Chronic active hepatitis describes any progressive inflammatory process within the liver. It is a histopathologic diagnosis in which there is evidence of sustained, aggressive, chronic liver disease. The histologic diagnosis is often cholangiohepatitis, because the inflammatory response is mainly in the periportal areas.
The exact etiology of chronic active hepatitis is not known. Infectious, immune-mediated, or toxic processes are thought to be involved. The early stages are associated with inflammation of the bile ducts and portal areas of the liver. Extension of bacterial infection through the bile duct or portal venous drainage may be responsible for the lesions in animals with suppurative cholangiohepatitis. When lymphocytes and plasma cells predominate in the cellular infiltrate, an immune-mediated process is more likely. Many causes of acute hepatic failure can progress to chronic active hepatitis.
The predominant clinical signs of chronic active hepatitis are weight loss, anorexia, depression, and lethargy. Icterus, behavioral changes, diarrhea, photosensitization, and hemorrhage are variably present. Fever may be persistent or intermittent, depending on the degree of cholangiohepatitis and fibrosis present. Dermatitis of the coronary band with regional sloughing of skin may develop. Recent or concurrent abdominal disease is often reported. Duration of clinical signs is variable, extending over days to months. Neurologic signs may seem to appear abruptly, even though there is histologic evidence of chronic disease. Alkaline phosphatase and γ-glutamyl transpeptidase or transferase (GGT) are moderately increased, as are sorbitol dehydrogenase (SDH) and glutamate dehydrogenase, which indicates ongoing hepatocyte damage. In chronic cases with marked hepatic fibrosis, enzyme activity may be normal, and BUN and albumin concentrations may be decreased. Serum total protein is either increased or normal. Globulins are usually increased. Serum total bile acid concentration is increased, and BSP® clearance prolonged. Cholestasis may cause hyperbilirubinemia, with >25% of total bilirubin being direct. With diminishing hepatic function, serum glucose and coagulation factors decrease, and one-stage prothrombin time and activated partial thromboplastin time become prolonged. Blood ammonia concentrations may be increased. There may be a neutrophilia or neutropenia with a left shift if endotoxemia develops. Anorexia can lead to hypokalemia. Ultrasonography generally reveals increased echogenicity in the liver, indicative of hepatic fibrosis. The liver may be smaller than normal, so much so it may be difficult to identify on ultrasonography.
Grossly, the liver is firm, pale brown to green in color, and often small. Irregular markings may be seen on the cut surface. Histologic lesions are predominantly in the periportal areas. Inflammatory cell infiltration may consist primarily of mononuclear cells, neutrophils with bacteria (often coliforms), or lymphocytes and plasma cells. The character of the infiltrate may indicate the nature of the primary disease process. Biliary hyperplasia may be marked if there is cholangiohepatitis. Variable degrees of necrosis and fibrosis are present.
Histologic examination of a liver biopsy is needed for a definitive diagnosis. The tissue should also be cultured, although in most cases significant isolates are not identified.
Supportive care should be provided, including fluid therapy with potassium chloride, glucose, and vitamin supplementation; dietary management (a diet low in protein and high in branched-chain amino acids and carbohydrates); and prevention of exposure to the sun if photodermatitis is present.
Corticosteroid therapy has been used successfully in horses with a lymphocytic-plasmacytic infiltrate on liver biopsy. Reportedly, steroids act to enhance appetite, stabilize cell membranes, and reduce inflammation and connective tissue formation. Different therapeutic regimens using prednisolone and dexamethasone have been recommended. One recommended regimen involves initial administration of dexamethasone at 0.04–0.08 mg/kg for 4–7 days, followed by a gradual reduction in dosage over 2–3 wk depending on response to therapy. Prednisolone (0.5–1 mg/kg/day, PO) may be required for an additional 2–4 wk. The risk of inducing laminitis or abortion in pregnant animals with corticosteroids must be discussed with the owner before initiating therapy. Alternatively, an antifibrotic agent, colchicine (0.03 mg/kg/day, PO), has been recommended, but its efficacy in hepatic failure and safety in pregnant animals is unproved. Possible adverse reactions to colchicine in horses include laminitis, diarrhea, and rarely bone marrow suppression affecting all cell lines. Malaise, vomiting, diarrhea, abdominal pain, myopathy, alopecia, and bone marrow suppression have been reported in people and other species. Other drugs recommended for arresting or slowing fibrosis include pentoxifylline (7.5 mg/kg, PO, bid) and SAMe (5 g/day, PO). In cases complicated with septic cholangiohepatitis, broad-spectrum antimicrobials are indicated. Ideally, antimicrobial therapy should be based on bacterial culture and sensitivity from the biopsy specimen.
Prognosis is variable and is best based on liver biopsy and response to therapy. Prognosis is fair to good in animals with less severe lesions, especially those with a lymphocytic-plasmacytic cellular infiltrate that responds well to corticosteroid therapy; however, it is poor in horses with hepatic failure, widespread fibrosis (or severe bridging fibrosis), and disruption of normal hepatic parenchyma.