This article is more than 5 years old. Information may no longer be current.

Genetics outweigh abstinence in alcoholic hepatitis survival

Patients with severe alcoholic hepatitis who were homozygous for the rs738409:G variant in the PNPLA3 gene have an increased risk for mortality even when they stop drinking alcohol, according to recently published data.

“The variant rs738409:G in PNPLA3 has been consistently associated with the risk of developing alcohol-related cirrhosis and has also been implicated in more rapid disease progression and the risk of developing hepatocellular carcinoma,” Stephen R. Atkinson, MBBS, MA, MRCP, clinical research fellow in the department of internal medicine at Imperial College London, U.K., and colleagues wrote. “Genotyping rs738409 in PNPLA3 will identify these individuals and the results could be taken into account in clinical decision-making, potentially allowing these particularly vulnerable individuals to be considered for early liver transplantation or novel therapies. The need to employ measures to assist patients with severe alcoholic hepatitis to attain and maintain abstinence is highlighted again in this study as of critical importance.”

Stephen R. Atkinson

To determine the short- to mid-term survival of patients with severe alcoholic hepatitis, specifically among those with the of rs738409:G variant, the researchers enrolled 867 patients and 1,175 controls. They treated patients with either prednisolone or pentoxifylline for 28 days and evaluated patients at 90 days and at 1 year to assess clinical status and self-reported alcohol use. The controls had a background of alcohol dependence, but no evidence of liver injury.

The patient cohort had a significantly higher frequency of rs738409:G than the control cohort (OR = 1.8; 95% CI, 1.55-2.08). There were no significant differences in age, sex, alcohol consumption or most clinical and laboratory variables among those with the variant.

The researchers gathered drinking behavior data after hospital discharge from 397 patients at day 90 and from 174 at 1 year. Sixty-five percent of patients at day 90 reported abstinence and 57% reported abstinence at 1 year.

After excluding in total 52 patients for not completing follow-up, mortality rates were 15% of 864 patients at day 28, 25% of 861 patients at day 90 and 44% of 813 patients at day 450. While there was no association between rs738409:G and mortality at day 28 and day 90, there was a significant association with increased mortality at day 450 (P = .04).

There was significant interaction between drinking consumption at day 90 with both serum bilirubin concentrations (P = .004) and neutrophil count (P = .002) related to survival. Compared with the 14.3% mortality rate at day 450 among those who reported abstinence at day 90, the mortality rate for those still drinking at day 90 was 35.5% (HR = 2.77; 95% CI, 1.79-4.29).

Homozygosity for rs738409:G did not affect survival rates in those who reported drinking at day 90; however, the variant was associated with a significantly higher mortality rate during the follow-up period in those who reported abstinence at day 90 (HR = 3.4; 95% CI, 1.54-7.49).

“Individuals with severe alcoholic hepatitis who survive the acute event and are homozygous for rs738409:G in PNPLA3 would appear to be at increased risk of mortality in the medium-term, even if they attain and maintain abstinence from alcohol,” the researchers concluded. “This study identifies rs738409:G as a risk factor for the development of severe alcoholic hepatitis. Many of the included cases had co-existing alcohol-related cirrhosis and a high proportion of the remainder are likely to develop cirrhosis over time. This finding is not, therefore, surprising but given the size and appropriateness of the case and control populations it provides robust confirmation of the results of the previous much smaller study.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.