• IMMUNE NETWORK
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• v.15 no.4
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• pp.191-198
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• 2015

Hepatitis B virus (HBV) is responsible for approximately 350 million chronic infections worldwide and is a leading cause of broad-spectrum liver diseases such as hepatitis, cirrhosis and liver cancer. Although it has been well established that adaptive immunity plays a critical role in viral clearance, the pathogenetic mechanisms that cause liver damage during acute and chronic HBV infection remain largely known. This review describes our current knowledge of the immune-mediated pathogenesis of HBV infection and the role of immune cells in the liver injury during hepatitis B.

• Clinical and Experimental Pediatrics
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• v.51 no.7
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• pp.696-703
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• 2008

Korea is now classified as an area of intermediate endemicity for hepatitis B virus (HBV), due to the implementation of universal HBV vaccination and national preventive programs for HBV infection. A national program of HBV vaccination was launched in Korea in 1988 for school-going children and was listed on a vaccination guideline in 1991. In 1995, universal vaccination for newborn infants was started for the prevention of perinatal HBV transmission. The prevalence of HBsAg among Korean middle school students has shown marked decreased from 3.2% in the late 1990s to 0.44% in 2007. HBsAg positivity in preschool children was 0.9% in 1995, decreased to 0.2% in 2007 by national prevention program of hepatitis B vertical transmission, launched in 2002. Vaccine failure rate of HBV immunoprophylaxis is 4.2% by this program. The infected children should be monitored per 6-12 months interval. Lamivudine and interferon are approved therapies for children with chronic hepatitis B in immune-clearance phase in Korea.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

• The Korean Journal of Nuclear Medicine
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• v.15 no.2
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• pp.59-66
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• 1981

Serum HBsAg and Anti-HBs obtained by radioimmunoassay were studied in 109 cases of various liver diseases who visited or were admitted to National Medical Center from December, 1980 to July, 1981. The results were as follows; 1) HBsAg was detected in 67.0% of total 109 cases; 71.9% of 32 cases with acute viral hepatitis, 71.4% of 14 cases with chronic hepatitis, 65.2% of 46 cases with liver cirrhosis and 58.8% of 17 cases with hepatoma. 2) Anti-HBs was detected in 32.1% of total 109 cases; 37.0% of 46 cases with liver cirrhosis, 29.4% of 17 cases with hepatoma, 28.6% of 14 cases with chronic hepatitis, 28.1% of 32 cases with acute viral hepatitis. 3) HBsAg or Anti-HBs, the markers of Hepatitis B virus was detected in 89.0% of total 109 cases; 93.6% of 32 cases with acute viral hepatitis, 89.1% of 46 cases with liver cirrhosis, 85.7% of 14 cases with chronic hepatitis and 82.4% of 17 cases with hepatoma, which strongly suggested that the various liver diseases were associated with hepatitis B virus infection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8405-8410
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• 2016

Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese population. We hypothesized that these polymorphisms might be related to HCC susceptibility in Thai population as well. Study subjects were divided into 3 groups consisting of CHB-related HCC (n=192), CHB without HCC (n=200) and healthy controls (n=190). The studied SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the distribution of different genotypes for both polymorphisms were in Hardy-Weinberg equilibrium (P>0.05). Our data demonstrated positive association of rs7574865 with HCC risk when compared to healthy controls under an additive model (GG versus TT: odds ratio (OR)=2.07, 95% confidence interval (CI)=1.06-4.03, P=0.033). This correlation remained significant under allelic and recessive models (OR=1.46, 95% CI=1.09-1.96, P=0.012 and OR=1.71, 95% CI=1.13-2.59, P=0.011, respectively). However, no significant association between rs2293152 and HCC development was observed. These data suggest that SNP rs7574865 in STAT4 might contribute to progression to HCC in the Thai population.

• Journal of Preventive Medicine and Public Health
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• v.19 no.2 s.20
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• pp.281-292
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• 1986

Infection by hepatitis B virus is one of the major health problems of this nation. HBsAg positive rates of general population and school children were known to be as about 8 percent and 3.9 to 5.9 percent respectively. To study the incidence rate of hepatitis B infection in school children of rural area, author had examined 475 school children of relatively isolated agricultural area for baseline prevalence of hepatitis B virus serologic markers and followed up 415 school children during 10 months to determined the frequency of serologic conversion. The major results are summarized as followings: 1) Among the 278 susceptible children who were followed up, 26 had seroconversion for HBsAg or Anti-HBs. Therefore, the cumulative incidence rate during 10 months is estimated 9.4%. 2) The incidence rate of hepatitis B infection tends to increase with age (6-9yrs: 3.2%, 10-14yrs: 9.5%, 15-17yrs: 18.9%), and the incidence rate in male (13.0%) was higher than in female (5.7%). 3) The incidence rates of hepatitis B virus infection were not different statistically among three economic classes (The rates of lower, middle and higher class were 11.8%, 7.1% and 10.5%.). 4) The incidence rates of hepatitis B virus infection were not different statistically between visitors and non-visitors of clinic or hospital, dental clinic, persons received IV and not received IV, and persons with familial history and without familial history of liver diseases. Therefore all of these factors were not identified as risk factor of hepatitis B virus infection. And the transmissibility within the class of school was not recognized, too. 5) Among the 25 children who were HBsAg positive when enrolled, 15 (60%) were still HBsAg positive, who were identified as chronic carrier 15 of 415 school children were chronic carriers, then chronic carrier rate was estimated 3.6%, and there was no difference between sexes. 6) Of 38 children who had been Anti-HBs positive when enrolled, 5 (13.2%) lost Anti-HBs. Therefore, the loss rate of Anti-HBs per year is estimated to be 15.8%.

• The Journal of the Korean Society for Microbiology
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• v.21 no.2
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• pp.233-241
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• 1986

Patients of chronic hepatic diseases(n=107) including chronic hepatitis caused by hepatitis B virus infections(n=31), liver cirrhosis(n=53), and hepatocellular carcinoma(n=23) were examined to ascertain genetic relationship between chronic hepatic diseases and histocompatibility antigen. Peripheral blood lymphocytes were separated from whole blood by the method of Ficoll/Hypaque gradient. Total 54 histocompatibility antigens(class I antigens: 41, class II antigens: 13) were analysed by performing of complement dependent microlymphocytotoxicity method using Terasaki's and Catholic Medical College tissue typing plates. HLA antigen frequencies were compared with those of 661 normal controls. The following results were obtained: 1. HLA antigen frequencies of HLA-Bw46, -Bw76, -Cw1, -Cw6, and HLA-DR8 in chronic hepatitis patients were shown to be higher than those in controls(P<0.01). 2. HLA antigen frequencies of HLA-Bw46, -Cw7(P<0.01), and HLA-B37, -Bw58, -Cw1, -MT1(P < 0.05) in liver cirrhosis patients were shown relatively higher frequencies than those in controls. 3. In patients with hepatocellular carcinoma, antigens of HLA-A1, -A26, -Cw3, -Cw7 and HLA-DR6 were dominantly detected. 4. There were negative associations with HLA-Cw4, and -DR4 in patients of chronic hepatic diseases(P < 0.05).

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1722-1728
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• 2008

The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBe, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5917-5935
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• 2012

Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.