WASHINGTON—Patients presenting with any alcohol use disorder who have diabetes and/or hepatitis C, and who do not identify as Black, may be at higher risk for developing advanced liver disease, according to new research presented at The Liver Meeting 2022. Screening for these coexisting conditions and getting patients into treatment could reduce the risk.
Because advanced liver disease frequently is diagnosed in late stages, Amir Gougol, MD, and his co-investigators identified clinical risk factors or laboratory values associated with the long-term risk for advanced liver disease that could be used to create a scoring system.
Dr. Gougol, at that time a gastroenterology fellow at the University of Pittsburgh, pulled records from nearly 72,000 patients with alcohol use disorder (AUD) seen at the Pittsburgh health system for inpatient, outpatient or emergency department visits between January 2006 and July 2017 and then followed up through August 2021. The first alcohol-related encounter was taken as the patient’s study entry point.
Patients included in the study were at least 18 years of age and had any ICD diagnosis of AUD, defined as a problematic pattern of alcohol use leading to clinical, behavioral and psychosocial impairment. Those included in the study had baseline levels of laboratory parameters such as aspartate aminotransferase, alanine aminotransferase and/ or decompensated platelets. Patients who had advanced liver disease (diagnosis of alcoholic hepatitis, compensated or decompensated cirrhosis, or hepatocellular carcinoma) within six months of entry were excluded. Patients also were excluded if they had no record of follow-up care.
Of 32,808 patients retained in the study, 12.3% developed advanced liver disease during a mean follow-up of 5.7 years. Patients were an average age of 48.7 years, 65% were male, and mean body mass index was 27.8 kg/m2. About 25% of the patients had diabetes, and 13% had hepatitis C.
Race as a Protective Factor
Looking at factors that contribute to the long-term risk for liver disease, age and sex had very small effects, said Dr. Gougol, now a transplant hepatology fellow at the University of California, San Francisco. In contrast, three factors stood out as important: Black race had a protective influence, decreasing the risk by 30% (hazard ratio [HR], 0.7; 95% CI, 0.67-0.79; P<0.001). Diabetes increased the risk for liver disease by 50% (HR, 1.52; 95% CI, 1.4-1.6; P<0.001). The presence of hepatitis C was the strongest predictor, increasing the risk threefold (HR, 3.1; 95% CI, 2.9-3.4; P<0.001). BMI did not play a role in liver disease development.
With these findings, investigators developed a 3-point AUD score to predict later risk for advanced liver disease, assigning 1 point each for diabetes, hepatitis C and any race other than Black. Applying that score to the cohort, patients who had a score of 3, having each of these factors, showed a 34% risk for advanced liver disease within five years and a 50% risk within 10 years. In contrast, patients who had none of these factors had a 6.5% risk for advanced liver disease.
In addition, investigators found that patients with elevated Fibrosis-4 (FIB-4) scores had an increased risk for advanced liver disease. Those with a FIB-4 score greater than 2.6 had a three times higher risk for long-term liver disease.
“We are recommending, based on this data, that healthcare visits for AUD complications can be considered a unique opportunity to identify, screen and monitor a patient for long-term liver disease,” Dr. Gougol reported. “We recommend screening for hepatitis C and diabetes mellitus at any healthcare encounter for AUD, given the high association, high coexistence and the effect on the risk of long-term liver disease.”
While it is not surprising that participants with chronic hepatitis C and type 2 diabetes—indicating likely underlying nonalcoholic fatty liver disease—were more likely to progress, the finding that Black race was protective is interesting, commented Binu John, MD, MPH, an associate professor at the University of Miami and the chief of gastroenterology and hepatology at the Bruce W. Carter VA Medical Center, in Miami.
“A possible explanation may be genetic factors,” he told Gastroenterology & Endoscopy News. “Specifically, an allele in the PNPLA3 gene encoding I148M, which is more common in whites and Hispanics, has been associated with progression of liver disease in both NAFLD and alcohol-associated liver disease. Another allele of PNPLA3 (rs6006460[T], encoding S453I) has been associated with lower hepatic fat content in Blacks. These and other genetic variants should be explored further in large, genome-wide association studies.”
An important limitation is that the study does not appear to have adjusted for the amount or duration of alcohol use, Dr. John said. “Adjusting for AUDIT-C [Alcohol Use Disorders Identification Test] or a measure of alcohol use in the multivariate analysis would strengthen these findings.”
—Karen Blum
Dr. Gougol reported no relevant financial disclosures. Dr. John reported financial relationships with Exact Sciences, Exelixis, GlaxoSmithKline and Glycotest.
This article is from the February 2023 print issue.