A 52-year-old man with 15 years of alcohol use disorder presents with ascites, spider angiomas, and hepatomegaly. Liver biopsy shows bridging fibrosis with regenerative nodules. Which single feature best distinguishes alcoholic cirrhosis from viral hepatitis C-induced cirrhosis?

## Alcoholic Cirrhosis vs Hepatitis C Cirrhosis: Key Discriminators ### Alcoholic Cirrhosis **Key Point:** The **pathognomonic feature** of alcoholic liver disease is the presence of **Mallory-Denk bodies** (also called Mallory hyaline) with **acute neutrophilic inflammation**. - Mallory-Denk bodies are aggregates of ubiquitinated proteins (keratin 8/18, ubiquitin) - Appear as eosinophilic, rope-like inclusions in hepatocytes - Surrounded by neutrophilic infiltration (neutrophils attacking damaged hepatocytes) - Steatosis (macrovesicular) is prominent in early-to-mid stages - Micronodular cirrhosis pattern (nodules <3 mm) is typical - Iron deposition is variable and not a discriminating feature ### Hepatitis C Cirrhosis **Key Point:** HCV-induced cirrhosis shows **lymphoid aggregates/follicles** and **bile duct proliferation** without Mallory-Denk bodies. - Chronic lymphocytic infiltration in portal tracts - Lymphoid follicles with germinal centers (B-cell aggregates) - Bile duct proliferation and ductular reaction - Steatosis may be present but is less prominent than in alcoholic disease - Macronodular or mixed nodular pattern - No characteristic acute neutrophilic inflammation ### Comparative Table | Feature | Alcoholic Cirrhosis | HCV Cirrhosis | | --- | --- | --- | | **Mallory-Denk bodies** | Present (pathognomonic) | Absent | | **Neutrophilic inflammation** | Prominent | Minimal | | **Lymphoid aggregates** | Absent/rare | Present (follicles) | | **Bile duct proliferation** | Minimal | Prominent | | **Steatosis** | Marked macrovesicular | Mild-moderate | | **Nodule pattern** | Micronodular | Macro- or mixed | | **Iron deposition** | Variable | Variable | **High-Yield:** Mallory-Denk bodies + neutrophilic infiltration = alcoholic liver disease. This combination is virtually diagnostic and absent in HCV cirrhosis. **Mnemonic:** **MALD** = **M**allory-Denk bodies + **A**lcoholic liver disease + **L**iver damage + **D**amage from ethanol. **Clinical Pearl:** Mallory-Denk bodies can also be seen in Wilson disease, non-alcoholic fatty liver disease (NAFLD), and primary biliary cholangitis, but the combination with acute neutrophilic inflammation and clinical history of alcohol use strongly favors alcoholic cirrhosis.