An exploratory analysis of the competing effects of alcohol use and advanced hepatic fibrosis on serum HDL

Jay Luther,Raymond T. Chung,Augustin G. L. Vannier,Vladislav Fomin,Russell P. Goodman,Amanda PeBenito,Esperance Schaefer

doi:10.1007/s10238-021-00736-6

Jay Luther, Raymond T. Chung

Open Access

https://doi.org/10.1007/s10238-021-00736-6

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Abstract

While alcohol use has been shown to increase serum HDL, advanced liver disease associates with decreased serum HDL. The combined influence of alcohol consumption and liver fibrosis is poorly defined. In this study, we sought to investigate the competing effects of alcohol use and hepatic fibrosis on serum HDL and to determine if the presence of advanced hepatic fibrosis ablates the reported effect of alcohol consumption on serum HDL. We performed a cross-sectional, exploratory analysis examining the interaction between alcohol use and advanced hepatic fibrosis on serum HDL levels in 10,528 patients from the Partners Biobank. Hepatic fibrosis was assessed using the FIB-4 index. We excluded patients with baseline characteristics that affect serum HDL, independent of alcohol use or the presence or advanced hepatic fibrosis. We observed an incremental correlation between increasing HDL levels and amount of alcohol consumed (P < 0.0001), plateauing in those individuals who drink 1–2 drinks per day, Contrastingly, we found a negative association between the presence of advanced hepatic fibrosis and lower HDL levels, independent of alcohol use (beta coefficient: -0.011075, SEM0.003091, P value: 0.0001). Finally, when comparing subjects with advanced hepatic fibrosis who do not use alcohol to those who do, we observed that alcohol use is associated with increased HDL levels (54.58 mg/dL vs 67.26 mg/dL, p = 0.0009). This HDL-elevating effect of alcohol was more pronounced than that seen in patients without evidence of advanced hepatic fibrosis (60.88 mg/dL vs 67.93 mg/dL, p < 0.0001). Our data suggest that the presence of advanced hepatic fibrosis does not blunt the HDL-elevating effect of alcohol use.

Highlights

Excessive alcohol use is a frequent cause of morbidity and mortality worldwide
The liver accounts for a majority of the total serum high-density lipoprotein (HDL) levels and is intimately involved in all aspects of HDL regulation, from synthesis to transport to metabolism
We investigated the interaction between alcohol use and the presence of advanced hepatic fibrosis in a large cohort of patients unaffected by major sources of HDL variation: hepatitis B or C infection, primary biliary cholangitis, poor glycemic control, obesity, heavy smoking or lipid-lowering medications

Summary

Introduction

Alcohol use is one of the most common causes of deaths and disability-associated life years (DALYs) [1], as it is mechanistically linked with the development of multiple diseases. Multiple observational studies have demonstrated a positive association between moderate alcohol use and high-density lipoprotein (HDL) levels [2,3,4,5,6]. Previous studies have demonstrated reduced HDL levels in patients with both acute and chronic liver diseases [7,8,9]. Reduced serum HDL levels have been associated with severity of liver disease, the presence of liver-related complications and mortality in patients with cirrhosis [10]

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