The Combined Effect of Alcohol and Body Mass Index on Risk of Chronic Liver Disease

A Systematic Review and Meta-analysis of Cohort Studies

Kate Glyn-Owen; Dankmar Böhning; Julie Parkes; Paul Roderick; Ryan Buchanan


Liver International. 2021;41(6):1216-1226. 

In This Article

Abstract and Introduction


Background & Aims: Increasingly populations are both overweight/obese and consume alcohol. The risk of liver disease from the combination of these factors is unclear. We performed a systematic review and meta-analysis to address this important gap in evidence. Protocol registered with PROSPERO(CRD42016046508).

Methods: We performed electronic searches of Ovid Medline, Embase Classic + Embase, until 17th June 2020 for cohort studies of adults without pre-existing liver disease. Primary outcome was morbidity/mortality from chronic liver disease. Exposures were alcohol consumption categorised as within or above UK recommended limits (14 units/112 g per week) and BMI categorised as normal, overweight or obese. Non-drinkers were excluded. A Poisson regression log-linear model was used to test for statistical interaction between alcohol and BMI and to conduct a one-stage meta-analysis.

Results: Searches identified 3129 studies—16 were eligible. Of these, nine cohorts (1,121,514 participants) had data available and were included in the analysis. The Poisson model showed no significant statistical interaction between alcohol consumption and BMI on the risk of chronic liver disease. Compared to normal weight participants drinking alcohol within UK recommended limits, relative risk of chronic liver disease in overweight participants drinking above limits was 3.32 (95% CI 2.88 to 3.83) and relative risk in obese participants drinking above limits was 5.39 (95% CI 4.62 to 6.29).

Conclusions: This meta-analysis demonstrated a significantly increased risk of chronic liver disease in participants who were both overweight/obese and consumed alcohol above UK recommended limits. This evidence should inform advice given to patients and risk stratification by healthcare professionals.


Global mortality from chronic liver disease is rising and it is now the 11th most common cause of death worldwide.[1] In the United Kingdom (UK), the mortality rate from liver disease has increased by 400% since 1970 and it now represents the third largest cause of premature mortality.[2] Alcohol consumption and obesity are leading causes of chronic liver disease.[3–5] Almost half of all global deaths from chronic liver disease are caused by alcohol-related liver disease (ALD).[6] The prevalence of obesity continues to rise, with associated Non-Alcoholic Fatty Liver Disease (NAFLD) now affecting one in four people in Western countries.[5,7]

Clustering of unhealthy behaviours is common.[8] A significant proportion of patients with cirrhosis are known to be multi-morbid at the time of diagnosis.[9] Those who are multi-morbid at the time of diagnosis are more likely to present with advanced disease and the presence of multi-morbidity is significantly associated with adverse outcomes.[9,10] The co-occurrence of risk factors for cirrhosis has been shown to increase the development and progression of liver disease. Specifically, the combination of Hepatitis C and harmful alcohol consumption significantly increases the rate of development of liver fibrosis and then progression to cirrhosis and hepatocellular carcinoma (HCC).[11] Several mechanisms for biological synergism between these risk factors have been proposed.[11] There is some evidence from individual studies of an increased risk of liver disease associated with a combination of elevated Body Mass Index (BMI) and alcohol. However, the potential biological mechanisms for this are unclear and findings from observational studies have been inconsistent.[12–15]

Understanding the risk of the combination of elevated BMI and alcohol is important. Firstly, if clinicians are unaware of their patients' risk of developing liver disease they may not advise them to modify harmful behaviours and conduct targeted testing for liver disease. Secondly, if patients are unaware of the risks they are exposing themselves to, they may be less motivated to change these behaviours.[16] Behaviour modification and the early diagnosis of liver disease are important because weight loss and decreased alcohol consumption reduce progression of liver disease and early diagnosis of significant fibrosis and established cirrhosis can facilitate life-saving interventions.[2,17–19]

The interplay of alcohol and obesity on the risk of liver disease is not well understood, yet it is clear that accurately quantifying the combined risks of alcohol and obesity will empower both clinicians and patients. To address this important gap in evidence we present a systematic review and meta-analysis that provides robust estimates for the increased risk of chronic liver disease associated with the combination of alcohol consumption and elevated BMI.