Hepatitis: Hwang SG

Song HU, Hwang SG. · Department of Internal Medicine, College of Medicine, Pochon CHA University, Seongnam, Korea. · Korean J Gastroenterol. · Pubmed #17464165 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has the third highest mortality rate among malignancies in South Korea. Despite the continuing efforts for the early detection of HCC, the mortality rate and prognosis have not been improved yet. Its clinical behavior is quite different from other cancers. High recurrence rate after curative treatment might be the reason for poor prognosis. Several methods including chemoprevention, blocking the development of HCC, have been under investigations. The vaccine for hepatitis, in the form of primary prevention, is considered to be the most effective one inhibiting the development of liver disease. Furthermore, keeping away from hepatotoxic agents is another way for preventing liver cell injuries. Secondary prevention is to stop the development of HCC in chronic liver diseases. Since the level of DNA in hepatitis B virus (HBV) hepatitis patients is closely related with the development of HCC, it is helpful to lower the DNA level using anti-viral agents. In addition, IFN, one of the anti-viral agents, can inhibit HCV hepatitis from tumorigenesis. Cyclo-oxygenase (COX)-2 inhibitors are also alleged to have a function in interrupting the development of HCC. Tertiary prevention means the prevention of recurrence of HCC after successful treatment. Because of high recurrence rate, the prevention of recurrence should be one of the important factors affecting the prognosis of HCC. Up to now, COX inhibitors, retinoic acids, vitamin K2, glycyrrhizin epigallocatechin-3-gallate (EGCG), and ginseng had been reported to be effective for the chemoprevention of HCC. Further studies are required for an advancement in the prevention of HCC.

Moon YM, Hwang SG, Kim BS, Rim KS, Cho M, Kim DJ, Han JY, Kim YS, Choi HS, Ahn SH. · Department of Internal Medicine, Kwandong University College of Medicine, Gangneung, Korea. · Korean J Hepatol. · Pubmed #18159148 links to  free full text

Abstract: BACKGROUND AND AIMS: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. METHODS: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. RESULTS: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. CONCLUSIONS: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

Yoo BC, Kim JH, Chung YH, Lee KS, Paik SW, Ryu SH, Han BH, Han JY, Byun KS, Cho M, Lee HJ, Kim TH, Cho SH, Park JW, Um SH, Hwang SG, Kim YS, Lee YJ, Chon CY, Kim BI, Lee YS, Yang JM, Kim HC, Hwang JS, Choi SK, Kweon YO, Jeong SH, Lee MS, Choi JY, Kim DG, Kim YS, Lee HY, Yoo K, Yoo HW, Lee HS. · Samsung Medical Center, Sungkyunkwan University, and Yonsei University Hospital, Seoul, Korea. · Hepatology. · Pubmed #17464992 No free full text.

Abstract: Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n=182) or placebo (n=61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P<0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P<0.0001). ALT normalization in the clevudine group was well maintained during post-treatment follow-up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. CONCLUSION: A 24-week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg-positive chronic hepatitis B.

Kwak SY, Kim UK, Cho HJ, Lee HK, Kim HJ, Kim NK, Hwang SG. · Department of Internal Medicine, College of Medicine, Pochon CHA University, Seongnam, South Korea. · Anticancer Res. · Pubmed #19035314 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death in South Korea, but genetic susceptibility factors of HCC have not been examined extensively. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) play an essential role in both DNA synthesis and methylation and polymorphisms in the MTHFR gene, 677C>T, 1298A>C and the MTRR gene, 66A>G, are associated with several types of malignancy. In this study, the allelic frequencies and genotype distribution of three polymorphisms in the MTHFR and MTRR genes from 96 hepatocellular carcinoma (HCC) patients and 201 controls were examined to assess the association between these polymorphisms and the development of HCC in this Korean population. The 66AG+GG (G allele-bearing) genotype of the MTRR gene was significantly associated with an increased risk of HCC (odds ratio, OR, 1.687; 95% confidence interval, CI=1.022-2.787). Moreover, the combination of MTHFR 1298AA/MTRR 66AG+GG (OR=1.854, 95% CI=1.005-3.420) and MTHFR 1298AC+CC/MTRR 66AG+GG (OR=2.733, 95% CI=1.195-6.249) showed a significant association with HCC risk. In the data classified by age and etiology, MTRR 66A>G over the age of 65 years, MTHFR 1298A>C under the age of 65 years and the MTRR 66AG+GG genotype in the hepatitis B virus (HBV) patients were increased risk factors for the disease. The MTHFR 1298A>C and the MTRR 66A>G genotypes were associated with an increased risk of HCC in this Korean population. Further studies involving larger and varied populations could provide a potential tool for cancer risk assessment in patients who are at risk of developing HCC.

Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, Heathcote EJ, Manns M, Bzowej N, Niu J, Han SH, Hwang SG, Cakaloglu Y, Tong MJ, Papatheodoridis G, Chen Y, Brown NA, Albanis E, Galil K, Naoumov NV, Anonymous00034. · Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. · Gastroenterology. · Pubmed #19027013 No free full text.

Abstract: BACKGROUND & AIMS: The GLOBE trial has compared the efficacy and safety of telbivudine versus lamivudine treatment over 2 years in patients with chronic hepatitis B. METHODS: Hepatitis B e antigen (HBeAg)-positive (n = 921) and HBeAg-negative (n = 446) patients received telbivudine or lamivudine once daily for 104 weeks. The primary outcome, assessed in the intent-to-treat population, was therapeutic response (hepatitis B virus DNA <5 log(10) copies/mL and either HBeAg loss or normalization of alanine aminotransferase [ALT] level). RESULTS: The therapeutic response to telbivudine was superior to that of lamivudine in HBeAg-positive (63% vs 48%; P < .001) and HBeAg-negative (78% vs 66%; P = .007) patients. HBeAg-positive patients given telbivudine also had better outcomes compared with lamivudine in terms of nondetectable viremia (< 300 copies/mL) at 55.6% versus 38.5% (P < .001), HBeAg loss at 35.2% versus 29.2% (P = .056), and viral resistance at 25.1% versus 39.5% (P < .001). Hepatitis B e antigen seroconversion was 29.6% versus 24.7% (P = .095) in all patients and 36% versus 27% (P = .022) in patients with baseline ALT level > or = 2 times normal. Telbivudine-treated HBeAg-negative patients showed higher rates of nondetectable viremia compared with lamivudine at 82.0% versus 56.7% (P < .001) and less resistance at 10.8% versus 25.9% (P < .001). Adverse events occurred with similar frequency, whereas grade 3/4 increases in creatine kinase levels were more common in patients given telbivudine (12.9% vs 4.1%, P < .001). Multivariate logistic regression analyses identified telbivudine treatment, among other variables, as an independent predictor of better week 104 outcomes. CONCLUSIONS: Telbivudine is superior to lamivudine in treating patients with chronic hepatitis B over a 2-year period.

Shi KD, Hwang SG, Choi JH, Hwang IJ, Yoon JH, Kim KI, Kwon CI, Hong SP, Park PW, Rim KS. · Department of Gastroenterology and Hepatology, Bundang CHA Hospital, College of Medicine, Pochon CHA University, Seongnam, Korea. · Korean J Hepatol. · Pubmed #18617767 links to  free full text

Abstract: BACKGROUNDS/AIMS: Negative hepatitis B core antigen (HBcAg) staining in hepatocytes is indicative of viral replication by an active immune response. HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with minimal liver injury in the absence of hepatocyte regeneration. The aim of this study was to elucidate whether the existence and expression pattern of HBcAg predicts the response to antiviral treatment. METHODS: The study involved 58 patients with biopsy-proven chronic hepatitis B who were treated with lamivudine. Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and alanine aminotransferase in serum were recorded every 3 months. The inflammation grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4 according to lobular inflammation, portal inflammation, periportal inflammation, and fibrosis. RESULTS: The 58 patients included 49(84%) HBcAg-positive patients, with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm and nuclei in 34(69%). The grade of lobular inflammation and the total histology score were significantly higher in patients with cytoplasmic expression of HBcAg than in HBcAg-negative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and 12 months differed significantly between the cytoplasmic and mixed expression groups (P<0.01). CONCLUSIONS: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment.

Kwon CI, Hwang SG, Shin SJ, Chang SW, Kim SY, Ko KH, Hong SP, Park PW, Rim KS, Kang MS, Chung HJ, Hong SP. · Department of Internal Medicine, College of Medicine, Bundang CHA Hospital, Pochon CHA University, Seongnam, Korea. · Liver Int. · Pubmed #18331240 No free full text.

Abstract: BACKGROUND/AIMS: The objective of this study was to document the prevalence rate of occult hepatitis B virus (HBV) in healthy pregnant woman and the possibility of transmission to the foetus. METHODS: This study was performed prospectively with 202 healthy pregnant women. HBV-DNA testing was performed using two specific quantitative tests with two independent sets of sera and cord blood. DNA sequencing analysis was carried out to confirm the specificity of polymerase chain reaction (PCR) product of HBV-DNA testing. RESULTS: Eight of 202 (4%) individuals with the TaqMan PCR assay and 23 of 202 (11.4%) with the COBAS Amplicor HBV Monitor test were HBV-DNA positive. Six (3%) individuals were positive with both methods. Sequencing and genotyping analysis of HBV polymerase gene with sera of the 75th subject resulted in genotype C. HBV-DNA testing with four cord blood samples showed that all were HBV-DNA negative. CONCLUSION: Occult HBV infection shows a difference in prevalence rate depending on the test method but the existence has been confirmed by sequencing analysis. Our results also suggest that vertical transmission through the cord blood is not so high as to be clinical problems and warrants further investigation.

Kim JH, Kwon CI, Ko EH, Kim DY, Kim HY, Jung SH, Ko KH, Hong SP, Shin SJ, Hwang SG, Park PW, Rim KS. · Departments of Internal Medicine and Obstetric, College of Medicine, Pochon CHA University, Seongnam, Korea. · Korean J Gastroenterol. · Pubmed #18172357 links to  free full text

Abstract: BACKGROUND/AIMS: Elevated transaminase levels are often detected during pregnancy. Causes are variable and difficult to differentiate. Furthermore, there is no practical guideline for abnormal transaminase levels in pregnancy. The aim of this study was to suggest a strategy for managing elevated transaminase level during pregnancy. METHODS: One hundred and fifty-five women with elevated transaminase level were included from an antenatal care center between January 1, 2003 and December 31, 2004. Another 221 women with normal transaminase levels were enrolled as control group. We analyzed documented causes, changes in laboratory tests, and pregnancy outcomes. RESULTS: Two groups showed no difference in baseline characteristics except the duration of pregnancy, parity, and albumin level. Of abnormal results, 39.4% occurred between 30 and 40 gestational weeks while 29% occurred between 10 and 20 gestational weeks. Common causes were hyperemesis gravidarum followed by pre-eclampsia, viral hepatitis, and HELLP syndrome. Excluding viral hepatitis, 69 patients showed abnormal results in the first two trimesters and the results were normalized during the follow-up period. AST and ALT levels were 52.9 (+/-49.6) IU/L and 83.3 (+/-77.0) IU/L during the first two trimesters in the patient group. Abnormal results during the third trimester were associated with shorter duration of pregnancy. CONCLUSIONS: Elevated transaminase levels up to 3 to 4 times of the upper normal limit during the first two trimesters could be safely observed with careful history taking and hepatitis viral antigen tests. However, abnormal results in the third trimester were associated with a shorter duration of pregnancy and should be managed carefully.

Kang JK, Cheong JY, Cho SW, Cho JH, Park JS, Kim YB, Kim DJ, Hwang SG, Yang JM, Park YN. · Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea. · Korean J Hepatol. · Pubmed #18159150 links to  free full text

Abstract: BACKGROUND AND AIMS: FibroScan is a new medical device that noninvasively measures liver stiffness. The aim of this study was to assess the accuracy of the liver stiffness measurement by FibroScan for making the diagnosis of liver fibrosis in patients with chronic viral hepatitis. METHODS: We studied 103 patients with chronic viral hepatitis B or C and they underwent FibroScan and liver biopsy between October 2005 and August 2006. Liver fibrosis was staged on a 0-4 scale according to the Korean Society of Pathologists Scoring System. The diagnostic accuracy was assessed by analysis of the receiver operator characteristics (ROC). RESULTS: The liver stiffness was 3.5-57.1 kPa (mean: 11.8, SD: 8.9). The mean value of liver stiffness in each fibrosis stage group (F1, F2, F3 and F4) was 5.8+/-1.8 kPa, 11.3+/-6.8 kPa, 11.8+/-6.0 kPa and 23.4+/-16.5 kPa, respectively. Liver stiffness measured by FibroScan showed reliable correlation with the liver fibrosis stage as confirmed by liver biopsy (r=0.56, p<0.001). The AUROC (95% CI) of > or = F2, > or = F3 and F4 was 0.93 (0.86-0.99), 0.72 (0.62-0.82) and 0.80 (0.67-0.92), respectively. The sensitivity and specificity of 7.5 kPa, which was the cutoff value for > or = F2, was 84% and 90%, respectively. CONCLUSIONS: FibroScan is a reliable method for the diagnosis of significant fibrosis (> or =F2) and cirrhosis in patients with chronic liver disease. The liver stiffness measurement by FibroScan showed good diagnostic performance for significant fibrosis.

Yoo BC, Kim JH, Kim TH, Koh KC, Um SH, Kim YS, Lee KS, Han BH, Chon CY, Han JY, Ryu SH, Kim HC, Byun KS, Hwang SG, Kim BI, Cho M, Yoo K, Lee HJ, Hwang JS, Kim YS, Lee YS, Choi SK, Lee YJ, Yang JM, Park JW, Lee MS, Kim DG, Chung YH, Cho SH, Choi JY, Kweon YO, Lee HY, Jeong SH, Yoo HW, Lee HS. · Sungkyunkwan University Samsung Medical Center, Seoul, South Korea. · Hepatology. · Pubmed #17647293 No free full text.

Abstract: Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log(10) copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log(10) reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. CONCLUSION: A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.

Kwon CI, Lee JH, Choi KH, Ko KH, Hong SP, Hwang SG, Park PW, Oh D, Rim KS, Kim S. · Department of Internal Medicine, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, Bundang-Gu, Seongnam, Korea. · Korean J Gastroenterol. · Pubmed #17189924 links to  free full text

Abstract: BACKGROUND/AIMS: Liver dysfunction and reactivation of hepatitis virus are well-described complications in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. However, there has been just few reports on such complications and on the preemptive use of lamivudine in Korea. The aims of this study were to determine the prevalence of hepatitis B and C virus infection and the incidence of liver dysfunction in patients with malignancies who receive chemotherapy, to determine the reactivation rate of hepatitis B virus (HBV) in those patients, to evaluate the effect of preemptive use of lamivudine in patients with HBV infection. METHODS: Among 1,477 patients who received chemotherapy due to various malignancies from January 2000 to June 2005, 668 patients with incomplete viral studies or hepatitis related malignancy were excluded. A retrospective study was conducted by reviewing the medical records of remaining 809 patients. RESULTS: The overall prevalence rate of hepatitis B or C virus in patients receiving chemotherapy was 6.55% (53/809). The incidences of liver dysfunction was not significantly different between hepatitis virus positive group and negative group. Reactivation rate of hepatitis B or C virus after chemotherapy was 15% (6/40). In all patients who received lamivudine therapy, aspartate aminotransferase and alanine aminotransferase level were normalized and HBV DNA negativity achieved. CONCLUSIONS: The existence of hepatitis virus in patients receiving chemotherapy did not significantly influence the development of severe liver dysfunction, owing probably to the lamivudine therapy. Further prospective studies are required to ascertain the reactivation of hepatitis virus in patients receiving chemotherapy and the need for prophylactic lamivudine therapy in HBV positive patients.

Hwang SG. · Department of Internal Medicine and Institute for Clinical Reserch, College of Medicine, Pochon CHA University, Sungnam, Korea. · Korean J Hepatol. · Pubmed #16380660 links to  free full text

This publication has no abstract.

Kim JK, Hwang SG, Park H, Choi HY, Cho HJ, Ko KH, Hong SP, Park PW, Kim NK, Rim KS. · Department of Internal Medicine, College of Medicine, Pochon CHA University, Sungnam, Korea. · Korean J Hepatol. · Pubmed #16177549 links to  free full text

Abstract: BACKGROUND/AIMS: The therapeutic strategies of applying adefovir for treating lamivudine resistant HBV mutants are controversial. Thus, we observed the clinical outcomes after discontinuation of lamivudine to establish the timing to initiate adefovir therapy. METHODS: Fifty chronic hepatitis B (CHB) patients with lamivudine resistant HBV mutants who had received lamivudine for more than 12 months were included in the study. We investigated the clinical outcomes at 6 months after the end of treatment (EOT). We compared the serial clinical outcomes among respective groups based on serum ALT at the EOT and the clinical characteristics of patients with or without acute exacerbation (AE) and the HBeAg loss. We also investigated the predictive parameters of AE and HBeAg loss. RESULTS: Fifteen patients (30%) had experienced AE at 6 months after the EOT. Four patients received antiviral agents because of their hepatic decompensation. Patients with AE had higher serum ALT values and lower HBV DNA titers at EOT compared with those patients without AE. Serum ALT at the EOT was the predictive parameter of AE. Eight patients (21.6%) had newly developed HBeAg loss at 6 months after EOT. The total bilirubin at EOT was the predictive parameter of HBeAg loss. CONCLUSIONS: CHB patients with lamivudine resistant HBV mutants had favorable clinical outcomes at 6 months after EOT. Therefore, we can consider observing the clinical courses after discontinuation of lamivudine and it is not always required to overlap the adefovir for treating lamivudine resistant HBV mutants except for the treatment of patients with a high risk of developing decompensation.

Hong SP, Kim NK, Hwang SG, Chung HJ, Kim S, Han JH, Kim HT, Rim KS, Kang MS, Yoo W, Kim SO. · GeneMatrix Inc., Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. · J Hepatol. · Pubmed #15094233 No free full text.

Abstract: BACKGROUND/AIMS: Mutations in hepatitis B virus (HBV) to lamivudine resistance that arise during prolonged treatment frequently cause amino acid substitutions in the YMDD motif of HBV DNA polymerase. Current methods of detecting such variants are time-consuming, labor intensive, and unsuitable for screening large numbers of samples. Here, we describe the development of a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) genotyping assay suitable for detecting HBV variants in a sensitive and specific manner. METHODS: The assay is based on PCR amplification and mass measurement of oligonucleotides containing sites of mutation of the YMDD motif. RESULTS: The MALDI-TOF MS-based genotyping assay is sufficiently sensitive to detect as few as 100 copies of HBV genome per millilitre of serum, with superior specificity for determining mixtures of wild-type and variant viruses. When sera from 40 patients were analyzed, the MALDI-TOF MS-based assay correctly identified known viral variants and additional viral quasi-species not detected by previous methods, as well as their relative abundance. CONCLUSIONS: The sensitivity, accuracy and amenability to high-throughput analysis makes the MALDI-TOF MS-based assay suitable for mass screening of HBV infected patients receiving lamivudine, and can help provide further understanding of disease progression and response to therapy.

Kim YS, Kim SI, Hwang SG, Kim JO, Cho JY, Lee JS, Lee MS, Hwang SD, Shim CS. · Institute for Digestive Research, Department of Internal Medicine, Soonchunhyang University, Seoul, Korea. · Eur J Gastroenterol Hepatol. · Pubmed #10514111 No free full text.

Abstract: BACKGROUND/AIMS: Transcription of HBV (hepatitis B virus) pre-core and pre-genomic mRNAs is controlled by core promoter. Therefore, mutations in the core promoter region might change the activity of liver diseases through an altered transcriptional level of the mRNA. The present study was carried out to determine the diversity of HBV core promoter sequences in chronic HBV carriers. METHODS: DNA sequences in the core promoter region were determined after cloning the PCR product. Two groups of chronic HBV carriers with HBeAg, including five cases of asymptomatic carriers (ASCs, 21 clones) and eight with chronic hepatitis (CH, 50 clones) were studied. RESULTS: Mutations in the core promoter were found in three out of the ASCs (11 clones), and in all eight cases in the CH group (48 clones). While mutations at nucleotide 1762 (A-->T) and 1764(G-->A) were not found in ASC, mutations at the same positions were found in all the cases of CH group (40 clones) (P=0.003). Diverse patterns of mutations in the core promoter were observed in each patient in the CH group. CONCLUSIONS: Further studies are needed to determine whether the diversity of HBV core promoter mutations has clinical significance such as the seroconversion of HBeAg to anti-HBe.