Interaction Between Metabolic Syndrome and Alcohol Consumption, Risk Factors of Liver Fibrosis

A Population-based Study

Elisa Pose; Guillem Pera; Pere Torán; Jordi Gratacós-Ginès; Emma Avitabile; Carmen Expósito; Alba Díaz; Isabel Graupera; Ana B. Rubio; Pere Ginès; Núria Fabrellas; Llorenç Caballeria


Liver International. 2021;41(7):1556-1564. 

In This Article

Abstract and Introduction


Background and Aims: Alcohol and metabolic syndrome (MS) coexist frequently as cofactors of liver disease. Previous studies suggest a deleterious effect of MS in advanced alcohol-related liver disease (ArLD). However, it is unknow whether MS can increase the risk of liver fibrosis in early stages of ArLD. The aim of this study was to investigate the effect of MS on liver fibrosis in subjects with alcohol consumption from a population-based cohort.

Methods: The number of subjects include 1760(58%) of 3014 who were randomly selected from the community consumed alcohol and were classified as current drinkers, divided in moderate (n = 1222) or high-risk drinkers (n = 275) (>21 units/week men, >14 units/week women for high-risk drinkers), or former drinkers (n = 263). Liver fibrosis was estimated by measuring liver stiffness(LS) with transient elastography (TE).

Results: Prevalence of significant LS using cutoff values of TE of 8 and 9.1kPa was increased in high-risk compared with moderate or former drinkers and lifetime abstainers. In subjects with alcohol consumption, LS was associated with male gender, AST, ALT, years of consumption, and MS. In high-risk drinkers, MS and intensity of consumption were the only factors associated with significant LS (OR 3.7 and 4.6 for LS ≥ 8 kPa and 3.9 and 9.2 kPa for LS ≥ 9.1 kPa, respectively). Presence of significant liver fibrosis in the liver biopsy was higher among high-risk as compared with moderate or former drinkers.

Conclusion: MS increases the risk of liver fibrosis in subjects with alcohol consumption. Among high-risk drinkers, only MS and consumption of high amount of alcohol are associated with risk of liver fibrosis.


Alcohol-related liver disease (ArLD) and nonalcoholic fatty liver disease (NAFLD) are among the most common causes of chronic liver disease, cirrhosis, hepatocellular carcinoma, and liver-related deaths worldwide.[1–3] The prevalence of ArLD in the general population varies depending on the area and is very high in many areas of the world, including the US and Europe.[4]

NAFLD is already a major health problem.[5,6] Fatty liver disease is associated with metabolic comorbidities, particularly obesity, type 2 diabetes, hyperlipidemia, and MS, the frequency of which are increasing rapidly worldwide. In this context, NAFLD prevalence and burden is expected to increase in the following years.[2,7]

A relevant aspect of the pathogenesis of liver diseases is that, frequently, two different risk factors for liver injury coexist in the same subject, potentially increasing the risk and severity of liver damage. In this regard, previous studies have reported an accelerated progression of liver disease in patients with viral hepatitis (particularly HCV) and concomitant alcohol intake.[8,9]

As mentioned before, alcohol consumption and MS are risk factors of chronic liver diseases that are very common and may therefore coexist in some subjects. Hence, a number of investigations have analyzed the potential interaction between the two risk factors and development of chronic liver disease. The approaches taken in these investigations have been either to evaluate the effect of alcohol consumption in cohorts of patients with hepatic steatosis caused by NAFLD or the effect of MS in cohorts of patients with advanced ArLD, particularly alcoholic hepatitis or cirrhosis.[10–15] However, there is very little information on the potential effect of MS as a cofactor for liver disease at the population level in cohorts of subjects categorized according to different levels of alcohol consumption.[16,17] This approach has the advantage over the two previous approaches of being able to unravel the effect of MS in early stages of ArLD before alcoholic hepatitis or cirrhosis develops.

Therefore, the current study was designed to answer the question as to whether the risk of chronic liver disease in patients with alcohol consumption is increased by the coexistence of MS. To this aim, we analyzed a cohort of subjects without known liver disease who was randomly selected from the population. Liver fibrosis was assessed in all subjects by transient elastography (TE) followed by liver biopsy in selected subjects. The role of MS was evaluated in subjects categorized according to their past or current history of alcohol consumption.