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Background and aim In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. Methods We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary endpoint was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5 %), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. Results Over a median 3.5 years of follow-up (range = 0.1 – 4.4), overt HE developed in 28 patients (18.2 %). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher model for end-stage liver disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. Conclusions In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

Background and aim Considering that inflammation and fibrosis are major factors for the indication of antiviral treatment, liver stiffness measurements could help identify patients who require antiviral treatment. This study evaluated factors that best identify patients who require antiviral treatment and to develop a new indicator for chronic hepatitis B (CHB). Methods Patients with CHB were randomly classified into a training or validation group, and a model for predicting necroinflammatory activity ≥ A3 or fibrosis grade ≥ F2 (A3F2) was established in the training group using binary regression analysis and validated in the validation group. Predictive efficacy was compared using area under the receiver-operating characteristics curve analysis. Results Four-hundred ninety-two patients were enrolled. In the training group, female sex, aspartate aminotransferase-to-platelet count ratio index (APRI), and liver stiffness were independent predictors of A3F2 on multivariate analysis. These variables were used to construct a novel model, called the LAW (liver stiffness, APRI, woman) index, as follows: 1.5 × liver stiffness value (kPa) + 3.9 × APRI + 3.2 if female. The LAW index was a better predictor of A3F2 than the APRI or liver stiffness measurement in both training group (0.870; 95% confidence interval, 0.822-0.910) and validation group (0.862; 95% confidence interval, 0.813-0.903). Conclusions The LAW index was able to accurately identify patients with CHB who required antiviral treatment. A LAW index of >10.1 could be a strong indicator for the initiation of antiviral treatment in patients with CHB.

AIMS Pancreatic cystic neoplasms (PCN) with malignant potential are thought to be less aggressive than ordinary ductal adenocarcinoma, even in the setting of malignant transformation. Therefore, deciding whether or not to carry out surgery is very difficult, especially in elderly and asymptomatic patients, because of the high risk of perioperative morbidities. The aim of the present study was to examine clinical outcomes of PCN patients aged 65 years or older. METHODS This retrospective analysis included patients with incidentally detected PCN with follow-up durations >1 year. Patients diagnosed with obvious simple cysts, pseudocysts or pancreatic cancer and patients with a history of pancreatic disease were excluded from the study. RESULTS The present study included 201 patients (older group 104 patients ≥65 years; younger group 97 patients

Chronic liver disease is a common comorbidity in surgery. To assess post-operative morbidity and mortality in relation to progression of chronic liver disease and to identify the risk factors.Six hundred and nine consecutive patients with chronic liver disease who underwent surgery were classified into two groups: non-cirrhotic (n = 363) and cirrhotic (n = 246). Randomly selected patients without underlying liver disease who underwent surgery were used as control group (n = 148).The occurrence of major post-operative complications was higher in the non-cirrhotic group than in the control group (11.8% vs. 6.1%, P = 0.051); age, type of surgery and serum albumin level were independent predictors for post-operative morbidity. The frequency of significant post-operative liver damage (14.9% vs. 12.2%, P = 0.920) and mortality (0.6% vs. 0.7%, P = 0.871) did not differ between the two groups. The cirrhotic group had markedly higher incidences of post-operative mortality (10.2%), major complications (32.5%) and significant liver damage (43.1%) than the control and non-cirrhotic groups (all P0.001). Type of surgery, Child-Pugh score and model for end-stage liver disease score were independently associated with post-operative morbidity and mortality in patients with cirrhosis. Specific data regarding post-operative morbidity and mortality were presented according to progression of liver disease and type of surgery.Non-cirrhotic chronic liver diseases were associated with higher risk of post-operative morbidity, particularly in cases of major surgery, older age and hypoalbuminaemia. Cirrhosis further increased the risk, even death, depending on degree of hepatic decompensation and type of surgery.

Background and Aim: Although the Psychometric Hepatic Encephalopathy Score (PHES) for the diagnosis of minimal hepatic encephalopathy (MHE) has been validated in several countries, further validation is required for its use in different populations. The aims of this study were thus to standardize the PHES in a healthy Korean population and evaluate the prevalence of MHE among Korean patients with liver cirrhosis. Methods: Two-hundred healthy subjects without evidence of liver disease and 160 patients with liver cirrhosis without overt HE were included. Blood sampling for routine laboratory tests and determination of venous ammonia concentration was performed on the day of PHES neuropsychological testing. Results: The age and education years of the control group were 41 ± 13 years and 13 ± 3 years, respectively; 100 of the subjects (50.0%) were men. The PHES for the control group was −0.31 ± 2.06 and the normal range was thus set at > −5 points. The age and education years of the liver cirrhosis group were 55 ± 8 and 11 ± 4 years, respectively; 102 of those in this group (63.8%) were men. Of the liver cirrhosis patients, 129 (80.6%), 21 (13.1%), and 10 (6.3%) had Child–Pugh grades A, B, and C, respectively. The PHES of the liver cirrhosis group was −2.94 ± 3.39. MHE was diagnosed in 41 patients (25.6%), of which 26 (20.2%), nine (42.9%), and six (60.0%) had Child–Pugh grades A, B, and C, respectively. Conclusions: The PHES was useful for detecting patients with MHE. A significant proportion of Korean patients with liver cirrhosis suffer from MHE.

Background and Aim: We investigated long-term outcomes and prognostic factors in patients with hepatitis B virus (HBV)-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents. Methods: Between January 1999 and February 2009, a total of 240 consecutive patients who had HBV-related cirrhosis without malignancy were treated with lamivudine and second line nucleos(t)ide analogs. The group of historical controls consisted of 481 consecutive patients with HBV-related cirrhosis who were managed without any antiviral treatment prior to 1999. Results: In 78% of the patients who received antiviral treatment, sustained viral suppression (serum HBV DNA 105 copies/mL at last follow-up) was an important independent risk factor of death (P

Background and Aims: Transient elastography (TE) is useful for predicting the fibrosis stage, but it is unsatisfactory as a substitute for liver biopsy, especially in patients with chronic hepatitis B (CHB). This study was performed to establish a reliable model for predicting significant fibrosis (SF) in patients with CHB. Methods: All CHB patients who were admitted to undergo liver biopsy were enrolled. They were randomly classified into either a training set (n = 139) or a validation set (n = 69). A model for predicting SF was established in the training set and validated in the validation set. Low and high cutoff values (COVs) were chosen for sensitivity ≥ 99% and specificity ≥ 99%, respectively. Results: A total of 208 patients were enrolled. Age was 39 ± 12 years and 149 (71.6%) were men. In the training set, liver stiffness values and serum haptoglobin, apolipoprotein A1, and α2-macroglobulin levels were independent predictors of SF on multivariate analysis. These variables were used to construct a novel model, called the HALF index. The area under the receiver operating characteristics curve of the HALF index for predicting SF was significantly higher than that of TE alone (0.915 vs 0.877, P = 0.010). Using low and high COVs of the HALF index, it appears that approximately half (47.1%) of patients could avoid liver biopsy, with an associated accuracy of 99.0%. Conclusion: A combination of liver stiffness and serum markers identified SF with a high degree of accuracy. Approximately half of all patients with CHB could avoid liver biopsy through the utilization of the HALF index.

Background and Aims: Bronchial asthma (BA) is considered an extra-esophageal syndrome of gastroesophageal reflux disease (GERD) with poor pathophysiological background. We analyzed the correlation between GERD and BA, examining esophageal epithelium with transmission electron microscopy (TEM), along with clinical findings. Methods: BA patients of controlled and partly-controlled levels were enrolled in the study. A pulmonary and gastrointestinal (GI) questionnaire was given. Patients with no symptoms joined the control group. Esophageal mucosal tissue was taken by esophagogastroduodenoscopy from both groups and processed for TEM. Intercellular space (IS) was measured with an image analyzing program, 100 times for each patient. Results: The control (n = 20) and BA (n = 20) groups revealed no significant differences in baseline characteristics. All BA patients were using corticosteroid inhalers, with seven patients having a recent history of acute exacerbation. Patients with at least one GI symptom made up 70% (14/20) of the BA group, and heartburn and/or regurgitation were detected in 40% of patients. Endoscopic findings of GERD were mucosal breaks (n = 3). The IS of the control group was 0.389 ± 0.297 um, while the BA group was 0.806 ± 0.556 um (P = 0.001). The presence of GERD symptoms (P = 0.306) and a history of recent asthma attacks (P = 0.710) did not show significant differences. Conclusions: The BA group showed a significant difference in the dilatation of IS compared to the control group, suggesting a higher prevalence of GERD in BA patients and a close pathophysiological correlation.

Background: Patients with cirrhosis have an increased risk of mortality after surgery. In 2007, a new model was suggested to calculate mortality risk at specific time points after surgery at the Mayo clinic. Aims: We investigated the mortality risks in Korean cirrhotic patients who underwent various surgeries and applied the Mayo clinic model to our study populations. Methods: We conducted a retrospective review of the charts of 160 patients with cirrhosis who underwent surgical procedures under general anaesthesia between January 1996 and December 2006 at two hospitals. Results: The overall 30-, 90-day and 1-year mortality rates were 7.5, 9.4 and 10.6% respectively. In multivariate analysis, the Child‐Turcotte‐Pugh (CTP) score, model for endstage liver disease (MELD) and the American Society of Anesthesiologists (ASA) physical status classification and age were significantly associated with mortality. The area under the receiver operating characteristic (AUROC) from the calculated value using Mayo model as a predictor of 30-, 90-day and 1-year mortality was 0.832, 0.803 and 0.822 respectively, of which, 1-year mortality was significantly different from AUROC of mortality prediction based on our patient’s data (P=0.025). In addition, the mean of predicted 1-year mortality rate (22.6 � 12.0%) using Mayo model was significantly higher than that from observed (8.9 � 1.4%, Po0.01). Conclusions: The CTP score or MELD score or ASA physical class and age were found to be significant predictors of postoperative mortality in cirrhotic patients. The risk prediction model developed at the Mayo clinic showed good performance in Korean cirrhotic patients. However, we found that the model tended to overestimate mortality, especially 1 year after surgery.

Background and Aim: It is still uncertain whether the accuracy of transient elastography (TE) in predicting the fibrosis stage is similar in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The present study was carried out to evaluate whether the underlying cause of chronic viral hepatitis affects the predictive accuracy of TE. Methods: Patients with CHB or CHC who were admitted for a liver biopsy were enrolled. Patients underwent TE and laboratory tests on the same day as the liver biopsy. The predictive accuracy was analyzed by comparing the areas under the receiver-operating characteristic curves (AUCs). Results: Two-hundred and seven patients were enrolled, comprising 121 CHB patients and 86 CHC patients). The patients were aged 44 ± 14 years, and 121 (58.5%) of them were men. AUCs for predicting significant fibrosis were significantly lower in CHB patients than in CHC patients (P = 0.043). The serum alanine aminotransferase (ALT) level was associated with overestimation and underestimation of the fibrosis stage, while the cause of chronic hepatitis was not. AUCs for predicting significant fibrosis were significantly lower in patients with ALT levels >70 IU/L (AUC, 0.830; 95% CI, 0.742–0.898) than in patients with ALT levels ≤70 IU/L (0.944; 0.882–0.979; P = 0.015). Conclusions: Although the predictive accuracy of TE in predicting significant fibrosis differed significantly with the cause of chronic hepatitis, this difference was due to the degree of serum ALT levels rather than to the cause of hepatitis itself. Avoiding performing TE in patients with elevated ALT levels is recommended to guarantee the predictive accuracy of TE.

Background: Proton pump inhibitor (PPI)-containing triple therapy with clarithromycin and amoxicillin is now a standard regimen for Helicobacter pylori eradication in Korea. Amoxicillin has time-dependent bactericidal activity against H. pylori; we therefore assumed a dosing schedule of amoxicillin would affect the eradication rate of H. pylori. The purpose of this study was to evaluate and compare the efficacy of different amoxicillin dosing schedules for the eradication of H. pylori. Materials and Methods: One hundred and eighty-six patients with H. pylori infection were eligible for this study. Patients were randomly assigned to one of two regimens: amoxicillin 1000 mg with clarithromycin 500 mg and omeprazole 20 mg twice daily for 2 weeks (BID group, n = 93), or amoxicillin 500 mg four times daily with clarithromycin 500 mg and omeprazole 20 mg twice daily for 2 weeks (QID group, n = 93). The success of H. pylori eradication was evaluated 4–5 weeks after completing treatment. Results: Overall eradication rate was 90.3%, and eradication rates were 91.4% in the BID group and 89.2% in the QID group (p = 0.62). Compliances was 95.7% in the BID group and 93.5% in the QID group (p = 0.516); this was the only factor that significantly affected H. pylori eradication in this study. Side effects in both groups were generally mild. Conclusions: Amoxicillin regimens with PPI and clarithromycin are found to be equally effective and safe in both the BID and QID groups for H. pylori eradication. Therefore, considering patient's comfort, we recommend a twice daily amoxicillin regimen.

Background and Aims: Recent progress in the treatment of variceal bleeding might have reduced the impact of variceal bleeding on survival in patients with esophageal varices. We conducted a retrospective cohort study in an attempt to re-evaluate the clinical significance of variceal bleeding. Methods: A cohort of 304 patients with liver cirrhosis and esophageal varices, who had no previous history of variceal bleeding and no prophylactic therapy, was studied. Results: During a median follow-up period of 32 months, 55 patients (18%) bled from varices and 111 (37%) died. Variceal hemorrhages accounted for 15% of total deaths. The mortality of first variceal bleeding was 25% in the whole group, but was remarkably different depending on liver function at the time of bleeding (0% in grade Child A vs 55% in grade C; P

Bioassay-guided fractionation leads to the isolation of novel licochalcone G (I) along with seven known chalcones.