Liver disease is the 13th leading cause of death worldwide, and hepatocellular carcinoma is the 2nd leading cause of cancer death. Finland has one of the highest liver-mortality rates in Europe.
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are the two most common types of chronic liver disease in the population. However, only 15–20% of heavy alcohol drinkers will ever develop liver cirrhosis, and <5% of NAFLD patients die from a liver-related cause. Individual susceptibility to progressive liver disease remains incompletely understood.
ALD and NAFLD are distinguished from each other by an arbitrary threshold of average alcohol intake of 30 g per day for men and 20 g per day for women. However, even lower amounts of alcohol intake have been linked to increased liver mortality. Weekly or monthly binge drinking may affect progression of NAFLD even when average alcohol intake is within the aforementioned limits. On the other hand, metabolic factors may affect progression of alcoholic liver disease. Both diseases also share some of the genetic risk factors (for instance, patatin-like phospholipases [PNPLAs]). This calls for a more holistic approach, where alcohol use and metabolic factors are taken into account at the same time in order to identify the individuals with a high risk of severe liver complications.
We investigated which metabolic factors best predict severe liver disease in the population with stratification by average alcohol intake. The study included 6,732 individuals without known liver disease who participated in the Health 2000 Study, which was conducted from 2000–2001. The cohort was representative of the general Finnish population. Follow-up data on liver-related hospital admissions, deaths, and liver cancer were collected until 2013.
We found that, at baseline, 46% of the adult population had metabolic syndrome and 22% were obese. Of these subjects, 12–13% were also alcohol risk drinkers (>30 g/day for men, >20 g/day for women). Of alcohol risk drinkers, 49% had metabolic syndrome, and 8% did not have at least one component of metabolic syndrome. This clearly shows that increased alcohol intake (alcohol risk use) and metabolic factors often coexist in the population.
In multivariate modelling, average alcohol use, total cholesterol, very low-density lipoprotein cholesterol, diabetes, homeostasis model assessment of insulin resistance, waist circumference, and low BMI emerged as significant predictors of severe liver disease. In the subgroup of alcohol risk users, the only factor that predicted liver disease was diabetes. A high waist circumference to BMI ratio emerged as a novel predictor of liver disease. This ratio was significant both among subjects with BMI 19–25 kg/m2, 25–30 kg/m2, and >30 kg/m2. It can be speculated that a high ratio reflects a metabolically unhealthy state, even when a person is considered lean merely by their BMI value.
Metabolic factors should not be overlooked in alcohol risk users. The dysmetabolic state that confers risk for complicated liver disease, on the other hand, cannot be evaluated by single variables such as BMI. For a comprehensive liver-risk assessment, lipid abnormalities, abdominal obesity, insulin resistance, diabetes, and alcohol use should all be addressed at the same time. These are also factors to be considered in future scores for quantifying individual risk for liver disease in the general population.