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Discontinuation of nucleos(t)ide analogues after NA-induced HBsAg seroclearance: a single-center 48-week
Yong-Hong Wang1, Ya-Chao Tao1, Meng-Lan Wang1
1Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
Insights
Most patients with chronic hepatitis B (CHB) maintained HBsAg-negative status after stopping nucleos(t)ide analogue (NA) therapy. Hepatitis B core-related antigen (HBcrAg) positivity predicted HBsAg reappearance, guiding safe treatment discontinuation in CHB patients.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Hepatitis B virus (HBV) infection is a significant cause of liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma.
- The safety of discontinuing nucleos(t)ide analogue (NA) therapy after HBsAg seroclearance in chronic hepatitis B (CHB) patients is a key clinical question.
Purpose of the Study:
- To determine the rate of sustained HBsAg-negative status after NA withdrawal in non-cirrhotic CHB patients who achieved HBsAg seroclearance.
- To identify predictors of HBsAg positivity (seroreversion) following NA discontinuation.
Main Methods:
- A retrospective study of non-cirrhotic CHB patients who achieved HBsAg seroclearance and discontinued long-term NA therapy.
- Serum HBV RNA and HBcrAg levels were measured at the time of NA cessation.
- Patients were followed for 48 weeks post-discontinuation to monitor HBsAg status.
Main Results:
- Of 54 patients who discontinued NA therapy, 90.7% remained HBsAg-negative at 48 weeks.
- HBsAg reappearance occurred in 9.3% of patients within 48 weeks, with some experiencing HBV DNA relapse.
- All patients who became HBsAg positive after NA withdrawal had elevated HBcrAg levels (>3 log10 U/mL) at treatment cessation.
Conclusions:
- The majority of non-cirrhotic CHB patients maintain HBsAg loss for at least 48 weeks after discontinuing long-term NA therapy.
- HBcrAg positivity at the end of NA treatment is a potential indicator for patients at higher risk of short-term HBsAg seroreversion.
- Further large-scale, long-term studies are needed to validate these findings.
Background:
Hepatitis B virus (HBV) infection is a major risk factor for liver fibrosis, cirrhosis, and hepatocellular carcinoma. Whether patients with chronic hepatitis B (CHB) receiving oral nucleos(t)ide analogue (NA) therapy can safely discontinue treatment after HBsAg seroclearance is attracting clinical attention.This study aimed to explore the maintenance rate of HBsAg-negative status and the predictors of HBsAg repositivity after drug withdrawal in non-cirrhotic CHB patients who had achieved HBsAg seroclearance following long-term NAs therapy.
Methods:
This is a single center retrospective study focusing on non-cirrhotic CHB patients who received NAs treatment and achieved HBsAg seroclearance.These patients were treated in the hepatitis clinic of West China Hospital of Sichuan University and followed up for a long time. CHB patients were required to have complete demographic and clinical data. Additionally, serum levels of HBV RNA and HBcrAg were measured in all patients at the time of NAs cessation.
Results:
A total of 137 non-cirrhotic CHB patients with HBsAg seroclearance were screened. Ultimately, 54 patients agreed to discontinue treatment, while 83 declined. Among the 54 patients who terminated treatment, 43 were male and 11 were female. Of these discontinued patients, 44 received continuous monotherapy, while 10 received combination therapy. All patients in this study received NAs antiviral treatment for more than 5 years. 79.6 % (43/54) of patients were found to be positive for HBsAb and 59.3 % (32/54) of patients had HBsAb≥200 IU/ml at the time of NAs discontinuation. Among the discontinued patients, all 54 patients were HBV RNA negative, and 87.0 % (47/54) were HBcrAg negative.The rates of HBsAg repositive were 3.7 % (95 % CI, 0.6 %-12.7 %) and 9.3 % (95 % CI, 3.8 %-19.7 %) at 24 and 48 weeks after drug withdrawal, respectively, and 3 of them were accompanied by HBV DNA relapse. All patients who regained HBsAg positivity after NAs discontinuation had serum HBcrAg levels greater than 3 log10 U/mL at the time of discontinuation.
Conclusion:
In this single-center cohort, most non-cirrhotic patients who achieved HBsAg seroclearance on long-term NAs therapy maintained HBsAg loss over 48 weeks after discontinuation. HBcrAg positivity at end of treatment was observed in all cases of HBsAg reappearance, suggesting HBcrAg may help identify patients at higher short-term risk of seroreversion. Larger, longer-term studies are required to confirm these findings.
