Coffee, Genetics May Block Hepatitis in Heavy Drinkers

LAS VEGAS -- Among heavy drinkers, those who also reported drinking coffee regularly were less than half as likely as coffee nondrinkers to develop alcoholic hepatitis, a researcher said here.

Additionally, those with the PNPLA3 C/C genotype also showed a markedly reduced risk of alcoholic hepatitis in the case-control study of 340 heavy drinkers, according to Naga P. Chalasani, MD, of the Indiana University School of Medicine in Indianapolis.

Just over 25% of participants who had the C/C genotype and drank coffee regularly had alcoholic hepatitis, versus 86% of those with the G/G genotype who didn't drink coffee, Chalasani told attendees at the American College of Gastroenterology's annual meeting.

The study examined a host of factors in 190 heavy drinkers -- men consuming an average of at least 60 g of ethanol daily and women at least 40 g for the past 5 years plus acknowledging current active drinking -- diagnosed with alcoholic hepatitis and 150 equally heavy drinkers without the condition. These individuals were part of an ongoing prospective study of heavy drinkers called TREAT 001, Chalasani told attendees.

Alcoholic hepatitis was diagnosed with "appropriate clinical and laboratory criteria," he said, with ambiguous cases confirmed with liver biopsy. Non-hepatitis controls were matched to hepatitis cases by gender, age, and race.

Participants were mostly in their mid-30s to mid-50s, predominantly white, and about 60% were male.

Chalasani and colleagues sought to identify baseline differences between cases and controls, other than those directly related to hepatitis (such as liver enzyme levels). The PNPLA3 genotype and self-reported coffee drinking jumped out as the most prominent, he said.

The latter, he was, "was a big surprise to us."

Only 20% of the hepatitis group reported regular coffee drinking, compared to 43% of controls (P<0.0001), which "persisted after controlling for relevant covariates including PNPLA3 genotype," he said.

The difference in multivariate analysis worked out to an odds ratio of 0.24 for hepatitis among coffee drinkers (95% CI 0.13-0.43).

Among hepatitis cases, the median daily self-reported consumption of coffee was 1 cup (interquartile range 1-3) versus 3 (IQR 2-4) in non-hepatitis controls.

PNPLA3 genotype was nearly as strongly associated with presence or absence of hepatitis, Chalasani reported. The odds ratio for hepatitis in those with the C/C genotype was 1.89 (95% CI 1.1-3.06), after controlling for coffee drinking and other factors.

Notably, Chalasani said, there appeared to be an interaction between PNPLA3 genotype and coffee habits. As indicated above, the lowest likelihood of hepatitis was in those with both the C/C genotype and regular coffee drinking, whereas the highest risk was among those with the G/G genotype and no coffee drinking. In between were those with other genotype combinations and coffee drinking.

Limitations to the study included reliance on self-reported data on alcohol and coffee drinking histories.

Chalasani told MedPage Today he believed the relationship with coffee is real and biological. He said he could only speculate on possible mechanisms -- in vitro studies are now underway that may shed more light -- but he suspected that some kind of antioxidant effect, such as is seen with flavonoid compounds, may be at work.

Asked if coffee drinking could be a marker for some other lifestyle factor that accounts for the relationship, he scoffed at the suggestion. "These people are alcoholics," he said, many of whom have been consuming upwards of 10 or 20 drinks daily for many years. He could not think of a plausible lifestyle factor in such individuals that could be as liver-protective as the study findings suggested.

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