Damian McNamara

October 26, 2016

LAS VEGAS — The risk for acute alcoholic hepatitis is elevated in heavy drinkers who carry a specific genotype, but that risk drops when these high-risk people drink coffee regularly, a multicenter, prospective, observational study demonstrates.

"Acute alcoholic hepatitis is rare, but when it happens, it's catastrophic, with very high mortality in the short term," said Naga Chalasani, MD, from the Indiana University School of Medicine in Indianapolis.

"This is really very interesting. There seems to be an interaction between the PNPLA3 genotype and coffee drinking — coffee drinking was protective, whereas the PNPLA3 G/G genotype was hazardous," he said here at the American College of Gastroenterology 2016 Annual Meeting.

In the Translational Research and Evolving Alcoholic Treatment (TREAT 001) study, 189 patients with acute alcoholic hepatitis who had been heavy drinkers for at least 6 months were compared with a control group of 150 people without liver disease matched for level of drinking, age, sex, and ethnicity.

Participants were primarily white, middle-aged, overweight men and were enrolled from May 2013 to May 2016. Appropriate clinical and lab data were used to diagnose acute alcoholic hepatitis. Follow-up was 12 months.

In the patients with hepatitis, total bilirubin was above 2 mg/dL at baseline, and aspartate aminotransferase (AST) levels were above 50 U/L. In the control group, AST and alanine transaminase (ALT) levels were in the normal range.

"Most who succumbed to their disease had progressive liver failure. There was one death in the control group from a heroin overdose," Dr Chalasani reported.

Table. Mortality in Patients With Acute Alcoholic Hepatitis

Days Percentage
30 9.6
90 16.0
180 22.5
365 27.5


PNPLA3 genotypes were determined for participants of European descent. "G/G is the bad player, and C/C is the good genotype," Dr Chalasani explained. This is reflected in the fact that the PNPLA3 G/G genotype was more common in patients with acute alcoholic hepatitis than in the control group (34% vs 22%), he added.

In the hepatitis group, total bilirubin was 13.9 mg/dL at baseline, but that improved to 4.1 mg/dL at 6 months and 2.6 mg/dL at 12 months. "Some patients stopped drinking," Dr Chalasani reported. In contrast, ALT and AST values "were surprisingly resistant."

The researchers also asked participants to record alcohol, coffee, and tea consumption.

Regular coffee consumption was significantly lower in patients with acute alcoholic hepatitis than in controls (20% vs 43%; odds ratio, 0.24; P < .0001). "This was a bit of a surprise to us," said Dr Chalasani.

The "relationship persisted after controlling for relative covariates and PNPLA3 genotype," he noted.

For people with the PNPLA3 C/C genotype who were regular coffee drinkers, the risk for acute alcoholic hepatitis was significantly lower than in people with the G/G genotype who did not drink coffee (27% vs 86%; P = .003).

These findings suggest that heavy drinkers who carry the G/G genotype but do not regularly drink coffee have the highest risk for acute alcoholic hepatitis, the researchers conclude.

After the presentation, a member of the audience asked whether caffeine content was uniform in the study. The team used a questionnaire to "capture the number of drinks," Dr Chalasani replied.

The finding of coffee use, if confirmed, would potentially confirm another beneficial effect of coffee on the liver. Dr Paul Kwo

Although further data are needed, "the PNPLA3 G/G phenotype may be a useful biomarker to identify a proportion of individuals who drink heavily who will be at risk for severe alcoholic hepatitis," said Paul Kwo, MD, from Stanford University in California.

"The finding of coffee use, if confirmed, would potentially confirm another beneficial effect of coffee on the liver," Dr Kwo told Medscape Medical News.

This study is "certainly provocative, but further studies will be needed," said Tram Tran, MD, from the Cedars–Sinai Medical Center in Los Angeles, California.

"Coffee has certainly shown a positive benefit in other studies on liver disease," she told Medscape Medical News. However, it is probably too early to draw conclusions about the interplay between the genetic risks and alcoholic hepatitis, "particularly since coffee and alcohol consumption was self-reported."

Dr Chalasani, Dr Kwo, and Dr Tran have disclosed no relevant financial relationships.

American College of Gastroenterology (ACG) 2016 Annual Meeting: Abstract 18. Presented October 17, 2016.

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