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Backgroud and aim <p>With the rising prevalence of chronic hepatitis B (CHB) co-occurring with metabolic dysfunction–associated fatty liver disease (MAFLD), an in-depth investigation into the impact and mechanisms of MAFLD on CHB is urgently needed. Prior studies have reported that patients with concomitant CHB and MAFLD exhibit lower levels of hepatitis B virus (HBV) replication; however, the underlying mechanistic basis remains unclear. Accumulating evidence indicates that induction of apoptosis is a critical mechanism for HBV clearance. Therefore, it remains to be determined whether lipotoxicity-induced hepatocyte apoptosis contributes significantly to the accelerated elimination of HBV. To investigate the effects and underlying mechanisms of fatty acids against HBV in HepG2.2.15 cells.</p> Methods <p>Human liver transcriptome data were used to analyze biological changes in CHB patients with MAFLD compared to those with CHB alone. In vitro, palmitic acid (PA) was used to simulate lipotoxicity in HepG2.2.15 cells, and oleic acid (OA) was used to reverse the effects of PA. The levels of HBsAg, HBeAg, and HBV-DNA in cell supernatants and lysates were detected by ELISA and PCR. Mitochondrial membrane permeability, oxidative stress, and apoptosis were evaluated to investigate the potential mechanisms of PA’s effects on HepG2.2.15 cells.</p> Results <p>Human hepatic transcriptome enrichment analysis showed upregulated apoptosis-related pathways and downregulated mitochondrial/redox genes in patients with comorbid CHB and MASH. Cell experiments showed that PA reduced the levels of HBsAg, HBeAg, and HBV-DNA in HepG2.2.15 cell supernatants and lysates. The underlying mechanism is that PA increased mitochondrial membrane permeability and ROS levels to activate Caspase-9, PARP, and Caspase-3, thereby inducing apoptosis. However, the unsaturated fatty acid OA restored mitochondrial function, reduced oxidative stress and apoptosis, and reversed HBV antigen levels.</p> Conclusion <p>PA activates the mitochondrial apoptotic pathway to promote HBV clearance, while OA can reverse this effect. This study provides new evidence for the interaction mechanism between CHB and MAFLD and suggests new treatment strategies for patients with this comorbidity.</p>

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Metabolic associated fatty liver disease induced hepatocyte apoptosis to eliminate hepatitis B virus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Jiayu Yu,
  • Xin Zheng

摘要

Backgroud and aim

With the rising prevalence of chronic hepatitis B (CHB) co-occurring with metabolic dysfunction–associated fatty liver disease (MAFLD), an in-depth investigation into the impact and mechanisms of MAFLD on CHB is urgently needed. Prior studies have reported that patients with concomitant CHB and MAFLD exhibit lower levels of hepatitis B virus (HBV) replication; however, the underlying mechanistic basis remains unclear. Accumulating evidence indicates that induction of apoptosis is a critical mechanism for HBV clearance. Therefore, it remains to be determined whether lipotoxicity-induced hepatocyte apoptosis contributes significantly to the accelerated elimination of HBV. To investigate the effects and underlying mechanisms of fatty acids against HBV in HepG2.2.15 cells.

Methods

Human liver transcriptome data were used to analyze biological changes in CHB patients with MAFLD compared to those with CHB alone. In vitro, palmitic acid (PA) was used to simulate lipotoxicity in HepG2.2.15 cells, and oleic acid (OA) was used to reverse the effects of PA. The levels of HBsAg, HBeAg, and HBV-DNA in cell supernatants and lysates were detected by ELISA and PCR. Mitochondrial membrane permeability, oxidative stress, and apoptosis were evaluated to investigate the potential mechanisms of PA’s effects on HepG2.2.15 cells.

Results

Human hepatic transcriptome enrichment analysis showed upregulated apoptosis-related pathways and downregulated mitochondrial/redox genes in patients with comorbid CHB and MASH. Cell experiments showed that PA reduced the levels of HBsAg, HBeAg, and HBV-DNA in HepG2.2.15 cell supernatants and lysates. The underlying mechanism is that PA increased mitochondrial membrane permeability and ROS levels to activate Caspase-9, PARP, and Caspase-3, thereby inducing apoptosis. However, the unsaturated fatty acid OA restored mitochondrial function, reduced oxidative stress and apoptosis, and reversed HBV antigen levels.

Conclusion

PA activates the mitochondrial apoptotic pathway to promote HBV clearance, while OA can reverse this effect. This study provides new evidence for the interaction mechanism between CHB and MAFLD and suggests new treatment strategies for patients with this comorbidity.