Clinical features and diagnosis of alcohol-associated hepatitis

INTRODUCTION — 

Liver disease related to harmful alcohol use ranges from acute liver inflammation (ie, alcohol-associated hepatitis) to chronic diseases including steatosis alone (fatty changes), advanced fibrosis, and ultimately cirrhosis. The term alcohol-associated hepatitis refers to the recent onset of symptomatic hepatitis, characterized by jaundice and elevated liver biochemistries. The amount and duration of alcohol intake that puts an individual at risk for developing alcohol-associated hepatitis is uncertain, but most patients have a history of heavy alcohol use. Several definitions of heavy or high-risk alcohol use exist (table 1), but we typically use >280 g per week for females and >420 g per week for males as the thresholds for risk of developing alcohol-associated hepatitis [1]. One standard drink contains 14 g of alcohol (figure 1).

This topic will review the clinical features and diagnosis of alcohol-associated hepatitis. Other aspects of alcohol-associated liver disease are discussed separately:

●Management of alcohol-associated hepatitis – (See "Management and prognosis of alcoholic hepatitis".)

●Pathogenesis of alcohol-associated liver disease (ALD) – (See "Pathogenesis of alcohol-associated liver disease".)

●Clinical features and diagnosis of alcohol-associated steatosis and cirrhosis – (See "Clinical manifestations and diagnosis of alcohol-associated steatosis and cirrhosis".)

●Management of chronic alcohol-associated steatosis and cirrhosis – (See "Management of alcohol-associated steatosis and alcohol-associated cirrhosis".)

Issues regarding alcohol use disorder are presented separately:

●(See "Risky drinking and alcohol use disorder: Epidemiology, clinical features, adverse consequences, screening, and assessment".)

●(See "Alcohol use disorder: Treatment overview".)

TERMINOLOGY — 

Alcohol-associated liver disease (ALD) represents alcohol-induced liver injury such as acute hepatitis or more chronic injury resulting in steatosis and liver fibrosis [2].

ALD can be classified as (table 1) [2,3]:

●Alcohol-associated hepatitis – Alcohol-associated hepatitis is an acute clinical syndrome manifested by the onset of jaundice within the previous eight weeks, ongoing harmful alcohol use (usually for a minimum of six months), and elevated aminotransferases and total serum bilirubin levels. (See 'Diagnostic evaluation' below.)

●Alcohol-associated steatosis without fibrosis – Liver imaging demonstrates steatosis without fibrosis or cirrhosis. (See "Clinical manifestations and diagnosis of alcohol-associated steatosis and cirrhosis".)

●Alcohol-associated cirrhosis – Histologic or clinical signs of cirrhosis are present (eg, imaging consistent with cirrhosis, features of portal hypertension such as ascites or variceal bleeding).

●Metabolic dysfunction- and alcohol-associated liver disease (MetALD) – Patients with liver steatosis, at least one metabolic risk factor (eg, obesity, diabetes mellitus, dyslipidemia, hypertension), and a history of increased alcohol use have metabolic dysfunction- and alcohol-associated liver disease (MetALD). This category recognizes that steatotic liver disease can involve a combination of metabolic dysfunction and alcohol. For MetALD, increased amounts of alcohol have been defined as 140 to 350 g per week for females and 210 to 420 g per week for males. This range of alcohol intake defines a spectrum between metabolic dysfunction-associated steatotic liver disease (MASLD)-predominant and alcohol-predominant disease. (See "Clinical features and diagnosis of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults".)

Several definitions of harmful alcohol use exist, and specific thresholds for high-risk alcohol intake vary among studies and professional societies (table 1) [1,3-5]. As an example, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines heavy alcohol consumption as >112 g per week for females and >210 g per week for males [4].

CLINICAL FEATURES

Patient presentation — Patients with alcohol-associated hepatitis present with jaundice, and may have anorexia, fever, and tender hepatomegaly [2]. Laboratory testing reveals moderately elevated aminotransferases (typically less than 10 times the upper limit of normal), with an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio of ≥1.5:1. Patients may report right upper quadrant/epigastric pain and have signs of hepatic encephalopathy and undernutrition.

Age of onset — Patients with alcohol-associated hepatitis are often between 40 and 50 years of age, with most patients presenting before the age of 60 years [6,7]. In a database study involving patients with alcohol-associated hepatitis who were hospitalized, the mean age was 48 years [6]. However, during the last 10 to 20 years, there has been a surge in alcohol-associated liver disease in younger patients [8,9].  

Patterns of alcohol use — Patients with alcohol-associated hepatitis usually have a history of daily heavy alcohol use (>40 g per day for females and >60 g per day for males), usually for at least six months but often for more than five years [1]. A standard drink in the United States (eg, 12 oz [360 mL] of beer, 5 oz [150 mL] of wine, 1.5 oz [45 mL] of 80-proof spirits) contains approximately 14 g of alcohol (figure 1).

Patients often stop drinking when they develop symptoms, so it is common for patients to report no alcohol use for several weeks (often two to three weeks) prior to presentation [10]. Drinking patterns may vary, however, and heavy drinking can be intermittent (ie, weekends only) or covert, such that caregivers and others may not recognize a pattern of harmful alcohol use.

Signs and symptoms — Common signs and symptoms of alcohol-associated hepatitis include [1,2]:

●Jaundice – Jaundice develops or worsens within eight weeks prior to presentation.

●General symptoms – General symptoms include anorexia, fever (temperature ≥37.8 degrees C), and malaise.

●Abdominal symptoms – Right upper-quadrant/epigastric abdominal pain is usually nonsevere. Abdominal distension is usually related to ascites.

Patients with severe alcohol-associated hepatitis and/or underlying cirrhosis may present with signs of hepatic encephalopathy and/or gastrointestinal (variceal) bleeding. Patients may also have symptoms related to undernutrition such as proximal muscle weakness due to muscle wasting. (See "Nutritional issues in adult patients with cirrhosis".)

Physical examination findings — On physical examination, patients typically have an enlarged liver, which often reflects the combined effects of liver steatosis and swelling of hepatocytes due to cell injury-associated protein retention [11]. (See "Overview of the evaluation of hepatomegaly in adults".)

The liver may be tender, but more diffuse abdominal pain is uncommon and suggests other diagnoses, such as spontaneous bacterial peritonitis. (See "Spontaneous bacterial peritonitis in adults: Diagnosis".)

A bruit heard over the liver is also a feature of severe alcohol-associated hepatitis and has been reported in >50 percent of patients [12].

Patients who have underlying cirrhosis may have spider angioma, splenomegaly, muscle wasting, palmar erythema, or gynecomastia [2]. Patients with decompensated cirrhosis may have ascites or peripheral edema. Ascites may also be related to transient portal venous obstruction from liver edema related to acute alcohol-associated hepatitis. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis", section on 'Physical examination'.)

Laboratory features

Liver biochemistries — Patients with acute alcohol-associated hepatitis usually have mildly to moderately elevated liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). The AST and ALT are usually at least two times the upper limit of normal but less than 400 units/L [1]. The pattern of elevated liver enzymes is a disproportionate rise in serum AST compared with ALT, resulting in an AST:ALT ratio of ≥1.5:1. This AST:ALT ratio may be seen in other liver diseases, especially in patients with cirrhosis, but the specificity for alcohol-associated hepatitis rises proportionally to the magnitude of the ratio [13,14].

The lower elevation of serum ALT relative to AST has been attributed to hepatic deficiency of pyridoxal 5'-phosphate in individuals with alcohol use disorder, which is a cofactor for the enzymatic activity of ALT [15]. According to this hypothesis, the altered ratio reflects a failure to appropriately increase the ALT, rather than a disproportionate rise in AST.

Patients with alcohol-associated hepatitis typically have elevated serum bilirubin (>3 mg/dL [>51 micromol/L]) and gamma-glutamyl transferase (GGT) levels [1,16,17]. In addition, serum albumin and prealbumin may be low in patients who are undernourished or who have impaired liver synthetic function. In a trial including 174 patients with alcohol-associated hepatitis, baseline mean bilirubin levels were 14 to 15 mg/dL (238 to 260 micromol/L), mean GGT levels were 223 to 309 units/L, and mean albumin levels were 2.4 to 2.5 g/dL (24 to 25 g/L) [16]. Similarly, in another study, the median bilirubin level was 13 mg/dL (222 micromol/L) and the median albumin level was 2.4 g/dL (24 g/L) [17]. (See "Nutritional issues in adult patients with cirrhosis", section on 'Laboratory studies'.)

Coagulation and hematologic abnormalities — Coagulation and hematologic tests are often abnormal in patients with severe alcohol-associated hepatitis (see "Hematologic complications of alcohol use"):

●International normalized ratio – The international normalized ratio (INR) is usually elevated due to impaired production of coagulation factors by the inflamed liver. In a study including 121 patients with severe alcohol-associated hepatitis, the median INR at baseline was 2.1 (range 1.3 to 6.4) [17].

●White blood cell count – Patients may have elevated white blood cell count (>12,000 cells/microL) that is not related to infection [16,18]. In a study of 174 patients with alcohol-associated hepatitis, the mean white blood cell count was 11,000 cells/microL [16]. The majority of the white blood cells are neutrophils, which are also commonly seen in liver biopsies from patients with alcohol-associated hepatitis, suggesting that these cells may play an important role in the pathogenesis of liver injury. (See "Pathogenesis of alcohol-associated liver disease".)

Rarely, extremely high white blood cell counts (>50,000 cells/microL, also referred to as a leukemoid reaction) are seen and are associated with an increased risk of mortality [19-21].

●Hemolysis – Zieve syndrome is a condition characterized by a triad of hemolytic anemia, cholestatic jaundice, and hyperlipidemia in the setting of heavy alcohol use, typically following an episode of acutely increased alcohol consumption [22,23].

●Other hematologic testing – Macrocytosis suggests longstanding disease and may reflect poor nutritional status, cobalamin or folate deficiency, alcohol toxicity, and/or increased lipid deposition on red cell membranes. Similarly, thrombocytopenia can result from primary bone marrow hypoplasia (which can be due to alcohol) and/or splenic sequestration due to portal hypertension and an enlarged spleen ("hypersplenism").

Other laboratory test abnormalities — Patients with alcohol-associated hepatitis may develop acute kidney injury and thus may have elevated creatinine. (See "Hepatorenal syndrome: Clinical presentation and diagnosis".)

Acute phase reactants such as ferritin and alpha 1-antitrypsin may be elevated in patients with severe alcohol-associated hepatitis [24,25]. (See "Hepatorenal syndrome: Clinical presentation and diagnosis", section on 'Clinical presentation' and "Acute phase reactants".)

Some patients with alcohol-associated hepatitis and liver impairment may have low ceruloplasmin because of impaired liver synthetic function. The evaluation of low ceruloplasmin and the diagnostic evaluation for Wilson disease are discussed separately. (See "Wilson disease: Clinical manifestations, diagnosis, and natural history".)

DIAGNOSTIC EVALUATION

When to suspect acute alcohol-associated hepatitis — Alcohol-associated hepatitis may be suspected in patients with a history of heavy alcohol use who present with jaundice and elevated serum aminotransferases and total bilirubin. The threshold of ongoing alcohol use leading to acute hepatitis has been defined as consuming >280 g of alcohol per week for females and >420 g per week for males (table 1) [1,3]. One standard drink contains 14 g of alcohol (figure 1).

Initial evaluation

History and physical examination — History taking includes the following:

●Assess symptoms – We ask patients to describe the onset, duration, and type of symptoms (eg, jaundice, abdominal pain, fever).

●Establish extent of alcohol consumption – We ask patients to describe the type of alcohol consumed, in addition to the amount, pattern, and duration of use. Obtaining an accurate alcohol history in patients with suspected alcohol-associated hepatitis may be limited since some patients may not readily admit to harmful alcohol use. In some cases, speaking with the patient's caregivers may help in obtaining a more accurate history. The approach to screening for alcohol use disorder is discussed separately. (See "Screening for unhealthy use of alcohol and other drugs in primary care".)

●Screen for other causes of acute hepatitis – We assess risk factors for other causes of acute hepatitis (eg, exposure to viral hepatitis, episodes of hypotension)

●Assess medication use – We ask patients about prescription and nonprescription medications including herbal supplements to assess the potential contribution and risk of drug-induced liver injury (eg, acetaminophen use). (See "Drug-induced liver injury".)

The physical examination includes assessing for hepatomegaly, for stigmata of chronic liver disease (eg, ascites, splenomegaly), and for extrahepatic manifestations such as skeletal muscle wasting or micronutrient deficiencies related to alcohol use disorder (table 2). (See "Overview of the risks and benefits of alcohol consumption".)

Laboratory studies — We measure the following laboratory studies to assess liver inflammation and function and to assess for substance use:

●Liver tests – Aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), alkaline phosphatase, total bilirubin, gamma-glutamyl transpeptidase (GGT).

●Serum albumin.

●Serum lipid profile.

●Coagulation studies – Prothrombin time/international normalized ratio (INR).

●Complete blood count with platelets.

●Urine drug testing. (See "Urine drug testing".)

●Serum phosphatidylethanol (PEth) level (a serum marker for detecting chronic alcohol use) if underreporting of alcohol consumption is suspected [26].

We obtain the following tests to evaluate for other causes of acute hepatitis [1]:

●Serum acetaminophen levels.

●Testing for viral hepatitis:

•Serum immunoglobulin (Ig) M anti-hepatitis A virus.

•Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc). (See "Hepatitis B virus: Screening and diagnosis in adults".)

In patients with positive HBsAg, we measure anti-hepatitis delta virus (HDV) antibody, and HDV RNA level by reverse transcription polymerase chain reaction if anti-HDV antibodies are present.

•Anti-hepatitis C virus antibody with reflex to hepatitis C viral RNA. (See "Screening and diagnosis of chronic hepatitis C virus infection".)

●Autoimmune markers (if clinical or laboratory features suggest autoimmune liver disease) - Antinuclear antibody, anti-smooth muscle antibody, IgG levels. (See "Overview of autoimmune hepatitis".)

Diagnostic imaging — We obtain transabdominal ultrasound with Doppler study to evaluate for other causes of jaundice (eg, biliary obstruction). Transabdominal ultrasound usually shows diffuse hyperechoic liver texture that reflects intracellular accumulation of fat inclusions and shows hepatomegaly [27]. Signs of portal hypertension (eg, ascites) may be seen but are not specific for alcohol-associated hepatitis.

Because alcohol-associated hepatitis may occur in patients with chronic liver disease, abdominal imaging may show liver steatosis or cirrhosis, with or without complications such as ascites. Doppler flow studies of the hepatic artery may reveal an elevated peak systolic velocity or an increase in vessel diameter [28].

Liver biopsy

Limited indications — Clinical, laboratory, and imaging findings are often adequate to establish a diagnosis of acute alcohol-associated hepatitis. Thus, we reserve liver biopsy for patients with suspected alcohol-associated hepatitis if the diagnosis remains uncertain despite laboratory and imaging tests or if an alternative etiology is suspected [29]. As examples, we may obtain liver biopsy in patients with suspected alcohol-associated hepatitis and any of the following [1]:

●Atypical laboratory findings including positive autoimmune markers (positive ANA >1:160 or anti-smooth muscle antibody >1:80).  

●Unclear alcohol use assessment (eg, patient denies heavy alcohol use).

●Risk factor(s) for ischemic hepatitis (eg, recent or ongoing hypotensive episodes or hemodynamic instability; cocaine use within seven days) in addition to liver enzymes that do not improve within 24 to 72 hours.

Liver biopsy is typically performed using a transjugular approach because such patients may be at increased risk for biopsy-related adverse events (eg, bleeding). (See 'Differential diagnosis' below and "Transjugular liver biopsy".)

Histologic findings — A histologic diagnosis of alcohol-associated hepatitis requires the presence of liver steatosis (usually macrovesicular) in addition to at least one of the following (picture 1 and picture 2) [30,31] (see "Pathogenesis of alcohol-associated liver disease"):

●Hepatocellular injury (ballooning with cytoplasmic rarefaction).

●Neutrophilic infiltration (neutrophils are less common in other causes of acute hepatitis such as viral hepatitis).

●Granulocytic demarcation of hepatocytes by Mallory-Denk bodies.

Mallory-Denk bodies are eosinophilic accumulations of intracellular protein aggregates within the cytoplasm of hepatocytes (picture 2) [31]. They represent condensations of intracellular "intermediate filaments" or cytokeratins, which are normal components of the hepatocyte cytoskeleton. The mechanisms underlying Mallory-Denk body formation in alcohol-associated hepatitis are unclear. Furthermore, they are not specific for alcohol-associated hepatitis and can be seen in metabolic dysfunction-associated steatohepatitis (MASH), malnutrition, after bariatric surgery (eg, jejunoileal bypass), or drug toxicity (eg, amiodarone). (See "Clinical features and diagnosis of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults" and "Drug-induced liver injury".)

Mallory-Denk bodies do not appear to have a pathogenic role in liver injury. However, their presence is an important marker of alcohol-induced injury. As an example, in a large cohort study, Mallory-Denk bodies were detected in 76 percent of patients with alcohol-associated hepatitis and 95 percent of patients who also had cirrhosis [32].

Other findings may include:

●Fibrosis with a perivenular, perisinusoidal, and pericellular distribution. In the early stages, the inflammatory changes affect the perivenular regions (zone 3) (figure 2). However, as the disease progresses, the histologic changes may extend to the portal tracts.

●Intracanalicular cholestasis.

●Bile duct proliferation.

A histologic scoring system has been developed to stratify disease severity based on pathology and to assess prognosis [33]. (See "Histologic scoring systems for chronic liver disease".)

Establishing the diagnosis — The diagnosis of acute alcohol-associated hepatitis is often established by clinical, laboratory, and imaging features in patients with the onset of jaundice within the previous eight weeks in addition to the following [1,34]:

●Alcohol use and pattern:

•Harmful alcohol use (>280 g per week for females and >420 g per week for males (figure 1)) usually for at least six months but often for more than five years, although alcohol use may be intermittent.

•Less than 60 days of abstinence before the onset of jaundice.

●Laboratory criteria:

•Aspartate aminotransferase (AST) >50 units/L.

•AST and alanine aminotransferase (ALT) both <400 units/L.

•AST:ALT ratio ≥1.5:1.

•Serum bilirubin (total) >3 mg/dL (51 micromol/L).

●Imaging - Liver imaging excludes other causes of jaundice such as biliary obstruction.

We typically reserve diagnostic liver biopsy with histologic evaluation for patients with suspected alcohol-associated hepatitis when the diagnosis remains uncertain despite clinical, laboratory, and imaging findings.

Assessing the severity of alcohol-associated hepatitis is discussed below. (See 'Post-diagnosis evaluation' below.)

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of acute alcohol-associated hepatitis is broad and includes other causes of acute hepatitis, jaundice, and elevated liver enzymes [35]:

●Acute viral hepatitis – Acute viral hepatitis (eg, hepatitis A virus infection, hepatitis B virus (HBV) infection, or hepatitis C virus infection) or an acute exacerbation of chronic HBV infection can be distinguished from alcohol-associated hepatitis by obtaining viral hepatitis serologies. (See 'Laboratory studies' above.)

●Autoimmune hepatitis – Criteria for autoimmune hepatitis include at least one elevated aminotransferase and at least one positive serologic marker (eg, antinuclear antibodies [ANA], anti-smooth muscle antibodies [ASMA] at a titer of at least 1:40) or increased total IgG or gamma-globulin levels. (See "Overview of autoimmune hepatitis", section on 'Diagnosis'.).

●Biliary obstruction – Patients with biliary obstruction usually present with right upper quadrant pain and liver enzymes in a cholestatic pattern (compared with the AST and ALT, there is disproportionate elevation of the alkaline phosphatase, gamma-glutamyl transferase, and bilirubin). Imaging with transabdominal ultrasound can evaluate for bile duct stones, dilated common bile duct, or obstructing lesions. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management".)

●Budd-Chiari syndrome – Budd-Chiari syndrome is usually related to hepatic vein thrombosis in patients with prothrombotic risk factors. The diagnosis can usually be excluded with transabdominal ultrasound with Doppler study. (See "Budd-Chiari syndrome: Epidemiology, clinical manifestations, and diagnosis".)

●Drug-induced liver injury – Common medications that have been associated with acute hepatitis include acetaminophen and some antibiotics. A searchable database of drugs associated with drug-induced liver injury is available. (See "Drug-induced liver injury".)

●Ischemic hepatitis – Patients with ischemic hepatitis have recent or ongoing hypotension and/or hemodynamic instability that may be related to sepsis, severe gastrointestinal bleeding, myocardial infarction, or recent cocaine use. The characteristic pattern of liver biochemistries consists of a rapid rise in serum aminotransferase levels. Peak aminotransferase levels are typically at least 25 times the upper limit of normal and are reached within one to three days of the hemodynamic insult. (See "Ischemic hepatitis, hepatic infarction, and ischemic cholangiopathy", section on 'Ischemic hepatitis (shock liver, hypoxic hepatitis)'.)

●Wilson disease – Patients with symptomatic Wilson disease may have elevated liver enzymes in addition to signs of copper overload (eg, Kayser-Fleischer rings, neurocognitive involvement) and a family history of Wilson disease. (See "Wilson disease: Clinical manifestations, diagnosis, and natural history".)

Some causes of acute hepatitis (eg, viral hepatitis, ischemic hepatitis, drug-induced liver injury) are often associated with aminotransferases greater than 10 times the upper limit of normal with an AST to ALT ratio of <2 (and often <1). Thus, aminotransferase concentrations >400 units/L should raise suspicion for liver injury due to a nonalcohol source [36].

The evaluation of abnormal liver biochemical tests is discussed in more detail elsewhere. (See "Approach to the patient with abnormal liver tests".)

POST-DIAGNOSIS EVALUATION

Assess disease severity — We assess the severity of alcohol-associated hepatitis by calculating the original Model for End-stage Liver Disease (MELD) score. (See "Model for End-stage Liver Disease (MELD)".)

Another scoring system for stratifying illness is the Maddrey discriminant function (DF) (calculator 1). Severe alcohol-associated hepatitis is typically defined by MELD score >20 or by DF ≥32 [37]. Severity of illness informs management, and this is discussed separately. (See "Management and prognosis of alcoholic hepatitis".)

Evaluate for liver fibrosis — We evaluate patients who have alcohol-associated liver disease (including alcohol-associated hepatitis) for liver fibrosis. For selected patients, we obtain a noninvasive study after the acute episode of alcohol-associated hepatitis has resolved and after at least six weeks of abstinence from alcohol [38]. Specifically, we obtain ultrasound-based transient elastography in patients who did not require a liver biopsy to establish a diagnosis of alcohol-associated hepatitis, who do not have a history of portal hypertension (eg, esophageal varices), and who do not have cirrhosis by imaging.  

If the liver stiffness measured by ultrasound-based elastography suggests advanced fibrosis or cirrhosis, further management includes screening for complications of cirrhosis (eg, hepatocellular carcinoma). (See "Cirrhosis in adults: Overview of complications, general management, and prognosis" and "Noninvasive assessment of hepatic fibrosis: Ultrasound-based elastography".)

When evaluating for liver fibrosis, we reserve liver biopsy for those with inconclusive findings on noninvasive testing.

Limitations of elastography in this setting include that cutoff values for diagnosing advanced fibrosis vary among studies and that liver stiffness measurements may be increased because of recent liver inflammation or may be decreased because of alcohol withdrawal/abstinence [38,39].  

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Alcohol-associated liver disease".)

SUMMARY AND RECOMMENDATIONS

●Background – Liver disease related to alcohol use ranges from acute liver inflammation (ie, alcohol-associated hepatitis) to chronic diseases including steatosis alone (fatty changes), advanced fibrosis, and ultimately cirrhosis.

The term alcohol-associated hepatitis refers to the recent onset of symptomatic hepatitis, characterized by jaundice and elevated liver biochemistries. Most patients with alcohol-associated hepatitis have a history of ongoing harmful alcohol use (ie, >280 g per week for females and >420 g per week for males) (table 1). One standard drink contains 14 g of alcohol (figure 1). (See 'Introduction' above and 'When to suspect acute alcohol-associated hepatitis' above.)

●Clinical features – Patients with alcohol-associated hepatitis present with jaundice, and may have anorexia, fever, and tender hepatomegaly. Patients may report right upper quadrant or epigastric pain and may have signs of hepatic encephalopathy and undernutrition. (See 'Clinical features' above.)

The classic laboratory pattern is moderately elevated aminotransferases, with an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio of ≥1.5:1.

●Diagnosis – The diagnosis of alcohol-associated hepatitis is established by clinical, laboratory, and imaging features in patients with jaundice and the following (see 'Diagnostic evaluation' above):

•Ongoing harmful alcohol use with less than 60 days of abstinence before the onset of jaundice (table 1).

•Laboratory criteria:

-Moderately elevated AST and ALT (ie, <400 units/L).

-AST >50 units/L, with AST:ALT ratio ≥1.5:1.

-Serum bilirubin (total) >3 mg/dL (51 micromol/L).

•Imaging – Liver imaging excludes other causes of jaundice (eg, biliary obstruction).

We typically reserve diagnostic liver biopsy for patients with suspected acute alcohol-associated hepatitis when the diagnosis remains uncertain despite laboratory and imaging tests.

●Post-diagnosis evaluation

•Assess disease severity – We assess the severity of alcohol-associated hepatitis by calculating the original MELD score. Another scoring system for stratifying illness is the Maddrey discriminant function (DF) (calculator 1).

Severe alcohol-associated hepatitis is typically defined by MELD score >20 or DF ≥32. (See "Management and prognosis of alcoholic hepatitis".)

•Evaluate for fibrosis – We evaluate for liver fibrosis using noninvasive testing in selected patients (ie, those who did not require a liver biopsy to establish the diagnosis, who do not have signs of portal hypertension, and who do not have cirrhosis by imaging). We obtain ultrasound-based transient elastography after the episode of acute alcohol-associated hepatitis has resolved and after at least six weeks of abstinence from alcohol.

If the liver stiffness measured by ultrasound-based elastography suggests advanced fibrosis or cirrhosis, further management includes evaluating for complications of cirrhosis (eg, hepatocellular carcinoma). (See "Cirrhosis in adults: Overview of complications, general management, and prognosis".)