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Biologics are increasingly vital medicines that significantly reduce morbidity as well as mortality, yet access continues to be an issue even in apparently wealthy countries, such as the USA. While patient access is expected to improve with the introduction of biosimilars, misperceptions in a significant part based on terminology continue to make a sustained contribution by biosimilars difficult. Patients are and will continue to suffer needlessly if biosimilars continue to be impugned. Consequently, it is increasingly urgent that semantics are clarified, and in particular, the implication that interchangeable biologics are better biosimilars dismissed. This paper distinguishes between the real differences between biologics that matter clinically to patients and discusses the actual meaning of a US Food and Drug Administration designation of interchangeability for a biosimilar product. This will help highlight where there is need for further Food and Drug Administration education and which stakeholders likely need that education the most.

Background/Aims: This study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared to no screening in the Korean population from societal and healthcare system perspectives.Methods: A published decision-tree plus Markov model was used to compare the expected costs and quality-adjusted life years (QALY) between one-time universal HCV screening and no screening in the population aged 40–65 years using the National Health Examination (NHE) program. Input parameters were obtained from analyses of the National Health Insurance claims data, Korean HCV cohort data, or from the literature review. The population aged 40–65 years was simulated in a model spanning a lifetime from both the healthcare system and societal perspectives, which included the cost of productivity loss due to HCV-related deaths. The incremental cost-effectiveness ratio (ICER) between universal screening and no screening was estimated.Results: The HCV screening strategy had an ICER of $2,666/QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared to no screening. In various sensitivity analyses, the most influential parameters on cost-effectiveness were the antibodies to HCV (anti-HCV) prevalence, screening costs, and treatment acceptance; however, all ICERs were consistently less than the threshold. If the anti-HCV prevalence was over 0.18%, screening could be cost-effective.Conclusions: One-time universal HCV screening in the Korean population aged 40–65 years using NHE program would be highly cost-effective from both healthcare system and societal perspectives.

Background/Aims: The risk factors for the development of primary biliary chol angitis (PBC) is unclear. This study aimed to investigate the risk factors associated with PBC in Korea through a questionnaire survey. Methods: Consecutively enrolled 103 PBC patients from six referral hospitals and 100 age- and sex-matched community controls participated in this study. A stan dardized questionnaire survey including demographics, lifestyle, individual and familial medical history and reproductive history was prospectively collected and analyzed. Results: The PBC patients had a mean age of 58.3 years and a female proportion of 86.4%. The age- and sex-matched controls had a similar educational level and economic status to the PBC patients. Among the lifestyle factors, the multivari able analysis showed smoking including both first-hand and second-hand (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.06 to 3.93), history of autoimmune diseases (OR, 2.46; 95% CI, 1.06 to 6.35), and family history of PBC (OR, 17.76; 95% CI, 1.77 to 2,418.74) were significantly associated with PBC, whereas alcohol intake was negatively associated with PBC. Among reproductive factors, the number of induced abortions was significantly associated with PBC, while the number of full-term deliveries was negatively associated with PBC. Conclusions: A family history of PBC, accompanying autoimmune diseases, and smoking were significantly associated with PBC. More induced abortions and less full-term deliveries were associated with PBC in women. In contrast, mild to moderate alcohol intake was negatively associated with PBC. Further studies are warranted to validate the results of this study and to search for clues about the pathogenesis of PBC.

Background/Aim: This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea. Methods: A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted. Results: The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naive and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event. Conclusions: EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.

Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

Lower extremity deep vein thrombosis (DVT) is a serious medical condition that can result in local pain and gait disturbance. DVT progression can also lead to death or major disability as a result of pulmonary embolism, postthrombotic syndrome, or limb amputation. However, early thrombus removal can rapidly relieve symptoms and prevent disease progression. Various endovascular procedures have been developed in the recent years to treat DVT, and endovascular treatment has been established as one of the major therapeutic methods to treat lower extremity DVT. However, the treatment of lower extremity DVT varies according to the disease duration, location of affected vessels, and the presence of symptoms. This article reviews and discusses effective endovascular treatment methods for lower extremity DVT.

The association between hepatitis virus infection and Parkinson's disease remains controversial. To determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are associated with an increased risk of Parkinson's disease in Korean aged ≥40 years, we completed a population-based prospective study including patients without infections and those with HBV, HCV and HBV/HCV infections from 2005 to 2015. We used the International Classification of Diseases 10th Revision to identify Parkinson's disease (G20) and chronic hepatitis C virus (B18.2) and chronic hepatitis B virus infections (B18.0 or B18.1). To identify Parkinson's disease risk, competing risk analysis adjusted for age, sex, comorbidities and death was performed. Overall, 1 010 317 patients (358 052, noninfection; 488 990, hepatitis B; 144 459 hepatitis C; and 18 680 hepatitis B/C) were included. The incidence density of Parkinson's disease per 10 000 person-years was highest in the hepatitis C group (8.0), followed by the hepatitis B/C (6.8) and hepatitis B (5.0) groups. Hypertension, ischaemic heart disease, epilepsy, stroke and depressive disorder increased the hazard of Parkinson's disease in all groups. The adjusted hazard ratios were 1.25 (95% confidence interval: 1.17-1.35), 1.39 (95% confidence interval: 1.27-1.52) and 1.46 (95% confidence interval: 1.14-1.85) in the HBV, HCV, and HBV/HCV groups, respectively. Our findings suggest that adult patient of 40 years and older with HBV and HCV infections should be monitored for signs of Parkinson's disease so that early intervention and accurate treatment can be provided for minimizing the development and consequences of Parkinson's disease.

This study aimed to evaluate the efficiency of imaging features and texture analysis (TA) based on baseline rectal MRI for the early prediction of therapeutic response to neoadjuvant chemoradiotherapy (nCRT) and tumor recurrence in patients with locally advanced rectal cancer (LARC). Consecutive patients with LARC who underwent rectal MRI between January 2014 and December 2015 and surgical resection after completing nCRT were retrospectively enrolled. Imaging features were analyzed, and TA parameters were extracted from the tumor volume of interest (VOI) from baseline rectal MRI. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal TA parameter cutoff values to stratify the patients. Logistic and Cox regression analyses were performed to assess the efficacy of each imaging feature and texture parameter in predicting tumor response and disease-free survival. In total, 78 consecutive patients were enrolled. In the logistic regression, good treatment response was associated with lower tumor location (OR = 13.284, p = 0.012), low Conv_Min (OR = 0.300, p = 0.013) and high Conv_Std (OR = 3.174, p = 0.016), Shape_Sphericity (OR = 3.170, p = 0.015), and Shape_Compacity (OR = 2.779, p = 0.032). In the Cox regression, a greater risk of tumor recurrence was related to higher cT stage (HR = 5.374, p = 0.044), pelvic side wall lymph node positivity (HR = 2.721, p = 0.013), and gray-level run length matrix_long-run low gray-level emphasis (HR = 2.268, p = 0.046). Imaging features and TA based on baseline rectal MRI could be valuable for predicting the treatment response to nCRT for rectal cancer and tumor recurrence. • Imaging features and texture parameters of T2-weighted MR images of rectal cancer can help to predict treatment response and the risk for tumor recurrence. • Tumor location as well as conventional and shape indices of texture features can help to predict treatment response for rectal cancer. • Clinical T stage, positive pelvic side wall lymph nodes, and the high-order texture parameter, GLRLM_LRLGE, can help to predict tumor recurrence for rectal cancer.

OBJECTIVES: Injection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data on this topic are available in Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).METHODS: We used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of a questionnaire survey on lifetime risk factors for HCV infection were analyzed according to a self-reported history of injection drug use (PWID vs. non-PWID group).RESULTS: Among the 2,468 patients, 166 (6.7%) were in the PWID group, which contained younger patients (50.6±8.2 vs. 58.2±13.1 years) and a higher proportion of male (81.9 vs. 48.8%) than the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not significantly differ between the groups.CONCLUSIONS: As of 2019, PWID constituted a minority of HCV-infected people in Korea. The epidemiological characteristics, but not treatment uptake and outcomes, were different between the PWID and non-PWID groups. Therefore, active HCV screening and treatment should be offered to PWID in Korea.

The Republic of Korea has a high prevalence of hepatitis B virus (HBV) infection, and the policies concerning costly antiviral medication have been revised recently. However, in the past 10 years, no related research on costs has been conducted. The objective of this study was to estimate the economic burden of viral hepatitis B and determine the trend of changes in its costs between 2002 and 2015. Claims data from the National Health Insurance Service were used. To identify viral hepatitis B cases, the ICD-10th code B16, B17.0, B18.0 and B18.1 were used based on a primary diagnosis. This study was conducted from a societal perspective regarding both direct and indirect costs. Annual costs were adjusted for inflation by calculations based on the 2015 costs. The number of patients with viral hepatitis B increased from 213 758 in 2002 to 342 672 in 2015. The total socio-economic costs increased from 127.1 million USD in 2002 to 459.1 million USD in 2015, mainly due to the increase in pharmaceutical costs, which accounted for the largest proportion of total costs since 2009-220.5 million USD in 2015, which was ~15 times higher than that in 2002. The healthcare costs for viral hepatitis B accounted for 0.13% of the national health expenditure in 2002, increasing to 0.31% in 2015. The economic burden of viral hepatitis B has increased in the Republic of Korea. It is therefore essential to reduce the healthcare costs of HBV infection by establishing an effective management policy.

Significance Septic shock commonly leads to multiorgan injury both directly via tissue inflammation and secondarily via hypoperfusion, but both can result in mitochondrial N-formyl peptide (mtFP) release into the circulation. However, no studies have evaluated the role of circulating mtFPs during septic shock. We found that a relatively high plasma nicotinamide adenine dinucleotide dehydrogenase subunit-6 (the most potent human mtFP) level was independently associated with the development of secondary infection in patients with septic shock and that the increased susceptibility to secondary infection is partly attributed to the suppression of polymorphonuclear leukocyte (PMN) chemotaxis by mtFP occupancy of formyl peptide receptor-1. Incorporation of these findings into therapeutic strategies may improve clinical outcomes in septic shock patients by preventing PMN chemotactic anergy., Secondary infections typically worsen outcomes of patients recovering from septic shock. Neutrophil [polymorphonuclear leukocytes (PMNs)] migration to secondarily inoculated sites may play a key role in inhibiting progression from local bacterial inoculation to secondary infection. Mitochondrial N-formyl peptide (mtFP) occupancy of formyl peptide receptor-1 (FPR1) has been shown to suppress PMN chemotaxis. Therefore, we studied the association between circulating mtFPs and the development of secondary infection in patients with septic shock. We collected clinical data and plasma samples from patients with septic shock admitted to the intensive care unit for longer than 72 h. Impacts of circulating nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) upon clinical outcomes were analyzed. Next, the role of ND6 in PMN chemotaxis was investigated using isolated human PMNs. Studying plasma samples from 97 patients with septic shock, we found that circulating ND6 levels at admission were independently and highly associated with the development of secondary infection (odds ratio = 30.317, 95% CI: 2.904 to 316.407, P = 0.004) and increased 90-d mortality (odds ratio = 1.572, 95% CI: 1.002 to 2.465, P = 0.049). In ex vivo experiments, ND6 pretreatment suppressed FPR1-mediated PMN chemotactic responses to bacterial peptides in the presence of multiple cytokines and chemokines, despite increased nondirectional PMN movements. Circulating mtFPs appear to contribute to the development of secondary infection and increased mortality in patients with septic shock who survive their early hyperinflammatory phase. The increased susceptibility to secondary infection is probably partly mediated by the suppression of FPR1-mediated PMN chemotaxis to secondary infected sites.

Acute appendicitis is one of the most common causes of abdominal emergencies. We investigated the feasibility of a neural-network-based diagnosis algorithm of appendicitis by using computed tomography (CT) for patients with acute abdominal pain visiting the emergency room (ER). A neural-network-based diagnostic algorithm of appendicitis was developed and validated using CT data from three institutions who visited the ER with abdominal pain and underwent abdominopelvic CT. For input data, 3D isotropic cubes including the appendix were manually extracted and labeled as appendicitis or a normal appendix. A 3D convolutional neural network (CNN) was trained to binary classification on the input. For model development and testing, 8-fold cross validation was conducted for internal validation and an ensemble model was used for external validation. Diagnostic performance was excellent in both the internal and external validation with an accuracy larger than 90%. The CNN-based diagnosis algorithm may be feasible in diagnosing acute appendicitis using the CT data of patients visiting the ER with acute abdominal pain.

Background and aim For genotype 2 chronic hepatitis C (CHC), the efficacy and safety of sofosbuvir plus ribavirin therapy (SOF + RBV) was better than pegylated interferon plus ribavirin therapy (PR) at a greater drug cost. This study investigated the cost-effectiveness of SOF + RBV compared with PR for treatment-naive genotype 2 CHC in South Korea. Methods Using a decision analytic Markov model, a cost-effectiveness analysis comparing SOF + RBV with PR or no treatment for treatment-naive genotype 2 CHC was performed with probabilistic and deterministic sensitivity analyses from the payer's perspective in 2017. Three cohorts of patients aged 40-49, 50-59, and 60-69 years were simulated to progress through the fibrosis stages F0-F4 to end-stage liver disease, hepatocellular carcinoma, or death. Published and calculated data on the clinical efficacy of the regimen, health-related quality of life, costs, and transition probabilities were used. Results While the incremental cost-effectiveness ratio for PR was dominant over no treatment, the incremental cost-effectiveness ratios for SOF + RBV were $20 058 for the patients in their 40s, $19 662 for those in their 50s, and $22 278 for those in their 60s compared with PR. Probabilistic sensitivity analysis indicated an 89.0% probability for the SOF + RBV to be cost-effective at a willingness to pay of $29 754.4 (per-capita gross domestic product in 2017) for the patients in their 40s and 94.1% and 89.1% for the patients in their 50s and 60s, respectively. Conclusions The SOF + RBV is a cost-effective option for genotype 2 treatment-naive CHC patients, especially for the patients with liver cirrhosis in Korea.

Autoimmune pancreatitis (AIP) is a distinct subtype of pancreatitis, which is classified into type 1 and 2 based on the clinicopathological features. According to the international consensus diagnostic criteria, pancreas resection or core biopsy specimens are recommended to make an accurate histological evaluation. However, the usefulness of endoscopic ultrasonography (EUS) guided fine needle aspiration (FNA) for histological evaluation has also been reported. Furthermore, the simultaneous presentation of type 2 AIP and Crohn's disease (CD) is very rare, especially in the Asian population. Therefore, we herein report a case of type 2 AIP with CD, which was diagnosed using EUS guided FNA with a 22-gauge needle.

Background/Aims: This study aimed to describe the health-related quality of life (HRQoL) outcomes for Korean chronic hepatitis C patients and to investigate the impact of patient and virus-related factors on HRQoL. Methods: HRQoL was assessed in 235 hepatitis C virus (HCV)-infected patients from seven nationwide tertiary hospital, including those with liver cirrhosis and hepatocellular carcinoma (HCC), using the Shor-Form 36 (SF-36) version 2 and the European quality of life questionnaire-5 dimensions (EQ-5D-3L). Results: The SF-36 physical (48.8±8.3) and mental (46.2±11.7) component summary scores of the HCV-infected patients were below normal limits. Of the eight domains, general health, vitality, and mental health tended to show low scores. Patients with decompensated cirrhosis had the lowest HRQoL, while HCC and chronic hepatitis patients had similar HRQoL results. The EQ-5D index was low (0.848±0.145) in the HCV infected patients. Multivariable analysis showed age ≤65 years, high monthly family income (>$2,641), low comorbidity score, and sustained virologic response (SVR) were independently asso ciated with favorable HRQoL. Conclusions: HRQoL in Korean patients with chronic HCV infection was low and was affected by cirrhosis severity, SVR, and comorbidity as well as income, which had the strongest effect. Therefore, HRQoL may be improved by antiviral therapy with reasonable costs to prevent cirrhosis progression. (Gut Liver 2018;12:440-448)

Background/Aims: This study aimed to investigate the epidemiology of hepatitis C virus (HCV) infection in the Korean general population and the awareness and treatment status of HCV infection among anti-HCV-positive persons. Methods: We used data from the Korea National Health and Nutrition Examination Survey (KNHNES) collected between 2012 and 2016. All the participants aged ≥10 years in the KNHNES were tested for the anti-HCV antibody. Anti-HCV-positive persons were tested for HCV RNA and assessed for their awareness and treatment experience regarding HCV infection. Results: The prevalence of anti-HCV was 0.66% (95% confidence interval, 0.56% to 0.78%) among Koreans aged ≥10 years, representing an estimated 278,819 anti-HCV-positive persons, and 0.71% (95% confidence interval, 0.60% to 0.84%) among Koreans aged ≥20 years. The prevalence of anti-HCV increased with age and had significant geographic variation. The positive rate of HCV RNA in anti-HCV-positive persons was 33.5% and increased with age. The rate of HCV infection awareness was 15.2% (35/250) among anti- HCV-positive persons and 30.5% (18/59) among HCV RNApositive persons. Among the participants, 13.5% of HCV RNA-positive persons had been treated for HCV infection. Conclusions: The prevalence of anti-HCV among Koreans aged ≥20 years was 0.71%; one-third of anti-HCV-positive persons tested HCV RNA-positive. The awareness and treatment rates of HCV infection were low among HCV-infected persons. Therefore, active measures should be taken to diagnose and treat persons unaware of HCV infection. (Gut Liver 2020;14:644-651)

Background/Aims: Sofosbuvir (SOF)-based therapy has been used in Korean patients with chronic hepatitis C virus (HCV) infection since January 2016. This study aimed to investigate the real-life effectiveness and safety of SOF-based therapy in genotype 2 HCV infection. Methods: From January to December 2016, 458 genotype 2 HCV-infected patients who received ≥1 dose of SOF-based therapy were consecutively enrolled in seven tertiary hospitals. Sustained virologic response (SVR) rates and safety were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. Results: The mean age of the patients was 61.0 years; 183 (40%) were male, and 13.1% showed a high viral load (>6,000,000 IU/mL). Among the 378 treatment-naive patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatment-experienced patients, the SVR rates were 96.3% (ITT) and 98.7% (PP). Patients with a relatively high fibrosis-4 index score (>3.25) had similar SVR rates to those with a relatively low score (p=0.756). A total of 314 patients (68.6%) were treated with a reduced ribavirin dose at the prescriber’s discretion, but they showed similar SVR rates to those treated with the weight-based dose (ITT: 95.5% and 92.3%, PP: 97.4% and 96.3%, respectively). Adverse events were observed in 191 patients (41.7%), including 86 (18.8%) with anemia, but only one (0.2%) discontinued antiviral therapy due to nausea. Conclusions: SOF-based therapy showed high real-life efficacy and tolerability in Korean patients with genotype 2 chronic HCV infection, regardless of previous antiviral treatment experience and fibrosis score. A reduced ribavirin dose can be considered in this patient cohort. (Gut Liver 2020;14:775-782)

This study aimed to investigate the real-life effectiveness and safety of daclatasvir (DCV) and asunaprevir (ASV) combination therapy in Korean patients. We consecutively enrolled patients with genotype 1b hepatitis C virus (HCV) infection treated with at least one dose of DCV/ASV combination therapy in seven tertiary hospitals of South Korea. The sustained virologic response (SVR) rates and safety according to intention-to-treat (ITT) and per-protocol (PP) analyses were evaluated. Among the 526 enrolled patients, 91% showed negative (87%) or "undetermined" (4%) resistance-associated substitution (RAS); 9% did not undergo RAS testing. The SVR rates for ITT and PP were 89.3% and 95.0% in treatment-naive patients and 93.2% and 95.6% in treatment-experienced patients, respectively. In PP analysis, negative RAS was associated with higher SVR (96.3%) than with "undetermined RAS" (85.7%) or "not tested for RAS" (84.4%). Adverse events were reported in 185 (35.4%) patients, and events leading to discontinuation were observed in 4.3% of the study population. Forty-two (8.0%) patients developed transaminase elevation (≥2 × upper normal limit), resulting in treatment discontinuation in six (1.1%) patients. DCV/ASV combination therapy showed acceptable efficacy in genotype 1b compensated HCV-infected patients with negative pretreatment RAS. Although most adverse events were tolerable to continue antiviral treatment, adequate monitoring for transaminase elevation is warranted.

Hepatitis C virus (HCV) requires epidemiological monitoring to estimate its disease burden and to develop countermeasures. This study aimed to investigate the difference between the 2015 and 2009 nationwide anti-HCV seroprevalence and to determine linkage to care estimates in South Korea. A total 268,422 examinees ≥ 20 years old were included in 2015 from 33 medical institutions nationwide. Electronically extracted data were retrospectively analyzed to calculate the age-, sex-, and area-adjusted anti-HCV prevalence. Seroprevalence in 2015 was measured using the same method as that in 2009. For anti-HCV-positive subjects, medical records were reviewed to see whether HCV RNA testing or antiviral treatment was performed. Adjusted anti-HCV prevalence was 0.60% (95% confidence interval, 0.57–0.63) based on general Korean population in 2015. It showed an increasing trend according to age; 0.23% in thirties, 0.38% in forties, 0.63% in fifties, 1.08% in sixties, and 1.65% in those aged ≥ 70 years. From 2009 to 2015, the adjusted anti-HCV prevalence decreased by 30%, with odds ratio of 0.70 (95% CI 0.70–0.71). There was significant intranational regional variation and changing pattern of seroprevalence. Among 1359 anti-HCV-positive subjects, HCV RNA test was performed in 60% and 25.4% had positivity. Treatment-initiated and cured rates in 2015 were 18.5% and 10.9%, respectively. Anti-HCV prevalence in South Korea was 0.6% in 2015, showing a 30% decrease from that in 2009. Although the HCV RNA testing rate was increased since 2009, this remains suboptimal. Moreover, the treatment uptake rate should be improved in South Korea.

In the present study, lactic acid bacteria (LAB) strains were collected from kimchi and were screened to isolate strains that inhibit lipopolysaccharide (LPS) production by Escherichia coli and p16 expression and nuclear factor-kappa B (NF-κB) activation in LPS-stimulated macrophages. Oral administration of Lactobacillus brevis OW38 (1×109 cfu/mouse) to aged mice (male, 18 months old) for 8 weeks reduced the LPS level in colon fluid and blood. In addition, OW38 treatment also reduced the ratio of Firmicutes or Proteobacteria to Bacteroidetes, which was significantly higher in aged mice than in young mice. Treatment with OW38 in aged mice inhibited the expression of inflammatory markers, such as myeloperoxidase, tumour necrosis factor (TNF), and interleukin (IL)-1β, and inhibited NF-κB activation. Furthermore, it induced the expression of colonic tight junction proteins zonula occludens-1, occludin, and claudin-1. OW38 treatment also suppressed the expression of senescence markers p16, p53, and SAMHD1 in the colon and the hippocampus of aged mice. In addition, it significantly restored spontaneous alternation as well as the expression of brain-derived neurotrophic factor and doublecortin in aged mice compared to that in young mice (P

AIM The purpose of the study was to investigate imaging predictors of Kirsten-ras (KRAS) mutations using magnetic resonance imaging (MRI) in patients with rectal cancer. PATIENTS AND METHODS A total of 275 patients with rectal cancer were enrolled. They underwent pretreatment rectal MRI, and then KRAS mutation evaluation following surgery. Two reviewers assessed diverse MRI findings associated with rectal cancer. RESULTS KRAS mutations were detected in 107 (38.9%). KRAS mutations were associated with N stage, gross tumor pattern, axial length of the tumor, and the ratio of the axial to the longitudinal dimensions of the tumor (p=0.0064, p

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

The purpose of this study was to evaluate the impact of the body composition changes on patients’ long-term outcomes after endoscopic resection or surgery for mucosal gastric cancer. This case-control study included 96 patients who underwent endoscopic resection or surgery after propensity score matching. Areas of fat and muscle measured on CT were compared between the 2 groups. The effects of the variables on disease-free and overall survival were assessed using Cox-regression analysis and Kaplan-Meier survival analysis. The median overall survival of the surgical and endoscopic resection groups was 91.1 and 93.9 months (P = .080). Fat area was decreased significantly more after surgery (P

Noise is the most frequently encountered type of environmental pollution in everyday life and has a direct negative effect on humans. Individuals who are constantly exposed to noise tend to have a high incidence of cardiovascular disease and hypertension. Noise sources range from construction sites to political rallies and assemblies, but traffic is one of the most long-lasting and chronic sources of noise. Previously, researchers have conducted valuations of road traffic noise reduction, but they did not consider residents’ annoyance levels in response to traffic noise. However, individuals’ annoyance levels affect the economic value of noise reduction policies and thus must be considered to obtain an accurate estimate. Therefore, this study investigated residents’ willingness to pay for traffic noise reduction depending on their annoyance level. We used the contingent valuation method and a survey to analyze how much 1022 respondents in Korea were willing to pay for noise reduction. We found that people who were annoyed and extremely annoyed by noise had a willingness to pay KRW 8422 (US $7.55) and KRW 9848 (US $8.83) annually per household, respectively, to reduce their annoyance level to zero. In addition, we determined the economic benefits of noise reduction policies using the respondents’ willingness to pay to reduce noise by 1 dB(A), which totaled KRW 3.28 billion (US $2.91 million) per year. The results of this study provide estimates of the annual benefits of traffic noise reduction considering residents’ annoyance level.

Background Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. Methods A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 or proteinuria as at least grade 2+ of urine protein. Results HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m2 (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m2 along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m2. Conclusion Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m2 and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted., Graphical Abstract

Environmental noise pollution is an important social problem. Noise is known to have an adverse effect on human emotions and bodies. However, the methodology of previous studies did not consider selection bias in eliminating participants during the screening process. Therefore, for this study, we propose a framework that combines propensity score matching with a generalized additive model to reduce that sampling problem. Within this framework, we use health data from the National Health Insurance Service and noise data from the National Noise Information System in Korea. Using the proposed framework and data set, we analyze the effects of noise on cardiocerebrovascular disease. Our results show that, when daytime noise increases by 1 A-weighted decibel (dB(A)), cerebrovascular disease increases by 0.66%, hypertension increases by 0.17%, and heart disease increases by 0.38%. Moreover, we conducted a scenario analysis to investigate the effects of noise reduction policies. When noise levels are reduced to meet regulatory targets, cerebrovascular diseases decrease by 2077 per million people, high blood pressure decreases by 5705 per million people, and heart disease decreases by 1151 per million people. Our results thus provide information about noise exposure–response functions in Korea that could be used to establish noise reduction policies.

PURPOSE To evaluate efficacy of cone-beam CT-based liver perfusion mapping obtained immediately following conventional transarterial chemoembolization of hepatocellular carcinoma (HCC) for assessing tumor vascularity, technical success of chemoembolization, and treatment response. MATERIALS AND METHODS From July 2015 to June 2016, 35 patients with 57 HCCs who underwent cone-beam CT with post-processing software via conventional transarterial chemoembolization for HCC and follow-up examination were included. Three reviewers evaluated technical success on angiography, unenhanced cone-beam CT, contrast-enhanced cone-beam CT, and cone-beam CT-based liver perfusion mapping after transarterial chemoembolization per tumor and per patient. Parenchymal blood volume (PBV) was measured. Treatment response was determined on follow-up CT, MR imaging, or histopathology according to modified Response Evaluation Criteria In Solid Tumors. Diagnostic performance for detection of a viable tumor was evaluated using multiple logistic regression with C-statistics. RESULTS Treatment response was 38, 17, 2, and 0 for complete response, partial response, stable disease, and progressive disease per tumor and 18, 15, 2, and 0 per patient. In multiple logistic regression, unenhanced cone-beam CT, contrast-enhanced cone-beam CT, cone-beam CT-based liver perfusion mapping, mean value of PBV, and maximum value of PBV of tumor were significant in response assessment for per tumor and per patient (per tumor, all P < .001; per patient, P = .015, P = .001, P < .001, P = .020, and P = .032). Mean value of PBV of tumor was excellent for evaluating technical success with the highest C-statistic (0.880 and 0.920 for per tumor and per patient), followed by that of visual assessment of cone-beam CT-based liver perfusion mapping (0.864 and 0.908). CONCLUSIONS Cone-beam CT-based liver perfusion mapping provided reliable images to evaluate technical success after transarterial chemoembolization of HCC by qualitative visual assessment and quantitative perfusion values.

Background/aim In the era of direct-acting antivirals (DAA), active screening for hidden hepatitis C virus (HCV) infection is important for HCV elimination. This study estimated the cost-effectiveness and health-related outcomes of HCV screening and DAA treatment of a targeted population in Korea, where anti-HCV prevalence was 0.6% in 2015. Methods A Markov model simulating the natural history of HCV infection was used to examine the cost-effectiveness of two strategies: no screening vs screening and DAA treatment. Screening was performed by integration of the anti-HCV test into the National Health Examination Program. From a healthcare system's perspective, the cost-utility and the impact on HCV-related health events of one-time anti-HCV screening and DAA treatment in Korean population aged 40-65 years was analysed with a lifetime horizon. Results The HCV screening and DAA treatment strategy increased quality-adjusted life years (QALY) by 0.0015 at a cost of $11.27 resulting in an incremental cost-effectiveness ratio (ICER) of $7435 per QALY gained compared with no screening. The probability of the screening strategy to be cost-effective was 98.8% at a willingness-to-pay of $27 205. Deterministic sensitivity analyses revealed the ICERs were from $4602 to $12 588 and sensitive to screening costs, discount rates and treatment acceptability. Moreover, it can prevent 32 HCV-related deaths, 19 hepatocellular carcinomas and 15 decompensated cirrhosis per 100 000 screened persons. Conclusions A one-time HCV screening and DAA treatment of a Korean population aged 40-65 years would be highly cost-effective, and significantly reduce the HCV-related morbidity and mortality compared with no screening.

Background & aims The population-based epidemiology of Budd-Chiari syndrome (BCS), a rare disease of hepatic venous outflow obstruction, is largely unknown. This study aimed to elucidate the nationwide population-based incidence, prevalence, complications, case fatalities and direct medical cost of BCS in South Korea from 2009 to 2013. Methods Using two large data sources, the Health Insurance Review and Assessment Service Claims database and Rare Intractable Disease registration program database in Korea, we identified all patients with BCS who were registered under International Classification of Diseases 10 (code I82.0). The age- and sex-adjusted incidence and prevalence of BCS were calculated with analysis of complications and direct medical costs. Results A total of 424 patients with BCS were identified in 2009-2013, with a female-to-male ratio of 1.8 and a median age of 51 years old. The average age- and sex-adjusted incidence from 2011 to 2013 was 0.87 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 5.29 per million population. Among them, 10.3% accompanied liver cancer and 3.3% underwent liver transplantation. Annual case-fatality rate was 2.8%. Direct medical costs excluding uninsured services for BCS increased by year from 385 720 USD in 2009 to 765 983 USD in 2013. Conclusions This is the first population-based study on the epidemiology of BCS in an Asian country, which presented a higher prevalence than in Western studies. It suggests early diagnosis or improved prognosis of BCS in recent years, and clinical features of BCS that differ by geography.

Summary Background As a rare disease, only a few population-based epidemiology studies of primary biliary cirrhosis (PBC) have been reported. Aims To elucidate the nationwide prevalence, incidence, complications, fatality and direct medical costs of PBC in South Korea. Methods The nationwide Health Insurance Review and Assessment Service claims data and Rare Intractable Disease registration data on PBC, identified with the International Classification of Diseases (ICD) 10 code of K74.3, were obtained from 2009 to 2013. Age- and gender-specific prevalence and incidence rates of PBC were calculated, and data on complications, comorbidities, prescribed drugs, therapeutic procedures and direct medical costs were analysed. Results A total of 2824 patients over 20 years old with PBC were identified in 2009–2013 (female-to-male ratio 6.2, median age 57 years old). The average age- and sex-adjusted incidence from 2011 to 2013 was 8.57 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 47.50 per million population. About 10% of patients presented with complications such as ascites (10.3%), variceal bleeding (5.8%) and/or hepatocellular carcinoma (HCC) (1.3%). Liver transplantation was undertaken in 71 patients (2.5%) for 5 years. Case fatality was 2.2% and the transplantation-free survival was 95.4% for 5 years. Conclusions This is the first report on the nationwide epidemiology of primary biliary cirrhosis in South Korea, demonstrating lower incidence and prevalence rates than those of Western countries, but a considerable disease burden, representing at least 10% were complicated with decompensated cirrhosis or hepatocellular carcinoma requiring liver transplantation.

Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies.

The effects of pelvic asymmetry and idiopathic scoliosis on postural balance during sitting were studied by measuring inclination angles, pressure distribution, and electromyography. Participants were classified into a control group, pelvic asymmetry group, scoliosis group, and scoliosis with pelvic asymmetry and then performed anterior, posterior, left, and right pelvic tilting while sitting on the unstable board for 5 seconds to assess their postural balance. Inclination and obliquity angles between the groups were measured by an accelerometer located on the unstable board. Pressure distribution (maximum force and peak pressure) was analyzed using a capacitive seat sensor. In addition, surface electrodes were attached to the abdominal and erector spinae muscles of each participant. Inclination and obliquity angles increased more asymmetrically in participants with both pelvic asymmetry and scoliosis than with pelvic asymmetry or scoliosis alone. Maximum forces and peak pressures of each group showed an asymmetrical pressure distribution caused by the difference in height between the left and right pelvis and curve type of the patients' spines when performing anterior, posterior, left, and right pelvic tilting while sitting. Muscle contraction patterns of external oblique, thoracic erector spinae, lumbar erector spinae, and lumbar multifidus muscles may be influenced by spine curve type and region of idiopathic scoliosis. Asymmetrical muscle activities were observed on the convex side of scoliotic patients and these muscle activity patterns were changed by the pelvic asymmetry. From these results, it was confirmed that pelvic asymmetry and idiopathic scoliosis cause postural asymmetry, unequal weight distribution, and muscular imbalance during sitting.

Background Data comparing EASL and mRECIST criteria for response evaluation in treatment of hepatocellular carcinoma are rare. We evaluated inter-observer variability by these two response evaluation criteria in treatment-naive patients undergoing chemoembolization. Methods For 133 patients undergoing chemoembolization, two radiologists independently measured sum of bi-dimensional and uni-dimensional diameters at baseline using both EASL criteria and mRECIST, and their changes on first follow-up for up to 5 target lesions. Results Concordance correlation coefficients for sum of bi-dimensional and uni-dimensional diameters at baseline between two observers were 0.992 and 0.988, respectively. However, those for their changes on follow-up were 0.865 and 0.877, respectively. Similarly, mean differences in sum of bi-dimensional and uni-dimensional diameters at baseline between two observers were small; −0.455 and 0.079 cm, respectively. However, mean differences in changes (%) in sum of bi-dimensional and uni-dimensional diameters on first follow-up between observers increased by −9.715% and −9.320%, respectively. Regarding tumour numbers, kappa-value between observers was 0.942. For treatment response (complete or partial response, stable disease and progression), kappa-value was 0.941 by both criteria. When only up to two target lesions were assessed, kappa-value was 1.000 by both criteria. Conclusions Inter-observer agreements using both response evaluation criteria were excellent, especially when up to two targets were assessed.

Purpose Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuron disease characterized by proximal muscle weakness, muscle atrophy, and fasciculation. Although SBMA is not uncommon in Korea, there is only one study reporting clinical characteristics and genotype-phenotype correlation in Korean patients. Materials and Methods In this study, age at the onset of symptoms, the score of severity assessed by impairment of activities of daily living milestones, and rate of disease progression, and their correlations with the number of CAG repeats in the androgen receptor (AR) gene, as well as possible correlations among clinical characteristics, were analyzed in 40 SBMA patients. Results The median ages at onset and at diagnosis were 44.5 and 52.5 years, respectively, and median interval between onset and diagnosis and median rate of disease progression were 5.0 years and 0.23 score/year, respectively. The median number of CAG repeats in the AR gene was 44 and the number of CAG repeats showed a significant inverse correlation with the age at onset of symptoms (r=-0.407, p=0.009). In addition, patients with early symptom onset had slower rate of disease progression. Conclusion As a report with the largest and recent Korean cohort, this study demonstrates clinical features of Korean patients with SBMA and reaffirms the inverse correlation between the age at disease onset and the number of CAG repeats. Interestingly, this study shows a possibility that the rate of disease progression may be influenced by the age at onset of symptoms.

Purpose The aim of this study was to compare the magnetic resonance imaging (MRI) evaluation of transplanted meniscal allograft with second-look arthroscopy and evaluate the sensitivity, specificity, and accuracy of MRI for assessing graft status. Methods From 1996 to 2012, among 290 knees that underwent meniscal allograft transplantation and received follow-up examination for more than 1 year, those knees that underwent second-look arthroscopy were reviewed. Patients with no postoperative MRI and patients with a time gap between postoperative MRI and second-look arthroscopy of more than 3 months were excluded. Anatomically, the meniscus was divided into 3 segments: anterior one-third, mid body, and posterior one-third. Each part of the meniscus was evaluated using both methods. Grade 3 MRI signal intensity was diagnosed as a meniscal tear radiologically. By use of second-look arthroscopy as the standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of postoperative MRI were assessed in each segment of the grafts. Results Twenty knees were retrospectively enrolled. The specificity, PPV, and accuracy for the anterior one-third were lower than those for the mid body and posterior one-third (specificity of 35.3% v 91.7% and 90%, respectively; PPV of 21.4% v 87.5% and 90.9%, respectively; and accuracy of 45% v 90% and 95%, respectively). However, the sensitivity and NPV were similar among the anterior one-third, mid body, and posterior one-third (sensitivity of 100%, 87.5%, and 100%, respectively; and NPV of 100%, 91.7%, and 100%, respectively). There were no significant differences in the comparison between the diagnostic MRI values of lateral grafts and medial grafts. Of 5 cases that showed grade 3 signal at only the anterior one-third section, 60% had no clinical signs. There were no graft tears in any cases. Conclusions The anterior one-third of grafts showed low specificity, PPV, and accuracy of postoperative MRI compared with the mid body and posterior one-third. MRI tended to grade the anterior one-third more poorly than second-look arthroscopy. These features should be considered when evaluating transplanted meniscal allografts on postoperative MRI. Level of Evidence Level III, study of non-consecutive patients evaluating a diagnostic test with a gold standard.

BACKGROUND/AIMS This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients. METHODS CHB patients treated with TDF monotherapy (300 mg/day) for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks. RESULTS In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naive, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9±2.3 log IU/mL (mean±SD), and was higher in the NA-naive group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P

Background:Osteophytes can be observed on the tibial plateau during meniscus allograft transplantation (MAT). However, no studies to date have evaluated the effect of these osteophytes on meniscus allograft extrusion.Hypothesis:Osteophyte excision in the tibial plateau could reduce extrusion of the transplanted meniscus and improve short-term clinical outcomes with meniscus allograft transplantation.Study Design:Cohort study; Level of evidence, 3.Methods:Between October 2004 and July 2012, a total of 323 patients underwent MAT at a single institution. Of these, 88 patients had a peripheral osteophyte in their tibial plateau, and they were enrolled in the study retrospectively. The mean age of the patients was 35.3 years (range, 15-56 years); there were 57 male and 31 female patients. Forty-four patients underwent osteophyte excision concomitantly with MAT and 44 patients underwent MAT only. The 2 groups showed no difference in terms of age, body mass index, time after meniscectomy, and preoperative knee scores. A medial meniscus allograft was transplanted in 13 cases (15%) and a lateral meniscus in 75 (85%). The absolute extrusion and relative percentage of extrusion were measured to evaluate allograft extrusion 12 months after MAT. The modified Lysholm scoring system and the Hospital for Special Surgery score at 2 years after MAT were used to evaluate clinical outcomes.Results:The mean absolute extrusions at 1 year postoperatively in the excision and nonexcision groups were 3.5 ± 1.5 and 5.5 ± 1.6 mm, respectively. The mean relative percentages of extrusion were 34.1% ± 15.9% and 54.7% ± 20.7%, respectively. The rates of allograft extrusion (>3 mm) were 28 of 44 (63.6%) and 41 of 44 (93.2%) in the excision and nonexcision groups, respectively. The intergroup differences in absolute extrusion, relative percentage of extrusion, and rate of allograft extrusion were statistically significant ( P < .001 for all 3 parameters). There were no significant differences in the clinical outcomes (modified Lysholm or Hospital of Special Surgery scores) at 2-year follow-up ( P < .762 and < .298, respectively).Conclusion:The excision of a peripheral osteophyte larger than 2 mm in the proximal tibial plateau was associated with less allograft extrusion after MAT.

Ultrasonography (US) is recommended as a standard surveillance tool for patients with a high risk of developing hepatocellular carcinoma (HCC). However, the low sensitivity of US for small HCC can lead to surveillance failure, resulting in advanced stage tumor presentations. For the early detection of HCC in high-risk patients and to improve survival and prognosis, a new efficient imaging tool with a high sensitivity for HCC detection is needed. The purpose of this study is to evaluate and compare the feasibility and efficacy of non-contrast magnetic resonance imaging (MRI) with US as a surveillance tool for HCC in patients with liver cirrhosis. MAGNUS-HCC is a prospective, multicenter clinical trial with a crossover design for a single arm of patients. This study was approved by six Institutional Review Boards, and informed consent was obtained from all participants. All patients will undergo liver US every 6 months and non-contrast liver MRI every 12 months during a follow-up period of 3 years. If a focal liver lesion suspected of harboring HCC is detected, dynamic liver computed tomography (CT) will be performed to confirm the diagnosis. After the last surveillance round, patients without suspicion of HCC or who are not diagnosed with HCC will be evaluated with a dynamic liver CT to exclude false-negative findings. The primary endpoint is to compare the rate of detection of HCC by US examinations performed at 6-month intervals with that of yearly non-contrast liver MRI studies during a 3-year follow-up. The secondary endpoint is the survival of the patients who developed HCC within the 3-year follow-up period. MAGNUS-HCC is the first study to compare the feasibility of non-contrast MRI with US as a surveillance tool for the detection of HCC in high-risk patients. We anticipate that the evidence presented in this study will establish the efficacy of non-contrast MRI as a surveillance tool for HCC in high-risk patients. The date of trial registration ( NCT02551250 ) in this study was September 15, 2015, and follow-up is still ongoing.

The aim of this study was to describe the clinical characteristics of acute hemorrhagic rectal ulcer (AHRU) and to elucidate its predictive factors.The medical records of patients with AHRU were retrospectively reviewed. Their baseline clinical characteristics were compared with those of patients with non-AHRU lower gastrointestinal bleeding to identify predictive factors for AHRU.Among the 118 patients who underwent emergency endoscopy due to acute massive hematochezia from 2013 to 2015, 25 (21.2%) were diagnosed as having AHRU. Of them, 22 (88.0%) were successfully managed endoscopically and 3 (12.0%) underwent surgery. Six (24.0%) patients developed rebleeding within 1-9 days after the initial bleeding, which was controlled by a repeat endoscopy. Five (20.0%) died during follow-up. A multivariate-adjusted logistic regression analysis revealed that a lower serum albumin level, worse Eastern Cooperative Oncology Group (ECOG) performance status and history of constipation were significant factors for predicting AHRU. Hypoalbuminemia (30 g/L) had a sensitivity, specificity and positive and negative predictive values of 84.0%, 78.5%, 51.2% and 94.8% for predicting AHRU, respectively.Approximately 20% of patients with massive hematochezia had AHRU. Most patients with AHRU can be managed endoscopically. Low serum albumin level, poor ECOG performance status and prior constipation could be used in distinguishing patients with and without AHRU, facilitating the selection of optimal bowel preparation method for massive hematochezia.

MicroRNAs post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to identify new target genes for microRNA polymorphisms (miR-146aC>G and miR-196a2T>C) in primary ovarian insufficiency (POI). We cloned and transfected miR-146aC>G and miR-196a2T>C into human granulosa cells and used microarrays and qPCR-arrays to examine the changes in the messenger RNA expression profile. We show miR-146aC>G and miR-196a2T>C change the mRNA expression patterns in granulosa cell. In each case, mRNAs were up or down-regulated after treatments with miR-146a C or G and miR-196a2 T or C. We found that miR-146a led to a significantly altered regulation of the mRNA levels of FOXO3, FOXL2 and CCND2 compared to controls. We also found that the polymorphisms of miR-146a led to a significantly altered regulation of CCND2 and FOXO3. Our results suggest that miR-146aC>G and miR-196a2T>C can regulate the levels of many of their target transcripts. In addition, specific target genes of miR-146aC>G polymorphisms may be involved in granulosa cell regulation.

The aim of this study was to determine (1) variations in the shape of the proximal, middle, and distal femur in a series of Korean patients who had undergone total knee arthroplasty (TKA), (2) the preoperative relationship between these three parameters and the distal valgus cutting angle referenced off the femoral intramedullary guide, and (3) whether there was any relationship between femoral bowing and variations in the shape of the proximal or distal femur in the coronal plane.The preoperative long-standing anteroposterior radiographs of 316 consecutive osteoarthritis patients who underwent primary TKA from 2009 to 2011 were examined. The femoral neck shaft angle, the femoral shaft bowing angle, and the mechanical lateral distal femoral angle were measured to assess the shape of the proximal, middle, and distal femur, respectively. The valgus cutting angle of the femur was defined as the angle between the distal anatomical and mechanical axes of the femur.The study population showed large variations in femoral shape. The mean femoral intramedullary guide angle was 6.5° ± 1.3° (range: 4°-13°). The femoral shaft bowing angle was the factor that showed the strongest correlation with this angle (P0.001). The mechanical lateral distal femoral angle showed only a weak correlation (P = 0.001), and the femoral neck shaft angle showed no correlation (n.s.). The femoral shaft bowing angle showed a weak correlation with the mechanical lateral distal femoral angle (P = 0.001), but was not significantly correlated with the femoral neck shaft angle (n.s.). Apparent femoral bowing (3° of lateral or medial bowing) was found in 42 (13.3 %) of cases (37 cases of lateral bowing and five of medial bowing). Cases with lateral apparent femoral bowing3° had a distal cutting angle of 8.6° ± 2.2° relative to the femoral intramedullary guide.The femoral intramedullary guide angle was mainly influenced by femoral shaft bowing among femoral deformities in the coronal plane. Therefore, to increase the accuracy of distal femoral cut during TKA, it is necessary to confirm femoral deformities and to measure the femoral intramedullary guide angle preoperatively from coronal radiographs covering the whole femur.IV.

Met is a receptor tyrosine kinase that promotes cancer progression. In addition, Met has been implicated in resistance of tumors to various targeted therapies such as epidermal growth factor receptor inhibitors in lung cancers, and has been prioritized as a key molecular target for cancer therapy. However, the underlying mechanism of resistance to Met-targeting drugs is poorly understood. Here, we describe screening of 1310 genes to search for key regulators related to drug resistance to an anti-Met therapeutic antibody (SAIT301) by using a small interfering RNA-based synthetic lethal screening method. We found that knockdown of 69 genes in Met-amplified MKN45 cells sensitized the antitumor activity of SAIT301. Pathway analysis of these 69 genes implicated fibroblast growth factor receptor (FGFR) as a key regulator for antiproliferative effects of Met-targeting drugs. Inhibition of FGFR3 increased target cell apoptosis through the suppression of Bcl-xL expression, followed by reduced cancer cell growth in the presence of Met-targeting drugs. Treatment of cells with the FGFR inhibitors substantially restored the efficacy of SAIT301 in SAIT301-resistant cells and enhanced the efficacy in SAIT301-sensitive cells. In addition to FGFR3, integrin β3 is another potential target for combination treatment with SAIT301. Suppression of integrin β3 decreased AKT phosphorylation in SAIT301-resistant cells and restored SAIT301 responsiveness in HCC1954 cells, which are resistant to SAIT301. Gene expression analysis using CCLE database shows that cancer cells with high levels of FGFR and integrin β3 are resistant to crizotinib treatment, suggesting that FGFR and integrin β3 could be used as predictive markers for Met-targeted therapy and provide a potential therapeutic option to overcome acquired and innate resistance for the Met-targeting drugs.

The diagnosis of acute hepatitis A virus (HAV) infection is made on the basis of the presence of anti-HAV immunoglobulin M (IgM) antibodies in patients with clinical features of acute hepatitis. Some patients show a negative serology at initial presentation, which may complicate the diagnosis of hepatitis A (HA). The aim of this study was to examine the characteristics of HA patients with an initially negative anti-HAV IgM test result.Patients with symptomatic acute hepatitis who underwent IgM anti-HAV testing at a single center were enrolled consecutively, with tests repeated in patients with negative initial serology.A total of 684 patients with acute hepatitis were tested, of whom 620 patients were initially or eventually diagnosed with HA. Anti-HAV IgM was initially negative in 67 of the 620 HA patients (10.9%), but was later confirmed by subsequent retests. These patients had on average a shorter time lapse from the onset of symptoms to the initial test, a higher rate of fever, and lower alanine aminotransferase and bilirubin levels compared with those with a positive initial serology. Cutoff index (COI) values of anti-HAV IgM were correlated positively with the duration of time from the onset of symptoms to the initial test. Fever, lower bilirubin levels, and higher COI values were predictive of seroconversion to anti-HAV positivity in patients with a negative initial serology.Taking into account the window period of HAV infection, anti-HAV IgM tests should be repeated, particularly in patients with features of the initial phase of hepatitis and a high COI value of anti-HAV IgM.

The purpose of this study is to investigate the technical and clinical efficacy of percutaneous bilateral stent-in-stent deployment using open cell-design stents and to compare the clinical outcomes of bilateral stent placement using T and Y configurations.From January 2006 to December 2010, 106 patients with malignant hilar biliary obstruction (Bismuth type II or higher) were included in this retrospective study. All patients were treated with percutaneous bilateral stent-in-stent deployment using open cell-design stents (64 in a T configuration and 42 in a Y configuration).Bilateral stent-in-stent deployment was technically successful in all patients. Seven patients (6.6%) had major complications, including one with severe hemobilia, two with acute cholecystitis, and four with cholangitis; seven (6.6%) patients had minor complications, including self-limiting hemobilia. Successful internal drainage was achieved in 94 patients (88.7%). Stent occlusion by tumor ingrowth, with or without overgrowth, occurred in 37 patients (34.9%). The median survival and stent patency times were 192 days (95% CI, 153.6-230.4 days) and 319 days (95% CI, 148.5-489.5 days), respectively. Stent configuration did not significantly affect technical success, complications, successful internal drainage, patient survival, or stent patency.Percutaneous bilateral stent-in-stent placement using open cell-design stents is effective for bilateral drainage in patients with malignant hilar biliary obstruction. In addition, there was no significant difference in technical and clinical outcomes between T and Y stent configurations.

European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumours (mRECIST) guidelines, which measure changes in arterialised hepatocellular carcinoma (HCC), differ in terms of number of target lesions (all versus ≤2) and calculation method (bidimensional versus unidimensional). We compared prognostic values of mRECIST for predicting overall survival (OS) with reference to EASL criteria in treatment-naïve HCC undergoing trans-arterial chemoembolisation (TACE).The ability to predict OS during longitudinal follow-up was expressed as C-index, and a sample size of 292 patients was required to validate its equivalence between each criteria. Treatment responses were assessed using both guidelines 4weeks after the first TACE, using dynamic computed tomography or magnetic resonance imaging. Kaplan-Meier and Cox regression analyses were used to explore differences in OS between responders (complete or partial) and non-responders (stable or progressive disease), defined by each method.C-index for EASL and mRECIST guidelines was 0.753 and 0.759, respectively, demonstrating equivalence between two methods. Differences in median OS between responders and non-responders were statistically significant for both EASL (30.1 versus 18.7 months, p0.001) and mRECIST (33.8 versus 17.1 months, p0.001) guidelines. In addition to radiological response, α-fetoprotein (p0.001), tumour number (p0.001) and tumour size (p=0.048) were significant predictors of OS. In multivariate analysis, radiological criteria, tumour number and α-fetoprotein were identified as independent predictors (all p0.05).mRECIST, a simpler method, provided prognostic values for predicting OS equivalent to EASL criteria in patients with HCC undergoing TACE as an initial treatment modality.

Background & Aims The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large-scale survey. Methods From January to December 2009, a total of 291 314 adults underwent health check-up in 29 centres nationwide. The data concerning anti-HCV antibody and biochemical tests were obtained from all participants. Among subjects with positive anti-HCV, such data as HCV RNA, genotypes and treatment detail were additionally analysed. Results Using an estimated 2009 population of Korea, the age, sex and area-adjusted anti-HCV positive rate was 0.78%. Anti-HCV prevalence in female patients (0.83%) was higher than that in male patients (0.75%). Gradual increase in anti-HCV positivity was observed, from 0.34% in those aged 20–29 years to 2.31% in those >70 years. The age- and sex-adjusted anti-HCV prevalence varied in different areas, being higher in Busan and Jeonnam (1.53–2.07%), mid-level in Seoul and surrounding districts (0.50–0.61%) and lower in Jeju (0.23%). The comparative analysis of laboratory variables between anti-HCV (+) and anti-HCV (−) group revealed significantly higher levels of alanine aminotransferase and lower levels of serum lipids in anti-HCV (+) group. Among 1 718 anti-HCV positive subjects, serum HCV RNA was measured only in 478 people, of whom 268 (56.1%) patients had detectable HCV RNA in serum. Among 50 patients for whom assessment of response to antiviral therapy was feasible, overall sustained virological response was achieved in 84% of patients. Conclusion The prevalence of HCV infection is low in South Korea. Studies to analyse risk factors are warranted to reduce HCV infection.

Background/Aims: To evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon- based therapy in a real-world setting. Methods: This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea. Subjects were followed retrospectively until March 2015, which was just before the approval of DAA therapy. Results: In total, 48.2% and 49.3% of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy was initiated in 541 patients (45.4%). The major reasons for no treatment included ineligibility (18.9%), concern about adverse events (22.3%), cost (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients and 74.7% in nongenotype 1 patients. Conclusions: Approximately one-third of newly diagnosed HCV patients in South Korea received interferon-based therapy and showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a less advanced liver status and reducing the DAA therapy cost may fulfill unmet needs. (Gut Liver 2017;11:543-550)

Magnetic resonance (MR) imaging is a useful imaging tool with superior soft tissue contrast for diagnostic evaluation. The MR environments poses unique risks to patients and employees differently from ionizing radiation exposure originated from computed tomography and plain x-ray films. The technology associated with MR system has evolved continuously since its introduction in the late 1970s. MR systems have advanced with static magnetic fields, faster and stronger gradient magnetic fields and more powerful radiofrequency transmission coils. Higher field strengths of MR offers greater signal to noise capability and better spatial resolution, resulting in better visualization of anatomic detail, with a reduction in scan time. With the rapid evolution of technology associated with MR, we encounter new MR-related circumstances and unexpected dangerous conditions. A comprehensive update of our knowledge about MR safety is necessary to prevent MR-related accidents and to ensure safety for patients and staff associated with MR. This review presents an overview about MR-related safety issues and updates.

The landscape of treatment for HCV infection has evolved substantially with the advent of highly effective direct-acting antiviral agents (DAA). The Korean Association for the Study of the Liver updated guideline for managemnt of hepatitis C in accordance with the introduction of DAA into practice in late 2015. Due to high effectiveness and few side effects of DAA, indications for treatment has been widened to include patients who had been contraindicated for the combination treatment of peginterferon-α and ribavirin, i.e. decompensated cirrhosis and pre- and post-liver transplant setting. As succeesul treatment of HCV can reduce complications of cirrhosis, development of hepatocelluar carcinoma and liver-related mortality, and improve extrahepatic manifestions, all HCV-infected patients with no contraindication should be considered for treatment. Considering the risk for morbidity and mortality and benefit of treatment, patients with advanced fibrosis ≥F3 including compensated and decompensated cirrhosis, those in the pre- and post-tranplasnt setting, and those with severe extrahepatic manifestations including HCV-related mixed cryoglobulinemia and glomerulonephritis should be given priority for treatment. (Korean J Gastroenterol 2016;67:123-126)

c-Met, the high affinity receptor for hepatocyte growth factor (HGF), is one of the most frequently activated tyrosine kinases in many human cancers and a target for cancer therapy. However, inhibitory targeting of c-Met with antibodies has proven difficult, because most antibodies have intrinsic agonist activity. Therefore, the strategy for reducing the agonism is critical for successful development of cancer therapies based on anti-c-Met antibodies. Here we developed a mechanism-based assay method for rapid screening of anti-c-Met antibodies, involving the determination of Akt phosphorylation and c-Met degradation for agonism and efficacy, respectively. Using the method, we identified an antibody, F46, that binds to human c-Met with high affinity (Kd = 2.56 nM) and specificity, and induces the degradation of c-Met in multiple cancer cells (including MKN45, a gastric cancer cell line) with minimal activation of c-Met signaling. F46 induced c-Met internalization in both HGF-dependent and HGF-independent cells, suggesting that the degradation of c-Met results from antibody-mediated receptor internalization. Further-more, F46 competed with HGF for binding to c-Met, resulting in the inhibition of both HGF-mediated invasion and angiogenesis. Consistently, F46 inhibited the proliferation of MKN45 cells, in which c-Met is constitutively activated in an HGF-independent manner. Xenograft analysis revealed that F46 markedly inhibits the growth of subcutaneously implanted gastric and lung tumors. These results indicate that F46, identified by a novel mechanism-based assay, induces c-Met degradation with minimal agonism, implicating a potential role of F46 in therapy of human cancers.