Hepatocellular carcinoma hepatitis

ViraUy induced (exogenous) cancers (hepatocellular carcinoma hepatitis C virus-induced squamous cell carcinoma of the uterine cervix or oral cavity (HPV-induced) are preventable with vaccines-induced immunity. The exogenously enforced virally induced cancers are reacted to with the induction of strong host immune defense, whereas the endogenously induced cancers often receive support from the subverted host, a reaction that a cancer vaccine is expected to break and reverse [1994-2000]. Some cancer vaccines caused tumor enhancement. Many cancer vaccines failed [2001a]. It is not clear at all what purpose the new review Cancer Vaccines served [2001b]. 

Steel J, Baum A, Carr B (2004) Quality of life in patients diagnosed with primary hepatocellular carcinoma hepatic arterial infusion of Cisplatin versus 90-Yttrium microspheres (Therasphere). Psychooncology 13 73-79... 

Staining Applications Bronchial elastic fibers chromosomes eosinophil granules " elastic fibers em-bryos fibronectin vitronectin hepatocytes hepa-titis B virus hepatitis hepatocellular carcinoma hepatitis B surface antigen (HBsAg) histamine Kupffer cells leukocytes lipids mucins lipoproteins " plasma proteins nucleic acids oocjdes hairs "- ... 

Hepatitis B virus (HBV) Hepatocellular carcinoma Progenomic RNA Inhibition of viral gene expression... 

HBV infection remains a major worldwide public health problem. The World Health Organization estimates that there are still 350 million chronic carriers of the vims, who are at risk of developing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The success of IFN-a treatment - mainly performed as combined treatment with adenine-arabinoside - has been measured by the normalization of liver enzymes, loss of HBe antigen and of detectable viral DNA in the serum of patients. It has been estimated from several clinical trials that as many as 40% of treated HBV patients would respond to therapy with IFN-a or combined treatment with nucleoside analogues and IFN-a. 

Similar to HBV, infections with hepatitis C virus (HCV) have a high rate of progression from an acute to a chronic state that frequently leads to cirrhosis or hepatocellular carcinoma [2]. Monotherapy for HCV infection with IFN-a or combined therapy with ribavirin and IFN-a is associated with initial rates of response as high as 40%. The rates of sustained responses are, however, lower and also depend on the viral genotype. In patients infected with HCV genotype 2 or 3, the response was maximal after 24 weeks of treatment, whereas patients infected with genotype 1 -the most frequent in the USA and Europe - required a minimum treatment course of 48 weeks for an optimal outcome. 

Hepatocellular carcinoma (HCC) develops in patients with chronic liver diseases associated with hepatitis B and hepatitis C vims infections with high incidences. Here, an acyclic retinoid has been shown to suppress the posttherapeutic recurrence after interferon-y or glycerrhicin treatment in cirrhotic patients who underwent curative treatment of preceding tumors. The retinoid induced the disappearance of serum lectin-reactive a-fetoprotein (AFP-L3), a tumor marker indicating the presence of unrecognizable tumors in the remnant liver, suggesting a deletion of such minute (pre)malignant clones (clonal deletion). As a molecular mechanism of the clonal deletion, a novel mechanism of... 

Worldwide, 15 million HBsAg carriers are also infected with hepatitis D/delta virus (HDV) (Gaeta et al. 2000). This situation represents a major therapentic challenge, as most of these patients have advanced liver disease, inclnding cirrhosis in 60-70% of cases, and hepatocellular carcinoma (Fattovich et al. 2000 Saracco et al. 1987). No specific HDV inhibitors have been developed, and IFN-a-based treatment is more difficnlt in HBV-HDV infection than in HBV monoinfection. HDV RNA levels in sernm can be nsed to monitor treatment efficacy. The endpoint of therapy is HDV RNA clearance and ALT normalization, and this is sometimes achieved after the end of treatment. A snstained response can lead to HBsAg clearance from serum. 

Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YE (2007) Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol 46 45-52... 

Individuals with chronic hepatitis B have a high risk to develop cirrhosis and, once cirrhosis is present, the 5-year cumulative risk to develop hepatocellular carcinoma is about 10-15% (Fattovich et al. 2004). 

Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH (2006) Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 295(l) 65-73... 

The list of vimses involved in other human cancers includes hepatitis B, which is associated with hepatocellular carcinoma human papilloma viruses with cervical, penile and some anal carcinomas human T-cell lymphotropic virus type 1 associated with adult T-cell leukaemia/lymphoma syndrome and HIV with Kaposi s sarcoma. 

Iron overload is known to be toxic and potentially fatal. The major pathological effects of hepatic iron overload are fibrosis and cirrhosis, and hepatocellular carcinoma (Bonkovsky, 1991). The role of free radicals in the pathology of hepatic iron overload has been the subject of a detailed review recently (Bacon and Britton, 1990). 

Hereditary hemochromatosis is an autosomal recessive disease of increased intestinal iron absorption and deposition in hepatic, cardiac, and pancreatic tissue. Hepatic iron overload results in the development of fibrosis, hepatic scarring, cirrhosis, and hepatocellular carcinoma. Hemochromatosis can also be caused by repeated blood transfusions, but this mechanism rarely leads to cirrhosis. 

Only 10% to 15% of patients have acute hepatitis C that resolves without any further sequelae.10 In more than 85% of cases, hepatitis C develops into a chronic disease. Approximately 70% of chronic HCV cases progress to mild, moderate, or severe hepatitis. While the natural history of the progression to cirrhosis is not clear, it is estimated that 10% to 20% of cases may take up to 20 to 40 years from the time of exposure to advance from fibrosis to cirrhosis.10 Fifteen to twenty percent of patients infected with HCV develop complications associated with cirrhosis. Once cirrhosis is confirmed, the rate of developing hepatocellular carcinoma increases to 1% to 4% per year.10 The estimated death rate from HCV infection is 1.8 deaths per 100,000 persons per year.12,15... 

General outcomes for treating hepatitis are to (1) prevent the spread of the disease (2) prevent and treat symptoms (3) suppress viral replication (4) normalize hepatic aminotransferases (5) improve histology on liver biopsy and (6) decrease morbidity and mortality by preventing cirrhosis, hepatocellular carcinoma, and ESLD. 

Hepatitis B virus is a blood-borne or sexually transmitted virus. Most acute infections occur in adults, while chronic infections usually occur in individuals infected as infants or children. However, about 10% of adults who contract hepatitis B virus will fail to clear their infection and develop chronic hepatitis B infection. Individuals with chronic hepatitis B infection are at risk for cirrhosis or hepatocellular carcinoma. Vaccination with hepatitis B vaccine is the most effective way to prevent hepatitis B infection.6... 

Hepatocellular carcinoma (liver Hepatitis B virus Not yet classified DNA... 

Chronic forms of hepatitis (in particular B, C and D) can result in liver cirrhosis and/or hepatocellular carcinoma. This occurs in up to 20 per cent of chronic hepatitis B sufferers and in up to 30 per cent of chronic hepatitis C sufferers. The scale of human suffering caused by hepatitis on a worldwide basis is enormous. Approximately 5 per cent of the global population suffer from chronic hepatitis B. An estimated 50 million new infections occur each year. Over 1.5 million of the 300 million carriers worldwide die annually from liver cirrhosis and hepatocellular carcinoma. 

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

Approximately 20% of patients with chronic HBV infection develop complications of decompensated cirrhosis, including hepatic insufficiency and portal hypertension. HBV is a risk factor for development of hepatocellular carcinoma. 

A statistically significant increase in hepatocellular carcinomas was seen in male and female mice that were dosed with 590 and 1,179 mg/kg/day hexachloroethane in com oil by gavage for 78 continuous weeks (Weisburger 1977). The incidence of tumors in the exposed mice was greater than that in controls on the basis of both the Fisher Exact test and the Cochran-Armitage test. There were no hepatic tumors in male or female rats with chronic exposure to doses of 10-423 mg/kg/day (NTP 1977, 1989 Weisburger 1977). 

There are data from animal studies in mice, rats, and pigs that indicate that both carbohydrate metabolism and lipid metabolism may be affected by exposure to heptachlor or heptachlor epoxide (Enan et al. 1982 Halacka et al. 1974 Kacew and Singhal 1973 Pelikan 1971). Alterations in gluconeogenic enzymes and an increase in cellular steatosis in the liver have been reported. Granulomas and fibrotic liver have also been observed. In addition, hepatocellular carcinoma was identified as causally related to heptachlor in the diet in a mouse study conducted by the National Cancer Institute (NCI 1977). The existing evidence suggests that heptachlor and heptachlor epoxide are hepatic toxicants. 

Abbreviations AFP, a-fetoprotein CK, cytokeratin ECM, extracellular matrix EMT, epithelial to mesenchymal transition HCC, hepatocellular carcinoma HNF, hepatocyte nuclear factor, HSC, hepatic stellate cell MFB, myofibroblast M2-PK, M2-pyruvate kinase PDGF, platelet-derived growth factor TGF, transforming growth factor. 

Murakami Y, Saigo K, Takashima H, Minami M, Okanoue T, Brechot C et al (2005). Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Guf 54 1162-1168. 

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