Alcohol-related liver disease and alcoholic hepatitis

• Alcohol-related liver disease (ALD) is a spectrum, from silent fatty change, through inflammation and scarring, to cirrhosis; only a minority of heavy drinkers progress all the way.
• The single most useful intervention at any stage is helping the patient to stop harmful drinking, because abstinence improves long-term survival.
• Alcoholic hepatitis (AH) is an acute, severe inflammatory flare that usually appears in people who have been drinking heavily for about five years or more, and it carries a high short-term mortality.
• Severity is judged mainly with the Model for End-Stage Liver Disease (MELD) score and the Maddrey discriminant function: a MELD score greater than 20 or a Maddrey score of 32 or higher defines severe disease. ^[1]
• The only drug with proven benefit in severe AH is corticosteroid therapy, given to suitable patients, with response re-checked after a few days and treatment stopped in non-responders.

By the end of this page you should be able to:

1. Describe the spectrum of ALD and the factors that decide whether a heavy drinker develops advanced disease.
2. Recognise steatosis, steatohepatitis, fibrosis, cirrhosis and AH on history, examination and tests.
3. Use the diagnostic criteria, fibrosis assessment tools and severity scores for AH, and plan first-line investigations.
4. Manage severe AH: steroids or not, nutrition, infection screening, and when to refer for transplantation.
5. Recognise and manage alcohol withdrawal in the presence of liver disease.
6. Adapt investigation and management for special groups and low-resource settings.

ALD is a family of related states rather than one disease ^[1]:

• Steatosis (fatty liver): fat droplets in hepatocytes, usually reversible if alcohol stops.
• Alcoholic steatohepatitis (ASH): steatosis plus hepatocyte ballooning, neutrophil infiltration and (in many) Mallory-Denk bodies; the lesion that drives progressive disease.
• Alcoholic fibrosis: collagen deposition around central veins and in portal tracts.
• Cirrhosis: widespread bridging fibrosis with regenerative nodules and architectural distortion. Portal hypertension and its complications are covered in the Cirrhosis topic.
• Alcoholic (alcohol-associated) hepatitis: an acute, symptomatic, inflammatory syndrome superimposed on the above.
• Hepatocellular carcinoma (HCC): a later complication, mainly of cirrhosis.

Current European usage favours "alcohol-related liver disease (ALD)" and "alcohol-associated liver disease", and retains "alcoholic hepatitis" because of longstanding usage ^[1].

Harmful alcohol use is a leading cause of liver disease worldwide. Global estimates differ by source and year of data: the ACG 2024 guideline attributes about 3 million deaths a year to harmful alcohol use (5.3% of all deaths, 13.5% in people aged 20 to 39 years) ^[1], whereas the WHO 2024 fact sheet estimates about 2.6 million alcohol-attributable deaths in 2019 (6.7% of all deaths in men and 2.4% in women, and 13% in people aged 20 to 39 years) ^[7]. In the United States about half of cirrhosis-related deaths are due to alcohol ^[1], and only roughly 10% to 20% of individuals with chronic heavy alcohol use develop cirrhosis ^[1].

The burden is rising. ALD contributes to about 48% of cirrhosis-related hospitalizations and more than 40% of liver transplant listings in the United States ^[1]. Younger adults, women and minority groups have seen the largest increases, and hospitalisations for ALD have nearly doubled while those for other aetiologies have stayed stable or fallen ^[1]. Women develop ALD at a lower daily intake of alcohol, probably because of a higher body fat fraction and lower gastric alcohol dehydrogenase activity ^[1]. ALD is the leading cause of liver-related illness and death in the US and Europe and the commonest reason for liver transplantation in those regions ^[3].

One standard drink contains about 14 g (0.6 fluid ounces) of pure ethanol ^[1]. Harmful drinking (a pattern leading to health or psychosocial problems) is defined here as at least 3 drinks per day or at least 21 per week in men, and at least 2 per day or at least 14 per week in women ^[1].

The amount and duration of alcohol use are the main determinants of ALD, and risk rises with dose ^[1]. Useful thresholds and risk modifiers:

• Consumption thresholds for liver risk. Long-term daily intake above 20 g in women (1.4 standard drinks) or above 30 g in men (2.1 standard drinks) can lead to ALD ^[3].
• Heavy drinking (US definitions). More than 4 drinks on any day or more than 14 per week for men, or more than 3 on any day or more than 7 per week for women ^[1].
• Minimal thresholds used for diagnosing AH. More than 3 drinks (about 40 g) per day in women or more than 4 drinks (about 50 to 60 g) per day in men. Heavy use for more than 5 years (NIAAA 2016 ^[4]) or for more than 6 months with less than 2 months of sobriety (AASLD 2019 ^[8]) is commonly required; intermittent abstinence is common. Trial patients often report more than 40 g of alcohol daily ^[2].

Only 10% to 20% of heavy drinkers develop cirrhosis, so cofactors matter ^[1]. Binge and high-intensity drinking add to daily use; drinking with meals seems lower risk than drinking outside meals; wine or beer may carry lower risk than spirits, although evidence is mixed ^[1].

Other risk factors include genetics (PNPLA3, TM6SF2, MBOAT7, alpha-1 antitrypsin variants), female sex, heavy smoking, obesity, type 2 diabetes and metabolic syndrome, prior Roux-en-Y gastric bypass, which is linked to an increased risk of alcoholic liver injury (ACG 2024 estimates 2- to 3-fold ^[1]; AASLD 2019 likewise notes the link ^[8]), viral hepatitis (B or C, which interact with alcohol to accelerate fibrosis and HCC), and acute insults such as infection, bleeding or withdrawal that precipitate decompensation ^[1].

Alcohol is metabolised chiefly by alcohol dehydrogenase to acetaldehyde (toxic) and then to acetate; chronic drinkers also recruit cytochrome P450 2E1 (microsomal ethanol oxidation), which generates oxidative stress. Consequences include lipid peroxidation, mitochondrial injury, acetaldehyde-protein adducts, immune activation, altered gut microbiome and a "leaky" intestinal barrier that lets endotoxin (lipopolysaccharide) reach Kupffer cells. The resulting cytokines (TNF-alpha, IL-6 and others) drive inflammation and stellate-cell activation. This explains why steatosis is reversible, why steatohepatitis often is not, and why repeated injury leads to scarring, nodular regeneration and cirrhosis ^[6].

• Steatosis. Alcohol shifts the NADH/NAD ratio in favour of lipogenesis and away from fatty acid oxidation; free fatty acids are also delivered in excess. Fat accumulates in hepatocytes, often without symptoms.
• Steatohepatitis to fibrosis. Acetaldehyde, reactive oxygen species and endotoxin activate stellate cells via cytokines and profibrotic signals such as transforming growth factor beta. Collagen accumulates around central veins and in portal tracts.
• Cirrhosis. Distorted architecture raises portal pressure, producing varices, ascites and encephalopathy, with hepatocyte failure added later.
• Alcoholic hepatitis. A severe flare of inflammation on top of previous fibrosis or cirrhosis, behaving at its worst like acute-on-chronic liver failure, with infection, renal injury and encephalopathy ^{[2] [6]}.

ALD is often silent until late and may be found incidentally on raised liver enzymes or steatosis on imaging. Advanced disease shows the features of cirrhosis. AH is more dramatic and acute.

History in AH. Recent onset or worsening jaundice; heavy alcohol use; malaise; anorexia and nausea; fever or rigors; often right upper quadrant pain; weight loss; dark urine; pale stools. Ask about the last drink, regular weekly intake, binges, prior detox or rehabilitation, and the psychosocial setting. Screening tools (AUDIT, or the 3-question AUDIT-Consumption) are recommended at every medical encounter ^[1]. Smokers, people with obesity or diabetes, or after bariatric surgery need particular attention to alcohol use.

Examination in AH. Patients often look acutely ill or septic, with jaundice and a tender enlarged liver. Ascites and peripheral oedema are variable. Fever without a clear source is common and is not necessarily bacterial infection. Signs of chronic liver disease (spider naevi, palmar erythema, gynaecomastia, wasting) may coexist. Encephalopathy or ascites means decompensation.

Withdrawal state. Alcohol withdrawal syndrome in people with AUD and ALD should be assessed with the CIWA-Ar protocol. Clinicians should differentiate AWS from hepatic encephalopathy, and the two can coexist ^[1]. Tremor, sweating, tachycardia, anxiety, insomnia, seizures or delirium tremens can occur.

Neurological care. Wernicke encephalopathy may coexist; give thiamine before any glucose-containing fluid in malnourished or withdrawing patients. Thiamine, vitamin B12 and zinc deficiencies are common in AH and should be supplemented ^[1].

Heavy drinking does not exclude any other diagnosis. Conditions that can look like AH or ALD, or be present at the same time, include viral hepatitis, non-alcoholic and metabolic-dysfunction associated steatotic liver disease, autoimmune hepatitis, drug-induced liver injury, Wilson disease, haemochromatosis, biliary obstruction and secondary (metastatic) liver disease. The pattern of enzyme rise, autoantibody and serological testing, and sometimes biopsy separates them ^{[2] [6]}. Biopsy is not required for staging fibrosis and is not needed to make a probable diagnosis of AH unless confounding factors exist ^{[1] [4]}.

Table. Features that separate common mimics of alcoholic hepatitis

First-line: full blood count (often macrocytosis), urea and electrolytes, liver panel (bilirubin, AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, albumin), prothrombin time/INR, renal function, glucose, blood gases, septic screen, urinalysis, chest radiograph and an electrocardiogram. A characteristic pattern in AH is an AST above 50 IU/L, an AST and ALT both less than 400 IU/L, and an AST to ALT ratio greater than 1.5 ^{[2] [4]}. Where direct markers are helpful (carbohydrate-deficient transferrin, ethyl glucuronide, ethyl sulphate, phosphatidylethanol) they can support or refute the reported intake, although biomarker choice depends on the time frame of interest ^[1].

Confirmatory and supportive: abdominal ultrasound with Doppler; fibrosis assessment with FIB-4 and transient elastography, which together are the best non-invasive tests for fibrosis in ALD; viral serology, autoantibodies, iron studies, caeruloplasmin in younger adults and alpha-fetoprotein in cirrhosis surveillance ^[1]. Liver biopsy, preferably transjugular in decompensated disease, is reserved for diagnostic doubt, to confirm steatohepatitis and to exclude other causes ^{[1] [4]}. Renal and cardiac assessment are often needed in severe disease, and endoscopy looks for varices in anyone with cirrhosis.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria are a practical guide to a probable diagnosis of AH. Probable AH applies in a person with heavy alcohol use, recent onset of jaundice (within 60 days by NIAAA criteria ^[4], within 8 weeks by AASLD 2019 ^[8], recent-onset jaundice within 3 months in trial cohorts such as CORTISAVE ^[2]), serum bilirubin above 3 mg/dL, AST above 50 IU/L (standard laboratory units; NIAAA 2016 prints IU/mL ^[4], while clinical sources such as CORTISAVE report IU/L ^[2]) with an AST to ALT ratio greater than 1.5, and no confounding factors ^[4]. A liver biopsy is not required in the absence of confounding factors ^{[1] [4]}.

Severity scores (all cut-offs from sources):

• Maddrey discriminant function (mDF). Less than 32 mild, 32 or higher severe ^[5]; an mDF of 32 or higher predicts 30-day mortality of about 20% to 50% ^[1] (some series report 30% to 60% for mDF above 32 ^[6]).
• MELD score. Greater than 20 defines severe AH; ACG 2024 estimates roughly 20% 90-day mortality ^[1], while severe AH series also report about 30% at 90 days ^[2]. MELD scores 25 to 39 appear to gain most benefit from corticosteroids; caution is needed above 50 ^[1]. MELD is more accurate than mDF for predicting short-term mortality in AH ^[1]. Severe AH should preferably be hospitalised ^[1].
• Lille score. Assesses steroid response at day 7 (or day 4); greater than 0.45 identifies non-responders, in whom corticosteroids should be stopped ^[1].
• Other scores. Child-Turcotte-Pugh, Glasgow Alcoholic Hepatitis Score (GAHS) and ABIC (Age, Bilirubin, INR, Creatinine). In a post-hoc analysis of STOPAH data (ACG 2024), mDF (area under the curve 0.67) was somewhat inferior to MELD, GAHS and ABIC (0.704 to 0.726) ^[1]; global cohorts similarly show mDF has a lower prognostic accuracy than MELD, GAHS or ABIC ^[9].
• Sodium-MELD. A sodium-MELD score of 21 carries an approximate 90-day mortality of 20% ^[6].

Table. Severity scores for alcoholic hepatitis

Management recommendations here use the ACG Clinical Guideline: Alcohol-Associated Liver Disease (Jophlin et al., 2024) and the NIAAA diagnostic criteria (Crabb et al., 2016); values from these are cited throughout. Where figures differ between sources, the cited value is the one given by these sources.

Approach to the heavy drinker with suspected ALD

• Hospitalise severe cases (MELD greater than 20): high short-term mortality, best cared for in hospital ^[1].
• Infection screening is essential; infection is common and worsens outcomes. Prophylactic antibiotics are not given routinely ^[1].
• Nutrition. Aim for about 35 kcal/kg/day with 1.2 to 1.5 g/kg of protein; patients consuming less than 21 kcal/kg/day should receive nutritional support, preferably oral or enteral. Thiamine, vitamin B12 and zinc are commonly deficient and should be supplemented, along with other deficiencies ^[1].
• Steroids. Prednisolone and prednisone are given at 40 mg per day for 4 weeks, or intravenous methylprednisolone 32 mg per day if oral medication cannot be used. Corticosteroids improve survival at around one month in roughly 50% to 60% of patients with severe AH ^[1]. N-acetylcysteine intravenously can be used as an adjuvant ^[1]. Pentoxifylline should not be used ^[1].
• Response monitoring. Check the Lille score at day 7 or day 4. In non-responders (Lille score greater than 0.45) corticosteroids should be stopped ^[1]. Steroids do not reduce mortality after the first month and may increase infection risk; benefit is most apparent in patients with MELD 25 to 39 ^{[1] [2]}. The CORTISAVE trial suggested that patients with severe AH who show early spontaneous bilirubin improvement (greater than 10% fall within 5 to 10 days) may not gain additional survival benefit from corticosteroids, although the trial was underpowered and cannot exclude a modest effect; infection rate was numerically higher with steroids (about 47% against 34%) ^[2]. Patients with 4 or more organ failures who are non-responsive to corticosteroids and ineligible for early transplantation are appropriate for palliative care discussions ^[1].

• Abstinence is the most effective treatment to prevent progression and improve long-term outcomes at any stage ^[1].
• AUD treatment. Offer integrated multidisciplinary care (hepatology, addiction medicine, psychology, social work). Brief motivational interventions, cognitive behavioural therapy, motivational enhancement, and 12-step or mutual-aid programmes help. Screening, brief intervention, referral and treatment can be delivered by any healthcare professional. For pharmacotherapy, baclofen (starting 5 mg three times daily, titrated to 15 mg three times daily as tolerated) is the option with most evidence in ALD and compensated cirrhosis; acamprosate and naltrexone may be used in compensated disease but avoided or used cautiously in decompensation or renal impairment; gabapentin and topiramate have acceptable profiles but need more evidence; disulfiram is contraindicated in liver disease of any severity ^[1].
• Transplantation. Selection should not be based on an arbitrary length of sobriety; psychosocial assessment by a social worker and addiction specialist informs the decision. Early transplant (less than 6 months' abstinence) for selected patients with severe AH unresponsive to medical therapy is increasingly accepted. Recipients need close follow-up for alcohol use. Tools such as SIPAT, HRAR, MAPS, HPSS or SALT may be used ^[1].
• Cirrhosis care. Patients with ALD cirrhosis are managed like cirrhosis of other causes (non-selective beta blockers, variceal treatment, ascites, nutrition, HCC surveillance), as in the Cirrhosis topic ^{[1] [6]}.

• Treat alcohol withdrawal syndrome as for other patients, with caution in hepatocellular failure: benzodiazepines are the drug of choice for severe AWS but need careful monitoring because they can precipitate or worsen hepatic encephalopathy ^[1].
• Thiamine is given early, before glucose, and Wernicke encephalopathy must be considered in any malnourished or withdrawing patient.
• Nutritional repletion (calories, protein, thiamine, B12, zinc, vitamin D) supports recovery and should start early.
• Refer severe or decompensated patients early to centres able to provide intensive care, renal replacement and (where appropriate) early transplantation.

Infection, acute kidney injury and hepatorenal syndrome, hepatic encephalopathy, coagulopathy and variceal bleeding, refractory ascites, progression to cirrhosis, hepatocellular carcinoma, malnutrition, and psychiatric complications with relapse to drinking. In severe AH infection is common, may be increased by corticosteroids and can precipitate renal injury and encephalopathy.

Prognosis is driven by abstinence: sustained abstinence is associated with long-term survival after both severe and moderate AH ^[1]. Those who relapse have higher later mortality, and many patients who do not recover within about three months have a low chance of spontaneous recovery ^[6]. Sustained abstinence is associated with long-term survival after both severe and moderate AH ^[1].Short-term mortality in severe AH (mDF 32 or higher, or MELD above 20) is high: about 20% to 50% by 30 days on mDF and around 20% at 90 days for MELD above 20; severe AH can reach roughly 30% at 90 days. Corticosteroid meta-analysis of individual patient data (2,111 patients with severe AH) found 1-month survival of 84% with corticosteroids against 76% without, but no benefit beyond one month ^[2]. In patients with early spontaneous bilirubin improvement (greater than 10% fall within 5 to 10 days), CORTISAVE found 90-day survival around 79% with corticosteroids against 83% without and concluded no additional benefit, although underpowered ^[2].

• Screen all patients for hazardous alcohol use: AUDIT or AUDIT-C (three questions) is recommended ^[1].
• Address alcohol use at every encounter using motivational interviewing; abstinence is the goal, reduction an intermediate step.
• In AUD with ALD offer pharmacotherapy where appropriate, especially baclofen, and non-pharmacological therapies.
• Vaccinate against hepatitis A and B in people with chronic liver disease.
• Advise tobacco abstinence, weight optimisation and glucose control; consider alcohol abstinence in people with obesity, type 2 diabetes or metabolic syndrome ^[1].
• Case-find early ALD with non-invasive tests (FIB-4, transient elastography) in heavy drinkers; early detection is cost-effective ^[1].
• Avoid heavy drinking in people with chronic hepatitis B or C, MASLD, haemochromatosis or a family history of cirrhosis ^[1].
• Public policy (pricing, taxation, availability, licensing, advertising) reduces alcohol-related harm ^[1].

• Pregnancy. Harmful alcohol use causes fetal alcohol spectrum disorders and can worsen liver injury; complete abstinence is advised.
• Children and young adults. ALD at these ages usually signals heavy drinking; involve paediatric hepatology and addiction services.
• Older adults. Polypharmacy and comorbidity complicate withdrawal and AUD pharmacotherapy; careful benzodiazepine use.
• Immunocompromised patients. Infection risk is high; avoid steroids unless clearly indicated; thorough septic work-up.
• Bariatric surgery patients. Higher risk of AH after Roux-en-Y gastric bypass; screen carefully ^[1].
• Women. Higher risk at lower intakes.
• Viral co-infection. Treat hepatitis and address alcohol together.

• A careful drinking history and a standard liver panel identify most early ALD; FIB-4 can be calculated without imaging.
• Ultrasound confirms steatosis and cirrhosis where available; without elastography, use clinical markers (low platelets, low albumin, prolonged INR, ascites, varices).
• MELD and mDF can be calculated from basic tests; patients with MELD greater than 20 need hospital-level care.
• N-acetylcysteine and corticosteroids are inexpensive; parenteral thiamine is cheap and should be widely available.
• If biopsy, intensive care or transplantation are not available, establish transfer arrangements early; many improve with abstinence, nutrition and withdrawal management.
• Patient and family counselling, and links to community alcohol services, are free and often the most effective interventions.

• ALD is a spectrum from reversible steatosis through steatohepatitis and fibrosis to cirrhosis; AH is an acute, severe flare.
• Only 10% to 20% of chronic heavy drinkers develop cirrhosis; modifiers matter. ^[1]
• Progression thresholds: above 20 g alcohol per day in women or 30 g per day in men can lead to ALD; a heavier intake (more than 3 drinks/day in women, more than 4/day in men) is a reasonable minimum for AH.
• Screen early and repeatedly.
• AH is likely when: heavy use, jaundice within 60 days (NIAAA) or within 8 weeks (AASLD 2019), bilirubin above 3 mg/dL, AST above 50 IU/L, AST/ALT ratio greater than 1.5, no confounding factors.
• Severity: mDF 32 or higher or MELD above 20 defines severe AH, with high short-term mortality.
• Corticosteroids: best evidence for one-month survival; prednisolone 40 mg/day or IV methylprednisolone 32 mg/day up to 4 weeks; N-acetylcysteine can be added.
• Lille score at day 7 or day 4; stop steroids if above 0.45.
• Steroids help most with MELD 25 to 39, caution above 50.
• Do not use pentoxifylline or universal prophylactic antibiotics.
• Abstinence improves long-term survival above all else; treat AUD with pharmacotherapy (baclofen in ALD) plus psychosocial care.
• Beware of withdrawal and Wernicke disease; use CIWA-Ar, benzodiazepines with caution, thiamine before glucose.
• Transplant can be offered to selected patients with severe AH and should not be gated on an arbitrary abstinence period.

Cirrhosis; Hepatitis B and D; Hepatitis C; Autoimmune hepatitis; abnormal liver function tests and jaundice.