Chronic Active Hepatitis

Jennifer L. Davis

Chronic active hepatitis (CAH) is an idiopathic progressive hepatopathy with insidious onset. The etiology and pathogenesis are unknown but may be similar to human autoimmune or hypersensitivity conditions.

Clinical signs are those of progressive liver failure and include weight loss, depression, anorexia, colic, icterus, and fever.² These signs may be intermittent. Signs of concurrent intra­abdominal diseases or other autoimmune diseases may also be present. In rare cases, a moist exfoliative coronary dermatitis may occur, which is thought to be an immune-mediated issue.³ Concurrent elevations in hepatic enzymes, particularly GGT and ALP, will be present, with lesser elevations in SDH and AST as well as bile acids and direct bilirubin. The degree of elevation in liver enzymes cannot be used as an indicator of disease severity, since the liver may have significant fibrosis at the time of diagnosis. Other supportive clinicopathologic findings include an inflammatory leukogram, bilirubinuria, prolonged BSP clearance, and a polyclonal gammopathy. Ultrasonography may reveal a small liver with increased echogenicity indicative of hepatic fibrosis. Differential diagnosis includes pyrrolizidine alkaloid toxicity, bile stones, abdominal abscesses, and other chronic wasting diseases.

The final diagnosis of chronic active hepatitis is made histologically via biopsy of the liver or at necropsy. The principal features are localized primarily along the portal or periportal areas and include infiltration of inflammatory cells, biliary hyperplasia, and fibrosis or cirrhosis.¹ A mononuclear cell infiltrate (lymphocytes or plasmacytes) often predominates, but a neutrophilic component may be present with a primary or secondary infectious process.

Treatment of CAH involves supportive care. Specific treat­ments can be determined based on biopsy results. If the predomi­nant cell types are lymphocytes or plasma cells, corticosteroids may be beneficial. Dexamethasone (0.05 to 0.1 mg/kg/day IV or IM decreased over 2 to 3 weeks) or prednisolone (1 mg/ kg/day PO for several weeks) is recommended. Antibiotics are indicated when a bacterial cholangiohepatitis is suspected on the basis of the histologic features of the liver, culture of the liver biopsy, and presence of a persistent intermittent fever. Other recommended therapies are aimed at resolving inflammation and preventing the progression of fibrosis. Flunixin (0.5 to 1 mg/kg PO q24h) or low-dose phenylbutazone (0.5 g/day PO q24h) can be used. Vitamin E (10,000 U PO q24h) is recommended to protect membrane phospholipids from oxidative damage and suppresses activation of inflammatory cells. Pentoxifylline (8 to 10 mg/kg PO q12h) has been used as a weak inhibitor of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin 6 (IL-6), although results are variable, possibly owing to the low oral bioavailability in horses. Colchicine (0.03 mg/kg PO q24h) can be used to inhibit production of collagen and macrophage- or cytokine-induced inflammation.

The prognosis for CAH is variable and depends on the underlying cause and duration of disease prior to diagnosis. A retrospective study reported that five of nine horses with CAH survived, but they were 7.4 times more likely to die than those where a diagnosis of unclassified hepatopathy was made.¹ Liver biopsy and response to therapy are the best guides in formulating a prognosis. The prognosis for improvement and long-term survival is extremely poor in horses that have functional hepatic failure with widespread fibrosis and disruption of normal hepatic parenchyma. The prognosis is fair to good in patients with early (less severe) lesions, particularly those with a lymphocytic or plasmacytic cellular infiltrate that responds well to corticosteroids. The presence of cirrhosis in the biopsy sample warrants a grave prognosis.