Hepatitis: Korea

Park NH, Song IH, Chung YH. · Division of Gastroenterology, Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Centre, Seoul, Korea. · Postgrad Med J. · Pubmed #16891440 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and has a wide geographical variation. Eighty per cent of HCC is attributed to hepatitis B virus (HBV). The predominant carcinogenic mechanism of HBV associated HCC is through the process of liver cirrhosis, but direct oncogenic effects of HBV may also contribute. Prevention of HBV infections as well as effective treatment of chronic hepatitis B is still needed for the global control of HBV associated HCC. Continued investigation of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver.

Lee JH, Nam IY, Myung H. · Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yongin 449-791, Korea. · Mol Cells. · Pubmed #16819294 No free full text.

Abstract: Since its identification in 1989, hepatitis C virus has been the subject of extensive research. The biology of the virus and the development of antiviral drugs are closely related. The RNA polymerase activity of nonstructural protein 5B was first demonstrated in 1996. NS5B is believed to localize to the perinuclear region, forming a replicase complex with other viral proteins. It has a typical polymerase structure with thumb, palm, and finger domains encircling the active site. A de novo replication initiation mechanism has been suggested. To date, many small molecule inhibitors are known including nucleoside analogues, non-nucleoside analogues, and pyrophosphate mimics. NS5B interacts with other viral proteins such as core, NS3, 4A, 4B, and 5A. The helicase activity of NS3 seems necessary for RNA strand unwinding during replication, with other nonstructural proteins performing modulatory roles. Cellular proteins interacting with NS5B include VAMP-associated proteins, heIF4AII, hPLIC1, nucleolin, PRK2, a-actinin, and p68 helicase. The interactions of NS5B with these proteins might play roles in cellular trafficking, signal transduction, and RNA polymerization, as well as the regulation of replication/translation processes.

Jang SK. · NRL, PBC, Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea. · Virus Res. · Pubmed #16377015 No free full text.

Abstract: The scanning hypothesis provides an explanation for events preceding the first peptide bond formation during the translation of the vast majority of eukaryotic mRNAs. However, this hypothesis does not explain the translation of eukaryotic mRNAs lacking the cap structure required for scanning. The existence of a group of positive sense RNA viruses lacking cap structures (e.g. picornaviruses) indicates that host cells also contain a 5' cap-independent translation mechanism. This review discusses the translation mechanisms of atypical viral mRNAs such as picornaviruses and hepatitis c virus, and uses these mechanisms to propose a general theme for all translation, including that of both eukaryotic and prokaryotic mRNAs.

Kim SY, Kim JK, Kim HJ, Ahn JK. · Department of Microbiology, School of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea. · IUBMB Life. · Pubmed #16203685 No free full text.

Abstract: Hepatitis B virus X protein (HBx) is a promiscuous transcriptional transactivator of many viral and cellular promoters. HBx plays an important role in hepatitis B virus pathogenesis related with liver diseases including hepatocellular carcinoma (HCC). HBx is also involved in the signal transduction and the apoptosis of HBV-infected cells. However, the exact mechanism of apoptosis by HBx is still controversial. To demonstrate the mechanism of apoptosis by HBx, we induced the apoptosis of HBx-expressing liver cells, HepG2-X, by UV irradiation. We found that HepG2-X was much more sensitive to the UV-induced apoptosis than normal liver cells by analyzing the DNA fragmentation and the cell viability. Very interestingly, when the Fas-associated death domain (FADD)-dominant negative mutant protein was present in HepG2-X, the sensitized apoptotic response of HepG2-X to UV was completely abolished suggesting that there is a close relationship between HBx and Fas pathway in apoptosis. Therefore we examined the transactivation of Fas receptor (Fas) promoter and Fas ligand (FasL) promoter by HBx. We found that HBx strongly transcriptionally transactivated FasL promoter, but not Fas promoter. In addition, it also turned out that the mRNA levels of FasL are higher than those of Fas in HepG2-X. Taken together, HBx sensitizes the apoptosis of UV-irradiated liver cells by transcriptional transactivation of FasL gene.

Suh DJ, Jeong SH. · Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. · Intervirology. · Pubmed #16166792 No free full text.

Abstract: Chronic liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC), has been a major cause of mortality in Korea. The prevalence rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in the general population of Korea are approximately 1 and 5%, respectively. The most common genotypes of HCV in Korea are 1b and 2a. The sustained virological response rates after antiviral therapies, including combined interferon-alpha and ribavirin, have been reported to be 38-59%. The annual incidence of HCC among HCV-related liver cirrhosis has been estimated at 5%, and approximately 12% of HCC is attributable to HCV and 68% to HBV in Korea. The mean age of patients with HCV-related HCC at the time of diagnosis was consistently 10 years older than that of patients with HBV-related HCC. Moreover, HCV-related HCC was accompanied by more advanced liver cirrhosis than HBV-related HCC. Coinfection with HBV seemed to increase the risk of developing HCC in chronic HCV infection. After the successful program of hepatitis B vaccination, HCV infection is now emerging as an important etiology of chronic liver disease in Korea, which warrants more detailed and large-scale studies.

Koh KC. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Hepatol. · Pubmed #15788882 links to  free full text

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Choi JY. · Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Korea. · Korean J Hepatol. · Pubmed #15788881 links to  free full text

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Suh KS. · Department of Surgery, Seoul National University College of Medicine, Korea. · Korean J Hepatol. · Pubmed #15788880 links to  free full text

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Yoon JH. · Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Korea. · Korean J Hepatol. · Pubmed #15788879 links to  free full text

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Kweon YO. · Department of Internal Medicine, College of Medicine, Kyungpook National University, Daegu, Korea. · Korean J Hepatol. · Pubmed #15788878 links to  free full text

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Kim YS. · Institute for Digestive Research, Soon Chun Hyang University, College of Medicine, Seoul, Korea. · Korean J Hepatol. · Pubmed #15788877 links to  free full text

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Cho M. · Department of Medicine, Pusan National University College of Medicine, Korea. · Korean J Hepatol. · Pubmed #15788876 links to  free full text

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Kim YJ, Lee HS. · Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. · Intervirology. · Pubmed #15785084 No free full text.

Abstract: It is estimated that there are millions of single nucleotide polymorphisms (SNPs) within human genome and there are likely to explain much of the genetic diversity of individuals. Hepatocellular carcinoma (HCC) is etiologically associated with hepatitis B virus (HBV) in 80% of cases, and is the dominant cause of death among HBV carriers. Among patients with chronic HBV infection, family history is a known risk factor for the development of HCC; therefore, genetic factors are likely to modify the risk of HCC. However, the genetic factors that determine progression to HCC remain mostly to be investigated. In this review, we discussed that the natural history of HBV infection and host genetic factors related to HCC, study design and target gene selection for the detection of SNPs related to the occurrence of HCC. Also, we reviewed that several SNPs or haplotypes, which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection. Screening of these polymorphisms might be useful in clinical practice to stratify the lower or higher risk group for HCC and might modify the design of HCC surveillance programs in patients with chronic HBV infection, if further genetic susceptibilities are identified.

Kang JH, Lee KY, Kim CH, Sim D. · Department of Pediatrics, Our Lady of Mercy Hospital, Catholic University of Korea, Incheon, South Korea. · Asian Pac J Allergy Immunol. · Pubmed #15783137 No free full text.

Abstract: Hepatitis A is a vaccine-preventable disease with 1.5 million people infected world-wide annually. Improvement in the socio-economic status and general public health measures of Asian countries over the last 20 years has led to a shift in the seroprevalence of hepatitis A in many of these countries. In Korea, like in many other developed countries, this lowered endemicity has caused an upward shift in the average age of infection, resulting in larger numbers of individuals at risk of clinically significant hepatitis A infection. Sporadic outbreaks increase the public health burden of the disease. Inactivated hepatitis A vaccines are an effective prevention measure and have been shown to be safe, efficacious and well-tolerated in Korean children. Given this changing epidemiology of the disease and the associated increase in morbidity, vaccination of young children who are not immune, as well as other high risk groups, should be recommended.

Chang YJ, Byun KS. · Department of Internal Medicine, Korea University College of Medicine, Seoul 152-703, Korea. · Korean J Gastroenterol. · Pubmed #15665573 links to  free full text

Abstract: Chronic infection with HCV represents second most common cause of end-stage liver diseases and hepatocellular carcinoma in Korea. The introduction of new agents and regimens for the treatment of chronic hepatitis C, such as pegylated forms of interferon-alpha (Peg-IFN) and combination with oral ribavirin has resulted in substantial improvement in sustained virologic response (SVR) rates. SVR rate of Peg-IFN and ribavirin combination therapy can be 40-46% of individuals infected with genotype 1 and approximately 75-85% with genotype 2 and 3. Peg-IFN/ribavirin combination therapy represents current standard therapy of chronic hepatitis C. This article reviews the treatment objectives, outcomes, optimal regimens, efficacy and predictors of response, monitoring during treatment, adverse events, retreatment of persons who failed to respond to previous treatments, and treatment of special patient groups in chronic hepatitis C.

Seo JH, Ryan HF, Claussen GC, Thomas TD, Oh SJ. · Department of Rehabilitation Medicine, School of Medicine, Chonbuk National University, Chonju, Republic of Korea. · Neurology. · Pubmed #15365139 No free full text.

Abstract: BACKGROUND: Vasculitis is not usually considered as a cause of symmetric sensory neuropathy. OBJECTIVE AND METHODS: To present the clinical, pathologic, and electrophysiologic features of 17 (16%) cases of sensory neuropathy in vasculitis (SNV) among 106 cases with histologically proven vasculitic neuropathy that were collected over the last 30 years. RESULTS: In 41% of cases, SNV was found as systemic vasculitic neuropathy in association with primary vasculitic disease. The most common clinical presentation was symmetric polyneuropathy, seen in 53% of cases. The most common nerve conduction pattern was diffuse neuropathy pattern of axonal degeneration. Sural nerve biopsy was diagnostic in 88% of cases. In two cases, muscle biopsy was necessary for the definite diagnosis of vasculitis. Non-systemic SNV is usually benign. Of 11 patients followed for longer than 2 years, none developed motor weakness due to neuropathy. CONCLUSION: Sensory neuropathy, regardless of symmetry, can be due to vasculitis.

Lim YS, Suh DJ. · Department of Internal Medicine, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea. · J Korean Med Sci. · Pubmed #15308835 links to  free full text

Abstract: During the past decade, major breakthroughs have been achieved in treatment of chronic hepatitis B. Currently, three therapeutic agents are approved for chronic hepatitis B: interferon-alpha, lamivudine and adefovir dipivoxil. In patients with HBeAgpositive chronic hepatitis B, all of these drugs achieve HBeAg loss (24-33%) and anti-HBe seroconversion (12-30%) rates that are superior to those observed in untreated controls. Interferon-alpha has several drawbacks, such as the parenteral administration and the development of frequent and potentially serious side effects. Lamivudine is a safe drug with rare and generally mild side effects. Lamivudine induces an initial virological remission in 70-90% of patients, but only 30-40% of patients remain in remission after the third year due to progressively increasing viral resistance. The main advantage of adefovir dipivoxil is the rare emergence of resistance, which has been identified in less than 2% of patients at 2 yr of treatment. Adefovir is also effective against lamivudine-resistant strains. This review will focus on the natural history and recently gained knowledge on the treatment of chronic hepatitis B.

Han KH, Yoon YH. · Department of Internal Medicine, Yonsei University College of Medicine, Korea. · Korean J Hepatol. · Pubmed #15218341 links to  free full text

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Park SM. · Department of Internal Medicine, Chungbuk National University College of Medicine, 62 Gaeshin-dong, Heungdeok-gu, Cheongju-si, Chungbuk 361-711, Korea. · Korean J Gastroenterol. · Pubmed #15100485 links to  free full text

Abstract: Stem cells are undifferentiated cells capable of undergoing self-renewal and differentiation into a variety of cell types. They are derived from adult tissues (adult stem cells) as well as embryonal blastocysts (embryonic stem cells). Embryonic stem cells have pleuripotent capacity able to form tissues of all three germ layers but many ethical controversies concerning resource allocation or methods of harvesting are arising. Recently, many studies have demonstrated the multipotency of adult stem cells, but the mechanism of the plasticity remains to be determined yet. Several studies have suggested the possibilities of application of stem cells or tissue specific cells to regenerate gastroenterologic diseases such as liver cirrhosis, hepatitis, or inherited metabolic disorders. However, most of those trials are still limited to animal models, although anecdotal claims of successful therapy in humans have been reported. Even though the expectations and the promise of cell therapy are high, clinical efficacy has not been definitely demonstrated at this time. Thus, the application of cell therapy cannot be recommended to the patients outside the clinical trial setting.

Ryu SH, Chung YH. · Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea. · Korean J Hepatol. · Pubmed #15096712 links to  free full text

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Cho YK, Kim BI. · Department of Internal Medicine, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Pyeong-dong, Jongno-gu, Seoul 110-746, Korea. · Korean J Gastroenterol. · Pubmed #14646571 links to  free full text

Abstract: In therapy of chronic hepatitis B, there are new and exciting developments in antivirals such as nucleotide analogues. Adefovir dipivoxil is an oral prodrug of adefovir, a nucleotide analogue of adenosine monophosphate. This agent has a potent in vitro and in vivo effect against herpes virus, retroviruses, and hepadnaviruses. In the hepatitis B virus (HBV) setting, adefovir dipivoxil inhibits both the wild type and lamivudine-resistant HBV strains. The safety profile of adefovir dipivoxil 10 mg is excellent, but higher doses can produce renal tubular damage, particularly when the drug is used for prolonged therapy. Adefovir dipivoxil is an important new addition to the current first-line treatments for HBeAg positive and negative chronic hepatitis B, as well as being rescue therapy for lamivudine-resistant HBV strains. It is also licensed for use in adults with decompensated liver disease, as well as compensated liver disease where there is evidence of active viral replication, persistently elevated serum alanine aminotransferase levels and active liver inflammation and fibrosis. However, a longer follow-up is needed to establish the long term safety and efficacy of adefovir dipivoxil in patients with chronic HBV infection.

Park TS, Oh SH, Choi JC, Kim HH, Chang CL, Son HC, Lee EY. · Department of Laboratory Medicine, College of Medicine, Pusan National University, Busan, Korea. · Am J Hematol. · Pubmed #14508800 No free full text.

Abstract: We describe a 23-year-old retired military officer who was immunocompetent but diagnosed with hemophagocytic syndrome (HPS) by Plasmodium vivax infection. Initially, the patient was suspected to have toxic hepatitis related to heavy drinking. But abnormal hematologic findings required a further bone marrow examination and the diagnosis of HPS was made. Antimalarial chemotherapy then brought complete remission. Plasmodium falciparum, a species causing more severe malarial infection, was listed as one of the major causes of HPS. However, P. vivax was not mentioned, and only one case was reported in the literature. In this study, we suggest that P. vivax malaria should be included in the differential diagnosis of HPS, even in an immunocompetent person.

Ryu WS. · Department of Biochemistry and National Research Laboratory of Tumor Virology, Yonsei University, Seoul 120-749, Korea. · J Biochem Mol Biol. · Pubmed #12542984 links to  free full text

Abstract: Of many viral causes of human cancer, few are of greater global importance than the hepatitis B virus (HBV). Over 250 million people worldwide are persistently infected with HBV. A significant minority of these develop severe pathologic consequences, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Earlier epidemiological evidence suggested a link between chronic HBV infection and HCC. Further, the existence of related animal viruses that induce acute and chronic infections of the liver, and eventually HCC, confirms the concept that HBV belongs to one of the few human oncogenic viruses. Although it is clear that chronic HBV infections are major risk factors, relatively little is understood about how the viral factors contribute to hepatocarcinogenesis. This review will introduce molecular aspects of the viral infection, and highlight recent findings on the viral contribution to hepatocarcinogenesis.

Han KH, Kim KH, Chang HY. · Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. · J Gastroenterol Hepatol. · Pubmed #12472958 No free full text.

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Park JG. · Laboratory of Cell Biology, Korean Cell Line Bank, Cancer Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744, Korea. · Gan To Kagaku Ryoho. · Pubmed #11890121 No free full text.

Abstract: The cellular and molecular characteristics of SNU human cancer cell lines established in Korean are summarized according to the genetic and epigenetic alterations and functional analysis, etc. We have characterized and reported 89 different cell lines since 1987. These cell lines have been distributed to biomedical researchers through the KCLB (Korean Cell Lines Bank). Some cell lines have several distinguishing characteristics; i) two hepatocellular cell lines (SNU-354 and -368) expressing the MDR1 gene and hepatitis B virus, ii) Gastric carcinoma cell lines with mutations in TGF-beta type II receptor gene, iii) uterine cervical carcinoma cell line (SNU-1000) having intact episomal HPV-16, and iv) ovarian carcinoma cell line (SNU-251) have a nonsense mutation of codon 1815 in exon 23 of the BRCA1 gene. The distributed SNU cell lines have proven to be of value in various scientific research fields.