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The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection
Institution:1. Artificial Organ and Transplantation Division, Department of Surgery, The University of Tokyo, Tokyo, Japan;2. Biostatistics Unit, Clinical Research Promotion Center, University of Tokyo Hospital, Tokyo, Japan;3. Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan;4. Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan;1. Department of Surgery, Mayo Clinic, Rochester, MN, USA;2. Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA;3. Division of Laboratory Medicine and Anatomic Pathology, Mayo Clinic, Rochester, MN, USA;4. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA;1. Division of General and Transplant Surgery, University of Pisa, Pisa, Italy;2. Division of Anesthesia and Intensive Care, University of Pisa, Pisa, Italy;1. Providence St. John''s Cancer Institute, Santa Monica, CA, USA;2. Providence Health and Services, Beaverton, OR, USA
Abstract:BackgroundWe assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection.MethodsAmong 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay.ResultsHBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval 95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001.ConclusionHBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.
Keywords:Anti-HBc"}  {"#name":"keyword"  "$":{"id":"pc_eTCEiZSUt7"}  "$$":[{"#name":"text"  "_":"antibody to hepatitis B core antigen  Anti-HBs"}  {"#name":"keyword"  "$":{"id":"pc_qvH1lc4yjt"}  "$$":[{"#name":"text"  "_":"antibody to hepatitis B surface antigen  Anti-HCV"}  {"#name":"keyword"  "$":{"id":"pc_fCbgyBDaNl"}  "$$":[{"#name":"text"  "_":"antibodies to hepatitis C virus  cccDNA"}  {"#name":"keyword"  "$":{"id":"pc_00l1VB8leT"}  "$$":[{"#name":"text"  "_":"covalently closed circular DNA  ddPCR"}  {"#name":"keyword"  "$":{"id":"pc_GJ9W8UOmh8"}  "$$":[{"#name":"text"  "_":"droplet digital polymerase chain reaction  HBsAg"}  {"#name":"keyword"  "$":{"id":"pc_5nYcd969Ch"}  "$$":[{"#name":"text"  "_":"hepatitis B surface antigen  HBV"}  {"#name":"keyword"  "$":{"id":"pc_KQxDPkUygX"}  "$$":[{"#name":"text"  "_":"hepatitis B virus  HCC"}  {"#name":"keyword"  "$":{"id":"pc_ACVT2hQfW1"}  "$$":[{"#name":"text"  "_":"hepatocellular carcinoma  NBNC-HCC"}  {"#name":"keyword"  "$":{"id":"pc_DkWPr01NKC"}  "$$":[{"#name":"text"  "_":"non-B  non-C hepatocellular carcinoma
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