Binge drinking speedrun

Diet and lifestyle 7. nov 2023 4 min Professor Torben Hansen, Professor og Department Chair Aleksander Krag Written by Eliza Brown

Alcohol-related liver disease is a major cause of death, but how binge drinking affects liver health remains unclear. Researchers have now conducted a study simulating binge drinking among 38 participants with various liver conditions, monitoring their liver activity in real time via catheters. The drinking led to changes in 32 inflammation markers, with surprising declines in most. However, increased levels of two markers were noted, especially among participants with steatosis. The findings could offer treatment potential for liver disease.

Perspective: this study demonstrates the unique inflammatory response to binge drinking, shedding light on liver disease mechanisms and potential treatment avenues. Further human studies in this field are crucial for advancing understanding and treatment options.

In Denmark, about 1,500 people a year die from alcohol-related liver disease. Previous research has demonstrated that even a single episode of binge drinking can affect the structure and function of the liver, but exactly what happens – and how that might differ for a person with liver disease – remains unclear.

A team of researchers in Denmark used an innovative study design to monitor the inflammatory effects of binge drinking in real time. The results, published in Liver International, demonstrate that people with liver disease respond differently to binge-drinking episodes than healthy controls – with implications for potential treatment strategies.

Fibrosis and fat tissue

Scientists define binge drinking as consuming four to five alcoholic beverages within a couple of hours. This kind of overindulgence is a particular concern for young people, according to Aleksander Krag, Professsor and Department Chair of Hepatology at Odense University Hospital.

“In Denmark, I would say in one month, probably 50% of young people have a binge-drinking episode,” explains Krag, a liver researcher and co-author of the study.

It is up to the liver to break down the alcohol in your blood, and excessive alcohol consumption – whether over time or in a burst like binge drinking – can change the liver’s architecture. Even a single bout of binge drinking can cause fat to accumulate in the liver, potentially leading to steatosis, in which fat comprises more than 5% of the liver by weight.

Over time, a fatty liver can become inflamed, and as damage from inflammation progresses, scar tissue called fibrosis can prevent the liver from functioning altogether. But a mystery of liver disease is that, although many people have liver steatosis – by some estimates, “30% of the global population,” according to Krag – comparatively few have problems with their liver.

“Only a minority of those progress to end-stage liver disease,” adds Torben Hansen, another co-author and professor at the University of Copenhagen who studies the intersection of genetics, obesity and alcohol-related disease. “A very early marker that a fatty liver could progress to liver disease is signs of inflammation.”

“But what is the mechanism behind what actually happens when you binge drink?” Krag asks. “That has never been studied in a controlled fashion.”

Down the hatch (with a nasogastric tube)

To learn how a binge-drinking episode provokes inflammation, the researchers recruited 38 volunteers for a first-of-its-kind study.

To simulate a binge-drinking episode, volunteers were given a hearty round of 40% ethanol – with a pour proportional to their body weight. (It was a special vintage distilled by the hospital pharmacy and worked out to be equivalent to five shots of 80-proof vodka for the average participant). But rather than being sipped, the alcohol was piped directly into the participants’ stomach via a tube through their nose over the course of 30 minutes.

Meanwhile, catheters at two key positions in the volunteers’ bodies enabled researchers to monitor the activity of the liver via changes in the blood over the next 3 hours. One catheter drew blood from the hepatic vein – the liver’s outflow as it sends processed blood back to the heart – and another drew blood from the jugular vein, which enabled the scientists to examine the blood in systemic circulation.

Whereas previous research on binge drinking has used young, healthy people as participants, the scientists aimed to study middle-aged people in various states of liver health.

Thirteen of the 38 participants had alcohol-related liver disease, 15 had metabolic dysfunction–associated steatotic liver disease (formerly referred to as nonalcoholic fatty liver disease) and 10 were healthy controls of similar age and weight.

Krag and Hansen say that they carefully weighed the ethics of administering an artificial binge-drinking episode to people already diagnosed with alcohol-related liver disease. The team ultimately recruited participants from FLASH – Center for Liver Research at the University of Southern Denmark who reported heavy alcohol intake and “no intention of abstaining” from alcohol.

Two liver hormones and the future of treatment

The researchers tested the blood for 72 markers of inflammation – first before the binge-drinking episode to establish a baseline, then 30 minutes after it ended and finally after 2.5 hours had elapsed.

They identified dozens of inflammation markers that appeared to change in response to the binge-drinking episode – 14 markers changed in both the hepatic and systemic circulation and an additional 18 in just the systemic circulation. To the researchers’ surprise, all but two inflammation markers declined after the binge drinking.

The two markers that increased are worth special consideration, the team says. Interleukin 6 is a hormone involved in regenerating and repairing the liver, and previous studies have demonstrated that levels of interleukin 6 increase after a binge-drinking episode. The second marker, fibroblast growth factor 21 (FGF21), is a liver hormone involved in regulating energy use and metabolism. Although FGF21 has been implicated in cravings for alcohol, “it might also be protective,” Hansen says.

The researchers found that the increase in FGF21 was blunted in participants with metabolic dysfunction–associated steatotic liver disease versus the healthy controls, and there are indications that giving people with steatosis an artificial boost in FGF21 levels could help their livers.

“Several drugs in the pipeline working with FGF21 analogues” are showing promise in clinical trials with liver steatosis and fibrosis, Krag adds.

The three groups – the participants with alcohol-related liver disease, metabolic dysfunction–associated steatotic liver disease and healthy livers – also differed in eight additional inflammation markers. Although these differences could result from the damaged livers, they may also “represent an underlying susceptibility mechanism” that made the first two groups more predisposed to developing liver disease in the first place, Krag explains.

Hansen emphasises that further studying people’s alcohol-related inflammation – and not just animals – is essential. “This study could essentially have been done 20 years ago, but people largely think that people with alcohol dependence, alcohol overuse or alcohol-related liver disease are so difficult to study,” Krag agrees. “This is a proof of concept that it actually can be done – you can study this, you can do it safely and you can really generate very high-quality knowledge.”

Binge drinking episode causes acute, specific alterations in systemic and hepatic inflammation–related markers” has been published in Liver International. Several authors are associated with the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, which is partly funded by the Novo Nordisk Foundation.

We perform genetic, microbiome and metabolome studies in monogenic diabetes, childhood obesity, Inuit in Greenland and large-scale genetic epidemiolog...

Aleksander Krag, MD, PhD, MBA is Professor and Department Chair, Department of Gastroenterology and Hepatology Odense University Hospital, Director of...

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