Quantitative characteristics of serum lipoprotein phenotypes for HBV patients

doi:10.3969/j.issn.1674-8115.2023.02.002

Abstract

Abstract:

Objective ·Previous studies showed that hepatitis B virus (HBV) infection caused outstanding changes in host lipoproteins. However, there are no reports on such component changes of lipoprotein subfractions. This study aimed to quantify the HBV-caused changes in the serum lipoprotein subfractions and their components. Methods ·Hepatitis B surface antigen-positive [HBsAg (+)] patients at Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March to June 2017 were included (n=40), and 40 HBsAg-negative [HBsAg (-)] population were matched as controls. Serum lipoprotein subfractions and their components were quantified by using ¹H-NMR. Orthogonal partial least-squares discriminant analysis (OPLS-DA), variance analysis between the two groups, logistic regression analysis and Spearman correlation analysis were conducted to reveal the lipoprotein changes in chronic HBV patients against controls. Results ·HBsAg (+) population had significantly lower levels in most lipoprotein subfractions than HBsAg (-) population. After adjustments for age, gender, hypertension, diabetes mellitus and coronary heart disease, the levels of total VLDL, VLDL1-VLDL3, IDL, HDL4, non-HDL and their components were protective factors for HBV infection (OR < 1, P < 0.01). In contrast, VLDL5-(TAG/LP) was a risk factor for HBV infection (OR > 1, P < 0.01). In addition, the severity of inflammation in the HBsAg (+) population was negatively correlated with the levels of lipids in HDL4 with correlation coefficient ranging from -0.71 to -0.51(P≤ 0.002). Six lipoprotein subfractions were obtained through feature screening, and the AUC of HBV infection diagnosis model was 0.861. Conclusion ·HBV infection causes significant changes in liver-excretion of lipoproteins and their circulation metabolism; the lipoprotein phenotypes can differentiate HBV-infected patients from controls.

Key words: lipoprotein, ¹H-NMR, hepatitis B virus, chronic hepatitis B

CLC Number:

R33.1

YI Xiaoxuan, HU Senlin, SUN Yang, HUANG Qingxia, TANG Huiru. Quantitative characteristics of serum lipoprotein phenotypes for HBV patients[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(2): 143-151.

Figures/Tables 4

TrendMD

References 26

1	中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 中华肝脏病杂志, 2019, 27(12): 938-961.
	Chinese Society of Infectious Diseases Chinese Medical Association, Chinese Society of Hepatology Chinese Medical Association. The guidelines of prevention and treatment for chronic hepatitis B (2019 version)[J]. Chinese Journal of Hepatology, 2019, 27(12): 938-961.
2	MCGLYNN K A, PETRICK J L, EL-SERAG H B. Epidemiology of hepatocellular carcinoma[J]. Hepatology, 2021, 73(S1): 4-13.
3	LIU Z Q, JIANG Y F, YUAN H B, et al. The trends in incidence of primary liver cancer caused by specific etiologies: results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention[J]. J Hepatol, 2019, 70(4): 674-683.
4	NGUYEN M H, WONG G, GANE E, et al. Hepatitis B virus: Advances in prevention, diagnosis, and therapy[J]. Clin Microbiol Rev, 2020, 33(2): e0046-e0019.
5	BAR-YISHAY I, SHAUL Y, SHLOMAI A. Hepatocyte metabolic signalling pathways and regulation of hepatitis B virus expression[J]. Liver Int, 2011, 31(3): 282-290.
6	HUANG Q X, LEI H H, DING L F, et al. Stimulated phospholipid synthesis is key for hepatitis B virus replications[J]. Sci Rep, 2019, 9(1): 12989.
7	JOO E J, CHANG Y, YEOM J S, et al. Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: a cohort study[J]. Hepatology, 2017, 65(3): 828-835.
8	WANG F B, ZHU C L, LIU X H, et al. HBV inhibits apoB production via the suppression of MTP expression[J]. Lipids Health Dis, 2011, 10: 207.
9	ZHU C L, GAO G S, SONG H, et al. Hepatitis B virus inhibits apolipoprotein A5 expression through its core gene[J]. Lipids Health Dis, 2016, 15(1): 178.
10	ZHU C L, ZHU H C, SONG H, et al. Hepatitis B virus inhibits the in vivo and in vitro synthesis and secretion of apolipoprotein C3[J]. Lipids Health Dis, 2017, 16(1): 213.
11	HSU C S, LIU C H, WANG C C, et al. Impact of hepatitis B virus infection on metabolic profiles and modifying factors[J]. J Viral Hepat, 2012, 19(2): E48-E57.
12	JAN C F, CHEN C J, CHIU Y H, et al. A population-based study investigating the association between metabolic syndrome and hepatitis B/C infection (Keelung Community-based Integrated Screening Study No. 10)[J]. Int J Obes (Lond), 2006, 30(5): 794-799.
13	QUAYE O, AMUZU B G, ADADEY S M, et al. Effect of hepatitis B virus (HBV) infection on lipid profile in Ghanaian patients[J]. Virology (Auckl), 2019, 10: 1178122X19827606.
14	TARGHER G, BERTOLINI L, PADOVANI R, et al. Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C[J]. J Hepatol, 2007, 46(6): 1126-1132.
15	ZUO D, AN H H, LI J H, et al. The application value of lipoprotein particle numbers in the diagnosis of HBV-related hepatocellular carcinoma with BCLC stage 0-A[J]. J Pers Med, 2021, 11(11): 1143.
16	KULKARNI K R. Cholesterol profile measurement by vertical auto profile method[J]. Clin Lab Med, 2006, 26(4): 787-802.
17	RÁDIKOVÁ Ž, PENESOVÁ A, VLČEK M, et al. Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?[J]. Lipids Health Dis, 2020, 19(1): 49.
18	KAUFMAN S L. Analysis of biomolecules using electrospray and nanoparticle methods: the gas-phase electrophoretic mobility molecular analyzer (GEMMA)[J]. J Aerosol Sci, 1998, 29(5/6): 537-552.
19	CLOUET-FORAISON N, GAIE-LEVREL F, GILLERY P, et al. Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling[J]. Clin Chem Lab Med, 2017, 55(10): 1453-1464.
20	JIMÉNEZ B, HOLMES E, HEUDE C, et al. Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by ¹H NMR spectroscopy in a multilaboratory trial [J]. Anal Chem, 2018, 90(20): 11962-11971.
21	YASUMOTO J, KASAI H, YOSHIMURA K, et al. Hepatitis B virus prevents excessive viral production via reduction of cell death-inducing DFF45-like effectors [J]. J Gen Virol, 2017, 98(7): 1762-1773.
22	ZHANG J X, LING N, LEI Y, et al. Multifaceted interaction between hepatitis B virus infection and lipid metabolism in hepatocytes: A potential target of antiviral therapy for chronic hepatitis B [J]. Front Microbiol, 2021, 12: 636897.
23	ARAIN S Q, TALPUR F N, CHANNA N A, et al. Serum lipids as an indicator for the alteration of liver function in patients with hepatitis B[J]. Lipids Health Dis, 2018, 17(1): 36.
24	OEHLER N, VOLZ T, BHADRA O D, et al. Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism[J]. Hepatology, 2014, 60(5): 1483-1493.
25	KONTUSH A, CHANTEPIE S, CHAPMAN M J. Small, dense HDL particles exert potent protection of atherogenic LDL against oxidative stress[J]. Arterioscler Thromb Vasc Biol, 2003, 23(10): 1881-1888.
26	HAN Y H, ONUFER E J, HUANG L H, et al. Enterically derived high-density lipoprotein restrains liver injury through the portal vein[J]. Science, 2021, 373(6553): eabe6729.

Characteristic	HBsAg （-）（n = 40）	HBsAg （+）（n = 35）	P value
Age/year	57.75 ± 9.15	58.66 ± 9.08	0.669
Gender （male）/n（%）	24 （60.00）	22 （62.86）	0.800
Hyperlipidemia/n（%）	2 （5.00）	3 （8.57）	0.877
Hypertension/n （%）	18 （45.00）	18 （51.43）	0.578
Diabetes/n（%）	11 （27.50）	13 （37.14）	0.372
CHD/n（%）	25 （62.50）	26 （74.29）	0.275
GPT/（U·L^-1）	22.20 ± 13.19	31.97 ± 34.24	0.310
GOT/（U·L^-1）	24.75 ± 19.94	33.31 ± 26.31	0.030
hsCRP/（mg·L^-1）	8.52 ± 28.90	1.25 ± 2.92	0.735
HCY/（μmol·L^-1）	11.74 ± 6.27	13.24 ± 6.62	0.319
Creatinine/（μmol·L^-1）	75.23 ± 14.80	72.83 ± 16.86	0.514
UA/（μmol·L^-1）	329.69 ± 95.37	314.88 ± 97.70	0.509
Glucose/（mmol·L^-1）	6.71 ± 4.47	6.76 ± 3.63	0.729
CH/（mmol·L^-1）	4.14 ± 0.77	3.68 ± 0.90	0.017
TAG/（mmol·L^-1）	1.70 ± 1.10	1.44 ± 0.76	0.339
HDL-Ch/（mmol·L^-1）	1.14 ± 0.22	1.09 ± 0.32	0.412
LDL-Ch/（mmol·L^-1）	2.41 ± 0.75	2.07 ± 0.57	0.032

Characteristic	HBsAg （-）（n = 40）	HBsAg （+）（n = 35）	P value
Age/year	57.75 ± 9.15	58.66 ± 9.08	0.669
Gender （male）/n（%）	24 （60.00）	22 （62.86）	0.800
Hyperlipidemia/n（%）	2 （5.00）	3 （8.57）	0.877
Hypertension/n （%）	18 （45.00）	18 （51.43）	0.578
Diabetes/n（%）	11 （27.50）	13 （37.14）	0.372
CHD/n（%）	25 （62.50）	26 （74.29）	0.275
GPT/（U·L^-1）	22.20 ± 13.19	31.97 ± 34.24	0.310
GOT/（U·L^-1）	24.75 ± 19.94	33.31 ± 26.31	0.030
hsCRP/（mg·L^-1）	8.52 ± 28.90	1.25 ± 2.92	0.735
HCY/（μmol·L^-1）	11.74 ± 6.27	13.24 ± 6.62	0.319
Creatinine/（μmol·L^-1）	75.23 ± 14.80	72.83 ± 16.86	0.514
UA/（μmol·L^-1）	329.69 ± 95.37	314.88 ± 97.70	0.509
Glucose/（mmol·L^-1）	6.71 ± 4.47	6.76 ± 3.63	0.729
CH/（mmol·L^-1）	4.14 ± 0.77	3.68 ± 0.90	0.017
TAG/（mmol·L^-1）	1.70 ± 1.10	1.44 ± 0.76	0.339
HDL-Ch/（mmol·L^-1）	1.14 ± 0.22	1.09 ± 0.32	0.412
LDL-Ch/（mmol·L^-1）	2.41 ± 0.75	2.07 ± 0.57	0.032

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