Effect of hepatocyte growth factor on inflammatory factors associated with CCL_(4)-induced hepatocyte injury

Objective:The aim of this study is to investigate the effects of Hepatocyte Growth Factor(HGF)on the expression levels of IL-8,TNF-α,IL-4,and IL-21 in mice with liver injury induced by CCL_(4).Methods:An acute liver injury mouse model was established using CCL_(4),and hepatocytes and white blood cells were separated by gradient density centrifugation.Different concentrations of HGF were added in vitro,and the expression levels of cytokines were detected using ELISA.Results:In the in vivo injury model,the hepatocyte experiment results showed that the expression level of IL-8 was reduced in the 10 ng/mL HGF group compared to the injured hepatocyte group(P<0.05),and increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.05).For IL-4,the expression levels were reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the injured hepatocyte group.The white blood cell experiment results showed that the expression levels of TNF-αwere reduced in both the 10ng/ml HGF group(P<0.05)and the 25 ng/mL HGF group(P<0.05)compared to the injured white blood cell group.In the in vitro injury model,hepatocyte experiment results showed that the expression levels of TNF-αwere reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the normal control group.For IL-4,the expression level was reduced in the 25 ng/mL HGF group compared to the normal control group(P<0.05).The white blood cell experiment results showed that the expression level of TNF-αwas increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.001);for IL-21,the expression levels were reduced in the CCL_(4) model group(P<0.05),10 ng/mL HGF group(P<0.05),25 ng/mL HGF group(P<0.05),and 50 ng/mL HGF group(P<0.05)compared to the normal control group.Conclusion:when the liver of mice is acutely damaged by CCL_(4),HGF can reduce the expression levels of inflammatory cytokines IL-8,TNF-α,IL-4 in hepatocytes,and TNF-αin liver white blood cells.

SARS-CoV-2 induced liver injury:Incidence,risk factors,impact on COVID-19 severity and prognosis in different population groups

Liver is unlikely the key organ driving mortality in coronavirus disease 2019(COVID-19)however,liver function tests(LFTs)abnormalities are widely observed mostly in moderate and severe cases.According to this review,the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5%to 96.8%worldwide.The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West.Multifactorial mechanisms are implicated in COVID-19-induced liver injury.Among them,hypercytokinemia with“bystander hepatitis”,cytokine storm syndrome with subsequent oxidative stress and endotheliopathy,hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury.Liver hypoxia may also contribute under specific conditions,while direct hepatocyte injury is an emerging mechanism.Except for initially observed severe acute respiratory distress syndrome corona virus-2(SARS-CoV-2)tropism for cholangiocytes,more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy(EM).The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA,S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization.New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery,suggesting a post-COVID-19 persistent live injury.

Protective effects of polydatin against CCl_4-induced injury to primarily cultured rat hepatocytes

AIM To investigate the protective effects of polydatin (PD) against injury to primarily cultured rat hepatocytes induced by CCl 4. METHODS Rat hepatocytes were separated by methods of liver infusion in vivo and cultured medium (7 5×10 5 cells/mL). Two mL or 0 2mL was added into 24 well or 96 well plates respectively. Twenty four hours after cell preculture, PD at concentrations of 10 -7 mol/L-10 -4 mol/L was added into each plate. At the same time injury to hepatocytes was induced by adding 10mmol/L CCl 4. Then, 0 1mL or 1mL culture solution was removed from the 96 well or 24 well plates at 6h , 12h , 24h and 48h after CCl 14 intoxication respectively for the determination of GPT, GSH and MDA. At 48h , the survivability of rat hepatocytes was assayed by the MTT colormetric method. RESULTS After CCl 4 challenge, the release of GPT and the formation of MDA in rat hepatocytes markedly increased and maintained at a high level in 48h , whereas PD with different concentrations could markedly inhibit this elevation with 10 -5 mol/L PD having the strongest effects and inhibiting rate was over 50%. PD could also improve the decreased content of GSH caused by CCl 4 in accordance with the doses used. CCl 4 evidently decreased the hepatocyte survivability from 91 0%±7 9% to 35 4%±3 8%. On the other hand, PD at 10 -7 mol/L-10 -4 mol/L could reverse this change and improve the cell survival rates to 56 1%±5 2%, 65 8%±5 0%, 88 7%±6 8% and 75 2%±7 3%, respectively. CONCLUSION PD at 10 -7 mol/L-10 -4 mol/L could protect primarily cultured rat hepatocytes against CCl 4 induced injury.

Hepatitis C Virus Clearance by Direct-acting Antiviral Results in Rapid Resolution of Hepatocytic Injury as Indicated by Both Alanine Aminotransferase and Aspartate Aminotransferase Normalization

Background and Aims:Hepatitis C virus(HCV)infection results in hepatocytic injury with elevation of both alanine aminotransferase(ALT)and aspartate aminotransferase(AST).It remains to be determined if direct-acting antiviral treatment can terminate hepatocytic injury following viro-logic response.To this end,we evaluated the pattern and predicting factors of ALT and AST normalization during and after direct-acting antiviral treatment with sustained virologic response at 12 weeks(SVR12).Methods:Single-center ret-rospective study on 115 HCV-infected patients who achieved SVR12 was performed.Results:At treatment week 2,100%and 45.9%showed decline in HCV RNA to<700 IU/mL and undetectable levels,respectively,and this was associated with 85.5%,83.9%and 77.4%ALT normalization,AST nor-malization and ALT and AST normalization.At end of treat-ment,85.6%of patients with baseline elevation of both ALT and AST had normalization of both ALT and AST.At posttreat-ment weeks 12 and 24,90.8%and 94.8%had normalization of both ALT and AST.HCV clearance also resulted in further decline of both ALT and AST in those with baseline<40 IU.Univariate analysis showed baseline Child-Pugh score of<6,model for end-stage liver disease score of<10,HCV geno-type 1,and HCV RNA of<500 IU/mL at treatment week 2 were associated with sustained normalization of both ALTand AST at posttreatment week 12.On multivariate analysis,baseline model for end-stage liver disease score of<10 was significantly associated with normalization of both ALT and AST at posttreatment week 12,independent of baseline Child-Pugh score<6,HCV genotype 1,and HCV RNA of<500 IU/mL at treatment week 2.Conclusions:During direct-acting antiviral therapy,85.5%and 83.9%had nor-malization of both ALTand ASTas early as in week 2,providing;biochemical evidence of hepatocytic injury resolution.Sustained normalization of both ALT and AST was seen in 90.8%at posttreatment weeks 12,and was independently associated with baseline model for end-stage liver disease score of<10.