International Liver Congress

International Liver Congress

Perspective from Laurent Castera, MD, PhD
April 14, 2016
2 min read

Alcoholism plus variants in PNPLA3, SLC38A4 increase risk for alcoholic hepatitis

Perspective from Laurent Castera, MD, PhD
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BARCELONA — Certain variants in the PNPLA3 and SLC38A4 genes — combined with heavy alcohol consumption — puts people at increased risk for developing alcoholic hepatitis, according to data presented at the International Liver Congress 2016.

“This may be a step forward in allowing us to work towards building an idea of which patients who drink in excess are at increased risk for developing severe forms of alcoholic hepatitis,” Stephen Atkinson, MBBS, MA, MRCP, clinical research fellow in the department of internal medicine at Imperial College London, UK, said during a press conference.

Stephen Atkinson, MBBS, MA, MRCP

Stephen Atkinson

Atkinson and colleagues hypothesized genetic factors contribute to the risk for developing severe alcoholic hepatitis. They performed a two-stage genome-wide association study with data comparing genetic differences of more than 2,000 patients — some with severe alcoholic hepatitis (n = 860) and some with alcohol dependence without alcoholic hepatitis (controls; n = 1,191) — to conclude which variants are risk factors for the disease.

In the exploration part of the study, the researchers considered many genetic markers.

“We compared them with cases of controls and looked at those most likely to be strongly associated with the disease. We took these [markers] forward to the replication cohort and reported those that had an independent association with disease,” Atkinson said.

Results indicated the rs738409 variant in PNPLA3 presented with a strong risk association with severe alcoholic hepatitis (OR = 2.21) and SLC38A4 gene was found to be a novel independent risk locus, or indicator, for alcoholic hepatitis (OR = 1.32).

“The gene at the novel locus is implicated in biological processes likely to be relevant to the pathogenesis of alcoholic hepatitis,” Atkinson said during his presentation.

Atkinson noted both variants in PNPLA3 and SLC38A4 genes are “very common,” with one in four people having the PNPLA3 variant and half of the population having variant of SLC38A4. He further stated that a particular variant of the PNPLA3 gene has already been identified as a risk factor for alcoholic hepatitis. However, variants in the SLC38A4 gene are “unique” to alcoholic hepatitis.

“I think [this] may start to give us more of an insight into other things that are going on in terms of the development of alcoholic hepatitis and whether there are specific treatments that some patients may benefit from more than others,” Atkinson said. – by Melinda Stevens


Atkinson S, et al. Abstract GS03. Presented at: International Liver Congress; April 13-17, 2016; Barcelona.

Disclosure: The researchers report no relevant financial disclosures.