Kim Soo Ryang, Kim Soo Ki
Department of Gastroenterology, Kobe Asahi Hospital, Kobe 653-0801, Japan.
Diagnostics (Basel). 2023 Oct 14;13(20):3212. doi: 10.3390/diagnostics13203212.
Though the world-wide hepatitis B virus (HBV) vaccination program has been well completed for almost thirty years in many nations, almost HBV-related hepatocellular carcinoma (HCC) occurs in unvaccinated middle-aged and elderly adults. Apparently, treating 80% of qualified subjects could decrease HBV-related mortality by 65% in a short period. Nevertheless, globally, only 2.2% of CHB patients undergo antiviral therapy. The HBV markers related to HCC occurrence and prevention are as follows: the HCC risk is the highest at a baseline of HBV DNA of 6-7 log copies/mL, and it is the lowest at a baseline of an HBV DNA level of >8 log copies/mL and ≤4 log copies/mL (parabolic, and not linear pattern). The titer of an HBV core-related antigen (HBcrAg) reflecting the amount of HBV covalently closed circular DNA (ccc DNA) in the liver is related to HCC occurrence. The seroclearance of HBs antigen (HBsAg) is more crucial than HBV DNA negativity for the prevention of HCC. In terms of the secondary prevention of hepatitis B-related HCC involving antiviral therapies with nucleos(t)ide analogues (NAs), unsolved issues include the definition of the immune-tolerant phase; the optimal time for starting antiviral therapies with NAs; the limits of increased aminotransferase (ALT) levels as criteria for therapy in CHB patients; the normalization of ALT levels with NAs and the relation to the risk of HCC; and the relation between serum HBV levels and the risk of HCC. Moreover, the first-line therapy with NAs including entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) remains to be clarified. Discussed here, therefore, are the recent findings of HBV markers related to HCC occurrence and prevention, unsolved issues, and the current secondary antiviral therapy for the prevention of HBV-related HCC.
尽管全球乙肝病毒（HBV）疫苗接种计划在许多国家已顺利完成近三十年，但几乎所有与HBV相关的肝细胞癌（HCC）都发生在未接种疫苗的中老年成年人中。显然，治疗80%的合格受试者可在短期内将HBV相关死亡率降低65%。然而，在全球范围内，只有2.2%的慢性乙型肝炎（CHB）患者接受抗病毒治疗。与HCC发生和预防相关的HBV标志物如下：在HBV DNA基线水平为6 - 7 log拷贝/mL时，HCC风险最高；在HBV DNA水平>8 log拷贝/mL和≤4 log拷贝/mL的基线时，风险最低（呈抛物线型，而非线性模式）。反映肝脏中HBV共价闭合环状DNA（ccc DNA）量的乙肝核心相关抗原（HBcrAg）滴度与HCC发生有关。对于HCC的预防，乙肝表面抗原（HBsAg）的血清学清除比HBV DNA转阴更为关键。在涉及核苷（酸）类似物（NAs）抗病毒治疗的乙肝相关HCC二级预防方面，尚未解决的问题包括免疫耐受期的定义；开始使用NAs进行抗病毒治疗的最佳时机；CHB患者中以转氨酶（ALT）水平升高作为治疗标准的局限性；使用NAs使ALT水平正常化及其与HCC风险的关系；以及血清HBV水平与HCC风险的关系。此外，包括恩替卡韦（ETV）、替诺福韦酯（TDF）和替诺福韦艾拉酚胺（TAF）在内的NAs一线治疗仍有待明确。因此，本文讨论了与HCC发生和预防相关的HBV标志物的最新研究结果、未解决的问题以及当前用于预防HBV相关HCC的二级抗病毒治疗。
