Pilot Study Using Machine Learning to Identify Immune Profiles for the Prediction of Early Virological Relapse After Stopping Nucleos(t)ide Analogues in HBeAg-Negative CHB.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Wübbolding, MaximilianLopez Alfonso, Juan Carlos
Lin, Chun-Yen
Binder, Sebastian
Falk, Christine
Debarry, Jennifer
Gineste, Paul
Kraft, Anke R M
Chien, Rong-Nan
Maasoumy, Benjamin
Wedemeyer, Heiner
Jeng, Wen-Juei
Meyer Hermann, Michael
Cornberg, Markus
Höner Zu Siederdissen, Christoph
Issue Date
2020-11-05
Metadata
Show full item recordAbstract
Treatment with nucleos(t)ide analogues (NAs) may be stopped after 1-3 years of hepatitis B virus DNA suppression in hepatitis B e antigen (HBeAg)-negative patients according to Asian Pacific Association for the Study of Liver and European Association for the Study of Liver guidelines. However, virological relapse (VR) occurs in most patients. We aimed to analyze soluble immune markers (SIMs) and use machine learning to identify SIM combinations as predictor for early VR after NA discontinuation. A validation cohort was used to verify the predictive power of the SIM combination. In a post hoc analysis of a prospective, multicenter therapeutic vaccination trial (ABX-203, NCT02249988), hepatitis B surface antigen, hepatitis B core antigen, and 47 SIMs were repeatedly determined before NA was stopped. Forty-three HBeAg-negative patients were included. To detect the highest predictive constellation of host and viral markers, a supervised machine learning approach was used. Data were validated in a different cohort of 49 patients treated with entecavir. VR (hepatitis B virus DNA ≥ 2,000 IU/mL) occurred in 27 patients. The predictive value for VR of single SIMs at the time of NA stop was best for interleukin (IL)-2, IL-17, and regulated on activation, normal T cell expressed and secreted (RANTES/CCL5) with a maximum area under the curve of 0.65. Hepatitis B core antigen had a higher predictive power than hepatitis B surface antigen but lower than the SIMs. A supervised machine-learning algorithm allowed a remarkable improvement of early relapse prediction in patients treated with entecavir. The combination of IL-2, monokine induced by interferon γ (MIG)/chemokine (C-C motif) ligand 9 (CCL9), RANTES/CCL5, stem cell factor (SCF), and TNF-related apoptosis-inducing ligand (TRAIL) was reliable in predicting VR (0.89; 95% confidence interval: 0.5-1.0) and showed viable results in the validation cohort (0.63; 0.1-0.99). Host immune markers such as SIMs appear to be underestimated in guiding treatment cessation in HBeAg-negative patients. Machine learning can help find predictive SIM patterns that allow a precise identification of patients particularly suitable for NA cessation.Citation
Hepatol Commun. 2020 Nov 5;5(1):97-111. doi: 10.1002/hep4.1626. PMID: 33437904.Affiliation
CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.Publisher
WileyJournal
Hepatology communicationsPubMed ID
33437904Type
ArticleLanguage
enEISSN
2471-254Xae974a485f413a2113503eed53cd6c53
10.1002/hep4.1626
Scopus Count
The following license files are associated with this item:
- Creative Commons
Related articles
- Combining Hepatitis B Virus RNA and Hepatitis B Core-Related Antigen: Guidance for Safely Stopping Nucleos(t)ide Analogues in Hepatitis B e Antigen-Positive Patients With Chronic Hepatitis B.
- Authors: Fan R, Peng J, Xie Q, Tan D, Xu M, Niu J, Wang H, Ren H, Chen X, Wang M, Sheng J, Tang H, Bai X, Wu Y, Zhou B, Sun J, Hou J, Chronic Hepatitis B Study Consortium
- Issue date: 2020 Jul 23
- Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B.
- Authors: Rinker F, Zimmer CL, Höner Zu Siederdissen C, Manns MP, Kraft ARM, Wedemeyer H, Björkström NK, Cornberg M
- Issue date: 2018 Sep
- Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients.
- Authors: Jung KS, Park JY, Chon YE, Kim HS, Kang W, Kim BK, Kim SU, Kim do Y, Han KH, Ahn SH
- Issue date: 2016 Aug
- Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients.
- Authors: Qiu YW, Huang LH, Yang WL, Wang Z, Zhang B, Li YG, Su TT, Zhou HY, Xu W, Wang XD, Dai YP, Gan JH
- Issue date: 2016 Feb
- Pregenomic HBV RNA and Hepatitis B Core-Related Antigen Predict Outcomes in Hepatitis B e Antigen-Negative Chronic Hepatitis B Patients Suppressed on Nucleos(T)ide Analogue Therapy.
- Authors: Carey I, Gersch J, Wang B, Moigboi C, Kuhns M, Cloherty G, Dusheiko G, Agarwal K
- Issue date: 2020 Jul