Virus-associated Chronic Hepatitis Research Articles

Frequent epigenetic inactivation of SFRP genes in hepatocellular carcinoma

Activation of the Wnt signaling pathway is frequently observed in hepatocellular carcinoma (HCC), though mutation of three of its components, CTNNB1, AXIN1, and AXIN2, is observed substantially less often. We examined the relationship between Wnt signaling and epigenetic alteration of secreted frizzled-related protein (SFRP) genes in HCC. We frequently detected the active form of beta-catenin and accumulation of nuclear beta-catenin in liver cancer cell lines. We detected methylation of SFRP family genes in liver cancer cell lines (SFRP1, 9/12, 75%; SFRP2, 7/12, 58%; SFRP4, 3/12, 25%; SFRP5, 7/12, 58%) and primary HCCs (SFRP1, 9/19, 47%; SFRP2, 12/19, 63%; SFRP5, 8/19, 42%), though methylation of SFRP4 was not found in primary HCCs. SFRP methylation also was detected in hepatitis B or C virus-associated chronic hepatitis (SFRP1, 6/37, 16%; SFRP2, 14/37, 38%; SFRP5, 5/37, 14%) and liver cirrhosis (SFRP1, 10/28, 36%; SFRP2, 9/28, 32%; SFRP5, 3/28, 11%), suggesting that methylation of these genes is an early event in liver carcinogenesis. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor (TCF/LEF) transcriptional activity in liver cancer cells, while overexpression of a beta-catenin mutant and depletion of SFRP1 using siRNA synergistically upregulated TCF/LEF transcriptional activity. Our results confirm the frequent methylation and silencing of Wnt antagonist genes in HCC, and suggest that their loss of function contributes to activation of Wnt signaling during hepatocarcinogenesis.

Hepatitis C en Chile: Magnitud del problema

Hepatitis C virus-associated chronic hepatitis is one of the most important causes of liver-related mortality and morbidity worldwide. This review analysis the available clinical and epidemiological information about this disease in Chile and compares it with data available from Latin America and other countries. Chronic hepatitis C seroprevalence in the general Chilean population is 1.15% by ELISA III and 0.85% by recombinant immunoblot assay (RIBA). Mortality due to cirrhosis (all causes) in Chile is one of the highest in the world. We show indirect evidence that chronic hepatitis C may account for a significant proportion of these deaths. The disease is the most common cause for liver transplantation in adults. Based on the available information, we conclude that chronic hepatitis C is an important cause of disease and mortality in Chile.

SEN virus infection influences the pathological findings in liver but does not affect the incidence of hepatocellular carcinoma in patients with chronic hepatitis C and liver cirrhosis

This investigation compared the histological findings in the livers of chronic hepatitis C patients who were or were not co-infected with SEN virus (SEN-V) to determine the histological and clinical characteristics of SEN-V infection in Japan. Three hundred and ninety-two patients with hepatitis C virus-associated chronic hepatitis (CH) or liver cirrhosis (LC) were included in the study. Serum samples were tested for the presence of SEN-V DNA by nested polymerase chain reaction. The liver biopsy specimen of each patient was examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal, and portal areas; F stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; damage to the bile ducts; steatosis and irregular regeneration of hepatocytes (IR). Of the 473 patients, 194 (41.0%) were positive for SEN-V DNA. The rate of progression of F stage correlated with SEN-V DNA positivity. The blood biochemical parameters did not differ significantly between the SEN-V DNA-positive and -negative patients. The histological features of the livers of SEN-V DNA-positive patients included more severe parenchymal inflammatory cell infiltration and more IR. In particular, among those at the F2, F3 and F4 stages, the degree of IR of the SEN-V DNA-positive patients was significantly greater than that of the SEN-V DNA-negative patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence and survival rate did not differ between the SEN-V DNA-positive and-negative patients. SEN-V co-infection may influence the histopathological features of the livers of patients with type C CH and LC but does not affect the outcome of patients with type C chronic liver disease.

Letter To The Editor: The Prevalence Of Hepatitis C Seropositive And Opisthorchiasis Among The Patients With Cholangiocarcinoma

Cholangiocarcinoma is the malignancy of the biliary duct system, originating in the liver and terminating at the ampulla of Vater. It is a tumor that arises from the intrahepatic or extrahepatic biliary epithelium. The etiology of most bile duct cancers remains undetermined. Presently, these malignant biliary tract diseases are common cancerous diseases among the people in the Southeast Asia, with the world highest prevalence at the northeastern Thailand and Laos (1). Concerning the pathogenesis, it has been suggested that longstanding inflammation, as with primary sclerosing cholangitis or chronic parasitic infection, could play a role by inducing hyperplasia, cellular proliferation, and, ultimately, malignant transformation (2). This carcinoma tends to grow slowly and to infiltrate the walls of the ducts, dissecting along tissue planes and leading to biliary tract obstruction. Opisthorchiasis, an important intestinal parasite infection with high prevalence in tropical countries, is proposed to be linked to the very high incidence rate of cholangiocarcinoma in the Northeast of Thailand (3). Liver fluke or Opisthorchis viverri is the corresponding pathogen for this infection (3). In addition to opisthorchiasis, hepatitis virus-associated chronic hepatitis or cirrhosis has recently been suggested to be involved in the pathogenesis of cholangiocarcinoma(4, 5). Here, we reported the prevalence of hepatitis C seropositive among the Thai patients with cholangiocarcinoma. We retrospectively reviewed on the medical records of all cholangiocarcinoma patients who admitted to King Chulalongkorn Memorial Hospital during year 1992 to 2001. In each case, the cholangiocarcinoma had been diagnosed from the final histopathological results. A total of 30 cases with known hepatitis C serology and stool examination result were selected for further prevalence study. The data collated from the records also included the sex and age of each patient. A total of 30 patients with cholangiocarcinoma, who admitted to King Chulalongkorn memorial Thailand during 1992 – 2001, with known hepatitis C serology was selected for further prevalence study. Of the total 30 cases (16 males and 14 females), the hepatitis C seropositive was found in 4 cases (2 males and 2 females, giving the total prevalence rate equaled to 13.3 % (12.5 % for male and 14.3 % for female). Concerning stool examination, opisthorchis viverrini eggs were detected in 2 cases (1 male and 1 female) giving the total prevalence rate equaled to 6.7 % (6.3 % for male and 7.1 % for female). All cases with opisthorchiasis also have hepatitis C seropositive. One of the relating risk for development of cholangiocarcinoma is chronic infection. According to the recent study of Donato et al (4) , HCV is a risk factor for cholangiocarcinoma. Here, we can demonstrate a high rate (13.3 %) of hepatitis C seropositive among the cholangiocarcinoma patients. This prevalence was about 5 times higher in comparison with the Thai local population (about 2.6 %)(6). These findings can state the high hepatitis C seropositive rate among the cholangiocarcinoma patients. In addition, the co-presentation of hepatitis C seropositive and opisthorchiasis in some cases also implies for a higher risk. Since the hepatitis C infection is believed to be one of the risk to development of the cholangiocarcinoma and both Letter To The Editor: The Prevalence Of Hepatitis C Seropositive And Opisthorchiasis Among The Patients With Cholangiocarcinoma 2 of 3 cholangiocarcinoma and hepatitis C infection are common in Thailand (1), the screening for hepatitis C, adding to the routine screening for liver fluke by stool examination, may be a useful strategy for decrease of the high rate of cholangiocarcinoma in Thailand. Further long-term study to study the relation of hepatitis C infection and cholangiocarcinoma is recommended.

The prevalence of hepatitis B seropositivity among patients with cholangiocarcinoma.

Cholangiocarcinoma is a malignancy of the biliary duct system. Presently, these malignant biliary tract diseases are common among the people in Southeast Asia, with the world's highest prevalence in northeastern Thailand and Laos. This carcinoma tends to grow slowly and to infiltrate the walls of the ducts, dissecting along tissue planes and leading to biliary tract obstruction. Recently, hepatitis virus-associated chronic hepatitis or cirrhosis has been suggested to be involved in the pathogenesis of cholangiocarcinoma. Here, we report the prevalence of hepatitis B seropositivity among Thai patients with cholangiocarcinoma. A total of 55 patients with cholangiocarcinoma, who were admitted to King Chulalongkorn Memorial Hospital, Thailand, during 1992-2001, with known hepatitis B serology was selected for further prevalence study. Of the 55 cases (32 males and 22 females), hepatitis B seropositivity was found in five cases (three males and two females), giving a total prevalence rate equal to 9.1% (9.4% for male and 9.2% for females). Since hepatitis B infection is believed to be a risk factor in the development of cholangiocarcinoma, and both cholangiocarcinoma and hepatitis B infection are common in Thailand, screening and vaccination for hepatitis B may be a useful strategy to decrease the high rate of cholangiocarcinoma in Thailand. Further long-term study to study the relation of hepatitis B infection and cholangiocarcinoma is recommended.