• Hepatic injury associated with inflammation. The inflammation may either be reactive to the injury or may cause it.
• Pathology of Hepatitis:
• Necrosis with minimal inflammation – Toxins, poisons, cytopathic viruses
• Necrosis with extensive lymphocytic inflammation, acidophilic bodies – Viral hepatitis (A, B, C, D, etc)
• Necrosis with extensive lymphocytic inflammation, acidophilic bodies, PMNs, and eosinophils – Drug toxicity
• Necrosis with PMNs, fat, and with or without Mallory bodies – Alcoholic and non-alcoholic hepatitis
• Abscess with PMNs – Bacterial Infection (e.g. staph)
• Granulomatous response with or without caseating necrosis and multinucleated giant cells – Tuberculosis, sarcoidosis, some drugs
• Multinucleated giant cells – Neonatal diseases

Acute Viral Hepatitis - hepatitis viruses A, B, C, D, E, and NANB (non-A non-B) other than C. All are hepatotropic.

• The changes seen in any individual case will depend on the type of virus, host response, severity of infection and passage of time. Most patients with classical acute viral hepatitis recover completely.
• Pathology of Acute Viral Hepatitis:
• Cell plate disarray - due to ballooning degeneration and necrosis of hepatocytes, and mononuclear inflammation.
• Hepatocellular necrosis -
• Spotty hepatocellular necrosis (classic)
• Confluent/bridging necrosis - central-portal bridging, central-central bridging.
• Periportal (piecemeal) necrosis - portal-portal bridging.
• Inflammatory response - Lymphocytes, MΦs, plasma cells, PMNs. Site: portal, periportal, lobular.
• Kupffer cell hypertrophy/hyperplasia - contain ceroid/lipofuscin pigment, iron, etc.
• Cholestasis
• Steatosis
• Viral particles - almost never seen in acute hepatitis, more common in chronic hepatitis.
• Regenerative hepatitis - mitoses, basophilic changes, multinuclear giant cells.
• Histologic Variations in Acute Viral hepatitis:
• Hepatitis A – Intense portal and periportal (zone 1) inflammation with necrosis and plasma cells
• Cholestasis
• Outcome: either resolves or patient dies (0.1% of cases)
• Hepatitis B – Lobular, perivenular inflammation (lymphocytes, Kupffer cell hyperplasia)
• "Ground-glass" hepatocytes indicate chronic disease
• Coinfection/superinfection with Hepatitis D encourages chronicity and enhances severity
• Outcome: >90% recover, 5% chronic infection, 1-2% fulminant infection (kills). Cirrhosis, and carcinoma.
• Hepatitis C – Polka-dot looking liver
• Macrovesicular steatosis
• Lymphoid aggregates and follicles
• Bile duct injury Þ cholestasis
• Outcome: 50-70% chronic infection, 15-25% cirrhosis with increased risk of carcinoma.
• Hepatitis D – Lymphocytes and plasma cells in portal tracts
• Microvesicular steatosis
• Acidophilic bodies are present
• Few lymphocytes in lobule (opposite Hepatitis B)
• Necrosis and collapse
• Hepatitis E – histologic changes in humans no yet studied
• Fate and morphological sequelae of acute viral hepatitis – many possibilities:
• Resolution - usual outcome of acute viral hepatitis. Residual liver changes may persist after recovery.
• Fatal outcome - hepatic necrosis with or without regeneration.
• Post-hepatic scarring - following confluent/bridging necrosis and multilobular necrosis.
• Carrier state with minimal disease - like Hepatitis B.
• Chronic hepatitis
• Cirrhosis
• Hepatocellular carcinoma
• Pathogenesis of Viral Hepatitis
• Cytopathic Necrosis - Virus directly causes necrosis of hepatocytes. Intense eosinophilic cytoplasmic changes in infected hepatocytes, with acidophilic bodies and few lymphocytes. Seen in Hepatitis D and some forms of NANB Hepatitis.
• Immune Mediated Necrosis - Hepatotoxicity against infected hepatocytes due to host's immunologic response (humoral, cell mediated, or both). Viral Hepatitis A, B, C, and possibly D. (therefore, the stronger the immune response the greater the liver damage).

• Pathogenesis: EtOH has multiple hepatotoxic effects. Both genetic (sex, race, etc.) and environmental factors are associated. For example, alcoholics seem to have an increased incidence of Hepatitis C infection.
• Pathology of Alcoholic Liver Disease:
• No change – <10% cases
• Fatty change – >90% cases
• Alcoholic hepatitis – occasional
• Cirrhosis – 25% cases
• Hepatocellular carcinoma – 5-15% of cirrhotics
• Histologic features of Alcoholic Hepatitis:
• Membrane alterations and peroxidation – may lead to a cytotoxic response by lymphocytes
• Fat accumulation
• Acute injury – fat accumulation due to Ý lipogenesis with Ý synthesis of triglycerides.
• Chronic injury – in addition to the above, failure of secretion of lipoproteins, further increasing the accumulation.
• Fibrosis - Early and constant feature of alcoholic liver disease. The lipocytes (Ito cells) lay down fibrous tissue in a pericellular distribution. Get an increase in procollagen, type IV collagen, fibronectin, and laminin.
• Sclerosing hyaline necrosis - Ballooning degeneration of hepatocytes, abundant Mallory bodies, PMN infiltration with satellitosis, and pericellular fibrosis.
• Mallory bodies - basophilic or eosinophilic cytoplasmic coagulum that usually surrounds nucleus. Contain intermediate filaments. Mechanism of formation unknown. May be chemotactic to PMNs.
• Megamitochondria – enlarged mitochondria. Cigar shaped in periportal hepatocytes and spherical in centrilobular hepatocytes.
• Inflammation – inflammation contributes to the progression of fibrosis and cirrhosis, though it is not a prerequisite. Mononuclear cells are commonly seen. Also PMNs in lobules and protal triads.
• Cirrhosis – Alcoholic hepatitis, sclerosing hyaline necrosis and pericentral sclerosis will progress to cirrhosis.
• Pathogenetic mechanisms in Alcoholic Liver Injury
• Three pathways for EtOH metabolism:
• (1) Alcohol dehydrogenase (ADH) pathway in the cytosol – major pathway
• (2) Microsomal ethanol oxidizing system in the endoplasmic reticulum (MEOS)
• (3) Catalase in peroxisomes – plays a minor role
• note: Excessive alcohol intake results in high concentration of cytoplasmic acetaldehyde which is injurious to the cell membranes. It binds to the membrane phospholipids, and depolymerizes proteins producing altered surface antigens.
• Non-Alcoholic Steatohepatitis
• Hepatic changes as described above can sometimes be seen in:
• Patients that have undergone jejuno-ileal bypass for obesity.
• Middle-aged females with diabetes, obesity, hypertension, and heart disease.