RGD Reference Report - Distinct Relapse Rates and Risk Predictors After Discontinuing Tenofovir and Entecavir Therapy. - Rat Genome Database

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Distinct Relapse Rates and Risk Predictors After Discontinuing Tenofovir and Entecavir Therapy.

Authors: Su, Tung-Hung  Yang, Hung-Chih  Tseng, Tai-Chung  Liou, Jyh-Ming  Liu, Chen-Hua  Chen, Chi-Ling  Chen, Pei-Jer  Chen, Ding-Shinn  Liu, Chun-Jen  Kao, Jia-Horng 
Citation: Su TH, etal., J Infect Dis. 2018 Mar 28;217(8):1193-1201. doi: 10.1093/infdis/jix690.
RGD ID: 14694973
Pubmed: PMID:29300980   (View Abstract at PubMed)
DOI: DOI:10.1093/infdis/jix690   (Journal Full-text)


Background: We investigated the patterns and predictors for virological relapse (VR), clinical relapse (CR), and sustained clinical response (SCR) and the outcomes of retreatment after nucleos(t)ide analogue (NUC) therapy discontinuation.
Methods: Patients with chronic hepatitis B who were discontinuing NUC therapy were prospectively enrolled. Viral and host predictors of relapse were evaluated, including hepatitis B virus (HBV) surface antigen (HBsAg) level, anti-HBV core antibody level, and presence of single-nucleotide polymorphisms in the genes encoding the receptors NTCP (rs2296651) and CTLA4 (rs231775) and in the 3' untranslated regions of the genes encoding HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535); posttherapy predictors of relapse were also investigated. Information about NUC retreatment and outcomes were recorded.
Results: Overall, 100 patients discontinuing 3-year entecavir (ETV) or tenofovir (TDF) therapy were enrolled. Patients discontinuing TDF exhibited significantly higher rates of VR (52.9% vs 6.1%; P < .001) and CR (15.2% vs. 1.5%, P = .007) at 3 months than those discontinuing ETV, but relapse rates at 12 months were comparable. The end-of-therapy HBsAg levels predicted VR (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.19-2.21), CR (HR, 1.78; 95% CI, 1.13-2.81), and SCR (OR, 0.57; 95% CI, .35-.94). The CTLA4 (rs231775) non-GG genotype predicted VR (HR, 1.74; 95% CI, 1.01-3.00) and CR (HR, 2.06; 95% CI, 1.04-4.11), while the HLA-DPA1 (rs3077) AA genotype predicted SCR (OR, 10.84; 95% CI, 1.12-105). The HBV DNA 1 month after NUC treatment cessation was an early predictor of subsequent relapse.
Conclusions: Discontinuation of tenofovir disoproxil fumarate treatment rather than entecavir treatment is associated with earlier relapse, and NUC-specific posttherapy monitoring is necessary.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
H2-PaMouseChronic Hepatitis B treatmentISOHLA-DPA1 (Homo sapiens)DNA:SNP: :rs3077(human)RGD 
HLA-DPA1HumanChronic Hepatitis B treatmentIAGP DNA:SNP: :rs3077(human)RGD 
RT1-HaRatChronic Hepatitis B treatmentISOHLA-DPA1 (Homo sapiens)DNA:SNP: :rs3077(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Ha  (RT1 class II, locus Ha)

Genes (Mus musculus)
H2-Pa  (histocompatibility 2, P region alpha locus)

Genes (Homo sapiens)
HLA-DPA1  (major histocompatibility complex, class II, DP alpha 1)


Additional Information