Tamaki Nobuharu, Huang Daniel Q, Lee Hyung Woong, Park Soo Young, Lee Yu Rim, Sinn Dong Hyun, Lim Tae Seop, Marusawa Hiroyuki, Lim Seng Gee, Ochi Hironori, Kondo Masahiko, Uchida Yasushi, Kobashi Haruhiko, Furuta Koichiro, Kurosaki Masayuki, Kim Beom Kyung
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
J Gastroenterol Hepatol. 2025 Jun;40(6):1595-1601. doi: 10.1111/jgh.16986. Epub 2025 Apr 27.
Among patients with hepatitis B virus (HBV)-infected compensated cirrhosis and low-level viremia, there are limited data for comparative outcomes between those treated with oral nucleos(t)ide analogs versus those not. We conducted a large, multi-ethnic, multi-center study to examine the impact of antiviral treatment (AVT) on long-term hepatocellular carcinoma (HCC) risk for compensated cirrhosis and low-level viremia.
Patients with compensated cirrhosis and low-level viremia (serum HBV-DNA 20-2000 IU/mL) at baseline or before AVT were screened for eligibility from 19 hospitals in South Korea, Singapore, and Japan. The primary outcome was HCC development, compared between those receiving AVT versus those untreated throughout follow-up.
Among 848 patients (mean age 55.7 years and 66.9% male), AVT (n = 233) was associated with significantly lower annual HCC incidence compared to non-AVT (n = 615); 1.72/100 versus 2.99/100 person-years (PY), respectively (p = 0.033). Multivariable Cox-regression analyses determined that AVT was associated with significantly lower HCC risk, compared to non-AVT (adjusted HR [HR] 0.514, 95% confidence interval [CI] 0.271-0.976; p = 0.042). In a landmark analysis, HCC incidence was similar between two groups until 18 months, but after this landmark, the treated group had the significantly lower HCC risk compared to untreated group (p = 0.012). Furthermore, propensity score-matching analysis consistently showed that AVT was associated with significantly lower HCC risk, compared to non-AVT; the annual HCC incidence of 1.45/100 PYs versus 2.73/100 PY, respectively (p = 0.043).
Patients with compensated cirrhosis and low-level viremia may benefit from long-term AVT, highlighting appropriate amendment of reimbursement guidelines.
在感染乙型肝炎病毒（HBV）的代偿期肝硬化且病毒血症水平较低的患者中，关于接受口服核苷（酸）类似物治疗与未接受治疗的患者之间比较结果的数据有限。我们开展了一项大型、多民族、多中心研究，以检验抗病毒治疗（AVT）对代偿期肝硬化且病毒血症水平较低患者的长期肝细胞癌（HCC）风险的影响。
在韩国、新加坡和日本的19家医院，对基线时或抗病毒治疗前有代偿期肝硬化且病毒血症水平较低（血清HBV-DNA 20 - 2000 IU/mL）的患者进行资格筛查。主要结局是HCC的发生情况，比较在整个随访期间接受AVT的患者与未接受治疗的患者。
在848例患者（平均年龄55.7岁，男性占66.9%）中，与未接受AVT的患者（n = 615）相比，接受AVT的患者（n = 233）的年度HCC发病率显著更低；分别为1.72/100人年和2.99/100人年（p = 0.033）。多变量Cox回归分析确定，与未接受AVT相比，AVT与显著更低的HCC风险相关（调整后风险比[HR] 0.514，95%置信区间[CI] 0.271 - 0.976；p = 0.042）。在一项标志性分析中，两组在18个月前HCC发病率相似，但在此标志性时间点之后，治疗组的HCC风险显著低于未治疗组（p = 0.012）。此外，倾向评分匹配分析一致显示，与未接受AVT相比，AVT与显著更低的HCC风险相关；年度HCC发病率分别为1.45/100人年和2.73/100人年（p = 0.043）。
代偿期肝硬化且病毒血症水平较低的患者可能从长期AVT中获益，这突出了适当修订报销指南的必要性。
