Heavy drinking was not associated with higher proportions of liver-related deaths or liver transplantation among patients with drug-induced liver injury (DILI), according to the results of a prospective multicenter cohort study reported in the May issue of Clinical Gastroenterology and Hepatology.

Anabolic steroids were the most common cause of DILI among heavy drinkers, defined as men who averaged more than three drinks a day or women who averaged more than two drinks daily, said Lara Dakhoul, MD, of Indiana University, Indianapolis, and her associates. There also was no evidence that heavy alcohol consumption increased the risk of liver injury attributable to isoniazid exposure, the researchers wrote in.

Although consuming alcohol significantly increases the risk of acetaminophen-induced liver injury, there is much less clarity about the relationship between drinking and hepatotoxicity from drugs such as duloxetine or antituberculosis medications, the researchers noted. In fact, one recent study found that drinking led to less severe liver injury among individuals with DILI. To better elucidate these links, the investigators studied 1,198 individuals with confirmed or probable DILI who enrolled in the DILI Network study (DILIN) between 2004 and 2016. At enrollment, all participants were asked if they consumed alcohol, and those who reported drinking within the past 12 months were offered a shortened version of the Skinner Alcohol Dependence Scale to collect details on alcohol consumption, including type, amount, and frequency.

In all, 601 persons reported consuming at least one alcoholic drink in the preceding year, of whom 348 completed the Skinner questionnaire. A total of 80 individuals reported heavy alcohol consumption. Heavy drinkers were typically in their early 40s, while nondrinkers tended to be nearly 50 years old (P less than .01). Heavy drinkers were also more often men (63%) while nondrinkers were usually women (65%; P less than .01). Heavy drinkers were significantly more likely to have DILI secondary to anabolic steroid exposure (13%) than were nondrinkers (2%; P less than .001). However, latency, pattern of liver injury, peak enzyme levels, and patterns of recovery from steroid hepatotoxicity were similar regardless of alcohol history.

A total of eight patients with DILI died of liver-related causes or underwent liver transplantation, and proportions of patients with these outcomes were similar regardless of alcohol history. These eight patients had no evidence of hepatitis C virus infection, but three appeared to have underlying alcoholic liver disease with superimposed acute-on-chronic liver failure. Heavy drinkers did not have significantly higher DILI severity scores than nondrinkers, but they did have significantly higher peak serum levels of alanine aminotransferase (1,323 U/L vs. 754, respectively; P = .02) and significantly higher levels of bilirubin (16.1 vs. 12.7 mg/dL; P = .03).

The two fatal cases of DILI among heavy drinkers involved a 44-year-old man with underlying alcoholic cirrhosis and steatohepatitis who developed acute-on-chronic liver failure 11 days after starting niacin, and a 76-year-old man with chronic obstructive pulmonary disease and bronchitis flare who developed severe liver injury and skin rash 6 days after starting azithromycin.

The study was not able to assess whether heavy alcohol consumption contributed to liver injury from specific agents, the researchers said. Additionally, a substantial number of drinkers did not complete the Skinner questionnaire, and those who did might have underestimated or underreported their own alcohol consumption. “Counterbalancing these issues are the [study’s] unique strengths, such as prospective design, larger sample size, well-characterized DILI phenotype, and careful, structured adjudication of causality and severity,” the researchers wrote.

Funders included the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute. Dr. Dakhoul had no conflicts of interest. On coinvestigator disclosed ties to numerous pharmaceutical companies.

SOURCE: Dakhoul L et al. Clin Gastro Hepatol. 2018 Jan 3. doi: 10.1016/j.cgh.2017.12.036.

Heavy drinking did not worsen clinical outcomes from drug-induced liver injury