Hepatitis: Yoo K

Song HJ, Kim TH, Song JH, Oh HJ, Ryu KH, Yeom HJ, Kim SE, Jung HK, Shim KN, Jung SA, Yoo K, Moon IH, Chung KW. · Department of Internal Medicine, Ewha Medical Research Institute, Ewha Womans University College of Medicine, Seoul, Korea. · J Korean Med Sci. · Pubmed #17449927 links to  free full text

Abstract: Vaccination against hepatitis A virus (HAV) is recommended for patients with chronic liver disease (CLD), but this has been deemed unnecessary in Korea since the immunity against HAV was almost universal in adults. However, this practice has never been reevaluated with respect to the changing incidence of adult acute hepatitis A. We retrospectively reviewed the medical records of 278 patients with acute hepatitis A diagnosed from January 1995 to November 2005 and prospectively tested 419 consecutive CLD patients from July to December 2005 for the presence of IgG anti-HAV. The number of patients with acute hepatitis A has markedly increased recently, and the proportion of adult patients older than 30 yr has been growing from 15.2% during 1995-1999, to 28.4% during 2000-2005 (p=0.019). Among 419 CLD patients, the seroprevalences of IgG anti-HAV were 23.1% for those between 26 and 30 yr, 64% between 31 and 35 yr, and 85.0% between 36 and 40 yr. These data demonstrate that immunity against HAV is no more universal in adult and substantial proportion of adult CLD patients are now at risk of HAV infection in Korea. Therefore, further study on seeking proper strategy of active immunization against HAV is warranted in these populations.

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.

Chung YH, Song BC, Lee GC, Shin JW, Ryu SH, Jung SA, Yoo K, Lee HC, Lee YS, Suh DJ. · Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Centre, Seoul, Korea. · Eur J Gastroenterol Hepatol. · Pubmed #12702905 No free full text.

Abstract: OBJECTIVE: In patients with chronic hepatitis B, viral relapse following interferon (IFN) therapy may be the result of a treatment duration that is too short to prevent hepatitis B virus (HBV) from replicating later. To reduce viral relapse in patients with chronic hepatitis B who responded to IFN, we individualized the duration of therapy according to serum HBV-DNA levels. METHOD: Treatment duration was prolonged to maintain negative serum HBV-DNA levels for the next 6 months in 30 patients who became HBV-DNA-negative following IFN therapy (group A). Another 35 patients were treated for only 6 months (group B). All patients had HBV-DNA as well as hepatitis B surface antigen (HBsAg) in their sera for more than 6 months and were proven histologically to have chronic hepatitis. Interferon alfa (IFN-alpha) was administered subcutaneously at a dose of 5 MU/m2 three times a week. RESULTS: There were no differences in age, gender, hepatitis B e antigen (HBeAg) positivity, serum alanine aminotransferase (ALT) levels, or serum HBV-DNA levels between the two groups. The mean duration of IFN therapy in group A was 7.2 months. At the end of treatment, serum HBV-DNA was negative in 16 patients in group A and in 18 patients in group B. The loss of serum HBV-DNA was maintained to the end of follow-up in 13 patients in group A but in only eight patients in group B. Similarly, serum ALT levels were normal in 14 patients in group A but in only nine patients in group B at the end of follow-up. CONCLUSION: Individualization of the duration of treatment to maintain serum HBV-DNA negativity for at least 6 months may reduce the viral relapse rate following IFN therapy.

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.

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.

Kim YS, Kim DY, Ryu KH, Song JH, Kim MS, Jung HS, Park JY, Jung HK, Yoo K, Moon IH, Baek JY. · Department of Internal Medicine, Ewha Womans University College of Medicine, Tongdaemun Hospital, 70 Jongro 6-ga, Jongro-gu, Seoul 110-783, Korea. · Korean J Gastroenterol. · Pubmed #14646578 links to  free full text

Abstract: BACKGROUND/AIMS: The clinical significance of serum CA 125 levels in patients with chronic liver disease has not been widely appreciated in relation to the severity of the disease. We examined serum CA 125 levels in patients with chronic liver disease according to the severity of liver disease and the presence of ascites. METHODS: Fasting serum CA 125 levels were measured by a commercial RIA kit in 92 patients with chronic liver disease: 22 with chronic hepatitis and 70 with liver cirrhosis (Child class A, 19; B, 28; C, 23). Forty-one patients (45%) had ascites. RESULTS: The patients with Child class C liver cirrhosis had significantly higher mean serum CA 125 level than those with class A (p<0.05). In Child class B patients, the mean serum CA 125 level was significantly higher in patients with ascites than in those without (p<0.05). A multiple regression analysis showed that the presence of ascites, serum albumin, and prothrombin time were independent factors related to the increase of serum CA 125 levels. CONCLUSIONS: The presence of ascites is more closely related to the increase of CA125 levels in patients with liver cirrhosis than the severity of liver disease.

Nag A, Datta A, Yoo K, Bhattacharyya D, Chakrabortty A, Wang X, Slagle BL, Costa RH, Raychaudhuri P. · Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, Chicago, Illinois 60612, USA. · J Virol. · Pubmed #11581406 links to  free full text

Abstract: The hepatitis B virus (HBV) X protein (HBx) is critical for the life cycle of the virus. HBx associates with several host cell proteins including the DDB1 subunit of the damaged-DNA binding protein DDB. Recent studies on the X protein encoded by the woodchuck hepadnavirus have provided correlative evidence indicating that the interaction with DDB1 is important for establishment of infection by the virus. In addition, the interaction with DDB1 has been implicated in the nuclear localization of HBx. Because the DDB2 subunit of DDB is required for the nuclear accumulation of DDB1, we investigated the role of DDB2 in the nuclear accumulation of HBx. Here we show that expression of DDB2 increases the nuclear levels of HBx. Several C-terminal deletion mutants of DDB2 that fail to bind DDB1 are able to associate with HBx, suggesting that DDB2 may associate with HBx independently of binding to DDB1. We also show that DDB2 enhances the nuclear accumulation of HBx independently of binding to DDB1, since a mutant that does not bind DDB1 is able to enhance the nuclear accumulation of HBx. HBV infection is associated with liver pathogenesis. We show that the nuclear levels of DDB1 and DDB2 are tightly regulated in hepatocytes. Studies with regenerating mouse liver indicate that during late G1 phase the nuclear levels of both subunits of DDB are transiently increased, followed by a sharp decrease in S phase. Taken together, these results suggest that DDB1 and DDB2 would participate in the nuclear functions of HBx effectively only during the late-G1 phase of the cell cycle.