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( Eileen L. Yoon ),( Jeong Han Kim ),( Won Hyeok Choe ),( So Young Kwon ),( Won-choong Choi ),( Byung-chul Yoo ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: Tenofovir (TDF) is a potent agent for chronic hepatitis B (CHB) and TDF monotherapy has been widely accepted for treatment of multi-drug resistance. We aimed to evaluate safety of switching to TDF monotherapy from TDF-based combination therapy. Methods: This is a retrospective study of CHB patients who had been treated with TDF-based combination therapy and switched to TDF monotherapy after achievement of virological response (VR; undetectable HBV DNA by real-time PCR) in Konkuk university hospital and Sanggye Paik Hospital. Results: Total 38 patients were included in this study. Median age was 51 years old and 28 patients were male (73.7%). HBeAg positive patients were 31 (81.6%). Combination types were lamivudine (LMV) plus TDF (19, 50%) and entecavir (ETV) plus TDF (19, 50%). VR duration before switching to monotherapy was median 16.1 months and monotherapy duration was median 7.5 months. Within 6 months, HBV DNA became detectable in 4 patients and one of them was related with poor compliance to antiviral treatment. Excluding one patient with poor compliance, two patients had been treated with LMV plus TDF combination therapy and one patient had been treated with ETV plus TDF combination therapy. Resistance types before combination treatment were LMV only resistance, ETV resistance, and adefovir only resistance each. VR durations of these patients were one month, 13 months and 6 months. Conclusions: Generally, switching to TDF monotherapy from TDF-based combination treatment was safe and effective. Some cases showed that longer consolidation therapy after achievement of VR might be required for safe switching to TDF monotherapy.
( Eileen L. Yoon ),( Tae Yeob Kim ),( Do Seon Song ),( Jin Mo Yang ),( Hee Yeon Kim ),( Chang Wook Kim ),( Young Kul Jung ),( Hyung Joon Yim ),( Soung Won Jeong ),( Sang Gyune Kim ),( Jae Young Jang ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: To investigate long-term mortality according to the severity of alcoholic hepatitis and the presence or absence of previous acute decompensation (AD) in alcoholic cirrhotic patients with acute deterioration. Methods: A total of 894 alcoholic cirrhotic patients (male 747, mean age 53.1 years) with acute deterioration were prospectively followed up. Severe alcoholic hepatitis (SAH) was defined by a modified discriminant function ≥32. Enrolled patients were divided into 3 groups according to the presence and severity of AH; group1, alcoholic cirrhosis without AH; group2, alcoholic cirrhosis with non-SAH; group3, alcoholic cirrhosis with SAH. AD was defined as: acute development of overt ascites, hepatic encephalopathy, gastrointestinal bleeding, and infection. Results: During follow-up duration (14.3±10.7 months), long-term mortality were higher in patients with group 3 than those in group 1 and 2, but there was no significant difference between group 1 and 2 (group 1, 160/596; group 2, 27/141; group 3, 76/157, P<0.001). Also, in 671 patients who survived for more than 3 months following acute deterioration (long-term survivors), long-term survival curve between groups showed a similar pattern (P=0.004). Interestingly, in group 1, the presence of previous AD negatively affected long-term survival in total and long-term survivors (P<0.001 and P=0.004, respectively). However, in group 3, previous AD negatively affected long-term survival in long-term survivors (P=0.009), but not in total patients (figure 1). Especially in long-term survivors of group 3, previous AD showed hazard ratio of 2.47 (95% confidence interval, 1.16-5.28, P=0.019). Conclusions: Compared with the long-term prognosis of patients with acute deterioration except for AH, that of SAH was poor, but that of non-SAH was similar. However, in patients with acute deterioration except for AH and SAH patients overcoming acute deterioration, the presence of previous AD had a great impact on long-term prognosis. These findings will help to determine the therapeutic plan.
Changing Trends in Liver Cirrhosis Etiology and Severity in Korea: the Increasing Impact of Alcohol
Yoon Jae Hyun,Jun Chung Hwan,Kim Jeong Han,Yoon Eileen L.,Kim Byung Seok,Song Jeong Eun,Suk Ki Tae,Kim Moon Young,Kang Seong Hee 대한의학회 2021 Journal of Korean medical science Vol.36 No.21
Background: Chronic hepatitis B is the most common cause of liver cirrhosis in South Korea. However, alcoholic liver disease has shown an increasing trend. Although the clinical implications surrounding liver cirrhosis have been changing over the years, few studies have recently examined cirrhosis epidemiology. Therefore, we aimed to investigate changes in liver cirrhosis etiology and severity in Korea. Methods: We retrospectively reviewed 16,888 records of cirrhotic patients from six tertiary hospitals in Korea from 2008 to 2017. Continuous and non-continuous variables were processed via linear and Poisson regression, expressed as beta (B) coefficients and as exponentiated values of coefficients (Exp[B]), respectively. Results: Chronic hepatitis B showed a decreasing trend (Exp[B] = 0.975, P < 0.001), whereas alcohol showed an increasing trend (Exp[B] = 1.013, P = 0.003), occupying the most common etiology in 2017. The Child-Turcotte-Pugh (CTP) score and decompensated liver cirrhosis prevalence did not change over the 10-year period. The incidence of variceal bleeding, severe ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis significantly decreased from 12.3% to 7.7%, 7.8% to 4.1%, 1.0% to 0.5%, and 1.9% to 1.1%, respectively (P < 0.05 for all). In the subgroup analysis, the chronic hepatitis B group showed improving CTP scores (B = −0.025, P < 0.001) and decreasing decompensated liver cirrhosis rates (Exp[B] = 0.977, P = 0.016), whereas the alcohol group demonstrated increasing CTP class C (Exp[B] = 1.031, P = 0.005) and model for end-stage liver disease scores (B = 0.081, P = 0.005) over 10 years. Conclusion: The chronic hepatitis B group exhibited improved results, whereas the alcohol group still presented poor liver functions and outcomes. Future national policies and systematic approaches addressing the incidence, prevention, and treatment of alcoholic liver cirrhosis are indispensable.
( Eileen L. Yoon ),( Jeong Han Kim ),( Won Hyeok Choe ),( So Young Kwon ),( Won-choong Choi ),( Byung-chul Yoo ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Chronic hepatitis B(CHB) patients with multi-drug experience are frequently switched to tenofovir-monotherapy, recently in Korea. We aimed to evaluate safety and efficacy of switching to tenofovir-monotherapy from tenofovir-based combination therapy upto 24 months. Methods: This is a retrospective study of multi-drug experienced CHB patients who have switched from tenofovir-based combination therapy to tenofovir-monotherapy after achievement of virologic response(VR, less than 20 IU/mL) in two centers from 2013 to 2018 Results: A total of 39 patients were included. Median age was 52 years old. Twenty nine patients were male(74.4%). HBeAg positive patients were 32(82.1%). Thirty three patients(84.6%) had experienced not only nucleoside analogues, but also nucleotide analogues previously. Median duration of VR before switching to monotherapy was 16.3 months and median duration of monotherapy was 32.0 months(range, 3-55). VR at 12 and 24 months were achieved in 36 patients. One patient lost to follow-up after 12 months of monotherapy without non VR. Two patients experienced virologic breakthrough during 24 months of tenofovir-monotherapy. All the 5 patients who experienced non VR easily achieved VR within 3 months with tenofovir-monotherapy, but all of them had experienced adefovir previously. Duration of consolidation with combination therapy after VR were less than 6 months in 4 out 5 patients who showed non-VR during 24 months of tenofovir-monotherapy. Conclusions: Switching to tenofovir-monotherapy in multi-drug experienced patients is generally safe and effective upto 24 months. Constant monitoring of virus may be required in patients with previous adefovir-exposure and short duration of consolidation after VR achievement.
Long-term Prognosis of Cirrhotic Patients Who Survived from Acute-on-chronic Liver Failure
( Eileen L. Yoon ),( Tae Yeob Kim ),( Do Seon Song ),( Hee Yeon Kim ),( Chang Wook Kim ),( Young Kul Jung ),( Dong Hyun Sinn ),( Kim Sang Gyune ),( Jae Young Jang ),( Soung Won Jeong ),( Won Kim ),( H 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Aims: This study aimed to investigate the impact of ACLF on long-term survival after surviving the ACLF events in patients with acute deterioration. Methods: A total of 1177 acutely deteriorated patients who survived more than 3 months were consecutively collected and followed up in KACLiF study. ACLF was defined by EASL CLIF-C definition. Kaplan-Meier method was used to calculate survival. Results: Mean duration of follow up was 18.2±9.1months. The prevalence of ACLF was 8.8%(74/838). Most common etiology of cirrhosis was alcohol(62.3%). The survival of ACLF group was shorter than no ACLF group(25.6±1.2months vs. 30.7±0.4months, p=0.013). In subgroup of 558 patients with prior decompensation, survival of ACLF group was shorter than no ACLF group (23.3±1.7months vs. 29.1±0.6months, p=0.020). However, in subgroup of 515 patients without prior decompensation, survivals were not different between groups (p=0.289). Additionally, survivals of grade 1 and no CLIF-C ACLF patients were not different regardless of presence of prior decompensation. However, with prior decompensation, survivals of grade 2 and higher ACLF patients were shorter than grade 1 and no ACLF patients (19.3±2.6months vs. 29.0±0.6months, p=0.008). According to etiology of cirrhosis, survivals of alcoholic patients were shorter than non-alcoholic patients(30.2±1.8months vs. 23.6±1.3months, p=0.045). In the presence of prior decompensation, the experience of ACLF had worse effect on survival in alcoholic patients than non-alcoholic patients (30.0±2.4 vs 20.1±1.8, p=0.027). However, the survivals of those patients were not different in the absence of prior decompensation. Conclusions: Long-term mortality after survival from ACLF is dependent on the presence of prior decompensation. In the presence of prior decompensation, grade 2 and higher ACLF negatively affects survival even after recovery of ACLF. Also, effects of ACLF experience is more potent in alcoholic patients. Therefore, efforts to prevent acute decompensation and progression of organ failures may be important to improve the survival of cirrhotic patients.
( Eileen L Yoon ),( Jong Eun Yeon ),( Ji Hye Je ),( Yang Jae Yoo ),( Keun Hee Kang ),( Hyun Jung Lee ),( Sang Jun Suh ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyun Joon Yim ),( Kwan Soo Byun ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: Sorafenib is an only treatment proven to be beneficial for survival in advanced HCC patients. However, aggravation of the patients` performance status (PS) frequently limits the use of sorafenib in field-practice. We aimed to assess the real-world efficacy of sorafenib and factors significantly resulting in the early discontinuation of sorafenib use less than 4-weeks. Methods: We retrospectively analyzed the medical records of 102 patients who were treated for advanced HCC with sorafenib in Korea University Guro Hospital, between 2008 and 2012. Patients were divided into “Early discontinuation (ED) group (n=32)” and “Traceable for response (TR) group (n=70)” according to the treatment duration. Results: Best response rates of our center in the TR group were as follow: CR (3/70, 4.3%), PR (9/70, 12.9%), SD (26/70, 37.1%), and PD (32/70, 45.7%). The median overall survival and time to progression were 11.29 months and 2.93 months. Cox regression analysis revealed that worse PS upon discontinuation in the TR group and lymph node involvement were negatively related to the survival [HR 2.92 (95% C.I 1.37-6.25, P=0.005) and HR 3.85 (95% C.I 1.33-11.16, P=0.013), respectively]. Baseline characteristics of patients, liver function, and tumor characteristics were compared between the groups. ECOG PS 0 patients accounted for 31.3% and 70.0% in ED and TR group (P<0.001). Prevalence of Child A patients were 50.0% and 82.9% in the ED and TR group, respectively (P=0.002). Infiltrative type of tumor and presence of macrovascular invasion were more frequent in the ED group (P=0.014 and P=0.016). Among the reasons of treatment discontinuation, aggravation of PS was noted as high as 65.6% and 37.1% in the ED and TR group, respectively (P=0.010). Conclusions: Not only tumor characteristics, but also the baseline PS and aggravation of PS significantly affected the field-practice of sorafenib in both the ED and TR group.
( Eileen L Yoon ),( Eun Jung Ko ),( Jong Eun Yeon ),( Ji Hye Je ),( Yang Jae Yoo ),( Keun Hee Kang ),( Sun Jae Lee ),( Hyun Jung Lee ),( Sang Jun Suh ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyun Joon Yi 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background: The modest efficacy, high cost, and significant adverse reactions are the limitations of sorafenib. There have been no reliable serum markers predictive of response to sorafenib. Circulating miRNAs can be ideal biomarkers. We aimed to identify the specific circulating miRNAs prognostic for good response or favorable survival in advanced HCC patients who are scheduled for sorafenib treatment. Methods: On the basis of miRNAs previously reported to be associated with HCC, 6 target miRNAs, miR-21, miR-221, miR-18a, miR-10b*, miR-139-5p, and miR-224 were chosen. Relative expressions were measured by real-time RT-PCR in the sera of 24 HCC patients collected prior to sorafenib treatment. The sera of 25 liver cirrhosis (LC) patients were used as control. The results were validated in the 16 HCC tissue specimens obtained by needle biopsy and various HCC cell lines. Results: All the miRNAs except miR-21 were found to be overexpressed in the sera of HCC patients compared with those of LC patients (P<0.05). In the sera, there was no miRNA which shows significant difference in the relative expression between responder and non-responder group of HCC patients. Among them, circulating miR-10b* was shown to be overexpressed in the worse survivor (Fold change 2.9, P=0.0082). Tissue- based miR-10b* expression in the worse survivor group was down-regulated (Fold change 0.3, P<0.0001). The presence of macrovascular invasion was the only significant predictive factor for longer survival in our HCC patients. Circulating miRNA-10b* expression level was higher in the presence of macrovascular invasion and miR-10b* was also overexpressed in HCC cell lines with invasive tumor characteristics (P<0.001). Conclusions: Circulating miRNAs can overcome the limitation of miRNAs in the tissue obtained by needle biopsy. Serum miR-10b* may affect the invasiveness of HCC and serves as a prognostic biomarker predicting better survival in advanced HCC patients who are treating with sorafenib.