TABLE 2.
Current knowledge on HBV integration in blood cells.
| Findings on HBV-DNA integration in blood cell | Study population | Frequency of HBV integration in blood cells | Technique for detecting HBV integration | References |
| First evidence of HBV-DNA integration in PBMCs of HBV-infected patients | 16 CHB patients | PBMCs (25%) | Southern blot | Pontisso et al., 1984 |
| 4 HIV + patients (1 CHB and 3 OBI) | PBMCs (100%) | Southern blot | Laure et al., 1985 | |
| HBV-DNA integration in PBMCs occurs in all phases of HBV infection, including acute and occult infection | 38 HBsAg + patients (8 AHB; 21 CHB, 6 CI, 3 HCC) and 34 OBI patients | PBMCs (100% AHB, 85.7% CHB; 33.3%; 66.6% HCC and 35.2% OBI) | Southern blot | Pasquinelli et al., 1986 |
| First sequencing analysis of HBV-human junctions in the setting of HBV-DNA integration of PBMCs | 10 CHB patients | PBMCs (20%) | Nested-PCR | Laskus et al., 1999 |
| Accumulating evidences on HBV-DNA integration as a frequent event at level of PBMCs of patients with ongoing or past HBV infection | 7 CHB patients; 9 OBI | PBMCs (42.8% CHB; 22.2% OBI) | Alu-PCR | Murakami et al., 2004 |
| 21 OBI | PBMCs (14.2%) | Inverse-PCR | Umeda et al., 2005 | |
| 30 CHB adults and 19 CHB children | PBMCs (86% adults; 65% children) | Sanger Sequencing | Wang et al., 2008 | |
| Multiple HBV-DNA integration events revealed in PBMCs of CHB patients with non-Hodgkin lymphoma (NHL) | 12 CHB with NHL diagnosis | Lymphoid malignant tissues (50%) | Next generation sequencing | Li M. et al., 2020 |
| HBV-DNA integration in PBMCs is enriched at level of genes associated with tumorigenesis. Patterns of HBV integration are sheared by tumoral liver cells and PBMCs. |
42 CHB patients | PBMCs (81%) A total of 271 integration events of which 58 in coding genes involved in oncogenetic pathway |
Alu-PCR; Next-generation sequencing | Lau et al., 2020 |
| Evidence of HBV-DNA integration in bone marrow hematopoietic stem cells (HSC) | 8 CHB patients | CD34 + HSC (62.5%) | FISH | Shi et al., 2014 |
AntiHBc-positive patients were defined as OBI.
PBMCs, Peripheral Blood Mononulear Cells; CHB, chronic hepatitis B; HIV, human immunodeficiency virus; HBsAg, Hepatitis B surface antigen; AHB, Acute Hepatitis B; CI, HBV Chronic Infection; HCC, hepatocellular carcinoma; HSC, Hematopoietic Stem cells; PCR, polymerase chain reaction; FISH, fluorescence in situ hybridization.