慢性乙型肝炎患者血清内质网应激指标变化及其临床意义*

doi:10.3969/j.issn.1672-5069.2021.04.008

Abstract

Abstract: Objective The aim of this study was to investigate the change of serum endoplasmic reticulum stress parameters in patients with chronic hepatitis B (CHB). Methods 109 patients with CHB, 91 patients with hepatitis B cirrhosis and 76 patients with primary liver cancer (PLC)], and 120 healthyvolunteers were recruited in this study between May 2017 and May 2020, and serum hyaluronic acid (HA) , laminin (LN), type Ⅲ collagen peptide (P Ⅲ P), and collagen type Ⅳ (Ⅳ - C) were assayed by RIA. Serum glucose-regulating protein 78 (GRP78), endoplasmic reticulum stress transcription factor CCAAT/enhancer binding protein homologous protein (CHOP) and aspartic cysteine-specific protease 12 (Caspase-12) were determined by ELISA. Results Serum ALT, AST, GGT and ALP levels in patients with CHB were (83.4±21.7)U/L, (63.7±20.5)U/L, (82.2±20.4)U/L and (95.7±20.8)U/L, they were (74.3±18.5)U/L,(51.5±18.9)U/L,(84.9±22.5)U/L and (94.8±19.8)U/L in patients with liver cirrhosis, and were (70.2±17.7)U/L, (52.6±18.8)U/L, (93.8±24.8)U/L and (106.8±22.4)U/L in patients with PLC, all significantly higher than those in healthy control (P＜0.05); serum HA,LN,Ⅳ-C and PⅢP levels in patients with CHB were (84.5±78.9)ng/mL, (52.8±24.1)ng/mL,(61.4±33.0)ng/mL and (10.9±7.4)ng/mL, in patients with liver cirrhosis were (155.2±75.6)ng/mL,(63.1±22.8)ng/mL, (82.2±30.1)ng/mL and (15.4±5.2)ng/mL, and in patients with PLC were (153.3±73.2)ng/mL, (64.6±20.4)ng/mL, (80.9±28.4)ng/mL and (15.4±3.1)ng/mL, all significantly higher than [(38.6±14.2)ng/mL,(34.2±13.3)ng/mL, (33.9±10.9)ng/mL and (6.8±1.6)ng/mL, respectively,P＜0.05] in healthy control; serum GRP78, CHOP and caspase-12 levels in patients with CHB were (44.0±12.4)μg/L, (2485.5±1200.0)μg/L and (699.8±204.2)pmol/L, in patients with liver cirrhosis were (51.7±15.9)μg/L, (2873.1±1314.2)μg/L and (752.2±241.5)pmol/L, and in patients with PLC were (62.7±17.1)μg/L, (3040.9±1440.3)μg/L and (842.8±289.4)pmol/L, all significantly higher than [(7.3±2.1)μg/L,(833.4±333.5)μg/L and (85.3±13.7)pmol/L,P＜0.05] in healthy persons. Conclusion Endoplasmic reticulum stress is activated in patients with CHB, and its implications warrants further investigation.

Key words: Hepatitis B, Endoplasmic reticulum stress, Glucose-regulating protein 78, CCAAT/enhancer binding protein homologous protein, Caspase-12

Wu Hui, Song Bo, Lyu Chengxiu, et al. Change of serum endoplasmic reticulum stress parameters in patients with chronic hepatitis B[J]. Journal of Practical Hepatology, 2021, 24(4): 484-487.

References

[1] Ahmad AA, Falla AM, Duffell E, et al. Estimating the scale of chronic hepatitis B virus infection among migrants in EU/EEA countries. BMC Infect Dis, 2018, 18(1):34-47.
[2] Choi YM, Lee SY, Kim BJ. Naturally occurring hepatitis B virus mutations leading to endoplasmic reticulum stress and their contribution to the progression of hepatocellular carcinoma. Int J Mol Sci, 2019, 20(3):597-612.
[3] Li X, Pan E, Zhu J, et al. Cisplatin enhances hepatitis B virus replication and PGC-1α expression through endoplasmic reticulum stress. Sci Rep, 2018, 8(1):3496-3509.
[4] Montalbano R, Honrath B, Elxnat M, et al. Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells. Oncotarget, 2016, 7(15):20312-20323.
[5] Koo JH, Lee HJ, Kim W, et al. Endoplasmic reticulum stress in hepatic stellate cells promotes liver fibrosis via PERK-mediated degradation of HNRNPA1 and Up-regulation of SMAD2. Gastroenterology, 2016, 150(1):181-193.
[6] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南(2019年版).实用肝脏病杂志,2020,23(1)S9-32.
[7] 中华人民共和国卫生部. 原发性肝癌诊疗规范(2011年版). 中华肝脏病杂志, 2012, 20(6):929-946.
[8] Falla AM, Ahmad AA, Duffell E, et al. Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a focus on migrants from anti-HCV endemic countries. BMC Infect Dis, 2018, 18(1):42-54.
[9] Lee H, Kim H, Lee SA, et al. Upregulation of endoplasmic reticulum stress and reactive oxygen species by naturally occurring mutations in hepatitis B virus core antigen. J Gen Virol, 2015, 96(7):1850-1854.
[10] Vyas AK, Sharma BC, Sarin SK, et al. Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients. Liver Int, 2018, 38(1):38-49.
[11] Zheng Q, Zhu YY, Chen J, et al. Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection. Clin Exp Immunol, 2015, 180(3):499-508.
[12] Mou HJ, Wu S, Zhao G, et al. Changes of Th17/Treg ratio in the transition of chronic hepatitis B to liver cirrhosis and correlations with liver function and inflammation. Exp Ther Med, 2019, 17(4):2963-2968.
[13] Chon YE, Park JY, Myoung SM, et al. Improvement of liver fibrosis after long-term antiviral therapy assessed by fibroscan in chronic hepatitis B patients with advanced fibrosis. Am J Gastroenterol, 2017, 112(6):882-891.
[14] 左中宝, 崔怀中, 黄从想, 等. FibroTouch与6种肝纤维化血清学模型评估慢性乙型肝炎患者程度的临床研究. 中华肝脏病杂志,2019, 27(6):430-435.
[15] Shao LN, Zhang ST, Zhou SH, et al. Atypical chemokine receptor 1 polymorphism cannot be used as an indicator of liver fibrosis progression in hepatitis C virus positive patients. Pak J Med Sci, 2017, 33(5):1134-1137.
[16] Ren F, Shi H, Zhang L, et al. The dysregulation of endoplasmic reticulum stress response in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B. J Viral Hepat, 2016, 23(1):23-31.
[17] He Q, Fu Y, Ding X, et al. High-mobility group box 1 induces endoplasmic reticulum stress and activates hepatic stellate cells. Lab Invest, 2018, 98(9):1200-1210.
[18] Li J, He J, Fu Y, et al. Hepatitis B virus X protein inhibits apoptosis by modulating endoplasmic reticulum stress response. Oncotarget, 2017, 8(56):96027-96034.
[19] 王慧娟, 徐玲, 田原, 等. 内质网应激在乙型重型肝炎(肝衰竭)中的作用研究. 中华肝脏病杂志, 2019, 27(4):244-249.
[20] 史晓燕, 李京涛. 内质网应激及其对肝纤维化调控作用的研究进展. 中华肝脏病杂志, 2018, 26(11):865-868.

Change of serum endoplasmic reticulum stress parameters in patients with chronic hepatitis B

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