Positive association between serum apolipoprotein M levels and hepatitis B virus DNA load in HBeAg-negative chronic hepatitis B

Lipids in Health and Disease, Dec 2016

Background Hepatitis virus B (HBV) has infected millions of people worldwide. Notably, such infections can be associated with hepatic complications. Levels of apolipoprotein M (apoM), a component of high-density lipoprotein (HDL), are known to be significantly elevated in patients with chronic hepatitis B (CHB). The aim of this study was to investigate the relationship between HBV DNA load in serum and serum apoM levels in patients with CHB. Methods A total of 73 HBeAg-negative CHB patients, 50 HBeAg-positive CHB patients, and 79 non-CHB controls were included in the study cohort. The age and body mass index (BMI) of the study participants were matched. Serum levels of apoM and the HBV antigens HBsAg and HBeAg were measured by enzyme-linked immunosorbent assay (ELISA) analysis. Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), cholesterol, and triglycerides (TG) were assessed using an automatic biochemical analyzer. Serum HBV DNA levels were quantified by real-time PCR analysis. Data were analyzed by Spearman’s rank correlation coefficient, Pearson correlation coefficient, and multivariate linear regression model (continuous variables), or Student’s t-test (mean differences). Results Both the HBeAg-negative CHB and HBeAg-positive CHB patient groups exhibited elevated serum levels of apoM. Moreover, serum apoM levels were positively correlated with serum HBV DNA levels in HBeAg-negative CHB patients (r = 0.394, p < 0.001). Conversely, there was no significant relationship between apoM and HBV DNA levels in the HBeAg-positive CHB group (r = 0.197, p = 0.170). The median log copies/mL value for HBV DNA (4.00) was considered the cutoff point for the HBeAg-negative CHB group. Notably, a significant number of patients with HBV DNA levels above the cutoff point also had higher serum apoM levels (63.38 ± 29.84 vs. 41.41 ± 21.84; p = 0.001). Conclusions Our findings reveal that the correlation between serum apoM levels and viral loads may depend on HBeAg status, as serum apoM levels were positively correlated with HBV DNA levels in HBeAg-negative CHB patients. These results suggest that HBeAg may play a role in apoM-related lipid metabolism and anti-inflammatory functions in hepatitis B patients. Thus, our findings may facilitate the clinical management of HBV infection.

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Positive association between serum apolipoprotein M levels and hepatitis B virus DNA load in HBeAg-negative chronic hepatitis B

Shen et al. Lipids in Health and Disease Positive association between serum apolipoprotein M levels and hepatitis B virus DNA load in HBeAg-negative chronic hepatitis B Ting Shen 0 Wei Min Wu 0 Wen Han Du 0 Lin Wang 0 La Gu He 0 Li Tan 0 ZeYou Wang 0 Ruohong Chen 0 Min Hu 0 Ya Ping Ren 0 0 Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University , Changsha 410011, Hunan Province , China Background: Hepatitis virus B (HBV) has infected millions of people worldwide. Notably, such infections can be associated with hepatic complications. Levels of apolipoprotein M (apoM), a component of high-density lipoprotein (HDL), are known to be significantly elevated in patients with chronic hepatitis B (CHB). The aim of this study was to investigate the relationship between HBV DNA load in serum and serum apoM levels in patients with CHB. Methods: A total of 73 HBeAg-negative CHB patients, 50 HBeAg-positive CHB patients, and 79 non-CHB controls were included in the study cohort. The age and body mass index (BMI) of the study participants were matched. Serum levels of apoM and the HBV antigens HBsAg and HBeAg were measured by enzyme-linked immunosorbent assay (ELISA) analysis. Serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), cholesterol, and triglycerides (TG) were assessed using an automatic biochemical analyzer. Serum HBV DNA levels were quantified by real-time PCR analysis. Data were analyzed by Spearman's rank correlation coefficient, Pearson correlation coefficient, and multivariate linear regression model (continuous variables), or Student's t-test (mean differences). Results: Both the HBeAg-negative CHB and HBeAg-positive CHB patient groups exhibited elevated serum levels of apoM. Moreover, serum apoM levels were positively correlated with serum HBV DNA levels in HBeAg-negative CHB patients (r = 0.394, p < 0.001). Conversely, there was no significant relationship between apoM and HBV DNA levels in the HBeAg-positive CHB group (r = 0.197, p = 0.170). The median log copies/mL value for HBV DNA (4.00) was considered the cutoff point for the HBeAg-negative CHB group. Notably, a significant number of patients with HBV DNA levels above the cutoff point also had higher serum apoM levels (63.38 ± 29.84 vs. 41.41 ± 21.84; p = 0.001). Conclusions: Our findings reveal that the correlation between serum apoM levels and viral loads may depend on HBeAg status, as serum apoM levels were positively correlated with HBV DNA levels in HBeAg-negative CHB patients. These results suggest that HBeAg may play a role in apoM-related lipid metabolism and anti-inflammatory functions in hepatitis B patients. Thus, our findings may facilitate the clinical management of HBV infection. Apolipoprotein M; Chronic hepatitis B; HBV DNA load - Background Hepatitis B virus (HBV) infection causes chronic liver disease in >350 million people worldwide and this disease is positively correlated with incidences of liver cirrhosis and hepatocellular carcinoma. Chronic liver diseases can interfere with hepatic metabolism of lipoproteins and apolipoproteins. Moreover, the ongoing replication of HBV in chronic hepatitis B (CHB) induces oxidative stress and is associated with inflammation of the liver [1–3]. Factors that govern viral replication and determine infection outcome remain unclear, but it is known that host factors play a major role in these processes [4]. Apolipoprotein M (apoM) is a 26-kD apolipoprotein that is primarily associated with high-density lipoproteins (HDL); however, a small proportion of this protein also interacts with triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL) in the serum. apoM is a member of the lipocalin protein superfamily and is exclusively expressed in hepatocytes and kidney tubular cells [5, 6]. This protein plays a variety of biological functions, e.g., anti-oxidative function [7], anti-inflammatory function [8], promoting pre-β HDL formation [9], and increasing cholesterol efflux from foam cells [10]. Previous studies reported that chronic hepatitis patients exhibit higher serum apoM levels than healthy control subjects [11, 12]. Similarly, HepG2 cells transfected with an infectious HBV clone were found to express significantly higher levels of apoM mRNA and protein than uninfected HepG2 cells in vitro. Moreover, apoM suppressed HBV replication in HepG2 cells [13]. However, the association between apoM expression and HBV replication rate in CHB patients is poorly understood. Therefore, the aim of the present study was to investigate the association between apoM and HBV replication rate to facilitate the management of anti-viral treatment in clinical practice. Methods Subjects CHB patients were recruited at the Second Xiangya Hospital (Changsha, Hunan, PR China) between June 2015 and June 2016. From the 200 individuals screened, 73 HBsAg(+) HBeAg(−) CHB patients and 50 HBsAg(+) HBeAg(+) CHB patients were enrolled in this study. T (...truncated)


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Ting Shen, Wei Wu, Wen Du, Lin Wang, La He, Li Tan, ZeYou Wang, Ruohong Chen, Min Hu, Ya Ren. Positive association between serum apolipoprotein M levels and hepatitis B virus DNA load in HBeAg-negative chronic hepatitis B, Lipids in Health and Disease, 2016, pp. 210, 15, DOI: 10.1186/s12944-016-0384-3