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

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.

HDL Function across the Lifespan: From Childhood, to Pregnancy, to Old Age

“…However, several issues have emerged surrounding this relationship, as all of the following are true: (1) it is possible to have high HDL-C and a higher risk of mortality [129], (2) it is possible to have low HDL-C and a lower risk of CVD incidence [130], and (3) drugs aimed at increasing HDL-C have not consistently reduced CVD risk [131]. In the first case, the mechanisms behind very high HDL-C and increased mortality are not completely understood; however, one contributing factor for high HDL-C is chronic alcohol use, which has been shown to increase HDL-C [132,133]. In the second case, genetically low HDL-C was observed in carriers of the ApoA1 Milano gene, whose HDL were found to be super functional and whose clearance was increased [130].…”