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Combined metabolic factors, alcohol use integral in liver disease risk assessment

Single metabolic parameters are insufficient in evaluating risks for severe liver disease, according to a recently published study. Instead, researchers advised that a comprehensive risk assessment must include multiple factors of the metabolic syndrome and any alcohol use.

“Even light alcohol consumption increased the risk for severe liver disease among individuals with metabolic risk factors,” Fredrik Åberg, MD, PhD, from the Transplantation and Liver Surgery Clinic, Helsinki University Hospital, told Healio.com/Hepatology. “Risk for liver disease cannot be evaluated by alcohol and obesity alone. Instead, focus should be on multiple factors including central obesity, diabetes, insulin resistance, lipid levels, etc.”

Patients (n = 6,732) were interviewed at their homes or at an institution and asked to report how often they consumed alcohol during the previous year and average amount consumed per week in the previous month.

The primary endpoint of the study was first hospitalization due to liver disease, liver-related death or diagnosis of a primary liver cancer. Mean follow-up was 11.4 years (range, 0-13 years).

At baseline, 46% of the patients had metabolic syndrome and 22% were obese with a BMI over 30 kg/m². Additionally, 13% of men were alcohol risk users (210 g or more per week) and 12% of women were alcohol risk users (140 g or more per week). Of alcohol risk users, 49% had full metabolic syndrome and 43% had at least one component.

During follow-up 60 patients were hospitalized for a severe liver event, 15 patients died due to liver-related disease and nine developed liver cancer. The first events occurred on average at 6.4 years (range, 0-12 years).

Among patients with mild to moderate alcohol consumption, the risk for incident liver disease increased with BMI over 30 kg/m², central obesity defined as a waist circumference over 102/88 cm, and diabetes. Among alcohol risk users, the researchers observed an increased risk for liver disease in combined factors of alcohol and diabetes or alcohol and increased waist circumference, but less so for alcohol and BMI.

After adjusting for age, sex, average alcohol intake, diabetes and homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride levels correlated with incident liver disease (HR = 1.16; 95% CI, 1.02-1.32). After LDL cholesterol was included, LDL cholesterol became a significant factor (HR = 0.75; 95% CI, 0.6-0.95), whereas triglyceride levels were no longer significant.

Abnormal lipids

The ratios of total cholesterol to LDL cholesterol (HR = 2.7; 95% CI, 1.72-4.19), non-HDL cholesterol to LDL cholesterol (HR = 2.62; 95% CI, 1.54-4.45) and triglycerides to LDL cholesterol (HR = 1.42; 95% CI, 1.07-1.89) all correlated significantly with incident liver events after adjusting for age, sex, average alcohol intake, diabetes and HOMA-IR

The ratio of waist circumference to BMI correlated significantly with incident liver events in unadjusted analysis (HR = 5.51; 95% CI, 2.77-10.96), age- and sex-adjusted analysis (HR = 3.73; 95% CI, 1.71-8.14), and after adjusting for age, average alcohol intake, diabetes, LDL cholesterol and HOMA-IR (HR = 2.83; 95% CI, 1.23-6.52).

Additionally, the ratio of waist circumference to BMI correlated with liver events among both patients with BMI less than 25 kg/m² (HR = 7.5; 95% CI, 2.42-23.3), those overweight with BMI between 25 kg/m² and 30 kg/m² (HR = 27; 95% CI, 6.64-110), and patients with obesity (HR = 6.75; 95% CI, 1.3-35).

“There is a rising proportion of patients who develop liver disease that is neither pure alcoholic liver disease nor pure nonalcoholic fatty liver disease, but instead a combination, a little bit of both,” Åberg concluded. “This needs to be recognized. And don’t let normal liver enzymes fool you — progressive liver disease may still be there!” – by Talitha Bennett

Disclosure: Åberg reports research grants from the Wilhelm and Else Stockmanns Foundation, Liv och Hälsa and Finska Läkaresällskapet. Please see the full study for the other authors’ relevant financial disclosures.