Moscow Clinical Scientific Center n.a. A.S. Loginov, Entuziastov Shosse, 86, 111123, Moscow, Russia.
Department Gastroenterology, Hepatology and Nutrition, Federal Research Center of Nutrition and Biotechnology, Kashirskoye Shosse, 21, 115446, Moscow, Russia.
Adv Ther. 2022 Jan;39(1):430-440. doi: 10.1007/s12325-021-01983-5. Epub 2021 Nov 11.
Viral infections, especially with hepatotropic viruses, may trigger autoimmune liver diseases (AILDs) and deteriorate their course. However, association of previous hepatitis B virus (HBV) infection (presence of anti-HBc with or without anti-HBs or HBV DNA in serum) with AILDs is poorly studied so far. The aim of the study was to assess the prevalence of previous hepatitis B virus infection markers and its clinical significance in patients with autoimmune liver diseases.
The study was based on the data obtained from 234 consecutive HBsAg-negative patients with AILDs [81 with autoimmune hepatitis (AIH), 122 with primary biliary cholangitis (PBC) and 31 with primary sclerosing cholangitis (PSC)] and 131 subjects of the control group without liver diseases. Blood samples of the enrolled patients were tested for anti-HBc and HBV DNA. Samples of liver tissue were examined by standard morphologic protocol and, in anti-HBc positive subjects, for HBV DNA. We assessed estimated risks of AILDs according to anti-HBc positivity and association of anti-HBc positivity with stage of liver fibrosis.
Anti-HBc was detected in 14.5% participants in the control group vs 26.1% (p = 0.016) in patients with AILDs (including 27.1% subjects with PBC (p = 0.021 vs control group), in 29% of PSC and 23.5% in AIH. HBV DNA was detected in three patients with PBC and in one with AIH. Positive anti-HBc test result was associated with higher risk of AILDs-odds ratio (OR) = 2.078 [95% confidence interval (CI) 1.179-3.665], especially in PBC: OR (95% CI) 2.186 (1.165-4.101). Odds of advanced stage of liver fibrosis (F3-F4 by METAVIR) in anti-HBc-positive subjects with PBC were also higher compared to those who had no previous HBV infection: OR (95% CI) 2.614 (1.153-5.926).
Significant proportions of patients with AILDs are anti-HBc positive, and some of them have OBI. Among patients with AILDs, anti-HBc-positivity is most widespread in the PBC group and in subjects with advanced stage of liver fibrosis. Our data may support the idea of an important role of previous HBV infection in the etiology and pathogenesis of AILDs (namely PBC).
病毒感染,特别是嗜肝病毒感染,可能会引发自身免疫性肝病(AILD)并使其病情恶化。然而,先前乙型肝炎病毒(HBV)感染(血清中存在抗-HBc,无论是否存在抗-HBs 或 HBV DNA)与 AILDs 的关联尚未得到充分研究。本研究的目的是评估先前 HBV 感染标志物在自身免疫性肝病患者中的流行情况及其临床意义。
该研究基于 234 例连续的 HBsAg 阴性 AILD 患者[81 例自身免疫性肝炎(AIH)、122 例原发性胆汁性胆管炎(PBC)和 31 例原发性硬化性胆管炎(PSC)]和 131 例无肝脏疾病对照组受试者的数据。对入组患者的血液样本进行抗-HBc 和 HBV DNA 检测。对组织样本进行标准形态学检测,并对抗-HBc 阳性患者进行 HBV DNA 检测。我们根据抗-HBc 阳性评估了 AILDs 的风险,并评估了抗-HBc 阳性与肝纤维化分期的关系。
对照组中有 14.5%的参与者检测到抗-HBc,而 AILD 患者中则有 26.1%(p=0.016)(包括 27.1%的 PBC 患者(p=0.021 与对照组相比)、29%的 PSC 和 23.5%的 AIH)。HBV DNA 在 3 例 PBC 患者和 1 例 AIH 患者中检测到。抗-HBc 阳性检测结果与 AILDs 的风险增加相关(比值比[OR]为 2.078[95%置信区间(CI)为 1.179-3.665]),尤其是在 PBC 中:OR(95%CI)为 2.186(1.165-4.101)。与无先前 HBV 感染的患者相比,抗-HBc 阳性的 PBC 患者肝纤维化晚期(METAVIR 的 F3-F4)的可能性也更高:OR(95%CI)为 2.614(1.153-5.926)。
相当一部分 AILD 患者抗-HBc 阳性,其中一些存在 OBI。在 AILD 患者中,抗-HBc 阳性在 PBC 组和肝纤维化晚期患者中最为常见。我们的数据可能支持先前 HBV 感染在 AILDs(特别是 PBC)发病机制中起重要作用的观点。