代谢功能障碍相关脂肪性肝病对慢性乙型肝炎感染患者肝细胞癌风险影响的异质性及其潜在原因分析

doi:10.16138/j.1673-6087.2026.02.12

摘要/Abstract

摘要：

代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated steatotic liver disease，MASLD）与慢性乙型肝炎（chronic hepatitis B，CHB）的共病率逐渐升高，二者均可独立导致肝硬化、肝细胞癌（hepatocellular carcinoma，HCC）等不良结局。但关于合并MASLD对CHB患者HCC发生风险的影响，研究结果存在显著异质性：一些研究提示MASLD可通过代谢炎症、脂毒性和胰岛素抵抗等机制，与乙型肝炎病毒(hepatitis B virus,HBV)引起的慢性炎症相互作用，加速疾病进展；然而，部分研究显示脂肪变性与较低的病毒复制水平及更高的乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)清除率相关，提示潜在保护效应。本文综述了MASLD与CHB相互作用的潜在机制，并重点探讨现有临床研究中MASLD对CHB患者HCC发生风险所呈现的“促进”或“保护”效应的不同研究结论，归纳了脂肪肝定义演变、病毒学状态及抗病毒治疗差异、肝纤维化程度以及诊断方法和人群特征不统一等可能导致异质性的因素。未来应积极干预上述共病患者的代谢异常，同时在统一定义、精细分层和方法学标准化的基础上开展研究，以明确不同代谢表型对CHB进展及HCC风险的真实作用，为精准风险预测和综合干预提供循证支持。

Abstract:

The comorbidity rate of metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic hepatitis B (CHB) is steadily increasing. Both MASLD and CHB can independently lead to adverse outcomes, including cirrhosis and hepatocellular carcinoma (HCC). However, the impact of coexisting MASLD on HCC risk in CHB patients shows high heterogeneity across current studies: some studies suggest that MASLD may accelerate disease progression through mechanisms such as metabolic inflammation, lipotoxicity, and insulin resistance, interacting with the chronic inflammation induced by hepatitis B virus (HBV); conversely, some studies report that hepatic steatosis is associated with lower viral replication levels and a higher rate of hepatitis B surface antigen (HBsAg) clearance, indicating a potential protective effect. This review outlines the potential mechanisms underlying MASLD and CHB interactions, focuses on the divergent findings from existing clinical research regarding whether MASLD exerts a “promoting” or “protective” effect on HCC risk in CHB patients, and summarizes factors that may contribute to this heterogeneity, including the definition evolvement of fatty liver disease, differences in virological status and antiviral treatment, degree of liver fibrosis, and inconsistency in diagnostic methods and population characteristics. In the future, active intervention should be taken to address metabolic abnormalities in patients with the aforementioned comorbidities. Meanwhile, studies based on unified definitions, precise stratification, and methodological standardization should be conducted to clarify the true impact of different metabolic phenotypes on CHB progression and HCC risk, thereby providing evidence-based support for precise risk prediction and integrated intervention.

Key words: metabolic dysfunction-associated steatotic liver disease, chronic hepatitis B, hepatocellular carcinoma, comorbidity, risk prediction, heterogeneity

石娅茹, 许文欣, 樊蓉. 代谢功能障碍相关脂肪性肝病对慢性乙型肝炎感染患者肝细胞癌风险影响的异质性及其潜在原因分析[J]. 内科理论与实践, 2026, 21(02): 176-182.

SHI Yaru, XU Wenxin, FAN Rong. Analysis of the heterogeneity in the effect of metabolic dysfunction-associated steatotic liver disease on hepatocellular carcinoma risk in patients with chronic hepatitis B infection and its potential causes[J]. Journal of Internal Medicine Concepts & Practice, 2026, 21(02): 176-182.

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序号	研究及发表年份	研究设计	肝脂肪变性诊断标准	样本量	CHB合并肝脂肪变性/ 脂肪性肝炎	单纯CHB	中位随访时间/月	主要观察终点	对HCC发生风险影响
1	Chan等^[10] (2017)	回顾性	肝穿刺活检	270	107	163	80	HCC发生率	增加
2	Yun等^[11] (2022)	回顾性	FLI≥30+存在代谢危险因素	197 346	66 149	131 197	84	HCC发生率	增加
3	Wong等^[28] (2020)	回顾性	瞬时弹性成像CAP≥248 dB/m	614	294	320	45	心血管事件、肝脏并发症、恶性肿瘤及死亡率	无显著影响
4	Mak等^[13] (2021)	前瞻性	瞬时弹性成像CAP分组，≥248 dB/m 和≥280 dB/m	2,403	706	1 247	46	HCC发生率	降低
5	Li等^[14] (2021)	回顾性	超声等影像学检查中发现脂肪浸润	6 786	1 079 （匹配后）	1 079 （匹配后）	132	肝硬化、HCC发生率及HBsAg清除率	降低
6	Choi等^[4] (2020)	回顾性	肝穿刺活检	1 089	185	904	120	肝脏失代偿、HCC、肝移植或死亡发生率	增加
7	Huang等^[12] (2023)	回顾性	超声等影像学检查中发现脂肪浸润+存在代谢危险因素（MASLD标准）	10 546	2 212	8 334	61	HCC发生率	增加
8	Hsueh等^[15] (2022)	前瞻性	超声等影像学检查中发现脂肪浸润	2 385	1 092	1 293	337	HBsAg清除；HCC发生；肝酶升高与肝硬化进展	降低
9	Chen等^[29] (2020)	回顾性	肝穿刺活检	196	94	102	55	HBeAg血清转换率	未提及
10	Ren等^[30] (2025)	回顾性	超声或计算机断层扫描等影像学检查中发现脂肪浸润+存在代谢危险因素（MASLD标准）	320	195	125	6	48周时的HBsAg应答率	未提及