Granulomatous hepatitis associated with carbamazepine therapy.
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Biomedical subjects
Publications and source records attributed to W C Maddrey.
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In eight patients with chronic portal-systemic encephalopathy who were symptomatic despite protein restriction and lactulose, a double-blind crossover comparison was conducted of branched-chain amino acids (68 mmol/d) versus ornithine salts of branched-chain ketoacids (34 mmol/d), both mixtures being administered orally for 7 to 10 days, after control periods, during a single hospitalization. Ornithine salts of branched-chain ketoacids markedly improved electroencephalographic abnormalities and clinical grade of encephalopathy; branched-chain amino acids had significantly lesser effects, which were of borderline statistical significance. To ascertain whether ornithine or branched-chain ketoacids were responsible for the improvement observed, we administered to six patients calcium salts of branched-chain ketoacids (34 mmol/d) after control periods; only slight improvement was seen.. Four patients received a daily dose of ornithine alpha-ketoglutarate containing the same quantity of ornithine; one did not change and three deteriorated rapidly. We conclude that the combination of ornithine and branched-chain ketoacids improves chronic portal-systemic encephalopathy more than its components given separately and more than branched-chain amino acids at twice the molar dose.
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A modification of the mesocaval interposition H shunt utilizes the anterior cephalad portion of the superior mesenteric vein on top of the uncinate process of the pancreas as the site of anastomosis. This site is above the branches of the superior mesenteric vein and ensures a vein of large caliber. When the graft is anastomosed to this portion of the vein, it assumes a C configuration.
Seven patients with cardiovascular disease had clinical episodes and marked transaminase elevations that suggested viral hepatitis, but all had morphologic evidence (from liver biopsy or autopsy specimens) that documented centrilobular necrosis (ischemic hepatitis) with no evidence of viral or drug injury. Several also had moderate or marked passive congestion of the liver so the liver biopsies of 15 additional patients were retrospectively reviewed. In this latter group congestion alone was associated with normal or minimal elevation in transaminases while all patients with notable (greater than 5 times normal) transaminase elevations had centrilobular necrosis. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis, or ischemic hepatitis, correlates with significant hypertransaminasemia, appears to result from failure of hepatic perfusion (with or without preceding hypotension), and presents with clinical and laboratory manifestations that suggest viral hepatitis.
The management of malignant obstruction of the biliary tree is difficult and often unsuccessful. Advances in the technique of percutaneous transhepatic catheterization have made possible the nonoperative internal drainage of obstructed lesions. We report successful decompression of ten patients with unresectable biliary neoplasms using percutaneously placed internal biliary stents.
Arterial plasma levels and hepatic extraction of renin and aldosterone (ALDO) were measured in 24 patients with alcoholic liver disease and in 14 normal subjects being evaluated as prospective kidney donors. Patients with liver disease had higher plasma concentrations and lower fractional hepatic extractions of both renin and ALDO than the normal subjects. The quantity of renin extracted by the liver was highly correlated with plasma renin in both normal subjects and patients. Plasma ALDO concentration was positively correlated with plasma renin (p less than 0.001) but not with serum sodium, potassium or albumin concentration, inferior vena cava pressure, corrected hepatic venous wedge pressure, plasma volume or sulfobromophthalein storage or transport. Sixteen patients were restudied after one month. Six had received 40 mg/day of prednisolone, and the remaining 10 had received a placebo. Neither group had a change in plasma volume, corrected hepatic venous wedge pressure, plasma concentration or hepatic extraction of renin or ALDO. Serum albumin concentration increased and inferior vena cava pressure decreased with prednisolone therapy. These studies document high plasma levels and impaired hepatic extraction of renin and ALDO in patients with liver disease that are not corrected by short-term prednisolone therapy.
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Lipoprotein X is considered to be an indicator of cholestasis, but its clinical usefulness is unclear owing to different methods of measurement in use and varying definitions of cholestasis. We investigated the reliability of the qualitative determination of lipoprotein X in predicting cholestasis, defined here as the presence of stainable bile in tissue sections. Liver tissue and serum were collected from 42 patients. Patients were divided into those who did and those who did not have stainable bile in tissue sections. Lipoprotein X was demonstrated by electrophoresis and polyanion precipitation. Lipoprotein X in serum correlated with the presence of stainable bile (p = 0.0006). A normal range of alkaline phosphatase values correlated with the absence (p = 0.04), but elevated values did not correlate with the presence of stainable bile. In patients known to have elevated alkaline phosphatase, the presence of lipoprotein X still correlated with the presence of bile (p = 0.008). We conclude that lipoprotein X is a reliable indicator of cholestasis and that it is more useful than alkaline phosphatase in this application.
Results in 44 patients with esophageal bleeding who underwent a mesocaval shunt utilizing a prosthetic graft are presented. Portal hypertension was secondary to alcoholic cirrhosis in 30 patients, to chronic active hepatitis in eight, to primary biliary cirrhosis in four, to cirrhosis secondary to inflammatory bowel disease in one, and to portal vein thrombosis following splenectomy in one. Thirty-six shunts were performed during the emergent or semiemergent time period, and only eight were performed electively. Sixteen of the patients were Child's class A, 16 were class B, and 12 were class C. There were no hospital deaths in the emergency shunt group (of eight patients); there was a 12% mortality rate for patients undergoing semiemergency shunts (two of 17 patients) and a 42% mortality rate for patients who had emergency shunts (eight of 19 patients). Death was related more closely to hepatic reserve, however, than to timing of the shunt. Among the 32 class A and B patients, there were only three deaths in hospital (9%), as compared with seven deaths among the 12 class C patients (58%). Portal-systemic encephalopathy was high in the period immediately after operation (13 of 34 patients, 38%), but it was a chronic problem following discharge from the hospital in only three of 34 patients (9%). The mesocaval shunt is a safe, effective procedure for the control of variceal bleeding in class A and class B patients in any time period, but it carries a high operative mortality risk in the class C patient when it is performed as an emergency operation.
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The probable etiology and outcome of bridging hepatic necrosis found on a liver biopsy performed within three months of the onset of clinical illness was evaluated in 42 consecutive patients with this finding. Eighteen of the patients (43%) had a probable drug etiology for their hepatitis. Ten patients had HBSAG-positive acute hepatitis. Fourteen patients had neither drug-induced disease nor proven HBSAg-positive hepatitis. One patient from the drug-induced group died, but the other 17 had complete clinical recovery. Eight of ten in the hepatitis B antigen-postive group cleared their antigen and had complete clinical recovery. Chronic hepatitis developed in two who remained persistently HGSAg positive. Eight of the patients in the group with unknown etiology recovered, while six developed evidence of active chronic liver disease. This incidence of active chronic liver disease is significantly greater than that found in the drug-induced group (P less than 0.02). We conclude that drug-induced hepatitiis accounts for a significant proportion of patients of acute hepatitis who have bridging hepatic necrosis on liver biopsy. However, in these drug-induced cases the finding of bridging hepatic necrosis does not appear to be associated with an increased risk of development of active chronic liver disease.
In a double-blind, randomized study the efficacy of lactulose was compared with neomycin-sorbitol in 45 episodes of acute nitrogenous portal-systemic encephalopathy (PSE) induced by dietary protein, azotemia, or gastrointestinal hemorrhage. All patients had underlying cirrhosis, and at the time of randomization had encephalopathy of at least grade 2 severity and arterial ammonia concentrations greater than 150 microgram/100 ml. Two thirds of the patients in each group returned to normal mental status and more than 80% in each group showed at least one grade improvement in mental state. In addition, there was equivalent improvement in asterixis, in the performance of the Number Connection Test, in the electroencephalographic pattern, and in arterial ammonia concentration. The principal difference between the two groups was a greater reduction in stool pH after lactulose therapy than after neomycin-sorbitol therapy. One patient randomized to neomycin-sorbitol had to be withdrawn from the study because of persistent vomiting related to the administration of the medication. Otherwise there were no complications attributable to therapy in either group. These data suggest that neomycin-sorbitol and lactulose are equally effective in the treatment of acute nitrogenous portal-systemic encephalopathy.
A patient is presented with the Budd-Chiari Syndrome. Because of a thrombosed inferior vena cava, none of the standard portal-systemic shunts could be utilized for decompression of the engorged liver. A new shunt constructed by interposing a Dacron graft between the superior mesenteric vein and the right atrium was performed. Portal pressure was reduced by the shunt from 30 cm of H2O to 10 cm of H2O. Patency has been confirmed post-operatively by catheterization and with angiography. The patient is asymptomatic with normal liver function tests nine months following the procedure. A surgical approach is outlined for symptomatic patients with the Budd-Chairi Syndrom.