Publications by authors named "Eun Sun Jang"

108 Publications

A cost-effectiveness study of universal screening for hepatitis C virus infection in South Korea: A societal perspective.

Clin Mol Hepatol 2021 Nov 5. Epub 2021 Nov 5.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aims: This study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared with 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 program (NHE). 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 productivity loss cost owing 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 $2,666QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay (WTP) threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared with no screening. In the 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 would be highly cost-effective from both healthcare system and societal perspectives.
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http://dx.doi.org/10.3350/cmh.2021.0236DOI Listing
November 2021

Validation of Dynamic Aspartate-to-Alanine Aminotransferase Ratio for Predicting Liver Disease Mortality.

Hepatol Commun 2021 Oct 29. Epub 2021 Oct 29.

Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

The dynamic aspartate-to-alanine aminotransferase ratio (dAAR) was developed recently to predict the risk of incident chronic liver disease among the Nordic adult population; however, the dAAR has not been externally validated in other ethnic cohorts. Therefore, we aimed to examine the predictive ability of dAAR for liver disease mortality in the South Korean adult population. As a population-based cohort study, we used the National Health Screening Cohort database, which included adult individuals who underwent standardized medical examinations between 2002 and 2003 in South Korea. The primary endpoint was liver disease mortality, defined as death due to liver disease. Liver disease mortality was evaluated between 2004 and 2015 (12 years). Analysis of data from 512,749 adults showed that 4,052 (0.8%) individuals died due to liver disease. On receiver operating characteristic (ROC) analyses, the area under curve for alanine aminotransferase (ALT), aspartate-to-ALT ratio (AAR), and dAAR for liver disease mortality were 0.74, 0.55, and 0.81, respectively. The cutoff point of dAAR was determined to be 0.72 on ROC analysis, using the Youden index method. On competing risk analysis using the Fine and Gray model, the dAAR > 0.72 group demonstrated a 4.43-fold higher rate of liver disease mortality (subdistribution hazard ratio: 4.43, 95% confidence interval: 4.11, 4.77; P < 0.001) after adjustment for covariates. Conclusion: The performance of dAAR in predicting liver disease mortality was better than that of AAR or ALT in South Korea. Our study suggests that dAAR scores can potentially be used for screening and predicting liver disease mortality among the general Korean population.
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http://dx.doi.org/10.1002/hep4.1844DOI Listing
October 2021

Comparison of biochemical response during antiviral treatment in patients with chronic hepatitis B infection.

Liver Int 2021 Oct 22. Epub 2021 Oct 22.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Background & Aims: This multicenter cohort study aimed to compare the real-world biochemical response rates during tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) treatment in chronic hepatitis B virus (HBV) infection patients.

Methods: Overall, 1282 treatment-naïve patients with CHB who commenced TAF (n = 270), TDF (n = 617), or ETV (n = 395) were analysed for biochemical response rates during the antiviral treatment using a time-dependent Cox proportional hazard model after the inverse probability of treatment weighting (IPTW).

Results: Patients treated with ETV were older (55.1 ± 11.5 years) than TAF or TDF (P < .0001). ETV was more frequently prescribed to patients with diabetes mellitus (DM, P = .003), hypertension (P < .0001), chronic kidney disease (P < .0001), and negative e-antigen (P < .0001). Cumulative biochemical response rate was independently lower in patients with radiologic fatty liver (HR, 0.75; 95% CI, 0.61-0.94) and obese patients without DM (HR, 0.85; 95% CI, 0.68-0.98) according to multivariable Cox analyses based on time-dependent variables after IPTW for age, sex, liver cirrhosis, baseline e-antigen, ALT, and HBV DNA levels. ETV treated patients (HR, 1.38; 95% CI, 1.13-1.68) showed higher biochemical response rates compared with TAF- or TDF-treated patients after adjusting for similar parameters.

Conclusions: In real-world practice, ETV was preferable for older, hepatitis B e-antigen negative patients with underlying comorbidities. Biochemical responses in patients treated with ETV, TAF, and TDF were significantly affected by metabolic factors such as fatty liver, obesity, and DM. However, the mechanism behind the higher biochemical response rate in patients treated with ETV should be investigated further.
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http://dx.doi.org/10.1111/liv.15086DOI Listing
October 2021

Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in South Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.

Epidemiol Health 2021 Oct 6:e2021077. Epub 2021 Oct 6.

Seoul National University Bundang Hospital , Seongnam, Korea.

Objectives: Injection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data are available in South 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 the questionnaire survey focused on the lifetime risk factors for HCV infection were analyzed based on the self-reported history of injection drug use.

Results: Among the 2,468 patients, 166 (6.7%) had a history of injection drug use (PWID group). In the PWID group, the patients were younger (50.68.2 vs. 58.213.1 years) and the proportion of males was higher (81.9% vs. 48.8%) than in 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 differ between the groups.

Conclusion: By 2019, PWID were a minority among the HCV-infected people in Korea. The epidemiological characteristics were different between the groups, but not the treatment uptake and outcomes. Therefore, active screening and treatment should be offered to PWID in Korea.
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http://dx.doi.org/10.4178/epih.e2021077DOI Listing
October 2021

The Role of Urinary -Acetyl-β-d-glucosaminidase in Cirrhotic Patients with Acute Kidney Injury: Multicenter, Prospective Cohort Study.

J Clin Med 2021 Sep 23;10(19). Epub 2021 Sep 23.

Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Korea.

Background And Aims: Currently, it is difficult to predict the reversibility of renal function and to discriminate renal parenchymal injury in cirrhotic patients with acute kidney injury (AKI). The aim of this study is to evaluate whether urine -acetyl-β-d-Glucosaminidase (NAG) can predict the survival and response to terlipressin in cirrhotic patients with AKI.

Methods: Two hundred sixty-two cirrhotic consecutive patients who developed AKI were prospectively enrolled from 11 tertiary medical centers in Korea between 2016 to 2019. AKI was defined as an increase in serum Cr (SCr) of 0.3 mg/dL or a 50% increase in baseline SCr. Patients diagnosed with hepatorenal syndrome (HRS-AKI) were treated with terlipressin plus albumin.

Results: The patients were 58.8 ± 12.9 years old on average and were predominantly male (72.5%). The mean MELD score was 25.3 ± 9.1. When classified according to the AKI phenotype, there were 119 pre-renal, 52 acute tubular necrosis, 18 miscellaneous, and 73 HRS-AKI patients. However, the urine NAG was not effective at discriminating AKI phenotypes, except for HRS-AKI. The baseline urine NAG increased as the baseline AKI stage increased ( < 0.001). In addition, within the same AKI stage, the urine NAG values were significantly lower in the AKI-resolved group than in the unresolved group. The urine NAG level was significantly lower in living patients compared with those who died or who underwent a liver transplant within 3 months ( = 0.005). In the multivariate analysis, the increased urine NAG was a significant risk factor for the 3-month transplant-free survival (TFS) rate, especially in patients with Child-Pugh class ≤ B or MELD < 24. The urine NAG did not predict the response to terlipressin treatment in patients with HRS.

Conclusions: Urine NAG is strongly associated with the severity of AKI in patients with liver cirrhosis and is useful for predicting the 3-month TFS.
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http://dx.doi.org/10.3390/jcm10194328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509706PMC
September 2021

An artificial intelligence model to predict hepatocellular carcinoma risk in Korean and Caucasian patients with chronic hepatitis B.

J Hepatol 2021 Oct 1. Epub 2021 Oct 1.

Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada.

Background & Aims: Several risk models were recently developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk.

Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from four hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development.

Results: In the derivation cohort and the two validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good prediction performance [concordance index (c-index), 0.79]. This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index, 0.79 vs. 0.64-0.74; all P < 0.001) and Caucasian validation cohorts [c-index, 0.81 vs. 0.57-0.79; all P < 0.05 except modified PAGE-B (P = 0.22)]. A calibration plot showed a satisfactory calibration function. When the patients were grouped into four risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up.

Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir.

Lay Summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance.
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http://dx.doi.org/10.1016/j.jhep.2021.09.025DOI Listing
October 2021

Prognostic role of plasma level of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor in hepatocellular carcinoma.

World J Gastroenterol 2021 Jul;27(27):4453-4467

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, South Korea.

Background: Most hepatocellular carcinomas (HCCs) are hypervascular, with characteristic features of hepatic arterial supply to the tumor. The factors involved in tumor angiogenesis include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF).

Aim: To investigate the profiles of plasma levels of angiogenesis markers in patients with HCC and evaluate their roles in predicting overall survival (OS) and progression-free survival (PFS).

Methods: Plasma samples from 240 prospectively enrolled HCC patients in the very early to advanced stages were used to measure the levels of Ang-1, Ang-2, and VEGF. Their associations with clinical characteristics, OS, and PFS were analyzed.

Results: The median plasma levels of Ang-1, Ang-2, and VEGF were 3216 pg/mL, 1684 pg/mL, and 26.5 pg/mL, respectively. The plasma level of Ang-2 showed a significant increase from early stage [Barcelona clinic liver cancer (BCLC) A] to intermediate (BCLC B) and advanced stage HCC (BCLC C/D), whereas Ang-1, VEGF, and alpha-fetoprotein (AFP) levels in the plasma did not show any such changes. Multivariable analysis, propensity score-matched analysis, and time-dependent receiver operating curve analysis revealed that Ang-2 levels had the highest predictive power for OS and PFS. Neither Ang-1 nor VEGF was significantly associated with OS or PFS. The neutrophil-to-lymphocyte ratio was an independent factor for OS and PFS.

Conclusion: The plasma levels of Ang-2 correlated with liver function, tumor stage, and tumor invasiveness, showing better performance in predicting OS and PFS than AFP, Ang-1, or VEGF.
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http://dx.doi.org/10.3748/wjg.v27.i27.4453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316901PMC
July 2021

Clinical Characteristics of Long-Term Survivors After Sorafenib Treatment for Unresectable Hepatocellular Carcinoma: A Korean National Multicenter Retrospective Cohort Study.

J Hepatocell Carcinoma 2021 18;8:613-623. Epub 2021 Jun 18.

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Background/aim: Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment.

Methods: This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles.

Results: The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P < 0.001), hand-foot skin reaction (aHR = 1.688; P = 0.003), and concomitant treatment with chemoembolization or radiotherapy (aHR = 2.766; P < 0.001). Poor prognostic factors of long-term survival were a Child-Pugh score of B (HR = 0.422; P < 0.001), the presence of extrahepatic metastasis (HR = 0.639; P = 0.005), main portal vein invasion (HR = 0.502; P = 0.001), and elevated alpha-fetoprotein (>1,000 ng/mL; HR = 0.361; P < 0.001).

Conclusion: This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.
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http://dx.doi.org/10.2147/JHC.S304439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219232PMC
June 2021

Long-term mortality due to infection associated with elevated liver enzymes: a population-based cohort study.

Sci Rep 2021 06 14;11(1):12490. Epub 2021 Jun 14.

Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam, 463-707, South Korea.

We aimed to investigate whether elevated liver enzymes in the adult population were associated with mortality due to infection. As a population-based cohort study, data from the National Health Insurance Service Health Screening Cohort were used. Adult individuals (aged ≥ 40 years) who underwent standardized medical examination between 2002 and 2003 were included, and infectious mortality was defined as mortality due to infection between 2004 and 2015. Aspartate transaminase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), AST/ALT ratio, and dynamic AST/ALT ratio (dAAR) were included in multivariable Cox modeling. A total of 512,746 individuals were included in this study. Infectious mortality occurred in 2444 individuals (0.5%). In the multivariable model, moderate and severe elevation in AST was associated with 1.94-fold [hazard ratio (HR):1.94, 95% confidence interval (CI) 1.71-2.19; P < 0.001] and 3.93-fold (HR: 3.93, 95% CI 3.05-5.07; P < 0.001) higher infectious mortality respectively, compared with the normal AST group. Similar results were observed for moderate and severe elevation in ALT and mild, moderate, and severe elevation in γ-GTP. Additionally, a 1-point increase in the AST/ALT ratio and dAAR was associated with higher infection mortality. Elevated liver enzymes (AST, ALT, AST/ALT ratio, γ-GTP, and dAAR) were associated with increased infectious mortality.
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http://dx.doi.org/10.1038/s41598-021-92033-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203630PMC
June 2021

Computed Tomography-Measured Liver Volume Predicts the Risk of Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients.

Dig Dis Sci 2021 Dec 25;66(12):4536-4544. Epub 2021 Feb 25.

Department of Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Aim: In this retrospective cohort study, we evaluated the significance of liver volume in the prediction of hepatocellular carcinoma (HCC) in 277 chronic hepatitis C (CHC) patients who received dynamic computed tomography (CT) during surveillance.

Methods: Liver volumes were measured on portal venous phase of CT images by using ImageJ software. Liver volume index, a ratio of the standard liver volume expected by weight and height to the measured liver volume, was calculated to adjust for normal variations. The cohort was randomly divided to derivation (n = 100) and validation sets (n = 177) for the generation of a liver volume-based Cox prediction model and validation of a liver volume-based nomogram, respectively.

Results: The liver volume index was independent of weight or height, and it predicted further development of HCC (hazard ratio [HR] 16.30, 95% CI 6.70-39.62; p < 0.001). Liver cirrhosis, gamma-glutamyl transferase, and liver volume index were independent predictors of HCC, and nomogram-based prediction score from these three parameters identified high-risk patients at the cutoff of 110 in both derivation (p < 0.001) and validation cohort (p < 0.001).

Conclusion: Liver volume-based prediction model stratifies the risk of developing HCC in CHC patients whose initial dynamic CT study gave negative results.
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http://dx.doi.org/10.1007/s10620-020-06762-wDOI Listing
December 2021

Effectiveness of 4-Week Oral Taurine Treatment for Muscle Cramps in Patients with Liver Cirrhosis: A Single-Arm Pilot Study.

Yonsei Med J 2021 Jan;62(1):21-28

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Purpose: Painful muscle cramps are a common complication in liver cirrhosis patients, and no effective treatment is available. This pilot study aimed to evaluate whether taurine supplementation improves muscle cramps in Korean cirrhotic patients.

Materials And Methods: Ten cirrhotic patients who experienced muscle cramps one or more times/week were enrolled in this prospective single-arm study and administered with an oral taurine solution (1 g/50 mL) thrice a day for 4 weeks. Taurine was discontinued for the subsequent 4 weeks. The frequency and intensity of muscle cramps were evaluated using a questionnaire at weeks 0, 2, 4, 6, and 8 after the start of treatment.

Results: At baseline, the median frequency of muscle cramps was six times/week, and all patients had severe pain. Muscle cramp scores (frequency×intensity) decreased in seven patients by weeks 4 and 8 after treatment initiation. Compared to baseline muscle cramp scores [median 21, interquartile range (IQR): 8-84], median muscle cramp scores were lower at week 4 (6.5, IQR: 3-12, =0.126) and week 8 (5, IQR: 1.5-56, =0.066). All five patients whose baseline plasma taurine levels were below the normal limit showed increased taurine levels at week 4; 60% of them experienced improvements in their muscle cramps. Of the five patients with normal or higher taurine levels, 80% experienced an improvement in symptoms at week 4. The safety and tolerability of the 4-week taurine therapy were excellent.

Conclusion: Oral taurine therapy for 4 weeks improved muscle cramps safely in cirrhotic patients.
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http://dx.doi.org/10.3349/ymj.2021.62.1.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820453PMC
January 2021

Deep learning model for prediction of hepatocellular carcinoma in patients with HBV-related cirrhosis on antiviral therapy.

JHEP Rep 2020 Dec 30;2(6):100175. Epub 2020 Aug 30.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background & Aims: Personalised risk prediction of the development of hepatocellular carcinoma (HCC) among patients with liver cirrhosis on potent antiviral therapy is important for targeted screening and individualised intervention. This study aimed to develop and validate a new model for risk prediction of HCC development based on deep learning, and to compare it with previously reported risk models.

Methods: A novel deep-learning-based model was developed from a cohort of 424 patients with HBV-related cirrhosis on entecavir therapy with 2 residual blocks, including 7 layers of a neural network, and it was validated using an independent external cohort (n = 316). The deep-learning-based model was compared to 6 previously reported models (platelet, age, and gender-hepatitis B score [PAGE-B], Chinese University HCC score [CU-HCC], HCC-Risk Estimating Score in CHB patients Under Entecavir [HCC-RESCUE], age, diabetes, race, etiology of cirrhosis, sex, and severity HCC score [ADRESS-HCC], modified PAGE-B score [mPAGE], and Toronto HCC risk index [THRI]) using Harrell's concordance ()-index.

Results: During a median 5.2 yr of follow-up (inter-quartile range 2.8-6.9 yr), 86 patients (20.3%) developed HCC. The deep-learning-based model had a Harrell's -index of 0.719 in the derivation cohort and 0.782 in the validation cohort. Goodness of fit was confirmed by the Hosmer-Lemeshow test ( >0.05). Moreover, this model in the validation cohort had the highest -index among the 6 previously reported models: PAGE-B (0.570), CU-HCC (0.548), HCC-RESCUE (0.577), ADRESS-HCC (0.551), mPAGE (0.598), and THRI (0.587) (all <0.001). The misclassification rate of this model was 23.7% (model accuracy: 76.3%) in the validation group.

Conclusions: The deep-learning-based model had better performance than the previous models for predicting the HCC risk in patients with HBV-related cirrhosis on potent antivirals.

Lay Summary: For early detection of hepatocellular carcinoma, it is important to maintain regular surveillance. However, there is currently no standard prediction model for risk stratification that can be used to establish a personalised surveillance strategy. We develop and validate a deep-learning-based model that showed better performance than previous models.
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http://dx.doi.org/10.1016/j.jhepr.2020.100175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581930PMC
December 2020

A Case of Autoimmune Hepatitis after Occupational Exposure to N,N-Dimethylformamide.

J Korean Med Sci 2020 Jul 20;35(28):e228. Epub 2020 Jul 20.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

N,N-dimethylformamide (DMF), a widely used solvent in the chemical industry, is known to induce toxic hepatitis. However, there have been no reported cases of DMF-associated autoimmune hepatitis. A 31-year-old healthy man working at a glove factory since July 2015 had intermittently put his bare hands into a diluted DMF solution for his first 15 days at work. After 2 months, he felt nausea, fatigue, and hand cramping, and a jaundice followed. His laboratory findings showed positive autoantibodies and elevated immunoglobulin G (IgG), and his liver biopsy pathology was typical of autoimmune hepatitis (AIH). Prednisolone and azathioprine therapy began, and he recovered rapidly without adverse events. Though his liver chemistry was normalized, the IgG level remained persistently upper normal range. His 2nd liver biopsy performed in April 2019 showed mild portal activity, and he was well under a low dose immunosuppressive therapy up to April 2020. This case warns of the hazard of occupational exposure to DMF, and clinicians should be aware of DMF-related AIH for timely initiation of immunosuppressive therapy.
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http://dx.doi.org/10.3346/jkms.2020.35.e228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371453PMC
July 2020

The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma.

Clin Mol Hepatol 2020 10 10;26(4):492-505. Epub 2020 Jul 10.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival.

Methods: Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017.

Results: The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients.

Conclusion: The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.
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http://dx.doi.org/10.3350/cmh.2020.0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641544PMC
October 2020

Comorbidities and Prescribed Medications in Korean Patients with Chronic Hepatitis C: A Nationwide, Population-Based Study.

Gut Liver 2021 Mar;15(2):295-306

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: Extrahepatic comorbidities and comedication are important to consider in the treatment of chronic hepatitis C (CHC) patients with direct-acting antivirals (DAAs) due to the risk of drug-drug interaction (DDI) and the effect of comorbidities on clinical outcomes. This study aimed to investigate the detailed profiles of comorbidities and comedication among Korean CHC patients.

Methods: All adult patients (≥18 years old) with a primary diagnostic code of CHC in 2013 were selected from the National Health Insurance claims database. For each patient, all ICD-10 codes listed as primary or secondary diagnoses and all prescribed medications were collected.

Results: Among 47,104 CHC patients (median age, 57 years; male, 49.3%), 84.8% had at least one comorbidity for a mean number of 2.4, which increased with age. The most prevalent comorbidities were hypertension, esophagitis, dyslipidemia, diabetes mellitus, and peptic ulcer. Overall, 96.8% of the patients took at least one prescribed medication, with a mean of 8.1 medications/ year, and the three most common drug types were analgesics, gastrointestinal agents, and antibacterials. Use of at least one drug with a DDI risk category of "contraindicated medication" or "required dose-reduction/additional monitoring" was observed in 97% of the overall patients. The proportion of prescribed medications that were contraindicated with DAAs varied from 2.0% to 38.9% depending on the hepatitis C virus regimen.

Conclusions: The majority of CHC patients had comorbidities; almost all patients took multiple prescribed medications, the number of which increased with age, and significant DDI risk was present in 97% of this Korean patient cohort. Comorbidities and comedication profiles should be considered during DAA therapy.
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http://dx.doi.org/10.5009/gnl19387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960981PMC
March 2021

Effectiveness and safety of elbasvir/grazoprevir in Korean patients with hepatitis C virus infection: a nationwide real-world study.

Korean J Intern Med 2021 03 17;36(Suppl 1):S1-S8. Epub 2020 Jun 17.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

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-naïve 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.

Conclusion: 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.
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http://dx.doi.org/10.3904/kjim.2019.357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009154PMC
March 2021

A case of acute liver failure due to hepatitis E virus, liver transplantation, and development of de novo autoimmune hepatitis.

Transpl Infect Dis 2020 Jun 23;22(3):e13287. Epub 2020 Apr 23.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

Acute hepatitis E virus (HEV) infection could lead to acute liver failure (ALF), which requires liver transplantation (LT). HEV infection could progress to chronic infection in an immunosuppressed host. De novo autoimmune hepatitis (AIH) is a rare occurrence of AIH during post-LT immunosuppressive therapy in patients who underwent LT due to not AIH but some other etiology. Here, we report the first case of ALF due to HEV infection, the recurrence of HEV after LT that responded to ribavirin therapy, and then the development of de novo AIH showing a complete response to glucocorticoid therapy but multiple relapses after steroid withdrawal. This peculiar case suggests that HEV could have a pathogenic role in the development of the de novo AIH; additionally, this case report could help clinicians make therapeutic decisions in the post-LT condition.
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http://dx.doi.org/10.1111/tid.13287DOI Listing
June 2020

Environmental risk factors and comorbidities of primary biliary cholangitis in Korea: a case-control study.

Korean J Intern Med 2021 03 26;36(2):313-321. Epub 2020 Mar 26.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aims: The risk factors for the development of primary biliary cholangitis (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 standardized 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 multivariable 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.

Conclusion: 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.
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http://dx.doi.org/10.3904/kjim.2019.234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969053PMC
March 2021

Comparison of the on-treatment risks for hepatocellular carcinoma between entecavir and tenofovir: A propensity score matching analysis.

J Gastroenterol Hepatol 2020 Oct 20;35(10):1774-1781. Epub 2020 Mar 20.

Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

Background And Aim: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) may reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). However, it is not clear whether there is difference in the on-treatment HCC risks between ETV and TDF.

Methods: In this retrospective cohort study, we compared the on-treatment HCC incidence of ETV and TDF in 1340 consecutive nucleos(t)ide analog-naïve CHB patients by propensity score (PS) matching analysis. PS was calculated by using age, sex, drinking history, diabetes, liver cirrhosis, hepatitis B e antigen positivity, hepatitis B virus DNA, hepatitis B s antigen titer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein, albumin, bilirubin, prothrombin time, platelet count, and calendar year of treatment initiation as covariates. The HCC risk was assessed by Cox regression with death and liver transplantation as competing risks in the 1:1 PS-matched cohorts (n = 596).

Results: TDF had higher cumulative virologic response (P = 0.027) whereas ETV showed higher AST and ALT normalization rates (P = 0.005 and < 0.001, respectively) in PS-matched cohorts. HCC risk was similar between ETV and TDF, either by PS-matching analysis (hazard ratio [HR] for TDF over ETV = 2.06, 95% confidence interval [CI] = 0.98-4.33, P = 0.058) or inverse probability of treatment weighting analysis (HR = 1.30, 95% CI = 0.81-2.10; P = 0.276).

Conclusions: ETV and TDF treatment was associated with similar risk for HCC development in CHB patients.
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http://dx.doi.org/10.1111/jgh.15031DOI Listing
October 2020

A Survey of the Knowledge of and Testing Rate for Hepatitis C in the General Population in South Korea.

Gut Liver 2020 11;14(6):808-816

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: To eliminate hepatitis C virus (HCV) infection, improving public knowledge of and access to HCV screening and treatment is essential. The aim of this study was to evaluate the knowledge of and testing rate for HCV and the opinions about the inclusion of the HCV test in the National Health Examination (NHE) among the general population in South Korea.

Methods: A telephone interview survey was conducted by an independent research company using a 16 item-questionnaire (demographics, knowledge of HCV, testing and results, need for screening) in May 2019. The sample population consisted of 1,003 adult Korean residents adjusted by age, sex, and area according to the standard Korean population in 2019.

Results: Among the 1,003 participants (505 women, mean age of 47.9 years), 56.4% recognized HCV; 44.4% understood that HCV is transmittable, and 56.8% thought that HCV is curable by medication. The recognition rate tended to increase with an increasing level of education. Testing for anti-HCV antibodies was reported by 91 people (9.1%); among them, 10 people (11.0%) reported a positive result, and eight people received treatment. The common reasons for HCV testing were a health check-up (58.5%), a physician's recommendation (11.0%) and elevated liver enzyme levels (10.7%). The majority of the population (75.1%) agreed with the integration of HCV into the NHE.

Conclusions: The level of knowledge of HCV is suboptimal, and the self-reported testing rate for HCV is less than 10%; however, once HCV infection is diagnosed, the treatment rate seems to be high in South Korea. More active campaigns and effective screening are needed.
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http://dx.doi.org/10.5009/gnl19296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667921PMC
November 2020

Real-Life Effectiveness and Safety of Sofosbuvir-Based Therapy in Genotype 2 Chronic Hepatitis C Patients in South Korea, with Emphasis on the Ribavirin Dose.

Gut Liver 2020 11;14(6):775-782

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

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-naïve patients, the SVR rates were 94.2% (ITT) and 96.7% (PP). Among the 80 treatmentexperienced 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.
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http://dx.doi.org/10.5009/gnl19260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667937PMC
November 2020

Work-Life Conflict and Its Health Effects on Korean Gastroenterologists According to Age and Sex.

Dig Dis Sci 2020 01 23;65(1):86-95. Epub 2019 Sep 23.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea.

Background: This study aimed to evaluate the work-life pattern and prevalence of occupation-related symptoms, as well as the effect of work-life balance on health status according to age and sex among Korean gastroenterologists.

Methods: A total of 222 gastroenterologists from 44 nationwide centers in South Korea participated in an anonymized self-responded electronic questionnaire survey about their daily activities and symptoms for 14 days. Musculoskeletal, gastrointestinal and mental symptoms were scored using a numerical scale. The Maslach Burnout Inventory was used to measure the burnout score.

Results: Korean gastroenterologists (124 men and 98 women) spent 71.5 ± 19.0 h/week for work (54.0 ± 16.2 in-hospital and 17.5 ± 9.5 out-of-hospital), without any differences regarding sex. However, women spent more time performing housework and parenting (20.7 ± 19.0) compared to men (14.3 ± 13.3, P = 0.007). Musculoskeletal pain was found in 199 respondents (89.6%), and women had a higher total pain score compared to men in all age groups (P = 0.016). Gastrointestinal and mental symptoms were found in 119 (53.6%) and 153 (68.9%), respectively. Work-life ratio was significantly correlated with musculoskeletal (P < 0.001), gastrointestinal (P = 0.048) and mental symptoms (P = 0.003). Using the Maslach Burnout Inventory, 64.4% of the respondents demonstrated burnout. Moreover, emotional exhaustion, depersonalization and personal accomplishment scores were worst in women in their 30s or 40s.

Conclusion: Korean gastroenterologists suffered from musculoskeletal, gastrointestinal and mental symptoms and were highly prone to burnout due to long and laboring work. Work-life imbalance and burnout were most severe in young women doctors due to their domestic demands.
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http://dx.doi.org/10.1007/s10620-019-05842-wDOI Listing
January 2020

ABO-incompatible liver transplantation using only rituximab for patients with low anti-ABO antibody titer.

Ann Hepatobiliary Pancreat Surg 2019 Aug 30;23(3):211-218. Epub 2019 Aug 30.

Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Backgrounds/aims: Graft survival after ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has increased due to advances in desensitization methods. We analyzed early outcomes following ABOi LDLT using only rituximab without any additional desensitization methods in recipients with low anti-ABO antibody titers (≤1:32).

Methods: Ten adult patients underwent ABOi LDLT between September 2014 and December 2016. All patients were administered a single dose of rituximab (300 mg/m) prior to LDLT. Three patients with baseline anti-ABO titer >1:32 underwent multiple sessions of plasmapheresis to reduce titers to <1:32 (rituximab+plasmapheresis, RP). Seven patients with low anti-ABO titer (≤1:32) did not undergo plasmapheresis (rituximab-only, RO). ABO-compatible LDLT patients during the same period were included for comparison (n=22).

Results: Post-transplantation titers were significantly lower in the RO than in the RP and showed no rebound rise (POD7 1.14±0.38 vs 28.0±31.7, =0.04), (POD30 1.26±0.45 vs 108±107, =0.02). There were no significant differences in rejection, biliary complications and infection between groups. There were no significant differences in outcome between the RO group and ABO-compatible except for infection.

Conclusions: This study shows that recipients with low baseline anti-ABO antibody titer (≤1:32) can undergo ABOi LDLT using conventional immunosuppression and rituximab alone.
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http://dx.doi.org/10.14701/ahbps.2019.23.3.211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728259PMC
August 2019

Real-life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance-associated substitution test.

J Med Virol 2019 12 9;91(12):2158-2165. Epub 2019 Sep 9.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.

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.
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http://dx.doi.org/10.1002/jmv.25575DOI Listing
December 2019

The change in the nationwide seroprevalence of hepatitis C virus and the status of linkage to care in South Korea from 2009 to 2015.

Hepatol Int 2019 Sep 20;13(5):599-608. Epub 2019 Aug 20.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1007/s12072-019-09975-yDOI Listing
September 2019

MicroRNA‑20 induces methylation of hepatitis B virus covalently closed circular DNA in human hepatoma cells.

Mol Med Rep 2019 Sep 27;20(3):2285-2293. Epub 2019 Jun 27.

Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.

Methylation was suggested to suppress the transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in hepatocytes. This may be associated with its low replicative activity during the inactive stage of chronic HBV infection; however, the exact mechanisms of methylation in HBV infection remain unknown. We have previously shown that short hairpin RNAs induced the methylation of the HBV genome in hepatoma cell lines. We also reported that the microRNA (miR) 17‑92 cluster negatively regulates HBV replication in human hepatoma cells. In addition, miR‑20a, a member of the miR 17‑92 cluster, has sequence homology with the short hairpin RNA that induces HBV methylation. In the present study, we investigated whether miR‑20a can function as an endogenous effector of HBV DNA methylation. The results indicated that overexpression of miR‑20a could suppress the replicative activity of HBV and increased the degree of methylation of HBV cccDNA in the HepAD38 hepatoma cell line. Argonaute (AGO)1 and AGO2, effectors of the RNA‑induced silencing complex, were detected in the nucleus of HepAD38 cells; however, only AGO2 was bound to HBV cccDNA. In addition, intranuclear AGO2 was determined to be bound with miR‑20a. In conclusion, miR‑20a may be loaded onto AGO2, prior to its translocation into the nucleus, inducing the methylation of HBV DNA in human hepatoma cells, leading to the suppression of HBV replication.
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http://dx.doi.org/10.3892/mmr.2019.10435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691198PMC
September 2019

Epidemiological and Clinical Characteristics of Hepatitis C Virus Infection in South Korea from 2007 to 2017: A Prospective Multicenter Cohort Study.

Gut Liver 2020 03;14(2):207-217

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Background/aims: This study aimed to elucidate the epidemiological and clinical characteristics of chronic hepatitis C (CHC) patients in South Korea from 2007 to 2017 and to compare the treatment patterns between two periods before and after the first approval of direct-acting antivirals (DAA) in South Korea in 2015.

Methods: This prospective, multicenter cohort enrolled 2,758 patients with hepatitis C virus (HCV) viremia at seven tertiary centers, and clinical data were prospectively collected with questionnaire surveys focused on lifetime risk factors related to HCV infection.

Results: The HCV patients had a mean age of 57.3 years (50.8% male). Among them, 14.3% showed a positive history of transfusion before HCV screening and 5.6% reported intravenous drug use (IVDU), with significant differences in these risk factors between men and women. The proportions of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) were 69.5%, 18.9%, and 11.5%, respectively. The mean alanine aminotransaminase level was within the upper normal limit at 49.9%, and the major genotypes were 1b (48.2%) and 2 (46.4%). The overall treatment rate was 53.8%, showing a rapid transition from interferon-based therapy to DAA therapy. In the post-DAA-approval era, the untreated group was older, had a higher prevalence of HCC, and had less education than the treated group.

Conclusions: More than 90% of CHC patients were over 40 years old, the major genotypes were 1b and 2, and IVDU was observed in less than 6% of CHC patients. Approximately half of the patients underwent antiviral therapy even in the DAA era, showing an unmet need with regard to HCV elimination.
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http://dx.doi.org/10.5009/gnl19005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096238PMC
March 2020

Diagnostic performance of a point shear wave elastography (pSWE) for hepatic fibrosis in patients with autoimmune liver disease.

PLoS One 2019 11;14(3):e0212771. Epub 2019 Mar 11.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Background & Aims: Elastography point quantification is a convenient method for measuring liver stiffness. It can be performed simultaneously with conventional ultrasonography. This study aimed to evaluate its diagnostic performance for assessing hepatic fibrosis in patients with autoimmune liver disease (AILD), including autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC).

Methods: The diagnostic performance of elastography point quantification (ElastPQ) was evaluated and compared with that of serum fibrosis markers, including the aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4), using the receiver operating characteristics analysis with histologic evaluation as the reference standard.

Results: In 49 AIH patients, sensitivity and specificity of ElastPQ were 93.6% and 44.4%, respectively, for significant fibrosis (≥ F2, cutoff 4.47 kPa), and 63.6% and 86.8% for cirrhosis (F4, cutoff 9.28 kPa). In 41 PBC patients, they were 81.8% and 73.3%, respectively, for significant fibrosis (≥ F2, cutoff 5.56 kPa), and 100% and 81.6%, respectively, for advanced fibrosis (≥ F3, cutoff 6.04 kPa). The areas under the receiver operating characteristic curves of ElastPQ for significant fibrosis (0.77, 95% CI 0.67-0.86) and cirrhosis (0.81, 95% CI 0.65-0.96) were higher than those of APRI and FIB-4 in AILD patients. According to the multivariable analysis, histological activity, steatosis, and body max index (BMI) were not significant factors that influenced the result of ElastPQ.

Conclusions: ElastPQ exhibited better diagnostic performance-without the influence of confounding factors-for assessing hepatic fibrosis in AILD patients than serum fibrosis markers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411150PMC
November 2019

Development of colorectal cancer predicts increased risk of subsequent hepatocellular carcinoma in patients with alcoholic liver disease: case-control and cohort study.

Sci Rep 2019 03 1;9(1):3236. Epub 2019 Mar 1.

Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

Alcohol increases the risk of both hepatocellular carcinoma (HCC) and colorectal neoplasia. In this hospital-based case-control and retrospective cohort study, we sought to determine whether development of colorectal neoplasia increases the risk of HCC in patients with alcoholic liver disease (ALD). In the phase I case-control analysis, the association between history of colorectal cancer (CRC) and HCC development was assessed in patients with ALD by logistic regression modeling (n = 1,659). In the phase II retrospective cohort analysis, the relative risk of HCC development was compared in ALD patients with respect to the history of CRC by a Cox model (n = 1,184). The history of CRC was significantly associated with HCC in the case-control analysis (adjusted odds ratio, 1.82; 95% CI, 1.06-3.15; P < 0.05). ALD patients with CRC had higher risk of developing HCC compared to those without CRC (adjusted hazards ratio [HR], 5.48; 95% CI, 1.63-18.36; P = 0.006) in the cohort analysis. Presence of CRC, liver cirrhosis, elevated baseline alpha-fetoprotein level, and low platelet counts were independent predictors of HCC development in ALD patients. Patients with history of CRC had an increased risk of HCC in both cirrhotic (HR, 3.76; 95% CI, 1.05-13.34, P = 0.041) and non-cirrhotic (HR, 23.46; 95% CI, 2.81-195.83, P = 0.004) ALD patients. In conclusion, ALD patients with CRC are at increased risk of developing HCC.
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http://dx.doi.org/10.1038/s41598-019-39573-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397178PMC
March 2019

Liver volume index predicts the risk of esophageal variceal hemorrhage in cirrhotic patients on propranolol prophylaxis.

Korean J Intern Med 2019 Nov 18;34(6):1233-1243. Epub 2019 Feb 18.

Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Background/aims: Non-selective β-blockers (NSBBs) are used for primary prevention of esophageal variceal hemorrhage (VH) in patients with portal hypertension, but a significant number of patients develop VH while on NSBB therapy. In this study, we sought to determine whether liver volume can predict the risk of primary prophylaxis failure in cirrhotic patients on NSBB therapy.

Methods: A retrospective cohort of 309 patients on prophylactic propranolol was analyzed. Liver volume was measured in portal venous phase images of multidetector computed tomography. Predictors of VH were assessed using a Cox proportional hazards model with competing-risks analysis. A nomogram was developed for estimation of the risk of primary prophylaxis failure.

Results: During a median follow-up of 36 months, 37 patients on propranolol developed VH. Liver volume index, the ratio of measured-to-expected liver volume, was an independent predictor of VH (adjusted hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.37 to 5.33; p = 0.004) as were the presence of large varices and the absence of ascites. A nomogram-based volume score of > 0.6 was predictive of prophylaxis failure (HR, 7.54; 95% CI, 2.88 to 19.73; p < 0.001). Time-dependent receiver operating characteristic curve analysis revealed that a nomogram-based risk score had significantly better discriminatory power than the North Italian Endoscopy Club index in predicting prophylaxis failure at 6 and 8 years.

Conclusion: Liver volume index is an independent predictor of first VH and a nomogram-based volume score stratifies the VH risk in cirrhotic patients on propranolol prophylaxis.
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http://dx.doi.org/10.3904/kjim.2018.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823564PMC
November 2019
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