Sook-Hyang Jeong

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.)

Hepatitis A: Clinical Manifestations and Management

Due to improved living conditions and subsequent changes in hepatitis A epidemiology, the disease burden of hepatitis A is increasing in many regions. Recently, Korea has faced a large, community-wide outbreak of hepatitis A, which has prompted a vaccination program. The clinical spectrum of hepatitis A virus infection ranges from asymptomatic infection to fulminant hepatitis. Clinical manifestations depend on the age of the host: less than 30% of infected young children are symptomatic, while about 80% of infected adults manifest severe hepatitis with remarkably elevated serum aminotransferases. Fulminant hepatitis is rare, with a reported incidence from 0.015 to 0.5%. Atypical manifestations include relapsing hepatitis and prolonged cholestasis, and complicated cases with acute kidney injury have been reported. Extrahepatic manifestations, such as autoimmune hemolytic anemia, aplastic anemia, pure red cell aplasia, pleural or pericardial effusion, acute reactive arthritis, acute pancreatitis, acalculous cholecystitis, mononeuritis, and Guillain-Barré syndrome, have been rarely reported. Management of hepatitis A includes general supportive care, and critical decisions regarding liver transplantation await further studies on prognostic predictors. Fundamental management of hepatitis A is active vaccination. However, a vaccination program should be adapted to the regional situation, according to differing epidemiology and disease burden.

Elevated plasma osteopontin levels in patients with hepatocellular carcinoma.

OBJECTIVES:Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC).METHODS:We determined plasma levels of OPN, α-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed.RESULTS:Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168–5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29–1,688) or of a healthy control group (155 ng/mL, 10–766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells.CONCLUSIONS:These data propose elevated plasma OPN levels as a potential biomarker for HCC.

The Effects of Probiotics on PPI-Triple Therapy for Helicobacter pylori Eradication

Background: This study was performed to evaluate whether the addition of probiotics to proton pump inhibitor (PPI)‐based triple therapy increases the likelihood of successful Helicobacter pylori eradication.

Bismuth‐Containing Quadruple Therapy as Second‐Line Treatment for Helicobacter pylori Infection: Effect of Treatment Duration and Antibiotic Resistance on the Eradication Rate in Korea

Background:  The eradication rate of first‐line Helicobacter pylori treatment is only 70–85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth‐containing quadruple therapy as second‐line treatment for H. pylori infection based on treatment duration.

High prevalence of hepatitis B virus infection in patients with B-cell non-Hodgkin's lymphoma in Korea.

This study assessed the association of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with non‐Hodgkins lymphoma in a highly HBV‐endemic area. The prevalence of either HBV or HCV infection in 235 patients with non‐Hodgkins lymphoma was compared with that of an age‐ and sex‐matched hospital control group of 235 patients. The prevalence of HBV infection was higher in B‐cell non‐Hodgkins lymphoma (15.5%) than control (8.1%), but the prevalence of HCV infection in the non‐Hodgkins lymphoma patients (2.1%) and control group (3%) was similar. HBV prevalence increased significantly with age in the B‐cell non‐Hodgkins lymphoma patients. The presence of HBV proteins and DNA in lymphoma tissues and peripheral blood mononuclear cells (PBMCs) from HBV‐infected non‐Hodgkins lymphoma patients was also investigated using immunohistochemistry and PCR. HBV DNA was frequently detected in PBMCs from HBV‐infected non‐Hodgkins lymphoma patients, but HBV antigens were not. Therefore, HBV infection, but not HCV infection, was associated with B‐cell non‐Hodgkins lymphoma in Korea, suggesting a possible role for HBV in the development of non‐Hodgkins lymphoma. J. Med. Virol. 80:960–966, 2008.

Hepatitis A in Korea: Epidemiological Shift and Call for Vaccine Strategy

Objective: The number of adult hepatitis A cases has progressively been increasing during the last several years in Korea. The aim of the present study was to describe the recent clinical features of hepatitis A and the seroprevalence of hepatitis A virus (HAV), and to discuss HAV vaccine strategy in Korea. Methods: Retrospective analysis of clinical characteristics of hepatitis A from 109 patients consecutively enrolled at a community hospital between 2003 and 2006 as well as cross-sectional study of seroprevalence of HAV from 307 patients of hospital population group during the same period were performed. Results: Most hepatitis A cases were young adults in their twenties or thirties, and the severity of the disease was related to the age of patients. The seroprevalence of HAV was 62%, which was dependent on the age of patients. HAV seroepidemiology in Korea is rapidly changing and a growing number of young adults are susceptible to HAV infection. Conclusions: The clinical features and the epidemiological shift of HAV urge Korea, as well as other countries which are experiencing similar issues, to promote childhood vaccination and consider catch-up vaccination for adolescents and young adults.

Germline mutations of the STK11 gene in Korean Peutz-Jeghers syndrome patients.

Peutz–Jeghers syndrome (PJS) is an autosomal dominantly inherited disease characterized by hamartomatous gastrointestinal polyps and mucocutaneous pigmentation, with an increased risk for various neoplasms, including gastrointestinal cancer. Recently, the PJS gene encoding the serine/threonine kinase STK11 (also named LKB1) was mapped to chromosome 19p13.3, and germline mutations were identified in PJS patients. We screened a total of ten Korean PJS patients (nine sporadic cases and one familial case including two patients) to investigate the germline mutations of the STK11 gene. By polymerase chain reaction–single-strand conformation polymorphism and DNA sequencing analysis, three kinds of mis-sense mutation and a frame-shift mutation were identified: codon 232 (TCC to CCC) in exon 5, codon 256 (GAA to GCA) in exon 6, codon 324 (CCG to CTG) in exon 8, and a guanine insertion at codon 342 resulting in a premature stop codon in exon 8. These mis-sense variants were not detected in 100 control DNA samples. Furthermore, we found an intronic mutation at the dinucleotide sequence of a splice-acceptor site: a one base substitution from AG to CG in intron 1, which may cause aberrant splicing. Most reported germline mutations of the STK11 gene in PJS patients were frame-shift or non-sense mutations resulting in truncated proteins. Together, these findings indicate that germline mis-sense mutations of the STK11 gene are found in PJS patients in addition to truncating mutations. The effects of these mutations on protein function require further examination. In summary, we found germline mutations of the STK11 gene in five out of ten Korean PJS patients.

Validation of diagnostic tests for Helicobacter pylori with regard to grade of atrophic gastritis and/or intestinal metaplasia.

Background and Aims:  To evaluate the validity of the biopsy‐based tests (histology, culture, and urease test) and serology in detecting current Helicobacter pylori infection against a background of atrophic gastritis (AG) or intestinal metaplasia (IM).