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慢性乙型肝炎病毒感染者肝脏疾病的长期自然史:应用马尔可夫链模型分析。

Long-term natural history of liver disease in patients with chronic hepatitis B virus infection: an analysis using the Markov chain model.

机构信息

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan.

Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.

出版信息

J Gastroenterol. 2018 Nov;53(11):1196-1205. doi: 10.1007/s00535-018-1467-x. Epub 2018 Apr 19.

Abstract

BACKGROUND

The relationship between the hepatitis B e antigen (HBeAg) seroconversion and the long-term natural history of liver disease has not been sufficiently investigated.

METHODS

A total of 408 [4352 person-year (PY) units] patients with chronic hepatitis B virus (HBV) without antiviral therapy were enrolled. The study patients were divided into three groups, as follows: Group A (2666 PY units), seroconverted of HBeAg at age < 40; Group B (413 PY units), seroconverted of HBeAg at age ≥ 40; Group C (1273 PY units), persistently HBeAg positive. Yearly transition probabilities from each liver state [chronic HBV infection, chronic hepatitis B, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) negativity] were calculated using the Markov chain model.

RESULTS

In the analysis of 1 year liver disease state transition probabilities, the liver states remained almost the same in Group A. In Groups B and C, each liver state tended to progress to a worse state. Assuming a chronic hepatitis B state at age 40 as the starting condition for simulation over the next 40 years, the chronic hepatitis B state accounted for approximately 60% of males aged ≥ 50 and approximately 40% of females aged ≥ 60 in Group A, and the HBsAg-negative state accounted for approximately 30-40% of males and females aged ≥ 60. In Groups B and C, the probabilities of patients with cirrhosis and HCC gradually increased with age.

CONCLUSIONS

Not only patients with persistent HBeAg positive, but also patients with delayed HBeAg seroconversion showed poor prognosis of liver-related natural history.

摘要

背景

乙型肝炎 e 抗原(HBeAg)血清学转换与肝脏疾病的长期自然史之间的关系尚未得到充分研究。

方法

共纳入 408 例(4352 人年[PY]单位)未接受抗病毒治疗的慢性乙型肝炎病毒(HBV)感染者。研究对象分为三组:A 组(2666PY 单位),HBeAg 在 40 岁前发生血清学转换;B 组(413PY 单位),HBeAg 在 40 岁及以上发生血清学转换;C 组(1273PY 单位),HBeAg 持续阳性。采用马尔可夫链模型计算每年从每种肝脏状态(慢性 HBV 感染、慢性乙型肝炎、肝硬化、肝细胞癌[HCC]和乙型肝炎表面抗原[HBsAg]阴性)转变的概率。

结果

在分析 1 年肝脏疾病状态的转变概率时,A 组的肝脏状态基本保持不变。B 组和 C 组中,每种肝脏状态均倾向于向更差的状态进展。假设 40 岁时的慢性乙型肝炎状态为模拟未来 40 年的起始条件,A 组中,大约 60%的≥50 岁男性和大约 40%的≥60 岁女性处于慢性乙型肝炎状态,HBsAg 阴性状态占≥60 岁男性和女性的大约 30%-40%。B 组和 C 组中,肝硬化和 HCC 的患者概率随着年龄的增长而逐渐增加。

结论

不仅持续 HBeAg 阳性的患者,而且 HBeAg 延迟血清学转换的患者也显示出肝脏相关自然史不良的预后。

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