Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients even under effective long-term oral antiviral therapy, but its pathogenesis in the setting of long-standing inhibition of viral replication has not been completely elucidated. We investigated whether species of circulating cell-free DNA (cfDNA) may be involved in the process of hepatocarcinogenesis in treated CHB patients. Serum samples were obtained from HBeAg-negative CHB patients with (HCC cases, n = 37) or without HCC development during the first 5 years of oral antiviral therapy (controls, n = 74). HCC cases and controls were matched 1:2 for age, sex and platelets. Determination of different circulating cfDNA species (before HCC diagnosis in HCC cases) including total cfDNA quantity, levels of Alu repeat DNA and RNase P coding DNA, copies of mitochondrial DNA and levels of 5-methyl-2′-deoxycytidine as an indicator of DNA methylation was performed. HCC cases compared with controls had higher median levels of Alu247 (123 vs 69 genomic equivalent, p =.042) and RNase P coding DNA (68 vs 15 genomic equivalent, p <.001). In contrast, median cfDNA concentration, Alu115 levels, Alu247/Alu115 ratio as an index of DNA integrity and mitochondrial DNA copies did not differ significantly between HCC cases and controls. Receiver operating characteristic curve analysis showed that levels RNase P coding DNA offered good prediction of subsequent HCC development (c-statistic: 0.80, p <.001). In conclusion, serum levels of RNase P coding DNA are increased years before HCC diagnosis and could be potentially helpful in the prediction of the HCC risk in treated HBeAg-negative CHB patients.
Circulating cell-free DNA species affect the risk of hepatocellular carcinoma in treated chronic hepatitis B patients / A. Papatheodoridi, A. Chatzigeorgiou, L. Chrysavgis, P. Lembessis, A. Loglio, F. Facchetti, E. Cholongitas, M. Koutsilieris, P. Lampertico, G. Papatheodoridis. - In: JOURNAL OF VIRAL HEPATITIS. - ISSN 1352-0504. - 28:3(2021 Mar), pp. 464-474.
|Titolo:||Circulating cell-free DNA species affect the risk of hepatocellular carcinoma in treated chronic hepatitis B patients|
LAMPERTICO, PIETRO (Penultimo) (Corresponding)
|Parole Chiave:||cirrhosis; hepatitis B; liver cancer; senescence; therapy|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||mar-2021|
|Data ahead of print / Data di stampa:||dic-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/jvh.13446|
|Appare nelle tipologie:||01 - Articolo su periodico|