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1.  Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension 
Clinical and Molecular Hepatology  2014;20(4):376-383.
Background/Aims
Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial.
Methods
Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders.
Results
The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups.
Conclusions
The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
doi:10.3350/cmh.2014.20.4.376
PMCID: PMC4278069  PMID: 25548744
Portal hypertension; Angiotensin receptor blocker; Non-selective beta blocker; Cirrhosis; Hepatic venous pressure gradient
2.  Alcoholic liver disease: Treatment 
World Journal of Gastroenterology : WJG  2014;20(36):12934-12944.
The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation.
doi:10.3748/wjg.v20.i36.12934
PMCID: PMC4177474  PMID: 25278689
Liver disease; Alcoholic; Treatment
3.  Clinical characteristics and outcomes of antenatal fetal intra-abdominal umbilical vein varix detection 
Obstetrics & Gynecology Science  2014;57(3):181-186.
Objective
This study reviewed clinical characteristics of fetal intra-abdominal umbilical vein (FIUV) varices that were detected during antenatal ultrasound examinations.
Methods
Between January 2006 and January 2012, 121 cases of FIUV varices were detected and 7 cases were lost to follow-up. We retrospectively reviewed the medical records of 114 patients and neonates.
Results
From a total 96,553 ultrasound examinations in 43,995 pregnancies, 121 cases of FIUV varices were identified (2.8 per 1,000 pregnancies). Gestational age at diagnosis was 32.0 ± 2.9 weeks (range, 20.1-36.3 weeks), the mean diameter of the FIUV varix was 12.6 ± 2.1 mm (range, 8.0-21.0 mm) at initial diagnosis and the mean maximal diameter was 13.1 ± 2.3 mm (range, 8.0-21.0 mm) during follow-up. The most severe pregnancy complications included one case of intrauterine fetal death and another case of fetal hydrops. Associated fetal anomalies (n = 11, 9.6%) detected by ultrasonography included bilateral renal pelvis dilatation, ventriculomegaly, cryptorchidism, incomplete renal duplication and pulmonary sequestration. A total of 104 cases (91.2%) were delivered at term and 10 cases (8.8%) were preterm deliveries before 37 weeks of gestation.
Conclusion
FIUV varices that are not associated with fetal anomalies based on ultrasound examination during prenatal care have favorable pregnancy outcomes. Nevertheless, close fetal monitoring is recommended to decrease perinatal complications.
doi:10.5468/ogs.2014.57.3.181
PMCID: PMC4038683  PMID: 24883288
Antenatal ultrasound; Umbilical veins; Varicose veins
4.  Invasive and non-invasive diagnosis of cirrhosis and portal hypertension 
With advances in the management and treatment of advanced liver disease, including the use of antiviral therapy, a simple, one stage description for advanced fibrotic liver disease has become inadequate. Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential, current diagnostic tests have not kept pace with the progression of this new paradigm. Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension (PHT), respectively, and they have diagnostic and prognostic value. However, they are invasive and, as such, cannot be used repeatedly in clinical practice. The ideal noninvasive test should be safe, easy to perform, inexpensive, reproducible as well as to give numerical and accurate results in real time. It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification. Recently, many types of noninvasive alternative tests have been developed and are under investigation. In particular, imaging and ultrasound based tests, such as transient elastography, have shown promising results. Although most of these noninvasive tests effectively identify severe fibrosis and PHT, the methods available for diagnosing moderate disease status are still insufficient, and further investigation is essential to predict outcomes and individualize therapy in this field.
doi:10.3748/wjg.v20.i15.4300
PMCID: PMC3989965  PMID: 24764667
Hepatic fibrosis; Portal hypertension; Liver biopsy; Hepatic venous pressure gradient; Non-invasive test; Transient elastography
5.  The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data 
Clinical and molecular hepatology  2013;19(4):370-375.
Background/Aims
Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis.
Methods
LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves.
Results
A strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively.
Conclusions
LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.
doi:10.3350/cmh.2013.19.4.370
PMCID: PMC3894436  PMID: 24459641
Portal hypertension; Liver stiffness measurement; Cirrhosis
6.  Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus 
Clinical and molecular hepatology  2013;19(4):421-425.
Glycogenic hepatopathy (GH) is an uncommon cause of serum transaminase elevation in type I diabetes mellitus (DM). The clinical signs and symptoms of GH are nonspecific, and include abdominal discomfort, mild hepatomegaly, and transaminase elevation. In this report we describe three cases of patients presenting serum transaminase elevation and hepatomegaly with a history of poorly controlled type I DM. All of the cases showed sudden elevation of transaminase to more than 30 times the upper normal range (like in acute hepatitis) followed by sustained fluctuation (like in relapsing hepatitis). However, the patients did not show any symptom or sign of acute hepatitis. We therefore performed a liver biopsy to confirm the cause of liver enzyme elevation, which revealed GH. Clinicians should be aware of GH so as to prevent diagnostic delay and misdiagnosis, and have sufficient insight into GH; this will be aided by the present report of three cases along with a literature review.
doi:10.3350/cmh.2013.19.4.421
PMCID: PMC3894443  PMID: 24459648
Glycogen hepatopathy; Transaminase; Type I diabetes mellitus
7.  2014 First-trimester ultrasound forum from the Korean Society of Ultrasound in Obstetrics and Gynecology 
A first-trimester ultrasound scan has become an essential part of antenatal care. The Korean Society of Ultrasound in Obstetrics and Gynecology held a first-trimester ultrasound forum on April 5, 2014. The forum aimed to present an updated review of the literature on the topic of first-trimester ultrasound in specific lectures and to host a panel discussion on several important issues regarding first-trimester scans. The forum provided evidence- and consensus-based best practice patterns for obstetricians in Korea. Here, we report the review and checklists presented from the forum.
doi:10.5468/ogs.2015.58.1.1
PMCID: PMC4303746  PMID: 25629012
Korean Society of Ultrasound in Obstetrics and Gynecology; Nuchal translucency measurement; Pregnancy trimester, first; Ultrasonography
8.  Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model 
BMC Gastroenterology  2014;14(1):198.
Background
Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model.
Methods
The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor β1 (TGF-β1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays.
Results
According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P <0.01). The percentage of the collagen proportionate area decreased from 16.72 ± 5.51 to 5.06 ± 1.27 after BM-MSC treatment (P <0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 ± 13.19) compared to the untreated cirrhotic group (85.81 ± 17.62; P <0.01). BM-MSC administration significantly decreased TGF-β1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-β1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation.
Conclusions
BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.
Electronic supplementary material
The online version of this article (doi:10.1186/s12876-014-0198-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12876-014-0198-6
PMCID: PMC4251876  PMID: 25425284
Bone marrow-derived mesenchymal stem cell; Cirrhosis; Hepatic fibrosis; Liver function
9.  Genome sequence of mungbean and insights into evolution within Vigna species 
Nature Communications  2014;5:5443.
Mungbean (Vigna radiata) is a fast-growing, warm-season legume crop that is primarily cultivated in developing countries of Asia. Here we construct a draft genome sequence of mungbean to facilitate genome research into the subgenus Ceratotropis, which includes several important dietary legumes in Asia, and to enable a better understanding of the evolution of leguminous species. Based on the de novo assembly of additional wild mungbean species, the divergence of what was eventually domesticated and the sampled wild mungbean species appears to have predated domestication. Moreover, the de novo assembly of a tetraploid Vigna species (V. reflexo-pilosa var. glabra) provides genomic evidence of a recent allopolyploid event. The species tree is constructed using de novo RNA-seq assemblies of 22 accessions of 18 Vigna species and protein sets of Glycine max. The present assembly of V. radiata var. radiata will facilitate genome research and accelerate molecular breeding of the subgenus Ceratotropis.
Mungbean is a fast-growing and warm-season legume crop, cultivated mainly in Asia. Here, the authors sequence the genomes of both wild and domesticated mungbean varieties and, together with detailed transcriptome data, provide insight into mungbean domestication, polyploidization and speciation.
doi:10.1038/ncomms6443
PMCID: PMC4241982  PMID: 25384727
10.  Gestational weight gain is an important risk factor for excessive fetal growth 
Obstetrics & Gynecology Science  2014;57(6):442-447.
Objective
To estimate the odds ratio of prepregnant body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) for excessive fetal growth, which we define as large for gestational age (LGA).
Methods
We included 16,297 women who delivered a live-born singleton baby at term. We fit logistic regressions to estimate the odds ratios of variables, including maternal age, parity, prepregnant BMI ≥23, GWG ≥15 kg, and GDM, for LGA. We classified GWG into four categories (<10, 10-14.9, 15-19.9, and ≥20 kg) and BMI into four categories (underweight, normal, overweight, and obese). After adjusting for age and parity, we analyzed the odds ratios of prepregnant BMI according to GWG between non-GDM and GDM women for LGA.
Results
The odds ratios of GWG ≥15 kg and prepregnancy BMI ≥23 for LGA were 2.40 (95% confidence interval [CI], 2.16-2.67) and 2.24 (95% CI, 1.99-2.51), respectively. The odd ratio of GDM was 1.37 (95% CI, 1.09-1.71). The risk of GDM women with normal/-overweight BMI and GWG <15 kg for LGA was not significantly greater than those of the reference group. The odd ratios of GDM women with overweight/obese BMI and GWG 15 to 19.9 kg were 3.95 (95% CI, 1.26-12.38) and 9.70 (95% CI, 3.79-24.87), respectively.
Conclusion
GWG ≥15 kg might be a more important risk factor for LGA than either prepregnancy BMI ≥23 or GDM. Risk for LGA was highest in obese GDM women with GWG ≥15 kg.
doi:10.5468/ogs.2014.57.6.442
PMCID: PMC4245336  PMID: 25469331
Birth weight; Body mass index; Diabetes; Gestational; Weight gain
11.  The clinical practice patterns of fetal ultrasonography in the first-trimester: A questionnaire survey of members of the Korean Society of Ultrasound in Obstetrics and Gynecology 
Obstetrics & Gynecology Science  2014;57(6):448-456.
Objective
This study aimed to survey the current clinical practice of first-trimester ultrasonography among members of the Korean Society of Ultrasound in Obstetrics and Gynecology (KSUOG) and to provide basic data for making practical recommendations about first-trimester ultrasonography scan in Korea.
Methods
This survey was conducted using a self-administered anonymous questionnaire. The first-trimester in this survey was divided into two parts: early and late first-trimester. The survey was focused on safety issue, nuchal translucency (NT) cutoff, the anatomic structures they check, and the need for practical recommendations or educational courses during the first-trimester.
Results
During the study period, 194 KSUOG members participated into this survey. The survey on early first-trimester scan reveal that 173 (89.2%) of respondents had used pulsed-wave Doppler or color Doppler imaging to monitor fetal heart beat. For the late first-trimester scan, 145 (74.7%) of respondents was found to check for fetal anatomical assessments during their NT screening performance; however, the clinical practice patterns were considerably varied among participants. More than half of the respondents used the criterion of NT ≥3.0 mm to define increased NT. Approximately 80% of respondents stated that the screening ultrasonography of fetal structures in the first-trimester was necessary. Furthermore, 187 (96.4%) of respondents were in favor of a recommendation for first-trimester ultrasonography in Korea.
Conclusion
This is the first survey of the current clinical practice of first-trimester ultrasonography in Korea. Our survey findings highlight the need for the practical recommendation or educational course for first-trimester ultrasonography.
doi:10.5468/ogs.2014.57.6.448
PMCID: PMC4245337  PMID: 25469332
Clinical practical pattern; Data collection; Pregnancy trimester, first; Ultrasonography
12.  Elective tracheostomy scoring system for severe oral disease patients 
Objectives
The purpose of this research was to create a scoring system that provides comprehensive assessment of patients with oromaxillofacial cancer or odontogenic infection, and to statistically reevaluate the results in order to provide specific criteria for elective tracheostomy.
Materials and Methods
All patients that had oral cancer surgery (group A) or odontogenic infection surgery (group B) during a period of 10 years (2003 to 2013) were subgrouped according to whether or not the patient received a tracheostomy. After a random sampling (group A: total of 56, group B: total of 60), evaulation procedures were observed based on the group classifications. For group A, four factors were evaluated: TNM stage, reconstruction methods, presence of pathologic findings on chest posterior-anterior (PA), and the number of systemic diseases. Scores were given to each item based on the scoring system suggested in this research and the scores were added together. Similarly, the sum score of group B was counted using 5 categories, including infection site, C-reactive protein level on first visit, age, presence of pathologic findings on chest PA, and number of systemic diseases.
Results
The scoring system rendered from this research shows that there is a high correlation between the scores and TNM stage in oral cancer patients, or infection sites in odontogenic infection patients. However, no correlation between pathologic findings on chest PA could be found in either group. The results also indicated that for both groups, the hospital day increased with the tracheostomy score. The tracheostomy score cutoff value was 5 in oral cancer patients and 6 in odontogenic infection patients which was used for elective tracheostomy indication.
Conclusion
The elective tracheostomy score system suggested by this research is a method that considers both the surgical and general conditions of the patient, and can be very useful for managing patients with severe oral disease.
doi:10.5125/jkaoms.2014.40.5.211
PMCID: PMC4217265  PMID: 25368833
Tracheostomy; Scoring system; Airway management; Mouth neoplasms; Odontogenic infection
13.  Pregnancy-associated pulmonary embolism during the peripartum period: An 8-year experience at a single center 
Obstetrics & Gynecology Science  2014;57(4):260-265.
Objective
The purpose of this study was to estimate the incidence, timing of onset, risk factors, and mortality rate of pregnancy-associated pulmonary embolism (PAPE).
Methods
We analyzed PAPE cases that occurred between January 2005 and December 2012 at Cheil General Hospital & Women's Healthcare Center. Those cases that were not confirmed by computed tomography scan or were confirmed as amniotic fuid embolisms were excluded. We analyzed various risk factors such as previous surgery, mode of delivery, maternal age, and obesity in PAPE.
Results
There were 57,092 deliveries over 8 years. Of them, 13 cases (0.023%) were diagnosed with PAPE. All cases occurred in the postpartum period after cesarean delivery. There were no cases of PAPE after vaginal deliveries. Of the total cases, 10 cases (76.9%) were diagnosed in the early postpartum period within 48 hours. Eight cases (61.5%) had a history of previous surgery. There were 3 cases (23.1%) of multiple pregnancy and 3 cases (23.1%) of preterm delivery. No cases had a history of venous thromboembolism. Among 13 cases, 10 cases improved with only anticoagulation, 2 cases received surgical thrombectomy, and one case was maternal death.
Conclusion
Our results indicated that the incidence of PAPE was very low (0.023%) and occurred mainly in the postpartum period after cesarean section. However, its maternal mortality rate was significantly high (7.7%). Therefore, we suggest that immediate diagnosis and prompt treatment should be prioritized for improvement of PAPE patients' survival rate.
doi:10.5468/ogs.2014.57.4.260
PMCID: PMC4124086  PMID: 25105098
Peripartum period; Pregnancy; Pulmonary; Thromboembolism
14.  Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut–liver axis of alcoholic liver disease 
Journal of Ginseng Research  2014;38(3):167-172.
Background
Roles of immune reaction and toll-like receptor-4 (TLR-4) have widely been established in the pathogenesis of alcoholic liver disease (ALD).
Methods
We evaluated the biologic efficacy of Korean Red Ginseng (KRG), urushiol, and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in mouse models of ALD. Sixty C57BL/6 mice were equally divided into six feeding groups for 10 weeks: normal diet, alcohol, control, alcohol + KRG, alcohol + urushiol, and alcohol + probiotics. Alcohol was administered via a Lieber–DeCarli liquid diet containing 10% alcohol. TLR-4 expression, proinflammatory cytokines, and histology, as well as the results of liver function tests were evaluated and compared.
Results
No between-group differences were observed with regard to liver function. TLR-4 levels were significantly lower in the KRG, urushiol, and probiotics groups than in the alcohol group (0.37 ± 0.06 ng/mL, 0.39 ± 0.12 ng/mL, and 0.33 ± 0.07 ng/mL, respectively, vs. 0.88 ± 0.31 ng/mL; p < 0.05). Interleukin-1β levels in liver tissues were decreased among the probiotics and KRG groups. The tumor necrosis factor-α level of liver tissue was decreased in the KRG group.
Conclusion
The pathological findings showed that alcohol-induced steatosis was significantly reduced by KRG and urushiol. As these agents improve immunologic capacity, they may be considered in potential anti-ALD treatments.
doi:10.1016/j.jgr.2014.04.002
PMCID: PMC4213850  PMID: 25378990
alcoholic liver disease; Lactobacillus; Panax ginseng; urushiol
15.  Metastatic testicular tumor presenting as a scrotal hydrocele: An initial manifestation of pancreatic adenocarcinoma 
Oncology Letters  2014;7(6):1793-1795.
Metastatic pancreatic adenocarcinoma involving the testis is a rare condition with a poor prognosis. The current study describes the case of a 69-year-old male who presented with a painful swelling of the left scrotum. Scrotal ultrasonography revealed hydroceles in the scrotal sacs, with the left one being larger in size. The patient underwent left hydrocelectomy and was eventually diagnosed with metastatic adenocarcinoma. Abdominal computed tomography, which was performed to detect the primary cancer, showed a pancreatic tail carcinoma with liver and multiple lymph node metastases, and peritoneal carcinomatosis. The patient received gemcitabine-based chemotherapy but resulted in progressive disease. This case shows that in a patient in whom a primary testicular tumor is unusual due to their age, a testicular mass or hydrocele should be a suspect for possible metastatic disease.
doi:10.3892/ol.2014.2009
PMCID: PMC4049672  PMID: 24932235
adenocarcinoma; neoplasm metastasis; pancreatic neoplasms; testicular hydrocele; testicular neoplasms
16.  Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease 
Journal of Korean Medical Science  2014;29(3):392-399.
Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.
Graphical Abstract
doi:10.3346/jkms.2014.29.3.392
PMCID: PMC3945135  PMID: 24616589
Hypertension, Portal; Nitric Oxide; Liver Cirrhosis
17.  Clinical outcomes of transjugular intrahepatic portosystemic shunt for portal hypertension: Korean multicenter real-practice data 
Background/Aims
This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis.
Methods
Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals.
Results
Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9±30.2 months (mean±SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality.
Conclusions
A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.
doi:10.3350/cmh.2014.20.1.18
PMCID: PMC3992326  PMID: 24757655
Liver cirrhosis; Transjugular intrahepatic portosystemic shunt; Portal hypertension
18.  Disease specific characteristics of fetal epigenetic markers for non-invasive prenatal testing of trisomy 21 
Background
Non-invasive prenatal testing of trisomy 21 (T21) is being actively investigated using fetal-specific epigenetic markers (EPs) that are present in maternal plasma. Recently, 12 EPs on chromosome 21 were identified based on tissue-specific epigenetic characteristics between placenta and blood, and demonstrated excellent clinical performance in the non-invasive detection of fetal T21. However, the disease-specific epigenetic characteristics of the EPs have not been established. Therefore, we validated the disease-specific epigenetic characteristics of these EPs for use in non-invasive detection of fetal T21.
Methods
We performed a high-resolution tiling array analysis of human chromosome 21 using a methyl-CpG binding domain-based protein (MBD) method with whole blood samples from non-pregnant normal women, whole blood samples from pregnant normal women, placenta samples of normal fetuses, and placenta samples of T21 fetuses. Tiling array results were validated by bisulfite direct sequencing and qPCR.
Results
Among 12 EPs, only four EPs were confirmed to be hypermethylated in normal placenta and hypomethylated in blood. One of these four showed a severe discrepancy in the methylation patterns of T21 placenta samples, and another was located within a region of copy number variations. Thus, two EPs were confirmed to be potential fetal-specific markers based on their disease-specific epigenetic characteristics. The array results of these EPs were consisted with the results obtained by bisulfite direct sequencing and qPCR. Moreover, the two EPs were detected in maternal plasma.
Conclusions
We validated that two EPs have the potential to be fetal-specific EPs which is consistent with their disease-specific epigenetic characteristics. The findings of this study suggest that disease-specific epigenetic characteristics should be considered in the development of fetal-specific EPs for non-invasive prenatal testing of T21.
doi:10.1186/1755-8794-7-1
PMCID: PMC3892082  PMID: 24397966
Trisomy 21; Non-invasive prenatal testing; Epigenetic markers
19.  Ultrasonographic scoring system score versus liver stiffness measurement in prediction of cirrhosis 
Clinical and molecular hepatology  2013;19(4):389-398.
Background/Aims
We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.
Methods
Two hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.
Results
The mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.
Conclusions
The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.
doi:10.3350/cmh.2013.19.4.389
PMCID: PMC3894439  PMID: 24459644
Ultrasonography; Elastography; Cirrhosis; Biopsy
20.  Risk Factors Associated with Group B Streptococcus Resistant to Clindamycin and Erythromycin in Pregnant Korean Women 
Infection & Chemotherapy  2013;45(3):299-307.
Background
The prevalence of group B streptococcus (GBS) among pregnant women and neonates in the Republic of Korea has increased. In addition, rates of resistance to antibiotics recommended for pregnant women allergic to penicillin, such as clindamycin and erythromycin, have increased. The aim of this study was to evaluate subject characteristics associated with GBS resistance to clindamycin and erythromycin.
Materials and Methods
A total of 418 clinical isolates from pregnant women in Korea were screened for antibiotic resistance from January 2006 to December 2011. Sociodemographic information, medical and obstetric history, and details of events during the previous 2 weeks were recorded using a standardized questionnaire.
Results
The resistance rates were 39.5% for clindamycin and 23.0% for erythromycin. In multiple logistic regression analysis, the subject characteristic significantly associated with resistance to both antibiotics was a history of symptomatic sore throat in the 2 weeks before obtaining the specimen (erythromycin: odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.10 to 4.13; clindamycin: OR: 2.31, 95% CI: 1.21, 4.42). Premature rupture of membranes (PROM) had an association of borderline significance.
Conclusions
In the urgent treatment of GBS-colonized pregnant women, the subject's history of previous sore throat and PROM should be considered when choosing appropriate antibiotics.
doi:10.3947/ic.2013.45.3.299
PMCID: PMC3848523  PMID: 24396631
Antibiotic resistance; Clindamycin; Erythromycin; Risk factors; Streptococcus agalactiae
21.  Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions 
The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data.
doi:10.3350/cmh.2013.19.1.1
PMCID: PMC3622850  PMID: 23593604
Guidelines; Contrast enhanced Ultrasonography (CEUS); Focal liver lesions (FLLs)
22.  Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data 
Background/Aims
While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.
Methods
The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.
Results
The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).
Conclusions
The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.
doi:10.3350/cmh.2013.19.1.36
PMCID: PMC3622854  PMID: 23593608
Gastric variceal bleeding; Rebleeding; Mortality; Cirrhosis
23.  Cell-Free Fetal DNA and Cell-Free Total DNA Levels in Spontaneous Abortion with Fetal Chromosomal Aneuploidy 
PLoS ONE  2013;8(2):e56787.
Background
Cell-free fetal DNA and cell-free total DNA in maternal circulation have been proposed as potential markers for noninvasive monitoring of the placental condition during the pregnancy. However, the correlation of and change in cell-free fetal DNA and cell-free total DNA in spontaneous abortion (SA) with fetal chromosomal aneuploidy have not yet been reported. Therefore, we investigated cell-free fetal DNA and cell-free total DNA levels in SA women with fetal chromosomal aneuploidy.
Methodology/Principal Findings
A nested case-control study was conducted with maternal plasma collected from 268 women in their first trimester of pregnancy. Subjects included 41 SA with normal fetal karyotype, 26 SA with fetal chromosomal aneuploidy, and 201 normal controls. The unmethylated PDE9A gene was used to measure the maternal plasma levels of cell-free fetal DNA. The GAPDH gene was used to measure the maternal plasma levels of cell-free total DNA. The diagnostic accuracy was measured using receiver-operating characteristic (ROC) curves. Levels of cell-free fetal DNA and cell-free total DNA were significantly higher in both SA women with normal fetal karyotype and SA women with fetal chromosomal aneuploidy in comparison with the normal controls (P<0.001 in both). The correlation between cell-free fetal DNA and cell-free total DNA levels was stronger in the normal controls (r = 0.843, P<0.001) than in SA women with normal karyotype (r = 0.465, P = 0.002) and SA women with fetal chromosomal aneuploidy (r = 0.412, P = 0.037). The area under the ROC curve for cell-free fetal DNA and cell-free total DNA was 0.898 (95% CI, 0.852–0.945) and 0.939 (95% CI, 0.903–0.975), respectively.
Conclusions
Significantly high levels of cell-free fetal DNA and cell-free total DNA were found in SA women with fetal chromosomal aneuploidy. Our findings suggest that cell-free fetal DNA and cell-free total DNA may be useful biomarkers for the prediction of SA with fetal chromosomal aneuploidy, regardless of fetal gender.
doi:10.1371/journal.pone.0056787
PMCID: PMC3574115  PMID: 23457614
24.  Usefulness of a Rapid Real-time PCR Assay in Prenatal Screening for Group B Streptococcus Colonization 
Annals of Laboratory Medicine  2012;33(1):39-44.
Background
Group B streptococcus (GBS) infection is a leading cause of neonatal morbidity and mortality worldwide. Here, we present the analytical and diagnostic usefulness of a new real-time PCR-based assay (Xpert GBS; Cepheid, USA) for rapid and accurate prenatal GBS screening.
Methods
We enrolled 175 pregnant women who were between 35 and 39 weeks of gestation. The analytical performance of the Xpert GBS assay was first tested using a reference GBS strain. Next, to test diagnostic performance, rectovaginal swabs were obtained from pregnant women who visited the hospital for regular antenatal screening after 34 weeks of gestation. The results of the Xpert GBS assay were compared to those of standard culture for the detection of prenatal GBS colonization.
Results
When any positive result from Xpert GBS or culture was considered a true positive, the sensitivity of the Xpert GBS assay and culture were 91% (20/22; 95% CI [confidence interval], 72-98) and 68% (15/22; 95% CI, 47-84), respectively. The specificity of both methods was 100% (153/153; 95% CI, 97-100). The sensitivity and specificity of the Xpert GBS assay, using the culture results as a reference, were 86.7% and 95.6%, respectively. In the Xpert GBS assay, the median threshold cycle of vaginally colonized samples was significantly lower than rectally colonized samples (P<0.01).
Conclusions
The Xpert GBS assay is an accurate, rapid, easy-to-use test for the detection of maternal GBS colonization in prenatal screening that might be especially useful in clinical settings where standard culture is not feasible.
doi:10.3343/alm.2013.33.1.39
PMCID: PMC3535195  PMID: 23301221
Streptococcus agalactiae; Prenatal diagnosis; Real-time PCR
25.  Relationship between the hepatic venous pressure gradient and first variceal hemorrhage in patients with cirrhosis: a multicenter retrospective study in Korea 
Clinical and molecular hepatology  2012;18(4):391-396.
Background/Aims
Variceal hemorrhage is one of the major complications of cirrhosis and is associated with significant mortality and morbidity. The development of gastroesophageal varices and variceal hemorrhage is the most direct consequence of portal hypertension. Correlations between the hepatic venous pressure gradient (HVPG) and first variceal hemorrhage were examined.
Methods
Patients with cirrhosis who underwent HVPG measurement between July 2009 and September 2010 were enrolled (n=535). All patients underwent esophagogastroduodenoscopy to enable the evaluation of gastroesophageal varices.
Results
The HVPG for all patients was 16.46±7.05 mmHg (mean±SD), and was significantly higher among those with first variceal hemorrhage than in those without it. The HVPG was significantly correlated with both Child-Turcotte-Pugh (r=0.488, P<0.001) and Model for End-stage Liver Disease (r=0.478, P<0.001) scores. An HVPG value of 11 mmHg was predictive of first variceal hemorrhage with a sensitivity of 92.4% and a specificity of 27.7%.
Conclusions
The HVPG was higher in patients with first variceal hemorrhage than in those without it.
doi:10.3350/cmh.2012.18.4.391
PMCID: PMC3540376  PMID: 23323255
Hepatic venous pressure gradient (HVPG); Variceal hemorrhage

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