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( Seun Joo Ahn ),( Dong Kyu Kim ),( Soon Sun Kim ),( Chang Bum Bae ),( Hyo Jung Cho ),( Han Gyeol Kim ),( Young Jip Kim ),( Joo Ho Lee ),( Hyo Jin Lee ),( Mi Yeon Lee ),( Kee Bum Kim ),( Jin Hee Cho ) 대한간학회 2012 Clinical and Molecular Hepatology(대한간학회지) Vol.18 No.3
Background/Aims: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. Results: The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. Conclusions: The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls. (Clin Mol Hepatol 2012;18:295-301)
( Seun Joo Ahn ),( Dong Kyu Kim ),( Soon Sun Kim ),( Chang Bum Bae ),( Hyo Jung Cho ),( Han Gyeol Kim ),( Young Jip Kim ),( Hyo Jin Lee ),( Mi Yeon Lee ),( Sung Jae Shin ),( Kee Myung Lee ),( Kwang Ja 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.-
Background/Aims: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determine disease outcome in hepatitis B virus (HBV) infected individuals, and to verify the association with the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods: This hospital based case-control study enrolled 183 subjects (47 healthy controls, 50 HBV originated liver cirrhosis, 86 HCC). ApoE genotypes were determined by ApoE genotyping kit, using a PCR method. To verify the biological significances of ApoE genotype, a serum ApoE levels were measured by ELISA kit. Results: The ε3 allele was the most common allele, with allele frequencies of 5.7% for ε2 allele, 84.7% for the ε3 allele and 9.6 % for ε4 allele in all participants. We identified that ApoE genotype was associated with the progression to liver cirrhosis in chronic HBV carriers. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. No influence of ApoE genotypes on the susceptibility to the occurrence of HCC was found. The serum ApoE measurements revealed a significantly higher level of ApoE in patients with liver cirrhosis than those in the healthy controls, but we observed no significant difference in the serum ApoE levels, with regard to ApoE genotype. Conclusion: This study indicates that ApoE genotypes may be a part of genetic variation underlying the susceptibility of individuals to disease progression of chronic HBV infection.
( Seun Joo Ahn ),( Dong Kyu Kim ),( Soon Sun Kim ),( Chang Bum Bae ),( Hyo Jung Cho ),( Han Gyeol Kim ),( Young Jip Kim ),( Hyo Jin Lee ),( Mi Yeon Lee ),( Sung Jae Shin ),( Kee Myung Lee ),( Kwang Ja 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background/Aims: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determine disease outcome in hepatitis B virus (HBV) infected individuals, and to verify the association with the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods: This hospital based case-control study enrolled 183 subjects (47 healthy controls, 50 HBV originated liver cirrhosis, 86 HCC). ApoE genotypes were determined by ApoE genotyping kit, using a PCR method. To verify the biological significances of ApoE genotype, a serum ApoE levels were measured by ELISA kit. Background: Portal vein thrombosis (PVT) is a surgical challenge in liver transplantation (LTx). Presence of PVT was considered as a contraindication for LTx in some centers due to the controversy revolving around the long term outcome of these patients. Therefore, we studied the long term outcome of adult patients with PVT in LTx in a tertiary institution with specialized transplantation unit. Methods: There were 570 cases of adult liver transplantation between 2004 and 2009 in our institution. We excluded 99 cases of deceased donor liver transplantations to facilitate incidence, outcome and surgical management. There were 56 patients with existing PVT before 471 living donor liver transplantations. Patients with PVT were divided into 2 groups according to Yerdal’s classification, mild PVT group (Yerdel group 1 & 2) 43 cases and severe PVT group (Yerdel group 3 & 4) 13 cases. Results: Patients with PVT constituted 11.8% (n=56) in our cohort. When comparing between patients without and with PVT, we did not find statistical difference in terms of age, gender, Child-Pugh score, MELD score & indication for LTx (benign vs malignancy). Rate of PV complication was 3.4% in the non-PVT group and 8.9% in PVT group (p=0.047). Duration of operation and total amount of blood transfusion were also comparable between two groups. The overall survival of PVT group was not significantly different compared to the non-PVT group (p=0.059). Demographics of 43 cases of mild PVT (76.7%) and 13 cases of severe PVT (23.3%) were not different except in severe PVT group had more malignancy cases (27 cases vs 2 cases, p=0.011). The median overall survival of mild PVT group is comparable with non-PVT group (p=0.059) and the median overall survival of severe PVT group is 32 months (1-88) and non-PVT group is 41 months (1-93) (p=0.066). 5-year survival rate of severe PVT is about 60%. Conclusions: Existing PVT prior to liver transplantation does not lead to poorer long term outcome. However in severe cases, we need more careful approach. Therefore, PVT should not be a contraindication to liver transplantation.
Original Article : Serum transferrin as Liver fibrosis biomarkerin patients with chronic hepatitis B
( Hyo Jung Cho ),( Soon Sun Kim ),( Seun Joo Ahn ),( Joo Han Park ),( Dong Joon Kim ),( Young Bae Kim ),( Sung Won Cho ),( Jae Youn Cheong ) 대한간학회 2014 Clinical and Molecular Hepatology(대한간학회지) Vol.20 No.4
Background/Aims: Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B. Methods: The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared. Results: Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B. Conclusions: Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.
( Hyo Jung Cho ),( Sun Young Park ),( Ga Won Song ),( Seun Joo Ahn ),( Ho Joong Kim ),( Joo An Hwang ),( Soon Sun Kim ),( Sung Won Cho ),( Jae Youn Cheong ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1
Background/aims: Liver biopsy remains the gold standard to assess hepatic fibrosis. To identify new candidate markers for liver fibrosis, we performed serum based proteomic approach in patients with chronic hepatitis B (CHB). Methods: Sera were obtained from 12 patients with CHB at the time of liver biopsy. Batt-Ludwig classification was used for staging liver fibrosis. Proteins in pooled sera of mild fibrosis (F1 or F2, n=6) and liver cirrhosis (F4, n=6) were compared and analyzed by using 2D gel electrophoresis. Protein spots varying among two groups were excised, digested and submitted for tandem mass spectrometry for protein identification. Validation study was done for new markers among 293 CHB patients who underwent liver biopsies. Results: We identified 147 proteins which were increased or decreased significantly in hepatic cirrhosis. Among these 147 proteins, we found 7 candidate biomarkers which were supposed to be correlated with liver fibrosis. Alpha2-macroglobulin, kininogen1, transferrin and alph1-antitrypsin (A1AT) were increased whereas inter-alpha inhibitor H2, apolipoprotein A4 and apolipoprotein A1 were decreased in patients with cirrhosis. We performed validation study for A1AT and transferrin which were suitable for quantification in 293 patients with CHB. However, A1AT and trasnferrin were not significantly associated with liver cirrhosis in validation cohort. Conclusions: We identified several candidate biomarkers for predicting liver cirrhosis in patients with CHB using proteomics technology, but could not be confirmed in large validation cohort. Further advances in proteomics techniques and establishment of simple and quantitative methods are required to identify non-invasive diagnostic marker of liver fibrosis.