Cause of hepatocellular

No evidence of another cause of hepatocellular injury, such as viral hepatitis, marked hypotension, or congestive heart failure. 

Rechallenge was not attempted, but other potential causes of hepatocellular injury were ruled out. 

A person s use of alternative medicine must be solicited. Many herbal remedies were once wisely abandoned because of their common adverse reactions. Comfrey tea is a common cause of hepatocellular damage. As in the case of the Chinese remedy jin bu huan, or as in the case of the more elegantly presented chaparral capsules containing grease wood leaves, the end of therapy with these types of agents is occasionally severe disability or death from fulminant hepatic failure." Pennyroyal oil, maragosa oil, and clove oil cause a dose-related hepatotoxicity." ... 

Persistent activation of PPARa can induce the development of hepatocellular carcinoma in susceptible rodent species by a nongenotoxic mechanism, i.e., one that does not involve direct DNA damage by peroxisome proliferator chemicals or their metabolites. This hepatocarcinogenic response is abolished in mice deficient in PPARa, underscoring the central role of PPARa, as opposed to that of two other mammalian PPAR forms (PPARy and PPAR5), in peroxisome proliferator chemical-induced hepatocarcinogenesis. Other toxic responses, such as kidney and testicular toxicities caused by exposure to certain phthalate... 

HBV is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. 

Yet another SET domain protein, which is directly related to cancers, is SMYD3 that gets upregulated in colorectal cancer and hepatocellular carcinoma, a leading cause of death in developed countries (Hamamoto et al, 2004). 

Rats fed diets containing 30 or 300ppm ammonium perfluorooctanoate for 2 years had increased liver weights with occasional necrosis and an apparent dose-dependent increase in Leydig cell adenomas, but there was no evidence of an increased incidence of hepatocellular carcinoma. In a follow-up study in male mice, 300ppm in the diet for 2 years caused increases in liver, Leydig cell, and pancreatic acinar cell tumors that may have been associated with the peroxisome-proliferating capabilities of the compound. Ammonium perfluorooctanoate also produced sustained increases in serum estradiol concentrations. ... 

In 2-year gavage studies there was some evidence of carcinogenic activity in male rats based on increased incidences of cholangiocar-cinomas and bile duct dysplasia and fibrosis. There was also some evidence of carcinogenicity in female mice based on increased incidences of hepatocellular adenomas. Male mice showed clear evidence of carcinogenicity based on increased incidences of hepatocellular adenomas and carcinomas. The development of liver tumors may be related to the chronic inflammatory effects noted at this site. In another experiment with hamsters, exposure to furfural vapor 7 hours/day, 5 days/week for 1 year caused irritation of the nasal mucosa and growth retardation but no evidence of carcinogenic effects. ... 

Gavage administration of 590 and 1179mg/kg/day to mice for 78 weeks caused a significant increase in the incidence of hepatocellular carcinomas, whereas no increase in these tumors was observed in rats given 212 or 423 mg/kg/day. A nonsignificant increase in renal tumors was seen in rats, and tubular nephropathy occurred in both species. In 2-... 

Large gavage doses, approximately 500 and lOOOmg/kg per day for 78 weeks, caused a statistically significant increase in the incidence of hepatocellular carcinomas in mice. Inhalation exposure by rats to 200 or 400 ppm for 2 years caused an increased incidence of mononuclear cell leukemia a dose-related trend for a rare renal tubular neoplasm was observed in males. ... 

In short-term renal toxicity studies in rats gavage administration of 1,1,2,2-tetra-chloroethane caused renal toxicity as evidenced by an increased renal tubule cell labeling index, indicating replicative DNA synthesis. In 2-year studies 1,1,2,2-tetrachloroethane administered by gavage produced an increased incidence of hepatocellular carcinomas in mice but not in rats. In one epidemiological study of exposed army workers there was a slight increase in deaths due to genital cancer and leukemia. Exposure levels were not available,... 

Toxaphene caused a dose-related increase of hepatocellular carcinomas in mice fed 98 or 198 ppm for 80 weeks. In rats, there was a significantly increased incidence of neoplastic thyroid lesions at the high dose." The lARC has determined that there is sufficient evidence in experimental animals for the carcinogenicity of toxaphene and that it is possibly carcinogenic to humans. ... 

Hepatotoxicity Naltrexone has the capacity to cause direct hepatocellular injury when given in excessive doses. It is contraindicated in acute hepatitis or liver failure, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects. 

Two studies were located that reported the occurrence of liver cancer in humans exposed to carbon tetrachloride fumes, both acutely (Tracey and Sherlock 1968) and for longer periods (Johnstone 1948). In the former case, a male died of hepatocellular carcinoma 7 years after acute intoxication with carbon tetrachloride at an age of 59, although he had a history of moderate alcohol consumption (without demonstrable liver cirrhosis). In the second case, a 30- year-old female died of "liver cancer" after 2-3 years of occupational exposure to carbon tetrachloride that was sufficient to produce signs of intoxication. However, this evidence is much too sparse to establish a cause-and-effect relationship. 

Hepatitis C virus (HCV) is an RNA virus that is a common cause of parenterally acquired viral hepatitis chronic infection follows acute infection in 80% to 85% of cases. Although liver disease resulting from chronic HCV infection is only slowly progressive, HCV is the most common cause of chronic liver disease in the United States, the most common etiology for hepatocellular carcinoma, and the leading indication for liver transplantation [34-36]. 

Similarly, modulation of hepatocellular proliferation by peroxisome proliferators has been implicated in the mechanism of carcinogenesis. This can theoretically result in increased levels of mutation by increasing the frequency of replicative DNA synthesis as well as increasing the number of hepatocytes at risk. Furthermore, hepatocellular proliferation is probably involved in the promotion of growth of pre-neoplastic hepatocytes. There is clear evidence that di(2-ethylhexyl) phthalate causes acute and sustained hepatocellular proliferation under bioassay conditions which resulted in liver tumours in rats (Marsman et al., 1988). 

Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly cancer. One million patients with HCC die each year. One of the major causes of HCC is infection with the hepatitis C virus (HCV), and the pathogenesis of HCV-related HCC in its incipient stage from the infection to the onset of cancer is being researched. 

Definition and causes of jaundice Jaundice (icterus) refers to the yellow color of the skin, nail beds, and sclerae caused by deposition of bilirubin, secondary to increased bilirubin levels in the blood. There are three major forms of jaundice hemolytic jaundice, caused by massive lysis of red blood cells, releasing more heme than can be handled by the reticuloendothelial system obstructive jaundice, resulting from obstruction of the bile duct and hepatocellular jaundice, caused by damage to liver cells that decreases the liver s ability to take up and conjugate bilirubin. In addition, neonatal jaundice is caused by the low activity of hepatic glucuronylation of bilirubin, especially in premature infants. 

The mechanisms underlying hepatotoxicity from halothane remain unclear, but studies in animals have implicated the formation of reactive metabolites that either cause direct hepatocellular damage (eg, free radical intermediates) or initiate immune-mediated responses. With regard to the latter mechanism, serum from patients with halothane hepatitis contains a variety of autoantibodies against hepatic proteins, many of which are in a trifluoroacetylated form. These trifluoroacetylated proteins could be formed in the hepatocyte during the biotransformation of halothane by liver drug-metabolizing enzymes. However, TFA proteins have also been identified in the sera of patients who did not develop hepatitis after halothane anesthesia. 

TCDD. Furthermore, chronic exposure to 6.5/ Kf g/kg/day of 2,7-DCDD in the feed caused leukemias, lymphomas, hemangiosarcomas, hemangiomas, and dose-related increased incidences of hepatocellular adenomas and carcinomas in male B6C3F, mice (NCI/NTP 1979a). In contrast, no cancer effects were observed following chronic exposure of Osbome-Mendel rats to 5 / 10" g/kg/day of... 

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