Add like
Add dislike
Add to saved papers

The Role of ALPK1 in Inhibiting HBV Replication Facilitates the Identification of ALPK1 P660L Variant for Predicting PegIFNα Therapy Response.

BACKGROUND: ALPK1 agonist has recently been reported to demonstrate anti-HBV efficacy via activating NF-κB signaling, which is crucial for maximizing interferon responses. Here, we investigated the impact of ALPK1 on HBV replication, and explored ALPK1 variants for predicting PegIFNα treatment response.

METHODS: The potential anti-HBV effect of ALPK1 was evaluated in HBV-integrated and HBV-infected hepatoma cells. The potentially functional genetic variants of ALPK1 were screened out and their correlations with PegIFNα treatment response were assessed in 945 HBeAg-positive chronic hepatitis B (CHB) patients.

RESULTS: We revealed that ALPK1 inhibited HBV replication in hepatocytes via activating the JAK-STAT pathway. ALPK1 overexpression improved the anti-HBV effect of IFNα in cell models. A missense variant, rs35389530 (P660L), of ALPK1 was strongly associated with combined response (CR, namely HBeAg seroconversion and HBV DNA level <3.3log10IU/ml) to PegIFNα treatment in CHB patients (P = 2.12 × 10-6). Moreover, a polygenic score (PGS) integrating ALPK1_rs35389530 and two additional genetic variants was further significantly associated with CR (Ptrend = 9.28 × 10-7), HBsAg level (Ptrend = 0.0002), and HBsAg loss (Ptrend = 0.025).

CONCLUSIONS: The anti-HBV effects of ALPK1 through activating JAK-STAT pathway provides a new perspective for CHB therapy. ALPK1_rs35389530 and PGS are potential biomarkers to predict PegIFNα treatment response and may be utilized for optimizing CHB treatment.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

Related Resources

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app