Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

BACKGROUND/AIMS: In addition to the globally endorsed Barcelona Clinic Liver Cancer (BCLC) staging system, other algorithms or staging systems have been developed, including the Hong Kong Liver Cancer (HKLC) staging system. This study aimed to validate the HKLC staging system relative to the BCLC staging system for predicting survival for hepatocellular carcinoma (HCC) patients in Korea. METHODS: From 2004 to 2013, 2,571 patients newly diagnosed with HCC were consecutively enrolled at three Korea University medical centers. RESULTS: Both staging systems differentiated survival well (p < 0.001). However, 1-year and 3-year survival were predicted better using the HKLC system than the BCLC system (area under the receiver operating characteristic curve: 0.869 vs 0.856 for 1 year, p=0.002; 0.841 vs 0.827 for 3 years, p=0.010). In hypothetical survival curves, the HKLC system exhibited better median overall survival than the BCLC system (33.1 months vs 19.2 months). In evaluations of prognosis according to either BCLC or HKLC treatment guidelines, risk of death was reduced in the group following only HKLC guidelines compared with the group following only BCLC guidelines (hazard ratio, 0.601; 95% confidence interval, 0.443 to 0.816; p=0.001). CONCLUSIONS: Although both staging systems predicted and discriminated HCC prognoses well, the HKLC system showed more encouraging survival benefits than the BCLC system.
Academic Medical Centers ; Carcinoma, Hepatocellular ; Hong Kong ; Humans ; Korea ; Liver Neoplasms ; Liver ; Neoplasm Staging ; Prognosis ; ROC Curve

BACKGROUND/AIMS: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. METHODS: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary objectives included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation. RESULTS: In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P < 0.0001), and week 240 (95.0% vs. 47.6%, P < 0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P < 0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P < 0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. CONCLUSIONS: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.
Alanine Transaminase ; DNA ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic* ; Hepatitis* ; Hepatitis, Chronic* ; Humans ; Incidence ; Lamivudine*

OBJECTIVE: This study aimed to examine clinical practice patterns in the management of pregnant women admitted with threatened preterm labor (TPL) in Korea. METHODS: Data from women admitted with a diagnosis of TPL were collected from 22 hospitals. TPL was defined as regular uterine contractions with or without other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and cervical changes. Data on general patient information, clinical characteristics at admission, use of tocolytics, antibiotics, and corticosteroids, and pregnancy outcomes were collected using an online data collections system. RESULTS: A total of 947 women with TPL were enrolled. First-line tocolysis was administered to 822 (86.8%) patients. As a first-line tocolysis, beta-agonists were used most frequently (510/822, 62.0%), followed by magnesium sulfate (183/822, 22.3%), calcium channel blockers (91/822, 11.1%), and atosiban (38/822, 4.6%). Of the 822 women with first-line tocolysis, second-line tocolysis were required in 364 (44.3%). Of 364 with second-line, 199 had third-line tocolysis (37.4%). Antibiotics were administered to 29.9% of patients (284/947) with single (215, 22.7%), dual (26, 2.7%), and triple combinations (43, 4.5%). Corticosteroids were administered to 420 (44.4%) patients. Betamethasone was administered to 298 patients (71.0%), and dexamethasone was administered to 122 patients (29.0%). CONCLUSION: Practice patterns in the management of TPL in Korea were quite various. It is needed to develop standardized practice guidelines for TPL management.
Adrenal Cortex Hormones ; Anti-Bacterial Agents ; Back Pain ; Betamethasone ; Calcium Channel Blockers ; Dexamethasone ; Diagnosis ; Female ; Humans ; Korea ; Magnesium Sulfate ; Muscle Cramp ; Obstetric Labor, Premature* ; Physician's Practice Patterns ; Pregnancy ; Pregnancy Outcome ; Pregnant Women ; Premature Birth ; Retrospective Studies* ; Tocolysis ; Tocolytic Agents ; Uterine Contraction ; Vaginal Discharge

Gestational diabetes mellitus (GDM) is a strong predictor of postpartum prediabetes and transition to overt type 2 diabetes (T2DM). Although many reports indicate that low magnesium is correlated with deteriorated glucose tolerance, the association between postpartum serum magnesium level and the risk for T2DM in women with a history of GDM has not been evaluated. We analyzed postpartum serum magnesium levels and development of prediabetes and T2DM in women with prior GDM according to American Diabetes Association (ADA) criteria using the Korean National Diabetes Program (KNDP) GDM cohort. During a mean follow-up of 15.6+/-2.0 months after screening, 116 women were divided into three groups according to glucose tolerance status. Ultimately, eight patients (6.9%) were diagnosed with T2DM, 59 patients (50.9%) with prediabetes, and 49 patients (42.2%) with normal glucose tolerance (NGT) after follow-up. The T2DM group had the lowest serum magnesium level (0.65 [0.63-0.68] mM/L) in the postpartum period, but there was no significant difference between the prediabetes group (0.70 [0.65-0.70] mM/L) and the NGT group (0.70 [0.65-0.70] mM/L) (P=0.073) Multiple logistic regression analysis showed that postpartum HOMA-IR was a significant predictor of both prediabetes and T2DM. Moreover, we found that postpartum serum magnesium level was also a possible predictor for T2DM development. Serum magnesium level in the postpartum period may be a possible predictor for T2DM development in women with a history of GDM.
Adult ; Blood Glucose ; Cohort Studies ; Diabetes Mellitus, Type 2/*blood/diagnosis ; Diabetes, Gestational/*blood ; Female ; Glucose Intolerance/*blood ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; Magnesium/*blood ; Postpartum Period/*blood ; Prediabetic State/diagnosis ; Pregnancy ; Prospective Studies ; Republic of Korea ; Risk Factors

Evidence suggests that diabetes mellitus (DM) is associated with idiopathic pulmonary fibrosis (IPF). According to the new IPF guidelines, high-resolution computed tomography (HRCT) is an essential means of diagnosing IPF. We investigated the relationship between IPF and DM in patients treated between 2003 and 2007. Newly diagnosed IPF patients in large university teaching hospitals in Korea were enrolled from January 2003 to December 2007. We retrospectively analyzed 1,685 patients using the interstitial lung disease (ILD) registry. In total, 299 IPF patients (17.8%) also had DM. The mean age of our subjects was 68.0 +/- 9.4 yr. HRCT showed significantly more reticular and honeycomb patterns in IPF patients with DM than in IPF patients without DM (P = 0.014, P = 0.028, respectively). Furthermore, significantly higher incidences of hypertension, cardiovascular diseases, and other malignancies (except lung cancer) were found in IPF patients with DM than in IPF patients without DM. In conclusion, IPF patients with DM are more likely to have the usual interstitial pneumonia (UIP) pattern, including reticular and honeycomb patterns, on HRCT than are those without DM.
Aged ; Cardiovascular Diseases/epidemiology/etiology ; Diabetes Mellitus, Type 2/*complications ; Female ; Humans ; Hypertension/epidemiology/etiology ; Idiopathic Pulmonary Fibrosis/complications/*diagnosis/radiography ; Incidence ; Male ; Middle Aged ; Neoplasms/epidemiology/etiology ; Registries ; Republic of Korea/epidemiology ; Retrospective Studies ; Tomography, X-Ray Computed

BACKGROUND/AIMS: The findings of several recent studies suggest that antinuclear antibodies (ANAs) are frequently detected in patients with acute hepatitis A (AHA). However, the clinical significance of a positive ANA test remains uncertain. This study was performed to evaluate the clinical significance of ANAs in AHA patients. METHODS: All patients admitted with AHA were consecutively enrolled in this study. An ANA assay was performed by indirect immunofluorescence during hospitalization. ANA positivity was defined as an ANA titer > or =1:80. The peak international normalized ratio (INR), peak alanine aminotransferase (ALT) and peak bilirubin levels were assessed over the duration of the hospitalization, and the incidence of AHA complications was evaluated. RESULTS: A total of 422 patients were enrolled in this study (age, 31+/-7 years), of which 260 (61.6%) were men. ANAs were detected in 179 AHA patients (42.4%). The proportion of ANA-positive patients varied significantly with AHA status on the day of the ANA assay (4.7% during the prodromal period vs 52.1% during the icteric or recovery period, p<0.001) and sex (56.2% in women vs 33.8% in men, p<0.001). The ANAs became undetectable in all ANA-positive patients within 3 months. The incidence of complications, including mortality, fulminant hepatic failure, renal dysfunction, relapse, and cholestatic hepatitis, did not differ significantly between ANA-positive and ANA-negative patients. CONCLUSIONS: ANAs were detected frequently and transiently in patients with AHA, especially after their peak-ALT day. The presence of ANAs may not be associated with the clinical outcome of AHA, but simply with AHA status on the ANA assay day.
Alanine Transaminase ; Antibodies, Antinuclear ; Bilirubin ; Female ; Fluorescent Antibody Technique, Indirect ; Hepatitis ; Hepatitis A ; Hospitalization ; Humans ; Incidence ; International Normalized Ratio ; Liver Failure, Acute ; Male ; Prodromal Symptoms ; Recurrence

BACKGROUND AND OBJECTIVES: Recent studies have reported that vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha are up-regulated in BRAF(V600E)-positive papillary thyroid carcinoma (PTC). We investigated whether papillary thyroid microcarcinomas (PTMCs) also exhibited increased expression of VEGF and HIF-1alpha. In addition, we analyzed the relationship between BRAF(V600E) mutation and clinicopathological parameters, as well as HIF-1alpha expression in PTMC. MATERIALS AND METHODS: We retrospectively selected 225 patients with PTMC. Immunohistochemical staining for HIF-1alpha and VEGF was performed using paraffinembedded PTMC tissue microarrays. BRAF(V600E) mutation status was analyzed by dideoxy sequencing. RESULTS: PTMCs larger than 0.5 cm tend to be related to aggressive clinicopathological features such as thyroid capsular invasion (p=0.023) and bilaterality (p=0.047). Immunoreactivity to HIF-1alpha (20.7%) and VEGF (30.2%) was more prominent in PTMCs as compared to normal follicular cells. However, HIF-1alpha and VEGF expression was not correlated with clinicopathological features. BRAF(V600E) mutation was found in 70.7% (159/225) of the PTMC cases. PTMCs harboring the BRAF(V600E) mutation exhibited larger tumor sizes as compared to PTMCs without the BRAF(V600E) mutation (p=0.038). However, BRAF(V600E) mutation status did not correlate with the expression of HIF-1alpha (p=0.623) or VEGF (p=0.990). CONCLUSION: HIF-1alpha and VEGF were more frequently detected in PTMCs as compared to normal thyroid tissues. However, BRAF(V600E) mutation status was not correlated with the expression of HIF-1alpha or VEGF in PTMCs.
Carcinoma ; Carcinoma, Papillary ; Humans ; Hypoxia-Inducible Factor 1 ; Proto-Oncogene Proteins B-raf ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms ; Vascular Endothelial Growth Factor A

BACKGROUND: Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated. METHODS: We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naive type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels. RESULTS: HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group. CONCLUSION: The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naive Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.
Body Weight ; Diabetes Mellitus, Type 2 ; Diarrhea ; Fasting ; Glucose ; Humans ; Hyperglycemia ; Hypoglycemia ; Hypoglycemic Agents ; Metformin ; Plasma ; Sulfonylurea Compounds ; Thiazolidinediones