Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketoconazole has only recently been recognized as a cause of hepatic injury, with most reports coming from outside the United States. In order to characterize more fully the U.S. experience, we undertook an analysis of 54 reports of alleged ketoconazole-induced liver injury submitted to the Food and Drug Administration from the time of initial marketing in 1980. Thirty-three reports were considered likely instances of ketoconazole-induced hepatitis. The majority of these cases occurred in women more than 40 yr of age. Jaundice was recorded in 27 individuals after therapy of 11-168 days with an average daily dose of 200 mg. Anorexia, malaise, nausea, and vomiting accompanied liver injury in one-third of cases. No instances of rash or eosinophilia were recorded. Serum transaminase and alkaline phosphatase values were consistent with acute hepatocellular injury in 18 patients, with primarily cholestatic injury in 5 patients, and with a mixed pattern in 9 individuals. Only one death seemed attributable to ketoconazole. In that patient, the drug was continued after the appearance of clinical and biochemical evidence of hepatic injury and massive hepatocellular necrosis was present at autopsy. The incidence of symptomatic, potentially serious hepatic injury appears to be very low, perhaps 1 in 15,000 exposed individuals. The presumed mechanism of injury is metabolic idiosyncrasy, although hypersensitivity has not been completely dismissed in some cases reported in the literature. The incidence of mild, asymptomatic, reversible elevations in serum transaminases occurring in ketoconazole recipients has been estimated to be 5%-10%. Periodic biochemical testing and monitoring for symptoms of hepatitis during ketoconazole therapy is recommended to help prevent the development of serious or fatal hepatic injury.
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PMID:Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. 631 20

VP-16-213 at standard dose is one of the more active agents for the treatment of germ cell tumors. In previous phase I studies, VP-16-213 has been investigated in suprastandard dose when hematopoietic reconstitution was assured by autologous bone marrow transplantation (ABMT). This phase II study was performed to explore the possibility that an augmented dose of VP-16-213 may be more active than standard dose against germ cell tumors. Eleven patients with progressive refractory germ cell tumors were treated with high-dose VP-16-213: 2,400 mg/m2 with ABMT every three to four weeks followed by 1,200 mg/m2 without ABMT. Seven patients had received VP-16-213 at standard dose prior to high-dose VP-16-213. Toxicity to high-dose VP-16-213 included severe myelosuppression, nausea, vomiting, alopecia, mucositis, and hepatitis. Of 10 evaluable patients, two complete responses and four partial responses, all of short duration, were obtained. However, some patients unresponsive to standard-dose VP-16-213 exhibited responses to the augmented-dose VP-16-213. Therefore, although more myelosuppressive, VP-16-213 may have increased activity against germ cell tumors when administered at augmented dose. High-dose VP-16-213 may be considered in designing new approaches for initial management of patients with germ cell tumors not expected to be cured with standard chemotherapy.
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PMID:High-dose VP-16-213 monotherapy for refractory germinal malignancies: a phase II study. 636 60

Many adverse reactions to quinine have been reported. A 65 year old woman taking quinine sulphate for nocturnal leg cramps presented for investigation of episodes of malaise, fever, nausea, vomiting, and polyarthralgia. Granulomatous hepatitis was diagnosed, for which no common cause was found. She was challenged with quinine sulphate; within hours her temperature had risen and her symptoms returned; transaminase activities rose within 48 hours, as did erythrocyte sedimentation rate. After withdrawal of the drug symptoms abated and transaminase activities returned to normal. The biochemical response to challenge with quinine implicates the drug as the cause of the liver disturbances. Quinine should be added to the list of drugs known to cause granulomatous hepatitis and should be considered in cases where symptoms are episodic or where no other cause is apparent.
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PMID:Quinine-induced granulomatous hepatitis. 640 64

A phase I-II study of KW2083, an analog of mitomycin C (MMC) was performed in a total of 22 patients. KW2083 was escalated by single intravenous administration of 40, 50, 60, 70, and 80 mg/m2 doses. Treatments were repeated every 4-6 weeks unless unacceptable toxicities occurred. The median times taken to reach nadir for each dose level were 9-12 days for leukocytes and 7-13 days for platelets respectively. The median times taken for recovery were 8-22 days for leukopenia and 10-37 days for thrombocytopenia. Variable and non-predictable hematological toxicity was observed in some cases. Biphasic hematological toxicity was observed in 4 courses. Acute toxicity occurred in 17 courses for 11 patients and consisted of nausea (44%), vomiting (13%), diarrhea (2.7%) and stomatitis (2.7%). Nephrotoxicity (elevation of BUN, 8.1% and proteinuria, 5.4%) occurred in 3 patients who had no previous impairment of renal function. Alopecia (8.1%) was also observed. Marked elevations of hepatic enzymes were noted in one patient who developed acute fulminant hepatitis with the second dose of KW2083. Objective response was observed in one of 20 evaluable patients. From this preliminary study, the maximum tolerable dose is 70 mg/m2 and the optimal dose of KW2083 was determined to be 50 mg/m2 at 6-week intervals. KW2083 has been introduced as an MMC analog of potential interest. However, hematological and non of hematological toxicities are very similar to those of MMC and does not appear that KW2083 will supersede MMC.
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PMID:[Phase I-II study of 7-N-(P-hydroxyphenyl)-mitomycin C (KW2083, M83)]. 647 44

Propylthiouracil-induced hepatitis is an uncommon entity. Two further cases are reported herein, and the clinical and laboratory features of the other six cases in the English literature are reviewed. The initial appearance of the disease is similar to that of viral hepatitis, characterized by nausea, vomiting, and jaundice. The biochemical pattern of injury is predominantly hepatocellular, with marked elevation of transaminase valves and less striking elevation of alkaline phosphatase values. Recovery is usually complete after withdrawal of the drug, but there have been at least two fatalities, including the first patient (to our knowledge) whose case is reported herein. Despite its rarity, the disease should be suspected in any patient receiving propylthiouracil in whom clinical or laboratory evidence of hepatocellular injury develops.
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PMID:Propylthiouracil and hepatitis. Two cases and a review of the literature. 660 33

Idiopathic perforation of the bile duct is rare in children. Sixty-seven cases were reported in the English literature to 1980. It is, nevertheless, the second commonest surgical cause of jaundice in the neonate. The etiology is unknown though distal obstruction and weakness in the bile duct wall have been postulated. Limited surgical treatment with external drainage is the preferred therapy. In isolated cases internal drainage procedures or repeated aspiration have been successful. The diagnosis should be suspected in the presence of jaundice and ascites with or without abdominal pain and signs of peritoneal irritation. We describe a 3-month-old girl presenting with anemia, vomiting, jaundice, and ascites. This was initially diagnosed as hepatitis but bilious fluid was found on paracentesis. Computerized tomography with cholangiography and 99 MTC Diisopropyl IDA cholescintigraphy confirmed the diagnosis. The latter seems to be more accurate than I-131 Rose Bengal. The perforation was at the junction of the hepatic and cystic ducts. It was treated successfully by external drainage and a cholecystostomy. Direct attempts to close the perforation, or more complicated surgical procedures, are unnecessary while nonoperative treatment carries a high mortality. At follow-up after 1 year the IV cholangiogram and liver-function tests are normal. Cholecystostomy provided good drainage of the biliary ducts as well as easy access for follow-up cholangiography.
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PMID:Idiopathic perforation of the biliary tract in infancy. 664 92

A 13% incidence of hepatitis was observed among 54 cases of multibacillary leprosy treated daily with the three-drug combination of dapsone, rifampin, and a thioamide (ethionamide or prothionamide). No hepatitis was observed among 109 cases of paucibacillary leprosy treated daily with the two-drug combination of dapsone and rifampin. Symptoms were jaundice in five cases and nausea plus vomiting associated with a significant increase of transaminase levels in two cases. In five cases, the symptoms appeared during the first two months of therapy and in two cases, later. Discontinuing treatment with rifampin and the thioamide but not dapsone resulted in recovery. When rifampin was resumed without the thioamide, the hepatitis did not recur. Viral etiology could be eliminated in six cases. Neither sex, age, weight nor the fact that the patient was a new case or a relapse case appeared to be a contributing factor. Hepatotoxicity caused by administration of a thioamide might have been potentiated by the concurrent administration of rifampin.
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PMID:Hepatitis in leprosy patients treated by a daily combination of dapsone, rifampin, and a thioamide. 668 70

In a one-year prospective study we assessed the incidence of Reye's syndrome in children presenting with the acute onset of vomiting after a prodromal upper-respiratory-tract infection or varicella, and with serum alanine or aspartate aminotransferase levels at least three times higher than normal, and a paucity of neurologic findings. Of 25 patients meeting the above criteria, 19 had liver biopsies yielding adequate tissue for diagnostic purposes. Biopsy specimens from 14 of these 19 patients (74 per cent) were diagnostic of Reye's syndrome, according to rigorous light-microscopical, histochemical, and ultrastructural criteria. None of the biopsy specimens contained evidence of other acute pathologic processes, including hepatitis. A wide spectrum of mitochondrial alterations existed at the ultrastructural level, ranging from mild to severe lesions that were indistinguishable from those seen in comatose patients with Reye's syndrome. Our findings suggest that the clinical complex of vomiting, hepatic dysfunction, and minimal neurologic impairment after varicella or an upper-respiratory-tract infection usually represents Reye's syndrome. This syndrome occurs more frequently than previously recognized.
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PMID:Grade I Reye's syndrome. A frequent cause of vomiting and liver dysfunction after varicella and upper-respiratory-tract infection. 686 12

A case is described wherein a 29 year old woman was admitted to the hospital because of the possibility of a hepatic tumor; symptoms included abdominal pain, diffuse hepatic enlargement and absence of uptake in an area of the right hepatic lobe. After a normal pregnancy and delivery 11 years earlier the patient used oral contraceptives (OCs) composed of norethindrone with mestranol until 8 years before entry; 5 years before admission she resumed use of an OC containing norethindrone and ethinyl estradiol. She smoked 1.5 packages of cigarettes and drank 1 glass of wine daily, and there was no history of nausea, vomiting, melena, jaundice, dark urine, light stools, hepatitis, or blood transfusions. Benign lesions which are known to be caused by OCs fall into 2 groups: designated focal nodular hyperplasia and liver-cell adenoma. The evidence linking the latter with OCs is more convincing since in case-controlled studies the risk of development of adenomas has been shown to increase with the estrogen strength of the OCs and duration of use; in women who have been taking OCs over 7 years the relative risk is 500 times that for matched control nonusers. The vascular complications of OC therapy include Budd-Chiari syndrome, peliosis hepatis, and periportal sinusoidal dilatation. The patient in this case was diagnosed to have periportal and midzonal hepatic sinusoidal dilatation association with OC medication. She underwent an operation on her liver which proved to be successful combined with cessation of OC use. The mechanism by which OCs cause these lesions is not known. In 5 of 13 cases similar to the one described here clinical and biochemical abnormalities resolved and 1 patient had a follow-up liver biopsy that revealed normal findings 10 months after cessation of OC therapy; there is no evidence to suggest that sinusoidal dilatation is irreversible.
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PMID:Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 40-1982. Tender hepatomegaly in a 29-year-old woman. 711 Feb 74

Forty cases of cerebral Plasmodium falciparum malaria seen at San Lazaro Hospital, Manila, Philippines from 1979-1981 were reviewed. These cases represented 7% of all Plasmodium falciparum cases seen during this period. All of the patients had fever and headache, 73% confusion, 70% chills, 68% jaundice or abdominal pain, 60% sweats. Findings more frequent in the fatal compared to the non-fatal cases were: the presence of schizonts in the peripheral smear, oliguria, coma, convulsions, urinary incontinence, jaundice, pulmonary symptoms and vomiting. Fatal cases were less likely to be clinically diagnosed as malaria and more likely to be diagnosed as hepatitis than malaria. The treatment and management of these cases is discussed.
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PMID:Cerebral malaria at San Lazaro Hospital, Manila, Philippines. 717 Jun 37


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