Failure of simple biochemical indexes to reliably differentiate fulminant Wilson's disease from other causes of fulminant liver failure.

Serum, urine and tissue biochemical findings were studied in 21 cases of fulminant Wilson's disease with respect to the value of a recently described biochemical index based on serum alkaline phosphatase and total serum bilirubin levels, and these cases were compared with 193 other cases of fulminant liver failure. Serum bilirubin, alkaline phosphatase and AST levels found in fulminant Wilson's disease were significantly different from those found in other cases of fulminant liver failure, but differentiation from other causes of fulminant liver failure on the basis of these biochemical parameters was not possible. The alkaline phosphatase/bilirubin and aspartate AST/bilirubin ratios derived from the above parameters were also significantly lower in fulminant Wilson's disease than in other categories of fulminant liver failure, but distinction between diagnostic categories on this basis was not possible. When ratios that correctly identified all cases of fulminant Wilson's disease were selected, 59/190 (31%) and 84/190 (44%) cases of non-Wilsonian fulminant liver failure would erroneously be assigned a diagnosis of fulminant Wilson's disease, by alkaline phosphatase/bilirubin and AST/bilirubin ratios, respectively. A low alkaline phosphatase-to-bilirubin ratio (< 0.57) in any category of fulminant liver failure suggested a significantly worse prognosis than in cases with higher ratios (chi 2, Yates' corrected = 5.37, p = 0.02). In the Wilson's disease group, serum and hepatic copper and ceruloplasmin concentrations were normal in 4/21, 2/15 and 2/19, respectively, whereas urinary copper level was elevated in 18/18 and was the most valuable test in diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Syphilitic hepatitis resulting in fulminant hepatic failure requiring liver transplantation

Syphilitic hepatitis is a rare but well described syndrome, typically manifesting as a mild clinical hepatitis, with complete resolution following therapy. There have been several cases of severe hepatitis, but none progressing to a fatal outcome. We present a case of fulminant hepatitis and hepatic failure in the setting of active secondary syphilis resulting in liver transplantation. The clinical syndrome of syphilitic hepatitis is discussed. This case should highlight and remind physicians of the varied and severe manifestations of syphilis, and prompt physicians to explore syphilis as a possible cause of unexplained hepatitis.     

Autoimmune hepatitis in children. Initial presentation as fulminant hepatic failure

There are few cases reported of autoimmune hepatitis (AIH) type 2 presenting as fulminant hepatic failure (FHF) in children. The purpose of this study was to report three girls with AIH type 2 that presented as FHF. METHODS: Over a period of 12 years, 123 patients with AIH diagnosed based on international criteria, 9 (7%) were type 2.3 of them presented as FHF. Other etiologies (viral, metabolic and toxic) were ruled out. The treatment was started with prednisone (2 mg-kg-day) and azathioprine (2 mg-kg-day). EVOLUTION: Patients 1 and 3 died while waiting for liver transplant (LT) at 72 and 48 hours after initiating medical treatment. Patient 2 underwent LT3 days after starting treatment, with excellent evolution at 3 years and 7 months of follow up. CONCLUSIONS: 1--AIH type 2 was very infrequent in our group. 2--33% of cases had initial presentation as FHF. 3--The course of the disease was aggressive, not responding to immunosuppressive therapy. The evolution was unfavorable in all patients. 4--LT is an alternative treatment for this severe disease.     

Clinical characteristics and prognostic indicators of drug-induced fulminant hepatic failure

BACKGROUND/AIMS: In most cases of drug-induced liver injury, it is difficult to diagnose whether these cases would progress to fulminant hepatic failure. We investigated the characteristics of non-viral and suspiciously drug-induced fulminant hepatic failure by comparing clinical data between cases that progressed and those that did not progress to fulminant hepatic failure. METHODOLOGY: Ninety-five cases of suspicious drug-induced liver injury including 22 cases that had been treated at our hospital, and subsequently progressed to fulminant hepatic failure were involved in this study. We investigated the characteristics of drug-induced fulminant hepatic failure by a comparison of non-fulminant and fulminant cases, and simultaneously of survivors and fatal cases in the group of fulminant cases. RESULTS: Many of the clinical variables were significantly deteriorated in fulminant cases. The latent period, which means the duration of drug administration, correlated with the severity of drug-induced liver injury including fulminant hepatic failure. Suspicious cases of drug-induced liver injury where the bilirubin level at the time of definite diagnosis stayed over 13 mg/dL for more than one month were likely to progress to fulminant hepatic failure. CONCLUSIONS: Our results suggest that the latent period and the peak level of total bilirubin would be prognostic factors for the severity of drug-induced fulminant hepatic failure. Early preparation of liver transplantation should be recommended by referring these characteristics.     

Clinical monitoring of intracranial pressure in fulminant hepatic failure.

Cerebral oedema is the commonest immediate cause of death in fulminant hepatic failure and an investigation was carried out to determine the value of monitoring intracranial pressure (ICP) and to examine the effects of ICP of dexamethasone therapy and mannitol administration. ICP values in 10 patients at the time of insertion of a subdural pressure transducer (grade IV encephalopathy) averaged 15.5 +/- SD 14.8 mmHg. Despite dexamethansone therapy, which had been started on admission, rises in ICP were subsequently observed in seven of the eight patients who died. In the two patients who survived, the highest reading were 47 and 35 mmHg. Mannitol consistently reversed or arrested ICP rises when pressure was < 60 mmHg. ICP monitoring provides additional information in the managment of patients and is essential if mannitol therapy is to be used.     

Frequency of arrhythmias and other cardiac abnormalities in fulminant hepatic failure.

In a series of 106 patients with fulminant hepatic failure and grade 4 encephalopathy, cardiac arrhythmias and other abnormalities occurred in 92 per cent. The most common was sinus tachycardia (75%) and this was the only abnormality in 22 per cent of the patients. Sudden cardiac arrest occurred in 25 per cent, various ectopic beats in 20 per cent, and heart block or bradycardia in 18 per cent. Other electrocardiographic abnormalities, mostly of the T wave and ST segment, were found in 31 per cent. Cardiac and respiratory arrests were usually unrelated to each other and both frequently occurred without warning. Only 7 out of 71 patients with arrhythmias other than sinus tachycardia survived, compared with 15 out of 31 patients without them (P less than 0-005). During the latter part of the series when an arrhythmia computer was used to monitor 38 patients, it was shown that significantly lower arterial oxygen levels occurred in those with arrhythmias, other than sinus tachycardia, than in those without. They were also found to be more acidotic and hyperkalaemic, and a higher number required dialysis and ventilation. Macroscopical cardiac abnormalities including scattered petechial haemorrhages, small pericardial effusions, and fatty, pale, and flabby ventricles, were found at necropsy in 64 per cent of the patients examined. Combinations of these macroscopical abnormalities occurred, particularly in the paracetamol overdose group. Another necropsy finding of possible significance in the pathogenesis of arrhythmias was cerebral oedema, present in 48 per cent of the patients examined, and often associated with coning of the brain stem. However, 7 of the 16 patients who suffered asystolic cardiac arrests had no macroscopical abnormality of either heart or brain. In the management of patients with fulminant hepatic failure continuous cardiac monitoring is essential. Correction of the biochemical and coagulation defects may decrease the frequency of arrhythmias but studies of the mechanism and control of cerebral oedema and its relation to cardiovascular function are urgently needed.     

Sulfasalazine-induced fulminant hepatic failure.

We report two cases of massive hepatic necrosis associated with sulfasalazine. Both patients had underlying inflammatory bowel disease. One of the patients had a history of an ill-defined autoimmune disorder (Sj?gren's syndrome). Symptoms and signs of a generalized hypersensitivity reaction were present in both patients. One patient died of a subarachnoid hemorrhage while awaiting transplant, the second died 2 weeks after transplant from disseminated aspergillosis. These two cases remind us of one of the potential hazards of sulfasalazine at a time when alternative therapies are now available.     

Nicotinic acid-induced fulminant hepatic failure

A 46-year-old man began taking nicotinic acid, 3 g daily, for hypercholesterolemia. A month later, he developed clinical and biochemical evidence of modest hepatocellular injury, and therapy was stopped. It was restarted 6 weeks later, and 10 weeks after that, the patient presented with fulminant hepatic failure, which resolved rapidly after cessation of nicotinic acid therapy. We suggest that nicotinic acid was the cause of his liver disease, that this case is of particular note because of the rather short period of therapy before the onset of liver injury and the severity of the hepatic failure, and that the probable increased use of nicotinic acid for serum cholesterol control makes it especially important for physicians and their patients to be alert to the signs of hepatotoxicity.     

Animal models of fulminant hepatic failure

The six requirements for a satisfactory animal model of fulminant hepatic failure are reversibility, reproducibility, death from liver failure, a therapeutic window, a large animal model, and minimal hazard to personnel. Different models may be required to evaluate the various types of liver failure seen in man. The available models include surgical anhepatic and devascularization procedures, as well as hepatotoxic drug administration using agents such as carbon tetrachloride, acetaminophen, or galactosamine. Currently combined surgical and drug models appear to provide the best model but the search for the ideal models continues.Presented at the Proceedings of the International Meeting on Normal and Neoplastic Growth in Hepatology, Bari, Italy, June 1989.     

乙型肝炎病毒再激活在暴发性肝衰竭中的意义及其治疗

暴发性肝衰竭 (FHF)是由于肝细胞大量坏死而出现以肝功能严重受损为特征的综合征。目前临床治疗尚无特效药物 ,以综合治疗为主 ,但其效果不佳 ,患者通常死于继全身炎症反应综合征 (systemicinflammatoryresponsesyndrome ,SIRS)后的严重感染[1] ,其病死率高达 80 %～ 90 % ,尤其合并有其他疾病时病死率更高。引起严重肝炎发病的原因有很多 ,但大部分是由病毒感染和药物所致。本文仅就免疫受损宿主的乙型肝炎病毒 (HBV)再激活所致的暴发性肝衰竭进行阐述。免疫受损宿主概念指的是患有免疫缺陷性疾病或使用细胞毒性或免疫抑制剂药物的患者…