Publications by authors named "Tae-Suk Kim"

95 Publications

Endothelial Cells Differentiated from Porcine Epiblast Stem Cells.

Cell Reprogram 2021 Apr;23(2):89-98

Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, Republic of Korea.

Pluripotent stem cells (PSCs) have the ability of self-renewal that can retain the characteristics of the mother cell, and of pluripotency that can differentiate into several body types. PSCs typically include embryonic stem cells (ESCs) derived from the inner cell mass of the preimplantation embryo, and epiblast stem cells (EpiSCs) derived from the epiblast of postimplantation embryo. Although PSCs are able to be used by differentiation into endothelial cells as a potential treatment for vascular diseases, human ESCs and induced PSCs (iPSCs) are followed by ethical and safety issues. Pigs are anatomically and physiologically similar to humans. Therefore, the goal of this study was to establish an efficient protocol that differentiates porcine EpiSCs (pEpiSCs) into the endothelial cells for applying the treatment of human vascular diseases. As a result, alkaline phosphatase (AP)-negative (-) pEpiSCs cultured in endothelial cell growth basal medium-2 (EBM-2) differentiation medium in association with 50 ng/mL of vascular endothelial growth factor (VEGF) for 8 days were changed morphologically like the feature of endothelial cells, and expression of pluripotency-associated markers (OCT-3/4, NANOG, SOX2, and C-MYC) in porcine differentiated cells was significantly decreased ( < 0.05). Additionally, when pEpiSCs were cultured in EBM-2 + 50 ng/mL of VEGF, porcine differentiated cells represented a common endothelial cell marker positive (CD31+) but monocytes and lymphocytes marker negative (CD45-). Therefore, these results indicated that pEpiSCs cultured in EBM-2 + 50 ng/mL of VEGF culture condition were efficiently differentiated into endothelial cells for the treatment of blood vessel diseases.
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http://dx.doi.org/10.1089/cell.2020.0088DOI Listing
April 2021

The longitudinal outcomes of applying non-selective beta-blockers in portal hypertension: real-world multicenter study.

Hepatol Int 2021 Apr 16. Epub 2021 Apr 16.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20, Ilsan-ro, Wonju, 26426, Korea.

Background/aim: We investigated the effect of non-selective β-blockers (NSBB) in real-world situations and whether low-dose NSBB is beneficial compared to maximally tolerated doses.

Methods: We performed a retrospective study of 740 patients with cirrhosis requiring prophylactic treatment of esophageal varices: 473 primary prophylaxis (PP: NSBB = 349, non-NSBB = 124) and 267 secondary prophylaxis (SP: NSBB = 200, non-NSBB = 67). The NSBB group was divided into low-dose (≤ 80 mg/day) and high-dose (> 80 mg/day).

Results: In the PP group, NSBB treatment reduced mortality and showed the most pronounced effect in patients with moderate/severe ascites (hazard ratio [HR], 0.46; p < 0.01), HVPG ≥ 16 mmHg (HR, 0.53; p = 0.04), or CTP class B/C (HR, 0.46; p < 0.01) but not in those with no/mild ascites, HVPG < 16 mmHg, or CTP class A. Low-dose NSBB group showed a significant reduction in mortality compared with non-NSBB (moderate/severe ascites: HR, 0.61; p = 0.02 and CTP class B/C: HR, 0.41; p < 0.01) and the effect size was stronger than the high-dose NSBB. NSBB was associated with a reduced risk of infection (HR, 0.36; p = 0.01). In the SP group, NSBB prolonged survival in patients with moderate/severe ascites (HR, 0.56; p = 0.02), HVPG ≥ 16 mmHg (HR, 0.42; p < 0.01), or CTP class B/C (HR, 0.52; p < 0.01). Low-dose NSBB was more beneficial with 56% risk reduction (p < 0.01) of mortality compared with 33% risk reduction in the high-dose NSBB (p = 0.05).

Conclusion: NSBB therapy was associated with longer survival in PP and SP groups who had an advanced stage of cirrhosis. Moreover, low-dose NSBB exhibited a better benefit than a standard-titrated high-dose NSBB with better tolerability.
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http://dx.doi.org/10.1007/s12072-021-10160-3DOI Listing
April 2021

Decreased cardiovascular death in schizophrenia patients treated with antipsychotics: A Korean national cohort study.

Schizophr Res 2021 Feb 5;228:417-424. Epub 2021 Feb 5.

Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Patients with schizophrenia have a reduced life expectancy, but the association between antipsychotic usage and cause of death is uncertain.

Methods: The authors observed associations of antipsychotic usage with the mortality rate and cause of death in a population-based cohort of the Korean National Health Insurance Service database from 2003 to 2017. A total of 86,923 patients with schizophrenia were categorized by the total duration of antipsychotic prescription after schizophrenia diagnosis into treated (n = 77,139) and untreated (n = 9784) groups. The main outcome was all-cause mortality; causes of death included cardiovascular disease, pulmonary disease, diabetes, cancer, accident, suicide and homicide.

Results: The numbers of all-cause deaths and deaths from individual causes were significantly lower in the antipsychotic-treated group than in the untreated group (all cases, p < 10). When adjusted for covariates (age, sex, income, body mass index, alcohol consumption, hypertension, cancer and cerebral stroke), mortality rates due to ischemic heart disease (hazard ratio, HR, 0.38 [95% CI, 0.18-0.77]) and stroke (HR, 0.39 [95% CI, 0.19-0.80]) were significantly lower in the antipsychotic-treated group. Among 4 atypical antipsychotics (olanzapine, risperidone, aripiprazole and quetiapine), only aripiprazole was associated with a decreased mortality risk relative to olanzapine (HR, 0.55 [95% CI, 0.32-0.96]).

Conclusions: Schizophrenia patients constantly prescribed antipsychotics had significantly lower rates of death from certain cardiovascular illnesses than untreated patients. Aripiprazole-treated schizophrenia was associated with a decreased risk of death compared with olanzapine-treated disease.
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http://dx.doi.org/10.1016/j.schres.2021.01.006DOI Listing
February 2021

Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study.

Cancers (Basel) 2020 Nov 12;12(11). Epub 2020 Nov 12.

Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24253, Korea.

Previous studies reported that serum myostatin is associated with sarcopenia. We aimed to elucidate the association between serum myostatin levels and hepatocellular carcinoma (HCC) development in patients with alcoholic liver cirrhosis (ALC). This retrospective, multicenter study assessed 1077 Asian ALC patients enrolled from 2007 to 2017. The primary endpoint was the development of HCC within 5 years. Cox proportional hazards model analyses were used to assess the association of serum myostatin levels and HCC development. The time-dependent areas under the receiver operating characteristic curve (AUROC) of serum myostatin for 5-year HCC development were calculated. Serum myostatin levels were measured using an enzyme-linked immunosorbent assay with samples collected on the index date. During a median follow-up of 2.5 years, 5-year cumulative HCC incidence rates were 6.7% in the total population. The median level of serum myostatin was 3.3 ng/mL (interquartile, 2.1-5.2 ng/mL). The AUROC of serum myostatin for 5-year HCC development was 0.78 (95% confidence interval [CI], 0.76-0.81). In Cox proportional hazards model analyses, age, gender, platelet counts, and serum myostatin levels were independent risk factors for HCC development (adjusted hazard ratios [HRs] of age, male gender, platelet counts, and serum myostatin: 1.03, 2.79, 0.996, 1.18, respectively; all < 0.05). Patients with high myostatin levels had a significantly higher risk of 5-year HCC development than those with low myostatin levels (HR 7.53, < 0.001). Higher serum myostatin levels were significantly associated with a higher risk of developing HCC in ALC patients, which could identify high-risk patients who need stringent surveillance.
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http://dx.doi.org/10.3390/cancers12113347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697795PMC
November 2020

Serrated Polyposis Syndrome with a Synchronous Colon Adenocarcinoma Treated by an Endoscopic Mucosal Resection.

Korean J Gastroenterol 2020 09;76(3):159-163

Department of Anatomic Pathology, Kangwon National University School of Medicine, Chuncheon, Korea.

Serrated polyposis syndrome (SPS) can transform to malignant lesions through the sessile serrated pathway and traditional serrated pathway. These pathways may cause rapid neoplastic progression compared to the adenoma-carcinoma sequence, which may cause interval colorectal cancer. The authors experienced a case of SPS with a synchronous colon adenocarcinoma that was treated with an endoscopic mucosal resection. In pathology reviews, other parts of the adenocarcinoma showed sessile serrated adenoma. Therefore, patients with SPS have a potential for malignant transformation, highlighting the need for strict colonoscopy surveillance starting at the time of SPS diagnosis.
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http://dx.doi.org/10.4166/kjg.2020.76.3.159DOI Listing
September 2020

Individualized surveillance of chronic hepatitis B patients according to hepatocellular carcinoma risk based on PAGE-B scores.

Eur J Gastroenterol Hepatol 2020 Aug 14. Epub 2020 Aug 14.

Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea.

Background And Aims: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-month ultrasonography. We aimed to compare detection rates of very-early-stage HCC in two groups: group A, undergoing 6-month ultrasonography versus group B, undergoing 6-month ultrasonography alternating with dynamic computed tomography (CT).

Methods: This retrospective study assessed 2151 CHB patients under entecavir/tenofovir therapy from 2007 to 2016. Detection rates of very-early-stage HCC were compared between groups A/B at intermediate/high risk based on platelets, age, gender-hepatitis B scores. The primary endpoint was the proportion of patients in each group with very-early-stage HCC. Cox proportional hazards model was used to assess the effect of surveillance modalities to detect very-early-stage HCC.

Results: Five-year cumulative HCC incidence rates in group A were 15.0% not significantly different from 18.2% in group B at high risk (P = 0.17). Detection rates of very-early-stage HCC were significantly higher in group B than in group A (P < 0.001), and surveillance using CT alternating with ultrasonography was significantly associated with detection of very-early-stage HCC (hazard ratio 3.89, P < 0.001). Among intermediate-risk patients, difference between detection rates of very-early-stage HCC in groups A and B was not significant (P = 0.30), and surveillance using CT alternating with ultrasonography was not significantly associated with detection of very-early-stage HCC (hazard ratio 1.61, P = 0.23).

Conclusion: In high-risk CHB patients, surveillance using CT alternating with ultrasonography led to higher detection rates of very-early-stage HCC compared to surveillance using ultrasonography.
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http://dx.doi.org/10.1097/MEG.0000000000001870DOI Listing
August 2020

Attenuated Visual Function in Patients with Major Depressive Disorder.

J Clin Med 2020 Jun 22;9(6). Epub 2020 Jun 22.

Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Background: We sought to investigate visual function, primarily, and structural changes in retinal ganglion cells, secondarily, in patients with major depressive disorder.

Methods: A total of 50 normal participants and 49 patients with major depressive disorder were included in this cross-sectional study. The participants underwent 24-2 standard automated perimetry and spectral-domain optical coherence tomography.

Results: The pattern standard deviation (PSD) in the visual field test was higher in the major depressive disorder patients than in the normal control subjects ( = 0.017). The patients with major depressive disorder showed reduced minimum ganglion cell-inner plexiform layer (GCIPL) thickness relative to the normal control participants ( = 0.015). The average score on the Hamilton Depression Rating scale showed a significant correlation with the PSD, minimum GCIPL thickness, and inferior GCIPL thickness (r = 0.265, = 0.009; r = -0.239, = 0.017; and r = -0.204, = 0.043, respectively). The multivariate analysis of factors associated with PSD showed old age and a high Hamilton Depression Rating score to be relevant ( = 0.002 and 0.028, respectively).

Conclusions: Visual function was decreased and the GCIPL thickness was reduced in major depressive disorder patients. The retinal neurodegenerative process in depression might be considered in patients with depression.
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http://dx.doi.org/10.3390/jcm9061951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356808PMC
June 2020

Liver Dysfunction in Sepsis.

Korean J Gastroenterol 2020 04;75(4):182-187

Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. During sepsis, the liver has essential roles, such as immune defense and metabolic adaptation to inflammation. In addition, it is a target for sepsis-related injury, including hypoxic hepatitis, cholestasis, drug-induced liver injury, and secondary sclerosing cholangitis in critically ill patients. In particular, the mortality rate due to sepsis is four times higher in patients with cirrhosis, warranting a high index of suspicion for infection, appropriate diagnosis, and prompt antimicrobial treatment. The most recent definition of sepsis (Sepsis-3) no longer uses systemic inflammatory response syndrome (SIRS) and is based on the signs of organ dysfunction, which can be assessed by the Sequential Organ Failure Assessment (SOFA) and quick SOFA (qSOFA) scores. The qSOFA score can be applied at the bedside before any tests and is believed to be suggestive of sepsis when at least two of the following criteria are met: altered consciousness, respiratory rate ≥22/min, and systolic blood pressure ≤100 mmHg. While the qSOFA score performs well in the general population, its role in cirrhotic patients is unclear. This paper briefly reviews the current knowledge of the pathogenesis, definition of sepsis, and sepsis-related liver dysfunction. Furthermore, this review summarizes the clinical applicability of Sepsis-3 in cirrhotic patients.
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http://dx.doi.org/10.4166/kjg.2020.75.4.182DOI Listing
April 2020

Association Between Macronutrients Intake and Depression in the United States and South Korea.

Front Psychiatry 2020 17;11:207. Epub 2020 Mar 17.

Department of Psychiatry, The Catholic University of Korea, Seoul, South Korea.

Although the risk for depression appears to be related to daily dietary habits, how the proportion of major macronutrients affects the occurrence of depression remains largely unknown. This study aims to estimate the association between macronutrients (i.e., carbohydrate, protein, fat) and depression through national survey datasets from the United States and South Korea. Association between the prevalence of depression and each macronutrient was measured from 60,935 participants from the National Health and Nutrition Examination Survey (NHANES) and 15,700 participants from the South Korea NHANES (K-NHANES) databases. When the proportion of calories intake by protein increased by 10%, the prevalence of depression was significantly reduced both in the United States [Odds Ratio, OR (95% CI), 0.621 (0.530-0.728)] and South Korea [0.703 (0.397-0.994)]. An association between carbohydrate intake and the prevalence of depression was seen in the United States [1.194 (1.116-1.277)], but not in South Korea. Fat intake was not significantly associated with depression in either country. Subsequent analysis showed that the low protein intake groups had significantly higher risk for depression than the normal protein intake groups in both the United States [1.648 (1.179-2.304)] and South Korea [3.169 (1.598-6.286)]. In the daily diet of macronutrients, the proportion of protein intake is significantly associated with the prevalence of depression. These associations were more prominent in adults with insufficient protein intake, and the pattern of association between macronutrients and depression in Asian American and South Korean populations were similar. Our findings suggest that the proportion of macronutrients intake in everyday life may be related to the occurrence of depression.
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http://dx.doi.org/10.3389/fpsyt.2020.00207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090018PMC
March 2020

Out-of-Hospital Cohort Treatment of Coronavirus Disease 2019 Patients with Mild Symptoms in Korea: an Experience from a Single Community Treatment Center.

J Korean Med Sci 2020 Apr 6;35(13):e140. Epub 2020 Apr 6.

Department of Neurosurgery, Kangwon National University School of Medicine, Chuncheon, Korea.

The outbreak of Coronavirus Disease 2019 (COVID-19) caused a worldwide pandemic. Less than 6 weeks after the first confirmed cases in Korea, the patient number exceeded 5,000, which overcrowded limited hospital resources and forced confirmed patients to stay at home. To allocate medical resources efficiently, Korea implemented a novel institution for the purpose of treating patients with cohort isolation out of hospital, namely the Community Treatment Center (CTC). Herein, we report results of the initial management of patients at one of the largest CTC in Korea. A total of 309 patients were admitted to our CTC. During the first two weeks, 7 patients were transferred to the hospital because of symptom aggravation and 107 patients were discharged without any complication. Although it is a novel concept and may have some limitations, CTC may be a very cost-effective and resource-saving strategy in managing massive cases of COVID-19 or other emerging infectious diseases.
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http://dx.doi.org/10.3346/jkms.2020.35.e140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131899PMC
April 2020

Improved detection of hepatocellular carcinoma by dynamic computed tomography in cirrhotic patients with chronic hepatitis B: A multicenter study.

J Gastroenterol Hepatol 2020 Oct 20;35(10):1795-1803. Epub 2020 Apr 20.

Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Korea.

Background And Aims: Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasonography (US). However, sensitivities of US to detect early-stage HCC in cirrhotic patients are suboptimal. We aimed to compare overall survival and detection rates of very-early-stage HCC in two groups: group A, undergoing 6-monthly US versus group B, undergoing 6-monthly US alternating with dynamic computed tomography (CT).

Methods: This retrospective multicenter study assessed 1235 cirrhotic patients with CHB under entecavir/tenofovir therapy from 2007 to 2016. The primary endpoint was overall survival rates between the two groups. The Cox proportional hazards model and propensity score matching analyses were used to assess the effect of surveillance modalities on overall survival and detection of Barcelona Clinic Liver Cancer stage 0 HCC after balancing.

Results: During a median follow-up of 4.5 years, 10-year cumulative HCC incidence rates of 16.3% were significantly higher in group B (n = 576) than 13.7% in group A (n = 659; P < 0.001). However, in patients with HCC, 10-year overall survival rates of 85.1% were significantly higher in group B than 65.6% in group A (P = 0.001 by log-rank test). CT exam alternating with US was independently associated with reduced overall mortality (hazard ratio 0.47, P = 0.02). Cumulative incidence of Barcelona Clinic Liver Cancer stage 0 HCC was significantly higher in group B than in group A (hazard ratio 2.82, P < 0.001).

Conclusion: In cirrhotic patients with CHB, dynamic CT exam alternating with US led to higher detection rates of very-early-stage HCC and benefit of overall survival than did US exams.
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http://dx.doi.org/10.1111/jgh.15046DOI Listing
October 2020

Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach.

Korean J Physiol Pharmacol 2020 Mar 20;24(2):185-191. Epub 2020 Feb 20.

Kangwon National University Institute of Medical Science, Chuncheon 24289, Korea.

Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 240.5, p = 0.047), and myenteric plexus (12.0 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = -0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.
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http://dx.doi.org/10.4196/kjpp.2020.24.2.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043993PMC
March 2020

Aspirin and the risk of hepatocellular carcinoma development in patients with alcoholic cirrhosis.

Medicine (Baltimore) 2020 Feb;99(9):e19008

Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon.

Aspirin therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether aspirin therapy lowers the risk of HCC in patients with alcoholic cirrhosis.A retrospective analysis of data from 949 consecutive patients with alcoholic cirrhosis who abstained from alcoholic drinking was performed. The primary and secondary outcomes were development of HCC and gastrointestinal bleeding events, respectively. Risk was compared between patients with aspirin treatment and patients who were not treated (non-aspirin group) using a time-varying Cox proportional hazards model for total population and propensity score-matching analysis.The aspirin group included 224 patients and the non-aspirin group had 725 patients. During the study period of median duration of 3.1 years, 133 patients (13.6%) developed HCC. In time-varying Cox proportional analyses, the aspirin group showed a significantly lower risk of HCC (adjusted hazard ratio [aHR]: 0.13; 95% confidence interval [CI]: 0.08-0.21; P < .001). In propensity score-matched pairs, aspirin therapy significantly reduced the risk of HCC (aHR: 0.14; 95% CI: 0.09-0.22; P < .001). In bleeding risk, treatment with aspirin alone was not significantly associated with a higher bleeding risk (aHR: 0.81; 95% CI: 0.45-1.44; P = .46).Aspirin therapy was associated with the lower risk of HCC in patients with alcoholic cirrhosis.
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http://dx.doi.org/10.1097/MD.0000000000019008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478404PMC
February 2020

Anxiety and Depression of the Patients with Hematological Malignancies during Hospitalization for Hematopoietic Stem Cell Transplantation.

Psychiatry Investig 2019 Oct 30;16(10):751-758. Epub 2019 Sep 30.

Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Objective: This study aimed to assess the anxiety and depression in patients undergoing hematopoietic stem cell transplantation (HSCT).

Methods: Eighty-seven adult patients with various hematologic diseases, who were scheduled to receive autologous or allogeneic HSCT, were enrolled. The M.D. Anderson Symptom Inventory and the Hospital Anxiety Depression Scale were applied prospectively at hospital admission (D-14), on the day of transplantation (D day), and at 7 (D7) and 14 days (D14) after transplantation.

Results: The severity of both anxiety and depressive symptoms increased over time, with a peak at D7, and then showed a downturn at D14. Physical distresses also started with mild intensity at base line, which were continuously aggravated until D7, and then a partial recovery afterwards. Approximately, 52% of the participants had significantly high anxiety or depression before the start of HSCT. The occurrence of aggravation of pain, nausea, shortness of breath, and lack of appetite was associated with the development of anxiety during isolation period. The patients with significant baseline anxiety had higher scores on fatigue and shortness of breath items at D7 compared to those without.

Conclusion: Our finding suggests the importance of psychiatric approaches, including preventive measures, for the patients undergoing HSCT.
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http://dx.doi.org/10.30773/pi.2019.07.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801322PMC
October 2019

Impact of Age at Childbirth on Maternal Mental Health among Premenopausal Women: The 2010-2012 Korean National Health and Nutrition Examination Survey.

Psychiatry Investig 2019 Sep 21;16(9):679-685. Epub 2019 Aug 21.

Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Objective: No reports have investigated the influence of age at first or last childbirth on maternal mental health. The aim of this study was to determine whether there is an association between age at first or last childbirth and the mental health of premenopausal women.

Methods: The data used in this study were collected from the 2010 to 2012 Korea National Health and Nutrition Examination Surveys. A total of 3,370 premenopausal women were considered. The association between childbirth age and maternal mental health factors, including stress, depressed mood, and suicidal ideations were analyzed using multiple logistic regression analyses adjusted for confounding factors.

Results: After adjusting confounding factors, younger maternal age at first childbirth was found to be associated with an increase in the prevalence of maternal depressed mood and suicidal ideations. Also, older maternal age at last childbirth was related to an increase in maternal stress, depressed mood and suicidal ideations.

Conclusion: Both younger first childbirth and older last childbirth maternal age may be risk factors for poor outcomes of premenopausal women's mental health. These data support the need for comprehensive mental health assessment for premenopausal women who either gave birth at an age too young or too old.
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http://dx.doi.org/10.30773/pi.2019.07.09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761791PMC
September 2019

Identifying depression in the National Health and Nutrition Examination Survey data using a deep learning algorithm.

J Affect Disord 2019 10 4;257:623-631. Epub 2019 Jul 4.

Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, 222 Banpo-Daero, Seocho-Gu, Seoul 06591, Republic of Korea. Electronic address:

Background: As depression is the leading cause of disability worldwide, large-scale surveys have been conducted to establish the occurrence and risk factors of depression. However, accurately estimating epidemiological factors leading up to depression has remained challenging. Deep-learning algorithms can be applied to assess the factors leading up to prevalence and clinical manifestations of depression.

Methods: Customized deep-neural-network and machine-learning classifiers were assessed using survey data from 19,725 participants from the NHANES database (from 1999 through 2014) and 4949 from the South Korea NHANES (K-NHANES) database in 2014.

Results: A deep-learning algorithm showed area under the receiver operating characteristic curve (AUCs) of 0.91 and 0.89 for detecting depression in NHANES and K-NHANES, respectively. The deep-learning algorithm trained with serial datasets (NHANES, from 1999 to 2012), predicted the prevalence of depression in the following two years of data (NHANES, 2013 and 2014) with an AUC of 0.92. Machine learning classifiers trained with NHANES could further predict depression in K-NHANES. There, logistic regression had the highest performance (AUC, 0.77) followed by deep learning algorithm (AUC, 0.74).

Conclusions: Deep neural-networks managed to identify depression well from other health and demographic factors in both the NHANES and K-NHANES datasets. The deep-learning algorithm was also able to predict depression relatively well on new data set-cross temporally and cross nationally. Further research can delineate the clinical implications of machine learning and deep learning in detecting disease prevalence and progress as well as other risk factors for depression and other mental illnesses.
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http://dx.doi.org/10.1016/j.jad.2019.06.034DOI Listing
October 2019

Identifying depression in the National Health and Nutrition Examination Survey data using a deep learning algorithm.

J Affect Disord 2019 10 4;257:623-631. Epub 2019 Jul 4.

Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea, College of Medicine, 222 Banpo-Daero, Seocho-Gu, Seoul 06591, Republic of Korea. Electronic address:

Background: As depression is the leading cause of disability worldwide, large-scale surveys have been conducted to establish the occurrence and risk factors of depression. However, accurately estimating epidemiological factors leading up to depression has remained challenging. Deep-learning algorithms can be applied to assess the factors leading up to prevalence and clinical manifestations of depression.

Methods: Customized deep-neural-network and machine-learning classifiers were assessed using survey data from 19,725 participants from the NHANES database (from 1999 through 2014) and 4949 from the South Korea NHANES (K-NHANES) database in 2014.

Results: A deep-learning algorithm showed area under the receiver operating characteristic curve (AUCs) of 0.91 and 0.89 for detecting depression in NHANES and K-NHANES, respectively. The deep-learning algorithm trained with serial datasets (NHANES, from 1999 to 2012), predicted the prevalence of depression in the following two years of data (NHANES, 2013 and 2014) with an AUC of 0.92. Machine learning classifiers trained with NHANES could further predict depression in K-NHANES. There, logistic regression had the highest performance (AUC, 0.77) followed by deep learning algorithm (AUC, 0.74).

Conclusions: Deep neural-networks managed to identify depression well from other health and demographic factors in both the NHANES and K-NHANES datasets. The deep-learning algorithm was also able to predict depression relatively well on new data set-cross temporally and cross nationally. Further research can delineate the clinical implications of machine learning and deep learning in detecting disease prevalence and progress as well as other risk factors for depression and other mental illnesses.
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http://dx.doi.org/10.1016/j.jad.2019.06.034DOI Listing
October 2019

Cerebral bioenergetic differences measured by phosphorus-31 magnetic resonance spectroscopy between bipolar disorder and healthy subjects living in two different regions suggesting possible effects of altitude.

Psychiatry Clin Neurosci 2019 Sep 3;73(9):581-589. Epub 2019 Jul 3.

Department of Psychiatry, University of Utah, Salt Lake City, USA.

Aim: Increased oxidative stress in cerebral mitochondria may follow exposure to the systemic hypobaric hypoxia associated with residing at higher altitudes. Because mitochondrial dysfunction is implicated in bipolar disorder (BD) pathophysiology, this may impact the cerebral bioenergetics in BD. In this study, we evaluated the cerebral bioenergetics of BD and healthy control (HC) subjects at two sites, located at sea level and at moderate altitude.

Methods: Forty-three veterans with BD and 33 HC veterans were recruited in Boston (n = 22) and Salt Lake City (SLC; n = 54). Levels of phosphocreatine, β nucleoside triphosphate (βNTP), inorganic phosphate, and pH over total phosphate (TP) were measured using phosphorus-31 magnetic resonance spectroscopy in the following brain regions: anterior cingulate cortex and posterior occipital cortex, as well as bilateral prefrontal and occipitoparietal (OP) white matter (WM).

Results: A significant main effect of site was found in βNTP/TP (Boston > SLC) and phosphocreatine/TP (Boston < SLC) in most cortical and WM regions, and inorganic phosphate/TP (Boston < SLC) in OP regions. A main effect analysis of BD diagnosis demonstrated a lower pH in posterior occipital cortex and right OP WM and a lower βNTP/TP in right prefrontal WM in BD subjects, compared to HC subjects.

Conclusion: The study showed that there were cerebral bioenergetic differences in both BD and HC veteran participants at two different sites, which may be partly explained by altitude difference. Future studies are needed to replicate these results in order to elucidate the dysfunctional mitochondrial changes that occur in response to hypobaric hypoxia.
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http://dx.doi.org/10.1111/pcn.12893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771782PMC
September 2019

A Rho-Associated Coiled-Coil Containing Kinase Inhibitor, Y-27632, Improves Viability of Dissociated Single Cells, Efficiency of Colony Formation, and Cryopreservation in Porcine Pluripotent Stem Cells.

Cell Reprogram 2019 02 8;21(1):37-50. Epub 2019 Jan 8.

1 Department of Animal Bioscience, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju, Republic of Korea.

The establishment of porcine epiblast stem cells (pEpiSCs) and induced pluripotent stem cells (piPSCs) derived from diametrical derivations is of great importance in developing biomedical models. However, pEpiSCs and piPSCs have been technically much harder to culture than mouse embryonic stem cells, showing problematic properties such as spontaneous differentiation and apoptosis after cryopreservation. Therefore, we demonstrated that Y-27632 as a Rho-associated coiled-coil containing kinase inhibitor could prevent dissociated pEpiSCs and piPSCs from undesirable differentiation and apoptosis in cryopreservation protocols. pEpiSC 2, 8 lines, Sendai virus-induced pluripotent stem cells (Sev-iPSCs), and lentivirus-induced pluripotent stem cells were cultured with 10 μM Y-27632 before collecting dissociated cells retrieved from colonies using various enzymes. Dissociated single cells were transferred into freezing mediums (open pulled straw vitrification, STEM-CELLBANKER (SCB), 10% dimethylsulfoxide in serum) for cryopreservation. The rates of viability and colony formation obtained from dissociated porcine stem cells after freezing/thawing were examined in the presence of Y-27632. The characteristics of pluripotency and in vitro differentiation were also examined in these stem cells treated with Y-27632 after cryopreservation. As a result, the viability and efficiency of colony formation of dissociated pEpiSCs (2, 8 lines) and Sev-iPSCs treated with 10 μM Y-27632 using the SCB cryopreservation protocol were significantly increased when compared with those of nontreated Y-27632 (p < 0.05). Pluripotency genes (OCT-3/4, NANOG, and SOX2) were positively expressed in Y-27632-treated porcine pluripotent stem cells. Also, in vitro differentiation of these stem cells was successfully induced in the presence of 10 μM Y-27632. These results indicated that treatment of Y-27632 for single-cell dissociation and the SCB cryopreservation protocol could facilitate handling porcine pluripotent stem cells and provide the widespread use of these stem cells.
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http://dx.doi.org/10.1089/cell.2018.0020DOI Listing
February 2019

Validation of modified fibrosis-4 index for predicting hepatocellular carcinoma in patients with compensated alcoholic liver cirrhosis.

Medicine (Baltimore) 2018 Nov;97(48):e13438

Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea.

Recently, modified fibrosis-4 index (mFIB-4) and the easy liver fibrosis test (eLIFT) were developed for predicting liver fibrosis in chronic liver disease patients. We evaluated whether the 2 tests can predict hepatocellular carcinoma (HCC) risk in alcoholic liver cirrhosis (ALC) patients.A retrospective cohort of 924 ALC patients was assessed for HCC development. Four non-invasive serum biomarkers, mFIB-4, the eLIFT score, fibrosis-4 index (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) were tested using time-dependent analysis of areas under receiver operating characteristic curve (AUROC), DeLong, and log-rank tests.During a median 4.8 years of follow-up, HCC occurred in 83 patients (9.0%). For predicting HCC development at 3 years, the mFIB-4 showed a significantly higher AUROC than APRI and eLIFT scores (0.71 vs 0.61 and 0.56, respectively, all P < .05). The AUROCs of the mFIB-4 for HCC development were not significantly different from those of the FIB-4. According to the mFIB-4, the risk of HCC development was significantly stratified by low index (≤4)/high index (>4) (P < .001 by log-rank test).The mFIB-4 showed better predictability of HCC development than APRI and eLIFT scores, and significantly stratified HCC risk in Asian ALC patients.
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http://dx.doi.org/10.1097/MD.0000000000013438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283079PMC
November 2018

Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy.

J Hepatol 2018 Nov 1;69(5):1066-1073. Epub 2018 Aug 1.

Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea. Electronic address:

Background & Aims: Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to improve the predictive performance.

Methods: From 2007 to 2017, we examined 3,001 Asian patients with CHB receiving entecavir/tenofovir therapy. We assessed the performances of PAGE-B, THRI, CU-HCC, GAG-HCC, and REACH-B for HCC development. A modified PAGE-B score (mPAGE-B) was developed (derivation set, n = 2,001) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation set, n = 1,000) were performed.

Results: The five-year cumulative HCC incidence rates were 6.6% and 7.2% in the derivation and validation datasets after entecavir/tenofovir onset. In the derivation dataset, age, gender, serum albumin levels, and platelet counts were independently associated with HCC. The mPAGE-B score was developed based on age, gender, platelet counts, and serum albumin levels (time-dependent area under receiver operating characteristic curves [AUROC] = 0.82). In the validation set, the PAGE-B and THRI showed similar AUROCs to CU-HCC, GAG-HCC, and REACH-B at five years (0.72 and 0.73 vs. 0.70, 0.71, and 0.61 respectively; all p >0.05 except REACH-B), whereas the AUROC of mPAGE-B at five years was 0.82, significantly higher than the five other models (all p <0.01). HCC incidence rates after initiation of entecavir/tenofovir therapy in patients with CHB were significantly decreased in all risk groups in long-term follow-up periods.

Conclusion: Although PAGE-B and THRI are applicable in Asian patients with CHB receiving entecavir/tenofovir therapy, mPAGE-B scores including additional serum albumin levels showed better predictive performance than the PAGE-B score.

Lay Summary: PAGE-B scores and Toronto HCC risk index were developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with CHB under potent antiviral therapy. This study validated these two scores in Asian patients with CHB and suggested that modified PAGE-B scores could improve the predictive performance. A modified PAGE-B score, which is based only on a patient's age, gender, baseline platelet counts, and serum albumin levels at treatment initiation, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in Asian patients with CHB. With a scoring range from 0 to 21 points, a modified PAGE-B score differentiates the HCC risk. A modified PAGE-B score significantly differentiates the five-year HCC risk: low ≤8 points and high ≥13 points.
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http://dx.doi.org/10.1016/j.jhep.2018.07.018DOI Listing
November 2018

Hepatitis B virus reactivation after radiotherapy for hepatocellular carcinoma and efficacy of antiviral treatment: A multicenter study.

PLoS One 2018 30;13(7):e0201316. Epub 2018 Jul 30.

Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p<0.001). HBV related hepatitis was also lower in the antiviral group (3.8% vs. 14.8%, p = 0.031). In multivariate analysis, absence of antiviral treatment (OR: 8.339, 95% CI: 2.532-27.470, p<0.001) and combined treatment of RT with transarterial chemoembolizatoin (TACE) (OR: 5.313, 95% CI: 1.548-18.232, p = 0.008) were risk factors for HBV reactivation. HBV reactivation can occur after radiotherapy. Combination treatment of RT with TACE and non-antiviral treatment are major risk factors for HBV reactivation during or after RT. Therefore, preventive antiviral therapy should be recommended for patients with HCC who are scheduled to receive RT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201316PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066246PMC
January 2019

Altered attentional control over the salience network in complex regional pain syndrome.

Sci Rep 2018 05 10;8(1):7466. Epub 2018 May 10.

Ewha Brain Institute, Ewha Womnans University, Seoul, South Korea.

The degree and salience of pain have been known to be constantly monitored and modulated by the brain. In the case of maladaptive neural responses as reported in centralized pain conditions such as complex regional pain syndrome (CRPS), the perception of pain is amplified and remains elevated even without sustained peripheral pain inputs. Given that the attentional state of the brain greatly influences the perception and interpretation of pain, we investigated the role of the attention network and its dynamic interactions with other pain-related networks of the brain in CRPS. We examined alterations in the intra- and inter-network functional connectivities in 21 individuals with CRPS and 49 controls. CRPS-related reduction in intra-network functional connectivity was found in the attention network. Individuals with CRPS had greater inter-network connectivities between the attention and salience networks as compared with healthy controls. Furthermore, individuals within the CRPS group with high levels of pain catastrophizing showed greater inter-network connectivities between the attention and salience networks. Taken together, the current findings suggest that these altered connectivities may be potentially associated with the maladaptive pain coping as found in CRPS patients.
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http://dx.doi.org/10.1038/s41598-018-25757-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945627PMC
May 2018

Feasibility of Psychosocial Distress Screening and Management Program for Hospitalized Cancer Patients.

Psychiatry Investig 2017 Nov 7;14(6):734-745. Epub 2017 Nov 7.

Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Objective: Although the diagnosis and treatment of cancer is associated with psychosocial distress, routine distress screening is difficult in hospitalized oncology settings. We developed a consecutive screening program for psychosocial distress to promote psychiatric treatment of cancer patients and evaluated the feasibility of our program by Distress Thermometer (DT) and Hospital Anxiety and Depression Scale (HADS).

Methods: Among 777 cancer inpatients recruited from the Catholic Comprehensive Institute of Seoul St. Mary's Hospital, 499 agreed to complete primary distress screening through DT. We conducted secondary distress screening through HADS in 229 patients who had high scores of DT.

Results: Of the 499 participants, 270 patients with low scores of DT were included in the distress education program. 229 patients with high scores of DT received secondary distress screening through HADS. Among 115 patients with low scores of HADS, 111 patients received distress management. Among 114 patients with high scores in the secondary distress screening, 38 patients received psychiatric consultation service whereas 76 patients refused psychiatric consultation.

Conclusion: Using consecutive screening for psychosocial distress appeared to be feasible in an inpatient oncology setting. Nevertheless, the low participation rate of psychiatric consultation service in cancer patients with high distress level should be improved.
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http://dx.doi.org/10.4306/pi.2017.14.6.734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714714PMC
November 2017

Association between mental health status and bone mineral density: Analysis of the 2008-2010 Korea national health and nutrition examination survey.

PLoS One 2017 13;12(11):e0187425. Epub 2017 Nov 13.

Department of Psychiatry, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

The current study aimed to investigate the association between mental health status and bone mineral density (BMD) using data from the Korean National Health and Nutrition Examination Survey (KNHANES) 2008-2010. We enrolled 15,876 South Korean participants (4,010 postmenopausal females, 4,836 premenopausal females, and 7,016 males, all aged 20 years or older). BMD was measured using dual-energy radiography absorptiometry at the femoral neck (NK), lumbar spine (LSP), and total femur (TFM). Mental health status data were obtained from a self-report questionnaire that assessed psychological stress, depressed mood, and suicidal ideation. Psychological stress was negatively correlated with BMD in the LSP, NK, and TFM for the male group. Depressed mood was associated with lower BMD in the LSP, NK and TFM for the premenopausal female group, and in the LSP for the male group. Suicidal ideation was associated with lower BMD in the NK and TFM for the male group. Mental health problems were associated with lower BMD, especially in premenopausal females and males. Future investigations should focus on the shared pathophysiology between mental health problems and BMD, and the interrelationship between increased BMD and recovery from mental health problems.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187425PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683604PMC
December 2017

Can More Aggressive Treatment Improve Prognosis in Patients with Hepatocellular Carcinoma? A Direct Comparison of the Hong Kong Liver Cancer and Barcelona Clinic Liver Cancer Algorithms.

Gut Liver 2018 Jan;12(1):94-101

Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Background/aims: In addition to the globally endorsed Barcelona Clinic Liver Cancer (BCLC) staging system, other algorithms or staging systems have been developed, including the Hong Kong Liver Cancer (HKLC) staging system. This study aimed to validate the HKLC staging system relative to the BCLC staging system for predicting survival for hepatocellular carcinoma (HCC) patients in Korea.

Methods: From 2004 to 2013, 2,571 patients newly diagnosed with HCC were consecutively enrolled at three Korea University medical centers.

Results: Both staging systems differentiated survival well (p<0.001). However, 1-year and 3-year survival were predicted better using the HKLC system than the BCLC system (area under the receiver operating characteristic curve: 0.869 vs 0.856 for 1 year, p=0.002; 0.841 vs 0.827 for 3 years, p=0.010). In hypothetical survival curves, the HKLC system exhibited better median overall survival than the BCLC system (33.1 months vs 19.2 months). In evaluations of prognosis according to either BCLC or HKLC treatment guidelines, risk of death was reduced in the group following only HKLC guidelines compared with the group following only BCLC guidelines (hazard ratio, 0.601; 95% confidence interval, 0.443 to 0.816; p=0.001).

Conclusions: Although both staging systems predicted and discriminated HCC prognoses well, the HKLC system showed more encouraging survival benefits than the BCLC system.
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http://dx.doi.org/10.5009/gnl17040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753690PMC
January 2018

Complete response of advanced hepatocellular carcinoma to sorafenib: another case and a comprehensive review.

Clin Mol Hepatol 2017 12 20;23(4):340-346. Epub 2017 Jun 20.

Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.
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http://dx.doi.org/10.3350/cmh.2016.0070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760007PMC
December 2017

Complete response of advanced hepatocellular carcinoma to sorafenib: another case and a comprehensive review.

Clin Mol Hepatol 2017 12 20;23(4):340-346. Epub 2017 Jun 20.

Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.
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http://dx.doi.org/10.3350/cmh.2016.0070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760007PMC
December 2017

Antiviral response is not sustained after cessation of lamivudine treatment in chronic hepatitis B patients: A 10-year follow-up study.

J Med Virol 2017 05 23;89(5):849-856. Epub 2016 Dec 23.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Republic of Korea.

Although the ideal end point for antiviral treatment in patients with chronic hepatitis B (CHB) is loss of HBsAg, the typical clinical end points are HBeAg seroconversion in HBeAg-positive patients and long-term DNA suppression in HBeAg-negative patients. We evaluated the long-term antiviral response after cessation of lamivudine treatment in CHB patients. A total of 157 patients who had discontinued lamivudine between 1997 and 2014 were enrolled (97 HBeAg-positive and 60 HBeAg-negative CHB patients). The long-term durability of the antiviral response (viralogical relapse; HBV DNA ≥10  copies/ml) and the clinical course of these patients were analyzed retrospectively. In HBeAg-positive patients, the mean follow-up period after discontinuation was 72.3 months. The cumulative probabilities of virological relapse at 1, 12, 24, 48, 60, 96, and 120 months were 10.3%, 40.2%, 55.6%, 62.8%, 65.9%, 67.0%, and 67.0%, respectively. In HBeAg-negative patients, the cumulative probabilities of a virological relapse at 1, 12, 24, 48, 60, 96, and 120 months were 25.0%, 35.0%, 41.7%, 43.3%, 43.3%, 46.7%, and 48.3%, respectively. Younger age (HR 1.732, 95%CI: 1.058-2.835, P = 0.02) was predictive of non-virological relapse in HBeAg-positive patients. And achievement of undetectable HBV DNA level within 3 months of treatment discontinuation was associated with decreased rate of virological relapse (HR 0.159, 95%CI: 0.069-0.367 P < 0.01) in HBeAg-negative patients. Despite meeting the requirements for treatment discontinuation, approximately half of the CHB patients treated with lamivudine relapsed. Thus, the antiviral response is not reliably sustained after lamivudine treatment cessation. J. Med. Virol. 89:849-856, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24715DOI Listing
May 2017

Treatment of Severe Alcoholic Hepatitis With Corticosteroid, Pentoxifylline, or Dual Therapy: A Systematic Review and Meta-Analysis.

J Clin Gastroenterol 2017 Apr;51(4):364-377

*Department of Internal Medicine, Korea University College of Medicine †Department of Preventive Medicine, Institute for Evidence-based Medicine, College of Medicine, Korea University, Seoul, Korea.

Background And Aims: Although both corticosteroids and pentoxifylline are currently recommended drugs for the treatment of patients with severe alcoholic hepatitis, their effectiveness in reducing mortality remains unclear. In this systematic review, we aimed to evaluate the therapeutic and adverse effects of corticosteroids, pentoxifylline, and combination by using Cochrane methodology and therefore determine optimal treatment for severe alcoholic hepatitis.

Methods: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from their inauguration until October 2015. Combinations of the following keywords and controlled vocabularies were searched: alcoholic hepatitis, corticosteroid, and pentoxifylline.

Results: A total of 2639 patients from 25 studies were included. The treatment groups did not differ significantly in terms of overall mortality. Analysis of 1-month mortality revealed corticosteroid monotherapy reduced mortality compared with placebo (OR=0.58; 95% CI, 0.34-0.98; P=0.04), but pentoxifylline monotherapy did not. The mortality with dual therapy was similar to corticosteroid monotherapy (OR=0.91; 95% CI, 0.62-1.34; P=0.63). However, dual therapy decreased the incidences of hepatorenal syndrome or acute kidney injury (OR=0.47; 95% CI, 0.26-0.86; P=0.01) and the infection risk (OR=0.63; 95% CI, 0.41-0.97; P=0.04) significantly more than corticosteroid monotherapy did. None of the treatments conferred any medium-term or long-term survival benefits in the present study.

Conclusions: Dual therapy was not inferior to corticosteroid monotherapy and could reduce the incidence of hepatorenal syndrome or acute kidney injury and risk of infection. Therefore, dual therapy might be considered in treatment of patients with severe alcoholic hepatitis.
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http://dx.doi.org/10.1097/MCG.0000000000000674DOI Listing
April 2017