Hepatic failure, fulminant/acute

Transthyretin. This protein has a short half-hfe of 24 to 48 hours, making it a sensitive indicator of current synthetic ability. Failure of transthyretin to increase is an indicator of fulminant hepatic failure in acute hepatitis and is associated with a poor prognosis. It is more commonly used as a measurement of nutritional status. 

A patient developed atorvastatin-induced severe autoimmune hepatitis and a lupus-like syndrome. Although the drug was immediately withdrawn, the disease persisted and deteriorated to a fulminant form with acute hepatic failure. There was no response to conventional immunosuppression with glucocorticoids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery. The patient had the HLA haplotypcs DR3 and DR4, which are well-known genetic factors associated with autoimmune diseases. 

Tenamfetamine ( ecstasy, MDMA methylenedioxymethamphetamine) is structurally related to mescaline as well as to amphetamine. It was originally patented in 1914 as an appetite suppressant and has recently achieved widespread popularity as a dance drug at rave parties (where it is deemed necessary to keep pace with the beat and duration of the music popular names reflect the appearance of the tablets and capsules and include White Dove, White Burger, Red and Black, Denis the Menace). Tenamfetamine stimulates central and peripheral a-and p-adrenoceptors thus the pharmacological effects are compounded by those of physical exertion, dehydration and heat. In susceptible individuals (poor metabolisers who exhibit the CYP450 2D6 polymorphism) a severe and fatal idiosyncratic reaction may occur with fulminant hyperthermia, convulsioirs, disseminated intravascular coagulation, rhabdomyolysis, and acute renal and hepatic failure. Treatment includes activated charcoal, diazepam for convulsions, P-blockade (atenolol) for tachycardia, a-blockade (phentolamine) for hypertension, and dantrolene if the rectal temperature exceeds 39°C. 

Ockner, S.A., Brunt, E.M., Cohn, S.M., Krul, E.S., Hanto, D.W., Peters, M.G. Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation. Hepatology 1990 11 59-64... 

Fulminant hepatic failure due to acute hepatitis B and delta co-infection probable bloodbome transmission associated with a spring-loaded fingerstick device. Amer. X Gastroenterol. 1991 86 895-897... 

De Andrade, D.R., Fujito Neto, F.G., Vieira, G.S., Tiberio, I.F., Worth, M.R, Carlich, L Acute hemolytic crisis followed by fulminant hepatic failure with fatal outcome as a first clinical manifestation of Wilson s disease. Rev. Hosp. Clin. Fac. Med. Sao Paulo 1994 49 69-75... 

Conway, E.E., Santorineou, M., Mitsudo, S. Fulminant hepatic failure in a child with acute lymphoblastic leukemia. J. Pediatr. Gastroenterol. Nutr. 1992 15 194-197... 

Uver, and it occurs in 1 35 000 halothane exposures. With repeated exposure to halothane within 1 month, the frequency of acute Uver failure increases to 1 3700. The overall incidence of halothane hepatitis is faUing, owing to reduced use of halothane. Survival after Uver transplantation in patients with fulminant hepatic failure is lower than that after Uver transplantation for other reasons. 

Fulminant hepatic failure occurs in 1-5% of cases of paracetamol overdosage 3-6 days after ingestion (71), with frequent deaths in people who take 20-25 g. There is only a narrow margin between the normal maximum 24-hour dosage and that which can cause liver damage and acute hepatic failure. Undoubtedly, some people are more susceptible than most to paracetamol toxicity, since although 6 g has been reported as toxic in some cases, most toxicity is seen with 12 g upwards (72,73). Nomograms have been developed to show the relation between plasma paracetamol concentrations over time and the risk of a serious outcome (SEDA-18, 94). 

Acute hver failure has been reported in a 60-year-old woman after concomitant ingestion of phenytoin and co-trimoxazole over 9 days (197). Autopsy showed acute fulminant hepatic failure. 

Tse W, Singer C, Dominick D. Acute fulminant hepatic failure caused by trimethoprim-sulfamethoxazole. Infect Dis Clin Pract 2000 9 302-3. 

Ilario MJ, Ruiz JE, Axiotis CA. Acute fulminant hepatic failure in a woman treated with phenytoin and trimethoprim-sulfamethoxazole. Arch Pathol Lab Med 2000 124(12) 1800-3. 

An 8-year-old boy with complex partial seizures had taken valproate for more than 3 years. His sister developed uncomplicated hepatitis A, and 1 month later he became jaundiced, developed fulminant hepatic failure, quickly became encephalopathic, and died, despite withdrawal of valproate, aggressive supportive therapy, and treatment with carnitine. He had positive hepatitis A IgM other causes for acute hepatitis were ruled out. Liver pathology showed distended hepatocytes with cholestasis and microvesicular changes. 

Russell RI, Mflls PR. Wilson s disease presenting as acute fulminant hepatic failure. Scott Med J 1990 35 118-9. 

The outcome of acute hepatitis is variable. In most cases, complete recovery occurs and hver regeneration leads to normal structure and function. With some viruses, failure to dear infection leads to development of chronic hepatitis. In a small percentage of cases, massive destruction of the fiver leads to acute (fulminant) hepatic failure, which is associated with high mortality unless fiver transplantation can occur. 

The important uses of laboratory tests in acute hepatitis are to identify individuals with fulminant hepatic failure, document recovery, and determine clearance of any infectious agents. The most important tests in determining extent of injury are not plasma activities of cytosolic enzymes, but evidence of impaired liver function. The most important indicator of prognosis in acute hepatitis is impairment in synthetic functions of which PT is a widely accepted indicator. In acute viral or alcoholic hepatitis, PT more than 15... 

Hepatitis A infection usually results in an acute, self-limited disease that rarely leads to fulminant hepatic failure. The clinical features of acute hepatitis A are summarized in Table 40-1. After an average incubation period of 28 days, with a range of 15 to 50 days, symptomatic individuals will experience an abrupt onset of anorexia, nausea, vomiting, malaise, fever, headache, and right upper quadrant abdominal pain. Patients with underlying liver disease such as chronic hepatitis C infection are more likely to develop fulminant hepatic failure. Clinical symptoms also vary with age. Children younger than 6 years old are usually asymptomatic or have a mild influenzalike illness without clinical jaundice. In conhast, more than 70% of infected adults and older children display the characteristic clinical syndrome of acute hepatitis with elevated hepatic transaminase levels and jaundice. ... 

Pharmacologic agents offer no clear benefit in the treatment of patients infected with HAV. Corticosteroids have been used in patients with acute HAV when cholestatic hepatitis or fulminant hepatic failure is evident. However, controlled trials have failed to demonstrate any benefit and in some cases the use of corticosteroids may worsen clinical outcomes. ... 

Liver injury that results in fulminant hepatic necrosis and acute hver failure is relatively rare. Wheu it occurs, death results iu days or weeks in nearly 80% of cases. Any potential hepatotoxic agent (e.g., acetaminophen) can be responsible, although viral hepatitis is the most common cause worldwide, especially HB V (1 % of patieuts with acute hepatitis B develop fuhniuaut hepatitis). " Fulmiuaut hepatitis caused by HAV occasiouaUy occurs acute liver failme caused by HCV is rare. ... 

No specific therapy is available for the management of acute HBV infection. Development of fulminant hepatitis secondary to acute HBV is rare and is managed with supportive care (see section on fulminant hepatitis). The long-term complications of chronic HBV include development of cirrhosis, liver failure, and HCC. Thekey goal of therapy for chronic HBV is to eradicate or permanently suppress HBV. The short-term objective is to limit hepatic inflammation and to reduce... 

The spectmm of DILI is highly variable, ranging from abnormalities in liver enzyme levels to fulminant hepatic failure resulting in liver transplantation or death. The predominant form of DILI is acute hepatocellular injury, representing up to 90% of cases (Larrey 2000). This type of hepatic damage, which is usually characterized by an initial early increase in ALT levels, manifests itself as cell death, characterized as either zonal or nonzonal, in the form of necrosis and/or... 

B. After 24-48 hours, when transaminase levels (AST and ALT) begin to rise, hepatic necrosis becomes evident. If acute fulminant hepatic failure occurs, death may ensue. Encephalopathy, metabolic acidosis, and a continuing rise in the prothrombin time (PT) indicate a poor prognosis. Acute renal failure occasionally occurs, with or without concomitant liver failure. 

However, encephalopathies with a metabohc basis tend to be the most problanatic for infants or children, with functional outcomes dependent upon timely and pradent interventions. Three varieties of metabolic encephalopathy in children are discussed here. The first two are closely related. Inborn (genetic) errors of metabolism can present in the newborn as severe encephalopathy from hyperammonemia alone. When a metabolic error presents months to years later, a degree of hepatic insufficiency may complicate the metabolic derangement. In acute or fulminant hepatic failure of any etiology (i.e., infections, drug-induced, toxin-related), the rise in serum ammonia may be only moderate but other factors contribute to the ensuing encephalopathy, which may be devastating within days. 

Depending on referral patterns the proportion of patients presenting with liver disease alone varies from 20 to 46%. Liver disease may mimic any forms of common liver conditions, ranging from asymptomatic transaminasania to acute hepatitis, fulminant hepatic failure (about one out of six patients with hepatic presentation), chronic hepatitis, and cirrhosis (about one out of three patients) with all of its complications. 

On the other hand, the disease may rapidly deteriorate and resanble fulminant hepatic failure with massive jaundice, hypoalbuminemia, ascites, severe coagulation defects, hyperammonania and hepatic encephalopathy. Hepatocellular neCTOsis results in the release of large amounts of stored copper. Hypercupriania results in hemolysis and severe hemolytic anemia compUcates acute hver disease. Although Wilson disease is a rare disease, in patients presenting with fiilminant hepatic failure it is not uncommon and accounts for 6-12% of patients with fulminant hepatic failure referred for anergency hver transplantation. 

In general, transaminases are only mildly increased, and deep jaundice combined with mild elevation of liver enzymes should raise the suspicion for fulminant Wilson disease. However, increases of transaminases may be indistinguishable from findings seen in acute hepatitis. Sometimes alkaline phosphatase activities are relatively low in patients with Wilson disease. A ratio of total serum bilirubin concentration and alkaline phosphatase activity (>2) may differentiate fulminant Wilson disease from other forms of fulminant hepatic failure. However, the usefulness of this test was not confirmed in larger series. 

Bruno MS, Ober WB (1968) Acute fulminant hepatic failure with bilateral tuberculous cavitation. NY State J Med 68 2934... 

Schneider R, Bercker S, Schubert S, Tillmann HL, Fangmann J, Hauss J, Bartels M. Successful liver transplantation in antituberculosis therapy-induced acute fulminant hepatic failure. Transplant Proc 2009 41(9) 3934-6. 

Acute fulminant hepatic failure has not been an important condition which has been treated to date with liver transplantation . This apparently paradoxical situation obtains because such patients rapidly deteriorate and consideration of transplantation as a therapeutic option usually is initiated only after advanced coma has occurred. In such case, brain edema leading to herniation usually occurs before an appropriate donor can be identified and transplantation can be accomplished. Moreover, the likelihood of recurrent infection in cases of fulminant viral hepatitis would seem to be great and therefore not warrant the procedure. 

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