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

Abstract

BackgroundHepatitis 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.MethodsA 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).ResultsBoth 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).ConclusionsOur 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.

Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

“…Hepatocytes are the major sites of apolipoprotein synthesis and lipoprotein assembly, secretion, uptake, and catabolism. Some clinical studies in HBV-infected population have found significantly decreased levels of plasma ApoA1 (Jiang et al, 2014;Wang Y. et al, 2016;Cui et al, 2019), ApoA5 (Zhu et al, 2016;Cui et al, 2019), ApoB (Wang et al, 2011;Cui et al, 2019), and ApoC3 (Zhu et al, 2017;Cui et al, 2019), whereas dramatically increased level of serum ApoM or ApoE (Gu et al, 2011;Shen et al, 2016). These results from clinical studies were consistent with observations from several experimental studies.…”

“…While expression of ApoE ( Shen et al, 2015 ) or ApoM ( Gu et al, 2011 ) increased after HBV infection. Changes in hepatic lipid metabolism induced changed lipid levels in peripheral blood, including increased SFA and MUFA ( Arain et al, 2018 ), decreased ApoA1, ApoA5, ApoB100, or ApoC3 ( Wang et al, 2011 ; Jiang et al, 2014 ; Wang Y. et al, 2016 ; Zhu et al, 2016 , 2017 ; Cui et al, 2019 ), or increased ApoE or ApoM ( Gu et al, 2011 ; Shen et al, 2016 ). However, the level of TG and TC showed a decrease in CHB patients compared to normal controls ( Wong et al, 2012 ; Cheng et al, 2013 ; Joo et al, 2017 ).…”

Hepatitis B virus inhibits the in vivo and in vitro synthesis and secretion of apolipoprotein C3

“…It was reported that HBV down-regulated the expression of ApoA1, ApoA5, ApoB and up-regulated the expression of ApoM [ 8 – 11 ].The main purpose of this study is to investigate the effect of HBV on the regulation of ApoC3 expression and its mechanism by in vivo and in vitro experiments.…”

Apolipoprotein M promotes the anti-inflammatory effect of high-density lipoprotein by binding to scavenger receptor BI

“…In plasma, apoM is transported with HDL, and apoM + HDL accounts for 5% of the total HDL. Recently, the antiinflammatory functions of apoM, mediated by HDL, have attracted increasing attention (11)(12)(13)(14). The ApoM gene is on chromosome 6 and located close to inflammatory genes, including TNF-α and TNF-β (8).…”