Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE)

Milan J Sonneveld; Jun Yong Park; Apichat Kaewdech; Wai-Kay Seto; Yasuhito Tanaka; Ivana Carey; Margarita Papatheodoridi; Florian van Bömmel; Thomas Berg; Fabien Zoulim; Sang Hoon Ahn; George N Dalekos; Nicole S Erler; Christoph Höner Zu Siederdissen; Heiner Wedemeyer; Markus Cornberg; Man-Fung Yuen; Kosh Agarwal; Andre Boonstra; Maria Buti; Teerha Piratvisuth; George Papatheodoridis; Benjamin Maasoumy

doi:10.1016/j.cgh.2020.12.005

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Prediction of Sustained Response After Nucleo(s)tide Analogue Cessation Using HBsAg and HBcrAg Levels: A Multicenter Study (CREATE)

Authors: Milan J Sonneveld ; Jun Yong Park ; Apichat Kaewdech ; Wai-Kay Seto ; Yasuhito Tanaka ; Ivana Carey ; Margarita Papatheodoridi ; Florian van Bömmel ; Thomas Berg ; Fabien Zoulim ; Sang Hoon Ahn ; George N Dalekos ; Nicole S Erler ; Christoph Höner Zu Siederdissen ; Heiner Wedemeyer ; Markus Cornberg ; Man-Fung Yuen ; Kosh Agarwal ; Andre Boonstra ; Maria Buti ; Teerha Piratvisuth ; George Papatheodoridis ; Benjamin Maasoumy

Citation: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, Vol.20(4) : e784-e793, 2022-04

Journal Title: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

ISSN: 1542-3565

Issue Date: 2022-04

MeSH: Antiviral Agents / therapeutic use ; DNA, Viral ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B virus / genetics ; Hepatitis B, Chronic* ; Humans

Keywords: HBcrAg ; HBsAg ; SCALE-B ; Sustained Response

Abstract: Background & aims: Predictors of successful nucleo(s)tide analogue (NA) therapy withdrawal remain elusive. We studied the relationship between end-of-treatment levels of hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg) and outcome after therapy cessation.

Methods: Patients who discontinued NA therapy in centers in Asia and Europe were enrolled. HBcrAg and HBsAg were measured at treatment cessation, and associations with off-treatment outcomes were explored. The SCALE-B (Surface antigen, Core-related antigen, Age, ALT, and tenofovir for HBV) score was calculated as previously reported. End points included sustained virologic response (VR; hepatitis B virus DNA level <2000 IU/mL), HBsAg loss, and alanine aminotransferase (ALT) flares (>3× upper limit of normal). Re-treated patients were considered nonresponders.

Results: We analyzed 572 patients, 457 (80%) were Asian and 95 (17%) were hepatitis B e antigen positive at the start of NA therapy. The median treatment duration was 295 weeks. VR was observed in 267 (47%), HBsAg loss was observed in 24 (4.2%), and ALT flare was observed in 92 (16%). VR (67% vs 42%) and HBsAg loss (15% vs 1.5%) was observed more frequently in non-Asian patients when compared to Asian patients (P < .001). Lower HBcrAg levels were associated with higher rates of VR (odds ratio [OR], 0.701; P < .001) and HBsAg loss (OR, 0.476; P < .001), and lower rates of ALT flares (OR, 1.288; P = .005). Similar results were observed with HBsAg (VR: OR, 0.812; P = .011; HBsAg loss: OR, 0.380; P < .001; and ALT flare: OR, 1.833; P < .001). Lower SCALE-B scores were associated with higher rates of VR, HBsAg loss, and lower rates of ALT flares in both Asian and non-Asian patients (P < .001).

Conclusions: In this multicenter study, off-treatment outcomes after NA cessation varied with ethnicity. Lower levels of HBcrAg and HBsAg were associated with favorable outcomes. A risk score comprising both factors can be used for risk stratification.