Management of chronic liver disease in dogs (Proceedings)
Antibiotic therapy is indicated for treatment of suppurative hepatitis, cholangiohepatitis and hepatic encephalopathy, and prevention of septicemia. The bactericidal function of the hepatic reticuloendothelial (RE) system may be compromised in hepatic disease, especially if hepatic blood flow or oxygen tension is altered, resulting in septicemia. In hepatic bacterial encephalopathy, antibiotics are used to help reduce colonic bacterial numbers in an effort to decrease ammonia formation. Cholangitis has several causes, including bacterial invasion, which warrants antibiotic therapy. The regimen may be modified in accordance with specific information obtained from cultures of bile, hepatic tissue or blood. In cases of compromised hepatic RE function (e.g. hepatitis from any cause, septicemia) the antibiotics selected generally are directed against intestinal organisms.
Antibiotics routinely used in treatment of patients with liver disease include penicillins (ampicillin 10 mg/lb TID, amoxicillin 10 mg/lb BID), cephalexin (Keflex, Dista) 10 mg/lb TID, enrofloxacin (Baytril) 1.2 - 2.3 mg/lb BID, and metronidazole (Flagyl, Searle) 5-10 mg/lb BID. Chloramphenicol and tetracycline are alternative choices that are effectively excreted in the bile, however, tetracycline is potentially hepatotoxic. Although high hepatic tissue levels are reached with chloramphenicol, the plasma half-life can be prolonged and toxicity may occur in patients with liver disease.Metronidazole is highly active against Bacteroides and other anaerobes that exist in high numbers in the colon. Bacteriologic studies have suggested that gram-negative anaerobes are major generators of ammonia from peptides. Metronidazole's effectiveness against these bacteria could help reduce production of endogenous ammonia, thus benefiting patients with hepatic encephalopathy. It may also be useful in treatment of any liver disorder complicated by inability of the hepatic RE system to clear bacteria absorbed through the portal circulation. The combination of metronidazole and an aminoglycoside may be superior for this purpose. Metronidazole may also be useful in treatment of some chronic inflammatory conditions because it helps reduce cell-mediated immune responses. I sometimes use metronidazole for 2-6 months or longer, in conjunction with maintenance levels of corticosteroids, for liver disease patients that may have both a bacterial and inflammatory component, or that are unable to tolerate required dosage levels of corticosteroids used alone to control the disease. Metronidazole is my routine drug of choice for chronic administration in hepatic encephalopathy patients. It can be used safely in combination with other antibiotics.
Antibiotics that should be avoided in treatment of liver disease include chloramphenicol, lincomycin, sulfonamides, erythromycin, and hetacillin. These drugs are either inactivated by the liver, require hepatic metabolism, or are capable of producing hepatic damage.
If septicemia or peritonitis occurs in conjunction with liver disease gentamicin 1 mg/lb TID IM or SC is administered for 5-7 days (while monitoring renal function carefully) in conjunction with cephalothin (Keflin, Lilly) at 10 mg/lb TID IV or cefoxitin (Mefoxin) at 10 mg/lb TID to QID IV for broad-spectrum coverage while awaiting culture and sensitivity results. If an anaerobic organism is identified on culture the antibiotics most likely to be effective include penicillin G 10,000 u/lb every 4-6 hours IV, metronidazole, or clindamycin 2.5-5 mg/lb BID PO.
Corticosteroid therapy is indicated in treatment of chronic active hepatitis, cholangiohepatitis, and immune-mediated hepatopathies. Corticosteroids have several therapeutic benefits in liver disease. They reduce the inflammatory component of liver disease and arrest destruction of hepatocytes in chronic active hepatitis and immune-mediated hepatopathies by reducing tissue lymphocyte and plasma cell numbers. They may also be of value in reducing mild degrees of fibrosis. Corticosteroid use may lead to an increase in serum albumin levels and bile flow and may decrease serum transaminase levels.
The preferred corticosteroids are prednisone or prednisolone. Because corticosteroids are normally metabolized by the liver before renal excretion, the dosage must be carefully calculated to avoid signs of corticosteroid excess. In general, the starting dosage of prednisone for inflammatory liver disease in dogs is 0.5 mg/lb divided BID for 2-4 weeks, followed by a decrease in dosage by one-half at each of several ensuing 2-6 week intervals, until an alternate day remission dosage of 0.1 - 0.2 mg/lb is reached.
Long-term therapy is usually necessary for chronic active hepatitis. Reinstitution of therapy after a relapse is not often as successful in controlling the disease as the initial therapy. The course of therapy for cholangiohepatitis is variable (3-4 months to several years). Affected animals should be monitored by periodic recheck of blood chemistry profiles and bile acid assays and repeat liver biopsies where possible.