Woon Geon Shin

Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition

The Korean College of Helicobacter and Upper Gastrointestinal Research first developed guidelines for the diagnosis and treatment of Helicobacter pylori (H. pylori) infection in 1998, and revised guidelines were proposed in 2009 by the same group. Although the revised guidelines were based on a comprehensive review of published articles and the consensus of expert opinions, the revised guidelines were not developed using an evidence‐based process. The new guidelines presented in this study include specific changes regarding indication and treatment of H. pylori infection in Korea, and were developed through the adaptation process using an evidence‐based approach. After systematic review of the literature, six guidelines were selected using the Appraisal of Guidelines for Research and Evaluation (AGREE) II process. A total of 21 statements were proposed with the grading system and revised using the modified Delphi method. After the guideline revisions, 11 statements about indication of test and treatment, four statements about diagnosis, and four statements about treatment of H. pylori infection were developed. The revised guidelines were reviewed by external experts before receiving official endorsement from the Korean College of Helicobacter and Upper Gastrointestinal Research, and disseminated to physicians and other medical professionals for use in clinical practice in Korea. The guidelines will continue to be updated and revised periodically.

Randomised clinical trial: the efficacy of a 10‐day sequential therapy vs. a 14‐day standard proton pump inhibitor‐based triple therapy for Helicobacter pylori in Korea

Aliment Pharmacol Ther 2011; 34: 1098–1105

Prognostic Values of α-fetoprotein and Protein Induced by Vitamin K Absence or Antagonist-II in Hepatitis B Virus-related Hepatocellular Carcinoma : A Prospective Study

Background/Aim Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are most widely used tumor markers in detecting hepatocellular carcinoma (HCC). Recently, there have been some studies about them as prognostic markers in hepatitis C virus-associated HCC. However, prognostic values of AFP and PIVKA-II remain clarified in hepatitis B virus (HBV)-associated HCC. This study was aimed to evaluate the prognostic values of AFP and PIVKA-II in HBV-associated HCC. Methods Patients (n=126) were divided into 4 groups according to median levels of AFP and PIVKA-II (L; low/low, A; high/low, P; low/high, H; high/high) at diagnosis. Clinical characteristics and survival were compared among the groups, and Cox regression analysis was performed to find independent factors for survival. Results Baseline host and viral factors were not significantly different among the 4 groups. High PIVKA-II groups (P and H) had more aggressive tumor characteristics (larger size of tumors, higher number of tumors, frequent portal vein thrombosis, P<0.05) and much shorter median survival time than low PIVKA-II groups (L and A) (P<0.05). In multivariate analysis, high PIVKA-II level was an independent predictor for survival (risk ration: 2.377, 95% confidence interval: 1.359-4.157, P=0.002) together with Child-Pugh score, advanced TMN stages, and treatment modality. Even after excluding 33 patients who had Child-Pugh class C and advanced tumor stages (tumor-nodes-metastasis stage III-IV) at diagnosis, high PIVKA-II level was still an independent predictor for survival (risk ration: 4.258, 95% confidence interval: 2.418-8.445, P<0.001). Conclusions Serum PIVKA-II level, not serum AFP, was a valuable independent prognostic factor in HBV-related HCC.

Polymorphisms of interleukin-1 and interleukin-2 genes in patients with gastric cancer in Korea

Background and Aim:  Interleukin (IL)‐1 gene polymorphism has been reported to be associated with the increment of gastric cancer (GC) and the decrement of duodenal ulcers (DU). In addition, IL‐2 is known to induce Helicobacter pylori (H. pylori)‐associated gastric atrophy, but it is not known whether IL‐2 gene polymorphism increases the risk of GC (GC) or peptic ulcer diseases. Therefore, we compared the genotypes of IL‐1B, IL‐1RN, and IL‐2 gene polymorphisms with risk of gastric ulcers (GU), GC, and DU in Korean patients.

Association of concurrent hepatitis B surface antigen and antibody to hepatitis B surface antigen with hepatocellular carcinoma in chronic hepatitis B virus infection.

Antibody to hepatitis B surface antigen (HBsAg) (anti‐HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti‐HBs (concurrent HBsAg/ anti‐HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti‐HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti‐HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti‐HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365–49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226–4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788–7.421; P < 0.001) and concurrent HBsAg/anti‐HBs (OR, 4.336; 95% CI, 1.956–9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti‐HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti‐HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C. J. Med. Virol. 81:1531–1538, 2009.

Trends in the eradication rates of Helicobacter pylori infection for eleven years

AIM To evaluate the trends in the eradication rate of Helicobacter pylori (H. pylori) over the past 11 years in a single center. METHODS This retrospective study covered the period from January 2000 to December 2010. We evaluated 5746 patients diagnosed with gastric ulcers (GU), duodenal ulcers (DU), GU + DU, or nonpeptic ulcers associated with an H. pylori infection. We treated them annually with the 2 wk standard first-line triple regimen, proton pump inhibitor (PPI) + amoxicilin + clarithromycin (PAC; PPI, clarithromycin 500 mg, and amoxicillin 1 g, all twice a day). The follow-up test was performed at least 4 wk after the completion of the 2 wk standard H. pylori eradication using the PAC regimen. We also assessed the eradication rates of 1 wk second-line therapy with a quadruple standard regimen (PPI b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.) after the failure of the first-line therapy. Statistical analysis was performed with 95%CI for the differences in the annual eradication rates. RESULTS A total of 5746 patients [2333 males (58.8%), 1636 females (41.2%); mean age of males vs females 51.31 ± 13.1 years vs 52.76 ± 13.6 years, P < 0.05, total mean age 51.9 ± 13.3 years (mean ± SD)] were investigated. Among these patients, 1674 patients were excluded: 35 patients refused treatment; 18 patients ceased H. pylori eradication due to side effects; 1211 patients had inappropriate indications for H. pylori eradication, having undergone stomach cancer operation or chemotherapy; and 410 patients did not undergo the follow-up. We also excluded 103 patients who wanted to stop eradication treatment after only 1 wk due to poor compliance or the side effects mentioned above. Finally, we evaluated the annual eradication success rates in a total of 3969 patients who received 2 wk first-line PAC therapy. The endoscopic and clinical findings in patients who received the 2 wk PAC were as follows: gastric ulcer in 855 (21.5%); duodenal ulcer in 878 (22.1%); gastric and duodenal ulcer in 124 (3.1%), erosive, atrophic gastritis and functional dyspepsia in 2055 (51.8%); and other findings (e.g., MALToma, patients who wanted to receive the therapy even though they had no abnormal endoscopic finding) in 57 (0.5%). The overall eradication rate of the 2 wk standard first-line triple regimen was 86.5%. The annual eradication rates from 2000 to 2010 were 86.7%, 85.4%, 86.5%, 83.3%, 89.9%, 90.5%, 88.4%, 84.5%, 89.1%, 85.8%, and 88.3%, sequentially (P = 0.06). No definite evidence of a significant change in the eradication rate was seen during the past eleven years. The eradication rates of second-line therapy were 88.9%, 82.4%, 85%, 83.9%, 77.3%, 85.7%, 84.4%, 87.3%, 83.3%, 88.9%, and 84% (P = 0.77). The overall eradication rate of 1 wk quadruple second-line therapy was 84.7%. There was no significant difference in the eradication rate according to the H. pylori associated diseases. CONCLUSION This study showed that there was no trend change in the H. pylori eradication rate over the most recent 11 years in our institution.

Eradication Rates of Helicobacter pylori in Korea Over the Past 10 years and Correlation of the Amount of Antibiotics Use: Nationwide Survey.

The efficacy of proton‐pump inhibitor–amoxicillin–clarithromycin therapy for H. pylori eradication has decreased over time.

Simple Tests to Predict Hepatic Fibrosis in Nonalcoholic Chronic Liver Diseases

BACKGROUND/AIMS Several simple tests for hepatic fibrosis employ indirect markers. However, the efficacy of using direct and indirect serum markers to predict significant fibrosis in clinical practice is inconclusive. We analyzed the efficacy of a previously reported indirect marker of hepatic fibrosis - the aspartate aminotransferase to platelet ratio index (APRI) - in patients with nonalcoholic chronic liver diseases (CLDs). METHODS A total of 134 patients who underwent a percutaneous liver biopsy with a final diagnosis of chronic hepatitis B (n=93), chronic hepatitis C (n=18), or nonalcoholic fatty liver disease (n=23) were enrolled. A single-blinded pathologist staged fibrosis from F0 to F4 according to the METAVIR system, with significant hepatic fibrosis defined as a METAVIR fibrosis score of >/=2. RESULTS The mean area under the receiver operating characteristic curve (AUROC) of APRI for predicting significant fibrosis in nonalcoholic CLDs was 0.84 [95% confidence interval (CI), 0.78-0.91]. APRI yielded the highest mean AUROC in the patients with chronic hepatitis B (0.85; 95% CI, 0.771-0.926). The positive predictive value of APRI >/=1.5 for predicting significant fibrosis was 89%. The negative predictive value of APRI <0.5 for excluding significant fibrosis was 80%. CONCLUSIONS APRI might be a simple and noninvasive index for predicting significant fibrosis in nonalcoholic CLDs.

Diagnostic value of PIVKA-II and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma

AIM To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB). METHODS A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared. RESULTS The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.

The COX-2-1195AA Genotype Is Associated with Diffuse-Type Gastric Cancer in Korea

Background/Aims The potential role of the cyclooxygenase (COX)-2 polymorphism has been reported in relation to the risk of gastrointestinal tract malignancies. Therefore, we investigated whether COX-2 polymorphisms are associated with the risk of gastric cancer (GC) in Korea, one of the areas with a high prevalence of this condition. Methods We evaluated the genotypic frequencies of COX-2-765 and -1195 in 100 peptic ulcer patients, 100 GC patients, and 100 healthy controls. The polymorphisms of the COX-2-765 and -1195 genes were analyzed by polymerase chain reaction and restriction fragment length polymorphisms. Results The frequencies of the COX-2-1195 GG, GA, and AA genotype were 20%, 60%, and 20% in intestinal-type GC and 8%, 48%, and 44% in diffuse-type GC, respectively (p=0.021). There were no significant differences in the frequency of COX-2-765 genotypes between intestinal-type GC and diffuse-type GC (p=0.603). Age- and sex-adjusted logistic regression analysis showed that the COX-2-1195 AA genotype was the independent risk factor of diffuse-type GC compared with the COX-2-1195 GG genotype (p=0.041; odds ratio, 6.22; 95% confidence interval, 1.077 to 35.870). Conclusions The COX-2-1195 AA genotype may render subjects more susceptible to diffuse-type GC.