Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.

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 end point 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.

The LAW index as an accurate indicator of the initiation of antiviral treatment in patients with chronic hepatitis B.

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.

The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years?

BACKGROUND & AIMS: There has been remarkable progress in the management of hepatocellular carcinoma (HCC) during the last several decades, but its effect on the prognosis of HCC patient needs clarification. We analysed the changes that affected prognosis of HCC patients diagnosed over two different eras. METHODS: A retrospective study of 1318 patients diagnosed with HCC from 1986 to 2012 was conducted. Analysis was done according to two cohorts, cohort 1 (patients diagnosed with HCC from 1986 to 1992) and cohort 2 (patients diagnosed from 2006 to 2012). RESULTS: Hepatitis B virus was the most common cause of liver disease for both cohorts (66.2% and 66.0%). The proportion of patients with Barcelona Clinic Liver Cancer stage 0/A was significantly lower in cohort 1 than in cohort 2 (14.4% vs. 39.5%, P < 0.001). The proportions of patients diagnosed during surveillance and general health check-up were significantly higher in cohort 2 than in cohort 1 (28.6% vs. 10.6% and 26.3% vs. 7.9%, respectively) while those diagnosed during symptomatic evaluation was significantly higher in cohort 1 than in cohort 2 (45.1 vs. 81.4%, P < 0.001). Surgical resection rate was similar between the two cohorts (26.1% vs 26%) while the transcatheter arterial chemoembolization rate which was the highest in cohort 1 (40.6%) was overtaken by radiofrequency ablation in cohort 2 (55%) at BCLC stage 0/A. Median survival duration in cohort 2 was significantly longer than cohort 1 (65.0 vs. 7.9 months, P < 0.001). CONCLUSIONS: Implementation of national cancer surveillance and the advancement of treatment modalities have likely led to early detection of HCC and improvements in prognosis over the last 20 years.

Clinical significance of hepatitis B virus precore and core promoter variants in Korean patients with chronic hepatitis B.

BACKGROUND/AIM: We aimed to clarify the clinical significance of precore (preC)/core promoter (CP) variants of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. METHODS: We assessed serum HBeAg, HBV DNA levels, alanine transferase (ALT) levels, and progression of liver fibrosis in 226 Korean CHB patients, presumed to be infected with genotype C HBV, to analyze HBV variants in the preC region (G1896A) and CP regions (A1762T, G1764A). RESULTS: CP and preC variants were more frequently found in HBeAg-negative patients than in HBeAg-positive patients (P<0.05). HBeAg-positive patients with CP variants had higher ALT levels and more advanced fibrosis scores (all P<0.01) than those without variants; those with preC variant had lower HBV DNA levels (P=0.009), with no significant difference in ALT levels and fibrosis scores. However, no significant correlation was found between HBV variants and clinicopathologic findings in HBeAg-negative patients. Furthermore, multivariate analysis revealed that (1) progression of liver fibrosis (≥F2) was associated with older age in both HBeAg-positive and HBeAg-negative patients (P<0.05) and with CP variants in the HBeAg-positive group (P=0.007), and (2) HBV DNA levels were positively correlated with ALT levels, irrespective of HBeAg (P<0.05), whereas they were negatively correlated with the presence of preC variant in the HBeAg-positive group (P=0.004). CONCLUSIONS: In HBeAg-positive CHB patients infected with genotype C HBV, preC variant was associated with enhanced host immune response with lower HBV DNA levels, whereas CP variants were associated with severe liver damage and liver fibrosis progression.

Risk Factors for Developing Hyponatremia During Terlipressin Treatment: A Retrospective Analyses in Variceal Bleeding.

GOALS: The aim of this study was to evaluate the risk factors and clinical significance of terlipressin-induced hyponatremia. BACKGROUND: Patients receiving terlipressin treatment frequently develop hyponatremia. However, its clinical significance and risk factors are not fully elucidated. STUDY: Records of patients treated with terlipressin for variceal bleeding were analyzed. Hyponatremia was defined as a decrease in serum sodium (Na) level of >5 mEq/L from the baseline level; severe hyponatremia as a decrease in serum Na level of >10 mEq/L from the baseline level; and rapid severe hyponatremia as a decrease in serum Na level of >10 mEq/L within 3 days of treatment. RESULTS: The study involved 151 patients (mean age, 55.1±11.8 y) with male predominance (80.8%). Baseline serum Na and creatinine levels were 137.2±6.1 mEq/L and 0.9±0.4 mg/dL, respectively. Patients were treated with terlipressin for 4.5±1.9 days. Changes in serum Na levels from baseline were 0.4±4.1, -1.1±4.8, -4.0±7.0, -6.5±9.1, and -6.1±11.2 mEq/L, whereas the frequencies of hyponatremia and severe hyponatremia were 13.6%, 30.4%, 50.8%, 63.5%, and 66.9% and 0%, 8.8%, 23.3%, 33.0%, and 38.8% on days 1, 2, 3, 4, and 5 of treatment, respectively. Younger age, lower Child-Pugh score, higher serum Na level, and longer duration of terlipressin treatment were independent risk factors. Rapid severe hyponatremia developed in 29 patients (19.2%); lower body mass index was an additional risk factor in this group. Mortality was not associated with hyponatremia. CONCLUSIONS: Terlipressin-induced hyponatremia occurred frequently, especially in young patients with good liver function and higher Na level. Caution is required when administering terlipressin to patients with low body mass index.

Role of hepatitis B surface antigen (HBsAg) in identifying true inactive HBsAg carriers infected with genotype C hepatitis B virus.

BACKGROUND: Inactive and active phases of hepatitis B e antigen-negative chronic hepatitis B virus (HBV) infection are diagnosed by serum HBV DNA levels, with cutoff at 2000 IU/mL. However, it is difficult to distinguish inactive carriers at a single time point because HBV DNA levels can transiently decrease to <2000 IU/mL even in noninactive carriers. GOALS: We aimed to establish the role of serum hepatitis B surface antigen (HBsAg) in identifying "true inactive carriers" among treatment-naive genotype C HBV-infected patients with low viremia. STUDY: A total of 133 hepatitis B e antigen-negative carriers with serum HBV DNA levels of <2000 IU/mL and normal alanine aminotransferase levels were enrolled and followed up for >12 months. RESULTS: Forty patients (30.1%) were classified as noninactive carriers (HBV DNA ≥2000 IU/mL and/or alanine aminotransferase >40 IU/L) during 12 months from enrollment. No baseline serum HBV DNA levels could identify true inactive carriers with 100% specificity, whereas baseline serum HBsAg levels (50 IU/mL) identified true inactive carriers with 100% specificity and 29% detection rate. Detection rate increased when different cutoff levels were applied to different age groups according to median age (46 y). It was comparable in both younger and older groups (37.2% vs. 38%) even when HBsAg cutoff level was increased in the former (400 vs. 50 IU/mL). Furthermore, none reversed to noninactive phase during long-term follow-up when these cutoff levels were applied. CONCLUSIONS: Baseline serum HBsAg levels at a single time point can identify persistently true inactive carriers, with different cutoff levels according to age.

A randomized, endoscopist-blinded, prospective trial to compare the preference and efficacy of four bowel-cleansing regimens for colonoscopy.

OBJECTIVES: The superiority of conventional polyethylene glycol (PEG) solution over sodium picosulfate with magnesium citrate (SPMC) for bowel preparation remains controversial. Therefore, this study compared the efficacy, safety, and tolerability of different regimens of SPMC and PEG solution in Koreans, who consume a traditional high-fiber diet. MATERIALS AND METHODS: A total of 200 outpatients undergoing elective colonoscopy were randomized into four groups receiving different bowel-preparation regimens in a prospective study: 4 L PEG in the morning on the day of colonoscopy, two 2 L split doses of PEG, split doses of 2 SPMC sachets, and split doses of 3 SPMC sachets. Bowel cleansing efficacy was assessed based on the Ottawa bowel preparation scale and the Aronchick scale by endoscopists blinded to treatment, and patients filled out a questionnaire to determine satisfaction. RESULTS: There was no difference among groups with respect to bowel cleansing grade (Ottawa scale, p = 0.314). Patients in the SPMC groups were less likely to have abdominal fullness, pain, nausea, or vomiting than patients in the PEG groups (p < 0.05). Patients reported SPMC was more palatable than PEG. There were no significant differences among groups with respect to polyp detection rate. CONCLUSION: SPMC is as effective as conventional high-volume PEG-electrolyte solution in Korean patients. SPMC groups reported superior palatability and tolerability compared to PEG groups.

Comparison of the efficacies of lamivudine versus entecavir in patients with hepatitis B virus-related decompensated cirrhosis.

BACKGROUND: Suppression of hepatitis B virus (HBV) DNA is more potent, and occurrence of resistant strain is rare with entecavir than lamivudine, but whether these merits result in a more favourable outcome in HBV-related decompensated cirrhosis patients is unclear. AIMS: To compare virologic response, changes in liver function, clinical course and predictive factors for early mortality after treatment between patients treated with lamivudine and those with entecavir in HBV-related decompensated cirrhosis patients. METHODS: HBV-related decompensated cirrhosis patients [Child-Turcotte-Pugh (CTP) score ≥ 7] treated with either lamivudine or entecavir were enrolled. Serum HBV DNA levels, CTP score and Model for End-stage Liver Disease (MELD) score were monitored every 3 months. RESULTS: Eighty-six patients were enrolled; mean age was 54 ± 11 years, and 63 (73.3%) patients were men; 41 (47.7%) and 45 (52.3%) patients were assigned to the lamivudine group and entecavir group respectively. Although suppression of serum HBV DNA level was more potent in the entecavir group, CTP or MELD scores during the course of treatment did not differ between the two groups. Similarly, 6-month survival rates did not differ between the two groups (95.1 vs 93.2%, P = 0.684). Baseline CTP score and MELD score at 3 months of treatment were significantly associated with 6-month mortality. The 6- and 12-month mortality rates for patients with baseline CTP score ≥ 11 and MELD score ≥ 17.5 after 3 months of treatment were 42.9 and 61.9% respectively. CONCLUSIONS: Although HBV DNA suppression was more potent in the entecavir group than the lamivudine group, early mortality rates did not differ between the two groups. The baseline CTP score and MELD score 3 months after initiating antiviral treatment were significant predictors of early mortality.

Psychometric hepatic encephalopathy score for the detection of minimal hepatic encephalopathy in Korean patients with liver cirrhosis.

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.

Prognosis of hepatitis B-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents.

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 < 10(5) copies/mL) was achieved during a mean follow-up period of 46 months. The occurrences of death, hepatic decompensation, and hepatocellular carcinoma (HCC) were less frequent in the treated cohort than in untreated historical controls, with the 5-year cumulative incidences being 19.4% versus 43.9% (log-rank P < 0.001), 15.4% versus 45.4% (P = 0.001), and 13.8% versus 23.4% (P = 0.074), respectively. For patients who received antiviral treatment, suboptimal viral suppression (HBV DNA > 10(5) copies/mL at last follow-up) was an important independent risk factor of death (P < 0.001) and hepatic decompensation (P = 0.019), and was linked to an increased risk of HCC (P = 0.042). Although the Child-Pugh grade remained a useful prognostic factor, no significant differences were found between patients with Child-Pugh grade B and C cirrhosis at the beginning of antiviral treatment (P = 0.656). CONCLUSIONS: Oral antiviral agents have improved the prognosis of patients with HBV-related cirrhosis and affected the prognostic values of factors constituting the Child-Pugh system, necessitating a more efficient prognostic system.

Validation of a Mayo post-operative mortality risk prediction model in Korean cirrhotic patients.

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 end-stage 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%, P<0.01). CONCLUSIONS: The CTP score or MELD score or ASA physical class and age were found to be significant predictors of post-operative 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.

Serum aminotransferase levels instead of etiology affects the accuracy of transient elastography in chronic viral hepatitis patients.

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.

Electron microscopic study of intercellular space: correlation analysis of bronchial asthma and gastroesophageal reflux disease.

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.

Healthy range for serum ALT and the clinical significance of "unhealthy" normal ALT levels in the Korean population.

BACKGROUND AND AIMS: It remains unclear whether the currently-used normal range for serum alanine aminotransferase (ALT) levels really reflects a healthy liver. The present study was conducted to evaluate the healthy range of serum ALT in the Korean adult population and to determine the clinical significance of unhealthy levels. METHODS: We reviewed the medical records, including questionnaires and the results of laboratory and radiological tests conducted at the Health Promotion Center at Korea University Anam Hospital between March 2005 and February 2007. The records, written in questionnaire form, included baseline data, such as physical status, social behaviors, medication history, and past and present disease histories. RESULTS: The mean age of the 7403 enrolled patients was 48 years, and 49.9% of these patients were male. A healthy cohort was selected after excluding patients who showed any abnormalities of the factors that were significantly associated with the serum ALT level upon multivariate regression analysis. The upper limit of the healthy range of the serum ALT level (i.e. 95th percentile) in the healthy population was 31 IU/L for males and 23 IU/L for females. The prevalence of metabolic syndrome and insulin resistance (IR) were significantly higher in patients with an 'unhealthy' normal ALT level than in those with a healthy ALT level. CONCLUSION: In our study, the upper limit of the healthy range of the serum ALT level was 31 IU/L for males and 23 IU/L for females. An unhealthy normal ALT level was associated with a higher prevalence of metabolic syndrome and IR.

Application of the HALF index obviates the need for liver biopsy in half of all patients with chronic hepatitis B.

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.

Effect of bowel preparation with polyethylene glycol on quality of capsule endoscopy.

BACKGROUND AND AIMS: Capsule endoscopy (CE) has the problem that lumen visualization is impaired by bubbles, bile, and debris. The benefits of bowel preparation are still controversial and the best method remains to be determined. The objective of this study was to evaluate the effect of the method of bowel preparation on the quality of visualization and on transit time. METHODS: The study sample consisted of 68 patients for CE. Patients were randomly allocated to three groups. In group A (n = 23), patients fasted for 12 h before CE. In groups B (n = 20) and C (n = 25), patients received 2 and 4 l of polyethylene glycol (PEG), respectively. Small bowel images were evaluated by use of a cleansing score system. Representative frames were serially selected at 5-min intervals and scored by assessment of two properties (proportion of luminal visibility and extent of obscuration). RESULTS: The median scores of image quality in groups A, B, and C were 2.26, 2.43, and 2.55 respectively, (P = 0.034). Cecal completion rates, gastric transit time, and small bowel transit time were no different among the three groups. Detection of lesions in groups A, B, and C was 56.5, 65.0, and 68.0%, respectively. CONCLUSIONS: Bowel preparation with PEG resulted in better image quality than fasting alone. No significant difference was observed between 2 and 4 l. PEG 2 l rather than 4 l may be a useful method of preparation for CE.

Is intercellular space different among layers in normal esophageal mucosa? An electron microscopic study.

BACKGROUND/INTRODUCTION: Dilatation of intercellular space (IS) of esophageal epithelial cells is described as a sensitive early marker for epithelial damage by refluxate. Esophageal epithelia are morphologically subdivided into three layers according to the shape of the cells and nuclei. Meanwhile, ten transmission electron microscopy (TEM) photographs and ten randomly selected measurements per photo from gastroesophageal reflux disease (GERD) patients have been widely accepted without any theoretical criticism. We assumed that the IS differs among each layer and thus studied IS according to subdivided layers of normal esophageal epithelium. We also evaluated an optimal number of IS measurements per photograph. MATERIALS AND METHODS: Esophagogastroduodenoscopy was performed in 15 healthy adults without any symptom of GERD, taking biopsies from mucosa above 5 cm from the squamo-columnar junction. Tissues were handled and prepared for TEM, verifying three layers of esophageal mucosa, i.e., squamous cell layer, prickle cell layer, and basal layer. Ten digital photomicrographs were taken from each three layers by TEM, and ISs were measured with a computerized image analysis program. For the method of measuring IS, 5, 10, 20, 30, and 40 measurements per photomicrograph were respectively performed by four different examiners. Mean value and intraclass correlation coefficient (ICC) was also yielded. RESULTS: Mean IS of lower esophagus irrelevant to three epithelial layers were 0.39 ± 0.30 µm. When subdivided into three layers, however, mean IS of squamous cell layer was 0.62 ± 0.23 µm, prickle cell layer 0.23 ± 0.19 µm, and basal layer 0.55 ± 0.36 µm, with their difference statistically significant (p < 0.05). On the other hand, ICC of 5, 10, 20, 30, and 40 measurements were 0.688, 0.917, 0.837, 0.790, and 0.765, respectively. CONCLUSIONS: Mean IS values of each three layers of esophageal epithelium in normal subjects were significantly different, and reconsideration of the standard measurement method is needed. Ten measurements per photo had an adequate inter-observer agreement.

Serum cystatin C level is a useful marker for the evaluation of renal function in patients with cirrhotic ascites and normal serum creatinine levels.

BACKGROUND/AIMS: Several studies suggested that serum cystatin C (CysC) is more useful than serum creatinine (Cr) for the assessment of renal function in patients with liver cirrhosis. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and normal Cr level. METHODS: We enrolled patients with cirrhotic ascites and a normal serum Cr level (<1.2 mg/dL). GFR was measured by (99m)Tc-DTPA renal scan. Serum Cr, CysC, and Cr clearance (CCr) were measured on the same day. Significant renal impairment and severe renal impairment were defined as GFR <60 mL/min and GFR <30 mL/min, respectively. RESULTS: Eighty-nine patients with cirrhotic ascites were enrolled in the study (63 men and 26 women; age, 55±11 years). Forty-seven (52.8%) and 42 (47.2%) patients were in Child-Pugh grade B and C, respectively. Serum Cr and CysC levels and GFR were 0.8±0.2 mg/dL, 1.1±0.3 mg/L, and 73.4±25.5 mL/min, respectively. Significant and severe renal impairment were noted in 28 (31.5%) and 2 (2.2%) patients, respectively. GFR was well correlated with serum Cr, CysC, and e-GFR(MDRD), while it was not correlated with e-GFR(C&G). In multivariate analysis, only CysC was significantly correlated with GFR (ß, 45.620; 95% CI, 23.042-68.198; P<0.001). Serum CysC level was the only independent predictor for significant renal impairment. CONCLUSIONS: Significant renal dysfunction was not rare in patients with cirrhotic ascites, even their serum Cr level is normal. Serum CysC is a useful marker for detecting significant renal dysfunction in these patients.

Terlipressin-induced hyponatremic seizure.

Terlipressin is a splanchnic constrictor that is used to control variceal bleeding and is considered to have a very good safety profile compared to vasopressin. However, side effects such as hyponatremia and seizure, although very rare, can occur. Recently, the authors have experienced a case of hyponatremia induced by infusion of terlipressin which resulted in generalized seizure. On admission, the patient's sodium level was 141 mmol/l but, 4 days after the initiation of terlipressin, it plummeted to 114 mmol/l, with serum osmolality also having fallen to 243 mOsm/kg. Hyponatremia could not be corrected despite correction with hypertonic saline but, after withdrawal of terlipressin, the serum sodium level showed a dramatic increase almost to the normal range the following day. Therefore, it is necessary to carefully monitor patients' electrolyte levels during the course of terlipressin therapy.

Dynamic changes in liver stiffness during the course of acute hepatitis A.

OBJECTIVE: Several recent studies have suggested that hepatic necroinflammation can alter the results of liver stiffness measurements (LSMs) obtained using the FibroScan device. However, the precise relationship between acute hepatic inflammation and LSMs remains unclear. The aim of this study was therefore to evaluate the dynamic changes in LSMs during the course of acute hepatic inflammation. MATERIAL AND METHODS: Thirty-one patients with acute hepatitis A (AHA) were enrolled in this study (mean +/- SD age 29 +/- 7 years; 32.3% male). Only AHA patients who visited our hospital before their alanine aminotransferase (ALT) levels peaked were included. The day when AHA-associated symptoms began was considered as Day 0. Serum levels of ALT and bilirubin (BIL), and the international normalized ratio (INR) were measured every 2 days, as were LSMs, until the peak levels of all parameters were identified. Subsequently, these parameters were measured every 1-2 weeks until they had normalized. RESULTS: Peak serum levels of ALT and BIL, the INR, and LSMs were 3723 +/- 1513 IU/l, 5.8 +/- 2.4 mg/dl, 1.3 +/- 0.3, and 11.9 +/- 5.7 kPa, respectively. The time taken for LSMs to peak from Day 0 (8 +/- 2 days) differed significantly from that for ALT (5 +/- 1 days), BIL (10 +/- 4 days), and INR (5 +/- 1 days). LSMs had normalized (< or = 5.5 kPa) in all patients at 34 +/- 17 days after Day 0. ALT level and the INR were significantly associated with peak LSMs and BIL level and the INR with the time taken for normalization of LSMs. CONCLUSIONS: LSMs changed dynamically during the course of AHA. The pattern of change appears to be related to the severity of hepatic necroinflammation.