Clinical Characteristics and Prevelance of Hepatitis Delta Virus Infection in Patients with Chronic Hepatitis B in Korea

( Young Kul Jung ),( Dong-won Lee ),( Ja Seol Koo ),( Jung Wan Choe ),( Sang Jun Suh ),( Seung Young Kim ),( Jong Jin Hyun ),( Sung Woo Jung ),( Hyung Joon Yim ),( Sang Woo Lee ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Hepatitis delta virus (HDV) and hepatitis B virus (HBV) coinfection is associated with more severe liver disease than HBV alone. More knowledge on the epidemiology and clinical impact of HDV-infected individuals is needed in Korea. Despite the development of new antiviral agents of HDV these days, it is not well known characteristics and prevelance of hepatitis delta virus infection in patients with chronic hepatitis B in Korea. Methods: Total 1263 HBV infected patients visiting liver clinic at Korea University Ansan Hospital from January to December 2014 were screened for anti-HDV antibodies using ELISA assays. Comfirmed positive samples were further tested for HDV RNA using a commercial RT-PCR assay. Clinical characteristics and biological data from patients were researched and compared based on anti-HDV antibodies and HCV RNA results Results: Most patients (n=814, 65%) were men and mean age was 49 years old. Anti-HDV anti-bodies were detected in 11 individuals (0.87%), 2 of whom were HDV RNA positive. Anti-HDV antibody positive patients showed similar clinical features, these had liver cirrhosis (45.5% vs. 33.8%, P=0.524) and HCC (18.2% vs. 12.9%, P=0.643) compared with HDV negative. However, all of 2 patients with HDV-RNA positivity showed significant cirrhosis. Conclusions: HDV infection is rare in patients with chronic hepatitis B in Korea, but is related with liver cirrhosis in HDV RNA positive patients. However, HDV co-infection may not have a clinical importance.

사례보고 : 원발성 간세포암종의 늑골전이를 경동맥화학색전술로 치료한 1예

정영걸 ( Young Kul Jung ),연종은 ( Jong Eun Yeon ),김청호 ( Chung Ho Kim ),이현정 ( Hyun Jung Lee ),이영선 ( Young Sun Lee ),윤아일린 ( Eileen L. Yoon ),정은석 ( Eun Suck Jung ),최종환 ( Jong Hwan Choi ),김지훈 ( Ji Hoon Kim ),변 대한간학회 2009 Clinical and Molecular Hepatology(대한간학회지) Vol.15 No.3

뼈는 간세포암종의 전이 장소 중 세 번째로 흔하게 발생하는 곳으로 이에 대한 치료는 제한적이다. 55세 남자 환자가 우하흉부 통증으로 내원하여 원발성 간세포암종과 우측 8번 늑골전이로 진단되었다. 혈관조영술에서 우측 8번 늑간동맥으로부터 공급되는 늑골의 종양이 관찰되어 총 3회의 경동맥 화학색전술을 시행하였고, 이후 두 차례의 컴퓨터 단층촬영에서는 우측 8번 늑골 종양 부위에 치밀한 리피오돌 침착이 관찰되었으며, 통증은 소실되었다. 이에 저자들은 경동맥화학색전술로 치료한 원발성 간세포암종 환자의 늑골전이 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Bone is a common site of metastasis in patients with hepatocellular carcinoma (HCC). We report a rare case of rib metastasis from HCC treated by transcatheter arterial chemoembolization (TACE). A 55-year-old man with liver cirrhosis presented with right lower chest pain. The diagnosis was an HCC with a bone metastasis in the right eighth rib. Intra-arterial injections of doxorubicin mixed with Lipiodol and Gelfoam particles were instituted through the right eighth intercostal artery. Computed tomography and a Tc99-labeled scan performed 2 months after the third TACE revealed no viable HCC in the right eighth rib. (Korean J Hepatol 2009;15:357-361)

Reversal of liver cirrhosis: current evidence and expectations

( Young Kul Jung ),( Hyung Joon Yim ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.2

In the past, liver cirrhosis was considered an irreversible phenomenon. However, many experimental data have provided evidence of the reversibility of liver fibrosis. Moreover, multiple clinical studies have also shown regression of fib-rosis and reversal of cirrhosis on repeated biopsy samples. As various etiologies are asso-ciated with liver fibrosis via integrated signaling pathways, a comprehensive un-derstanding of the pathobiology of hepatic fibrogenesis is critical for improving clinical outcomes. Hepatic stellate cells play a central role in hepatic fibrogenesis upon their activation from a quiescent state. Collagen and other extracellular material components from activated hepatic stellate cells are deposited on, and damage, the liver parenchyma and vascular structures. Hence, inactivation of hepatic stellate cells can lead to enhancement of fibrolytic activity and could be a potential target of antifibrotic therapy. In this regard, continued efforts have been made to develop better treatments for underlying liver diseases and antifibrotic agents in multiple clinical and therapeutic trials; the best results may be expected with the integration of such evidence. In this article, we present the underlying mechanisms of fibrosis, current experimental and clinical evidence of the revers-ibility of liver fibrosis/cirrhosis, and new agents with therapeutic potential for liver fibrosis.

Clinical system 2 : The epidemiologic concern in alcoholic liver disease

( Young Kul Jung ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.2

Alcoholic liver disease remains a significant health burden in Korea and worldwide. The clinical spectrum of this disease spans from simple fatty liver to fibrosis and overt cirrhosis (characterized by ascites, varix, and hepatic encephalopathy). The annual costs associated with the consumption of alcohol in Korea were estimated to be 2.86% of the GDP in 2006; this included medical costs for the treatment of alcohol-related diseases, indirect costs (loss of productivity and decreases in the available workforce resulting from premature death), and other costs. A nationwide knowledge of alcohol consumption and drinking problems can provide a foundation for planning and implementing national intervention programs. However, the consumption of alcohol and alcohol related problems in Korean have not been extensively studied despite the associated social, economic, and public health burdens. So, an exact evaluation of alcoholic epidemiology and risk factors is very important. Through this review, we suggest that high alcohol consumption and alcohol-related problems in Korean are not negligible and require intervention, and also Korean guideline for clinician is necessary.

Ribavirin May Help to Improve Sustained Virological Response of Daclatasvir Plus Asunaprevir for Chronic Hepatitis C 1b Patients

( Young Kul Jung ),( Sang Jun Suh ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon ),( Kwan Soo Byun ),( Soon Ho Um ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Daclatasvir is a nonstructural protein 5A inhibitor, and asunaprevir is a nonstructural protein 3 protease inhibitor with activity against genotypes 1, 4, 5, and 6. Despite a 90% sustained virologic response (SVR) rate without baseline NS5A-L31/ Y93H polymorphisms, the SVR rate is slightly lower than that of other DAA agents combination. Therefore, an alternative regimen under the consideration of cost-effectiveness would be important. Whether the addition of ribavirin could improve the SVR rate among this group of patients remains unknown and so we investigated ribavirin effect. Methods: Total 262 CHC patients with genotype 1b were prospectively enrolled in three KUMC hospital. 218 patients of them were treated with daclatasvir plus asunaprevir with (n=30) or without rivabirin (n=188). The other patients were excluded because of other DAA agents or loss during treatment. Results: Mean age was 60 years old and Male was 43.6% (n=95). Gradually RVR, ETR, and SVR was 90.8%, 90.8%, and 84.4% by ITT protocol, respectively. RVR, ETR, and SVR was 96.6%, 94.7%, and 92% by Per protocol. IFN experienced patients was 23.2% (n=46) and SVR was 95.7%, which is similar rate compared with naïve patients 92.1% (P=0.528). Liver cirrhosis patients was 32.3% (n=64) and SVR was 90.6%, which is also similar rate compared with non cirrhotic patients 94% (P=0.555). However, RBV additional therapy patients was 11.6% (n=23) and SVR was 100% which is slightly improved compared with non RBV therapy patients 87.5% (P=0.230). No patients developed significant adverse effects during and after the treatment. Conclusions: In genotype 1b chronic hepatitis C patients without NS5A-Y93H polymorphism, the addition of ribavirin to daclatasvir/asunaprevir may increase the SVR12 rate with minimal side effects, and thus deserves more comprehensive trials in resource-limited areas

Comparison of the Efficacy of Entecavir and Tenofovir Monotherapy for the Treatment of Treatment-naive

( Young Kul Jung ),( Sang Jun Suh ),( Hyung Joon Yim ),( Oh Sang Kwon ),( Yun Soo Kim ),( Duck Joo Choi ),( Ju Hyun Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Current treatment guidelines recommend either entecavir (ETV) or tenofovir (TDF) as first line treatment for management of chronic hepatitis B patients given their high antiviral potency, favorable tolerability profile, and high genetic barriers to the development of antiviral resistance. However, it is not clear whether the efficacy reported from head-to-head trial is similar to the outcomes seen in routine practice. So, our aim is to investigate the treatment outcomes of antiviral therapy in a clinical practice. Methods: We conducted a prospective cohort study of 130 treatment- naive patients who started either ETV or TDF by randomization manner between Januanry 2013 and December 2014. Primary endpoint was complete viral suppression rate (HBV DNA real-time PCR < 20 IU/mL) at 12 month after treatment (ClinicalTrials.gov Identifier: NCT01776814). Results: Total 130 CHB patients were enrolled and randomized in both group. However, 15 patients were dropped by any lesion and 104 patients (80%) were remain at 12 months. The majority of patients in both ETV and TDF group were male (73%), HBeAg negative (60%), and non-cirrhotic patients (52%). Pretreatment serum ALT, HBV DNA level, bilirubin, and albumin level were similar between two groups (p=n.s.). At treatment 12 months, both group achieved similar complete virological response: 85% vs. 86%, respectively (p=0.26). Biochemical response is also similar: 95% vs. 96%, respectively (p=0.3). Among HBeAg positive patients, 6 patients showed HBeAg loss ( 2 patients in ETV, 4 in TDF) and 2 patients achieved HBeAg seroconversion (1 at ETV, 1 at TDF). 3 patients experienced side effect and stopped medication (1 at ETV, 2 at TDF). However, there was no serious side effect during treatment period. Conclusions: Treatment-naive CHB patients treated with either ETV or TDF achieved a similar rate of complete virological and biochemical response at 12 months. However, drop rate was slightly high regardless of drug and attention to medication adherence is needed in a clinical practice.

Treatment Response and Safety of Sofosbuvir plus Ribavirin for the Treatment of HCV Genotype 2 Infection: Results of Tertiary Hospitals Experience

( Young Kul Jung ),( Sang Jun Suh ),( Ji Hoon Kim ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon ),( Kwan Soo Byun ),( Soon Ho Um ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infected patients in KASL guideline based on clinical trials. However, there is a few data in real world setting. So, we investigated effectiveness and safety of this regimen for HCV GT2 infected patients in tertiary hospitals. Methods: Three tertiary center, prospective observational cohort study evaluates clinical practice data (Korea university Anam, Guro, and Ansan) between January 2015 and December 2016. Clinical data were centrally collected from medical records. Selection of treatment regimen and duration was the investigator’s choice. The primary efficacy outcome was sustained virological response 12 weeks after therapy (SVR12). Results: 146 patients were visited and 131 patients were treated SOF plus RBV during 12 weeks (n=122) or 16 weeks (n=9). Overall, EVR, ETR, and SVR12 by ITT analysis were 90.0%, 96.2% and 87%. In addition, EVR, ETR, and SVR12 by PP analysis 97.5%, 99.2% and 96.3%, respectively. In subgroup analysis, SVR12 in patients with treatment-naïve and treatment-experience were 97.2% or 94.7%, respectively. SVR12 in patients with and without cirrhosis were 94.4% and 97.4%, respectively. In patients with high viral load (>800,000 IU/mL), SVR rate was 95.3% and there was no differentiation comparing with non-high viral load. In the multivariate analysis, liver cirrhosis, lower serum albumin and RBV dose at baseline were not associated with SVR12. Common adverse events (AEs) included fatigue, anaemia, nausea, headache, insomnia, rash and flu-like symptoms. Discontinuation due to AEs occurred in only 1 patient by severe anemia. Conclusions: In this clinical practice setting, SOF and RBV was safe and effective for treatment of patients with HCV GT2 infection.

HCV, Alcoholic : PE-082 ; Relationship of IL28B gene polymorphism with liver fibrosis and hepatocellular carcinoma of chronic hepatitis C patients in Korea

( Young Kul Jung ),( Soo Yong Park ),( Min Young Rim ),( In Ku Yo ),( Min Su Ha ),( Ju Seung Kim ),( Ju Won Lee ),( Oh Sang Kwon ),( Yun Soo Kim ),( Duck Joo Choi ),( Ju Hyun Kim ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-

Background/Aims: Single-nucleotide polymorphisms (SNPs) near the IL28B gene have recently been associated with spontaneous hepatitis C virus (HCV) clearance and response to interferon-based therapies in patients with chronic hepatitis C (CHC). Because IL28B SNPs appears to influence HCV-related immune response, any effect of IL28B SNP on the risk of progression to cirrhosis and hepatocelluar carcinoma (HCC) might be more easily developed in a specific genetic population. Methods: In a cross-sectional design, liver cirrhosis, HCC and rs12979860 genotypes were analysed in 134 CHC patients. IL28B genotypes were determined by a pyrosequencing assay. In CHC patients, 4 HCV related HCC were analyzed according to rs12979860 genotypes. Results: A total of 134 HCV-infected individuals were analyzed [mean age, 44 years; 66 (49.3%) were male; and 21 (15.7%) were HCV-related cirrhosis], of whom 4 (3%) had HCC. And HCV genotype showed as follows: genotype 1, 86 (64.2%); genotype 2, 47 (35.1%); genotype 6, 1 (0.7%). IL28B genotype distribution was as follows: CC, 87.3%; CT, 12.7%; and TT, 0%. Cirrhosis showed an even distribution in CC and CT genotype (16.2% vs 11.8%; p=0.742). 4 HCCs were diagnosed during follow-up period and all of them showed a CC genotype, however, there was no statistically significant difference according to IL28B genotype (Log Rank test, p= 0.365). Conclusions: The IL28B rs12979860 CC genotype is not associated with a higher prevalence of cirrhosis and HCC in HCV infected patients than CT genotypes. However, additional large-scale study is needed.

Aspects of Primary Biliary Cholangitis Diagnosis and Treatment Response in a Single Institutional Experience

( Young Kul Jung ),( Tae Hyung Kim ),( Jong Jin Hyun ),( Seung Young Kim ),( Sung Woo Jung ),( Ja Seol Koo ),( Hyung Joon Yim ),( Sang Woo Lee ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Primary biliary cholangitis is an autoimmune liver disease that is common among middle-aged women, and the small bile ducts are lost by non-purulent cholecystitis and can gradually progress to cholestasis, liver fibrosis, and cirrhosis. For a type of autoimmune disease, Anti Mitochondrial Antibody(AMA) is found in about 90-95% of patients. However, the incidence is relatively low, and furthermore, studies on the evaluation of treatment response in Korea are very rare. This study was designed to analyze the patterns and treatment trends of patients diagnosed with PBC in a single institution. Methods: From 2010 to 2020, the medical records of Korea Univ. Ansan Hospital were investigated and 95 patients suspected or diagnosed as PBC have been checked to analyze 92 patients, excluding those with missing records or insufficient diagnosis. Among these patients, the response rate of UDCA treatment was evaluated in 67 patients who were followed up for more than one year. For diagnosis and evaluation of treatment response refer to 2018 AASLD PBC Practice Guidance. The treatment response was based on the normalization of ALP at the first year of treatment. In the serum test, the Anti Mitochondrial Antibody (AMA) test was performed using the Fluorescent antibody test. Results: A total of 95 patients had an mean age of 56 years, of which 87 were female and 8 were male, with a sex ratio of 10.9: 1. At the time of diagnosis, 33 patients (34.7%) had cirrhosis and 48 patients (50.5%) had auto-immune related comorbidities. The most common was thyroid disease (13 patients, hypothyroidism), and Sicca syndrome, Raynaud disease, Behcet’s disease, SLE, and so on. Symptoms usually complained of itching and pruritis. but most were asymptomatic. In serologic examination, 92 AMA positive PBC (96.8%), and the other 3 showed negative findings in gp210 or sp100, but the diagnosis was progressed by clinical pathological findings. In further studies with stored samples, gp210 and sp100 were positive in 33% and 15%, respectively. In addition, PBC / AIH overlap was diagnosed in 13 patients (13.7%) on serological histological examination. Eight patients (11.9%) showed insufficient treatment response in 67 patients following follow-up of UDCA for more than one year, especially positive (33%) in gp210 and Ro-52 antibodies and with autoimmune hepatitis( AIH). More than half the patients with insufficient treatment response showed PBC / AIH overlap feature. Conclusions: PBC patients are often accompanied by systemic autoimmune disease at the time of diagnosis, and some patients are accompanied by AIH when diagnosed, and they often do not reach a sufficient response within 1 year of treatment with UDCA. In addition, antibody diagnostics other than AMA may be helpful in predicting treatment response during diagnosis of these patients.

The Korean Society of Gastroenterology & SIDDS 2056 : Slide Session ;K-LI-03 : Liver ; Several Factors May Be Considered When Applying the Liver Stiffness by Transient Elastography in Patients with Chronic Hepatitis B

( Young Kul Jung ),( Kwang Seok Kim ),( Ji Kyoung Lee ),( Sang Yoon Chung ),( Chang Bum Bae ),( Joo Hee Park ),( Sang Jun Suh ),( Seung Young Kim ),( Jong Jin Hyun ),( Ja Seoul Koo ),( Hyung Joon Yim 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: The aim of this study is to compared with transient elastography and other invasive fi brosis marker, and to investigate several factors infl uencing the liver stiffness measurement (LSM) in chronic hepatitis B patients. Methods: Two hundred twenty eight patients with chronic hepatitis B who underwent liver biopsy and TE in the same time were recruited from January 2008 to December2013. Results: 159 (69.7%) of them were Male, and mean age was 41.9 years old. Mean of AST and ALT were 114.9 IU/L and 165.1 IU/L, respectively. Platelet count was 1.75 x 103 cell/uL.. 102 (44.7%) patients had HBeAg positivity. In liver Biopsy, 39 patients (17.1%) had F0-1, 57 (25.0%) had F2, 76 (33.3%) had F3, and 56 (24.6%) had F4, respectively. In view of the signifi cant fi brosis (F4), TE showed signifi cantly good estimate of liver fi brosis, and corresponding area under the ROC curves of LSM was 0.733 that showed slightly good estimate value compared with APRI (0.468) and fiB-4 (0.641). Among the lower ALT patients (ALT under 100 IU/L) corresponding area under the ROC curves of LSM was 0.804, and among HBeAg negative patients corresponding area under the ROC curves of LSM was 0.755. The cutoff LSM values for >F2, >F3, and F4 were 6.9, 8.5, and 10.1 kPa, respectively, whereas they were 6.2, 7.5, and 9.6 kPa, respectively, in those with ALT <X2 UNL. Conclusions: TE has good estimate performance for liver stiffness and fi brosis compared with AFRI and fiB-4 in chronic hepatitis B patients. However, ALT and HBeAg could influence liver stiffness. So, different cutoff LSM values may be applied in chronic hepatitis B patients.