Chapter 38 CHRONIC NON-VIRAL HEPATITIS
INTRODUCTION
Definition
Chronic non-viral hepatitis is a disease of the liver characterised by chronic inflammation and liver cell necrosis, that is due to non-viral causes and which persists without improvement for at least 6 months. However, in autoimmune hepatitis, the 6- month requirement is no longer required to establish chronicity as the condition may present acutely. Also, drug or toxin-induced liver disease is sometimes considered a chronic disease when the duration of liver inflammation extends beyond 3 months.
CAUSES
The causes of non-viral chronic hepatitis are listed in Table 38.1. The principal cause is autoimmune hepatitis. Less common causes include drug-induced hepatitis and cryptogenic hepatitis. The hereditary metabolic liver diseases, Wilson’s disease and alpha1-antitrypsin deficiency, may also cause a chronic hepatitis-like picture. Diseases mimicking chronic hepatitis include non-alcoholic steatohepatitis, sclerosing cholangitis and primary biliary cirrhosis.
Cause | Specific histology |
---|---|
Autoimmune hepatitis | Interface and lobular hepatitis, plasma cell and lymphocytic infiltrate, rosette formation, bridging and confluent necrosis |
Drugs and toxins | Similar to chronic viral hepatitis; may be autoimmune hepatitis-like; ± eosinophils; ± granulomas |
Cryptogenic | Similar to autoimmune hepatitis |
Wilson’s disease | Copper deposits |
Alpha1-antitrypsin deficiency | Eosinophilic globules in periportal zones |
Autoimmune hepatitis
Autoimmune hepatitis (AIH) accounts for about 20% of cases of chronic hepatitis. The disease has a female preponderance, affects all ages and has a worldwide distribution. There is a genetic association with the human leucocyte antigens B8, DR3 and DR4. The cause of AIH is unknown. Autoantibodies including antinuclear antibody (ANA) and anti-smooth muscle antibody (SMA) are very common but not specific for the disease or of pathogenetic significance. At least two types of AIH are recognised.
Drug-induced hepatitis
Drugs associated with inducing hepatitis are listed in Table 38.2. For more information on drug-induced hepatotoxicity, see Chapter 41.
Cryptogenic hepatitis
Around 10%–20% of patients with chronic hepatitis have no definable cause and are classified as cryptogenic hepatitis. It is a diagnosis of exclusion. It may be due to an unknown virus, burnt-out non-alcoholic steatohepatitis or an autoimmune process. The condition may clinically resemble type 1 AIH in age and sex distribution, necroinflammatory activity, HLA status and response to therapy.
CLINICAL FEATURES
Autoimmune hepatitis
The clinical features of severe AIH are shown in Table 38.3. An acute onset is observed in about 25% of patients. Fulminant hepatitis occurs rarely. Common extrahepatic associations are autoimmune thyroid disease, ulcerative colitis and synovitis.
Clinical features at presentation | Frequency (%) |
Symptoms | |
• Fatigue and loss of energy | 85 |
• Dark urine and/or light stools | 77 |
• Abdominal pain/discomfort | 48 |
• Anorexia, nausea | 30 |
• Pruritus | 36 |
• Polymyalgias | 30 |
• Diarrhoea | 28 |
• Amenorrhoea (women) | 89 |
• Cosmetic changes (facial rounding, hirsutism, acne) | 19 |
Clinical signs | |
• Hepatomegaly | 78 |
• Spider naevi | 58 |
• Palpable spleen | 32–56 |
• Scleral icterus/jaundice | 46 |
• Ascites | 20 |
• Encephalopathy | 16 |