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( Eileen L. Yoon ),( Dae Won Jun ),( Sang Bong Ahn ),( Yong Kyun Cho ),( Do Seon Song ),( Jae Yoon Jeong ),( Hee Yeon Kim ),( Young Kul Jung ),( Myeong Jun Song ),( Sung Eun Kim ),( Hyoung Su Kim ),( 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: To evaluate the impact of L-carnitine on the improvement of quality of life (QOL) and cognitive function in liver cirrhosis patients with covert hepatic encephalopathy (HE). Methods: We conducted a multi-center, double-blind, randomized, phase III clinical trial in patients with covert HE. A total of 150 covert HE patients were randomized 1:1 to L-carnitine (1 g) or placebo for 24 weeks. Changes in QOL and cognitive function were assessed at 6 months. West Haven criteria, 36- Item Short Form Health Survey (SF-36), psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. Results: The L-carnitine supplement improved QOL compared to baseline. PHES scores were improved and normalization rates of minimal HE were increased in the L-carnitine group compared to baseline; however, median PHES scores and normalization rates were not different between the L-carnitine group and the placebo group at Week 24. Assessment of cognitive inhibition via the Stroop test showed significant improvement following 24 weeks of treatment in the L-carnitine group. Model for end stage liver disease scores were increased in the placebo group and significantly decreased in the L-carnitine group. Changes in total carnitine level positively correlated with rate correct scores of the Stroop test in the L-carnitine group. The incidence of adverse events was not different between the treatment groups. Conclusions: L-carnitine supplement was safe and effective for the improvement of QOL and cognitive dysfunction in covert HE patients with liver cirrhosis. (Clinical trial No. KCT0002029)
( Eileen L. Yoon ),( Sang Bong Ahn ),( Dae Won Jun ),( Yong Kyun Cho ),( Do Seon Song ),( Jae Yoon Jeong ),( Hee Yeon Kim ),( Young Kul Jung ),( Myeong Jun Song ),( Sung Eun Kim ),( Hyoung Su Kim ),( 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.4
Background/Aims: L-carnitine is potentially beneficial in patients with hepatic encephalopathy (HE). We aimed to evaluate the impact of L-carnitine on the quality of life and liver function in patients with liver cirrhosis and covert HE. Methods: We conducted an investigator-initiated, prospective, multi-center, double-blind, randomized phase III trial in patients with covert HE. A total of 150 patients were randomized 1:1 to L-carnitine (2 g/day) or placebo for 24 weeks. Changes in quality of life and liver function were assessed at 6 months. The model for end-stage liver disease (MELD), the 36-Item Short Form Survey (SF-36), the psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. Results: The total SF-36 score significantly improved in the L-carnitine group after 24 weeks (difference: median, 2; interquartile range, 0 to 11; p < 0.001); however, these values were comparable between the two groups. Furthermore, there was a significant ordinal improvement in PHES scores among patients with minimal HE who were in the L-carnitine group (p = 0.007). Changes in the total carnitine level also positively correlated with improvements in the Stroop test in the L-carnitine group (color test, r = 0.3; word test, r = 0.4; inhibition test, r = 0.5; inhibition/switching test, r = 0.3; all p < 0.05). Nevertheless, the MELD scores at week 24 did not differ between the groups. Conclusions: Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.
Therapeutic mechanisms and beneficial effects of non-antidiabetic drugs in chronic liver diseases
Han Ah Lee,Young Chang,Pil Soo Sung,Eileen L. Yoon,Hye Won Lee,Jeong-Ju Yoo,Young-Sun Lee,Jihyun An,Do Seon Song,Young Youn Cho,Seung Up Kim,Yoon Jun Kim 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3
The global burden of chronic liver disease (CLD) is substantial. Due to the limited indication of and accessibility to antiviral therapy in viral hepatitis and lack of effective pharmacological treatment in nonalcoholic fatty liver disease, the beneficial effects of antidiabetics and non–antidiabetics in clinical practice have been continuously investigated in patients with CLD. In this narrative review, we focused on non-antidiabetic drugs, including ursodeoxycholic acid, silymarin, dimethyl- 4,4’-dimethoxy-5,6,5’,6’-dimethylenedixoybiphenyl-2,2’-dicarboxylate, L-ornithine L-aspartate, branched chain amino acids, statin, probiotics, vitamin E, and aspirin, and summarized their beneficial effects in CLD. Based on the antioxidant, anti-inflammatory properties, and regulatory functions in glucose or lipid metabolism, several non–antidiabetic drugs have shown beneficial effects in improving liver histology, aminotransferase level, and metabolic parameters and reducing risks of hepatocellular carcinoma and mortality, without significant safety concerns, in patients with CLD. Although the effect as the centerpiece management in patients with CLD is not robust, the use of these non-antidiabetic drugs might be potentially beneficial as an adjuvant or combined treatment strategy.
Validation of Korean Stroop Test in the Screening of Minimal Hepatic Encephalopathy
( Eileen L. Yoon ),( Dae Won Jun ),( Jae Yoon Jeong ),( Tae Yeob Kim ),( Do Seon Song ),( Sang Bong Ahn ),( Hee Yeon Kim ),( Young Kul Jung ),( Myeong Jun Song ),( Sung Eun Kim ),( Hyoung Su Kim ),( S 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Minimal hepatic encephalopathy (mHE) has poor prognosis but hardly drawn attention when patients have no symptoms. We aimed to validate Korean stroop test in the screening of mHE. Methods: Chronic hepatitis B related liver cirrhosis (LC) patients without history of overt hepatic encephalopathy were recruited prospectively from 13 centers for two years. All participants completed Portosystemic encephalopathy syndrome test (PHES) and Korean stroop test. Korean stroop test is consisted of 2 On-states (color, word) and 2 Off-states (inhibition, switching). Correct response rates and response times were measured. Four types of “OnTime+OffTime” have been analyzed (color+inhibition, color+switching, word+inhibition, and word+switching). mHE was diagnosed when PHES scores less than -4. Healthy controls (HC) were also recruited (n=376). Results: Among 223 LC patients, 67.3% was male. Mean age was 53 years. Prevalence of mHE was 20.6%. Response times for each states showed negative correlation with PHES scores (P<0.001). Also color+inhibition, color+switching, word+inhibition, and word+switching showed negative correlation with PHES scores, -0.361, -0.310, -0.442, and -0.336, respectively(all P<0.001). The highest AUC in the discrimination of mHE among various “OnTime+OffTime” was word+inhibition (AUC 0.75, 95% C.I 0.67-0.84, P<0.001). Mean values of word+inhibition were significantly different among the three groups, which were 54.6±13.2sec, 63.4±18.2sec, and 83.4±27.8sec in HC, LC without mHE, and LC with mHE, respectively (all P<0.001). Among various factors, time for word+inhibition was the only significant factor (OR 1.04, 95% C.I 1.02-1.06, P<0.001) in multivariate analysis for diagnosis of mHE. Conclusions: Korean stroop test is simple and valid method for screening of mHE.
Eileen L. Yoon,연종은,고은정,이현정,제지혜,유양재,강성희,서상준,김지훈,서연석,임형준,변관수 대한의학회 2017 Journal of Korean medical science Vol.32 No.2
The prognostic role of aberrant serum miRNA expression for predicting response to sorafenib treatment in advanced hepatocellular carcinoma (HCC) patients has not been well characterized. We aimed to identify specific serum miRNAs that are associated with positive radiologic responses or improved survival in sorafenib-treated HCC patients. miR-18a, miR-21, miR-139-5p, miR-221, miR-224, and miR-10b-3p, were selected for analysis. Serum samples from 24 patients with advanced stage HCC and 25 patients with liver cirrhosis (LC) were analyzed. All of the miRNAs except miR-21 were found to be upregulated in serum samples from HCC patients. None of the miRNAs assayed differed significantly in terms of expression between the responder and non-responder groups among HCC patients. However, miR-10b-3p levels were significantly higher in the subgroup of HCC patients with worse overall survival (fold change = 5.8, P = 0.008). Serum miRNA-10b-3p was upregulated in the presence of macrovascular invasion (MVI), and those with higher serum miRNA-10b-3p had significantly shorter survival during treatment (P = 0.042). Although no single serum miRNA was predictive of response to sorafenib treatment, analysis of serum miR-10b-3p levels may be valuable for diagnosis of HCC and prediction of survival of sorafenib-treated patients.
( 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.
Impact of Previous Acute Decompensation on Tolerance to Acute-on-Chronic Liver Failure
( Eileen L. Yoon ),( Do Seon Song ),( Hee Yeon Kim ),( Chang Wook Kim ),( Jin Mo Yang ),( Young Kul Jung ),( Hyung Joon Yim ),( Baek Gyu Jun ),( Jung Gil Park ),( Young Chang ),( Jeong-ju Yoo ),( Sang 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1
( 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.
( 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.