1/271. Nefazodone-induced liver failure: report of three cases. BACKGROUND: liver failure is a rare but devastating result of drug toxicity. OBJECTIVE: To describe three cases of subfulminant liver failure that were probably caused by nefazodone, a new antidepressant that is a synthetically derived phenylpiperazine. DESIGN: Case series. SETTING: Two university medical centers and a children's hospital. patients: Three women 16 to 57 years of age. INTERVENTION: Two patients underwent liver transplantation; the third was listed for transplantation but subsequently improved. MEASUREMENT: Liver biopsy. RESULTS: Nefazodone was administered for 14 to 28 weeks before the onset of symptoms. The duration of jaundice before onset of encephalopathy ranged from 4 to 6 weeks. All cases of liver failure had similar histologic appearance, with prominent necrosis in the centrolobular areas (zone 3). One patient had successful liver transplantation, one underwent transplantation but died, and one improved without transplantation. The temporal onset of disease after the start of nefazodone therapy suggested severe hepatocellular injury caused by the drug. CONCLUSIONS: Because nefazodone seems to cause severe hepatocellular injury in an idiosyncratic manner, routine liver chemistries should be performed before starting nefazodone therapy and patients should be monitored regularly. Therapy should be discontinued if liver enzyme concentrations become abnormal. ( info) |
2/271. Exacerbation of chronic hepatitis d during interferon alpha administration. Acute and severe impairment of liver function with jaundice and ascites occurred in two out of seven patients with chronic hepatitis d during interferon alpha administration (10 MU three times a week). Both of them were young women with histological diagnoses of moderate to severe chronic hepatitis and cirrhosis with no signs of portal hypertension. Only a slow and partial recovery was observed after interferon withdrawal. autoantibodies against basal cell layer tested positive in these two patients. In the remaining five patients with hepatitis d who did not experience liver impairment during interferon administration, basal cell layer antibodies were found only in one case. We conclude that severe decompensation of liver cirrhosis related to hepatitis d may occur during interferon administration. Positivity of basal cell layer antibodies may be associated with the risk of developing such an adverse event but our data are not sufficient to prove this association. ( info) |
| To identify and describe the frequency and severity of hepatotoxicity in patients who received flutamide therapy for prostate cancer, 22 patients were treated with the combination of flutamide and goserilin or orchiectomy. After diagnosis and staging of prostate cancer, baseline results were obtained for a set of five liver function tests (LF Ts). Hepatotoxicity was assessed according to the WHO criteria. After initiation of flutamide therapy, LF Ts were performed at 4, 8 and 12 weeks and every 2 months thereafter. Severe hepatotoxicity appeared in two of 22 (9%) patients. Following the discontinuation of flutamide, one patient died due to acute liver failure. On the other patient an improvement of LF Ts occurred after cessation of flutamide. The observed severe hepatotoxicity in two of 22 (9%) patients occurred more frequent than is predicted in the literature. patients treated with flutamide, having symptomatic or asymptomatic liver enzyme elevations, should be taken off therapy as soon as possible. ( info) |
4/271. Management of liver failure in a haemophilic patient co-infected with human immunodeficiency and hepatitis c viruses. We present a case of liver failure in a haemophilic patient coinfected with transfusion acquired human immunodeficiency (hiv) and hepatitis c (HCV) viruses. The case illustrates the interaction of multiple viruses with accelerated progression to end stage liver disease and ultimately death. We report the impact on the patient management of two liver biopsies, which diagnosed an initial drug induced hepatitis and subsequently an atypical HCV related hepatitis. ( info) |
5/271. Hemophagocytic syndrome presenting as acute hepatic failure in two infants: clinical overlap with neonatal hemochromatosis. Two patients with hemophagocytic lymphohistiocytosis who presented with acute liver failure are reported. Both presented with fever, hepatosplenomegaly, markedly elevated liver function tests, abnormal coagulation profiles, and an increase in serum ferritin. Both infants were diagnosed with neonatal hemochromatosis based on a clinical picture of hepatic insufficiency with hyperferritinemia and were referred for liver transplantation. The first patient died of liver failure and septicemia before transplantation. review of autopsy material revealed a hepatitis-like pattern and extensive infiltration of liver and other organs including bone marrow by histiocytes, some of which were hemophagocytic. The second patient underwent liver transplantation but died 44 days thereafter from progressive hemophagocytic lymphohistiocytosis. Examination of the resected liver demonstrated a hepatitis-like pattern, proliferation of histiocytes, and hemophagocytosis, and the bone marrow revealed hemophagocytic histiocytosis. Hemophagocytosis recurred in the allograft. Hepatic manifestations are common in hemophagocytic lymphohistiocytosis and overt hepatic failure may occur, but initial presentation as fulminant hepatic failure is not well recognized. Elevated serum ferritin can make the distinction from neonatal hemochromatosis and other forms of neonatal liver failure difficult. Hemophagocytic lymphohistiocytosis should be considered in the differential diagnosis of neonatal liver disease, especially when it is accompanied by cytopenias. ( info) |
6/271. Treatment of copper associated liver disease in childhood. BACKGROUND / AIMS: copper associated liver disease is accompanied with high liver copper concentrations and progressive liver disease in infancy or childhood. The disease is thought to be due to excessive dietary copper overload (copper-enriched water supply) and in addition to be based on a genetic predisposition. Treatment with penicillamine in Indian childhood disease, which probable has the same etiology, is effective when it is started early enough as well as in Wilson's disease. We aimed to describe the clinical features of copper associated liver disease and report our experience with different treatment options in German children. methods / RESULTS: Two boys presented at the age of 6 and 10 months with abdominal distension due to hepatosplenomegaly. The diagnosis of copper associated liver disease was made based on feeding history, standard liver function parameters, liver biopsy and assessment of dry weight copper concentration and urinary excretion of copper. Both had micronodular cirrhosis, ballooning of hepatocytes and mallory bodies. In child A improvement of liver function was observed after introduction of penicillamine therapy and copper-reduced diet. The treatment was stopped after 18 months, when normalisation of copper concentration in the liver had occured. In child B acute liver failure developed despite initiation of treatment. The boy was transplanted successfully. Both children are presently healthy 10 years after transplantation and 4 years after begin of chelating therapy, respectively. CONCLUSIONS: We conclude, that early chelating therapy with penicillamine can be successful in children with copper associated liver disease. In case of delayed diagnosis and acute liver failure liver transplantation is necessary. Our case reports highlight the urgent need of rapid diagnosis of copper associated liver disease in order to initiate early chelating therapy. copper associated liver disease should obviously be considered in liver disease of unknown origin. Possible causes of excessive dietary copper intake should be ascertained. ( info) |
7/271. Living donor liver transplantation in critically ill children. From December 1993, St Christopher's Hospital for Children, philadelphia, PA, USA has provided living donors the opportunity to donate a portion of their liver to children who are critically ill. This report evaluates the results of living donor liver transplants (LDLT) in critically ill children. We retrospectively reviewed the first 22 LDLT at our institution and compared the patient and graft survival of the nine critically ill children with the 13 stable children. Twenty-two LDLT have been performed at our institution between December 1993 and October 1997. Nine of 22 transplants [United Network for Organ Sharing (UNOS) Status I] were performed in children who were critically ill. Thirteen of the LDLT (UNOS Status II and III) were performed on stable children either in the hospital or admitted electively from home. The median weight and age at the time of transplant were 7 kg (range 4.6-54.5 kg) and 16 months (range 3 months-12 yr), respectively, and there was no statistical difference between the two groups. In critically ill children the 1-yr allograft and patient survival was 66% and 89%, respectively, exceeding the published results from UNOS for patients on life support (59.5% graft and 69.7% patient survival at 1 yr). One-yr allograft and patient survival in the stable children was 92.3% and 100%, respectively. All living donors are alive and well with normal liver function. In conclusion, our results show that LDLT is a viable approach for transplantation in critically ill children with liver failure and should be offered to potential donors. ( info) |
8/271. Fatal liver failure associated with valproate therapy in a patient with Friedreich's disease: review of valproate hepatotoxicity in adults. PURPOSE: Valproate (VPA)-associated hepatotoxicity is usually considered a problem of young children with polytherapy, mental retardation, and underlying metabolic defects. methods: An adult patient with fatal liver failure during treatment with VPA is presented, and a review of the literature on other adult patients is given. RESULTS: A 29-year-old female patient with Friedreich's ataxia and partial seizures with acute liver failure during VPA treatment is reported. The first symptoms of liver failure (i.e., apathy during febrile upper airway infection) occurred 2 months after starting VPA therapy. VPA was discontinued 10 days later on hospital admission, when she had hepatic encephalopathy and severe bleeding diathesis. The patient died of severe liver failure and bronchopneumonia after 4 weeks of supportive treatment. CONCLUSIONS: Twenty-six adult patients (>17 years) with VPA-associated fatal hepatotoxicity have been reported in the literature. Of the 26 adult patients, three were receiving VPA monotherapy. The age ranged between 17 and 62 years. The duration of VPA treatment before the first symptom varied between 7 days and 6 years. Twelve of the 26 affected adults had no underlying disease or a clearly nonmetabolic and non-hepatic disease. Therefore VPA-associated severe side effects also must be considered in adult patients without any evidence of a metabolic defect or underlying neurologic disease. ( info) |
9/271. anorexia nervosa with severe liver dysfunction and subsequent critical complications. A twenty-year-old woman with anorexia nervosa (body mass index=11) suffered from severe liver dysfunction (aspartate aminotransferase 5,000 IU/l, alanine aminotransferase 3,980 IU/l, prothrombin time 32%), hypoglycemia (serum glucose 27 mg/dl), and pancreatic dysfunction (amylase 820 IU/l, lipase 558 IU/l). She fell into a depressive state with irritability, which was not improved by intravenous glucose. Despite treatment with plasmapheresis for the liver dysfunction, she subsequently developed pulmonary edema, acute renal failure, gastrointestinal bleeding, and disseminated intravascular coagulation. Hemodialysis, mechanical ventilation and drug therapy including prednisolone, prostaglandin E1, and branched-chain amino acid, improved her critical condition. In this case, malnutrition may have been the cause for the liver dysfunction and subsequent complications. ( info) |
10/271. A rapidly progressive cataract in a patient with autoimmune hypoparathyroidism and acute liver and renal failure. cataract is a well-known complication of hypoparathyroidism, albeit the mechanism is obscure. The progression of cataract is typically slow in patients with idiopathic hypoparathyroidism. We describe a case of an extremely rapid evolution of typical hypocalcemic cataracts in a patient with familial autoimmune hypoparathyroidism during acute idiopathic hepatic and renal failure, while serum calcium and phosphorus were unbalanced. physicians and ophthalmologists must be aware of cataracts developing rapidly in the setting of such metabolic derangements. ( info) |