Extracorporal liver support with molecular adsorbents recirculating system in patients with hepatitis B-associated fulminant hepatic failure

Hepatitis B virus (HBV) infection is the most prevalent cause of fulminant hepatic failure (FHF) in the Far East. HBV-associated FHF is characterised by rapidly progressive end organ dysfunction/failure and a very poor prognosis. To investigate how molecular adsorbent recirculating system (MARS) treatment impacts multiple organ system function in HBV-associated FHF. Ten consecutive patients were treated with MARS in a period of 12 months. Clinical, biochemical and haemodynamic parameters were assessed before and after MARS. Various disease severity scoring systems including model for end-stage liver disease, APACHE II, APACHE III, sequential organ failure assessment and organ system failure scores were also assessed. There were significant improvements in hepatic encephalopathy grading (p < 0.001), mean arterial pressure (p < 0.001), plasma renin activity (p = 0.027), bilirubin (p < 0.001), ammonia (p = 0.001) and creatinine levels (p < 0.001). There were also significant improvements in all the scoring systems evaluated. Meanwhile, platelet count was significantly decreased (p < 0.001). One patient was successfully bridged to liver transplantation. Three patients were alive at 3 months of follow-up. MARS can improve multiple organ functions in HBV-associated FHF. On the basis of these findings, randomised controlled studies are indicated and justified.     

Recent progress in the treatment of fulminant hepatic failure in Japan

Orthotopic liver transplantation is regarded as the only reliable treatment of fulminant hepatic failure in Western countries. The majority of hepatologists in Japan agree with this opinion. Liver transplantation is, however, only a symptomatic treatment of liver failure. The cause of fulminant hepatic failure is not taken into consideration in the decision of whether to proceed with liver transplantation. The term “fulminant hepatitis,” often used instead of “fulminant hepatic failure” in Japan, implies that the underlying liver disease is hepatitis in nature. Therefore, patients with fulminant hepatitis should be treated not only for the symptoms of liver failure, but for the underlying hepatitis as well. Such treatment includes antivirals and immunosuppressants for fulminant viral hepatitis, and immunosuppressants for fulminant autoimmune and drug-induced hepatitis. Using these treatment strategies, we have obtained a survival rate of 23/31 (74.1%) for the past 3.5 years in patients with fulminant hepatitis. We are currently attempting to cure all cases of severe hepatitis by predicting fulminant hepatitis and starting the treatment of hepatitis before the onset of coma.     

Serum octopamine, coma, and charcoal haemoperfusion in fulminant hepatic failure

Serum octopamine levels were significantly higher in twenty patients with fulminant hepatic failure (FHF) during the first 48 h of grade IV coma than in health control subjects (3.38 +/- 0.20 ng/ml and 1.75 +/- 0.19 ng/ml respectively, P less than 0.001). Serial measurements in five patients who died without regaining consciousness showed serum octopamine to remain raised, and concentrations in the cerebrospinal fluid at death reflected serum levels. In five patients who regained consciousness, improvement in encephalopathy was associated with a significant reduction in serum octopamine. Renal failure in patients with FHF was found to contribute to raised serum octopamine but could not alone account for the observed levels. Patients given neomycin therapy did not have significantly lower serum octopamine levels than an untreated group. There was, however, a significant correlation between elevated serum octopamine and the occurrence of gestrointestinal bleeding during the previous 24 h. Charcoal haemoperfusion did not appreciably reduce serum octopamine levels.     

Detrimental effects of nitric oxide inhibition on hepatic encephalopathy in rats with thioacetamide-induced fulminant hepatic failure

Hepatic encephalopathy is a complex neuropsychiatric syndrome seen secondary to acute liver failure, chronic parenchymal liver disease, or portal-systemic anastomosis. Vasodilatation induced by nitric oxide (NO) may be involved in the development of hepatic coma. However, there are no comprehensive data concerning the effects of NO inhibition on the severity of hepatic encephalopathy. Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of thioacetamide (TAA, 350 mg kg-1 day-1) for 3 days. Rats were divided into two groups to receive either NG-nitro-L-arginine methyl ester (L-NAME, 20 mg kg-1 day-1 via intragastric gavage) or normal saline (N/S) from 2 days prior to TAA administration for 5 days. Severity of encephalopathy was assessed by counts of motor activity and neurobehaviour test scores. Plasma levels of endotoxin, tumour necrosis factor-alpha and nitrate/nitrite were determined by the chromogenic Limulus assay, enzyme-linked immunosorbent assay and colorimetric assay, respectively. Compared with N/S-treated rats, the mortality rate was significantly higher in rats receiving L-NAME (59% vs. 18%, P < 0.01). Inhibition of NO had detrimental effects on the counts of motor activities (P < 0.05) and neurobehaviour score (P < 0.01). Rats treated with L-NAME had significantly higher plasma levels of endotoxin (26.7 +/- 3.8 pg mL-1) and tumour necrosis factor-alpha (29.4 +/- 6.5 pg mL-1) compared with rats treated with N/S (13.2 +/- 2.7 pg mL-1 and 11.2 +/- 2.6 pg mL-1, respectively, P < 0.01). Plasma levels of endotoxin and tumour necrosis factor-alpha, but not of nitrate/nitrite, were significantly correlated with the severity of hepatic encephalopathy (P < 0.05). Chronic L-NAME administration had detrimental effects on the severity of encephalopathy in TAA-treated rats, suggesting a protective role of NO in the development of fulminant hepatic failure.     

Therapeutic plasma exchange for fulminant hepatic failure secondary to Wilson's disease

Wilson's disease (WD) is an autosomal‐recessive disorder of impaired copper metabolism resulting in accumulation of copper primarily in the liver but ultimately in many organs and tissues. A small number of patients with WD initially present with fulminant hepatic failure (FHF), hypercupremia, and intravascular hemolysis. The therapeutic goals for these patients include quickly removing the copper and preparing the patient for liver transplantation. Here, we report on a 6‐year‐old male with WD in FHF with anemia, renal insufficiency, and coagulopathy. The patient received a series of therapeutic plasma exchanges (TPE) as adjunctive therapy to remove copper and stabilize his coagulopathy and anemia until a transplant was possible. A total of five single plasma volume (1500 mL) TPE were performed over the course of 11 days with plasma as the replacement fluid. Laboratory results demonstrated temporary improvement after each procedure. Liver transplantation was performed 12 days after beginning TPE and 35 days after admission to the hospital. TPE was a successful adjunctive therapy to bridge this patient with WD to transplantation. J. Clin. Apheresis 27:282–286, 2012. © 2012 Wiley Periodicals, Inc.     

Role of hepatitis C virus infection in German patients with fulminant and subacute hepatic failure

To investigate the possible role of hepatitis C virus (HCV) in fulminant and subacute liver failure, we tested serum and liver of 13 patients undergoing orthotopic liver transplantation for the presence of HCV RNA. HCV RNA was detected in specimens from two out of eight patients negative for all viral markers with suspected hepatitis non-A, non-B infection and in one out of four patients with hepatitis B virus infection. Only in this patient replication of HCV could be demonstrated. We conclude, that fulminant and subacute hepatic failure is induced by hepatitis C virus only in few patients with hepatitis non-A, non-B.     

Fulminant hepatic failure associated with propylthiouracil: a case report with treatment emphasis on the use of plasmapheresis

Propylthiouracil is a commonly used medication for hyperthyroidism. Though propylthiouracil-induced hepatotoxicity is a rarely encountered problem, death due to fulminant hepatic failure may occur. In the English literature, only 34 cases have been described with severe hepatotoxicity secondary to this drug. Here we report a case of fulminant hepatic failure due to propylthiouracil and review the issues of treatment and management with special emphasis on the use of plasmapheresis in such situations.     

Early prognostic biochemical indicators of fulminant hepatic failure

We investigated whether prognostic factors could be used for selecting appropriate therapy in patients with fulminant hepatic failure, for which orthotopic liver transplantation is often considered necessary. As, however, some patients survive without transplantation, a method is required to enable early distinction between patients requiring immediate transplantation and those who would survive without transplantation. As a number of prognostic indicators proposed for the identification of patient types are not completely satisfactory, in this retrospective study we investigated whether laboratory tests to evaluate severity of illness are best performed on the day of the appearance of the transaminase peak or the day of admission. The study included 44 patients with acute non-acetaminophen-induced liver failure. All patients received the same supportive care. Fourteen (group A) survived without transplantation and 20 (group B) died during hospitalization. Ten patients were excluded either because they underwent liver transplantation or data were incomplete. We studied prothrombin times and alpha-fetoprotein levels; values increased in the group of survivors throughout the period of illness, whereas they were low in patients who died. Both parameters allowed differentiation between patients of the two groups as from the 1st day after peak (P<0.05). The method proposed allows us to improve the predictive capacity of these laboratory tests in fulminant hepatic failure at an early stage of disease and to make an early selection of candidates for liver transplantation.     

Alternating therapeutic plasma exchange (TPE) with double plasma molecular adsorption system (DPMAS) for the treatment of fulminant hepatic failure (FHF)

Alternating therapeutic plasma exchange with double plasma molecular adsorption system can rapidly remove bilirubin and ammonia and supplement the essential substance from the blood, which could be used as an effective treatment for fulminant hepatic failure.