Medications for alcohol use disorder generally are safe with respect to drug-induced liver injury, except for disulfiram, according to a new prospective analysis presented at The Liver Meeting 2024.
“The field of medical management of alcohol use disorder [AUD] is growing in importance and is underscored by the growing burden of acute and chronic alcohol-associated liver disease. Pharmacotherapy is an important component of treatment to try and help patients with their addiction. Beyond surviving the first few months after presentation, the long-term ability to abstain from alcohol use is an important determinant of long-term outcomes,” said co-presenter Marwan Ghabril, MD, a hepatologist at the Indiana University School of Medicine, in Indianapolis.
He and his co-investigators conducted a prospective study of 1,975 individuals with high-confidence DILI who were enrolled between September 2004 and March 2024, examining those taking medications for AUD (MAUD; abstract 2438).
Among the 13 DILI cases attributed to MAUD, the probable cause was determined to be disulfiram in 11 cases, naltrexone in one case and baclofen in one case. No DILI cases were associated with acamprosate.
The average age of the disulfiram cases was 43.8 years, with a range of 31.5 to 61.3 years, and 72.7% were female. The ages were 61 and 59.7 years in the baclofen and naltrexone cases, respectively, and both were female. The outcomes were severe in some, including two liver transplants and one resulting death.
Looking at a group of patients with available DILI HLA data (456 control cases not attributable to disulfiram and nine cases attributable to disulfiram), the investigators found associations between disulfiram-related DILI risk and two HLA alleles: HLA-C×01:02 (odds ratio [OR], 6.29; 95% CI, 1.10-24.1; P=0.020) and HLA-DRB1×09:01 (OR, 10.16; 95% CI, 1.01-52.7; P=0.024).
DILI attributable to disulfiram had some phenotypic patterns, including mild inflammation focused in the portal area, with no apparent necrosis or damage to the parenchyma, as well as bile duct injury in portal areas, canalicular cholestasis, and extensive confluent necrosis with ductular reaction and a solitary nodule of hepatocytes.
“The majority of idiosyncratic DILI from MAUD is related to disulfiram. Other agents certainly can do it, but they’re much less likely to do so and are, therefore, safer. There is also emerging corroborating data from other studies suggesting that naltrexone and acamprosate are quite a bit safer than disulfiram as relates to the risk of idiosyncratic hepatotoxicity,” Dr. Ghabril told Gastroenterology & Endoscopy News.
The take-home message is that physicians should feel comfortable using MAUDs but avoid disulfiram, he said. “DILI is still rare, but why use disulfiram when we have effective and safer alternatives?”
Dr. Ghabril reported no relevant financial disclosures.
This article is from the December 2024 print issue.