Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants.

IF 1.5 Q3 GASTROENTEROLOGY & HEPATOLOGY

International Journal of Hepatology Pub Date : 2022-08-23 eCollection Date: 2022-01-01 DOI:10.1155/2022/6046677

Turyadi, Billy Witanto, Korri E El-Khobar, M Luthfi Parewangi, M Rezki Rasyak, Dhita P Wibowo, Meta D Thedja, Irawan Yusuf, Muh Nasrum Massi, Ilhamjaya Patellongi, Din Syafruddin, David H Muljono

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引用次数: 1

Abstract

Background: The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients.

Methods: A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI.

Results: No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects' age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001), and LR to ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605-11.023, P = 0.004).

Conclusions: Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.

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慢性乙型肝炎自然史中的宿主因素:遗传决定因素的作用。

背景:宿主免疫系统在乙型肝炎病毒(HBV)感染表现中起重要作用。几种炎症细胞因子的遗传多态性，包括TNF-α和IL-10，与慢性乙型肝炎(CHB)的进展有关，尽管结果相互矛盾。慢性乙型肝炎的进展可分为四个阶段:免疫耐受(IT)、免疫清除(IC)、低/无复制(LR)和e阴性肝炎(ENH)，其中HBeAg血清转化是一个重要的里程碑。在这里，我们确定了TNF-α (rs1800629)和IL-10 (rs1800896和rs1800872) snp在印度尼西亚CHB患者CHB自然病程进展中的相关性，特别是与HBeAg血清转化的相关性。方法:共招募287名受试者，并根据HBeAg、病毒载量和ALT水平将其分为不同的CHB期。采用PCR-RFLP检测TNF-α和IL-10 snp，并直接测序确认。SNP基因型与CHB动力学之间的关系采用95% CI的优势比(OR)来确定。结果:在所有基因模型中，IL-10 -592A/C多态性与IT和IC向LR期、IT和IC向ENH期、LR向ENH期进展均无显著相关性。IL-10 rs1800896和TNF-α rs1800629不能用logistic回归分析。受试者年龄(≥40岁)与IT和IC / LR (OR: 2.191, 95% CI 1.067-4.578, P = 0.034)、IT和IC / ENH (OR: 7.460, 95% CI 3.316-18.310, P < 0.001)、LR / ENH (OR: 5.252, 95% CI 2.010-14.858, P = 0.001)显著相关。男性与LR和ENH相关(OR: 4.077, 95% CI 1.605-11.023, P = 0.004)。结论:年龄和男性性别与CHB期进展相关，而不是TNF-α和IL-10多态性。研究宿主决定因素和病毒因素对慢性乙型肝炎病毒期进展的影响，有助于了解慢性乙型肝炎病毒期进展的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Hepatology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

15 weeks

期刊介绍： International Journal of Hepatology is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to the medical, surgical, pathological, biochemical, and physiological aspects of hepatology, as well as the management of disorders affecting the liver, gallbladder, biliary tree, and pancreas.