FRI-139
Intrahepatic transcriptional profiling of chronic hepatitis B
Patients during interferon-alpha treatment
Ning Li1, Kangkang Yu1, Minhui Dong1, Feizhen Wu2, Jiming Zhang1.
1Huashan Hospital, Fudan University, Shanghai, China; 2Institute of
Biomedical Sciences, Fudan University, Shanghai, China
Email: [email protected]
Background and aims: Interferon-alpha (IFN-alpha) treatment for
Chronic hepatitis B (CHB) is favored for inducing long-term
Immunological control with a finite duration treatment, but high
Variability of response has been observed. The interplay between
Viral replication and host immune responses during IFN-alpha
Treatment remains to be clarified. We aim to comprehensively
Analyze the changes of intrahepatic host gene expression during
Pegylated IFN-alpha (PegIFN-alpha) treatment in CHB patients.
Method: Gene expression profile of seventeen CHB patients with
Paired liver biopsies at baseline and week 24 of PegIFN-alpha
Treatment of compared.
During PegIFN-alpha treatment were estimated by cell-type identification
By estimating relative subsets of RNA transcripts
(CIBERSORT). Gene set enrichment analysis (GSEA) of innate and
Adaptive immunity were correlated to treatment response.
Results: Intrahepatic transcriptional profiling revealed a significant
Upregulation of antiviral effectors. Immune cell composition analysis
Show that CD8 T cells significantly reduced, while B cells
Strong increased after 24 weeks of PegIFN-alpha treatment.
GSEA results suggested an enhanced regulation of both innate and
Adaptive immune responses, and comparison of several most
Significantly differentially expressed genes (DEGs), including RSAD2,
DDX60, CD8A, IL18A, between responders and non-responders
Suggested that PegIFN-alpha treatment had boosted innate immune
Response in both groups of patients, while some adaptive immune
Effectors almost residual at the same levels in responders but were
Significantly downregulated in non-responders after treatment.
Conclusion: These data showa remarkable alteration of intrahepatic
Gene expression profile in CHB patients during PegIFN-alpha
Treatment. Innate immune response is enhanced, while T cell
Response is estimated to be unchanged, or even attenuated, which
Might also correlate to poor treatment response.
Validation, this study would help achieve better understanding of
The antiviral mechanisms of IFN-alpha treatment and facilitate
Patient selection.作者: StephenW 时间: 2019-4-17 18:26