The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients

Wen-Xiong Xu; Yang-Mei Li; Jian-Guo Li; Yong-Yu Mei; You-Ming Chen; Xue-Jun Li; Chao-Shuang Lin; Hong Deng; Zhi-Xin Zhao; Dong-Ying Xie; Zhi-Liang Gao; Liang Peng

doi:10.1093/gastro/goab013

The 96-week clinical outcomes after cessation of nucleos(t)ide analog treatment in chronic hepatitis B patients

Gastroenterol Rep (Oxf). 2021 Apr 10;9(4):313-322. doi: 10.1093/gastro/goab013. eCollection 2021 Aug.

Authors

Wen-Xiong Xu^{1

2}, Yang-Mei Li³, Jian-Guo Li^{1

2}, Yong-Yu Mei^{1

2}, You-Ming Chen^{1

2}, Xue-Jun Li^{1

2}, Chao-Shuang Lin^{1

2}, Hong Deng^{1

2}, Zhi-Xin Zhao^{1

2}, Dong-Ying Xie^{1

2}, Zhi-Liang Gao^{1

2}, Liang Peng^{1

2}

Affiliations

¹ Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
² Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
³ Department of Prevention and Health Care, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.

Abstract

Background: Chronic hepatitis B (CHB) patients have a high virological relapse rate after cessation of nucleos(t)ide analog (NA) treatment, but the clinical outcome remains unclear. This study aimed to investigate the 96-week clinical outcomes and the risk factors for relapse in CHB after cessation of NAs.

Methods: This study was a prospective trial; 74 eligible patients were enrolled. The patients underwent NA cessation and follow-up according to the 2012 Asian Pacific Association for the Study of the Liver Guideline. Symptoms, biochemical (aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, urea nitrogen, creatinine), virological data (hepatitis B surface antigen [HBsAg], hepatitis B e antigen [HBeAg], hepatitis B e antibody [HBeAb], hepatitis B virus [HBV] DNA levels), and color Doppler ultrasound examination results were recorded and analysed.

Results: After NA cessation, 19 cases were HBsAg-negative without relapse during the 96-week follow-up. Of the 55 cases of HBsAg-positive after cessation, four types of clinical outcomes were observed. Twelve patients had no relapse during the 96-week follow-up (type A, 21.8%), 7 patients underwent virological relapses but spontaneously had a non-virological relapse (type B, 12.7%), 10 patients maintained virological relapse (type C, 18.2%), and 26 patients turned to clinical relapse, received NA retreatment, and achieved ALT normalization and negative conversion of HBV DNA within 12 months (type D, 47.3%). The 2-year overall cumulative rates of virological and clinical relapses were 58.1% and 24.3%, respectively. Independent factors associated with virological relapse were duration of negative HBV DNA, EOT (end of treatment) HBsAg, and original status of HBeAg. The EOT HBsAg was also an independent factor for clinical relapse.

Conclusions: There are four types of clinical outcomes in patients with CHB after cessation of NA treatment. Further research is needed to explore the mechanism of different clinical outcomes. The EOT HBsAg level is an independent factor associated with both virological and clinical relapse.

Keywords: cessation; chronic hepatitis B; hepatitis B virus; nucleos(t)ide analogs; relapse.