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Currently, because the population is aging, use of medications has been increasing, including use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents. This study aims to investigate whether NSAIDs can cause damage to the small bowel (SB) mucosa. Endoscopic videos of subjects who had undergone capsule endoscopy (CE) were evaluated by three experts in order to identify SB injury. All medications taken within 2 weeks from the time of CE were investigated. Cases with a final diagnosis of intestinal tuberculosis, inflammatory bowel disease, Behcet’s disease, Peutz–Jeghers syndrome, small bowel lymphoma, or Henoch–Schonlein purpura were excluded from the analysis. Among the 273 subjects, 125 (45.8%) had SB erosions or ulcers (erosion group) and the remaining 148 (54.2%) did not (no erosion group). SB erosions or ulcers were more common in females, patients aged > 60 years, and subjects taking NSAIDs (p = 0.048, 0.032, and

BACKGROUND AND AIM Infliximab has been widely prescribed for treating inflammatory bowel disease (IBD). However, the response rates to infliximab differ among patients. Therefore, we aimed to identify the genetic and clinical markers that predict infliximab response. METHODS A total of 139 Korean patients with IBD who received infliximab were classified according to infliximab response as follows: (i) primary response vs nonresponse and (ii) sustained response vs loss of response. We performed an association study using whole-exome sequencing data to identify genetic variants associated with infliximab response. Candidate variants were validated in 77 German patients with IBD. Stepwise multivariate logistic regression was performed to identify predictors. RESULTS We found five candidate variants that were associated with primary nonresponse to infliximab (P

Myelosuppression is a life-threatening complication of thiopurine therapy, and the incidence of thiopurine-induced myelosuppression is higher in East Asians than in Europeans. We investigated genetic factors associated with thiopurine-induced leukopenia in patients with IBD.A genome-wide association study (GWAS) was conducted in thiopurine-treated patients with IBD, followed by high-throughput sequencing of genes identified as significant in the GWAS or those involved in thiopurine metabolism (n=331). Significant loci associated with thiopurine-induced leukopenia were validated in two additional replication cohorts (n=437 and n=330). Functional consequences ofThe GWAS identified two loci associated with thiopurine-induced leukopenia (rs16957920,The results suggest that the hypomorphic

Crohn’s disease (CD) is a chronic inflammatory bowel disease and a genetic variant in the OCTN2, g.-207G > C is significantly associated with CD susceptibility. This study was aimed to identify novel OCTN2 functional promoter variants and their roles in transcriptional regulation using various in vitro assays. In addition, we investigated the association between OCTN2 genotypes and CD through genetic analysis using DNA samples from 193 patients with CD and 281 healthy controls. Among the three major promoter haplotypes of OCTN2 identified, one haplotype, H3, showed a significant decrease in promoter activity: two polymorphisms in H3 were associated with a significant reduction in promoter activity. In particular, we found that the reduced transcriptional activity of those two polymorphisms results from a reduction in the binding affinity of the activators, NF-E2 and YY1, to the OCTN2 promoter. The functional haplotype of the OCTN2 promoter was associated with clinical course of CD such as the disease behavior and need for surgery. However, genetic variants or haplotypes of OCTN2 did not affect the susceptibility to CD. Our results suggest that a common promoter haplotype of OCTN2 regulates the transcriptional rate of OCTN2 and influences the clinical course of CD.

Background A dysregulated mucosal immune response to the intestinal environment in a genetically susceptible host is hypothesized to be critical to the pathogenesis of Crohn's disease (CD). Therefore, we examined CD-susceptibility genes involved in the immune response through a genome-wide association study and consecutive genotyping of human leukocyte antigens (HLAs) and killer cell immunoglobulin-like receptors. Methods An initial genome-wide association study was performed with 275 CD patients and 2369 controls from a Korean population. To validate the loci identified in the genome-wide association study, replication genotyping was performed in a different cohort of 242 CD patients and 1066 controls. Finally, high-resolution genotyping of HLA and killer cell immunoglobulin-like receptor was performed. Results Four susceptibility loci, a promoter region in tumor necrosis factor (ligand) superfamily member (TNFSF15) and 3 independent regions in HLAs, showed significant associations with CD. Among them, rs114985235 in the intergenic region between HLA-B and HLA-C showed the strongest association, with an increased risk of CD (P = 8.71 × 10; odds ratio, 2.25). HLA typing in this region showed HLA-C*01 to be responsible for the association of CD among 43 HLA-B and HLA-C genotypes identified in the Korean population. However, the interaction of HLA-C with killer cell immunoglobulin-like receptor had little effect on the development of CD. Conclusions We newly identified HLA-C*01 as a prominent CD-susceptibility HLA allotype in the Korean population. In addition, these results confirm that genetic variations in immune response genes, such as HLAs and TNFSF15, are important host factors for the pathogenesis of CD.

Liver stiffness measurement (LSM) using transient elastography (FibroScan) can accurately assess the degree of liver fibrosis and predict the development of hepatocellular carcinoma (HCC) and variceal bleeding in patients with chronic hepatitis B (CHB).We compared the accuracy of noninvasive liver fibrosis prediction methods in predicting the development of HCC or hepatic decompensation in patients with CHB.A total of 1126 patients with CHB who underwent LSMs and attended regular follow-ups to detect the development of HCC and hepatic decompensations (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatorenal syndrome) were enrolled. Noninvasive liver fibrosis prediction methods included, age-spleen-to-platelet ratio index, LSM, LSM-spleen diameter-to-platelet ratio index (LSPI), P2/MS, and FIB-4.During follow-up (median, 30.7 mo), HCC and hepatic decompensation developed in 63 and 68 patients, respectively. The accuracy of LSM and LSPI in predicting the development of HCC or hepatic decompensation was higher than that of aspartate aminotransferase-to-platelet ratio index, age-spleen-to-platelet ratio index, P2/MS, or FIB-4 (areas under the receiver operating characteristic curve=0.789 and 0.788 vs. 0.729, 0.756, 0.696, and 0.744 for HCC development; areas under the receiver operating characteristic curve=0.820 and 0.848 vs. 0.787, 0.799, 0.812, and 0.784 for hepatic decompensation). On multivariate analyses, LSM and LSPI were identified as independent predictors of the development of HCC [hazard ratio (HR), 1.040 (LSM); HR, 1.001 (LSPI)] and hepatic decompensation [HR, 1.033 (LSM); HR, 1.002 (LSPI)].Our results suggest that LSM or LSPI may be useful predictors of the development of HCC and hepatic decompensation in patients with CHB.

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

BACKGROUND/AIM Clevudine and entecavir are highly potent antiviral agents being used in treatment of chronic hepatitis B. However, no data comparing clinical efficacy and safety of these 2 drugs over a long-term period is available. The aims of this study are to compare virologic, biochemical, and serologic response rates of clevudine and entecavir, as well as treatment failure rates up to 2 years. METHODS Data of patients who started clevudine (n = 86) or entecavir (n = 159) as a primary treatment for chronic hepatitis B at Korea University Ansan or Guro Hospital between January 2007 and June 2008 were analyzed. RESULTS Treatment responses were compared at 3-month intervals up to 24 months. Per protocol analysis showed no difference in virologic responses between the 2 groups at all time points, except at 18 months. When analyzed on intention-to-treat basis for virologic response at 24 months, the response rates were 45.3% in the clevudine group and 72.3% in the entecavir group, which are significantly different (P < 0.001). Rates of biochemical response and HBeAg seroconversion were not significantly different between the groups at all time points. Up to 24 months, antiviral resistance developed in 18 patients (24.4%) in the clevudine group. Clevudine was discontinued owing to muscle-related problems in 10 patients (11.6%). CONCLUSIONS Although both drugs showed potent antiviral activity, entecavir showed better virologic response at 24 months, primarily owing to treatment failures in the clevudine group that were associated with development of drug resistance and muscle-related problems.

Visceral adipose tissue has emerged as a key organ contributing to the development of coronary artery disease (CAD). However, defining central obesity by waist circumference (WC) may underestimate visceral adiposity in lean patients. The aim of this study was to investigate the relationship between visceral adiposity and severity of CAD in subjects with normal WC.Among 365 patients with documented CAD, 90 male subjects with normal WC (90 cm) were selected and their visceral fat areas (VFA) were examined using computed tomography. Lipid profiles and levels of adipokines including lipocalin-2, high molecular weight adiponectin, and monocyte chemoattractant protein (MCP)-1 were measured. Patients were divided into tertiles based on VFA at the L4 vertebra level.Patients with single-vessel disease had significantly lower VFA than those with multi-vessel disease (P0.05; 86.0 vs. 97.5 vs. 99.6 cm(2) for single- , double- , and triple-vessel diseases, respectively). Positive association between the extent of CAD and VFA was clearly demonstrated and logistic regression analysis showed that subjects in the upper tertile for VFA had a 4.5-fold higher risk of having multi-vessel disease compared with those in the lowest tertile (P0.05; odds ratio=4.51; 95% confidence interval=1.10-18.45). Circulating levels of lipocalin-2 and MCP-1 were significantly higher in the upper tertiles of VFA.Increased visceral adiposity is significantly associated with the severity of CAD, even in subjects without central obesity as determined by WC measurements. Abnormalities in adipokine regulation may provide a novel mechanistic connection between visceral adiposity and associated cardiovascular complications.

Background/Aim: We investigated changes in hepatitis B surface antigen (HBsAg) level and its correlation with clinical outcomes in treatment-naive chronic hepatitis B (CHB) patients undergoing entecavir therapy. Patients and Methods: Among 51 hepatitis B e antigen (HBeAg)-positive treatment-naive CHB patients receiving entecavir for more than 1 year, 28 were enrolled. HBsAg levels were measured at baseline, 6 months, and 12 months after treatment using the Architect HBsAg QT assay (Abbott, dynamic; range: 0.05 to 125,000 IU/mL). Serum alanine aminotransferase, HBeAg, anti-HBe, and hepatitis B virus (HBV) DNA (Cobas Taqman: low detection limit 1.84 log 10 copies/mL) were measured at baseline and every 3 months. The HBsAg response was defined as an HBsAg level that decreased more than 1 log 10 IU/mL from baseline level at 12 months after entecavir treatment. Results: Twenty-eight patients were treated for a median period of 21 months (range: 18 to 24mo). Serum HBsAg level showed a mean of 4.0, 3.7, and 3.6 log 10 IU/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P < 0.001). Serum HBV DNA level showed a mean of 8.1, 3.1, and 2.4 log 10 copies/mL at pretreatment, 6, and 12 months, respectively, and declined significantly (P < 0.001). The decline in HBsAg level was significantly correlated with that of the HBV DNA level at 12 months from baseline (γ=0.391, P=0.044). Five patients showed an HBsAg response, and cumulative incidence of HBeAg loss at 1 year after entecavir treatment was 80% versus 30% in patients with an HBsAg response and those without, respectively (P=0.034). Conclusions: Monitoring changes in quantitative HBsAg level could be a useful parameter for assessing the response to entecavir therapy in HBeAg-positive treatment-naive CHB patients.

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.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.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.LSMs changed dynamically during the course of AHA. The pattern of change appears to be related to the severity of hepatic necroinflammation.

Recently, new methods, including the concept of viable enhancing tumor such as EASL and mRECIST, have been proposed for substitution of the conventional WHO and RECIST criteria in hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Herein, we evaluated the differences of four methods and compared the association of these methods with the prognosis of HCC patients undergoing TACE.We retrospectively reviewed 114 consecutive newly diagnosed HCC patients who underwent TACE as initial treatment. We evaluated the intermethod agreement (κ values) between the methods and compared their association with the prognosis of HCC patients.The κ values for EASL vs. WHO, EASL vs. RECIST, mRECIST vs. WHO, and mRECIST vs. RECIST were low, of 0.102, 0.088, 0.112, and 0.122, respectively. However, good correlations were observed for WHO vs. RECIST and EASL vs. mRECIST (κ=0.883, κ=0.759, respectively p0.001). The median OS was 32.3 months. Hazard ratios (HR) for survival in responders compared with non-responders were 0.21 (95% CI; 0.12-0.37, p0.001) for EASL and 0.27 (95% CI; 0.15-0.48, p0.001) for mRECIST. The mean survival of responders was significantly longer than that of non-responders in both EASL (40.8 vs. 16.9 months, p0.001) and mRECIST (41.1 vs. 20.7 months, p0.001). In multivariate analysis, EASL response (HR 0.21, 95% CI 0.11-0.40, p0.001) and mRECIST response (HR; 0.31, 95% CI, 0.17-0.59, p0.001) were independently associated with survival.The response assessment by EASL and mRECIST could reliably predict the survival of HCC patients undergoing TACE and could be applicable in practice in preference to the conventional WHO and RECIST criteria.

Clinical outcomes and factors predictive of favorable response after 5-aminosalicylates or sulfasalazine (5-ASA/sulfasalazine) treatment alone have not been well established in the treatment of mild to moderate ulcerative colitis (UC). We evaluated the clinical course of Korean UC patients treated with 5-ASA/sulfasalazine as a maintenance therapy in terms of relapse and predictive factors of clinical relapse.A total 256 UC patients, treated with 5-ASA/sulfasalazine at the Severance Hospital between January 2000 and December 2008, were analyzed retrospectively. We sought to investigate relapse rates and to determine independent predictors for relapse.Of the 256 patients, 127 patients (49.6%) had a disease relapse. The cumulative relapse rate was 21.5% after 1 year, 36.5% after 2 years, 46.9% after 3 years and 59.8% after 5 years. On multivariate analysis, left-sided or extensive colitis at diagnosis (hazard ratio=1.46; 95% CI=1.01-2.10; p=0.04) and initial hemoglobin level10.5g/dL (hazard ratio= 0.43; 95% CI=0.22-0.81; p=0.01) were found to be independent factors for clinical relapse.Our study showed that both disease extent at diagnosis and anemia were major predictive factors for clinical relapse after 5-ASA/sulfasalazine therapy for Korean patients with mild to moderate UC.

Background: Recent European ancestry genome-wide association studies have identified genetic variants of IRGM as significant susceptibility loci for Crohn's disease (CD). Therefore, we investigated whether genetic variants of IRGM confer genetic susceptibility to CD or ulcerative colitis (UC) and evaluated the genotype–phenotype associations in the Korean population. Methods: This study included 510 inflammatory bowel disease (IBD) patients (253 patients with CD and 257 with UC) and 520 healthy controls in Koreans. Initially, we performed direct sequencing analysis to identify unique IRGM single nucleotide polymorphisms (SNPs). Three selected haplotype-tagging SNPs and one risk locus (rs72553867, rs10065172, rs4958847, and rs12654043) within the IRGM were then genotyped in patients and controls. Results: IRGM SNP rs10065172 was significantly associated with CD susceptibility in terms of allelic frequency (P = 0.004; odds ratio [OR] = 1.42) and genotype frequency (dominant model, P = 0.008; OR = 1.62). We also found a relationship between SNP rs72553867 and CD susceptibility in the analysis of allelic frequency (P = 0.0117; OR = 0.67) and genotype frequency (dominant model, P = 0.002; OR = 0.55). In addition, we observed that the association of CD with rs10065172 became stronger in patients with younger age at diagnosis (≤20 years) or male gender. However, there was no significant association between the four SNPs and UC susceptibility. Conclusions: This is the first study to identify SNP rs10065172 and rs72553867 in IRGM as principal CD susceptibility loci in an Asian population. (Inflamm Bowel Dis 2012;)

PURPOSE: This study was conducted to identify prognostic factors affecting the course of ischemic colitis and to develop a prognostic scoring model. METHODS: We analyzed medical records of consecutive patients with ischemic colitis treated between October 2002 and September 2008 at Severance Hospital, Seoul, Republic of Korea. Patients were excluded if results of endoscopy were unavailable. Patients were classified as having severe ischemic colitis on the basis of outcome (improvement delayed for more than 2 weeks, complications requiring surgery, or death). Univariate analyses and multivariate logistic regression analyses with backward stepwise selection were used to identify clinical, endoscopic, and laboratory variables associated with severe ischemic colitis. A novel prognostic scoring model was derived from the data, with probability of severe ischemic colitis and risk index determined for 8 risk groups based on independent risk factors identified by multivariate analyses. Predictive power was tested by means of 10-fold cross-validation, with area under the receiver operating characteristic curve representing discrimination accuracy. RESULTS: Analyzable data were available for 153 of 173 consecutive patients. Ischemic colitis was classified as severe in 20 patients. Multivariate analyses showed the following significant independent predictors of severe ischemic colitis: tachycardia (adjusted odds ratio = 4.6; 95% CI, 1.4-14.7), shock within 24 hours after admission (adjusted odds ratio = 6.5; 95% CI, 2.0-21.2), and endoscopic evidence of ulceration (adjusted odds ratio = 9.9; 95% CI, 2.0-48.8). Probability of severe ischemic colitis and risk index were 74 times higher for patients with all 3 risk factors (group 8) than for patients with none (group 1). Internal validation showed the area under the receiver operating characteristic curve to be 0.91 (95% confidence interval, 0.86-0.96). CONCLUSIONS: Endoscopic findings and instability of vital signs were associated with the disease course of ischemic colitis. A novel scoring model based on presence of tachycardia, shock within 24 hours after admission, and endoscopic evidence of ulceration provides a method of assessing patient prognosis and should be further validated.

BACKGROUND/AIMS An association between past history of hepatitis B virus (HBV) infection and pancreatic cancer (PC) has recently been reported. We investigated whether HBV and hepatitis C virus (HCV) infections are associated with the development of PC in Korea. METHODS We retrospectively recruited patients with PC and sex- and, age-matched control patients with stomach cancer (SC) during the previous 5 years. Serum HBsAg and anti-HCV were examined, and data on smoking, alcohol intake, diabetes, and the history of chronic pancreatitis (CP) were collected. RESULTS A total of 506 PC and 1008 SC were enrolled, with respectively 58.1% and 97.3% of these cases being confirmed histologically. The mean age and sex ratio (male:female) were 63.5 years and 1.5:1 in the PC patients and 63.9 years and 1.5:1 in the SC patients respectively (P>0.05). The odds ratios (95% confidence interval, 95% CI) in univariate analysis were 0.90 (0.52-1.56; P=0.70) for HBsAg, 1.87 (0.87-4.01; P=0.11) for anti-HCV, 2.66 (2.04-3.48; P

Background and Aim: Recently, various non-invasive blood markers and indices have been studied to overcome the limitations of liver biopsy, such as its invasiveness and sampling errors. However, the majority of these studies have focused on patients with chronic hepatitis C. Accordingly, this study was performed to evaluate the significances of various non-invasive serum markers in terms of predicting the presence of liver cirrhosis in chronic hepatitis B. Methods: We included 125 chronic hepatitis B patients who had undergone liver biopsy. Fibrosis stage was assessed using the METAVIR scoring system (F0–F4), which defines liver cirrhosis as F4. In addition, we measured various blood markers at times of liver biopsy. Results: Thirty four of the 125 patients (27.2%) were rated as F4 by liver biopsy. Age, platelet, white blood cells, aspartate aminotransferase (AST), alanine aminotransferase, haptoglobin, apolipoprotein-A1 (Apo-A1), collagen-IV, hyaluronic acid, α2-macroglobulin, matrix metalloproteinase-2, and YKL-40 were significantly different between patients with chronic hepatitis and those with liver cirrhosis. However, multivariate analysis showed that only platelet, AST, haptoglobin, and Apo-A1 independently predicted the presence of liver cirrhosis. Having identified these four factors, we devised a system, which we refer to as platelet count, AST, haptoglobin, and Apo-A1 (PAHA). The area under the receiver-operating characteristics (AUROC) of PAHA indices for the presence of liver cirrhosis was 0.924 (95% confidence interval, 0.877–0.971), which was significantly greater than the AUROC of other indices of fibrosis. Conclusion: The devised PAHA system was found to be useful for predicting the presence of liver cirrhosis in patients with chronic hepatitis B.

Background/Aims: Serum creatinine (Cr) is not a reliable marker for early detection of renal dysfunction in patients with cirrhotic ascites. Several reports have suggested that cystatin C (CysC) is more sensitive than Cr for detecting reduced renal function in these patients. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and a normal serum Cr level. Methods: We enrolled patients with ascites and a normal serum Cr level (

Success rate of cecal intubation, endoscopist's difficulty, and procedure-related patient pain are still problems for beginners performing colonoscopy. New methods to aid colonoscopic insertion such as warm water instillation and oil lubrication have been proposed. The aim of this study is to evaluate the feasibility of using warm water or oil in colonoscopy.Colonoscopy was performed in 117 unsedated patients by three endoscopists-in-training. Patients were randomly allocated to three groups, using a conventional method with administration of antispasmodics, warm water instillation, and oil lubrication, respectively. Success rate of total intubation within time limit (15 min), cecal intubation time, degree of endoscopist's difficulty, and level of patient discomfort were compared among the three groups.Cecal intubation time was shorter in the warm water group than in the conventional and oil groups. Degree of procedural difficulty was lower in the warm water group, and patient pain score was higher in the oil lubrication group, compared with the other groups. However, there was no significant difference in success rate of intubation within time limit among the three groups.The warm water method is a simple, safe, and feasible method for beginners. Oil lubrication may not be a useful method compared with conventional and warm water method.

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined asor =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Cholestasis in a patient with Hodgkin's disease is uncommon, and the causes of cholestasis are mainly direct tumor involvement of the liver, hepatotoxic effects of drugs, viral hepatitis, sepsis and opportunistic infections. Vanishing bile duct syndrome (VBDS) represents a very rare cause for cholestasis in this disease. We report here on a case of a 45-year-old man who developed VBDS during the complete remission stage of Hodgkin's lymphoma. There was no history of hepatitis or intravenous drug abuse, and the patient had negative results for hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. The serological studies for antinuclear antibodies, anti-mitochondrial antibodies and anti-smooth muscle antibodies were also negative. Liver biopsy disclosed the absence of interlobular bile ducts in 9 of 10 portal tracts without any active lymphocyte infiltration and there were no Reed-Sternberg cell in the liver. The patient's cholestasis was in remission and the serum bililrubin level was normalized after two months without treatment, but tumor recurrence was noted at multiple sites of the abdominal lymph nodes on follow-up abdomino-pelvic computed tomogram.

To develop a novel endoscopic severity model of intestinal Behcet's disease (BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease (DAIBD).We reviewed the medical records of 167 intestinal BD patients between March 1986 and April 2011. We also investigated the endoscopic parameters including ulcer locations, distribution, number, depth, shape, size and margin to identify independent factors associated with DAIBD. An endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was evaluated. To determine factors related to the discrepancy between endoscopic severity and clinical activity, clinical characteristics and laboratory markers of the patients were analyzed.A multivariate regression analysis revealed that the number of intestinal ulcers (≥ 2, P = 0.031) and volcanoshaped ulcers (P = 0.001) were predictive factors for the DAIBD. An endoscopic severity model (Y) was developed based on selected endoscopic variables as follows: Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 × ≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographic-shaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 × ≥ 20 mm of intestinal ulcers. However, endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD variance. Patients with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome (21.4% vs 4.9%, P = 0.026) and a lower rate of corticosteroid use (50.0% vs 75.6%, P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the model.Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD scores. However, the correlation between endoscopic severity and DAIBD (r = 0.434) was weak.

Backgrounds/Aims: In some patients with chronic hepatitis, liver stiffness (LS) findings do not reflect fibrosis stage. This study was performed to evaluate whether acute liver inflammation could influence LS findings. Methods: Patients with acute hepatitis A admitted to our hospital were included. Hepatitis was classified on admission using serum ALT and bilirubin levels as inflammation phase, jaundice phase, or recovery phase. Patients who admitted during the recovery phase (whose ALT and bilirubin levels fell continuously during hospitalization) and therefore, their peak-ALT and peak bilirubin levels could not be determined were exduded. Enrolled patients underwent FibroScan during hospitalization and after discharge. Results: Seventy-six patients with acute hepatitis A were enrolled (median age, 29 years; 46 men and 30 women). Among them, 33 (43.4%) and 43 (56.6%) patients were admitted during the inflammation phase and jaundice phase, respectively. For patients admitted during the inflammation phase, mean (±SD) time from symptom-onset day to maximum ALT level was 7 (±3) days. For all patients, mean time from symptomonset to maximum bilirubin level was 11 (±4) days. Mean LS during admission was 8.9 (±3.3) kPa (median, 8.4 kPa). LS was significantly correlated with serum bilirubin level, which was the only factor found to be significantly associated with the increased LS (>7.08 kPa). In all patients, LS increased gradually from the symptom-onset and peaked at 8-9 days later. Conclusions: Severe hepatic inflammation can affect the LS findings and thus, care is required when assessing fibrosis stage using LS measurement in patients with severe inflammation. (Korean J Hepatol 2008;14:465-473)