Fulminant necrosis

Only one report of human death attributed to 1,4-dichlorobenzene exposure has been located in the literature. A 60-year-old man and his wife died within months of each other due to acute yellow atrophy of the liver (also known as massive hepatic necrosis or fulminant hepatitis) (Cotter 1953). Their home had been "saturated" with 1,4-dichlorobenzene mothball vapor for a period of about 3-4 months, but no air measurements were available. Clinical symptoms included severe headache, diarrhea, numbness, clumsiness, slurred speech, weight loss (50 pounds in 3 months in the case of the husband), and jaundice. The wife died within a year of the initial exposure however, it was not clear if 1,4-dichlorobenzene was the primary cause of death. This case study did not address whether these individuals consumed excessive amounts of alcohol or had previous medical problems, such as a chronic liver infection. 

Hepatic Nicotinic acid hepatotoxicity (including cholestatic jaundice) has occurred. Cases of severe hepatic toxicity, including fulminant hepatic necrosis, have occurred in patients who have substituted sustained-release nicotinic acid products for immediate-release nicotinic acid at equivalent doses. Monitor ALT prior to treatment, every 6 to 12 weeks during the first year, and periodically thereafter (approximately 6-month intervals). 

Potentially fatal reactions to sulfonamides Fatalities have occurred, although rarely, as a result of severe reactions to sulfonamides (eg, zonisamide), including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. 

Severe, life-threatening, and, in some cases, fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, has been reported in patients treated with nevirapine (see Warnings). 

Fulminant liver failure results from massive necrosis of liver tissue. Diminution of mental function results, and this often leads to coma. The body undergoes a buildup of toxic products, alteration of its acid balance, and a decrease in cerebral blood flow. Impaired blood coagulation and intestinal bleeding occur as well. Other malfunctions and diseases of the liver include viral infections and alcoholic hepatitis. In 1999, of the 14,707 individuals on a waiting list for transplants, 4,498 received transplants and 1,709 died while waiting. As of February 2002, 18,434 people awaited liver transplants. 

Fulminant liver failure results from massive necrosis of liver tissue with a concurrent buildup in toxic products, disruption of acid balance, and a decrease in cerebral blood flow. Impaired blood coagulation and intestinal bleeding result. The main physiological effect is diminution of mental function that often leads to coma. 

Warnings Deaths due to following severe reactions have occurred after treatment with SMX Stevens-Johnson syndrome Toxic epidermal necrolysis Fulminant hepatic necrosis Agranulocytosis Aplastic anemia Other blood dyscrasias Hypersensitivity of the respiratory tract Should not be used for the treatment of streptococcal pharyngitis o c D [Pg.43]

Adverse effects Diarrhea is the most common side effect of tolcapone. As expected, /evocfopa-related adverse effects increase when tolcapone is added. These include postural hypotension, nausea, sleep disorders, anorexia, dyskinesias, and hallucinations. Most seriously, fulminating hepatic necrosis is associated with tolcapone use. Baseline and frequent, regular determinations of hepatic serum enzymes are suggested by the manufacturer. Any elevations above normal are cause for discontinuation. Because of the hepatotoxicity, tolcapone should only be used as an adjunct in patients on levodopa/carbidopa who are experiencing symptom fluctuations. 

Although NSAID-induced hepatotoxicity can occur at any time, it usually occurs within six to 12 weeks of the start of treatment [28]. Effects range from asymptomatic rises in LFTs to, rarely, fulminant hepatic necrosis resulting in death or the need for transplantation [30]. Mortality has been estimated at <1/100 000 patient-years of exposure... 

There is one published report of unintentional tramadol overdose causing acute fulminant hepatic necrosis and death. The exact amount taken was not known, but may have been more than twice the maximum daily dose of 100 mg four times a day for a period of days. Hepatitis and liver failure are listed as possible adverse effects in some US, but no UK product information [54]. 

Figure 31-3 Hemorrhagic/fulminant form of cytomegalovirus retinitis, with fuU-thickness retinal necrosis and hemorrhage. The patient s CD4-I- count was 2 cells per mm. ...

Because CAIs are sulfonamides, care should be taken to exclude a known sulfonamide allergy. Severe reactions to sulfonamides such as aplastic anemia, Stevens-Johnson syndrome, and fulminant hepatic necrosis are uncommon but have been known to occur. CAIs should be discontinued if any signs or symptoms of these conditions occur. 

There have been reports on the transition from virus-induced acute liver failure to chronic hepatitis. As the final stage of fulminant viral hepatitis (also known as acute liver dystrophy or submassive hepatitic necrosis), a postdystrophic scarred liver ( potato liver ) can develop. (s. fig. 35.14) Cicatricial distortions with a continuing effect, regenerative processes, intrahepatic vascular disorders and hypoxia-related damage lead to the conclusion that a posthepatitic, postdystrophic scarred liver may well be a special form of cirrhosis. 

R.S. Fulminant hepatic failure with massive necrosis as a result of hepatitis A infection. X. Clin. Gastroenterol. 1993 17 158—162... 

Exceptionally, fulminant hepatic failure with massive necrosis has been seen in patients taking sulfasalazine (63). Two fatal cases were reported in 1992 (SEDA-17, 424). 

Fulminant liver necrosis requiring liver transplantation occurred in a young pregnant woman who had taken chlormezanone 600 mg/day for 3 weeks (SEDA-17,157). 

Two cases of serious or fatal toxicity have been described in two infants who had been treated with herbal tea containing pennyroyal oil (4). One infant developed fulminant liver failure with cerebral edema and necrosis the other infant developed hepatic dysfunction and a severe epileptic encephalopathy. 

Fulminant hepatic failure due to massive hepatic necrosis occurred in a 58-year-old woman who took nimesulide for a few weeks for osteoarthritis (4). In the months before, she had received a first short course of the drug, apparently without problems. When she resumed nimesulide therapy she complained of non-specific symptoms, including nausea, and appeared jaundiced. The drug was withdrawn and Uver transplantation was performed, but she died of multiorgan failure. 

Rifampicin is rarely used as monotherapy. The risk of hepatotoxicity appears to be very low in patients with normal liver function, especially if rifampicin is given continuously. When given with isoniazid, rifampicin can cause a fulminant liver reaction. This may be attributable to enhancement of isoniazid hepatotoxicity as a result of enzyme induction by rifampicin. In some cases, jaundice occurred within 6-10 days after beginning isoniazid plus rifampicin (52). High serum transaminase activities, disturbances of consciousness, and centrilobular necrosis were found. All the patients recovered. 

A previously healthy 46-year-old man developed acute fulminant hepatitis following treatment with rabepra-zole, citalopram hydrobromide, terbinafine, and a multivitamin formulation (41). Liver biopsy showed submassive centrilobular necrosis and intrahepatic cholestasis with florid bile duct proliferation. 

Fulminant liver failure developed in a 39-year-old woman after she had taken topiramate for about 4 months, in addition to carbamazepine. The condition occurred after she increased the dosage of topiramate to 300 mg/day, and was preceded for a few days by tiredness and somnolence (50). She made an uncomplicated recovery after hver transplantation. Histological examination showed centrilobular necrosis, compatible with drug-induced fulminant liver failure. 

In contrast, type II hepatotoxicity is associated with massive centrilobular liver cell necrosis that can lead to fulminant liver failure. Type II hepatotoxicity is characterized by fever, jaundice, and very high serum transaminase levels. It may be immune-medi-ated and is thought to occur in genetically predisposed individuals. The incidence of type II hepatotoxicity 1 35 000 with one exposure to halothane and... 

Hepatotoxicity is a concern. During the first few months of therapy, transient elevation of hepatic transaminases occurs in an average 11% (up to 40%) of patients. Fulminant hepatic failure will develop in 1 in 5000-10000 patients. In these cases there is hepatic necrosis, steatosis, and a Reye s syndromelike illness. Fatal hepatic injury is most likely in children less than 2 years old and in those patients on multiple-drug therapy. 

The packaging of the kava products was unavailable for identification purposes. Liver biopsy revealed active fulminant hepatitis with extensive necrosis and tests for viral hepatitis were negative. She underwent a successful liver transplantation and was able to return to normal activity upon recovery (34). Unfortunately, no information was provided indicating that acetaminophen toxicity had been ruled out, and the observed toxic effect could also have been associated with a large, undiagnosed acetaminophen ingestion. 

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