Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
PLoS One. 2021 Dec 28;16(12):e0261878. doi: 10.1371/journal.pone.0261878. eCollection 2021.
BACKGROUND & AIMS: There is insufficient data on the clinical course of chronic hepatitis B (CHB) patients in the immune-tolerant (IT) and immune-clearance, inactive (IC) phases over a long follow-up period.
We enrolled 466 CHB patients from our historical cohort, including 56 IT+MA (mildly active), 134 IC, 230 with chronic active hepatitis (CH) and 46 with liver cirrhosis (LC), who were categorized to each phase by at least one year of follow-up period from the first visit to our hospital. We investigated long-term risks, and their factors, of developing hepatocellular carcinoma (HCC), and the transition between the clinical phases, especially in the IT+MA and IC groups.
Of the 56 patients in the IT+MA group, 27 remained the IT+MA phase, but 29 transitioned to the CH phase and started nucleot(s)ide analogue (NA) treatment during the follow-up period. Meanwhile, of the 134 patients in the IC group, only 5 started NA treatment after progressing to the CH phase. The development of HCC from the IT+MA, IC, CH, and LC groups was observed in 2, 2, 9, and 20 cases, respectively. The cumulative incidence rates of developing HCC in the IT+MA, IC, CH, and LC groups were 9.9, 1.8, 3.0, and 53.1% at 10 years. In the CH and LC group, patients who developed HCC were older, had higher levels of FIB-4 index, M2BPGi, HBcrAg and AFP, and had lower levels of albumin and platelet counts. In CH patients, FIB-4 index levels were elevated at the diagnosis of HCC compared to baseline, whereas these decreased during the follow-up period in non-HCC patients.
HCC occurred at a certain rate among patients in the IT+MA and IC groups. Careful follow-up is required for CH patients with higher levels of FIB-4 index and/or M2BPGi because of the high incidence of HCC development. (299 words).
在长期随访中，关于免疫耐受（IT）和免疫清除、非活动（IC）期慢性乙型肝炎（CHB）患者的临床病程数据不足。
我们从历史队列中招募了 466 名 CHB 患者，包括 56 名 IT+MA（轻度活动）、134 名 IC、230 名慢性活动性肝炎（CH）和 46 名肝硬化（LC）患者，他们根据首次就诊时的至少一年随访期被归类到每个阶段。我们研究了发展为肝细胞癌（HCC）的长期风险及其因素，以及特别是在 IT+MA 和 IC 组中临床阶段之间的转变。
在 IT+MA 组的 56 名患者中，27 名患者仍处于 IT+MA 阶段，但 29 名患者转变为 CH 阶段，并在随访期间开始核苷（酸）类似物（NA）治疗。同时，在 IC 组的 134 名患者中，仅有 5 名患者在进展为 CH 阶段后开始 NA 治疗。在 IT+MA、IC、CH 和 LC 组中观察到 HCC 的发展分别为 2、2、9 和 20 例。在 IT+MA、IC、CH 和 LC 组中，HCC 的累积发生率分别为 10 年后的 9.9%、1.8%、3.0%和 53.1%。在 CH 和 LC 组中，发生 HCC 的患者年龄较大，FIB-4 指数、M2BPGi、HBcrAg 和 AFP 水平较高，白蛋白和血小板计数较低。在 CH 患者中，与基线相比，HCC 诊断时 FIB-4 指数水平升高，而在非 HCC 患者中，该指数在随访期间下降。
在 IT+MA 和 IC 组患者中，一定比例的患者发生 HCC。对于 FIB-4 指数和/或 M2BPGi 水平较高的 CH 患者，需要进行仔细随访，因为 HCC 发展的发生率较高。（299 字）
