Jin Bong Kim

A prospective nationwide study of drug-induced liver injury in Korea.

OBJECTIVES:To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.METHODS:From May 2005 to May 2007, cases of DILI (alanine transferase >3 × upper normal limit or total bilirubin >2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.RESULTS:A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included “herbal medications” (102, 27.5%), “prescription or non-prescription medications” (101, 27.3%), “health foods or dietary supplements” (51, 13.7%), “medicinal herbs or plants” (35, 9.4%), “folk remedies” (32, 8.6%), “combined” (30, 8.2%), “herbal preparations” (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hys law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.CONCLUSIONS:DILI appears to be a highly relevant health problem in Korea. “Herbal medications” are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.

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.

Non-invasive model predicting clinically-significant portal hypertension in patients with advanced fibrosis

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily‐available data in predicting the presence of significant portal hypertension and esophageal varices.

Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut–liver axis of alcoholic liver disease

Background Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD). Methods We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a Lieber–DeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared. Results No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group (0.37 ± 0.06 ng/mL, 0.39 ± 0.12 ng/mL, and 0.33 ± 0.07 ng/mL, respectively, vs. 0.88 ± 0.31 ng/mL; p < 0.05). Interleukin-1β levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-α level of liver tissue was decreased in the KRG group. Conclusion The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.

Management of endoscopic retrograde cholangiopancreatography-related perforations

Purpose The purpose of this study is to analyze the treatment strategies of patients with endoscopic retrograde cholangiopancreatography (ERCP)-related perforations. This is a retrospective study. Methods We experienced 13 perforations associated with ERCP. We reviewed the medical recordsand classified ERCP-related perforations according to mechanism of injury in terms of perforating device. Injury by endoscopic tip or insertion tube was classified as type I, injury by cannulation catheter or sphincterotomy knife as type II, and injury by guidewire as type III. Results Of four type I injuries, one case was managed by conservative management after primary closure with a hemoclip during ERCP. The other three patients underwent surgical treatments such as primary closure orpancreatico-duodenectomy. Of five type II injuries, two patients underwent conservative management and the other three cases were managed by surgical treatment such as duodenojejunostomy, duodenal diverticulization and pancreatico-duodenectomy. Of four type III injuries, three patients were managed conservatively and the remaining patient was managed by T-tube choledochostomy. Conclusion Type I injuries require immediate surgical management after EPCP or immediate endoscopic closure during ERCP whenever possible. Type II injuries require surgical or conservative treatment according to intra- and retro-peritoneal dirty fluid collection findings following radiologic evaluation. Type III injuries almost always improve after conservative treatment with endoscopic nasobilliary drainage.

Helicobacter pylori infection and peptic ulcer disease in patients with liver cirrhosis.

Background/Aims We investigated the prevalence and relationship of peptic ulcer disease and Helicobacter pylori infection to liver cirrhosis. Methods We examined 288 patients with liver cirrhosis, 322 patients with non-ulcer dyspepsia, and 339 patients with peptic ulcer disease. Rapid urease test and Wright-Giemsa staining were used for diagnosis of H. pylori infection. Results The prevalence of peptic ulcer disease in patients with cirrhosis was 24.3%. The prevalence of peptic ulcer disease in patients with cirrhosis divided into Child-Pugh classes A, B, and C was 22.3%, 21.0%, and 31.3%, respectively (p>0.05). The prevalence of H. pylori infection in the patients with cirrhosis, non-ulcer dyspepsia, and peptic ulcer without chronic liver disease were 35.1%, 62.4%, and 73.7%, respectively (p<0.001). The prevalence of H. pylori infection did not differ depending on whether there was peptic ulcer (35.6%) or not (34.9%) in patients with liver cirrhosis (p>0.05). The prevalence of H. pylori infection in patients with hepatitis virus-related liver cirrhosis and in the patients with alcohol-related liver cirrhosis was 42.5% and 22.0%, respectively (p<0.001). The prevalence of H. pylori infection in patients with Child-Pugh classes A, B, and C liver cirrhosis was 51.5%, 30.5%, and 20.0%, respectively (p<0.001). Conclusions Factors other than H. pylori may be involved in the pathogenesis of peptic ulcer disease in the setting of liver cirrhosis.

Mosapride treatment for functional dyspepsia: A meta‐analysis

The aim of this study was to assess the therapeutic effect of mosapride in patients with functional dyspepsia (FD).

Helicobacter pylori Eradication for Prevention of Metachronous Recurrence after Endoscopic Resection of Early Gastric Cancer

Controversies persist regarding the effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer (EGC). The aim of this study was to assess the efficacy of Helicobacter pylori eradication after endoscopic resection of EGC for the prevention of metachronous gastric cancer. A systematic literature review and meta-analysis were conducted using the core databases PubMed, EMBASE, and the Cochrane Library. The rates of development of metachronous gastric cancer between the Helicobacter pylori eradication group vs. the non-eradication group were extracted and analyzed using risk ratios (RRs). A random effect model was applied. The methodological quality of the enrolled studies was assessed by the Risk of Bias table and by the Newcastle-Ottawa Scale. Publication bias was evaluated through the funnel plot with trim and fill method, Eggers test, and by the rank correlation test. Ten studies (2 randomized and 8 non-randomized/5,914 patients with EGC or dysplasia) were identified and analyzed. Overall, the Helicobacter pylori eradication group showed a RR of 0.467 (95% CI: 0.362-0.602, P < 0.001) for the development of metachronous gastric cancer after endoscopic resection of EGC. Subgroup analyses showed consistent results. Publication bias was not detected. Helicobacter pylori eradication after endoscopic resection of EGC reduces the occurrence of metachronous gastric cancer.

Comparison of hepatic venous pressure gradient and two models of end-stage liver disease for predicting the survival in patients with decompensated liver cirrhosis

Goals: We evaluated the efficacy of initial and follow-up hepatic venous pressure gradient (HVPG), models of end-stage liver disease (MELD), and MELD-Na for predicting the survival of patients with decompensated liver cirrhosis (LC). Background: MELD with/without Na score and HVPG have been important predictors of mortality in patients with LC. Study: Between January 2006 and 2011, a total of 57 patients with decompensated LC, all of whom underwent >2 HVPG measurements for the confirmation of propranolol dosing, were enrolled. MELD and MELD-Na scores were calculated on the day of HVPG measurement. The prognostic accuracy of the initial and follow-up HVPG, MELD, and MELD-Na were analyzed, and independent factors for mortality were evaluated. Results: Ten patients (17.5%) died from LC. Initial HVPG (0.883), initial MELD-Na (0.877), follow-up HVPG (0.829), and follow-up MELD-Na (0.802) showed good area under the receiver operating characteristic curve scores in predicting 1-year mortality. In predicting 2-year mortality, only follow-up HVPG (0.821, cut-off value 18 mm Hg) showed good score. Overall area under the receiver operating characteristic curves (initial and follow-up) were 0.843 and 0.864 in HVPG, 0.721 and 0.674 in MELD, and 0.762 and 0.715 in MELD-Na, respectively. In the Cox regression analysis, only follow-up HVPG (P=0.02; odds ratio, 1.11) was associated with mortality. Conclusions: The efficacy of HVPG for predicting mortality is excellent compared with that of MELD or MELD-Na. Therefore, aside from the confirmation of adequate propranolol dosing, HVPG may be needed for predicting the survival of patients with decompensated LC.

Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma

AIM To evaluate the clinical characteristics of patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 and A hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). METHODS Between January 2001 and September 2011, 129 patients with BCLC stage 0 and stage A HCC who underwent TACE were retrospectively enrolled. Patient characteristics, routine computed tomography and TACE findings, survival time and 1-, 5-, and 10-year survival rates, risk factors for mortality, and survival rates according to the number of risk factors were assessed. RESULTS The mean size of HCC tumors was 2.4 ± 1.1 cm, and the mean number of TACE procedures performed was 2.5 ± 2.1. The mean overall survival time and 1-, 5-, and 10-year survival rates were 80.6 ± 4.9 mo and 91%, 63% and 49%, respectively. In the Cox regression analysis, a Child-Pugh score > 5 (P = 0.005, OR = 3.86), presence of arterio-venous shunt (P = 0.032, OR = 4.41), amount of lipiodol used (> 7 mL; P = 0.013, OR = 3.51), and female gender (P = 0.008, OR = 3.47) were risk factors for mortality. The 1-, 5-, and 10-year survival rates according to the number of risk factors present were 96%, 87% and 87% (no risk factors), 89%, 65%, and 35% (1 risk factor), 96%, 48% and unavailable (2 risk factors), and 63%, 17%, and 0% (3 risk factors), respectively (P < 0.001). CONCLUSION TACE may be used as curative-intent therapy in patients with BCLC stage 0 and stage A HCC. The Child-Pugh score, arterio-venous shunt, amount of lipiodol used, and gender were related to mortality after TACE.