Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

ObjectiveTo investigate the protective effect and mechanism of verbenalin on mouse mononuclear macrophage leukemia cells （RAW264.7） damaged by human coronavirus （HCoV）-229E infection， thereby providing experimental evidence for its development and application. MethodsRAW264.7 macrophages were infected with different concentrations of HCoV-229E to establish a coronavirus-induced macrophage injury model using the cell counting kit-8 （CCK-8） assay for assessing cell proliferation and viability. Cells were randomly divided into four groups： normal control， verbenalin group （125 μmol·L^-1）， model group （HCoV-229E）， and HCoV-229E + verbenalin group （HCoV-229E + 125 μmol·L^-1 verbenalin）. Cell viability was measured using the CCK-8 assay， and the maximum non-toxic concentration （CC₀）， half-maximal cytotoxic concentration （CC₅₀）， half-maximal effective concentration （EC₅₀）， and selectivity index （SI） of verbenalin were calculated. Calcein/PI double staining was used to assess cell viability and cytotoxicity， and JC-1 staining was applied to evaluate changes in mitochondrial membrane potential （MMP）. mito-Keima adenovirus labeling was used to assess mitophagy levels in each group. ResultsA macrophage infection model was successfully established by infecting RAW264.7 cells with the original concentration of HCoV-229E for 36 h. The CC₀ of verbenalin was 125 μmol·L^-1. The CC₅₀ was 448.25 μmol·L^-1. The EC₅₀ against HCoV-229E-infected cells was 46.28 μmol·L^-1， and the SI was 9.68. Compared with the normal group， the model group showed significantly reduced cell survival rate （P<0.01）， increased cell death rate （P<0.01）， decreased MMP （P<0.01）， and suppressed mitophagy （P<0.01）. In contrast， verbenalin treatment significantly improved cell survival rate （P<0.01）， reduced cell death rate （P<0.01）， alleviated MMP loss （P<0.01）， and enhanced mitophagy levels （P<0.01） compared with the model group. ConclusionVerbenalin can enhance the survival rate of macrophages following HCoV-229E infection. The underlying mechanism may be associated with the activation of mitophagy， maintenance of MMP stability， and alleviation of mitochondrial damage.

ObjectiveThis paper aims to investigate the therapeutic effects of Jidesheng Sheyao tablets on varicella-zoster virus （VZV） and its associated postherpetic neuralgia （PHN） to provide experimental evidence for the clinical application and secondary development of Jidesheng Sheyao tablets. MethodsFifty-six guinea pigs were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.92， 0.96， 0.48 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.96 g·d^-1 + 1.2 g·kg^-1·d^-1）. The skin on the back of the guinea pigs in each group was depilated and then abraded with sandpaper. Except for the normal group， 200 μL of VZV solution was dropped on the damaged parts of the back of the guinea pigs in the other groups， and the infection lasted for 2 consecutive days. The drug administration started 2 hours after the infection on the first day and lasted for 7 days. The pathological changes of the back of the guinea pigs in each group were observed every day starting from the second day after the infection. On the 7^th day， the guinea pigs were sacrificed by CO₂ anesthesia. The locally infected skin was taken， and the viral DNA nucleic acid load was detected by real-time polymerase chain reaction （Real-time PCR）. The pathological histology examination was carried out after hematoxylin-eosin （HE） staining. Seventy rats were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.08， 0.54， 0.27 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.54 g·d^-1 + 1.2 g·kg^-1·d^-1）. The rats in each group （except the normal group） were subcutaneously inoculated with 50 μL of VZV suspension between the web of the first and second fingers of the left forelimb. The skin on the back of the rats was depilated， and the drug administration started 2 hours after the infection and lasted for 10 days. The mechanical withdrawal threshold of the paws of the rats was detected by a Von Frey filament algometer before inoculation and on the 1^st， 3^rd， 6^th， 8^th， and 10^th days after inoculation， and the thermal withdrawal reflex latency of the paws of the rats was detected by a hot and cold plate algometer. On the 10^th day after the virus inoculation， the rats were anesthetized after the behavioral examination， and the dorsal root ganglia of the spinal cord and spinal cord segments were taken. The contents of substance P （SP）， neurokinin （NK）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） in the dorsal root ganglia of the spinal cord and spinal cord were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with those in the normal group， the guinea pigs in the model group had obvious skin herpes lesions （P<0.01）. The viral nucleic acid load was high （P<0.01）， and there were disorganized subcutaneous cellular structures and obvious infiltration of inflammatory cells and cell necrosis （P<0.01）. The mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats were significantly decreased （P<0.05）， and the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats were significantly increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of topical administration of Jidesheng Sheyao tablets and the group of oral administration combined with topical application could significantly improve the lesions such as skin redness and herpes of the guinea pigs caused by VZV infection （P<0.01）， reduce the VZV viral nucleic acid load in the skin tissues of the guinea pigs （P<0.01）， alleviate the degree of inflammatory cell infiltration and skin cell necrosis in the skin tissue （P<0.05）， significantly increase the mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats （P<0.05）， and decrease the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats （P<0.01）. ConclusionJidesheng Sheyao tablets demonstrated significant therapeutic effects on VZV-induced skin infections and postherpetic neuralgia （PHN）， providing a promising candidate for the prevention and treatment of VZV infections.

ObjectiveTo investigate the protective effect and mechanism of verbenalin on mouse mononuclear macrophage leukemia cells （RAW264.7） damaged by human coronavirus （HCoV）-229E infection， thereby providing experimental evidence for its development and application. MethodsRAW264.7 macrophages were infected with different concentrations of HCoV-229E to establish a coronavirus-induced macrophage injury model using the cell counting kit-8 （CCK-8） assay for assessing cell proliferation and viability. Cells were randomly divided into four groups： normal control， verbenalin group （125 μmol·L^-1）， model group （HCoV-229E）， and HCoV-229E + verbenalin group （HCoV-229E + 125 μmol·L^-1 verbenalin）. Cell viability was measured using the CCK-8 assay， and the maximum non-toxic concentration （CC₀）， half-maximal cytotoxic concentration （CC₅₀）， half-maximal effective concentration （EC₅₀）， and selectivity index （SI） of verbenalin were calculated. Calcein/PI double staining was used to assess cell viability and cytotoxicity， and JC-1 staining was applied to evaluate changes in mitochondrial membrane potential （MMP）. mito-Keima adenovirus labeling was used to assess mitophagy levels in each group. ResultsA macrophage infection model was successfully established by infecting RAW264.7 cells with the original concentration of HCoV-229E for 36 h. The CC₀ of verbenalin was 125 μmol·L^-1. The CC₅₀ was 448.25 μmol·L^-1. The EC₅₀ against HCoV-229E-infected cells was 46.28 μmol·L^-1， and the SI was 9.68. Compared with the normal group， the model group showed significantly reduced cell survival rate （P<0.01）， increased cell death rate （P<0.01）， decreased MMP （P<0.01）， and suppressed mitophagy （P<0.01）. In contrast， verbenalin treatment significantly improved cell survival rate （P<0.01）， reduced cell death rate （P<0.01）， alleviated MMP loss （P<0.01）， and enhanced mitophagy levels （P<0.01） compared with the model group. ConclusionVerbenalin can enhance the survival rate of macrophages following HCoV-229E infection. The underlying mechanism may be associated with the activation of mitophagy， maintenance of MMP stability， and alleviation of mitochondrial damage.

ObjectiveThis paper aims to investigate the therapeutic effects of Jidesheng Sheyao tablets on varicella-zoster virus （VZV） and its associated postherpetic neuralgia （PHN） to provide experimental evidence for the clinical application and secondary development of Jidesheng Sheyao tablets. MethodsFifty-six guinea pigs were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.92， 0.96， 0.48 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.96 g·d^-1 + 1.2 g·kg^-1·d^-1）. The skin on the back of the guinea pigs in each group was depilated and then abraded with sandpaper. Except for the normal group， 200 μL of VZV solution was dropped on the damaged parts of the back of the guinea pigs in the other groups， and the infection lasted for 2 consecutive days. The drug administration started 2 hours after the infection on the first day and lasted for 7 days. The pathological changes of the back of the guinea pigs in each group were observed every day starting from the second day after the infection. On the 7^th day， the guinea pigs were sacrificed by CO₂ anesthesia. The locally infected skin was taken， and the viral DNA nucleic acid load was detected by real-time polymerase chain reaction （Real-time PCR）. The pathological histology examination was carried out after hematoxylin-eosin （HE） staining. Seventy rats were randomly divided into seven groups according to their body weight， namely the normal group， the model group， the positive control group， the high-dose group， medium-dose group， and low-dose group of Jidesheng Sheyao tablets （1.08， 0.54， 0.27 g·d^-1）， and the group treated with oral administration combined with topical application of Jidesheng Sheyao tablets （0.54 g·d^-1 + 1.2 g·kg^-1·d^-1）. The rats in each group （except the normal group） were subcutaneously inoculated with 50 μL of VZV suspension between the web of the first and second fingers of the left forelimb. The skin on the back of the rats was depilated， and the drug administration started 2 hours after the infection and lasted for 10 days. The mechanical withdrawal threshold of the paws of the rats was detected by a Von Frey filament algometer before inoculation and on the 1^st， 3^rd， 6^th， 8^th， and 10^th days after inoculation， and the thermal withdrawal reflex latency of the paws of the rats was detected by a hot and cold plate algometer. On the 10^th day after the virus inoculation， the rats were anesthetized after the behavioral examination， and the dorsal root ganglia of the spinal cord and spinal cord segments were taken. The contents of substance P （SP）， neurokinin （NK）， tumor necrosis factor-α （TNF-α）， and interleukin-1β （IL-1β） in the dorsal root ganglia of the spinal cord and spinal cord were detected by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with those in the normal group， the guinea pigs in the model group had obvious skin herpes lesions （P<0.01）. The viral nucleic acid load was high （P<0.01）， and there were disorganized subcutaneous cellular structures and obvious infiltration of inflammatory cells and cell necrosis （P<0.01）. The mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats were significantly decreased （P<0.05）， and the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats were significantly increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of topical administration of Jidesheng Sheyao tablets and the group of oral administration combined with topical application could significantly improve the lesions such as skin redness and herpes of the guinea pigs caused by VZV infection （P<0.01）， reduce the VZV viral nucleic acid load in the skin tissues of the guinea pigs （P<0.01）， alleviate the degree of inflammatory cell infiltration and skin cell necrosis in the skin tissue （P<0.05）， significantly increase the mechanical withdrawal threshold of the paws and the thermal withdrawal reflex latency of the paws of the rats （P<0.05）， and decrease the contents of NK， SP， TNF-α， and IL-1β in the dorsal root ganglia of the spinal cord and spinal cord of the rats （P<0.01）. ConclusionJidesheng Sheyao tablets demonstrated significant therapeutic effects on VZV-induced skin infections and postherpetic neuralgia （PHN）， providing a promising candidate for the prevention and treatment of VZV infections.

ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E （HCoV-229E） and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis. MethodsIn vitro， the cell counting kit-8 （CCK-8） for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells（A549）. A549 cells were divided into five groups： normal group， model group， and three verbenalin treatment groups （125， 62.5， and 31.25 μmol·L^-1）. The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo， 30 BALB/c mice were randomly divided into normal group， model group， chloroquine group， and high-dose， low-dose verbenalin groups （40 and 20 mg·kg^-1）， with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay （ELISA）， while the lung morphology and structure were analyzed by micro-computed tomography （Micro-CT）. Hematoxylin and eosin （HE） staining was used to assess histopathological changes in lung tissue. Additionally， four-dimensional data-independent acquisition （4D-DIA） proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice， through differential protein expression screening， functional annotation， enrichment analysis， and protein-protein interaction network analysis. ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L^-1， and the half-maximal cytotoxic concentration （CC₅₀） was 288.8 μmol·L^-1. Compared with the normal group， the model group showed a significant decrease in cell viability （P<0.01）， a significant increase in the proportion of dead cells （P<0.01）， mitochondrial damage， and a significant reduction in mitochondrial membrane potential （P<0.01）. After treatment with different concentrations of verbenalin （125， 62.5， and 31.25 μmol·L^-1）， cell viability was significantly increased （P<0.01）， and the proportion of dead cells was reduced （P<0.01）， with mitochondrial membrane potential restored （P<0.01）. In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group， the model group showed a significant increase in the lung index （P<0.01）， severe lung tissue injury， lung volume enlargement， and a significant increase in the expression of inflammatory cytokines， including interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） （P<0.01）. In contrast， in the verbenalin treatment groups， these pathological changes were significantly improved， with a reduction in the lung index （P<0.01）， alleviation of lung tissue injury， reduced lung volume enlargement， and a significant decrease in inflammatory cytokine expression （P<0.01）. Proteomics analysis revealed that， compared to the normal group， the model group showed enrichment in several antiviral immune-related signaling pathways， including the nuclear factor-κB （NF-κB） signaling pathway （P<0.05）. Compared to the model group， the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy （P<0.05）， suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways. ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models， with its mechanism likely related to the NOD-like receptor protein 3 （NLRP3） inflammasome pathway and mitochondrial autophagy.

Objective:To explore the effects of melatonin on streptozotocin(STZ)-induced diabetic pulmonary fibrosis and regulatory mechanisms.Methods:C57BL/6 mice were randomly divided into the control group, STZ group, STZ+ low-dose melatonin(5 mg/kg) group, STZ+ high-dose melatonin(30 mg/kg) group using random number table, and a single intraperitoneal injection of STZ(150 mg/kg) was administered to establish a diabetic pulmonary fibrosis mouse model. Two weeks later, blood glucose levels ≥16.7 mmol/L confirmed successful modeling. Subsequently, melatonin was administered orally for 4 weeks, and the mice were sacrificed at 16 weeks for tissue sampling. Human umbilical vein endothelial cells were divided into the control group(glucose concentration is 5.5 mmol/L), high glucose group(glucose concentration is 33.3 mmol/L), high glucose+ low-dose melatonin(5 μmol/L) group, high glucose+ high-dose melatonin(20 μmol/L) group, and cells in each group were collected for subsequent detection after drug stimulation. Masson staining and immunofluorescence staining were used to observe fibrotic lesions, Western blotting was used to detect the expression related proteins, and sirtuin 3(Sirt3) siRNA was transfected to knock down Sirt3.Results:Significant fibrotic lesions were observed in the lung tissue of the STZ group compared to the control group, however, the STZ+ low-dose melatonin group and STZ+ high-dose melatonin group showed reduced fibrosis compared to the STZ group. In addition, compared to the control group, the endothelial cell marker platelet endothelial cell adhesion molecule-1(CD31) was significantly decreased in the STZ/high glucose group( P<0.001; P<0.001), and the interstitial fibrosis markers collagen 3, Vimentin, and α-smooth muscle actin(α-SMA) were significantly increased( P<0.001, P=0.035, P<0.001; P<0.001, P<0.001, P<0.001), but these trends were partially reversed after melatonin treatment in the STZ/high glucose+ low-dose melatonin group and the STZ/high glucose+ high-dose melatonin group. Moreover, the protein expression of Sirt3 was significantly reduced in the STZ/high glucose group compared to the control group( P<0.001; P<0.001), while it was increased in the STZ/high glucose+ low-dose melatonin and STZ/high glucose+ high-dose melatonin groups compared to the STZ/high glucose group( P=0.047, P<0.001; P=0.048, P<0.001). After transfecting Sirt3 siRNA to knock down the expression of Sirt3, the endothelial cell marker CD31 was significantly reduced( P=0.026), and interstitial fibrosis markers collagen 3, Vimentin, and α-SMA were significantly increased in the high glucose+ high-dose melatonin+ Sirt3 siRNA group compared to the high glucose+ high-dose melatonin group( P<0.001, P<0.001, P<0.001). Conclusion:Melatonin inhibits endothelial-mesenchymal transition by activating Sirt3 expression, thereby alleviating pulmonary fibrosis in STZ-induced diabetic mice.

Chronic hepatitis B virus （HBV） infection is the main cause of the disease burden of viral hepatitis worldwide， and meanwhile， due to changes in lifestyle and dietary habits， the incidence rate of metabolic associated fatty liver disease （MAFLD） is constantly increasing， making MAFLD the leading chronic liver disease around the world. Chronic HBV infection comorbid with MAFLD is becoming more and more common in clinical practice. Metabolic factors， rather than viral factors， are the main cause of chronic HBV infection comorbid with MAFLD. During disease progression， steatohepatitis and fibrosis， rather than steatosis， are the main influencing factors for the progression to liver cirrhosis and hepatocellular carcinoma. For patients with chronic HBV infection and MAFLD， integrated management of virus and metabolic factors is of great importance. This article reviews the tissues regarding the interaction， prognosis， and clinical management of chronic HBV infection and MAFLD.