G-W Song1, C-S Ahn1, S-G Lee2, S Hwang1, K-H Kim1, D-B Moon1, T-Y Ha1, D-H Jung1, G-C Park1, S-H Kang1, B-H Jung1, N Kim3. 1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 2. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: sglee2@amc.seoul.kr. 3. Asan Center for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Abstract
BACKGROUND AND AIMS: Despite the application of prophylaxis, the risk of hepatitis B virus (HBV) recurrence remains. However, actual mechanism(s) and definite risk factor(s) are obscure. The present study examined the correlation between the HBV load in liver explants and post-liver transplant (OLT) HBV recurrence. METHODS: HBV DNA was extracted from liver tissue taken from 50 living donor OLT (LDLT) patients using the QuickGene DNA Tissue Kit S (Fujifilm, Tokyo, Japan) and subjected to real-time polymerase chain reaction with the following primers: 5'-CACATGGCCTCCAAGGAGTAA-3' (forward primer) and 5'-TGAGGGTCTCTCTCTTCCTCTTGT-3' (reverse primer). To prevent HBV infection, patients were treated daily with high-dose (10,000 IU) hepatitis B immunoglobulin (HBIG) for the first week after LDLT. They then received weekly doses for the next month and then monthly doses for ≤1 year. If the anti-hepatitis surface antigen antibody titer was <1,000 IU/L, an antiviral agent (AVA) was added to the regimen. RESULTS: The mean (±SD) tissue HBV DNA and covalently closed circular DNA (cccDNA) loads were -0.8 ± 1.2 (range, -2.9 to 2.6) and -2.3 ± 1.1 (range, -4.6 to 0.6) log10 copies/cell, respectively. There was a significant correlation between serum and tissue HBV DNA (r = 0.65; P = .00) and cccDNA concentrations (r = 0.55; P = .00). Six patients suffered HBV recurrence and 9 required additional AVA. There was no direct correlation between HBV recurrence and tissue cccDNA concentration. However, the concentration of cccDNA was significantly greater those patients suffering recurrence and receiving AVA treatment (high-risk group). CONCLUSION: High tissue cccDNA concentrations may be a risk factor for HBV recurrence despite high-dose HBIG prophylaxis.
BACKGROUND AND AIMS: Despite the application of prophylaxis, the risk of hepatitis B virus (HBV) recurrence remains. However, actual mechanism(s) and definite risk factor(s) are obscure. The present study examined the correlation between the HBV load in liver explants and post-liver transplant (OLT) HBV recurrence. METHODS:HBV DNA was extracted from liver tissue taken from 50 living donor OLT (LDLT) patients using the QuickGene DNA Tissue Kit S (Fujifilm, Tokyo, Japan) and subjected to real-time polymerase chain reaction with the following primers: 5'-CACATGGCCTCCAAGGAGTAA-3' (forward primer) and 5'-TGAGGGTCTCTCTCTTCCTCTTGT-3' (reverse primer). To prevent HBV infection, patients were treated daily with high-dose (10,000 IU) hepatitis B immunoglobulin (HBIG) for the first week after LDLT. They then received weekly doses for the next month and then monthly doses for ≤1 year. If the anti-hepatitis surface antigen antibody titer was <1,000 IU/L, an antiviral agent (AVA) was added to the regimen. RESULTS: The mean (±SD) tissue HBV DNA and covalently closed circular DNA (cccDNA) loads were -0.8 ± 1.2 (range, -2.9 to 2.6) and -2.3 ± 1.1 (range, -4.6 to 0.6) log10 copies/cell, respectively. There was a significant correlation between serum and tissue HBV DNA (r = 0.65; P = .00) and cccDNA concentrations (r = 0.55; P = .00). Six patients suffered HBV recurrence and 9 required additional AVA. There was no direct correlation between HBV recurrence and tissue cccDNA concentration. However, the concentration of cccDNA was significantly greater those patients suffering recurrence and receiving AVA treatment (high-risk group). CONCLUSION: High tissue cccDNA concentrations may be a risk factor for HBV recurrence despite high-dose HBIG prophylaxis.
Authors: Gil Chun Park; Shin Hwang; Myoung Soo Kim; Dong Hwan Jung; Gi Won Song; Kwang Woong Lee; Jong Man Kim; Jae Geun Lee; Je Ho Ryu; Dong Lak Choi; Hee Jung Wang; Bong Wan Kim; Dong Sik Kim; Yang Won Nah; Young Kyoung You; Koo Jeong Kang; Hee Chul Yu; Yo Han Park; Kyung Jin Lee; Yun Kyu Kim Journal: J Korean Med Sci Date: 2020-02-17 Impact factor: 2.153