Kwon Yoo

Twenty‐four‐week clevudine therapy showed potent and sustained antiviral activity in HBeAg‐positive chronic hepatitis B

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. (HEPATOLOGY 2007;45:1172–1178.)

Clevudine is highly efficacious in hepatitis B e antigen‐negative chronic hepatitis B with durable off‐therapy viral suppression

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 log10 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 log10 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. (HEPATOLOGY 2007.)

A 12‐week clevudine therapy showed potent and durable antiviral activity in HBeAg‐positive chronic hepatitis B

Clevudine is a nucleoside analog with an unnatural β‐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. (HEPATOLOGY 2006;43:982–988.)

An association between obesity and the prevalence of colonic adenoma according to age and gender

BackgroundEpidemiologic data on obesity as a risk factor for colonic adenoma with respect to gender have not yet been confirmed. Here, we aimed to compare the prevalence of colonic adenoma and of advanced polyps in age-stratified men and women at baseline, to examine the role of body mass index (BMI) on colonic adenoma risk according to age and gender, and to examine the influence of menopausal status.MethodsA total of 1744 asymptomatic patients (946 men, 798 women) who underwent colonoscopy for cancer screening at Ewha Mokdong Hospital, Seoul, Korea, between February and June 2005, were eligible. BMI was assessed, and histology, size, and location of the adenoma were examined for each patient. Women were interviewed for menopausal status and a history of hormone replacement therapy.ResultsA significant increase in the prevalence of colonic adenoma and of advanced polyps was found to occur with age (P for trend < 0.01). The prevalences of adenoma and advanced polyps were higher in men in most age groups (P < 0.01), but no significant difference in prevalences was observed between genderes in patients 70 years of age or older. Moreover, a positive association between BMI and the prevalence of colonic adenoma and advanced polyps was shown in relatively young individuals of both gender (men in their thirties, P < 0.05; women in their forties, P < 0.05), and premenopausal women according to hormonal status (P = 0.01).ConclusionsOur data suggest that obesity increases the risk of colonic adenoma in relatively young people and in premenopausal women subject to estrogen effects.

Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer

BackgroundMatrix metalloproteinases (MMPs) are one of the major classes of proteolytic enzymes involved in tumor invasion and metastasis, being inhibited by naturally occurring tissue inhibitors of metalloproteinases (TIMPs). In this study, we examined the expression of MMP-2, MMP-9, membrane-type 1 (MT1)-MMP, TIMP-1, and TIMP-2 in biopsy tissues of gastric cancer, and the correlation between their expression and clinicopathological parameters.MethodsBiopsy specimens from 66 patients with gastric carcinoma were available for this study. To determine the expression of MMP-2, MMP-9, MT1-MMP, TIMP-1, and TIMP-2, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out on tumor and normal tissues, respectively, sampled during diagnostic gastroscopic examination. Immunohistochemical staining of representative samples using monoclonal antibody directed against MT1-MMP was done, and the clinicopathological variables were reviewed retrospectively.ResultsThe expression level of MMPs and TIMPs was evaluated using the tumor : normal (T/N) ratios of MMPs and TIMPs. The T/N ratio of MT1-MMP mRNA showed a significant correlation with lymph node metastasis and tumor stage (P < 0.05). The other RT-PCR data of MMP-2, MMP-9, TIMP-1, and TIMP-2 did not show any significant correlation with clinicopathological parameters. Immunohistochemistry for MT1-MMP showed a positive immunoreaction in gastric adenocarcinoma and negative staining in normal mucosa.ConclusionsThe correlation between the increased expression of MT1-MMP and clinicopathological variables reflects a role in predicting the aggressive behavior of gastric cancer. Because an RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of MT1-MMP expression in biopsy specimens by RT-PCR may provide useful preoperative information on tumor aggressiveness.

Comparison of oral omeprazole and endoscopic ethanol injection therapy for prevention of recurrent bleeding from peptic ulcers with nonbleeding visible vessels or fresh adherent clots

OBJECTIVES:Omeprazole is a potent inhibitor of gastric acid secretion. Recently it was reported that p.o. omeprazole therapy reduced the rebleeding rate in patients with nonbleeding visible vessels or adherent clots. The aim of this study was to ascertain whether p.o. administration of omeprazole can be an effective alternative to endoscopic injection therapy in peptic ulcers with stigmata of recent hemorrhage.METHODS:A total of 101 patients who had peptic ulcer bleeding based on endoscopic findings of nonbleeding visible vessels or fresh adherent clots were randomly assigned to receive omeprazole (40 mg p.o. every 12 h) or endoscopic ethanol injection therapy.RESULTS:Rebleeding rates were 22.9% (11 of 48) in the omeprazole group and 20.8% (11 of 53) in the endoscopic injection therapy group. The rebleeding rates of clinical significance were 14.6% and 13.2%, respectively. There was no significance difference in the rebleeding rate, requirement for surgery, total units of blood transfused, or mortality between the two groups.CONCLUSIONS:Oral omeprazole administration is comparable to endoscopic ethanol injection therapy for prevention of rebleeding in patients with nonbleeding visible vessels or adherent clots.

The Clinicopathological Significance of Tissue Levels of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor in Gastric Cancer

Background/Aims Hypoxia-inducible factor-1α (HIF-1α) is a mediator of tumor progression. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor known to be induced by HIF-1α. We investigated the clinicopathological significance of HIF-1α and VEGF levels in biopsied gastric cancer tissue. Methods Endoscopic biopsy specimens from 67 patients with gastric carcinoma who underwent surgery were available for this study. Semiquantitative RT-PCR was applied to biopsied tumors and normal tissues to determine the expressions of HIF-1α and VEGF. The expression levels of HIF-1α and VEGF were evaluated using the tumor:normal (T/N) ratios of HIF-1α and VEGF mRNA. The clinicopathological variables were reviewed retrospectively. Results The T/N ratios of HIF-1α mRNA showed significant correlation with lymph-node metastases, distant metastases, stage, and recurrence within 3 years (p<0.05). The T/N ratios of VEGF mRNA showed significant correlation with lymph-node metastases and distant metastases (p<0.05). There was a significant correlation between the T/N ratios of HIF-1α and VEGF mRNA (r=0.72, p<0.01). Conclusions The increased expression of HIF-1α and VEGF mRNA could reflect aggressive tumor behavior, including the recurrence of gastric cancer. Examination of HIF-1α mRNA in biopsy specimens by RT-PCR assay might provide useful preoperative information on tumor aggressiveness.

Emerging Need for Vaccination against Hepatitis A Virus in Patients with Chronic Liver Disease in Korea

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.

Serum cytokine profiles in patients with Plasmodium vivax malaria: A comparison between those who presented with and without thrombocytopenia

Abstract One of the peculiar features of Plasmodium vivax malaria in South Korea is the surprisingly high frequency of thrombocytopenia. The mechanism by which this malaria-related thrombocytopenia develops and its role in the pathology and progress of human infection with P. vivax have not yet been completely understood. In the present study, the serum cytokine profiles of cases of P. vivax malaria who presented with thrombocytopenia were compared with those of similar cases who did not have thrombocytopenia at presentation. The subjects were the 94 consecutive cases of P. vivax malaria who presented at five hospitals in South Korea (all near the Demilitarized Zone) between May 2000 and October 2002, 47 of whom had thrombocytopenia at presentation. When mean values and (S.E.) were compared, the thrombocytopenic patients were found not only to be generally older than the non-thrombocytopenic [25.3 (1.1) v. 21.3 (0.18) years; P < 0.001] but also to have presented with higher serum concentrations of aspartate aminotransferase [77.6 (16.6) v. 32.3 (7.4) U/litre; P < 0.0001], alanine aminotransferase [96.7 (19.0) v. 44.7 (12.0) U/litre; P = 0.0001], interleukin-1 [49.9 (7.4) v. 23.7 (5.1) pg/ml; P < 0.001], interleukin-6 [174.9 (26.4) v. 57.3 (14.6) pg/ml; P = 0.001], interleukin-10 [308.2 (39.6) v. 137.9 (23.1) pg/ml; P < 0.002] and transforming growth factor-β [1134.3 (387.5) v. 416.6 (183.8) pg/ml; P < 0.0001], and higher levels of parasitaemia [4345.7 (966.6) v. 1443.8 (222.7) parasites/μl; P = 0.03). The non-thrombocytopenic patients, however, had relatively high total leucocyte counts [5.8 (0.24) v. 5.4 (0.66) leucocytes/nl; P = 0.03]. The thrombocytopenia associated with P. vivax malaria in South Korea therefore appears to be associated with elevated serum concentrations of both pro- and anti-inflammatory cytokines. To define the role of each cytokine in the development of thrombocytopenia during the course of acute P. vivax malaria, further prospective studies are needed.

Impact of Shiftwork on Irritable Bowel Syndrome and Functional Dyspepsia

Disturbances in biological rhythms could lead to unfavorable health impact. This study aimed to evaluate the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS) in rotating shift workers, and to determine the factors that have significant association with the prevalence of FD and IBS. The research had been carried out among nurses and nursing assistants working at Ewha Womans University Mokdong Hospital between December 2010 and February 2011. The subjects completed self-reported questionnaires, including the quality of the sleep and the level of stress. The prevalence of FD and IBS defined by ROME III criteria, and factors associated the disorders in rotating shift workers were compared with those of day workers. A total of 207 subjects were included in the study with 147 rotating shift workers (71.0%), and 60 (29.0%) day workers. The prevalence of IBS in rotating shift workers was higher than that in day workers (32.7% vs 16.7%, P = 0.026). However, no significant difference in the prevalence of FD was observed between the two groups (19.7% vs 20.0%, P = 0.964). In the multivariate analysis, the risk factors for IBS were rotating shift work (OR, 2.36; 95% CI, 1.01-5.47) and poor sleep quality (OR, 4.13; 95% CI, 1.82-9.40), and the risk factors for FD were poor sleep quality (OR, 2.31; 95% CI, 1.01-5.28), and severe stress (OR, 2.19; 95% CI, 1.06-4.76). A higher prevalence of IBS among rotating shift workers could be directly associated with the circadian rhythm disturbance. The circadian rhythm disturbance may be related with the pathogenesis of IBS.