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( Young Chang ),( Jeong-hoon Lee ),( Sung Won Chung ),( Minseok Albert Kim ),( Sun Woong Kim ),( Hyo Young Lee ),( Junsik Yoon ),( Yun Bin Lee ),( Eun Ju Cho ),( Su Jong Yu ),( Yoon Jun Kim ),( Jung-h 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Although antiviral therapy for chronic hepatitis B virus (HBV) infection reduces risk of hepatocellular carcinoma (HCC), the risk is reportedly higher in the antiviral-induced viral suppression than inactive carriers. In this study, we aimed to compare the effect of the phases when the antiviral treatment started on the HCC development Methods: This retrospective study included chronic hepatitis B patients with suppressed HBV DNA (<2,000 IU/mL) and normal alanine aminotransferase levels and without evidence of cirrhosis from eight referral hospitals in Korea. Study subjects were categorized into four groups: patients underwent antiviral treatment from immune-tolerant phase (IT group), HBeAg-positive hepatitis phase (HBeAg+ group), or HBeAg-negative hepatitis phase (HBeAg- group); or inactive carriers without any antiviral treatment (IC group). Primary endpoint was an HCC development. Kaplan-Meier survival analysis and Cox proportional hazard model were used for statistical analysis. Results: A total of 887 patients were included: 63 in IT group, 151 in HBeAg+ group, 365 in HBeAg- group, and 308 in IC group. In univariate analyses, there was no significant difference in the risk of HCC development between IT group and IC group (hazard ratio [HR]=0.85, 95% confidence interval [CI]=0.10-7.15, P=0.98). However, both HBeAg+ (HR=4.01, 95% CI=1.57-10.28, P=0.001) and HBeAg- (HR=3.04, 95% CI=1.29-7.07, P=0.007) groups showed significantly higher risk of HCC occurrence. The 5-year risk of HCC occurrence was 5.6% in IT group, 10.9% in HBeAg+ group, 8.3% in HBeAg- group, and 1.9% in IC group (Figure 1). In multivariate analyses, IT group consistently showed similar risk of HCC development compared to IC group (adjusted HR [aHR]=0.85, 95% CI=0.10-7.15, P=0.88). Both HBeAg+ (aHR=2.91, 95% CI=1.13-7.42, P=0.03) and HBeAg- (aHR=2.48, 95% CI=1.05- 5.85, P=0.04) groups showed significantly higher risk of HCC development than IC group. Conclusions: Even if HBV DNA suppression has equally achieved, the risk of HCC development varies depending on the phase of initial antiviral therapy. Early antiviral therapy from immune-tolerant phase is associated with low risk of HCC similar to that of natural inactive carriers which is significantly lower than the risk of patients treated from immune-active phases.
( Young Chang ),( Ki Tae Suk ),( Soung Won Jeong ),( Jeong-ju Yoo ),( Sang Gyune Kim ),( Young Seok Kim ),( Sae Hwan Lee ),( Hong Soo Kim ),( Seong Hee Kang ),( Soon Koo Baik ),( Dong Joon Kim ),( Moo 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: We aimed to derive a model to discriminate cirrhotic patients with poor prognosis even if the Model for End Stage Liver Disease (MELD) score is low. Methods: This study enrolled 700 cirrhotic patients with MELD score of less than 20 who underwent hepatic vein pressure gradient (HVPG) measurement. A novel model using HVPG to predict overall survival was derived and specified as the H6C score. Internal and external validations were conducted with the derivation and validation cohorts. Results: The H6C score using the HVPG and Child-Pugh scores was developed on the basis of a multivariate Cox regression analysis. The H6C score showed great predictive power for overall survival with a time-dependent AUC of 0.733, which was superior to that of a MELD of 0.602. In patients with viral etiology, the performance of the H6C score was much improved with a time-dependent AUC of 0.850 and was consistently superior to that of the MELD (0.748). Patients with an H6C score below 45 demonstrated an excellent overall survival with a 5-year survival rate of 91.5%. Whereas patients with an H6C score above 64 showed a dismal prognosis with a 5-year survival rate of 51.1%. The performance of the H6C score was further verified to be excellent in the validation cohort. Conclusions: This new model using the HVPG provides better predictive power than the MELD in cirrhotic patients, especially with viral etiology. In patients with H6C above 64, it would be wise to consider early liver transplantation in order to positively impact long-term survival, even when these patients have a low MELD score.
Clinical Impact of Exosomal microRNA as a Novel Biomarker of Liver Fibrosis
( Young Chang ),( Jae-a Han ),( Suk Min Kang ),( Soung Won Jeong ),( Tom Ryu ),( Han Seul Park ),( Jeong-ju Yoo ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Young Seok Kim ),( Hong Soo Kim ),( So Young Jin 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Many approaches have been suggested for the non-invasive diagnosis of liver fibrosis, including the use of serum biomarkers and ultrasound-based elastography, but none has yet replaced liver biopsy. MicroRNAs (miRNAs) have been suggested as potential diagnostic tools for liver diseases. We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at a large-volume academic hospital in Korea. Exosomes were extracted from serum samples, and next-generation sequencing (NGS) of miRNAs was conducted in patients from different stages of liver fibrosis. Differential expression of miRNAs was quantified using targeted real-time quantitative polymerase chain reaction (RT-qPCR). A model was derived to discriminate advanced fibrosis based on miRNA levels using multivariate logistic regression. The performance of this model was evaluated and compared using area under the receiver operator characteristic (ROC) curve (AUC) and De- Long’s test. Results: NGS data revealed the relationship between exosomal miR-122 expression and liver fibrosis progression. The level of miR-122 decreased as the pathologic fibrosis grade progressed from stage 0 to 4. Patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P<0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis with an AUC of 0.77, which improved to 0.86 in combination with fibrosis-4 score (FIB-4) and transient elastography (TE). This value was higher than that reported for any other non-invasive modalities, including TE (AUC of 0.80) or FIB-4 (AUC of 0.57) alone. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker improved, evident from the increase in the AUC value to 0.87. In this subpopulation, the combination model of miR- 122, FIB-4, and TE showed the best discrimination ability (AUC of 0.90), which was significantly higher than that of TE alone (AUC of 0.83; DeLong’s test P=0.046). Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of collagen- 1A, a-smooth muscle actin, fibronectin, and transforming growth factor-ß. Conclusions: Exosomal miR-122 may serve as a novel biomarker for discriminating advanced liver fibrosis, and its accuracy may enhanced in combination with other non-invasive tests such as FIB-4 and TE.
( Young Chang ),( Won Hyeok Choe ),( Dong Hyun Sinn ),( Jeong-hoon Lee ),( Joon Yeul Nam ),( Hyeki Cho ),( Young Youn Cho ),( Eun Ju Cho ),( Su Jong Yu ),( Yoon Jun Kim ),( Jung-hwan Yoon ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: The antiviral treatment for chronic hepatitis B (CHB) patients in highly replicative but low inflammatory phase (including immune tolerant phase) is still controversial. The aim of this study is to assess whether antiviral treatment can improve survival in HBeAg-positive CHB patients with high HBV DNA but normal to mildly elevated ALT level. Methods: This multi-center retrospective study included 602 patients diagnosed as HBeAg-positive CHB with HBV DNA above 20,000 IU/mL and ALT below 80 IU/L without evidence of liver cirrhosis (LC) in three large volume medical centers in Korea. The involved patients were categorized into two groups; antiviral treatment group (n=69) and control group (n=533). Primary endpoint was overall survival (OS) and secondary endpoints were development of LC and hep atocellular carcinoma (HCC). To compare the endpoints, baseline characteristics of the two groups were adjusted or balanced by Cox proportional hazards model and inverse probability weighting (IPW). Results: Baseline liver function was more favorable for the control group. In multivariate analysis, the treatment group showed significantly lower risk of developing LC (adjusted hazard ratio [aHR〕=0.326; P=0.006) and HCC (aHR=0.202; P=0.016), and consequently longer OS (aHR=0.137; P=0.052) than the control group. After balancing the baseline characteristics between the two groups by IPW, antiviral treatment significantly prolonged OS (aHR=0.067; P=0.016) (Figure 1) and the risk of LC (aHR=0.169; P<0.001) and HCC (aHR=0.101; P<0.001) in the treatment group were also reduced significantly compared to the control group. Assuming to treat the relevant patients with entecavir, the additional costs for reducing one patient of LC, HCC, and death were supposed to be approximately 10,000 USD, 25,000 USD, and 45,000 USD, respectively, in Korea. Conclusions: Antiviral therapy for CHB patients with high viral load prolongs OS and reduces the risk of LC and HCC even if ALT levels would not exceed two times of upper limit of normal.
S-156 Management of Gastric Variceal Bleeding
( Young Chang ),( Joon Yeul Nam ),( Eun Ju Cho ),( Jeong-hoon Lee ),( Su Jong Yu ),( Jung-hwan Yoon ),( Yoon Jun Kim ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1
Background:?Gastric varices (GV) is one of the major cause of upper gastrointestinal bleeding in patients with liver cirrhosis. Although bleeding from GV is less common than from esophageal varices (EV), GV bleeding is known to be more severe to be associated with high mortality and morbidity than EV bleeding. In this study, we aimed to compare the efficacy and the rate of complications of the two methods of management of GV bleeding: the balloon-occluded retrograde transvenous obliteration (BRTO) and the transjugular intrahepatic portosystemic shunt (TIPS).?Methods:?This retrospective study included consecutive patients who received BRTO or TIPS to control GV bleeding from January 2005 to December 2014 at a single tertiary hospital in Korea. The rate of complications of the two groups who recieved either of the procedures were compared using the Pearson’s Chi-square test. The overall survival (OS) of the two groups were estimated by the Kaplan-Meier method and the Cox proportional hazards model.?Results:?A total of 176 patients were included: the BRTO group (n=157) and the TIPS group (n=19). Both the immediate bleeding control rate (p=0.03; OR=4.72; 95% confidence interval [CI]=1.08-20.70) and the rate of progression of ascites (p=0.02; OR=7.93; 95% CI=1.03-61.09) were significantly higher in the BRTO group than the TIPS group. Otherwise, there were no significant differences in the rate of aggravation of pleural effusion (p=0.06), EV (p=0.29), portal hypertensive gastropathy (p=0.23), and portosystemic encephalopathy (p=0.48) between the two groups. There was no significant difference in OS between the two groups in univariate analysis (log-rank?p=0.50), however, after adjusting several confounding factors using multivariate Cox analysis, the BRTO group showed significantly longer OS (p=0.04; adjusted hazard ratio=1.86, 95% CI=1.02-3.36) than the TIPS group.?Conclusions:?If feasible, the BRTO procedure is superior to the TIPS procedure in terms of bleeding control and the OS despite it could aggravate portal hypertension which causes several complications such as ascites.
Clinical Impact of Exosomal microRNA in Liver Fibrosis: Based on Next-Generation Sequencing Analysis
( Young Chang ),( Jae-a Han ),( Suk Min Kang ),( Soung Won Jeong ),( Tom Ryu ),( Han Seul Park ),( Jeong-ju Yoo ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Young Seok Kim ),( Hong Soo Kim ),( So Young Jin 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1