Deng D L, Jiang J N, Su M H, Wang R M, Zang W W, Ling X Z, Wei H L, Liang X S, Zhou H K, He W M, Guo R S
Department of Infectious Diseases, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Zhonghua Gan Zang Bing Za Zhi. 2020 Dec 20;28(12):1013-1017. doi: 10.3760/cma.j.cn501113-20201028-00584.
To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% . 3.8%, = 0.046). For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.
回顾性分析HBeAg阴性、HBV病毒载量低的慢性乙型肝炎(CHB)患者的血清学、病毒学、生化、肝脏组织学状况及临床结局,探讨此类患者抗病毒治疗的必要性。从随访队列中纳入99例基线时进行肝活检、HBV DNA水平<4 lg拷贝/ml的HBeAg阴性CHB患者。其中,23例在随访期间接受了第二次肝活检。分析肝组织炎症和纤维化程度、HBsAg和HBcAg状态、年龄、性别、家族史、HBV DNA载量、血清学标志物等指标之间的关系。比较两次肝活检检查的病理差异。分析核苷(酸)类似物(NAs)治疗对患者临床结局的影响。进行多因素分析时,采用二元逻辑回归模型。采用对数秩检验比较NAs治疗组和未接受NAs治疗组肝细胞癌(HCC)的累积发病率。基线肝组织学状况显示,58.6%(58/99)的患者在基线肝组织病理学检查中有明显肝组织损伤(G≥2和/或S≥2)。单因素逻辑回归分析显示,肝硬化(LC)家族史、HBsAg阳性家族史、基线丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平是肝组织损伤的正相关因素。多因素逻辑回归分析显示,LC家族史是肝组织损伤的主要危险因素。23例患者在间隔4.5年后接受了第二次肝活检。在10例未治疗的病例中,第二次肝活检结果显示明显肝组织损伤(G≥2和/或S≥2)率从50.0%升至90.0%。在其他13例接受NAs治疗的病例中,第二次肝活检显示肝组织学有改善,明显肝组织损伤率从61.5%降至46.2%。未接受NAs治疗患者的5年HCC累积发病率显著高于接受NAs治疗的患者(17.7%对3.8%,P = 0.046)。对于大多数病毒载量低的HBeAg阴性CHB患者,肝组织病理学结果提示符合抗病毒治疗指征,尤其是有LC家族史的患者。未经抗病毒治疗,这些患者的肝组织损伤将逐渐加重,HCC发病率高。因此,建议对于病毒载量低的HBeAg阴性CHB患者,无论丙氨酸氨基转移酶水平如何,应尽早开始抗病毒治疗,尤其是对于年龄超过30岁、有LC或HCC家族史的患者。