If testing positive for Hepatitis B surface antigen (HBsAg), undergo liver ultrasound plus serum AFP screening every six months: initiate antiviral therapy upon physician evaluation and never discontinue medication autonomously

For individuals carrying chronic hepatitis B virus (HBV), biannual screening with liver ultrasound and alpha-fetoprotein (AFP) reduced liver cancer mortality by nearly 40% in a landmark trial. Higher circulating viral loads directly predict higher lifetime liver cancer incidence. For patients with advanced fibrosis or cirrhosis, starting antiviral therapy cuts liver cancer risk by roughly half. Antiviral treatment is long-term; stopping unilaterally causes severe viral rebound.

Low cost. Visit hepatology or infectious disease outpatient clinics twice a year for routine blood draws and abdominal sonography; centralized volume-based procurement (VBP) in China has reduced annual generic entecavir antiviral medication expenses to just over 100 RMB. The difficulty is adhering to biannual surveillance and daily long-term oral medication while completely asymptomatic.

In a randomized controlled trial in Shanghai involving 18,816 individuals aged 35–59 with chronic HBV infection or history of chronic hepatitis, the screening arm was invited for biannual AFP and ultrasound examinations, while the control arm received routine care without screening. Liver cancer mortality was 83.2 per 100,000 in the screening group vs. 131.5 per 100,000 in the control group, representing a 37% reduction in hepatocellular carcinoma (HCC) mortality (rate ratio 0.63, 95% CI: 0.41–0.98). In the screening group, 46.5% of detected HCC cases underwent curative surgical resections compared to only 7.5% in the control group. In a long-term Taiwanese prospective cohort study (REVEAL-HBV) following 3,653 HBsAg-positive individuals aged 30–65 for a mean of 11.4 years, higher baseline serum HBV DNA levels exhibited a dose-response gradient with HCC incidence: HCC incidence was 108 per 100,000 person-years for viral loads <300 copies/mL vs. 1,152 per 100,000 person-years for >=1,000,000 copies/mL (cumulative HCC incidence of 1.3% vs. 14.9%), persisting after adjustment for age, sex, smoking, alcohol, ALT, and cirrhosis. In an Asian multicenter randomized trial of 651 chronic hepatitis B patients with advanced fibrosis or cirrhosis, lamivudine monotherapy reduced disease progression by 55% (HR 0.45) and HCC incidence by ~50% (3.9% vs. 7.4%, HR 0.49, P = 0.047) over a median of 32.4 months. Chinese Medical Association (CMA) guidelines recommend abdominal ultrasound and AFP screening every 6 months for all chronic HBV carriers, and every 3 to 6 months for high-risk patients. For asymptomatic carriers not meeting treatment criteria, monitor liver panels, viral load, AFP, and ultrasound every 6–12 months. When treatment criteria are met, initiate antiviral therapy immediately; all patients >30 years with detectable HBV DNA are advised to start antivirals regardless of ALT levels, as are patients with family histories of HBV-related cirrhosis or HCC. Modern first-line oral regimens favor high-barrier nucleoside analogues such as entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF).

Controversy: The Cochrane 2003 and 2012 reviews re-analyzed the Shanghai trial using different statistical modeling, concluding that the reduction in HCC mortality did not reach conventional significance (OR 0.81, 95% CI: 0.54–1.22) and citing risk of bias in cluster randomization reporting. Nonetheless, international clinical guidelines uniformly recommend biannual surveillance. Lamivudine was an older agent with a 49% drug resistance mutation rate in trials; modern guidelines recommend entecavir or tenofovir with high genetic barriers to resistance. Treatment initiation and cessation must be determined by a specialist based on viral load, liver biochemistry, fibrosis staging, and family history. Screening uninfected individuals and hepatitis B vaccination are covered in Chapter 1, Rule 14. Hepatitis C antibody screening is covered in Chapter 1, Rule 45. Alcohol-induced liver damage is detailed in Chapter 2, Rule 19.

Zhang BH, Yang BH, Tang ZY (2004). Randomized controlled trial of screening for hepatocellular carcinoma. Journal of Cancer Research and Clinical Oncology, 130(7), 417-422. https://doi.org/10.1007/s00432-004-0552-0；Chen CJ, Yang HI, Su J, et al.; REVEAL-HBV Study Group (2006). Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA, 295(1), 65-73. https://doi.org/10.1001/jama.295.1.65；Liaw YF, Sung JJ, Chow WC, et al.; Cirrhosis Asian Lamivudine Multicentre Study Group (2004). Lamivudine for patients with chronic hepatitis B and advanced liver disease. New England Journal of Medicine, 351(15), 1521-1531. https://doi.org/10.1056/NEJMoa033364；中华医学会肝病学分会, 中华医学会感染病学分会 (2022). 慢性乙型肝炎防治指南（2022 年版）. 中华肝脏病杂志, 30(12), 1309-1331. https://doi.org/10.3760/cma.j.cn501113-20221204-00607；同一指南的英文版：You H, Wang F, Li T, et al. (2023). Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). Journal of Clinical and Translational Hepatology, 11(6), 1425-1442. https://doi.org/10.14218/JCTH.2023.00320；Wun YT, Dickinson JA (2003). Alpha-fetoprotein and/or liver ultrasonography for liver cancer screening in patients with chronic hepatitis B. Cochrane Database of Systematic Reviews, CD002799. https://doi.org/10.1002/14651858.CD002799（反方）；Aghoram R, Cai P, Dickinson JA (2012). Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B. Cochrane Database of Systematic Reviews, CD002799.pub2. https://doi.org/10.1002/14651858.CD002799.pub2（反方）；国家医疗保障局 (2025). 中国医保惠民生 积跬步、至长远（七）：医药集采规范化制度化常态化：「乙肝治疗一线用药恩替卡韦，过去患者吃一年的费用大约5000元……集采后恩替卡韦年费用降到100多元」. https://www.nhsa.gov.cn/art/2025/12/29/art_14_19172.html