Hepatitis: Paik SW

Paik SW. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Gastroenterol. · Pubmed #18604138 links to  free full text

Abstract: Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis worldwide. Up to 85% of individuals infected with HCV develop chronic infection, which can progress to cirrhosis and hepatocellular carcinoma. The primary goal in the treatment of HCV infection is to reduce the mortality by preventing liver-related deaths associated with the development of hepatocellular carcinoma and decompensated cirrhosis. Pegylated interferons together with ribavirin are currently the standard of care for patients with chronic hepatitis. Here, I discuss the goals of treatment, indication and treatment of chronic hepatitis C.

Lee KS, Byun KS, Chung YH, Paik SW, Han JY, Yoo K, Yoo HW, Yoo BC, Lee HS. · Yonsei University Hospital, Seoul, Korea. · Intervirology. · Pubmed #17622789 No free full text.

Abstract: OBJECTIVES: The objectives of the study were to evaluate the safety and antiviral activity of 24-week treatment with clevudine 30 mg in HBeAg(+) chronic hepatitis B patients. Biochemical and serological responses were also assessed. METHOD: Twenty-one patients received clevudine 30 mg for 24 weeks and were followed up for another 24 weeks off therapy. RESULTS: Median decreases from baseline in HBV DNA were 4.65 and 1.96 log(10) copies/ml at week 24 (end of treatment) and week 48 (24 weeks off therapy), respectively. Analysis of individual data showed that HBV DNA levels were below the lower limit of detection (300 copies/ml) by Amplicor PCR assay in 19, 57, 19 and 0% at week 12, 24, 34 and 48, respectively. The proportion of patients with normal ALT were 67, 81 and 75% at week 24 (end of treatment), 34 and 48 (24 weeks off therapy), respectively. The rates of HBeAg loss were 24 and 20% at week 24 and 48, respectively. No viral breakthrough during treatment was observed. CONCLUSION: Clevudine 30 mg treatment for 24 weeks was well tolerated and exhibited more potent antiviral activity and a higher ALT normalization rate than 12-week treatment with durable efficacy at week 24 off therapy.

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.

Sung YM, Choi D, Lim HK, Lee WJ, Kim SH, Kim MJ, Paik SW, Yoo BC, Koh KC, Lee JH, Choi MS. · Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Radiol. · Pubmed #16969048 links to  free full text

Abstract: OBJECTIVE: To evaluate the long-term follow-up results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in Korea. MATERIALS AND METHODS: Sixty-eight nodular HCCs initially detected in 64 patients, were subjected to US-guided PEI as a first-line treatment. Long-term survival rates, local tumor progression rates, and complications were evaluated, as were the influences of tumor size and Child-Pugh class on these variables. RESULTS: No major complications occurred. The overall survival rates of the 64 patients at three and five years were 71% and 39%, and their cancer-free survival rates were 22% and 15%, respectively. The overall survival rate of patients with a small HCC (< or =2 cm) was significantly higher (p = 0.014) than that of patients with a medium-sized HCC (< or =2 cm). The overall survival rate of patients with Child-Pugh class A was significantly higher (p = 0.049) than that of patients with Child-Pugh class B. Of 59 cases with no residual tumor, local tumor progression was observed in ablation zones in 18, and this was not found to be significantly influenced by tumor size or Child-Pugh class. CONCLUSION: The results of our investigation of the long-term survival rates of PEI in HCC patients in Korea (a hepatitis B virus-endemic area) were consistent with those reported previously in hepatitis C endemic areas. Patients with a smaller tumor or a better liver function exhibited superior survival rates.

Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, Chang WY, Berg T, Flisiak R, McCloud P, Pluck N, Anonymous00057. · Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China. · N Engl J Med. · Pubmed #15987917 links to  free full text

Abstract: BACKGROUND: Current treatments for chronic hepatitis B are suboptimal. In the search for improved therapies, we compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. METHODS: A total of 814 patients with HBeAg-positive chronic hepatitis B received either peginterferon alfa-2a (180 microg once weekly) plus oral placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine alone. The majority of patients in the study were Asian (87 percent). Most patients were infected with hepatitis B virus (HBV) genotype B or C. Patients were treated for 48 weeks and followed for an additional 24 weeks. RESULTS: After 24 weeks of follow-up, significantly more patients who received peginterferon alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19 percent [P<0.001] and 27 percent vs. 19 percent [P=0.02], respectively) or HBV DNA levels below 100,000 copies per milliliter (32 percent vs. 22 percent [P=0.01] and 34 percent vs. 22 percent [P=0.003], respectively). Sixteen patients receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001). The most common adverse events were those known to occur with therapies based on interferon alfa. Serious adverse events occurred in 4 percent, 6 percent, and 2 percent of patients receiving peginterferon alfa-2a monotherapy, combination therapy, and lamivudine monotherapy, respectively. Two patients receiving lamivudine monotherapy had irreversible liver failure after the cessation of treatment--one underwent liver transplantation, and the other died. CONCLUSIONS: In patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.

Park SJ, Paik SW, Choi MS, Lee JH, Koh KC, Kim SJ, Joh JW, Lee SK. · Division of Gastroenterology, Samsung Medical Center, Sungkyunkwan Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Transplant Proc. · Pubmed #12072331 No free full text.

This publication has no abstract.

Lee KW, Lee SK, Joh JW, Kim SJ, Park JH, Chon SE, Choi SH, Heo JS, Paik SW, Koh KW, Lee JH, Choi MS, Kim YI, Lee BB. · Department of Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea. · Transplant Proc. · Pubmed #11750547 No free full text.

This publication has no abstract.

Suh HJ, Park MK, Lee HIe, Gwak GY, Koh KC, Paik SW, Yoo BC, Lee JH. · Department of Internal Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Gangnam-gu, Seoul, Korea. · Korean J Gastroenterol. · Pubmed #19458467 links to  free full text

Abstract: BACKGROUND/AIMS: The aim of this study was to elucidate the antiviral efficacy of lamivudine (LMV)-adefovir (ADV) combination therapy in chronic hepatitis B patients who showed resistance to LMV and ADV consecutively. METHODS: A retrospective review was performed in eighteen patients with chronic hepatitis B who developed virologic breakthroughs during LMV-ADV sequential mono-therapy and treated with LMV-ADV combination therapy. RESULTS: The median duration of follow up was 17 months (range, 6-27) after the start of LMV-ADV combination therapy. Mean HBV DNA level in log10 IU/mL was 6.08+/-0.95, 4.05+/-1.66, 3.17+/-1.58, 3.18+/-2.16, and 2.35+/-1.52 at 0, 3, 6, 12, and 24 months, respectively. Sixteen patients (88.9%) showed HBV DNA reduction below detection limit (<20,000 IU/mL). HBeAg seroconversion was observed in one patient (7.1%) after 8 months of combination therapy. Virologic breakthrough occurred in only one patient after 21 months of combination therapy. Viral rebound occurred in two patients at 12 months and 14 months of combination therapy. Normalization of serum ALT was achieved in twelve patients (66.7%). Primary non-response was observed in two cases (11.1%). CONCLUSIONS: LMV-ADV combination treatment was effective in 88.9% of patients with resistance to LMV and ADV in a short-term follow up. It may be applied as a bridge therapy until another effective antiviral regimen becomes available.

Jung HW, Choi MS, Kim KH, Park SH, Yeon KK, Lee JH, Koh KC, Paik SW, Yoo BC. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Hepatol. · Pubmed #19346785 links to  free full text

Abstract: BACKGROUNDS/AIMS: It has been shown that adefovir dipivoxil is an effective antiviral agent in the treatment of chronic hepatitis B (CHB), not only in wild-type hepatitis B virus (HBV) infection, but also in lamivudine-resistant (LAMV-R) cases. However, little is known about the durability of the virologic response to adefovir in LAMV-R CHB patients. METHODS: Fifteen HBV e-antigen (HBeAg)-positive, LAMV-R CHB patients showed a virologic response to adefovir monotherapy. These patients received additional adefovir for at least a further 12 months. The virologic relapse rate after discontinuation of adefovir was evaluated. In addition, predictive factors associated with virologic relapse were investigated. RESULTS: The median level of serum HBV DNA before adefovir administration was 7,457,840 IU/mL (range 107,920-99,524,960 IU/mL). The median duration of adefovir treatment was 30 months (range 14-46 months). During a median follow-up period of 14 months after discontinuation of adefovir, the 1-, 2-, 3-, 6-, and 12-month cumulative relapse rates were 26.7%, 53.3%, 73.3%, 80%, and 80%, respectively. High pretreatment HBV DNA levels were found to be the only factor that was predictive of off-therapy relapse. CONCLUSIONS: Our data suggest that the adefovir-monotherapy-induced virologic response is not durable in most patients with LAMV-R HBeAg-positive CHB, especially in those with a high pretreatment HBV DNA level.

Gwak GY, Lee DH, Moon TG, Choi MS, Lee JH, Koh KC, Paik SW, Park CK, Joh JW, Yoo BC. · Department of Medicine and Digestive Disease Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Hepatogastroenterology. · Pubmed #19260471 No free full text.

Abstract: BACKGROUND/AIMS: Recent research has proposed a role for HBV pre-S mutation in the development of HCC. Although the mechanism is not clear, pre-S mutant-induced endoplasmic reticulum (ER) stress and oxidative DNA damage may participate in this process. Therefore, we investigated the correlation of HBV pre-S mutation with ER stress and cellular oxidative DNA damage in HBV-related HCC patients. METHODOLOGY: Thirty HBV-related HCC patients and 8 control patients were included. HBV DNA was extracted from sera and the HBV S coding region was analyzed by PCR and sequencing. Immunohistochemical staining for 8-oxoG and OGG1 were performed in HCC and non-neoplastic tissues. RESULTS: Study subjects were categorized into three groups: the pre-S mutant HBV-infected HCC patients (group 1, n=20), wild-type HBV-infected HCC patients (group 2, n=10) and HBV non-infected patients (group 3, n=8). The expression level of 8-oxoG and OGG1 in non-neoplastic tissue was higher in group 1/2 than in group 3; however, there was no significant difference between group 1 and 2. There was no significant difference in 8-oxoG/OGG1 expressions between HCC and non-neoplastic tissues. CONCLUSIONS: The present study did not support a pathophysiologic role for HBV pre-S mutation, related to ER stress and oxidative DNA damage, in hepatocarcinogenesis.

Sinn DH, Paik SW, Kang P, Kil JS, Park SU, Lee SY, Song SM, Gwak GY, Choi MS, Lee JH, Koh KC, Yoo BC. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. · Liver Int. · Pubmed #18710426 No free full text.

Abstract: BACKGROUND/AIMS: The present study aimed to assess the incidence of advanced cirrhotic complications and to identify the risk factors associated with such complications in chronic hepatitis C. METHODS: The data of 1137 chronic hepatitis C patients were retrospectively reviewed. We analysed the incidence rate and risk factors for 'disease progression', as defined by the occurrence of an increase of at least 2 points in the Child-Pugh score, oesophageal/gastric variceal bleeding, spontaneous bacterial peritonitis, hepatic encephalopathy, death related to liver disease or development of hepatocellular carcinoma (HCC). RESULTS: Of the 1137 patients enrolled for analysis, 490 patients received antiviral treatment. The overall annual incidence rate of disease progression was 0.8 and 3.7% for patients with and without antihepatitis C virus (anti-HCV) therapy respectively. The development of HCC was the most common cause of disease progression. In patients with anti-HCV therapy, treatment response, platelet level and aspartate aminotranferase:platelet ratio index (APRI) were independent factors associated with disease progression. For those without anti-HCV therapy, older age, male sex, diabetes, platelet level and APRI were independent factors for disease progression. APRI was strongest predictor for disease progression. CONCLUSIONS: The present study demonstrated that the development of HCC was the most common cause of disease progression, and we also identified the risk factors associated with disease progression. Thus, patients at such risks need close monitoring for disease progression, and especially for detecting HCC. Moreover, the active application of antiviral therapy and efforts to improve the antiviral response are required.

Kim JH, Lee JH, Park SJ, Bae MH, Kim JH, Kim do Y, Kim JK, Choi MS, Koh KC, Paik SW, Yoo BC. · Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea. · Hepatogastroenterology. · Pubmed #18613411 No free full text.

Abstract: BACKGROUND/AIMS: Although the natural seroclearance rate of Hepatitis B surface antigen (HBsAg) is reported to be 0.4-2% in western countries, this is not well known in Korea. This study aimed to elucidate the rate of natural HbsAg seroclearance, factors associated with seroclearance and prognosis after seroclearance. METHODOLOGY: In 1999, 250 chronic HBsAg carriers without any history of antiviral treatment and without any evidence of liver cirrhosis or hepatocellular carcinoma were selected. Follow-up HBsAg/ anti-HBs tests were performed annually till 2004. During a mean follow-up period of 48 months, 24 patients were lost and 11 received antiviral treatment. Finally, 215 patients completed the study. RESULTS: HBsAg seroclearance was observed in 11 patients (6 males, 5 females). One-year seroclearance rate was 1.4%. All patients who achieved seroclearance were HBeAg (-)/HBV DNA (-) at the time of enrollment. Additionally, old age and normal serum alanine aminotransferase (ALT) level were the factors associated with seroclearance (p < 0.05, respectively). During the follow-up period, only mild transient elevations of ALT were observed in 4 patients and no serious complications were observed. CONCLUSIONS: Natural seroclearance occurred exclusively in patients who were HBeAg (-)/HBV-DNA (-), and annual rate of natural HBsAg seroclearance was 1.4%. No significant complications were observed after seroclearance.

Fried MW, Piratvisuth T, Lau GK, Marcellin P, Chow WC, Cooksley G, Luo KX, Paik SW, Liaw YF, Button P, Popescu M. · University of North Carolina, Chapel Hill, NC 27599-7584, USA. · Hepatology. · Pubmed #18220290 No free full text.

Abstract: The aims of this study were to evaluate the usefulness of quantitative hepatitis B e antigen (HBeAg) values for predicting HBeAg seroconversion in patients treated with peginterferon alfa-2a and to assess the dynamic changes in quantitative HBeAg during therapy, compared with conventional measures of serum hepatitis B virus DNA. Data were analyzed from a large, randomized, multinational phase III registration trial involving 271 HBV-infected HBeAg-positive patients who received peginterferon alfa-2a plus oral placebo for 48 weeks. HBeAg levels were measured serially during therapy using a microparticle enzyme immunoassay validated with in-house reference standards obtained from the Paul Ehrlich Institute (PEIU/mL). In patients who achieved HBeAg seroconversion, levels of HBeAg consistently decreased during treatment and remained at their lowest level during the 24 weeks of posttreatment follow-up. After 24 weeks of treatment, 4% of patients with the highest levels of HBeAg (>or=100 PEIU/mL) achieved HBeAg seroconversion, yielding a negative predictive value of 96%, which was greater than that obtained for levels of HBV DNA (86%). Late responders to peginterferon alfa-2a could also be differentiated from nonresponders by continued decrease in HBeAg values, which were not evident by changes in HBV DNA. CONCLUSION: These analyses suggest quantitative HBeAg is a useful adjunctive measurement for predicting HBeAg seroconversion in patients treated with peginterferon when considering both sensitivity and specificity compared with serum HBV DNA.

Yi M, Choi EO, Paik SW, Kim KS, Kwak S, Lee HJ. · College of Nursing, Seoul National University, 28 Yongon-dong, Jongno-gu, Seoul 110-799, Korea. · Taehan Kanho Hakhoe Chi. · Pubmed #17804933 No free full text.

Abstract: PURPOSE: The purpose of this study was to explore the experiences of people with chronic hepatitis B (CHB) in Korea. The specific aim was to identify major problems that people with CHB face and strategies that they are dealing with. METHODS: A grounded theory method was utilized. The data were collected by individual in-depth interviews from 12 CHB patients from one of the major hospitals in Korea. RESULTS: After constant comparative analysis, a core category emerged as "illness management with self-reliance and will." Seven major strategies that were identified in dealing with the illness were maintaining receptive and positive attitudes; restraining excessive work and greed; searching for information; controlling illness information; adhering to practices for not spreading the viral disease; abstaining from alcohol and smoking and maintaining healthy eating habits; nd using alternative therapies. The outcomes that result from employing these strategies were identified as burden, depression and helplessness, stress for maintaining compliance, and dispirited interpersonal relationships. CONCLUSION: The results of this study suggest that most people with CHB in Korea have problems in psychosocial area. Thus health professionals need to provide not only informational support but also emotional one to improve quality of life of the people with CHB.

Kim HJ, Lee DH, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC. · Department of Internal Medicine, Chung Ang University Hospital, Seoul, South Korea. · Liver Int. · Pubmed #17498248 No free full text.

Abstract: BACKGROUND/AIMS: As the core gene of hepatitis B virus (HBV) is a major immunological target, its mutation may evoke or evade immune clearance. We investigated the frequency and location of HBV core gene substitutions according to hepatitis B e antigen (HBeAg) status and viral replication status, and evaluated the association of these substitutions with the different stages of chronic HBV infection in Korean patients. METHODS: The study population included 45 HBeAg-positive/DNA-positive patients (group I), 49 HBeAg-negative/DNA-positive patients (II) and 50 HBeAg-negative/DNA-negative patients (III). The HBV core gene was analysed by polymerase chain reaction (PCR) and sequencing. RESULTS: The frequency of core gene substitutions increased from group I to group III. Substitutions were commonly detected at codons 87, 97, 112 and 130. The frequency of substitutions at codons 87 and 112 was higher in groups II/III than in group I. The frequency of the codon I97F substitutions was the highest in group III. However, the codon 130 substitution was more frequently found in groups I/II than in group III. CONCLUSION: Core gene substitutions were more frequently detected in HBeAg-negative and/or HBV DNA-negative patients. The substitutional hot spots were codons 87, 97, 112 and 130; substitutions at these codons might play a role in immune-modulation during the course of chronic HBV infection.

Song YB, Lee JH, Choi MS, Koh KC, Paik SW, Yoo BC, Choi YH, Sohn HJ, Lee KH, Rhee JC. · Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Hepatol. · Pubmed #17380072 links to  free full text

Abstract: BACKGROUNDS AND AIMS: The epidemiology of hepatitis A is associated with socioeconomic and hygiene status. Recently, the prevalence of hepatitis A in young adults has been steadily increasing in Korea. This study is to investigate the age-specific seroprevalence of hepatitis A virus in Korea. METHODS: Stored sera from 250 healthy adult subjects who visited the health promotion center in Samsung Medical Center between July and August 2006 were tested for IgG hepatitis A virus antibody (anti-HAV). RESULTS: The prevalence of anti-HAV was 2%, 72%, 92%, 94%, 100% in 20's, 30's, 40's, 50's, and 60's, respectively. The prevalence of anti-HAV was significantly lower in subjects below age 40 compared to those above 40 (37.0% vs. 95.3%, p<0.001). The seroprevalence was higher in area outside of Seoul compared to those living in Seoul in age group below 40 (25.6% vs. 55.6%, p=0.01). In Seoul area, the prevalence was significantly lower in Kangnam-Gu, Seocho-Gu, and Songpa-Gu district compared to the other areas of Seoul in the age group below 40 (20.0% vs. 42.1%, p<0.05). CONCLUSION: The seroprevalence of hepatitis A virus antibody in Korean population below 40 is quite low and immunity to hepatitis A virus in those subjects can be a public health issue. In view of changing seroepidemiology, a policy for hepatitis A vaccination in population below 40 might be warranted.

Kim do Y, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC, Joh JW, Lee SK, Rhee JC. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Liver Int. · Pubmed #17311622 No free full text.

Abstract: BACKGROUND AND AIMS: The significance of donor age in living donor liver transplantation (LDLT) for hepatitis B virus (HBV) infection has not been fully evaluated. METHODS: We analyzed the data of 136 patients who underwent LDLT for HBV-related liver diseases from January 1999 to April 2004. The recipients were divided into an older donor group (donor age > or = 40) and a younger donor group (donor age < 40). Posttransplant clinical outcomes and survival were compared between two groups, and predictors of survival after LDLT were evaluated. RESULTS: Baseline characteristics were not different between the two groups, except for more number of female donors and higher positive donor anti-HBc rate in the older group. The frequencies of acute rejection and early mortality after transplantation were similar in the two groups. The long-term survival rates for the older donor group were significantly lower than those of the younger donor group (1-, 3-, 5-year survival rate = 84%, 75%, 46% vs. 92%, 86%, and 83%, P = 0.03). Multivariate analysis showed that older donor age was the only independent risk factor associated with survival after LDLT (HR = 2.3; 95% CI = 1.1-5.6, P = 0.04). CONCLUSIONS: Our study suggests that older donor allografts would be associated with poor patient survival after LDLT for HBV-related liver diseases.

Choi MS, Kim DY, Lee DH, Lee JH, Koh KC, Paik SW, Rhee JC, Yoo BC. · Department of Medicine and Digestive Disease Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. · J Viral Hepat. · Pubmed #17305881 No free full text.

Abstract: We investigated the overall and site-specific prevalence of pre-S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre-S mutations were determined by nucleotide sequence analysis. Possible correlations between pre-S mutations and clinical/virological parameters were examined. Pre-S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre-S2 deletion was the most commonly found mutation (10.7%), followed by pre-S2 start codon mutation (9.7%), pre-S1-S2 deletion (3.0%) and both pre-S2 deletion and start codon mutation (2.7%). Pre-S2 deletion and pre-S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre-S mutations were associated with older age and higher rates of positive HBV DNA (>/=0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre-S mutations by logistic regression analysis. These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.

Kim JH, Choi MS, Lee H, Kim do Y, Lee JH, Koh KC, Yoo BC, Paik SW, Rhee JC. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · J Gastroenterol Hepatol. · Pubmed #16638104 No free full text.

Abstract: BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the clinical features of young HCC patients have not been fully studied. In the present study, we investigated the prevalence, clinical characteristics and prognosis of young HCC patients. METHODS: A retrospective analysis was performed for HCC patients in our center using Korean cancer registry data. Among 4234 patients enrolled, there were 38 patients younger than 30 years of age (0.9%). We compared clinical characteristics and survival data of these patients (group I) with those of sex-matched, randomly selected HCC patients aged 30-59 years (group II; n = 231) and 60 years or older (group III; n = 147). RESULTS: Group I showed distinct features compared with groups II and III as follows: low frequency of smoking history, high positive rate of hepatitis B s antigen, no association with anti-hepatitis C virus antibody, high frequency of alpha-fetoprotein > or = 400 ng/mL, well-preserved liver function, larger tumor size, more advanced tumor-node-metastasis (TNM) stage and Cancer of the Liver Italian Program (CLIP) score and more frequent application of surgical resection and chemotherapy as initial treatment. The overall survival of group I was worse than that of group II, but similar to that of group III. Multivariate analysis showed that TNM stage and CLIP score, not age itself, were independent predictive factors for survival. CONCLUSIONS: The results suggest that young HCC patients tend to have a poor prognosis owing to advanced tumor stage, despite well-preserved liver function and aggressive treatment. Further studies regarding the role of HCC screening in young people may be useful, especially in hepatitis B virus carriers from high endemic areas.

Lee HS, Chung YH, Lee K, Byun KS, Paik SW, Han JY, Yoo K, Yoo HW, Lee JH, Yoo BC. · Seoul National University Hospital, South Korea. · Hepatology. · Pubmed #16628625 No free full text.

Abstract: Clevudine is a nucleoside analog with an unnatural beta-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n=32), 30-mg clevudine (n=32), and 50-mg clevudine (n=34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels.

Lee H, Choi MS, Paik SW, Kim JH, Kim DY, Lee JH, Koh KC, Yoo BC, Rhee JC, Song SM. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Hepatol. · Pubmed #16565604 links to  free full text

Abstract: BACKGROUND/AIMS: Combination therapy with peginterferon and ribavirin is a standard therapy for western patients with chronic hepatitis C; however, its efficacy remains unclear in East Asian patients. We evaluated the efficacy and safety of administering peginterferon alfa-2a plus ribavirin in native Korean patients with chronic hepatitis C. METHODS: Seventy-five patients with detectable HCV RNA (52.0% male, median age: 50.8 years) were eligible for the study. The patients were treated with peginterferon alfa-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks (for genotype non-1, n=46) or 1000-1200 mg/day for 48 weeks (for genotype 1, n=29). The early virologic response (EVR), the end of treatment virologic response (ETVR), the sustained virologic response (SVR), the biochemical response and the adverse event were analyzed. RESULTS: EVR was seen in 86.2% of the patients with genotype 1. The ETVR was 58.6% in the genotype 1 group and 84.8% in the genotype non-1 group (P=0.02). The overall SVR was 70.7%: 55.2% in the genotype 1 group and 80.4% in the non-1 group (P=0.04). The sustained biochemical response was 64.0%. Multivariate analysis showed that the baseline HCV RNA level (Odds ratio: 0.045, 95% CI: 0.011-0.183, P<0.001) and genotype (Odds ratio: 0.247, 95% CI: 0.063-0.969, P=0.045) had an independent effect on the SVR. Neutropenia, anemia, flu-like symptoms and itching were the common adverse events. Aggravated liver function led to discontinuation of therapy for six patients. Dose modification in twenty-nine patients was effective without producing a significant reduction of the SVR. CONCLUSIONS: Our data suggest that the efficacy of peginterferon plus ribavirin therapy in Koreans is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C patients. The baseline HCV RNA level and the genotype can be significant factors influencing the SVR.

Cho DH, Choi MS, Kim DH, Kim DY, Shim SG, Lee JH, Koh KC, Paik SW, Yoo BC, Rhee JC. · Department of Medicine, Samsung Medical Center, Seoul, Korea. · Korean J Hepatol. · Pubmed #16177552 links to  free full text

Abstract: BACKGROUND/AIMS: Exclusion of liver disease from other causes such as autoimmune hepatitis is necessary for diagnosis of nonalcoholic fatty liver disease (NAFLD). However, there has been no study on the prevalence and significance of autoantibodies in the patients with clinically suspected NAFLD in Korea, where hepatitis B is endemic and autoimmune hepatitis is relatively uncommon. METHODS: We prospectively tested for anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-mitochondrial antibody (AMA) in 135 serially enrolled patients with suspected NAFLD. We compared the clinical characteristics and biochemical indices of the ANA-positive or ASMA-positive group with those of the autoantibody-negative group. RESULTS: Sixteen patients (11.8%) had serum autoantibodies; there was ANA in 8 patients (5.9%), ASMA in 7 (5.1%), and AMA in 2 (1.5%). Both ANA and AMA were positive in one patient. The ANA-positive or ASMA-positive group showed an older age (49.5+/-13.0 vs. 42.0+/-10.9 years, respectively, P=0.018) and higher levels of serum globulin (3.1+/-0.4 vs. 2.9+/-0.4 g/dL, respectively, P=0.037), compared with the autoantibody-negative group. Two cases with positive ANA or ASMA fulfilled the diagnostic criteria for probable autoimmune hepatitis and two cases with positive AMA were suspected as primary biliary cirrhosis. CONCLUSIONS: These findings suggest that autoantibodies could be found in some patients with suspected NAFLD in Korea, AMA-positivity or ASMA-positivity could be associated with old age and high serum globulin, and some of the autoantibody-positive cases could be diagnosed as autoimmune hepatitis or primary biliary cirrhosis. Further studies are necessary to clarify the clinical significance of autoantibody positivity in those patients.

Moon W, Choi MS, Moon YM, Paik SW, Lee JH, Koh KC, Yoo BC, Rhee JC, Shim SG. · Department of Medicine, Gastrointestinal Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Hepatol. · Pubmed #15980671 links to  free full text

Abstract: BACKGROUND/AIMS: Adefovir dipivoxil is effective in patients with lamivudine-resistant hepatitis B virus (HBV). However, little is known about its role in Korean patients with decompensated liver cirrhosis. We retrospectively evaluated the efficacy and safety of adefovir dipivoxil in patients with decompensated liver cirrhosis with lamivudine resistance, and we compared this to the patients having compensated liver disease. METHODS: The patients with lamivudine-resistant chronic liver disease were enrolled and they received adefovir dipivoxil 10 mg daily. The clinical course and the biochemical and virological response of the decompensated cirrhosis group were compared with those of the patients with compensated liver disease group. RESULTS: One-hundred and one patients (the decompensated cirrhosis group, n=53; the compensated liver disease group, n=48) were evaluated. During the following up, 13 patients in the decompensated group and 4 patients in the compensated group dropped out of the treatment (P=0.011). After adefovir treatment, the proportion of patients with serum HBV DNA below 0.5 pg/mL in the decompensated group was less than that in the compensated group (50.9% vs. 83.3%, P=0.001), but the rates of normalized ALT, HBeAg loss and HBeAg seroconversion did not differ. The change of the Child-Pugh score in the decompensated group was 9.1 +/- 1.8 to 6.9 +/- 1.6 (P<0.001). The biochemical response in decompensated group was slower than that in the compensated group. Renal toxicity was not observed in either group. CONCLUSIONS: These results suggest that adefovir dipivoxil would be an effective and safe treatment for patients with decompensated liver cirrhosis with lamivudine resistance, but its effect might be limited and slower for decompensated cirrhosis.

Song PS, Koh KC, Yoo BC, Paik SW, Lee JH, Choi MS, Ryu DR, Lee JY. · Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · Korean J Gastroenterol. · Pubmed #15973079 links to  free full text

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies. Many factors are considered to be etiology associated with HCC; the important factors are hepatitis B and C viruses and alcohol. Cirrhosis is present in the majority of patients with HCC. It is assumed that all diseases, which lead to liver cirrhosis, may be complicated by the development of HCC. We report a 36-year-old man with HCC which developed from cardiac cirrhosis caused by constrictive pericarditis in whom both hepatitis B virus and hepatitis C viral marker tests were all negative. CT scan of his heart showed pericardial calcification with diastolic dysfunction of right ventricle. Abdominal CT scan revealed mottled mosaic pattern of contrast enhancement of liver parenchyme and two hepatic lesions that were considered to be HCCs. Left lateral segmentectomy of liver was performed. There were two well-circumscribed masses which were confirmed to be HCC and the remaining hepatic parenchyma showed bridging fibrosis between central zonal regions. To our knowledge, this is the first case of HCC complicating cardiac cirrhosis in Korea.

Lee SY, Choi MS, Lee D, Lee JH, Koh KC, Paik SW, Yoo BC. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. · J Korean Med Sci. · Pubmed #15953865 links to  free full text

Abstract: Disappearance of hepatitis B surface antigens (HBsAg) in chronic hepatitis B usually indicates clearance of hepatitis B virus (HBV) infection. However, false HBsAg negativity with mutations in pre-S2 and 'a' determinant has been reported. It is also known that YMDD mutations decrease the production of HBV and escape detection of serum HBsAg. Here, we report overlapping gene mutations in a patient with HBsAg loss during the lamivudine therapy. After 36 months of lamivudine therapy in a 44-yrold Korean chronic hepatitis B patient, serum HBsAg turned negative while HBV DNA remained positive by a DNA probe method. Nucleotide sequence of serum HBV DNA was compared with the HBV genotype C subtype adr registered in NCBI AF 286594. Deletion of nucleotides 23 to 55 (amino acids 12 to 22) was identified in the pre-S2 region. Sequencing of the 'a' determinant revealed amino acid substitutions as I126S, T131N, M133T, and S136Y. Methionine of rtM204 in the P gene was substituted for isoleucine indicating YIDD mutation (rtM204I). We identified a HBV mutant composed of pre-S2 deletions and 'a' determinant substitutions with YMDD mutation. Our result suggests that false HBsAg negativity can be induced by combination of overlapping gene mutations during the lamivudine therapy.