Hepatitis B surface antigen (HBsAg) levels in the prediction of spontaneous HBsAg seroclearance

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.

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P679 LEVEL OF HEPATITIS B SURFACE ANTIGEN AND NOT HBV DNA LEVEL AFTER HBeAg SEROCLEARANCE IS PREDICTIVE OF HBsAg SEROCLEARANCE

Journal of Hepatology ◽

10.1016/s0168-8278(14)60841-2 ◽

2014 ◽

Vol 60 (1) ◽

pp. S295

Author(s):

J. Fung ◽

C.-L. Lai ◽

D.K. Wong ◽

W.-K. Seto ◽

M. Kopaniszen ◽

...

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Hbsag Seroclearance

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Mo1902 Hepatitis B Surface Antigen (HBsAg) Seroclearance Rate in a Multicenter U.S. Cohort Study

Gastroenterology ◽

10.1016/s0016-5085(12)63855-4 ◽

2012 ◽

Vol 142 (5) ◽

pp. S-994

Author(s):

Long H. Nguyen ◽

Pelu Tran ◽

Kevin T. Chaung ◽

Vincent G. Nguyen ◽

Lily H. Kim ◽

...

Keyword(s):

Cohort Study ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbsag Seroclearance

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Usefulness of a Hepatitis B Surface Antigen-Based Model for the Prediction of Functional Cure in Patients with Chronic Hepatitis B Virus Infection Treated with Nucleos(t)ide Analogues: A Real-World Study

Journal of Clinical Medicine ◽

10.3390/jcm10153308 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3308

Author(s):

Gian Paolo Caviglia ◽

Yulia Troshina ◽

Enrico Garro ◽

Marcantonio Gesualdo ◽

Serena Aneli ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Functional Cure ◽

Hbsag Loss ◽

Chronic Hepatitis B Virus ◽

Long Term Treatment ◽

Hbsag Seroclearance

In patients with chronic hepatitis B (CHB) under long-term treatment with nucleso(t)ide analogues (NAs), the loss of hepatitis B surface antigen (HBsAg) is a rare event. A growing body of evidence supports the use of quantitative HBsAg for the prediction of functional cure, although these results are mainly derived from studies performed on Asian patients with hepatitis B e antigen (HBeAg)-positive CHB. Here, we investigated the clinical role of quantitative HBsAg in a real-life cohort of CHB patients under treatment with NAs in a tertiary care center from North-West Italy. A total of 101 CHB patients (HBeAg-negative, n = 86) undergoing NAs treatment were retrospectively enrolled. HBsAg was measured at baseline (T0), 6 months (T1), 12 months (T2) and at the last follow-up (FU). Median FU was 5.5 (3.2–8.3) years; at the end of FU, 11 patients lost the HBsAg (annual incidence rate = 1.8%). Baseline HBsAg levels were significantly different between patients with no HBsAg loss and those achieving a functional cure (3.46, 2.91–3.97 vs. 1.11, 0.45–1.98 Log IU/mL, p < 0.001). Similarly, the HBsAg decline (Δ) from T0 to T2 was significantly different between the two groups of patients (0.05, −0.04–0.13, vs. 0.38, 0.11–0.80 Log IU/mL, p = 0.002). By stratified cross-validation analysis, the combination of baseline HBsAg and ΔHBsAg T0–T2 showed an excellent accuracy for the prediction of HBsAg loss (C statistic = 0.966). These results corroborate the usefulness of quantitative HBsAg in Caucasian CHB patients treated with antivirals for the prediction of HBsAg seroclearance.

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Role of quantitative hepatitis B surface antigen in predicting inactive carriers and HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients

Medicine ◽

10.1097/md.0000000000006554 ◽

2017 ◽

Vol 96 (13) ◽

pp. e6554 ◽

Cited By ~ 10

Author(s):

Teerapat Ungtrakul ◽

Tassanee Sriprayoon ◽

Pattama Kusuman ◽

Pitchayachuda Chunnuan ◽

Kamonwan Soonklang ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbsag Seroclearance ◽

Negative Chronic Hepatitis

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

10.21203/rs.2.16279/v3 ◽

2020 ◽

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 ◽

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.

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