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1.  Anxiety and depression propensities in patients with acute toxic liver injury 
AIM: To investigate anxiety and depression propensities in patients with toxic liver injury.
METHODS: The subjects were divided into three groups: a healthy control group (Group 1, n = 125), an acute non-toxic liver injury group (Group 2, n = 124), and a group with acute toxic liver injury group caused by non-commercial herbal preparations (Group 3, n = 126). These three groups were compared and evaluated through questionnaire surveys and using the Hospital Anxiety-Depression Scale (HADS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and the hypochondriasis scale.
RESULTS: The HADS anxiety subscale was 4.9 ± 2.7, 5.0 ± 3.0 and 5.6 ± 3.4, in Groups 1, 2, and 3, respectively. The HADS depression subscale in Group 3 showed the most significant score (5.2 ± 3.2, 6.4 ± 3.4 and 7.2 ± 3.4 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2). The BAI and BDI in Group 3 showed the most significant score (7.0 ± 6.3 and 6.9 ± 6.9, 9.5 ± 8.6 and 8.8 ± 7.3, 10.7 ± 7.2 and 11.6 ± 8.5 in Groups 1, 2, and 3, respectively) (BAI: P < 0.01 vs Group 1, P < 0.05 vs Group 2) (BDI: P < 0.01 vs Group 1 and 2). Group 3 showed a significantly higher hypochondriasis score (8.2 ± 6.0, 11.6 ± 7.5 and 13.1 ± 6.5 in Groups 1, 2, and 3, respectively) (P < 0.01 vs Group 1, P < 0.05 vs Group 2).
CONCLUSION: Psychological factors that present vulnerability to the temptation to use alternative medicines, such as herbs and plant preparations, are important for understanding toxic liver injury.
PMCID: PMC3870561  PMID: 24379633
Liver injury; Herb; Toxic; Anxiety; Depression
2.  Intrahepatic Portosystemic Venous Shunt: Successful Embolization Using the Amplatzer Vascular Plug II 
Korean Journal of Radiology  2012;13(6):827-831.
A 67-year-old woman presented with memory impairment and behavioral changes. Brain MRI indicated hepatic encephalopathy. Abdominal CT scans revealed an intrahepatic portosystemic venous shunt that consisted of two shunt tracts to the aneurysmal sac that communicated directly with the right hepatic vein. The large tract was successfully occluded by embolization using the newly available AMPLATZERTM Vascular Plug II and the small tract was occluded by using coils. The patient's symptoms disappeared after shunt closure and she remained free of recurrence at the 3-month follow-up evaluation.
PMCID: PMC3484308  PMID: 23118586
Hepatic encephalopathy; Portosystemic shunt; Surgical; Embolization; Therapeutic
3.  Inhibitory effects of rapamycin on the different stages of hepatic fibrosis 
AIM: To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis.
METHODS: We performed bile duct ligation (BDL) in male Wistar rats (n = 24). The experimental rats were classified into four groups: the BDL+/Rapa- group (un-treated control, n = 4), the BDL+/Rapa+ group (treated 14 d after BDL, n = 8), the BDL+/Rapa++ group (treated on the day after BDL, n = 8), and the BDL-/Rapa- group (un-treated, sham -operated control, n = 4). The BDL+/Rapa+ and BDL+/Rapa++ groups were administered rapamycin (2 mg/kg) for 28 d. The liver tissues were tested by immunohistochemical staining for α-smooth muscle actin (α-SMA) and cytokeratin.
RESULTS: The liver mRNA levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were measured using the polymerase chain reaction. The protein levels of liver p70s6K and p-p70s6k were determined using Western blotting. α-SMA expression was lowest in the BDL+/Rapa++group. TGF-β1 and PDGF expression levels in the rapamycin-treated group were lower than those in the un-treated group and higher than those in the control groups (TGF-β1: 0.23 ± 0.00 vs 0.34 ± 0.01, 0.23 ± 0.0 vs 0.09 ± 0.00, P < 0.0001; PDGF: 0.21 ± 0.00 vs 0.34 ± 0.01, 0.21 ± 0.0 vs 0.09 ± 0.00, P < 0.0001). The p70s6k and p-p70s6k levels decreased in the treated groups and were lowest in the BDL+/Rapa++group (p70s6k: 1.05 ± 0.17 vs 1.30 ± 0.56, 0.40 ± 0.01 vs 1.30 ± 0.56, P < 0.0001; p-p70s6k: 1.40 ± 0.5 vs 1.67 ± 0.12, 0.70 ± 0.01 vs 1.67 ± 0.12, P < 0.0001).
CONCLUSION: The results of our study indicate that rapamycin has inhibitory effects on liver fibrosis, and the treatment is most effective in the early stages of fibrosis.
PMCID: PMC4064090  PMID: 24966615
Liver cirrhosis; Sirolimus; Transforming growth factor beta; Platelet-derived growth factor; Ribosomal protein S6 kinases
4.  Risk factors and therapeutic results of early local recurrence after transcatheter arterial chemoembolization 
AIM: To identify factors affecting early local recurrence after transcatheter arterial chemoembolization (TACE) and investigate treatments and outcomes for local recurrence.
METHODS: Early local recurrence and no early local recurrence groups drawn from 134 patients who were initially diagnosed with hepatocellular carcinoma (HCC) and showed a complete response (CR) to TACE treatment between January 1, 2006, and January 31, 2012, were analyzed by univariate and multivariate analyses. Additionally, the subsequent treatment for patients with recurrence was analyzed, and in cases in which TACE had been performed, the cumulative recurrence rates were calculated using the Kaplan-Meier method and compared with those of the primary lesion.
RESULTS: The 1-, 2-, and 3-year survival rates were 92.3%, 60.2%, and 39.8%, respectively, in the early local recurrence group, which were significantly lower than those in both the late local and no local recurrence groups (P < 0.001). On multivariate analyses, non-compact lipiodol uptake, large tumor size, and an alpha-fetoprotein > 20 ng/mL after achieving a CR were significant predictors. When TACE was performed for early and late locally recurrent lesions, a CR was observed in 15 patients (41.7%) and 11 patients (78.6%), and the cumulative recurrence rates at 6, 12, and 24 mo were 17.9%, 43.3%, and 71.2%, respectively, which did not differ significantly from those after the first CR of 20.5%, 44.0%, and 58.6%, respectively (P = 0.639).
CONCLUSION: Closer monitoring and active treatments must be provided to patients with risk factors for early local recurrence of HCC.
PMCID: PMC4051943  PMID: 24944494
Chemoembolization; Hepatocellular carcinoma; Recurrence; Survival; Lipiodol
5.  Reactivation of tuberculosis in hepatocellular carcinoma treated with transcatheter arterial chemoembolization: A report of 3 cases 
World Journal of Radiology  2012;4(5):236-240.
Pulmonary tuberculosis is an opportunistic infection that can be reactivated in immunocompromised conditions, for example, in malignancy or after liver transplantation. Hepatocellular carcinoma (HCC) has a high mortality rate because it is frequently diagnosed at an advanced stage. Although surgical resection is the established curative measure for HCC, it is only feasible for early-stage HCC. Transcatheter arterial chemoembolization (TACE) is the most common treatment modality for patients with unresectable HCC. However, repeated TACE sessions and, occasionally, the tumor itself can further impair the reserve hepatic function and immunity. We report 3 recent cases of HCC with reactivation of pulmonary tuberculosis after TACE.
PMCID: PMC3386538  PMID: 22761986
Hepatocellular carcinoma; Reactivation; Transcatheter arterial chemoembolization; Tuberculosis
6.  Is there correlation between pancreatic enzyme and radiological severity in acute pancreatitis? 
AIM: To investigate the correlation between the changes of pancreatic enzyme, the biochemical markers and the clinical results according to the Balthazar computer tomography (CT) grade.
METHODS: Between July 2004 and July 2005, we reviewed the charts of 119 patients who were admitted to our hospital with acute pancreatitis.
RESULTS: Eighty-three patients (69.7%) were male, and the mean age of the patients was 57 ± 15.7 years. The biliary pancreatitis patients had an older mean age. Forty-nine patients (41.1%) had biliary pancreatitis and forty-six (38.6%) had alcoholic pancreatitis. Group 3 patients had a longer duration of pain (2.51 ± 1.16 vs 3.17 ± 1.30 vs 6.56 ± 6.13, P < 0.001), a longer period of fasting (7.49 ± 4.65 vs 10.65 ± 5.54 vs 21.88 ± 13.81, P < 0.001) and a longer hospital stay (9.17 ± 5.34 vs 14.63 ± 8.65 vs 24.47 ± 15.52, P < 0.001) than the other groups. On the univariate analysis, the factors that affected the radiological grade were the leukocyte count at admission (P = 0.048), the hemoglobin (P = 0.016) and total bilirubin concentrations (P = 0.023), serum lipase (P = 0.009), the APACH II scores at admission (P = 0.017), the APACH II scores after 24 h (P = 0.031), the C-reactive protein (CRP) titer (P = 0.0001) and the follow up CRP titer (P = 0.003). But the CRP level (P = 0.001) and follow up CRP titer (P = 0.004) were only correlated with the radiological grade on multivariate analysis. According to the ROC curve, when we set the CRP cut off value at 83 mg/L, the likelihood ratio for a positive test was 3.84 and the likelihood ratio for a negative test was 0.26 in group 3.
CONCLUSION: In conclusion, our study suggests that the CRP with the radiological severity may be used to estimate the severity of acute pancreatitis.
PMCID: PMC2705097  PMID: 18416469
Acute pancreatitis; Computed tomography; C-reactive protein
7.  Prognostic Significance of p53, mTOR, c-Met, IGF-1R, and HSP70 Overexpression after the Resection of Hepatocellular Carcinoma 
Gut and Liver  2014;8(1):79-87.
The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival.
We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs.
p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant.
p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.
PMCID: PMC3916692  PMID: 24516705
p53; mTOR; c-Met; Receptor, IGF type 1; Carcinoma, hepatocellular
8.  Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B 
AIM: To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B (CHB).
METHODS: We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d. The biochemical response, as assessed by serum alanine aminotransferase (ALT) activity, virologic response, as assessed by serum hepatitis B virus DNA (HBV DNA) titer, serologic response, as assessed by hepatitis B e antigen (HBeAg) status, and virologic breakthrough with genotypic mutations were assessed.
RESULTS: Two-hundred and fifty-four patients [clevudine (n = 118) vs entecavir (n = 136)] were enrolled. In clevudine-treated patients, the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96 (80.9% and 91.2% in the entecavir group, respectively), the mean titer changes in serum HBV DNA were -6.03 and -6.55 log10 copies/mL (-6.35 and -6.86 log10 copies/mL, respectively, in the entecavir group), and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1% (74.4% and 83.8%, respectively, in the entecavir group). These results were similar to those of entecavir-treated patients. The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine, which was similar to patients treated with entecavir (22.8% and 27.7%, respectively). The virologic breakthrough in the clevudine group occurred in 9 (7.6%) patients at weeks 48 and 15 (12.7%) patients at week 96, which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M. There was no virologic breakthrough in the entecavir group.
CONCLUSION: In antiviral-naive CHB patients, long-term treatment outcomes of clevudine were not inferior to those of entecavir, except for virologic breakthrough.
PMCID: PMC3531678  PMID: 23322992
Chronic hepatitis B; Hepatitis B virus; Clevudine; Entecavir; Treatment outcomes
9.  Spectrum of final pathological diagnosis of gastric adenoma after endoscopic resection 
AIM: To investigate how many discrepancies occur in patients before and after endoscopic treatment of referred adenoma and the reason for these results.
METHODS: We retrospectively reviewed data from 554 cases of 534 patients who were referred from primary care centres for adenoma treatment and treated for endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) at Chungnam National University Hospital, from July 2006 to June 2009. Re-endoscopy was examined in 142 cases and biopsy was performed in 108 cases prior to treatment. Three endoscopists (1, 2 and 3) performed all EMRs or ESDs and three pathologists (1, 2 and 3) diagnosed most of the cases. Transfer notes, medical records and endoscopic pictures of these cases were retrospectively reviewed and analyzed.
RESULTS: Adenocarcinoma was 72 (13.0%) cases in total 554 cases after endoscopic treatment of referred adenoma. When the grade of dysplasia was high (55.0%), biopsy number was more than three (22.7%), size was no smaller than 2.0 cm (23.2%), morphologic type was depressed (35.8%) or yamada type IV (100%), and color was red (30.9%) or mixed-or-undetermined (25.0%), it had much more malignancy rate than the others (P < 0.05). All 18 cases diagnosed as adenocarcinoma in the re-endoscopic forceps biopsy were performed by endoscopist 1. There were different malignancy rates according to the pathologist (P = 0.027).
CONCLUSION: High grade dysplasia is the most im-portant factor for predicting malignancy as a final pathologic diagnosis before treating the referred gastric adenoma. This discrepancy can occur mainly through inappropriately selecting a biopsy site where cancer cells do not exist, but it also depends on the pathologist to some extent.
PMCID: PMC3243884  PMID: 22215942
Discrepancy; Adenoma; High grade dysplasia; Endoscopic mucosal resection; Endoscopic submucosal dissection
10.  The retrospective cohort study for survival rate in patients with advanced hepatocellular carcinoma receiving radiotherapy or palliative care 
The Korean Journal of Hepatology  2011;17(3):189-198.
This study was conducted to investigate the assessment of treatment efficacy of radiotherapy (RT) and other therapeutic modalities compared with palliative care only for treatment with advanced hepatocellular carcinoma (HCC).
From 2002 to 2010, based on the case of 47 patients with advanced HCC, we have investigated each patients' Child-Pugh's class, ECOG performance, serum level of alpha fetoprotein and other baseline characteristics that is considered to be predictive variables and values for prognosis of HCC. Out of overall patients, the 29 patients who had received RT were selected for one group and the 18 patients who had received only palliative care were classified for the other. The analysis in survival between the two groups was done to investigate the efficacy of RT.
Under the analysis in survival, the mean survival time of total patients group was revealed between 30.1 months and 45.9 months in RT group, while it was 4.8 months in palliative care group, respectively. In the univariate analysis for overall patients, there were significant factors which affected survival rate like as follows: ECOG performance, Child-Pugh's class, the tumor size, the type of tumor, alpha fetoprotein, transarterial chemoembolization, and RT. The regressive analysis in multivariate Cox for total patients. No treatment under radiotherapy and high level of Child-Pugh's class grade were independent predictors of worse overall survival rate in patients. In contrast, for the subset analysis of the twenty-nine patients treated with radiotherapy, the higher serum level of alpha fetoprotein was an independent predictors of worse overall survival rate in patients.
We found that the survival of patients with advanced HCC was better with radiotherapy than with palliative care. Therefore, radiotherapy could be a good option for in patients with advanced HCC.
PMCID: PMC3304653  PMID: 22102385
Hepatocellular carcinoma; Radiotherapy; Survival rate; Alpha-fetoprotein; Child-Pugh class
11.  Efficacy of Initial Treatment with Clevudine in Naive Patients with Chronic Hepatitis B 
Clevudine, a pyrimidine nucleoside analogue, has potent antiviral effects in patients with chronic viral hepatitis B (CHB). We report the efficacy of initial treatment with clevudine in naïve patients with CHB living in Daejeon and Chungcheong Province, South Korea.
One hundred five adults with CHB were administered 30 mg of clevudine per day for an average of 51 weeks. We evaluated viral markers and liver biochemistry retrospectively every 3 months.
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA before the treatment were 184 ± 188 IU/L, 150 ± 138 IU/L, and 7.1 ± 1.2 log copies/mL, respectively. Undetectable rates (< 60 IU/mL) of DNA were 36.2%, 68.9%, 83.6%, 76.2%, and 75.8% at 12, 24, 36, 48, and 60 weeks, respectively. Seroconversion rates were 9.1%, 13.6%, 24.6%, 26.5%, and 26.1% and ALT normalization rates were 64.5%, 78.1%, 87.9%, 90.0% at 12, 24, 36, and 48 weeks, respectively. Six patients (5.7%) had a viral breakthrough.
Clevudine is a useful drug in the initial treatment of patients with CHB, with a potent antiviral effect and low incidence of viral breakthrough.
PMCID: PMC2997965  PMID: 21179274
Clevudine; Drug resistance; HBV seroconversion; Hepatitis B, chronic
12.  Distal Cholangiocarcinoma with Gastric Metastasis Mimicking Early Gastric Cancer 
Gut and Liver  2009;3(3):222-225.
We report an unusual case of distal cholangiocarcinoma with gastric metastasis mimicking early gastric cancer. A 67-year-old woman presented with a 4-month history of abdominal pain after eating. Computed tomography showed a malignant tumor of the common bile duct located just above the intrapancreatic segment, and endoscopy revealed a 2-cm, flat, elevated lesion with convergence of the surrounding folds, situated at the gastric angle. Based on the endoscopic biopsy results, an adenocarcinoma, thought to be an early gastric cancer, was diagnosed. The patient underwent Whipples's operation. Histopathological findings showed that the adenocarcinomatous tissue was clearly demarcated and infiltrated the gastric mucosa and submucosa, leaving the gastric superficial mucosa intact. Both tumors showed similar pathological features and were positive for cytokeratin (CK)-19 and CK-7. These finding suggest distal cholangiocarcinoma with gastric metastasis.
PMCID: PMC2852712  PMID: 20431751
Cholangiocarcinoma; Stomach; Metastasis
13.  Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey 
AIM: To investigate prevalence of Clonorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea.
METHODS: Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire.
RESULTS: Of 3080 patients with gastrointestinal diseases, 396 (12.9%) had clonorchiasis and 1140 patients (37.2%) had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 (20.9%) patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than non-infected patients [34/396 (8.6%) vs 145/2684 (5.4%), P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation (P = 0.008). Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis.
CONCLUSION: Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.
PMCID: PMC2653299  PMID: 19115472
Clonorchis sinensis; Epidemiology; Cholangiocarcinoma; Korea; Multicenter study; Clonorchiasis
14.  Amiodarone-induced Hepatitis and Polyneuropathy 
Amiodarone chlorhydrate is a diiodated benzofuran derivative, and it is used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone, and symptomatic hepatic dysfunction occurs in fewer than 1% of the patients taking amiodarone. Cirrhosis is a rare complication that's been confirmed in 12 cases. Peripheral neuropathy occurs in 10% of patients taking aminodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity and peripheral neurotoxicity. A 75 year old man with normal liver function was given amiodarone for treating his atrial fibrillation and heart failure. He developed nausea, vomiting, muscle weakness and wasting after 17.8 months therapy with amiodarone (400 mg orally once per day). Liver biopsy showed the presence of foam cells in the hepatic sinusoids and Mallory bodies in the periportal hepatocytes on light microscopy. Sural nerve biopsy showed demyelination, and nerve conduction studies showed mixed sensorimotor polyneuropathy. These observations show the necessity of monitoring the hepatic function and conducting neurologic examination of the patients treated with amiodarone.
PMCID: PMC2687697  PMID: 17939344
Amiodarone; Hepatitis; Polyneuropathy
15.  Association between Levels of Serum Ferritin and Bone Mineral Density in Korean Premenopausal and Postmenopausal Women: KNHANES 2008–2010 
PLoS ONE  2014;9(12):e114972.
As women go through menopause, serum estrogen decreases and ferritin increases. Decreased serum estrogen is well known to cause detrimental effects on bone health; however, data on the associations of serum ferritin with BMD before and after menopause are still lacking. Therefore, this study aimed to investigate the association between serum ferritin levels and BMD in premenopausal and postmenopausal Korean women.
This study was performed using data from the 2008–2010 Korean National Health and Nutrition Examination Survey, including 7300 women (4229 premenopausal and 3071 postmenopausal). BMD was measured using dual X-ray absorptiometry at the femur and the lumbar spine, and serum ferritin levels were measured by chemiluminescent immunoassay.
Median serum ferritin levels in postmenopausal women were higher than those in premenopausal women despite the same age ranges. Serum ferritin levels were only significantly correlated with BMD on the lumbar spine (β = −0.189, p-value = 0.005) in premenopausal women after adjusting confounding factors. Additionally, BMD on the lumbar spine had tended to decrease as serum ferritin quartiles increase (P for trend = 0.035) in premenopausal women after adjusting confounding factors. On the other hand, there were no significant associations between serum ferritin levels and BMD on the total femur and, femur neck in premenopausal women, and BMD on the total femur, femur neck, and lumbar spine in postmenopausal women.
Increased serum ferritin levels were significantly associated with BMD in premenopausal women, particularly on the lumbar spine, but not in postmenopausal women.
PMCID: PMC4270774  PMID: 25522357
16.  Prevalence of Metabolic Syndrome Is Higher among Non-Obese PCOS Women with Hyperandrogenism and Menstrual Irregularity in Korea 
PLoS ONE  2014;9(6):e99252.
Hyperandrogenism (HA) has been linked with several components of metabolic syndrome (MetS). Few studies in Asian women have evaluated the important risk factors for and prevalence of MetS according to PCOS subtype. In this study, we investigated differences in metabolic parameters and the prevalence of MetS in two major phenotypic subgroups of PCOS in Korea. Furthermore, we investigated the relationship between HA-associated parameters and MetS.
Materials and Methods
This cross-sectional observational study was conducted from May 2010 to December 2011 in Korea. A total of 837 females with PCOS, aged 15–40, were recruited from Departments of Obstetrics and Gynecology at 13 hospitals. Of those, 700 subjects with either polycystic ovaries (PCO)+HA+oligomenorrhea/amenorrhea (O) or PCO+O were eligible for this study. MetS was diagnosed according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines and the International Diabetes Federation (IDF) criteria.
MetS was more prevalent in the PCO+HA+O group (19.7%) than in the PCO+O (11.9%) group. There were statistically significant trends for an increased risk of MetS in the PCO+HA+O group compared to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk of MetS was not different in obese patients. Multivariate logistic regression analysis showed that high free androgen index and low sex hormone-binding globulin were significantly associated with MetS in non-obese women with PCOS, with odds ratios of 4.234 (95% CI, 1.893–9.474) and 4.612 (95% CI, 1.978–10.750), respectively. However, no associations were detected between MetS and SHBG and FAI in obese PCOS subjects.
Our results indicate that HA and its associated parameters (FAI and SHBG) are significantly associated with MetS in non-obese PCOS subjects, whereas this association was not observed in obese subjects.
PMCID: PMC4047097  PMID: 24901345
17.  Satisfaction and health-related quality of life in women with heavy menstrual bleeding; results from a non-interventional trial of the levonorgestrel-releasing intrauterine system or conventional medical therapy 
To evaluate the patient satisfaction and health related quality of life (HRQoL) for levonorgestrel-releasing intrauterine system (LNG-IUS) versus conventional medical treatments ([CMTs] combined oral contraceptives, oral progestins, and antifibrinolytics, alone or in combination) in Asian women with heavy menstrual bleeding (HMB).
Patients and methods
A total of 647 patients diagnosed with HMB were recruited to this non-interventional study from the eight participating countries in Asia. Patient satisfaction was recorded at the last visit (at 12 months or premature discontinuation). At each visit (at 3, 6, and 12 months), patients completed the menorrhagia multi-attribute scale (MMAS) to assess HRQoL.
A total of 83.5% of patients on the LNG-IUS were “very satisfied” or at least “satisfied” with the therapeutic effect of HMB treatment, compared with 59.2% of patients with CMTs (P<0.05). The mean (± standard deviation) MMAS score increased from 41.4±24.5 to 87.7±21.4 in the LNG-IUS arm, and from 44.1±24.9 to 73.1±25.3 in the CMTs arm. This increase was significantly higher in patients on the LNG-IUS, as compared with those on CMTs (P<0.05). The improvement in HRQoL in both treatment groups correlated with the body mass index of the patient, with larger improvement obtained in women with a higher body mass index.
The majority of women using the LNG-IUS or CMTs for HMB were satisfied with their treatment, and both treatment modalities were associated with significant improvements in HRQoL over time. The improvement was greater with the LNG-IUS, compared with CMTs.
PMCID: PMC4043813  PMID: 24920936
HRQoL; MMAS; menorrhagia; tranexamic acid; dysfunctional uterine bleeding
18.  Association between Vitamin D Status and Risk of Metabolic Syndrome among Korean Postmenopausal Women 
PLoS ONE  2014;9(2):e89721.
This study aimed to investigate the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome along with its associated risk factors in Korean postmenopausal women. This study was performed using data from the KNHANES 2008–2010 study and included 4,364 postmenopausal Korean women. Clinical and other objective characteristics, seasonality, and presence of metabolic syndrome with its five components were evaluated and correlated with the serum levels of 25(OH)D. Although no statistically significant associations were observed between the levels of serum 25(OH)D and the prevalence of metabolic syndrome, the adjusted OR for elevated blood pressure, elevated triglycerides (TGs), and reduced high-density lipoprotein cholesterol (HDL-C) showed tendency to decrease sequentially as tertiles of serum 25(OH)D levels increased (p for trends  = 0.066, 0.043, and 0.010, respectively). Women in the highest tertile of serum 25(OH)D showed a significant decrease in the prevalence of elevated blood pressure, elevated TGs, and reduced HDL-C as compared with those in the lowest tertile of serum 25(OH)D (p = 0.020, 0.014, and 0.002, respectively). Based on these results, we consider that adequate serum levels of 25(OH)D in Korean postmenopausal women may not entirely indicate a lower risk of developing metabolic syndrome. However, adequate serum levels of 25(OH)D are significantly associated with a decrease in elevated blood pressure, elevated TGs, and reduced HDL-C levels in postmenopausal women.
PMCID: PMC3931824  PMID: 24586986
19.  A Case of Liver Fibrosis with Splenomegaly after Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer 
Journal of Korean Medical Science  2013;28(12):1835-1838.
Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and α-smooth muscle actin (α-SMA) were conducted with control group. The immunohistochemical stains for CD31 and α-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.
PMCID: PMC3857384  PMID: 24339718
Liver Cirrhosis; Splenomegaly; Oxaliplatin
20.  Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study 
Clinical and molecular hepatology  2013;19(2):165-172.
Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.
130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.
Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment.
ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
PMCID: PMC3701849  PMID: 23837141
Hepatitis B; Carnitine; Entecavir
22.  A Rare Case of a Signet Ring Cell Carcinoma of the Colon Mimicking a Juvenile Polyp 
Gut and Liver  2012;6(1):129-131.
Primary signet ring cell carcinoma (SRC) of colon at early stage is quite rare. Only 26 cases were reported until now. We report an early stage of primary SRC which was misdiagnosed as a juvenile polyp and treated with polypectomy followed by surgical resection. A 21-year-old male was administered for hematochezia. Abdominopelvic enhanced computed tomography revealed a polyp with active bleeding at the proximal rectum just below the rectosigmoid junction. Colonoscopy examination revealed a colon polyp with 0.5 cm sized head. Polypectomy was performed with snare and the polyp was completely removed. Biopsy revealed SRC. Surgical resection was also performed and there were no residual tumor or lymph node metastasis in the surgical specimen.
PMCID: PMC3286732  PMID: 22375184
Signet ring cell carcinoma; Early colon cancer; Juvenile polyp; Polypectomy
23.  The Effects of Lifestyle Modification on Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: A Prospective Observational Study 
Gut and Liver  2011;5(4):472-477.
Although notably common, irritable bowel syndrome (IBS) has no specific cure. Lifestyle modification may be as important as medication; however, few studies support the effectiveness of such modifications. We performed this observational study of IBS patients to explore further the role of lifestyle changes in treatment.
This study included 831 men who enlisted in 2010 as armed surgeon cadets and 85 women who concurrently entered the Armed Forces Nursing Academy. Of these 916 participants, 89 were diagnosed with IBS using the Rome III criteria. Subjective changes in bowel habits, quality of life, pain, stress, stool frequency and stool consistency were surveyed before and after 9 weeks of army training. We evaluated the lifestyle risk factors that impacted improvement in IBS symptoms by comparing those who responded to lifestyle modification (the responding group) to those who did not respond (the nonresponding group).
More than half of the participants (63%) reported that their symptoms improved after training. The quality of life and levels of pain and stress significantly improved after military training. Initial stress levels before military training and smoking history affected IBS symptom improvement.
Lifestyle modification may be effective in managing IBS patients.
PMCID: PMC3240791  PMID: 22195246
Irritable bowel syndrome; Life style; Smoking; Stress
24.  Clinical Outcomes of Endoscopic Submucosal Dissection for Undifferentiated or Submucosal Invasive Early Gastric Cancer 
Clinical Endoscopy  2011;44(2):116-122.
Early gastric cancer (EGC) that is undifferentiated or shows submucosal invasion has not been generally accepted as an indication for endoscopic treatment. But recently, experiences with endoscopic submucosal dissection (ESD) for undifferentiated EGC or submucosal invasive (SM) EGC have increased. The aim of this study was to evaluate clinical outcomes of ESD for EGC with undifferentiation or submucosal invasion.
Between August 2005 and August 2009, among 210 EGCs treated using ESD at our hospital, 18 lesions were diagnosed as undifferentiated gastric cancer and 41 as SM gastric cancer. A retrospective analysis was done on the medical records of these patients.
Mean follow-up periods were 19.39±11.2 months. During the follow-up period, local recurrence was noted in 4 lesions. Local recurrence rates of the EGC groups (group 1, mucosal cancer with undifferentiation; group 2, SM cancer with differentiation; group 3, SM cancer with undifferentiation) were 10%, 4.5%, and 50%, respectively. Groups 1 and 2 were not significantly different in local recurrence rates compared to the mucosal cancer with differentiation group (p=0.061, p=0.125, respectively). The undifferentiated EGC group was significantly lower in curability using ESD than the differentiated EGC group (55.6% vs. 89.6%, p=0.000). The curability of the SM EGC group was lower than the mucosal EGC group (36.6% vs. 98.9%).
Complete resection using ESD is difficult in undifferentiated and SM gastric cancers. SM cancer with undifferentiation should be treated immediately by salvage operation. For mucosal cancer with undifferentiation or SM cancer with differentiation, one should consider careful short-term follow-up.
PMCID: PMC3363057  PMID: 22741122
Endoscopic submucosal dissection; Undifferentiated early gastric cancer; Submucosal invasive early gastric cancer
25.  A case of concomitant Gilbert's syndrome and hereditary spherocytosis 
The Korean Journal of Hepatology  2010;16(3):321-324.
We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilbert's syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene.
PMCID: PMC3304593  PMID: 20924216
Hereditary spherocytosis; Gilbert's syndrome; UGT1A1

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