恩替卡韦联合多烯磷脂酰胆碱治疗慢性乙型肝炎合并非酒精性脂肪性肝炎的疗效分析

摘要/Abstract

摘要： 目的评价恩替卡韦联合多烯磷脂酰胆碱治疗慢性乙型肝炎(CHB)合并非酒精性脂肪性肝炎(NASH)患者的疗效。方法回顾2022年1月—2025年1月于中国人民解放军联勤保障部队第九〇四医院就诊的102例CHB合并NASH患者,并作为研究对象,根据治疗方案分为单纯组(恩替卡韦,n=52)、联合组(恩替卡韦联合多烯磷脂酰胆碱,n=50),比较两组病毒学、肝功能、代谢炎症指标及肝组织学改善情况。结果治疗48周后,联合组HBV DNA水平显著低于单纯组[(2.1±0.7)lg U/mL vs. (2.7±0.8)lg U/mL,P<0.05],ALT水平亦明显低于单纯组[(28.4±13.2)U/L vs. (36.2±17.5)U/L,P<0.05]。联合组ALT正常化率为88.0%(44/50),高于单纯组的65.4%(34/52)(P<0.05)。肝纤维化及脂肪变性指标方面,联合组APRI、FIB-4、LSM、CAP及MRI-PDFF分别为(0.7±0.3)kPa、(1.8±0.7)kPa、(6.8±2.1)kPa、(243.2±28.4)dB/m及(11.8±3.7)%,均显著低于单纯组[(1.0±0.4)kPa、(2.2±0.8)kPa、(7.8±2.3)kPa、(273.0±30.8)dB/m、(14.6±4.2)%,均P<0.05]。代谢及炎症指标方面,联合组HOMA-IR、TG、hs-CRP、IL-6分别为(2.3±0.9)mmol/L、(1.7±0.5)mmol/L、(2.5±1.1)mg/L、(5.9±2.1)pg/mL,均低于单纯组[(2.8±1.0)mmol/L、(1.9±0.5)mmol/L、(3.3±1.2)mmol/L、(6.9±2.3)pg/mL,均P<0.05]。肝组织学结果显示,联合组NAS总评分、Ishak纤维化评分及CPA分别为(3.1±1.0)分、(2.4±0.8)分及(4.9±1.8)%,显著低于单纯组[(4.2±1.1)分、(3.1±0.9)分及(6.8±2.1)%,P<0.05]。结论恩替卡韦联合多烯磷脂酰胆碱治疗可显著改善CHB合并NASH患者的病毒学、肝功能及代谢炎症指标,减轻肝脂肪变性与纤维化程度,促进肝组织结构修复。

关键词: 慢性乙型肝炎, 非酒精性脂肪性肝炎, 恩替卡韦, 多烯磷脂酰胆碱

Abstract: Objective To evaluate the therapeutic efficacy of entecavir combined with polyene phosphatidylcholine (PPC) in patients with chronic hepatitis B (CHB) complicated by nonalcoholic steatohepatitis (NASH). Methods A total of 102 patients with CHB complicated by NASH who were treated in the 904th Hospital of the Joint Service Support Force of the Chinese People′s Liberation Anny from January 2022 to January 2025 were enrolled. According to the treatment regimen, patients were divided into two groups: the monotherapy group (entecavir alone, n=52) and the combination group (entecavir plus PPC, n=50). Virological indicators, liver function, metabolic and inflammatory parameters, as well as histological improvements were compared between the two groups. Results After 48 weeks of treatment, the HBV DNA level in the combination group (2.1±0.7) lg U/mL was significantly lower than that in the monotherapy group [(2.7±0.8) lg U/mL, P<0.05). The ALT level in the combination group (28.4±13.2) U/L was also significantly lower than that in the monotherapy group [(36.2±17.5) U/L, P<0.05]. The rate of ALT normalization was 88.0% (44/50) in the combination group, higher than 65.4% (34/52) in the monotherapy group (P<0.05). Regarding hepatic fibrosis and steatosis indices, the combination group showed APRI, FIB-4, LSM, CAP, and MRI-PDFF values of (0.7±0.3) kPa, (1.8±0.7) kPa, (6.8±2.1) kPa, (243.2±28.4) dB/m and (11.8±3.7) %, respectively, which were all significantly lower than those in the monotherapy group [(1.0±0.4) kPa, (2.2±0.8) kPa, (7.8±2.3) kPa, (273.0±30.8) dB/m and (14.6±4.2) %, P<0.05]. For metabolic and inflammatory parameters, HOMA-IR, TG, hs-CRP, and IL-6 levels in the combination group were (2.3±0.9) mmol/L, (1.7±0.5) mmol/L, (2.5±1.1) mg/L and (5.9±2.1) pg/mL, respectively, lower than those in the monotherapy group [(2.8±1.0) mmol/L, (1.9±0.5) mmol/L, (3.3±1.2) mmol/L and (6.9±2.3) pg/mL, P<0.05]. Histological results showed that the NAS total score, Ishak fibrosis score, and CPA in the combination group were (3.1±1.0) points, (2.4±0.8) points and (4.9±1.8)%, respectively, which were significantly lower than those in the monotherapy group [(4.2±1.1) points, (3.1±0.9) points and (6.8±2.1)%, P<0.05]. Conclusion Entecavir combined with polyene phosphatidylcholine can significantly improve virological, hepatic, metabolic, and inflammatory indicators in patients with CHB complicated by NASH, alleviates hepatic steatosis and fibrosis, and promotes structural repair of liver tissue.

Key words: Chronic hepatitis B, Nonalcoholic steatohepatitis, Entecavir, Polyene phosphatidylcholine

杨敏, 孙舒. 恩替卡韦联合多烯磷脂酰胆碱治疗慢性乙型肝炎合并非酒精性脂肪性肝炎的疗效分析[J]. 肝脏, 2026, 31(4): 560-564.

YANG Min, SUN Shu. Efficacy of entecavir combined with polyene phosphatidylcholine in the treatment of patients with chronic hepatitis B complicated by nonalcoholic steatohepatitis[J]. Chinese Hepatolgy, 2026, 31(4): 560-564.

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参考文献

[1] Shan S, Zhao X, Jia J. Comprehensive approach to controlling chronic hepatitis B in China[J]. Clin Mol Hepatol, 2024, 30(2):135-143.
[2] Jiang P, Jia H, Qian X, et al. Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B[J]. Hepatology, 2024, 79(1):167-182.
[3] Buti M, Heo J, Tanaka Y, et al. Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B[J]. J Hepatol, 2025, 82(2):222-234.
[4] Schwabe R F, Tabas I, Pajvani U B. Mechanisms of fibrosis development in nonalcoholic steatohepatitis[J]. Gastroenterology, 2020, 158(7):1913-1928.
[5] Younossi Z M, Golabi P, Paik J M, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review[J]. Hepatology, 2023, 77(4):1335-1347.
[6] Llovet J M, Willoughby C E, Singal A G, et al. Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment[J]. Nat Rev Gastroenterol Hepatol, 2023, 20(8):487-503.
[7] Hanif H, Khan M M, Ali M J, et al. A new endemic of concomitant nonalcoholic fatty liver disease and chronic hepatitis B[J]. Microorganisms, 2020, 8(10):1526.
[8] Wang L, Lu C, Zhang Y, et al. Association of chronic hepatitis B infection with hepatic steatosis and injury in nonalcoholic fatty liver disease children[J]. BMC Gastroenterol, 2024, 24(1):2.
[9] Tian Y, Jellinek M J, Mehta K, et al. Membrane phospholipid remodeling modulates nonalcoholic steatohepatitis progression by regulating mitochondrial homeostasis[J]. Hepatology, 2024, 79(4):882-897.
[10] Bao H, Murakami S, Tsuge M, et al. Alteration of gene expression after entecavir and pegylated interferon therapy in HBV-infected chimeric mouse liver[J]. Viruses, 2024, 16(11):1743.
[11] Zhang J, Zang X, Lv J, et al. Changes in lipidomics, metabolomics, and the gut microbiota in CDAA-induced NAFLD mice after polyene phosphatidylcholine treatment[J]. Int J Mol Sci, 2023, 24(2):1502.
[12] 中华医学会肝病学分会,中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 实用肝脏病杂志, 2023, 26(3):后插1-后插22.
[13] 中华医学会肝病学分会, 范建高, 南月敏, 等. 代谢相关(非酒精性)脂肪性肝病防治指南(2024年版)[J]. 实用肝脏病杂志, 2024, 27(4):494-510.
[14] Huang S C, Liu C J. Chronic hepatitis B with concurrent metabolic dysfunction-associated fatty liver disease: Challenges and perspectives[J]. Clin Mol Hepatol, 2023, 29(2):320-331.
[15] Luo J, Du Z, Liang D, et al. Gamma-glutamyl transpeptidase-to-platelet ratio predicts liver fibrosis in patients with concomitant chronic hepatitis B and nonalcoholic fatty liver disease[J]. J Clin Lab Anal, 2022, 36(8):e24596.
[16] Lu Y, Feng T, Zhao J, et al. Polyene phosphatidylcholine ameliorates high fat diet-induced non-alcoholic fatty liver disease via remodeling metabolism and inflammation[J]. Front Physiol, 2022, 13:810143.
[17] Li Y, Chen A, Li Z, et al. Effectiveness of polyene phosphatidylcholine and its combination with other drugs in patients with liver diseases based on real-world research[J]. Expert Rev Clin Pharmacol, 2022 15(11):1363-1375.
[18] Xu Z, Hao W, Xu D, et al. Polyene phosphatidylcholine interacting with TLR-2 prevents the synovial inflammation via inactivation of MAPK and NF-κB pathways[J]. Inflammation, 2022, 45(4):1507-1519.
[19] Chen X, Du J, Zhan W, et al. Polyene phosphatidylcholine promotes tibial fracture healing in rats by stimulating angiogenesis dominated by the VEGFA/VEGFR2 signaling pathway[J]. Biochem Biophys Res Commun, 2024, 719:150100.
[20] Feng T T, Yang X Y, Hao S S, et al. TLR-2-mediated metabolic reprogramming participates in polyene phosphatidylcholine-mediated inhibition of M1 macrophage polarization[J]. Immunol Res, 2020, 68(1):28-38.