Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels

Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-...

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Vydané v:Journal of hepatology Ročník 76; číslo 5; s. 1042 - 1050
Hlavní autori: Sonneveld, Milan J., Chiu, Shao-Ming, Park, Jun Yong, Brakenhoff, Sylvia M., Kaewdech, Apichat, Seto, Wai-Kay, Tanaka, Yasuhito, Carey, Ivana, Papatheodoridi, Margarita, van Bömmel, Florian, Berg, Thomas, Zoulim, Fabien, Ahn, Sang Hoon, Dalekos, George N., Erler, Nicole S., Höner zu Siederdissen, Christoph, Wedemeyer, Heiner, Cornberg, Markus, Yuen, Man-Fung, Agarwal, Kosh, Boonstra, Andre, Buti, Maria, Piratvisuth, Teerha, Papatheodoridis, George, Chen, Chien-Hung, Maasoumy, Benjamin
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Netherlands Elsevier B.V 01.05.2022
Elsevier Science Ltd
Elsevier
Predmet:
Antigens
Antiviral agents
Antiviral Agents - therapeutic use
DNA, Viral
Ethnicity
Genotype
Genotype & phenotype
Genotypes
HBcrAg
HBsAg
HBsAg loss
HBV genotype
Hepatitis B
Hepatitis B Core Antigens
Hepatitis B e antigen
Hepatitis B e Antigens
Hepatitis B surface antigen
Hepatitis B Surface Antigens
Hepatitis B virus - genetics
Hepatitis B, Chronic - drug therapy
Human health and pathology
Humans
Hépatology and Gastroenterology
Life Sciences
Minority & ethnic groups
Patients
Probability
HBV genotype
HBsAg
HBcrAg
HBsAg loss
ISSN:0168-8278, 1600-0641, 1600-0641
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Shrnutí:Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders. We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p <0.001), and in patients with lower HBsAg (aHR 0.243, p <0.001) and HBV core-related antigen (HBcrAg) (aHR 0.718, p = 0.001) levels. Combining HBsAg (<10, 10-100 or >100 IU/ml) and HBcrAg (<2log vs. ≥2 log) levels improved prediction of HBsAg loss, with extremely low rates observed in patients with HBsAg >100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490–4.174, p = 0.001). The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal. A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) – so-called functional cure – after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss. [Display omitted] •A minority of patients with chronic hepatitis B may achieve HBsAg clearance after withdrawal of antiviral therapy.•In this multicenter study comprising 1,216 patients, non-Asian ethnicity was associated with the highest chance of HBsAg loss.•Among Asian patients, genotype C was associated with a higher chance of HBsAg loss.•Low HBsAg levels (<100 IU/ml) and undetectable HBcrAg levels were associated with a higher chance of HBsAg loss.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0168-8278
1600-0641
1600-0641
DOI:10.1016/j.jhep.2022.01.007