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. 2026 Jan 1;69(1):68-80.
doi: 10.4103/ejpi.EJPI-D-25-00054. Epub 2026 Feb 6.

Very Low-density Lipoprotein-triacylglyceride Promotes Hepatitis B Virus Reactivation

Cian-Ru Yang  1   2 , Pei-Yin Liao  1   3 , Wen-Jen Lin  1   3   4   5 , Pei-Chun Shen  1   3 , Ke Wang  6 , Yu-Ting Su  1 , Wei-Chung Cheng  1 , Wei-Chun Chang  1 , Jen-Chih Lee  7 , Cheng-Yuan Peng  8 , Hsueh-Chou Lai  8   9 , Wen-Lung Ma  1   3   10
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Free article

Very Low-density Lipoprotein-triacylglyceride Promotes Hepatitis B Virus Reactivation

Cian-Ru Yang et al. J Physiol Investig. .
Free article

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) inhibits hepatitis B virus (HBV) activity while simultaneously exacerbating liver fibrosis/cirrhosis (LF/LC) in chronic HBV (CHB)-infected patients. To date, no model is available to investigate this discrepancy. The established HBV-MASLD-LF/LC mouse model in this report mimics the promotion of LF/LC and suppression of HBV levels by MASLD. Very low-density lipoprotein (VLDL)-loading triacylglyceride (TAG) was positively correlated with the HBV titer and LC/LF in both HBV+ patients and the HBV-MASLD-LF/LC mouse model. TAG treatment could upregulate the HBV titer and fibrotic markers in vitro, thus demonstrating a causal relationship. Hepatocyte-specific VLDL receptor knockout (VRKO) reduced the HBV titer but promoted LF/LC in the HBV-MASLD-LF/LC mouse model. VLDL-TAG was reduced in VRKO HBV-MASLD-LF/LC mice compared to wild-type mice. The VLDL level and VLDL-loading are considered LF/LC risk factors in hepatitis B e antigen-negative CHB patients (considered at low risk of developing LF/LC). In conclusion, this report explains the discrepancies in HBV, MASLD, and LF/LC at the physiological level. VLDL-TAG is considered a novel risk factor of HBV reactivation and deserves further study.

Keywords: Chronic liver disease; hepatitis B virus; lipidome; lipoproteins; metabolome.

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References

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