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Background Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods. Methods We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared. Results A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3–73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P Conclusion The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.

This study sought to clarify sex differences in KRAS mutations and clinical predictors of KRAS 13 codon mutations.Sex differences in KRAS mutations and predictors for KRAS codon 13 mutations in colorectal cancer (CRC) are unclear.Between October 2007 and May 2016, 328 patients underwent surgery for CRCs that were analyzed for KRAS mutations at a referral university hospital. Sex differences in the rates and distributions of KRAS mutations, and factors predictive of overall KRAS and KRAS codon 13 mutations were analyzed.KRAS mutations were significantly more common in women than men patients (46.0% vs. 34.4%, P0.033). However, no sex differences were detected for KRAS mutations by codon subtypes (P=0.592). The Gly13Asp (GGCGAC) point mutation was identified only within codon 13 in both sexes. For right-sided CRC, KRAS mutations were twice as frequent in men as in women (univariate analysis; P=0.016, multivariate analysis; P=0.019). High-plasma cholesterol level was an independent predictive factor of KRAS codon 13 mutations by univariate (odds ratio, 1.013; 95% confidence interval, 1.003-1.023) and multivariate analysis (odds ratio, 1.011; 95% confidence interval, 1.001-1.021).Sex differences may affect the presentation of KRAS mutations, as they were more frequently detected in women and in right-sided CRC in men. KRAS codon 13 mutations were significantly associated with high-plasma cholesterol. Further studies are needed on the clinical implications of this finding.

GOALS We determined appropriate intervals for administering the fecal immunochemical test (FIT) and performance outcomes in an Asian national colorectal cancer (CRC) screening program. BACKGROUND The optimal interval for FIT in CRC screening is unclear, especially in Asian populations. STUDY Between January 2009 and December 2015, 13,480 individuals aged 50 years or older with an initial negative FIT result underwent 2 rounds of FIT screening at intervals of 1 (annual group, 5333), 2 (biennial group, 7363), or 3 years (triennial group, 784). Positive rates of FIT, colonoscopy acceptance, colonoscopy findings, and detection rates for CRC and advanced neoplasia were compared according to FIT intervals. RESULTS The overall positivity rate of FIT in the second screening round was significantly higher in men and in older subjects than in the entire sample. Younger subjects were less likely to undergo annual FIT (36.0% vs. 46.4%, P

The incidence of lower gastrointestinal bleeding (LGIB) is increasing; however, predictors of outcomes for patients with LGIB are not as well defined as those for patients with upper gastrointestinal bleeding (UGIB). The aim of this study was to identify the clinical outcomes and the predictors of poor outcomes for patients with LGIB, compared to outcomes for patients with UGIB. We identified patients with LGIB or UGIB who underwent endoscopic procedures between July 2006 and February 2013. Propensity score matching was used to improve comparability between LGIB and UGIB groups. The clinical outcomes and predictors of 30-day rebleeding and mortality rate were analyzed between the two groups. In total, 601 patients with UGIB (n = 500) or LGIB (n = 101) were included in the study, and 202 patients with UGIB and 101 patients with LGIB were analyzed after 2:1 propensity score matching. The 30-day rebleeding and mortality rates were 9.9% and 4.5% for the UGIB group, and 16.8% and 5.0% for LGIB group, respectively. After logistic regression analysis, the Rockall score (P = 0.013) and C-reactive protein (CRP; P = 0.047) levels were significant predictors of 30-day mortality in patients with LGIB; however, we could not identify any predictors of rebleeding in patients with LGIB. The clinical outcomes for patients with LGIB are not better than clinical outcomes for patients with UGIB. The clinical Rockall score and serum CRP levels may be used to predict 30-day mortality in patients with LGIB., Graphical Abstract

Patients with inflammatory bowel disease (IBD) have an elevated risk of venous thromboembolism compared with the general population. The most common sites of venous thromboembolism in IBD patients are the deep veins of the legs, the pulmonary system, and portal and mesenteric veins. However, cerebral venous thrombosis is rarely associated with IBD. This report describes a case of cerebral venous thrombosis in a patient with Crohn's disease. A 17-year-old girl, diagnosed 4 years earlier with Crohn's disease, presented with headache and vomiting. Magnetic resonance imaging of the brain with venography showed venous thrombosis in the cortical veins, superior sagittal sinus, right transverse sinus, and right internal jugular vein. The patient immediately started anticoagulation therapy with intravenous heparin infusion followed by daily oral rivaroxaban 10 mg. Follow-up imaging after 2 weeks showed resolution of the thrombosis, with recanalization of the cortical veins, superior sagittal sinus, right transverse sinus, and right internal jugular vein. She continued rivaroxaban therapy for 6 months, and remained well, without neurologic sequelae. A high level of concern for cerebral venous thrombosis may be important when treating active IBD patients, because anticoagulation treatment can prevent fatal complications.

Background Risk scoring systems are used to evaluate patients with upper gastrointestinal bleeding (UGIB). We compared Glasgow-Blatchford score (GBS), modified GBS (mGBS), and Pre-endoscopy Rockall score (Pre-E RS) for immediate application without endoscopic findings in predicting the need of interventions and the 30-day mortality in patients with UGIB. Methods Patients who visited the emergency room with UGIB from January 2007 to June 2016 were included. GBS, mGBS, and Pre-E RS were obtained for all patients. The area under the receiver-operating characteristic curves (AUC) was used to assess the accuracy of the scoring systems to determine the need for interventions and 30-day mortality. Also, we investigated the potential cutoff scores for predicting 30-day mortality and the need for interventions. Results In predicting the need for interventions, GBS (AUC = 0.727) and mGBS (AUC = 0.733) outperformed Pre-E RS (AUC = 0.564, P

Supplemental Digital Content is available in the text, Background: The clinical significance of KRAS codon 13 mutation in patients with colorectal cancer (CRC) remains controversial. A systematic review and meta-analysis is necessary for a more precise estimation of the predictive role of KRAS codon 13 mutations in CRC patients. Methods: We performed a systematic search using the MEDLINE, EMBASE, and Cochrane library databases from January 2000 to November 2016. The prognostic value of KRAS codon 13 mutation for overall survival (OS) was investigated by measuring the hazard ratio (HR) and 95% confidence interval (CI). Data were analyzed with Review Manager Version 5.3 and the Canadian Agency for Drugs and Technologies in Health software. Results: OS in CRC patients with KRAS codon 13 mutation was worse than that in CRC patients with KRAS wild-type (pooled HR = 1.37, 95% CI: 1.03–1.81, P = .03). Subgroup analysis of studies of enrolled CRC patients treated with antiepidermal growth factor receptor (EGFR) therapy showed no significant difference in OS associated with KRAS codon 13 mutation in comparison to KRAS wild-type (pooled HR = 1.57, 95% CI: 0.98–2.51, P = .06). In the indirect comparison, no statistically significant association was observed between codon 12 and 13 mutations for OS in CRC patients (pooled HR = 0.88, 95% CI: 0.65–1.20, P = .43). Conclusion: The current meta-analysis suggests that Codon 13 mutation of KRAS gene seems to correlate with the OS of patients with CRC, but has similar OS to those with KRAS wild-type in patients receiving anti-EGFR therapy. No difference was detected in the OS of CRC patients with codon 13 mutation versus codon 12 mutation.

Polydeoxyribonucleotide (PDRN) interacts with the adenosine A2A-receptor and stimulates vascular endothelial growth factor (VEGF) expression. While it has been indicated that PDRN might accelerate wound healing, its impact on gastric ulcers (GU) is still unknown. We investigated the effects of PDRN on VEGF expression in relation to inflammation and apoptosis in GU by using Mongolian gerbils. GU was induced by injection of acetic acid into the subserosal surface of the stomach. The gerbils in the PDRN-treated groups received daily intraperitoneal injections of PDRN over 2 weeks. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay, immunohistochemistry for caspase-3, and western blot for VEGF, Bax, and Bcl-2 were conducted. Acetic acid injection induced GU, and VEGF expression in the gastric mucosa was enhanced by GU. PDRN treatment decrea...

Although current guideline recommends selective use of pre-endoscopic prokinetics to increase diagnostic yield in upper gastrointestinal bleeding (UGIB) patients, no data to guide the use of these drugs are available. We aimed to investigate predictive factors for endoscopic visibility and develop simple and useful strategies for pre-endoscopic prokinetics use in UGIB patients. A total of 220 consecutive patients who underwent upper endoscopy for suspicious UGIB were enrolled. Patients were randomly allocated to either a training or a validation set at a 2:1 ratio. Significant parameters on univariate analysis were subsequently tested by a classification and regression tree (CART) analysis. Time to endoscopy and nasogastric aspirate findings were independently related to endoscopic visibility. The CART analysis generated algorithms proposed sequential use of time to endoscopy (≤5.2 vs. >5.2 h) and nasogastric aspirate findings (red blood or coffee rounds vs. clear aspirate) for predicting endoscopic visibility. Prediction of unacceptable visibility in the validation set produced sensitivity, specificity, positive predictive value, and negative predictive value of 75.8, 67.5, 65.8, and 77.1 %, respectively. Accurate prediction for visibility was identified in 52 of 73 patients (71.2 %). Time to endoscopy and nasogastric aspirate findings were independently related to endoscopic visibility in patients with UGIB. A decision-tree model incorporating these two variables may be useful for selecting UGIB patients who benefit from pre-endoscopic prokinetics use.

Background/aims Gallbladder polyps and colorectal adenomas share many common risk factors; however, their association has never been studied. The aim of this study was to investigate this association in asymptomatic healthy subjects. Methods Consecutive asymptomatic subjects who underwent both screening colonoscopy and abdominal ultrasonography at Kyung Hee University Hospital in Gang Dong between July 2010 and April 2011 were prospectively enrolled. The prevalence of colorectal adenoma was compared between subjects with or without gallbladder polyps. Furthermore, a logistic regression analysis was performed to determine the independent risk factors for colorectal adenoma in these subjects. Results Of the 581 participants, 55 presented with gallbladder polyps and 526 did not have gallbladder polyps. Participants with gallbladder polyps showed a trend toward a higher prevalence of colorectal adenoma than those without gallbladder polyps (52.7% vs. 39.2%, P=0.051). Although the result was not statistically significant, gallbladder polyps were found to be a possible risk factor for colorectal adenoma (odds ratio=1.796, 95% confidence interval=0.986-3.269, P=0.055), even after adjusting for potential confounding factors. There was no difference observed in colorectal adenoma characteristics between the two groups. Conclusions Our results suggest a possible association between gallbladder polyps and colorectal adenomas. Future studies with larger cohorts are warranted to further investigate this matter.

Background/Aims To identify the predicting factors of present hepatitis C virus (HCV) infection among patients with positivity for antibodies to HCV (anti-HCV). Methods We analyzed patients who showed positive enzyme immunoassay (EIA) results and performed an HCV RNA test as a confirmatory test at Kyung Hee University Hospital at Gangdong from June 2006 to July 2012. The features distinguishing the groups with positive and negative HCV RNA results were reviewed. Results In total, 490 patients were included. The results of the HCV RNA test were positive and negative in 228 and 262 patients, respectively. The index value of anti-HCV, mean age, platelet counts, total bilirubin, prothrombin time international normalized ratio, albumin and alanine transaminase (ALT) levels differed significantly between the two groups. On multivariable analysis, an index value of anti-HCV >10 [odds ratio (OR)=397.27, P40 IU/L (OR=3.64, P=0.001), and albumin

We report a case of patient with acute toxic hepatitis induced by weight-loss herbal supplement. A patient took natural extract supplement containing Garcinia cambogia for only two days and visited Kyung Hee University Hospital at Gangdong complaining of abdominal discomfort and jaundice. Serum ceruloplasmin level was decreased and hepatic copper levels on liver biopsy specimen were increased. Although, those were mimicking Wilson’s disease, pathological findings and clinical manifestations were consistent with drug-induced acute hepatitis. Genetic test was negative for Wilson’s disease. After one month of hospitalization, the patient improved and was discharged home in good condition. She was followed up for four months and her symptoms and signs of hepatitis continued to improve steadily with normal liver function tests. Our case emphasizes the importance of taking a caution when taking herbal supplements for the purpose of weight loss. This case also demonstrates the importance of suspicion of medication-related adverse events, even though the duration of taking the materials seems to be too short to affect the patients.

The advantage of the quantitative fecal immunochemical test (FIT) is the flexibility to set the positivity threshold. However, the diagnostic success of the FIT has not been compared for standard and low cut-off thresholds.The purpose of this study was to compare the diagnostic success of FIT for standard and low cut-off thresholds.In 2009 and 2010 a standard cut-off threshold (20 μg Hb/g feces) was used as positivity criterion for the FIT; in 2012 a low cut-off (10 μg Hb/g feces) was used. Diagnostic success was compared between the two groups.Of the total of 14,289 participants, 195 (1.4 %) had positive FIT results. Positivity of the FIT was significantly higher in the low cut-off group than in the standard cut-off group (1.8 vs. 1.0 %, p = 0.000). Although detection of advanced neoplasia lesions was comparable, proximal neoplasia was more frequently detected in the low cut-off group (33.3 vs. 20.9 %, p = 0.016). With the low cut-off threshold, 39 (0.7 %) participants were also classified as having positive results, and 18 (46.2 %) of these had colorectal neoplasias. The number of positive results from the FIT was increased by 54.9 %, and detection of advanced neoplasia was increased by 60 % with the low cut-off threshold compared with the standard cut-off.A low cut-off threshold for the FIT resulted in better detection of proximal neoplasia in population-based screening. These results indicate the cut-off threshold for positive FIT should be properly chosen and adjusted in colorectal cancer screening.

Hemoglobin concentration of fecal immunochemical test may be decreased at high ambient temperature, and fecal samples in FIT may be exposed to high ambient temperature. The aim of this study was to determine whether a high ambient temperature on the day of screening may decrease the performance of FITs in population-based screening. We performed FITs for asymptomatic participants aged 50 years or older. Fecal hemoglobin concentration, the probability of a positive FIT and a detection rate of colorectal neoplasms were compared between low (

The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known.We evaluated the efficacy of entecavir (ETV) plus adefovir dipivoxil (ADV) combination therapy for patients with resistance to LMV and ETV. We reviewed the medical records of 12 patients, and treated all 12 patients with ETV plus ADV combination therapy for at least 18 months. Quantitative hepatitis B virus (HBV) DNA levels, serologic markers, and hepatic panel values were monitored at baseline and 3-month intervals thereafter for 18 months.The baseline mean serum HBV DNA level was 7.26 ± 1.11 log(10) copies/ml. The mean reductions in serum HBV DNA levels from baseline to 3, 6, 9, 12, 15, and 18 months were -1.98 ± 1.03, -2.87 ± 1.02, -3.32 ± 1.10, -3.92 ± 1.30, -4.36 ± 1.22, and -4.57 ± 1.18 log(10) copies/ml, respectively. Complete virological response (HBV DNA of2 log(10) copies/ml) at 6, 12, and 18 months was observed in 1 (8.3%), 4 (33.3%), and 6 (50.0%) patients, respectively. The 2 patients with baseline HBV DNA of6 log(10) copies/ml achieved complete virological response at 18 months, while 4 of 10 patients with baseline HBV DNA of ≥6 log(10) copies/ml achieved complete virological response at 18 months. None of the 12 patients experienced virological breakthrough during follow-up.ETV plus ADV combination therapy effectively reduced serum HBV DNA levels in patients with CHB who developed resistance to both LMV and ETV. Additional long-term studies are needed to assess the effect of long-term treatment with these drugs.

Hepatocellular carcinoma (HCC) is a type of hypervascular tumor, and angiogenesis is important for HCC tumor growth. Eph receptor B1 (EPHB1), a member of the Eph family, mediates embryonic vascular system development and adult angiogenesis. This receptor may be involved in carcinogenesis of the digestive tract. Our aim was to examine the relationships between EPHB1 polymorphisms and HCC in the Korean population. Genomic DNA was extracted from 182 patients with HCC and 266 healthy subjects. EPHB1 polymorphisms were determined by polymerase chain reaction and direct sequencing. Multiple logistic regression models (log-additive, dominant, and recessive models) were used for odds ratios, 95% confidence intervals, and p values. Five polymorphisms (rs11929692, rs7644369, rs6776570, rs3821502, and rs6766459) of the EPHB1 gene and alleles of 2 polymorphisms (rs1502174 and rs9877457) were associated with HCC (p < 0.05 for both). Our results suggest that EPHB1 polymorphisms may be associated with susceptibility to HCC in the Korean population.

Studies regarding the discrimination of non-neoplastic lesion, adenoma, and cancer of the stomach using magnifying endoscopy with flexible spectral imaging color enhancement system (FIME) in each different channel of that system have not yet been reported.To ascertain the usefulness of FIME discriminating among the three kinds of gastric lesions.When finding a lesion to be a possible neoplasm using conventional endoscopy, the examiner discriminated among the three kinds of gastric lesions by observing the pit pattern on the lesion using magnifying endoscopy with white light (WLME) and then recorded the image. The procedure was repeated three more times with FIME with channel 0, 2, and 4. The four recorded images per lesion were then given to four raters for discriminating among the three kinds of gastric lesions.The proportion of agreement and the degree of agreement between endoscopic and pathological diagnosis (AEP) by WLME were 0.85 and 0.76, respectively, and those by FIME were 0.91 and 0.86, respectively. All AEPs from discriminations with FIME was higher than that with WLME. AEPs from the discriminations with FIME with channel 4 were higher than those with FIME with channel 0 or 2. The degree of interobserver agreement among the results of the four raters was 0.42 for WLME and 0.50-0.59 for FIME with each of the three different channels.FICE is useful in discriminating among non-neoplastic lesions, adenoma, and cancer of the stomach, and channel 4 of the FICE is better than channel 0 and 2 for the discriminations.

Untreated benign biliary stricture can lead to serious complications including recurrent cholangitis, biliary cirrhosis, hepatic failure, and death. Benign stricture of a postoperative anastomosis site is also a problematic issue after biliary surgery. Percutaneous transhepatic cholangioscopy (PTCS) with balloon dilatation is a recently introduced noninvasive therapeutic option for biliary stricture. Guidewire insertion through the stricture site is essential for the success of PTCS treatment. Recently, we treated a difficult case with complete bilioenteric anastomosis stricture that failed to allow passage of the guidewire for balloon dilation. The stricture was treated with artificial bilioenteric fistula using a needle-knife papillotome during the PTCS.

Patient satisfaction is a key quality indicator of gastrointestinal endoscopy (GIE). The gastrointestinal endoscopy satisfaction questionnaire (GESQ) was recently developed to assess patient satisfaction undergoing GIE in Europe; however, it was not validated in Asian countries. We aimed to translate and validate the GESQ in Korea and identify predictors for patient satisfaction during GIE. Translation of the original GESQ was performed according to accepted linguistic validation guidelines. Between March 2016 and July 2016, 350 consecutive patients were asked to complete a GESQ after GIE at Kyung Hee University Hospital. Total sum of scores was transformed from 0 to 100 by the formula: (Score-lowest possible/Score range) × 100. Exploratory and confirmatory factor analyses for construct validation reconfirmed that 4 factors were extracted from the Korean GESQ. Internal consistency reliability was acceptable with an overall Cronbach α score of 0.87. Female and nonsmoker were associated with less satisfaction with GIE (P = .021 and .006, respectively). Other factors, including age, alcohol, education or economic level, sedative endoscopy, gastroscopy with or without colonoscopy, experience of previous endoscopy, and additional examinations such as biopsy, were not associated with patient satisfaction during GIE. The Korean version of the GESQ was a valid and acceptable tool to measure satisfaction in patients who had undergone a GIE in Korea. Patient satisfaction measurement could contribute to systematic improvement of qualified GIE.

Cytomegalovirus (CMV) infection is usually subclinical in immunocompetent individuals, however it can be life threatening in an elderly immunocompetent individual. We report a case of CMV enteritis causing ileal perforation in a physically active elderly man. An 88-year-old healthy man presented with abdominal pain and diarrhea. After initial conservative treatment, emergency laparotomy was performed for ileal perforation. The diagnosis of CMV enteritis was based on histological findings revealing many large cells with CMV inclusion bodies in the surgical specimen. In elderly individuals, even though they are immunocompetent, CMV enteritis may result in major complications such as bowel perforation, and it should be included in the differential diagnosis of diarrhea if it is resistant to conventional treatment.

Plasmablastic lymphoma (PBL) is a recently identified entity that is considered to be a type of diffuse large B-cell lymphoma with a unique immunophenotype and a predilection for the oral cavity of patients with the human immunodeficiency virus (HIV). Although its clinical features may help in the differential diagnosis, an extraoral location in a patient without HIV makes it more difficult to suspect clinically. This case report is the first to describe a patient with PBL originating from the jejunum in a 60-yr-old, HIV-seronegative man. Computed tomography of the face, chest and abdomen showed about a 9.4 x 9.0 cm mass of the proximal jejunum, multiple masses in the musculoskeletal soft tissue, and multiple lymphadenopathies. The histological examinations demonstrated a large cell lymphoma with plasmablastic differentiation. The neoplastic cells were diffusely positive for MUM1, epithelial membrane antigen and lambda light chains, and focally positive for CD79a; but negative for CD3, CD20, CD30, CD34, CD45RO, CD56, CD99, and CD117. The proliferation index by Ki-67 immunohistochemistry was approximately 70%. These findings were compatible with the diagnosis of PBL. The findings in this case suggest that PBL should be included in the differential diagnosis of a small bowel mass even in a HIV-negative patient.

Background/Aim: The goal of antiviral therapy for chronic hepatitis B (CHB) is to improve survival of the patients by achieving a complete virological response (CVR). This study aimed to evaluate long-term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in nucleos(t)ide analog (NA)-naïve and NA-experienced Korean patients with CHB and to determine the incidence of cirrhosis-related complications in these patients. Patients and Methods: We retrospectively reviewed medical records of all patients treated with ETV or TDF from July 2007 to January 2017. We examined CVR and analyzed the predictive factors influencing the rate of CVR and evaluated the incidences of cirrhosis-related complications. Results: The proportion of patients who achieved CVR was 94.2% in the ETV group and 91.1% in the TDF group (P = 0.358). Among patients who achieved CVR, the mean time to CVR was 13.5 ± 14.3 months in the ETV group and 11.5 ± 10.6 months in the TDF group (P = 0.169). Positive predictive factors for CVR included the current treatment with TDF, a low hepatitis B virus DNA level, negative hepatitis B e-antigen status, and high alanine aminotransferase level in baseline laboratory test. The annual incidence rate of HCC was 127 per 10,000 patient-years (1.27% per year) in ETV group, and 85 per 10,000 patient-years (0.85% per year) in TDF group (P = 0.526). Conclusion: Both ETV and TDF therapy resulted in a high CVR, and the annual incidence rates of HCC and other cirrhosis-related complications were not significantly different between the two treatment groups.

A common and important problem in patients with chronic hepatitis B is the progression of liver fibrosis. Matrix metalloproteinases (MMPs) play an important role in the progression of liver fibrosis. Our aim of this study was to examine the association of MMP-3 polymorphism with liver cirrhosis in Korean patients with chronic hepatitis B. Genomic DNA was extracted from 127 patients with chronic hepatitis B (CHB), 92 patients with hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC), and 146 healthy subjects. MMP-3 polymorphism was determined by polymerase-chain reaction-based assays, and the association with the progression of liver cirrhosis was investigated. With regard to MMP-3 polymorphism, there was no statistical difference in genotype distributions among the three groups. However, the peripheral platelet count of the 5A carriers was significantly lower than that of the 6A homozygotes in the HBV-LV group (85.0 +/- 36.9 vs. 109.8 +/- 47.0 x 10(9)/l; P = 0.02). With MMP-3 promoter polymorphism (rs3025058), a lower peripheral blood platelet count, which was related to advanced liver cirrhosis, was observed in 5A carriers. Therefore, more studies of MMP-3 gene polymorphism with larger populations should be conducted to further understand its role in the progression of liver cirrhosis.

Benign schwannomas arise in neural crest-derived Schwann cells. They can occur almost anywhere in the body, but their most common locations are the central nervous system, extremities, neck, mediastinum, and retroperitoneum. Schwannomas occurring in the biliary tract are extremely rare and mostly present with obstructive jaundice. We recently experienced a case of extrahepatic biliary schwannomas in a 64-yr-old female patient who presented with intra- and extrahepatic bile duct and gallbladder stones during a screening program. To the best of our knowledge, extrahepatic biliary schwannomas associated with bile duct stones have not been reported previously in the literature.

Rebleeding and mortality rates remain high in patients with nonvariceal upper gastrointestinal bleeding. To identify clinical and endoscopic risk factors for rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding. This study was performed in patients with nonvariceal upper gastrointestinal bleeding who underwent upper endoscopic procedures between July 2006 and February 2013. Clinical and endoscopic characteristics were compared among patients with and without rebleeding and mortality. Logistic regression analysis was performed to determine independent risk factors for rebleeding and mortality. After excluding 64 patients, data for 689 patients with nonvariceal upper gastrointestinal bleeding were analyzed. Peptic ulcer (62.6 %) was by far the most common source of bleeding. Endoscopic intervention was performed within 24 h in 99.0 % of patients, and successful endoscopic hemostasis was possible in 80.7 % of patients. The 30-day rebleeding rate was 13.1 % (n = 93). Unsuccessful endoscopic hemostasis was found to be the only independent risk factor for rebleeding (odds ratio 79.6; 95 % confidence interval 37.8–167.6; p = 0.000). The overall 30-day mortality rate was 3.2 % (n = 23). Unsuccessful endoscopic hemostasis (odds ratio 4.9; 95 % confidence interval 1.7–13.9; p = 0.003) was also associated with increased 30-day mortality in patients with nonvariceal upper gastrointestinal bleeding. Successful endoscopic hemostasis is an independent protective factor for both rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding.

Vasculopathy is rarely reported in neurofibromatosis type 1, but when it occurs it primarily involves the aorta and its main branches. Among vasculopathies, aneurysmal dilatation is the most common form. Although several case reports concerning aneurysms or pseudoaneurysms of visceral arteries in neurofibromatosis type 1 patients have been reported, there are no reports describing gastroduodenal artery aneurysms associated with neurofibromatosis type 1. We experienced a case of life-threatening duodenal ulcer bleeding from a ruptured gastroduodenal artery aneurysm associated with neurofibromatosis type 1. We treated our patient by transarterial embolization after initial endoscopic hemostasis. To our knowledge, this is the first reported case of its type. High levels of suspicion and prompt diagnosis are required to select appropriate treatment options for patients with neurofibromatosis type 1 experiencing upper gastrointestinal bleeding. Embolization of the involved arteries should be considered an essential treatment over endoscopic hemostasis alone to achieve complete hemostasis and to prevent rebleeding.

There are discrepancies in the classification of early carcinoma in colorectal neoplasia between Japanese and Western criteria. However, no studies have investigated the clinicopathological risk factors associated with early carcinoma according to these criteria.We compared the clinicopathological risk factors of early carcinoma with those of dysplasia, and used multivariate analysis to elucidate the independent risk factors associated with early carcinoma. Lesions with severe cytologic or architectural changes confined to the mucosa are classified as carcinoma in Japanese criteria and as high grade dysplasia (HGD) in Western criteria.Pathologically, 625 total patients were diagnosed with low grade dysplasia (n=321), HGD (n=244), intramucosal carcinoma (n=35) or submucosal carcinoma (n=25). In multivariate analysis, age, large lesion size, and non-polypoid appearance were associated with carcinoma in Japanese criteria; however, only large lesion size was associated with carcinoma in Western criteria. The clinicopathological characteristics of intramucosal carcinoma were similar to those of submucosal carcinoma rather than HGD.The clinicopathological characteristics for early carcinoma were not identical between Japanese and Western criteria. Japanese criteria classifying intramucosal carcinoma as carcinoma rather than HGD may be supported by our findings.

Previous studies on the association between dyslipidemia and the presence of colorectal adenoma showed conflicting results, and were limited due to small sample sizes, inconsistent definitions of dyslipidemia, or a lack of data on full lipid profiles. The aim of this study was to determine the association between colorectal adenomas and dyslipidemia according to the definition by the National Cholesterol Education Program- Adult Treatment Panel III.We conducted a retrospective, cross-sectional study in subjects who underwent screening colonoscopy and blood tests for full lipid profiles. Serum dyslipidemia profiles were compared between the adenoma group and the control group, and multivariate analysis was performed to identify independent predictors of the presence of colorectal adenomas.Patients with hyper-LDL cholesterolemia were more frequently included in the adenoma group than the control group (46.7% vs. 32.1%, respectively, p=0.023), and hyper-LDL cholesterolemia (OR = 1.954, 95% CI=0.981-3.893, p=0.057) showed a statistical trend for the positive association with the presence of colorectal adenomas by multivariate analysis. Furthermore, proximal colorectal adenomas were more prevalent in the hyper-LDL cholesterolemia group than in the normal LDL cholesterolemia group (p=0.026).Hyper-LDL cholesterolemia was associated with the presence of colorectal adenomas, especially in the proximal colon.

Conditionally immortalized hepatocytes (CIH) established with a gene for the temperature-sensitive mutant of the T antigen (tsT) have characteristics to stop proliferating and to differentiate at nonpermissive temperatures (37-39 degrees C) due to inactivation of the T antigen. Therefore, they may be a good alternative to primary hepatocytes for experimental investigations or clinical applications. Deinduction of the T antigen results in a transient increase of p53 in these cells, leading to reexpression of normal senescence because of the telomere attrition occurring during the early stages of immortalization. To determine this T antigen dependency for the maintenance of immortality, a type of rat CIH was cultured continuously at 39 degrees C. The frequency of occurrence of T-antigen-independent clones ranged from 0.053% to 0.093%. These clones maintained the temperature-sensitive property of the T antigen; nevertheless, they were able to progress to the S phase and proliferate without undergoing apoptosis at 39 degrees C as at 33 degrees C, a permissive temperature. The temperature-sensitive point mutation of tsT was not affected in these clones and the T antigen was functioning properly. The integrity of the p53 pathway was also maintained from the point of Western blot analysis of p21. Although the telomerase continued to be expressed and the telomere length was maintained, marked chromosomal damage could not be avoided in these cells. It is a plausible explanation that this escape phenomenon from conditional immortalization may be related to the change of other genes involved in cell cycles, which have yet to be elucidated. In conclusion, CIH could lose their temperature-sensitive characteristics without the change of tsT, itself, and the T antigen is not always necessary to maintain their immortality. Therefore, the results obtained from experimental investigations using these cells should be interpreted carefully, and unpredictable phenotypic changes should also be taken into consideration when using them in clinical applications.

Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non-suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35-year-old woman with autoimmune cholangitis associated with thymoma who presented with pruritus, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non-suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English-written literature.

We describe a previously healthy woman who developed liver cirrhosis as a sequela of acute hepatic injury that was induced by ketoconazole administration to treat onychomycosis. The initial presentation of the disease was of a typical acute hepatitis, characterized by nausea, anorexia, fatigue, and jaundice that developed during the administration of ketoconazole. Many other causes of hepatitis were absent in the patient. Even though the hepatic injury was gradually resolved for several months after cessation of the drug, the liver function was not completely restored. Six months after the onset of illness, a follow-up abdominal computed tomography and peritoneoscopic liver biopsy were performed. They revealed a marked reduction in the liver volume and a definite cirrhotic change, which persisted for more than 5 years. The case suggests that the administration of ketoconazole can cause liver cirrhosis through acute hepatic injury within a short time under certain circumstances.

Background: Conditionally immortalized hepatocytes (CIH) have been used in hepatocyte transplantation as an alternative to primary hepatocytes to cope with the shortage of donor organs. However, CIH are known to undergo apoptosis at body temperature and survive in vivo for a short period. In the present study, we investigated whether CIH function or not and how long their function is maintained in vivo. Methods: Various CIH cell lines that were established with temperature-sensitive Simian virus 40 large T antigen were transplanted into the spleen of Gunn rats, which are defective in bilirubin uridine diphosphate glucuronoside transferase (BUGT). Then, we measured biological changes over 3 months. Results: Serum bilirubin of the syngeneic CIH recipients decreased by 30%, which was maintained for 8 weeks. Thereafter, it began to rise to basal levels. The recipients of allogeneic CIH showed a minor reduction of bilirubin, although this was not statistically significant. However, there was no significant change in the bilirubin level in recipients of BUGT-defective congeneic CIH throughout the study period. Bilirubin monoglucuronides in the bile were not detected in the recipients of BUGT-defective CIH. However, they appeared in recipients of non-defective CIH and made up approximately 41% of total bile pigments. Conclusions: Conditionally immortalized hepatocytes expressed hepatocyte function in vivo as well as in vitro, but the function lasted for a couple of months. According to our previous study, the limited functional duration may be related to the inevitable occurrence of apoptosis of these cells at body temperature. These data suggest that CIH can be used in hepatocyte transplantation only for temporary hepatic support. © 2002 Blackwell Publishing Asia Pty Ltd

Background/Aims: There is substantial evidence supporting a role of inflammation in the pathogenesis of colorectal cancer; however, little is known about the association between serum C-reactive protein (CRP) and the risk of colorectal adenoma. This study was conducted to investigate the association between serum CRP and colorectal adenoma risk.Methods: A retrospective cross-sectional study was performed on first-time screening colonoscopies in asymptomatic subjects who also had their serum CRP level measured during a routine health check-up between September 2006 and September 2009 in Korea. Serum CRP level was compared between high-risk and low-risk adenoma groups and independent predictors of high-risk adenoma were analyzed using multivariate regression analysis.Results: Among the 3,309 eligible patients, the high-risk adenoma group had higher serum CRP levels than the low-risk adenoma group (P=0.000). In addition, patients with a high-risk adenoma were more frequently included in the high CRP group than in the low CRP group (8.6% vs. 4.0%, P

Smoking is a major environmental factor associated with periodontal diseases. However, we still have a very limited understanding of the relationship between smoking and subgingival microflora in the global population. Here, we investigated the composition of subgingival bacterial communities from the pooled plaque samples of smokers and non-smokers, 134 samples in each group, in Korean patients with moderate chronic periodontitis using 16S rRNA gene-based pyrosequencing. A total of 17,927 reads were analyzed and classified into 12 phyla, 126 genera, and 394 species. Differences in bacterial communities between smokers and non-smokers were examined at all phylogenetic levels. The genera Fusobacterium, Fretibacterium, Streptococcus, Veillonella, Corynebacterium, TM7, and Filifactor were abundant in smokers. On the other hand, Prevotella, Campylobacter, Aggregatibacter, Veillonellaceae GQ422718, Haemophilus, and Prevotellaceae were less abundant in smokers. Among species-level taxa occupying > 1% of whole subgingival microbiome of smokers, higher abundance (≥ 2.0-fold compared to non-smokers) of seven species or operational taxonomic units (OTUs) was found: Fusobacterium nucleatum, Neisseria sicca, Neisseria oralis, Corynebacterium matruchotii, Veillonella dispar, Filifactor alocis, and Fretibacterium AY349371. On the other hand, lower abundance of 11 species or OTUs was found in smokers: Neisseria elongata, six Prevotella species or OTUs, Fusobacterium canifelinum, Aggregatibacter AM420165, Selenomonas OTU, and Veillonellaceae GU470897. Species richness and evenness were similar between the groups whereas diversity was greater in smokers than non-smokers. Collectively, the results of the present study indicate that differences exist in the subgingival bacterial community between smoker and non-smoker patients with chronic moderate periodontitis in Korea, suggesting that cigarette smoking considerably affects subgingival bacterial ecology.

Increasing evidence supports the contribution of the pro-/anti-inflammatory cytokine balance and genetic factors to hepatocellular carcinoma (HCC). Here, we investigated whether genetic interferon gamma polymorphisms were associated with HCC in Korean patients with chronic hepatitis B.We genotyped a single nucleotide polymorphism (SNP, rs2430561, +874A/T) and a microsatellite (rs3138557, (CA) (n) repeat), located in the first intron of the interferon gamma gene, by direct sequencing and the gene scan method. A population-based case-control study of HCC was conducted and included 170 patients with chronic hepatitis and HCC, and 171 with chronic hepatitis B patients without hepatocellular carcinoma in a Korean population.Genotype and allele distributions of the interferon gamma gene SNP were associated with HCC. The frequencies of the AA genotype and the A allele were significantly increased in hepatocellular carcinoma subjects (p0.05). Combined analysis using the genotype of rs2430561 and the number of microsatellites revealed that the frequencies of AT-CA12, and TT-CA12 increased significantly in hepatocellular carcinoma subjects (p0.0001).Our results suggest that the interferon gamma gene may be a susceptibility gene and a risk factor for HCC in the Korean population.

To develop and validate a risk stratification-based screening model for predicting colorectal advanced neoplasia in Korea.Colorectal advanced neoplasia is the relevant finding of screening colonoscopy. Risk estimation for advanced neoplasia may be helpful to improve compliance and to develop more cost-effective approaches toward screening.We developed Korean Colorectal Screening (KCS) score by optimizing and adjusting Asia-Pacific Colorectal Screening (APCS) score to predict advanced neoplasia in an asymptomatic Korean population who received screening colonoscopies from September 2006 to September 2009. Moreover, we validated the KCS score in another Korean cohort who received screening colonoscopies from October 2009 to February 2011. We also assessed the predictive power and diagnostic performance of both KCS and APCS scores.There were 3561 subjects in the derivation cohort and 1316 subjects in the validation cohort, with a prevalence of advanced neoplasia of 4.7% and 4.3%, respectively. After a multivariate analysis, KCS was developed as 0 to 8 points comprising of age, sex, body mass index, smoking, and family history of CRC. Using KCS scores to stratify the validation cohort, the prevalences of advanced neoplasia in the 3 risk tiers (average, moderate, and high) were 2.0%, 3.7%, and 10.9%, respectively. Moderate-risk and high-risk tiers showed 2.1- and 6.5-fold increased prevalences, respectively, of advanced neoplasia compared with average risk tier. In addition, KCS score showed relatively good discriminative power (ROC=0.681) and higher sensitivity compared with APCS score for the high-risk tier.KCS score may be clinically simple and useful for assessing advanced neoplasia risk in Korea. However, racial disparity should be considered in risk stratification-based screening in each country.

Background: Hepatocyte transplantation has been shown to be effective in the treatment of liver failure; however, the shortage of donor organs limits its clinical application. Several reports have suggested that conditionally immortalized hepatocytes (CIH) could be an alternative to primary hepatocytes. However, CIH are known to undergo apoptosis in vitro at a non-permissive temperature, which is similar to body temperature. Methods: To investigate the duration of survival and in vivo apoptosis of CIH in the syngeneic host, the L2A2 cells (a kind of CIH) that were established from hepatocytes of a Lewis rat with a gene for a temperature-sensitive Simian Virus 40 (SV40) large T antigen were transplanted into the spleen. Cells were isolated from the spleen that was removed periodically up to 6 months, and used to detect the presence of the L2A2 cells among them with the selective culture for CIH and T-antigen PCR. In situ apoptosis of L2A2 cells was also examined. In order to improve the survival of transplanted L2A2 cells in the host, a group of rats were partially hepatectomized 1 day before transplantation was performed. Results: The L2A2 cells secreted albumin at a rate of 1.17 ± 0.18 μg/24 h per 106 cells in vitro. After transplantation, L2A2 cell colonies and PCR amplification bands appeared up to 14 and 7 days, respectively, but this duration was not prolonged by a partial hepatectomy. The spleen showed a large number of hepatocytes that were in the process of dying on the 5th day, and only a number of ghost hepatocytes were present on the 7th day of transplantation. No tumors were found during the 6-month observation period. Conclusions: Conditionally immortalized hepatocytes can survive in the spleen for a limited period, in spite of the growth stimulation, most likely because they undergo apoptosis in vivo as well as in vitro at a non-permissive temperature. These data suggest that the use of these cells in hepatocyte transplantation be limited to temporary hepatic support.

Although symptomatic propylthiouracil (PTU)-induced hepatic injury is known to be rare, there have been few reports about its exact incidence in patients with hyperthyroidism. We tried to evaluate its incidence in a single center and its clinical course.Medical records of 912 hyperthyroid patients who had been diagnosed between March 1990 and December 1998 were reviewed about clinical characteristics, management, and laboratory findings. Symptomatic PTU-induced hepatic injury was defined as the development of jaundice or hepatitis symptoms with at least a 3-times elevation of liver function tests (LFT) without other causes.Four hundred ninety-seven patients (age 42.6 +/- 10.7 yr, male/female 140/357) were included. Clinically overt hepatitis developed in six patients (1.2%; age, 43.7 +/- 14.8 yr; male:female ratio, 3:3) between 12 and 49 days after PTU administration. Jaundice and itching developed in five patients, fever in two, rash in two, and arthralgia in one. Bilirubin, ALT, and ALP increased in five, four, and six patients, respectively (293 +/- 288 micromol/L, 143 +/- 111 U/L, and 265 +/- 81 U/L; normal,117 U/L). The type of hepatic injury was cholestatic in three, hepatocellular in one, and mixed in two patients. None resulted from viral hepatitis. There were no statistical differences in age, sex, PTU dose, or T4 and T3 levels at initial diagnosis between patients with and without hepatic injury. LFT normalized in all patients between 16 and 145 (72.8 +/- 46.4) days after the PTU withdrawal.Symptomatic hepatic injury develops usually within the first few months of PTU administration with rare frequency, but its clinical course is relatively benign once the drug is withdrawn. However, it may be difficult to predict its development, so all patients should be monitored for rise in LFTs at regular intervals, especially during the early period.

The rat hepatocytes were immortalized using a temperature-sensitive mutant of SV40 large T antigen (tsT) to develop as a possible substitute for primary hepatocytes. Four rat hepatocyte lines that have been developed and maintained more than passage 50, were characterized for their cellular morphology, T antigen and p53 expression, chromosomes, liver-specific differentiation, telomerase activity and anchorage independent growth. All of four cell lines showed a typical epithelial cell morphology, but the population-doubling time became short with passage: 18 to 60%. T antigen expression was increased with passage about 3 to 65 times at permissive temperature but decreased significantly at non-permissive temperature. The expression level of p53 unchanged during passages was also decreased at non-permissive temperature. The distribution of chromosome number changed somewhat with passage. The production levels of albumin and urea in four cell lines were 2.4 to 13.0% and 7.5 to 19.9% of those produced in primary hepatocytes, respectively and were decreased to an undetectable level with passage. Telomerase activity was increased 10 fold following immortalization of cells, but anchorage independent growth of cells did not develop. These results indicate that conditionally immortalized hepatocytes become dedifferentiated with in vitro passage, which may be caused by marked chromosomal damages that occur with compulsive and continuous replications by the increment of T antigen content with passage and its sequential inhibition of p53 function.