursement criteria is necessary for its practical implementation in clinical settings.

Professor Gi-Ae Kim of Kyung Hee University Hospital (Secretary of the KASL Publications Committee) stated, “The core of this revision is the shift toward evaluating disease progression and establishing treatment strategies based on HBV DNA levels rather than ALT levels. This change is consistent with the direction of global clinical guidelines.”

Professor Kim added, “Patients with moderate viremia have been shown to carry the highest risk of hepatocellular carcinoma, so we revised the guideline to recommend treatment regardless of ALT levels. This represents a fundamental change from the previous treatment paradigm.”

Kim also noted, “For these newly proposed recommendations to translate into actual patient care, discussions regarding expanded treatment access and revisions to reimbursement criteria will be necessary. Managing healthcare expenditures associated with the broader treatment population and improving long-term treatment adherence will also be important challenges moving forward.”