1.Changing Features of Liver Injury in COVID-19 Patients: Impact of Infection with the SARS-CoV-2 Delta (B.1.617.2) Variants
Chang Wan CHOI ; Ho Kyung SUNG ; Jae Yoon JEONG ; Dae Hyun LIM ; Jongkyoung CHOI ; Hyeok Choon KWON ; Seongwoo NAM ; Yeonjae KIM ; BumSik CHIN
Infection and Chemotherapy 2022;54(4):744-756
		                        		
		                        			 Background:
		                        			There is growing evidence that abnormal liver function tests (LFTs) are common in patients with coronavirus disease 2019 (COVID-19). However, it is not known whether viral involvement in the liver differs according to the strain. We investigated the impact on liver injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variants. 
		                        		
		                        			Materials and Methods:
		                        			We conducted a single-center, retrospective cohort study, including 372 patients admitted during the pre-Delta period (PDP: between February 1 and November 30, 2020) and 137 patients admitted during the Delta period (DP: between August 1 and August 31, 2021). Initial liver injury was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 × the upper limit of normal (ULN) or alkaline phosphatase (ALP) or total bilirubin ≥2 × the ULN within 3 days from admission. 
		                        		
		                        			Results:
		                        			Of 509 patients with COVID-19 included in our study, 38 (7.5%) patients had initial liver injury. The DP group had a significantly higher rate of initial liver injury than the PDP group (PDP: 5.9% vs. DP: 11.7%, P = 0.028). The DP group (adjusted odds ratio [aOR]: 2.737, 95% confidence interval [CI]: 1.322 – 5.666) was independently associated with initial liver injury. During hospitalization, 160 (31.4%) patients had severe COVID-19. The DP group and initial liver injury had higher odds of progressing to severe COVID-19 (aOR: 2.664, 95% CI: 1.526 - 4.648, and aOR: 4.409, 95% CI: 1.816 - 10.707, respectively). The mediation analysis suggested that initial liver injury mediates the relationship between SARS-CoV-2 Delta variant infection and severe COVID-19 (unstandardized beta coefficient = 0.980, Standard error = 0.284, P = 0.001). 
		                        		
		                        			Conclusion
		                        			Initial liver injury is more common in COVID-19 patients with Delta variants. Also, Delta variants and initial liver injury are associated with poor clinical outcomes. 
		                        		
		                        		
		                        		
		                        	
2.A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon KIM ; Hyuk-Sang KWON ; Suk Kyeong KIM ; Jung-Hyun NOH ; Cheol-Young PARK ; Hyeong-Kyu PARK ; Kee-Ho SONG ; Jong Chul WON ; Jae Myung YU ; Mi Young LEE ; Jae Hyuk LEE ; Soo LIM ; Sung Wan CHUN ; In-Kyung JEONG ; Choon Hee CHUNG ; Seung Jin HAN ; Hee-Seok KIM ; Ju-Young MIN ; Sungrae KIM
Diabetes & Metabolism Journal 2022;46(6):855-865
		                        		
		                        			 Background:
		                        			Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. 
		                        		
		                        			Methods:
		                        			In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. 
		                        		
		                        			Results:
		                        			Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. 
		                        		
		                        			Conclusion
		                        			Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings. 
		                        		
		                        		
		                        		
		                        	
3.Hepatectomy outcomes in patients with hepatitis C virusrelated hepatocellular carcinoma with or without cirrhosis
Jong Man KIM ; Jinsoo RHU ; Sang Yun HA ; Gyu-Seong CHOI ; Choon Hyuck DAVID KWON ; Jae-Won JOH
Annals of Surgical Treatment and Research 2022;102(1):1-9
		                        		
		                        			 Purpose:
		                        			Hepatocellular carcinoma (HCC) is rare in HCV patients without cirrhosis, and little is known about the postoperative results of these patients. The present study compares the outcomes of cirrhotic and non-cirrhotic groups after liver resection (LR) in solitary HCV-related HCC patients and identifies risk factors for prognosis according to the presence or absence of cirrhosis in these patients. 
		                        		
		                        			Methods:
		                        			Two hundred and 7 adult hepatectomy patients with treatment-naïve solitary HCV-related HCC were identified prospectively at our institution between July 2005 and May 2019. 
		                        		
		                        			Results:
		                        			The non-cirrhotic group had better liver function than the cirrhotic group based on platelet count, liver function tests, liver stiffness measurement, and indocyanine green retention rate at 15 minutes but were older than the cirrhotic group. Consistently, noninvasive markers in the cirrhotic group were significantly higher than in the non-cirrhotic group. The cumulative disease-free survival and overall survival in the non-cirrhotic group were significantly higher than in the cirrhotic group. HCC recurrence was related to major LR and α-FP of >40 ng/mL and death was related to long hospitalization and α-FP of >40 ng/mL in multivariate analysis. Noninvasive markers and the presence of cirrhosis were not related to HCC recurrence or death in multivariate analyses. 
		                        		
		                        			Conclusion
		                        			The cirrhotic group showed poor prognosis due to poor liver function after LR compared to the non-cirrhotic group, but this was not sustained in multivariate analysis. The factors influencing HCC recurrence and death were different in the cirrhotic and non-cirrhotic groups. 
		                        		
		                        		
		                        		
		                        	
4.Realization of improved outcomes following liver resection in hepatocellular carcinoma patients aged 75 years and older
Jong Man KIM ; Jinsoo RHU ; Sang Yun HA ; Gyu-Seong CHOI ; Choon Hyuck DAVID KWON ; Gaabsoo KIM ; Jae-Won JOH
Annals of Surgical Treatment and Research 2021;101(5):257-265
		                        		
		                        			 Purpose:
		                        			Little is known about liver resection (LR) in hepatocellular carcinoma (HCC) patients older than 75 years of age. This study aimed to compare the postoperative and long-term outcomes of hepatectomy in this patient population according to operation period. 
		                        		
		                        			Methods:
		                        			This study included 130 elderly patients who underwent LR for solitary treatment-naïve HCC between November 1998 and March 2020. Group 1 included patients who underwent LR before 2016 (n = 68) and group 2 included those who underwent LR during or after 2016 (n = 62). 
		                        		
		                        			Results:
		                        			The proportion of major LR, anatomical LR, and laparoscopic LR (LLR) in group 1 was significantly lower than those in group 2. Also, the median operation time, amount of blood loss, hospitalization length, rates of intraoperative blood transfusion, and complications in group 2 were less than those in group 1. In the subgroup analysis of group 1, high proteins induced by vitamin K absence or antagonist-II, long hospitalization, and LLR were closely associated with mortality. In the subgroup analysis of group 2, however, none of the factors increased mortality. Nevertheless, the presence of tumor grade 3 or 4 and the incidence of microvascular invasion were higher in group 1 than in group 2, and the disease-free survival and overall survival were better in group 2 than in group 1 because of minimized blood loss and quicker recovery period by increased surgical techniques and anatomical approach, and LLR. 
		                        		
		                        			Conclusion
		                        			LR in elderly HCC patients has been frequently performed recently, and the outcomes have improved significantly compared to the past. 
		                        		
		                        		
		                        		
		                        	
5.Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma
Jae-Woo JUNG ; Hae-Sim PARK ; Choon-Sik PARK ; Sang-Heon CHO ; Inseon S. CHOI ; Hee-Bom MOON ; Soon Seog KWON ; Ho Joo YOON ; Jung Won PARK ; Jong-Myung LEE ; Dong-Chull CHOI ; Byoung Whui CHOI
The Korean Journal of Internal Medicine 2021;36(4):1001-1013
		                        		
		                        			Background/Aims:
		                        			Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. 
		                        		
		                        			Methods:
		                        			This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. 
		                        		
		                        			Results:
		                        			Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). 
		                        		
		                        			Conclusions
		                        			Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.
		                        		
		                        		
		                        		
		                        	
6.Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma
Jae-Woo JUNG ; Hae-Sim PARK ; Choon-Sik PARK ; Sang-Heon CHO ; Inseon S. CHOI ; Hee-Bom MOON ; Soon Seog KWON ; Ho Joo YOON ; Jung Won PARK ; Jong-Myung LEE ; Dong-Chull CHOI ; Byoung Whui CHOI
The Korean Journal of Internal Medicine 2021;36(5):1260-
		                        		
		                        		
		                        		
		                        	
7.Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma
Jae-Woo JUNG ; Hae-Sim PARK ; Choon-Sik PARK ; Sang-Heon CHO ; Inseon S. CHOI ; Hee-Bom MOON ; Soon Seog KWON ; Ho Joo YOON ; Jung Won PARK ; Jong-Myung LEE ; Dong-Chull CHOI ; Byoung Whui CHOI
The Korean Journal of Internal Medicine 2021;36(4):1001-1013
		                        		
		                        			Background/Aims:
		                        			Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. 
		                        		
		                        			Methods:
		                        			This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. 
		                        		
		                        			Results:
		                        			Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). 
		                        		
		                        			Conclusions
		                        			Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.
		                        		
		                        		
		                        		
		                        	
8.Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma
Jae-Woo JUNG ; Hae-Sim PARK ; Choon-Sik PARK ; Sang-Heon CHO ; Inseon S. CHOI ; Hee-Bom MOON ; Soon Seog KWON ; Ho Joo YOON ; Jung Won PARK ; Jong-Myung LEE ; Dong-Chull CHOI ; Byoung Whui CHOI
The Korean Journal of Internal Medicine 2021;36(5):1260-
		                        		
		                        		
		                        		
		                        	
9.Clinical Characteristics and Treatment Outcomes of Patients with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection: Experience at a Single Center in Korea
Dae Hyun LIM ; Jae Yoon JEONG ; Seongwoo NAM ; Jongkyoung CHOI ; Hyeok Choon KWON ; Yong Bum YOON ; Yeonjae KIM ; BumSik CHIN
Journal of Korean Medical Science 2021;36(46):e308-
		                        		
		                        			 Background:
		                        			Because of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea. 
		                        		
		                        			Methods:
		                        			We performed a retrospective cohort study of all HCV-monoinfected and HCV/ HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020. 
		                        		
		                        			Results:
		                        			We enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/ HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients.Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/ HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs.HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480). 
		                        		
		                        			Conclusion
		                        			In Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCVmonoinfected patients. 
		                        		
		                        		
		                        		
		                        	
10.Serial Observations of Muscle and Fat Mass as Prognostic Factors for Deceased Donor Liver Transplantation
Jisun LEE ; Woo Kyoung JEONG ; Jae-Hun KIM ; Jong Man KIM ; Tae Yeob KIM ; Gyu Seong CHOI ; Choon Hyuck DAVID KWON ; Jae-Won JOH ; Sang-Yong EOM
Korean Journal of Radiology 2021;22(2):189-197
		                        		
		                        			 Objective:
		                        			Muscle depletion in patients undergoing liver transplantation affects the recipients’ prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT). 
		                        		
		                        			Materials and Methods:
		                        			This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans.Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI [%] = [SMI at Pre-LT - SMI at 1 yr Pre-LT] / SMI at Pre-LT x 100;preoperative ΔFMI [%] = [FMI at Pre-LT - FMI at 1 yr Pre-LT] / FMI at Pre-LT x 100) and assessed for correlation with patient survival. 
		                        		
		                        			Results:
		                        			SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, -13.04%, p < 0.001). In the multivariable analysis, preoperative ΔSMI (p = 0.016) and model for end-stage liver disease score (p = 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ -30%) was significantly shorter than for other patients (p = 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period (p = 0.009) in all patients. 
		                        		
		                        			Conclusion
		                        			A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT. 
		                        		
		                        		
		                        		
		                        	
            
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