What is steatohepatitis?

What is Steatohepatitis?

Steatohepatitis is a liver condition characterized by the presence of ≥5% hepatic fat accumulation (steatosis) combined with inflammation and hepatocyte injury (ballooning degeneration), with or without fibrosis. 1

Core Pathological Features

Steatohepatitis represents an advanced, inflammatory form of fatty liver disease that includes three essential histological components:

• Steatosis: Predominantly macrovesicular fat accumulation exceeding 5% of liver weight 1
• Inflammation: Inflammatory cell infiltration, primarily polymorphonuclear leukocytes in the alcoholic form 1, or lobular inflammation in the non-alcoholic form 1
• Hepatocyte injury: Ballooning degeneration of hepatocytes, which distinguishes steatohepatitis from simple steatosis 1
• Variable fibrosis: May be present but is not required for diagnosis, though it indicates disease progression 1

Clinical Context and Types

Steatohepatitis occurs in two main forms based on alcohol consumption:

Alcoholic Steatohepatitis

• Develops in patients with significant alcohol consumption (>210 g/week in men, >140 g/week in women) 1
• Represents a necessary step in progression to alcoholic liver fibrosis and cirrhosis 1
• Severity determined by environmental factors including alcohol quantity, lifestyle, and dietary habits 1

Nonalcoholic Steatohepatitis (NASH)

• Occurs in patients without significant alcohol consumption 1
• Affects 3-6% of the US population, with 25-30% of NAFLD patients progressing to NASH 2, 3
• Strongly associated with metabolic risk factors: obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome 2

Clinical Significance and Prognosis

The key clinical importance of steatohepatitis is its potential for progression to cirrhosis, liver failure, and hepatocellular carcinoma, unlike simple steatosis which typically remains benign. 1

• Approximately 20% of NASH patients will develop cirrhosis 2
• Liver-related mortality in biopsy-proven NASH reaches 25.6 per 1,000 person-years 4
• Fibrosis stage is the strongest predictor of mortality 4
• NASH is predicted to become the leading indication for liver transplantation in the United States 2

Pathophysiological Mechanisms

The development of steatohepatitis involves multiple pathogenic "hits" beyond simple fat accumulation:

• Lipotoxicity and oxidative stress: Oxygen free radical production, lipid peroxidation, and mitochondrial dysfunction 1, 5
• Acetaldehyde toxicity (in alcoholic form): Combines with proteins and DNA, acts as auto-antigen, causes mitochondrial damage 1
• Pro-inflammatory cytokines: TNF-α, IL-17, and chemokines activate inflammatory pathways (NF-κB, STAT-JAK, JNK) 1
• Endotoxin-mediated inflammation: Increased intestinal permeability leads to lipopolysaccharide activation of Kupffer cells via TLR4 pathway 1
• Dietary cholesterol: Modified plasma lipoproteins can drive hepatic inflammation independent of steatosis severity 6

Diagnostic Considerations

• Liver biopsy remains the gold standard for definitive diagnosis of steatohepatitis 2
• Patients are frequently asymptomatic or have nonspecific symptoms (fatigue) until advanced disease develops 1
• Ultrasound shows increased liver echogenicity with sensitivity of 84.8% and specificity of 93.6% for moderate-to-severe steatosis, but cannot distinguish steatohepatitis from simple steatosis 3
• AST:ALT ratio helps differentiate causes, with higher ratios suggesting alcoholic etiology 3