Alcoholic hepatitis

Did You Know?

• Females are more susceptible to alcohol-associated liver injury and are at higher risk of alcoholic hepatitis.
• Genetic variations in the PNPLA3-encoding gene are thought to influence disease severity.
• Infection risk in alcoholic hepatitis is 12–26%, rising to 50% with corticosteroid use.

Signs and symptoms

Alcoholic hepatitis may present with feeling unwell, liver enlargement, ascites, and modestly elevated liver enzymes. Hepatic encephalopathy can cause confusion, decreased consciousness, or asterixis. Severe cases show acute jaundice, obtundation, and progressive critical illness. Patients may also exhibit alcohol withdrawal symptoms such as tremors, tachycardia, or seizures upon abstinence. Long-term alcohol effects like Dupuytren contraction and temporal muscle wasting can appear. Alcoholic hepatitis is distinct from cirrhosis, though both may coexist; cirrhosis stigmata include jaundice, palmar erythema, and spider angiomata. Some alcoholics develop acute hepatitis as an inflammatory reaction to fatty change, termed alcoholic steatohepatitis, which may predispose to fibrosis via hepatic stellate cell activation.

Pathophysiology

The mechanisms are incompletely understood but involve direct hepatocyte damage from alcohol and its metabolites, plus increased intestinal permeability. Heavy alcohol consumption damages enterocytes and tight junctions, allowing gut bacteria like Enterococcus faecalis or immunogenic fungi to enter the portal circulation and reach the liver. Enterococcus faecalis releases an exotoxin directly damaging liver cells. Chronic alcohol use alters the gut microbiome, promoting pathogenic bacteria that carry Pathogen Associated Molecular Patterns (PAMPs), triggering an exaggerated inflammatory response. Alcohol is metabolized to acetaldehyde via CYP2E1 and aldehyde dehydrogenase, generating reactive oxygen species and DNA adducts, leading to lipid peroxidation, mitochondrial damage, and glutathione depletion. Damaged hepatocytes release Danger Associated Molecular Patterns (DAMPs), further activating inflammation. Chronic inflammation causes a distinctive fibrotic response with peri-cellular 'chickenwire fibrosis', leading to portal hypertension and sequelae such as esophageal varices, ascites, and splenomegaly.

Diagnosis

Diagnosis is largely clinical, categorized as definite, probable, or possible. Definite cases require clinical criteria plus confirmatory liver biopsy. Probable cases meet criteria without confounding factors; possible cases have confounding factors like unclear alcohol history, conflicting labs, or comorbidities such as drug-induced liver injury or viral hepatitis. Clinical suspicion arises in patients with significant chronic alcohol intake, worsening liver function tests, and jaundice within 8 weeks. Inclusion criteria include ≥6 months of continued alcohol intake (>40 g/day for females, >60 g/day for males) and jaundice within 60 days of abstinence. Initial workup includes liver function tests (elevated total bilirubin >3.0 mg/dL, aminotransferases <400 IU/L, AST:ALT ratio ≥2), complete blood count (leukocytosis, thrombocytosis, thrombocytopenia, macrocytic anemia), basic metabolic panel (to assess acute kidney injury or hepatorenal syndrome), and right upper quadrant ultrasound (to detect hepatic steatosis, hepatomegaly, cirrhosis, and rule out gallstones or hepatocellular carcinoma).

Management

Management aims to stabilize acute-on-chronic liver injury. The most important intervention is encouraging alcohol discontinuation to prevent progression to cirrhosis or hepatocellular carcinoma. Patients should be monitored for alcohol withdrawal syndrome using CIWA-Ar screening and managed with long- or short-acting benzodiazepines as appropriate. Counseling services should be offered to prevent relapse. Chronic alcohol users are at risk for malnutrition; a thorough history and physical exam, plus dietician support, are recommended. Improved nutrition enhances liver function and reduces encephalopathy and infections. Current guidelines recommend daily intake of 1.2–1.5 g/kg protein and 35–40 kcal/kg calories.