Genetic variant linked to reduced severe alcoholic hepatitis risk

People who carry a certain genetic variant are at lower risk for developing severe alcoholic hepatitis, according to research presented at The Digital International Liver Congress.

Stephen Atkinson, MBBS, PhD, of the department of metabolism, digestion and reproduction at Imperial College London, said that severe alcoholic hepatitis typically occurs in patients with a background of fibrosis or heavy cirrhosis, but it is not clear what factors might contribute to increased risk for this condition.

“A role has been proposed for alterations in drinking patterns, nutritional intake and, additionally, genetic variation,” he said in his presentation.

While carriage of PNPLA3 variant rs738409:G increases the risk for developing severe alcoholic hepatitis, Atkinson said that rs72613567, a genetic variation of HSD17B13, decreased the risk for developing alcohol-related cirrhosis and hepatocellular carcinoma, and attenuated the risk associated with rs738409:G.

The aim of the presented study was to determine the effect of rs72613567 on severe alcoholic hepatitis risk, as well as its risk relationship with rs738409.

Researchers conducted genotyping for rs738409 and rs72613567 in 3,511 patients, including 898 with severe alcoholic hepatitis, 327 with alcohol-related cirrhosis, 1,911 with alcohol misuse but no liver injury and 1,095 healthy control individuals.

Atkinson and colleagues linked carriage of rs738409 with an increased risk for developing severe alcoholic hepatitis (OR = 1.85; 95% CI, 1.58-2.16), while carriage of rs72613567 showed a decreased risk (OR = 0.85; 95% CI. 0.74-0.98). Additionally, researchers believe that the population attributable fractions associated with each variant (25.5% [17.2-34] in rs738409 and 6.3%[-15.8 to 3.5] in rs7261356; 20.8% [4.1-36.3] combined) indicate an attenuation of the effect of rs738409 by rs72613567.

Atkinson linked carriage of rs72613567 with lower prothrombin times, Maddrey Discriminant Function, Glasgow Alcoholic Hepatitis scores and lower serum concentrations of K18, a marker is epithelial cell death.

He said these findings show that carriage of rs72613567:TA protects against the development and severity of severe alcoholic hepatitis.

“This is reflected in lower levels of K18, greater steatosis and less inflammation on biopsy, and lower disease severity scores,” he said. “It is possible that this protective effect is mediated by a reduction in non-programmed cell death.”