scholarly journals Persistence of intrahepatic hepatitis B virus DNA integration in patients developing hepatocellular carcinoma after hepatitis B surface antigen seroclearance

2021 ◽  
Vol 27 (1) ◽  
pp. 207-218
Author(s):  
Jeong Won Jang ◽  
Jin Seoub Kim ◽  
Hye Seon Kim ◽  
Kwon Yong Tak ◽  
Heechul Nam ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
Next Generation Sequencing Technology ◽  
Tumor Tissues ◽  
Hbsag Seroclearance ◽  
B Virus ◽  
Integration Sites

Background/Aims: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following hepatitis B surface antigen (HBsAg) seroclearance remains unknown. Our study aimed to investigate and characterize HBV integration events in chronic hepatitis B (CHB) patients who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.<br/>Methods: Using probe-based HBV capturing followed by next-generation sequencing technology, HBV integration was examined in 10 samples (seven tumors and three non-tumor tissues) from seven chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.<br/>Results: HBV integration was observed in six patients (85.7%) and eight (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.<br/>Conclusions: The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAgserocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma

Hepatology ◽  
1995 ◽  
Vol 21 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Patrizia Paterlini ◽  
Karine Poussin ◽  
Michael Kew ◽  
Dominique Franco ◽  
Christian Brechot
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
B Virus ◽  
Selective Accumulation

scholarly journals Cumulative Incidence of Hepatocellular Carcinoma and Hepatitis B Surface Antigen Seroclearance after Nucleos(t)ide analogue-induced Hepatitis B e Antigen Seroclearance

2019 ◽  
Author(s):  
Hyun Woong Lee ◽  
Jung Il Lee ◽  
Saein Kim ◽  
Sora Kim ◽  
Hye Young Chang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Cumulative Incidence ◽  
Hepatitis B Surface Antigen ◽  
Significant Proportion ◽  
Hepatitis B E Antigen ◽  
Hbsag Seroclearance ◽  
B Virus ◽  
The Mean

Abstract Background: Hepatitis B e antigen (HBeAg) seroclearance has been considered as the treatment endpoint in HBeAg-positive patients with chronic hepatitis B (CHB). Although HBeAg seroclearance has been accomplished, some aspects are yet unclear. We investigated the cumulative incidence of hepatocellular carcinoma (HCC) and evaluated hepatitis B surface antigen (HBsAg) seroclearance in patients undergoing nucleos(t)ide analogue (NA)-induced HBeAg seroclearance. Methods: In this retrospective cohort study, 203 patients with CHB were HBsAg and HBeAg seropositive before NA (entecavir or tenofovir) treatment. All patient who experienced NA -induced HBeAg seroclearance were recruited. Patients with documented HBeAg seroclearance were followed-up every 6 months. Baseline characteristics and laboratory results were recorded. Results: The mean age at HBeAg seroclearance was 40 years (range, 20-84), and the mean follow-up duration was 5 years (range, 2-11). The cumulative incidence of HCC was 1.5% to 11.5% at 1 to 8 years after HBeAg seroclearance. Cirrhosis was the only significant factor for HCC development (hazard ratio [HR], 24.651; confidence interval [CI], 3.018 to 201.365; P = 0.003). The cumulative incidence of HBsAg seroclearance was 3.5% to 18.7% after 1 to 8 years from HBeAg seroclearance. Conclusions: A significant proportion of patients developed HCC after NA-induced HBeAg seroclearance. The presence of liver cirrhosis at the time of HBeAg seroclearance serves as an independent factor for HCC development. Some patients with NA-induced HBeAg seroclearance achieved HBsAg seroclearance. Keywords: hepatitis B virus; hepatitis B e antigen seroclearance; hepatitis B s antigen seroclearance; hepatocellular carcinoma

Sign in / Sign up

Export Citation Format

Share Document