Abstract
Background & Aims
Binge drinking is a common pattern of alcohol intake often considered particularly harmful. However, its immediate effects on the development of hepatic steatosis and early alcohol-related liver injury are not well established. This study aimed to investigate the acute effects of binge drinking on the liver and its reversibility in healthy individuals.
Methods
Healthy adults were studied in a real-world setting before, the day after, and 10 days after attending a 3-day festival. The participants were alcohol abstinent 1 week prior to the first visit and between the last two visits. Each visit included liver MRI-proton density fat fraction and elastography, and blood tests. Alcohol and food intake were self-reported during the festival, and blood alcohol concentration was measured once daily.
Results
Fifteen participants (9 male, 6 female) aged 36 ± 5 years with a BMI of 23.2 ± 2.7 kg/m2 completed the study. They consumed 186 ± 56 g of alcohol per day resulting in a 2.5-fold increase in hepatic fat fraction from 1.9% (IQR 1.6%-2.5%) to 4.6% (IQR 2.4%-5.7%), p <0.0001. Six participants (40%) developed steatosis; compared to those without steatosis, they had higher baseline BMI, triglycerides and glucagon, and lower free fatty acids, while there was no difference in alcohol or energy consumption. Binge drinking also increased liver stiffness and triglycerides, while LDL-cholesterol decreased. After 10 days of abstinence, all outcome measures were normalised.
Conclusions
Three days of recreational binge drinking increased liver fat content and stiffness in most participants. This early consequence of excessive alcohol intake was resolved after 10 days of abstinence, suggesting that the acute hepatic effects of binge drinking are readily reversible if followed by short-term abstinence.
Impact and implications
Binge drinking is considered a high-risk pattern of alcohol intake associated with various health hazards, yet its immediate effects on the liver are not well understood. This study provides direct real-world evidence that one episode of binge drinking (3 days) can acutely induce hepatic steatosis in healthy individuals, particularly those with subclinical metabolic dysfunction. Importantly, all consequences of binge drinking were normalised following 10 days of alcohol abstinence. These findings offer timely insight into the health risks of recreational binge drinking and contribute knowledge with potential implications for public health messaging and recommendations, clinical guidance, and alcohol policies.
Keywords: Alcohol-related liver disease, Steatotic liver disease, MetALD, Alcohol
Graphical abstract
Highlights
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Three days of recreational binge drinking increased hepatic fat fraction by 2.5-fold in healthy adults.
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Six of fifteen (40%) participants developed hepatic steatosis.
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Binge drinking also induced increased liver stiffness and plasma triglycerides, while LDL cholesterol decreased.
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All changes normalised following 10 days of alcohol abstinence.
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Participants with hepatic steatosis had higher baseline BMI, hepatic fat fraction, plasma triglycerides and glucagon.
Introduction
Excessive alcohol intake constitutes a major global health burden with alcohol-related liver disease being responsible for most of the liver-related morbidity and mortality worldwide.[1], [2], [3] It is estimated that 90% of individuals with continued excessive alcohol intake will develop liver steatosis, which may progress to inflammation, fibrosis, and ultimately cirrhosis.4 While there is evidence of a linear dose-response relationship between alcohol intake and the risk of cirrhosis, several factors modify this risk, including the pattern of consumption.[5], [6], [7]
Binge drinking is defined as an excessive alcohol intake in a short period of time and considered a high-risk pattern of intake associated with health hazards such as injuries, traffic incidents, violence, and alcohol poisoning.8,9 In Western countries, up to 30% of the general adult population have engaged in such drinking in the past month, with the highest prevalence observed in young adults.1 The frequency of alcohol binges is associated with increased markers of liver injury at a population-based level,10,11 and some studies suggest binge drinking is associated with higher risk of alcohol-related liver disease compared with chronic intake.6,7,[12], [13], [14] However, the acute hepatic effects of binge drinking are poorly described.7
Hepatic steatosis represents the earliest structural consequence of excessive alcohol intake, which contributes towards chronic liver inflammation and fibrosis.15 Importantly, alcohol-related steatosis is associated with increased mortality as opposed to metabolic dysfunction-associated steatotic liver disease (MASLD).16 Binge drinking has been shown to cause immediate hepatic steatosis in animal studies and is believed to do so in humans.[17], [18], [19], [20] However, direct evidence that one bout of binge drinking induces acute hepatic steatosis is sparse. Likewise, the reversibility of this condition remains unexplored.
We aimed to address this knowledge gap by describing the acute hepatic effects of binge drinking in healthy individuals and its reversibility after 10 days of alcohol abstinence.
Patients and methods
Study design
This is a before-and-after, real-world, study of healthy individuals attending a 3-day music festival in June 2022 (Northside, Aarhus, Denmark). The participants were studied three times: The week leading up to the festival (Visit 1), the day after the end of the festival (Visit 2), and 10 days after the end of the festival (Visit 3). Each visit comprised Magnetic Resonance Imaging - proton density fat fraction (MRI-PDFF) and MR elastography of the liver, and blood samples obtained in the fasting state (min. 8 h). At Visit 1, BMI was measured, and a history of alcohol intake and smoking was recorded.
Participants abstained from alcohol during the week leading up to Visit 1, and between Visit 2 and 3. During the festival, participants consumed ad libitum alcohol and food, and recorded their intake, as described below. Blood alcohol concentration (BAC) was measured by breath test once daily. The primary outcome measure was change in hepatic fat fraction measured by MRI-PDFF, and secondary measures were changes in liver stiffness measured by MR elastography, blood markers of liver injury and fibrosis, lipids, and glucometabolic markers.
Study participants and ethics
Healthy volunteers planning to attend the festival were recruited through social media using the following criteria: Inclusion criteria: Age ≥30 years, BMI <30 kg/m2, average daily alcohol intake ≤20/30 g for women and men, respectively. Exclusion criteria: Any alcohol intake during the 1 week before Visit 1 or between Visit 2 and 3, any chronic disease, pregnancy, metal implants, or other contraindications for MRI, e.g. claustrophobia. The participants were recruited on a first-come, first-served basis and were compensated with a ticket to the festival or 500 DKK if they had already purchased one. The study was approved by The Central Denmark Region Committees on Health Research Ethics (1-10-72-95-20) and conducted in accordance with the Helsinki Declaration. Written informed consent was acquired by all participants. There were no complications to the procedures or adverse events in relation to alcohol intake.
Alcohol and food intake
During the festival, participants recorded their alcohol intake in real-time using a smartphone application (‘DrinkControl: Alcohol Tracker’ for iPhone or ‘AlcoDroid’ for Android). The most common definition of binge drinking stated by the NIAAA (National Institute on Alcohol Abuse and Alcoholism) is a pattern of alcohol intake that induces a BAC of 0.8 ‰ or higher;8 for a typical adult, this corresponds to consuming 4 (female) or 5 (male) American units in 2 h (equivalent to 56/70 g alcohol).8 One alcohol unit was defined as 10 g alcohol according to the European Association for Study of the Liver Clinical Practice Guidelines.7 In addition, a spot BAC was measured by the investigators once per day between 6 and 7 PM using a validated Breathalyzer (ALKOtest AT 1.0, ALKOtest.dk). Participants reported food intake by taking photos of all meals and the caloric intake from each meal was estimated by the investigators using an online calorie calculator (MyFitnessPal: Calorie Counter; MyFitnessPal, Inc). The caloric intake from alcoholic beverages was calculated using the self-reported alcohol intake, considering one standard alcoholic drink as 150 kcal (one 330 ml beer).
MRI
The participants were placed in supine position in a SIGNA 3.0T PET/MR scanner (GE Healthcare, Chicago, USA), and the elastography probe was applied on the upper right quadrant of the abdomen. An anatomical scan of the abdomen was performed (3-plane localizer) followed by PDFF imaging (Ax 3D IDEAL IQ BH) and an elastography sequence (Ax 2D MR Touch elastography).
The hepatic fat fraction (%) was measured in MRI-PDFF images as the mean of two regions of interest (ROIs) drawn onto the right liver lobe. The ROIs were at least 500 mm2 (mean 677 ± 137 mm2) and drawn to contain liver tissue while avoiding large intrahepatic blood vessels and bile ducts. Liver stiffness (kPa) was measured in elastograms generated by the MR elastography sequence as the mean of ROIs drawn on two axial elastograms. With masks eliminating areas unfit for analysis, the ROIs were drawn to include the entire right liver lobe while avoiding large intrahepatic blood vessels and bile ducts. All scans were analysed by an investigator blinded to participant ID and Visit number.
Blood samples
Blood samples were drawn from a cubital vein. The following blood measurements were performed at the Department of Clinical Biochemistry, Aarhus University Hospital: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin, albumin, prothrombin-proconvertin ratio, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, haemoglobin, platelets, white blood cell count, C-reactive protein, FIB-4 (Fibrosis-4) score, soluble CD163, glucose, insulin, ethanol, sodium and potassium. 3-hydroxybutyrate was measured in blood using an amperometric device (FreeStyle Precision; Abbott Laboratories, Chicago, USA). PRO-C3 (N-terminal pro-peptide of type III collagen) was measured using an ELISA, as previously described.21 Plasma free fatty acids (FFA; NEFA-HR(2) Assay, FUJIFILM, Neuss, Germany) and glucagon (Mercodia, Uppsala, Sweden) were measured using commercial assays following manufacturer’s instructions.
Statistical analyses
Statistical analyses were performed using Stata 17 (StataCorp LLC, TX, USA). Normality of data was checked by quantile-quantile plots of data residuals, and sphericity by residual-vs.-fitted plots. If assumptions of normality and sphericity were met for raw or log-transformed data, data were analysed using repeated measures ANOVA with post hoc pairwise comparisons adjusted for multiple testing using Tukey’s test. If assumptions were not met, data were analysed using Friedman’s test with post hoc pairwise comparisons using Dunn’s test. The correlation between change in hepatic fat fraction before and after binge drinking (Visit 1 vs. Visit 2) and covariates were analysed using Pearson’s correlation coefficient on normally distributed data, and Spearman’s rank correlation coefficient on skewed data. Groups were compared using Student’s t test or Wilcoxon test if assumptions of normality or equal distribution were not met. The following were tested as explanatory variables: Age, sex, BMI, baseline measures of hepatic fat fraction, LDL-cholesterol, HDL cholesterol, triglycerides, FFAs, homeostatic model assessment for insulin resistance (HOMA-IR), glucagon, alcohol intake (g), and energy from food intake (kcal) during the festival. The following were tested as associated changes: Change in plasma triglycerides, ALT and AST. Normally distributed data were reported as mean ± SD and skewed data as median (IQR). A p value below 0.05 was considered statistically significant in a two-tailed test.
Results
Participant characteristics and consumption
A total of 16 healthy adults were included, of whom one participant withdrew consent for personal reasons. Fifteen participants completed the study (9 males, 6 females) with a mean age of 36 ± 5 years and a BMI of 23 ± 3 kg/m2 (Table 1). The participants had a habitual alcohol intake of 0-150 g per week (Table 1) and normal liver blood biochemistry, lipid levels, glucometabolic measures, and markers of inflammation at inclusion (Table 2).
Table 1.
Baseline participant characteristics, and alcohol and food intake during the festival.
| Participant characteristics | Men (n = 9) | Women (n = 6) | All (N = 15) |
|---|---|---|---|
| Age (years) | 39 (35-40) | 35 (33-38) | 36 (34-40) |
| BMI (kg/m2) | 24 ± 3 | 22 ± 2 | 23 ± 3 |
| Weekly alcohol intake (g): 0-50/50-100/100-150/>150 | 3/5/1/0 | 5/1/0/0 | 8/6/1/0 |
| Frequency of binge drinking: never/every 6 months/monthly/1-2 weekly | 2/5/1/1 | 3/3/0/0 | 5/8/1/1 |
| Smoking: never/former/current | 6/1/2 | 3/1/2 | 9/2/4 |
| Festival days | |||
| Daily alcohol intake (g) | 190 ± 58 | 178 ± 57 | 186 ± 56 |
| BAC (‰) | 0.98 (0.84-1.06) | 0.82 (0.53-0.84) | 0.85 (0.77-1.06) |
| Daily food intake (kcal) | 1,971 ± 425 | 1,858 ± 247 | 1,926 ± 359 |
| Total energy intake (kcal) | 4,353 ± 773 | 4,086 ± 587 | 4,246 ± 695 |
Continuous data are reported as mean ± SD. Habitual binge drinking was defined as the intake of ≥40 g/50 g alcohol (4/5 units) in women and men, respectively, within a few hours. BAC, blood alcohol concentration.
Table 2.
Blood biochemistry on the three study visits.
| Biochemistry | Visit 1 | Visit 2 | Visit 3 |
|---|---|---|---|
| ALT (U/L) | 22 (15-29) | 26 (14-32) | 24 (17-34) |
| AST (U/L) | 25 (22-28) | 26 (22-39) | 26 (20-33) |
| GGT (U/L) | 17 (12-30) | 20 (16-33) ∗ | 19 (16-39) ∗∗ |
| FIB-4 | 0.77 (0.64-0.94) | 0.78 (0.66-1.41) | 0.74 (0.61-0.85) |
| PRO-C3 (ng/ml) | 46 (41-52) | 47 (39-53) | 50 (40-63) |
| sCD-163 (mg/L) | 1.7 ± 0.4 | 1.8 ± 0.4 | 1.8 ± 0.5 |
| Cholesterol (mmol/L) | 4.7 ± 0.8 | 4.2 ± 0.8 ∗∗ | 4.7 ± 1.0 |
| LDL-C (mmol/L) | 2.7 ± 0.7 | 2.0 ± 0.6 ∗∗∗ | 2.7 ± 0.8 |
| HDL-C (mmol/L) | 1.5 ± 0.4 | 1.7 ± 0.4 | 1.5 ± 0.4 |
| Triglycerides (mmol/L) | 0.73 (0.63-1.08) | 0.95 (0.62-1.32) | 0.74 (0.59-0.98) |
| FFA (mmol/L) | 0.70 ± 0.25 | 0.66 ± 0.33 | 0.73 ± 0.36 |
| Glucose (mmol/L) | 4.9 ± 0.3 | 5.0 ± 0.4 | 4.7 ± 0.3 |
| HOMA-IR | 0.9 (0.5-1.3) | 0.8 (0.5-1.2) | 0.9 (0.4-1.9) |
| Glucagon (pmol/L) | 5.4 (3.8-6.7) | 5.4 (2.7-10.4) | 4.2 (2.6-6.2) |
| 3-hydroxybutyrate (mmol/L) | 0.2 (0.2-0.3) | 0.2 (0.2-0.3) | 0.2 (0.2-0.3) |
| Albumin (g/L) | 44 ± 2 | 42 ± 3 | 43 ± 3 |
| Bilirubin (μmol/L) | 13 (11-20) | 13 (10-17) | 10 (10-13) ∗ |
| Sodium (mmol/L) | 140 ± 2 | 140 ± 2 | 139 ± 2 |
| Potassium (mmol/L) | 3.6 ± 0.2 | 3.8 ± 0.2 | 3.6 ± 0.2 |
| Creatinine (μmol/L) | 65 (62-83) | 62 (59-79) ∗ | 62 (57-79) |
| Haemoglobin (mmol/L) | 8.9 ± 0.8 | 8.4 ± 0.8 ∗∗ | 8.7 ± 0.8 |
| WBC (109/L) | 5.5 (4.5-6.4) | 6.7 (5.7-8.6) ∗ | 5.5 (5.1-7.1) |
| Platelets (109/L) | 241 ± 41 | 236 ± 36 | 242 ± 34 |
| PP | 0.84 ± 0.17 | 0.93 ± 0.18 ∗∗ | 0.85 ± 0.16 |
The table describes blood biochemistry obtained during the week before binge drinking (Visit 1), after the 3 days of binge drinking (Visit 2), and after 10 days of alcohol abstinence following binge drinking (Visit 3). Data are reported as mean ± SD or median (IQR). Visits were statistically compared using repeated measures ANOVA or Dunn’s test. ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001 compared to Visit 1. ALT, alanine aminotransferase; AST, aspartate aminotransferase; FFA, free fatty acids; FIB-4, Fibrosis-4 score; GGT, gamma-glutamyltransferase; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment for insulin resistance; LDL-C, low-density lipoprotein cholesterol; PP, prothrombin-proconvertin ratio; PRO-C3, N-terminal pro-peptide of type III collagen; sCD163, soluble CD163; WBC, white blood cell count.
During the festival, each participant consumed on average 186 ± 56 g alcohol (19 ± 6 units) per day, ranging from 70 to 360 g in 1 day (Table 1). Mean BAC measured on the 3 days was 0.90 ± 0.30‰, ranging from 0.15‰ to 2.25‰. The mean energy intake from food was 1,926 ± 359 kcal per day, while the total energy intake including beverages was 4,246 ± 695 kcal per day (Table 1).
Liver fat content and stiffness
At Visit 1, the median hepatic fat fraction was 1.9% (IQR 1.6-2.5%) with one participant having grade 1 steatosis (fat fraction 5.7 %) (Fig. 1A). Three days of binge drinking increased the median hepatic fat fraction by 2.5-fold to 4.6% (IQR 2.4-5.7%), p <0.0001. Following 10 days of alcohol abstinence, the hepatic fat fraction normalised to 2.0% (IQR 1.6-2.3%). The change in hepatic fat fraction markedly varied between participants; it more than doubled in two-thirds of the participants, whereas one-third only had a minor or no increase (Fig. 1B). In 6 of 15 participants (40%), hepatic fat fraction increased to above 5% after binge drinking, defining hepatic steatosis. The change in hepatic fat fraction was similar between men and women. Mean liver stiffness marginally increased from 2.5 ± 0.2 kPa to 2.7 ± 0.3 kPa (p = 0.048) after binge drinking and decreased to 2.3 ± 0.3 kPa at Visit 3 (p = 0.4 compared to Visit 1) (Fig. 1C).
Fig. 1.
Liver fat content and liver stiffness. The figure shows individual participant measures of hepatic fat fraction (%) evaluated by MRI-PDFF (A) and liver stiffness (kPa) evaluated by MR elastography (B) obtained during the week before binge drinking (Visit 1), after the 3 days of binge drinking (Visit 2), and after 10 days of alcohol abstinence following binge drinking (Visit 3). Visits were statistically compared using repeated measures ANOVA or Dunn’s test. p values are reported for differences between Visit 1 and 2. MRI-PDFF, MRI-proton density fat fraction.
Markers of liver injury and blood lipids
There were no changes in mean ALT or AST whilst GGT increased to levels within the normal range (p = 0.03). However, notable increases in AST were observed in four participants (Fig. 2B). There were no changes in the fibrosis markers FIB-4, PRO-C3 or soluble CD163. Plasma triglycerides tended to increase after binge drinking from 0.73 (IQR 0.63-1.08) mmol/L to 0.95 (IQR 0.62-1.32) mmol/L (p = 0.056), whereas LDL-cholesterol decreased from 2.7 ± 0.7 mmol/L to 2.0 ± 0.6 mmol/L (p < 0.0001), and HDL cholesterol remained unchanged. Fasting metabolic parameters and hormones (FFA, 3-hydroxybutyrate, glucose, insulin, HOMA-IR, and glucagon) did not change. White blood cell count and prothrombin-proconvertin ratio increased, and haemoglobin decreased (Table 2). Except for GGT (p = 0.008 compared to Visit 1), all measurements returned to baseline levels following 10 days of alcohol abstinence.
Fig. 2.
Liver biochemistry and blood lipids. The figure shows individual participant measures of ALT (A), AST (B), PRO-C3 (C), LDL-C (D), HDL-C (E), and triglycerides (F) obtained during the week before binge drinking (Visit 1), after the 3 days of binge drinking (Visit 2), and after 10 days of alcohol abstinence following binge drinking (Visit 3). p values are reported for differences between Visit 1 and 2. ALT, alanine aminotransferase; AST, aspartate aminotransferase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; PRO-C3, N-terminal pro-peptide of type III collagen.
Explanatory factors for liver fat accumulation
Group comparisons between participants who developed hepatic steatosis following binge drinking (hepatic fat fraction ≥5% at Visit 2) vs. those who did not are reported in Table 3. The participants who developed hepatic steatosis had higher BMI (p = 0.01) and baseline hepatic fat fraction (p = 0.02), elevated baseline triglycerides (p = 0.03) and glucagon (p = 0.03), and lower baseline FFA (p = 0.005). There was no difference between the two subgroups in terms of age, sex, baseline HOMA-IR, LDL and HDL cholesterol, alcohol intake or energy from food intake during the festival. In correlation analyses, only BMI correlated positively with the increase in hepatic fat fraction before and after binge drinking (r = 0.54; p = 0.038), whereas there was no correlation with the remaining measures. An increase in hepatic fat fraction correlated positively with the increase in triglycerides (r = 0.62; p = 0.01) following binge drinking but not with changes in other metabolic markers, hormones, or markers of liver injury or fibrogenesis.
Table 3.
Group comparisons between participants that developed hepatic steatosis following binge drinking vs. participants who did not.
| Hepatic steatosis (n = 6) | Not hepatic steatosis (n = 9) | |
|---|---|---|
| Characteristics and consumption | ||
| Age (years) | 36 ± 5 | 34 ± 6 |
| Sex (male/female) | 5/1 | 4/5 |
| BMI (kg/m2) | 25 ± 3∗ | 22 ± 2 |
| Baseline hepatic fat fraction (%) | 3.2 ± 0.6∗ | 1.8 ± 0.1 |
| Δ Hepatic fat fraction (% points) | 3.5 ± 0.5∗∗ | 1.4 ± 1.2 |
| Total alcohol intake (g) | 609 ± 191 | 522 ± 152 |
| Total energy intake (kcal) | 12,768 ± 2,101 | 11,171 ± 1,436 |
| Baseline blood tests | ||
| LDL-C (mmol/L) | 3.1 ± 0.9 | 2.5 ± 0.5 |
| HDL-C (mmol/L) | 1.4 ± 0.3 | 1.6 ± 0.4 |
| Triglycerides (mmol/L) | 1.15 ± 0.43∗ | 0.74 ± 0.20 |
| FFA (mmol/L) | 0.50 ± 0.13∗∗ | 0.84 ± 0.22 |
| HOMA-IR | 1.11 (0.84-1.29) | 0.63 (0.44-1.15) |
| Glucagon (pmol/L) | 8.1 (6.4-12.4)∗ | 4.4 (3.6-5.4) |
Hepatic steatosis was defined as a hepatic fat fraction ≥ 5% at Visit 2. Data are reported as mean ± SD or median (IQR). Groups were statistically compared using Student’s t test or Wilcoxon test. ∗p <0.05, ∗∗p <0.01. FFA, free fatty acids; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment for insulin resistance; LDL-C, low-density lipoprotein cholesterol.
Discussion
This before-and-after, real-world study provides novel and direct evidence describing the acute effects of binge drinking on the liver as well as its reversibility in healthy individuals engaging in real-life recreational binge drinking. Firstly, the results show that 3 consecutive days of binge drinking more than doubled the median hepatic fat fraction, resulting in a fat fraction of above 5% in 6 out of 15 participants, defining steatotic liver disease. This was accompanied by a marginal increase in liver stiffness along with increased triglycerides and decreased LDL-cholesterol, but with no changes in markers of liver injury or fibrosis. Secondly, all changes but GGT returned to baseline levels following 10 days of alcohol abstinence. Lastly, there was a notable variation in the hepatic response to binge drinking; about two-thirds experienced more than a doubling in hepatic fat fraction, while the remaining showed little or no increase. The participants who developed hepatic steatosis were characterised by higher BMI, and subclinical metabolic dysfunction exhibited by increased baseline hepatic fat fraction, plasma triglycerides and glucagon. The numerical change in hepatic fat fraction after binge drinking was correlated to baseline BMI only, and not to alcohol intake, caloric intake, or baseline hepatic fat fraction. Thus, our findings were in accordance with our a priori expectations that hepatic steatosis is rapidly induced by binge drinking with no sustained structural changes following a short period of alcohol abstinence.
The participants reported an average intake of 186 g alcohol (19 units) each day of the 3-day festival, a substantial increase compared to their habitual intake of below 150 g per week. While we recognise the possibility of inaccuracies in self-reporting data, daily breath measurements confirmed that all participants reached a BAC of above 0.8‰ on at least one of the festival days, consistent with the NIAAA definition of binge drinking.8 Notably, one participant reported a higher habitual intake of 100-150 g and binge drinking 1-2 times per week. This participant had an increased hepatic fat fraction at baseline (5.7%), whilst the absolute increase following binge drinkingwas similar to that of the other participants.
The rapid development of hepatic steatosis was most likely driven by the well-known biochemical effects of ethanol metabolism in the hepatocyte. Here, the two-step enzymatic oxidation of ethanol produces NADH, shifting the redox potential in favour of increased de novo lipogenesis and inhibition of beta-oxidation, together resulting in triglyceride deposition in the hepatocyte.22 In addition, the participants’ total energy intake much exceeded the daily gender- and age-standardised recommendations, where approximately half of it was from alcoholic beverages, presumably beer as the predominant beverage. A longstanding hypercaloric intake of fat and carbohydrates may in itself contribute to hepatic steatosis, also known as MASLD. However, the marked but short-term effects of excessive alcohol intake on hepatic steatogenesis represent a metabolic mechanism that is fundamentally different from MASLD, supported by our findings that binge drinking did not induce any negative changes in metabolic hormones, plasma lipids and ketone bodies. The impact of a hypercaloric intake during binge drinking is uncertain, but it is notable that previous experiments of feeding a hypercaloric diet to healthy people for 3-8 weeks show increased liver fat content to only similar levels or lower than those observed in the present study.[23], [24], [25]
Pioneering studies by Charles E. Lieber and others showed that heavy alcohol intake induced a rapid accumulation of triglycerides in liver biopsies from healthy young adults.[26], [27], [28] However, advancements in research ethics have limited further investigations in this area until the recent emergence of advanced non-invasive imaging techniques. In young men, Demant et al. showed that 1 week of heavy alcohol intake induced ultrasound-detectable hepatic steatosis in nearly one-third of participants, but with no quantifiable changes in hepatic fat content measured using the controlled attenuation parameter score.19 Using state-of-the-art MRI-PDFF, we found more than a doubling in liver fat content after just 3 days of heavy alcohol intake. Another study in healthy men found no change in liver fat content measured by MR spectroscopy following 5 h of ad libitum alcohol and high calory foods.18 However, the authors noticed a substantial variation in the hepatic fat change among participants with similar energy intake, in line with our findings highlighting the biological variation in susceptibility towards alcohol- and diet-induced steatosis. We did not observe any elevations in markers of liver injury or fibrogenesis in contrast with previous studies investigating the acute consequences of binge drinking in healthy people.19,29 This discrepancy may be due to differences in alcohol exposure and study population as well as the timing of sampling and rapid resolution of biomarkers. Although our study was conducted in healthy individuals, we found that those who developed hepatic steatosis following binge drinking had higher BMI along with elevated fasting glucagon and triglycerides at baseline, suggesting that subclinical impairments in metabolic function can increase the risk of alcohol-induced steatosis. As such, our experimental findings support emerging epidemiological evidence linking cardiometabolic risk factors to an increased risk of alcohol-related liver disease from binge drinking30,31 and stresses the relevance of the newly defined MetALD as a distinct clinical entity.32,33
The study has some limitations, which include a small study sample and a lack of externally validated measurements of alcoholic beverages and food intake, including the type of beverage. Therefore, imprecise reporting is a potential bias which also hinders further interpretation of the contribution from pure alcohol vs. hypercaloric intake, and the impact of various alcoholic beverages. Moreover, we did not collect data on physical activity, sleep or drug use which are often altered with festival behaviour. Importantly, the real-world setting of our study, applicable to typical recreational drinking in the general population, is an essential strength that secures the generalisability of our findings. Also, in contrast to previous studies, we included both men and women and found no sex differences, though cautioned by the small sample size. To further explore the biological factors important for the hepatic susceptibility to binge drinking, future studies should examine the impact of known genetic polymorphisms or repeat this study design in patients with the metabolic syndrome. Finally, our study highlights the need for further investigation into the long-term clinical harms of repeated binge drinking.
In conclusion, our study shows that just a few days of recreational binge drinking may lead to acute development of hepatic steatosis in otherwise healthy individuals. Furthermore, we showed that all changes were resolved after 10 days of alcohol abstinence, and the binge drinking did not leave any increases in markers of compromised metabolism, parenchymal liver injury or fibrogenesis. Thus, our results imply that the hepatic consequences of one episode of excessive alcohol intake are minor and fully reversible if followed by short-term alcohol abstinence. Finally, we found distinct variability in the hepatic response to binge drinking, where participants that developed hepatic steatosis were characterised by subclinical impairments in metabolic markers and hormones, supporting an increased risk of alcohol-related liver injury associated with metabolic dysfunction.
Abbreviations
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BAC, blood alcohol concentration; FFAs, free fatty acids; GGT, gamma-glutamyltransferase; HDL, high-density lipoprotein; HOMA-IR, homeostatic model assessment for insulin resistance; LDL, low-density lipoprotein; MRI-PDFF, MRI-proton density fat fraction; ROI, regions of interest.
Financial support
The study was funded by grants from the Novo Nordisk Foundation (NNF21OC0068121), Tømmerhandler Johannes Fogs Fond, and Oda og Hans Svenningsens Fond.
Authors’ contributions
All authors met the International Committee of Medical Journal Editors criteria for authorship, take integrity for the work, were involved in the critical review and drafting of the manuscript, and approved the final version. KK, KLT and PLE designed and conceived the study. KK wrote the first draft with input from JRY, KLT, and HV. KK and JRY did the statistical analysis. KK, JRY, KLT and PLE have directly accessed and verified the underlying data reported in the manuscript. JRY recruited the participants and performed the study investigations together with KK, ACDM, EM, and AFW. AZ performed laboratory analyses. All authors contributed important intellectual content and data interpretation, had access to the study data, and carried final responsibility for the decision to submit for publication.
Data availability
Individual participant data that underlie the results reported in this article, after de-identification, are available from the corresponding author on reasonable request.
Conflict of interest
This was an investigator-initiated study with no involvement from funding sources. The authors declare no competing interests. KLT reports grants from the Novo Nordisk Foundation.
Please refer to the accompanying ICMJE disclosure forms for further details.
Acknowledgements
The authors would like to thank Margit Haislund and Louise Forsmann Grønnemark for their valuable assistance with practical planning and execution of the MRI scans. Furthermore, we thank the participants for engaging in this study. The graphical abstract was designed using BioRender.
Footnotes
Author names in bold designate shared co-first authorship
Supplementary data to this article can be found online at https://doi.org/10.1016/j.jhepr.2025.101623.
Supplementary data
The following are the Supplementary data to this article.
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Data Availability Statement
Individual participant data that underlie the results reported in this article, after de-identification, are available from the corresponding author on reasonable request.