Molecular mechanism of Solanum Nigrum Linn in alcoholic liver damage based on network pharmacology and molecular docking

Solanum Nigrum Linn,the purpose of this study was to characterize the chemical components of the extract of Solanum Nigrum Linn by LC-MS/MS,and to identify 29 compounds by positive and negative total ion flow maps.The potential mechanism of action of Solanum Nigrum Linn in treating alcoholic liver injury was investigated by means of network pharmacology and molecular docking.A total of 288 component target genes and 1010 disease target genes were obtained,and 98 intersection targets and 7 core targets were obtained after the intersection of the two genes.GO analysis and KEGG analysis respectively obtained 20 signaling pathways such as anti-inflammation and anti-apoptosis.The results of molecular docking showed that the blood components could successfully dock with the target proteins of the disease such as GAPDH,IL6,SRC,EGFR and ESR1.This study provided a scientific basis for the development and application of Solanum Nigrum Linn.

Therapeutic effect of natural melanin from edible fungus Auricularia auricula on alcohol-induced liver damage in vitro and in vivo

This study explored the therapeutic effects of Auricularia auricula melanin(AAM)on alcoholic liver damage in vitro and in vivo.Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury.The results show that AAM signifi cantly elevated the cell viability,ameliorated the cell morphology,reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells.Then,mice were administered with ethanol to induce acute alcoholic liver damage,and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice.As a result,AAM reduced the levels of ALT,AST,TG,and MDA,increased the levels of ADH,SOD,and CAT in liver damage mice.The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase.The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.

Cyclosporin A protects Balb/c mice from liver damage induced by superantigen SEB and D-GaIN

AIM To investigate the pathogenic effect ofSEB and D-GalN on liver and the protection ofcyclosporin A, the relationship between hepaticapoptosis and necrosis and the possiblemechanism of acute hepatic necrosis.METHODS After staphylococcal enterotoxin B(SEB ) mixed with D--galactosamine (D-GaiN )were injected intraperitoneally into Balb/c miceand those previously treated with cyclosporin A,blood samples were collected and livers wereisolated at 2, 6, 12 and 24 h. Patterns othepatocellular death were studiedmorphologically and biochemically, circulatingcytokines (TNF-a, IFN--y ) and mice mortalitywithin 24h was assessed.RESU’LTS The SEB could induce the typicalapoptotic changes of hepatocytes, the D-GaiNcould induce hepatocytes apoptosis anddegeneration at the same time, and the micehaving received the SEB + D-GaiN injectionsdeveloped apoptosis at 2 and 6 h, but after 12 hhepatocytes were characterized by severein jury, whereas all the examinations in thecyclosporin A treated mice were normal.CONCLUSION Hepatic cell apoptosis might berelated to necrosis, and massive hepatocyteapoptosis is likely the initiating step of acutehepatic necrosis in mice. The effects induced bySEB and D--GaiN on hepatocytes might bemediated by T cells, and could be prevented bycyclosporin A.

Effect of Buzhong Yiqi Decoction (补中益气汤) on Murine Liver Damage Induced by Food Allergy

Objective: To investigate the effect of Buzhong Yiqi decoction (补中益气汤, BZYQD) on liver damage induced by food allergy in mice. Methods: Nc/Jic strain mice with high levels of serum IgE were sensitized by ovalbumin (OVA), and then divided into two groups and respectively treated with BZYQD (treated group) or normal saline (model group). Samples of serum, liver tissues and small intestine were collected two weeks later, and another group of non-sensitized mice was set as the normal group. The levels of serum alanine aminotransferase (ALT) were measured with spectrophotometry. The liver tissue and small intestine were stained with hematoxylin and eosin (HE) for pathologic analysis. The liver samples were also subjected to analysis of CD4-T helper cell and cytokine (interleukin-4, IL-4, interleukin-6, IL-6) expression with immunohistochemical (avidin-biotin complex, ABC) method. Results: Serum ALT levels decreased and obvious pathologic improvements were seen in the mice treated with BZYQD. And compared with the model mice, the number of positive cells of IL-4, IL-6 and CD4 cell decreased significantly in those treated with BZYQD. Conclusion: BZYQD can effectively decrease the production of cytokines associated with allergic reaction in the liver of mice thus effective in treating liver damage caused by food allergy.

Liver Damage during Dengue Fever in Ouagadougou

Dengue fever is widespread in all tropical and subtropical areas of the world and is the main public health problem posed by arboviroses. In Burkina Faso, an outbreak of dengue serotype “DENV-2”, which is responsible for severe forms of dengue, has been reported. In this study, we will discuss liver damage during this disease. The aim of this study was to describe the sociodemographic, diagnostic, therapeutic and evolutionary aspects of dengue patients with hepatic cytolysis. Patients and Methods: This was a prospective cross-sectional study of dengue disease in 2 facilities in the city of Ouagadougou. The study was spread over a period of 3 months from August to November 2019. The study population consisted of all patients hospitalised for dengue with a positive AgNS1 and/or IgM rapid diagnostic test (RDT) and presenting signs of liver damage. Results: During our study period we recruited 134 patients with dengue fever of which 93 or 69.4% had at least one elevated transaminase. The sex ratio was 1.90 and the average age was 35 years. Symptoms of liver damage were rare with right hypochondrial pain in 4.30% of cases and jaundice in 1.07% of cases. Dengue haemorrhagic fever was found in 5 patients. IgG was negative in 77.42%. The majority of patients (44% or 47.31%) had at least one transaminase value elevated to the upper limit of normal (ULN);and a minority, 14 patients or 15.06%, had transaminases above 10 ULN. A small proportion of patients had hepatocellular failure 26.92% with a lowered prothrombin level. Ninety-four per cent (94.62%) of the patients received analgesics. Level 1 analgesic (paracetamol) was the most widely administered, particularly in 76 patients (86.36%). More than half of the patients (57.14%) had a length of stay of less than or equal to 3 days and the outcome was favourable in 91.40%. Conclusion: Dengue virus causes alterations in the liver parenchyma. The degree of liver damage is variable. As clinical symptoms are almost non-existent, the measurement of transaminases remains important.

Protective Effect of Vitamin E on Liver Damage Induced by 2-Chloro-1, 3-butadiene

The present study was performed to determine the influence of lipid peroxidation and perturbance of Ca2+ homeostasis on liver damage induced by 2-chloro-1, 3-butadiene (CBD) and the protective effects of vitamin E in Wistar rats. Animals were given intraperitoneally different doses (8,40 or 200 mg·kg-1 daily) of CBD for 21 days, and the following dose-dependent events were observed: liver damage, significant increase in liver lipid peroxides, and decreases in activities of erythrocytic glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The pretreatment of rats with vitamin E (po 150 mg·kg-1) before administering CBD (iP 60 mg·kg-1 ) daily for 21 days prevented the following CBD-induced changes, the increase in serum cholylglycine (CG), hepatic LP, hepatic mitochondrion LP, hepatic oxidized glutathione (GSSG) (while the significant increase of reduced glutathione (GSH) was not affected) and the decrease in activities of erythrocytic SOD and hepatic mitochondrial calcium sequestration. These results suggest that lipid peroxidation and perturbance of Ca2+ homeostasis appear to contribute to the hepatotoxicity of CBD, and vitamin E might prevent the liver damage induced by CBD. The decrease in activities of GSH-Px and SOD in erythrocytes might be used as biomarkers for adverse effects of CBD on defense system against lipid peroxidation.

Yunpi Qushi Jiangzhuo Recipe Alleviates Lipid Deposition and Reduces Liver Damage in Mice with Non-alcoholic Fatty Liver Disease

Background:Non-alcoholic fatty liver disease(NAFLD)is a multifactorial liver metabolic disease,which af-fects nearly a quarter of the world’s population.Yunpi Qushi Jiangzhuo Recipe(QSJZR)is a traditional Chi-nese medicine compound,which is composed of Amomum kravanh Pierre ex Gagnep,Coix lacryma-jobi L.var.ma-yuen(Roman.)Stapf,Prunus armeniac a L.var.ansu Maxim,Salvia miltiorrhiza Bge,Nelumbo nucifera Gaertn,Alisma plantago-aquatica Linn,Polyporus umbellatus(Pers.)Fries,Poria cocos(Schw.)Wolf,and Artemisia capillaris Thunb.QSJZR has a certain therapeutic effect on NAFLD patients,but its specific mechanism is not clear.Objective:To investigate the effect of QSJZR on high-fat diet(HFD)-fed NAFLD mice and its mechanism.Methods:Twenty-four SPF female C57BL/6 J mice(21.0±0.5 g)were randomly divided into normal diet(ND)group,HFD group and QSJZR group.ND group was given basal diet,while the other two groups were given HFD.Meanwhile,each mouse in QSJZR group was given 0.2 mL/day(containing 2.27 g crude drug per mL)QSJZR,ND group and HFD group were given the same amount of normal saline for 13 consecutive weeks.Then,the serum was collected for biochemical assay,and the liver was removed for pathological examination and biochemical analysis.Results:Body weight and white fat weight of the HFD-induced NAFLD mice significantly decreased after min-istration with QSJZR,while liver weight had no significant change.QSJZR also significantly reduced liver and serum triglyceride levels,and alleviated hepatocyte lipid deposition by regulating genes and proteins expression related to lipid metabolism,including AMPK,SREBP1C,CPT1A and ACC.In addition,compared with HFD group,liver malondialdehyde(MDA)content was lower in QSJZR group,while glutathione peroxidase(GPx)content was higher.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were lower in QSJZR group than those in HFD group.Treatment with QSJZR significantly alleviated liver injury by increasing BCL2/BAX protein ratio and down-regulating ASK1/JNK pathway.Conclusion:Administration of QSJZR to NAFLD mice once daily for 13 weeks can decrease lipid levels,and alleviate liver damage.These results suggest that QSJZR might be used to treat NAFLD,although more studies need to be conducted for further verification.

Genistein Improves Liver Damage in Male Mice Exposed to Morphine

Background： Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim of this study was to evaluate the effects of genistein against morphine damages on mouse liver. Methods： Between May 2017 and March 2018, 48 male mice were divided into six groups （n = 8 in each group）. Various doses of genistein （25 and 50 mg/kg） and morphine plus genistein （25 and 50 mg/kg） were administered intraperitoneally to 48 male mice for 20 consequent days. Aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, alkaline phosphatase （ALP）, serum nitric oxide （NO） levels, liver weight, and the diameter of hepatocytes and central hepatic vein were studied and compared using one-way analysis of variance. Results： Morphine administration significantly increased the mean diameter of the central hepatic vein （22.76 ± 1.9 μm vs. 15.04 ± 0.60μm, x^2= 21.814, P = 0.001） and hepatocytes （3.03 ± 0.10 μm vs. 1.10 ± 0.05 μm, x^2 = 9.873, P = 0.001） respectively, blood serum NO level （38.00% ± 2.09% vs. 18.72% ±4.40%, x^2 = 20.404, P 〈 0.001 ）, liver enzyme level （AST： 111.80 ± 5.10 ng/ml vs. 81.93 ±2.20 ng/ ml, x^2 = 32.201, P 〈 0.0001; ALT： 45.14 ± 4.10 ng/ml vs. 35.49 ± 2.50 ng/ml, x^2= 18.203, P 〈 0.0001; and ALP： 3.28 ± 0.20 ng/ml vs. 2.14± 0.10, x^2= 5.04, P 〈 0.0001, respectively）, and decreased liver weight （18.50 ± 0.90 g vs. 27.15 ± 0.50 g, x^2 = 22.415, P=0.001 ） compared to saline group （0.535±3.750, P 〈 0.0001）. However, administration of genistein plus morphine significantly enhanced liver weight （25 mg/kg： 21.15 ±2.13 g vs. 18.50 ±0.90 g, x^2= 19.251 P 〈 0.0001 ; 50 mg/kg： 21.20 ±1.00 g vs. 18.5± 0.9 g, x^2= 19.502, P 〈 0.0001, respectively） and reduced the mean diameter of hepatocyte （25 mg/kg： 2.17±0.30 μm vs. 3.03 ± 0.10 μm, x^2 = 22.780, P =0.001 ; 50 mg/kg： 2.01± 0.20 μm vs. 3.03 ±0.10 μm x^2 = 7.120, P = 0.001, respectively）, central hepatic vein （25 mg/kg： 19.53 ± 1.00 μm vs. 22.76 ±1.90 μm, x^2= 20.681, P = 0.001; 50 mg/kg： 19.44 ± 1.20 μm vs. 22.76 ± 1.90 μm, x^2 = 18.451, P = 0.001, respectively）, AST （25 mg/kg： 95.40 ± 5.20 ng/ml vs. 111.80 ±5.010 ng/ml, P 〈 0.0001：50 mg/kg： 90.78 ± 6.00 ng/ml vs. 111.80 ± 5.10 ng/ml, x^2= 17.112, P 〈 0.0001, respectively）, ALT （25 mg/kg： 35.78 ± 5.01 ng/ml vs. 45.14 ± 4.10 ng/ml, x^2= 15.320, P 〈 0.0001 ; 50 mg/kg： 33.78±2.60ng/mlvs. 45.14±4.10ng/ml,x^2= 14.023, P〈0.0001,respectively）,ALP（25mg/kg：2.35±0.30ng/mlvs. 3.28±0.20ng/ml, x^2=4.101, P 〈 0.0001; 50 mg/kg： 2.34 ± 0.10 ng/ml vs. 3.28 ± 0.20 ng/ml, x^2=2.033, P 〈 0.0001, respectively）, and NO levels （25 mg/ kg： 25.92% ± 2.30% vs. 38% ± 2.09%, x^2= 17.103, P 〈 0.0001 ; 50 mg/kg： 24.74% ± 4.10% vs. 38% ± 2.09%, x^2 = 25.050, P - 0.001, respectively） compared to morphine group. Conclusion： It seems that genistein administration might improve liver damages induced by morphine in mice.

Protective Effect of Chlorogenic Acid against Carbon Tetrachloride-induced Acute Liver Damage in Rats

Objective To evaluate the protective effect of chlorogenic acid （CGA） on carbon tetrachloride （CCh）-induced liver injury of rats. Methods The anti-oxidative activity of CGA was investigated with several established in vitro systems. The hepatoprotective activity of CGA against CCI4-induced acute liver injury in eats was studied. The levels of alanine aminotranferase （ALT）, aspartate aminotransferase （AST）, alkaline phosphatase （ALP）, and total bilirubin （TB） were measured. The histopathological examination was carried out to supplement the biochemical results. Results CGA possessed strong anti-oxidative ability in vitro. The CCh-induced liver toxicity experiment showed that the rats pretreated with CGA （300 or 500 mg/kg） had lower levels of ALT, AST, ALP, and TB than those of the CCI4-treated group. These data were supplemented with histopathological examination of rat liver sections. CGA did not show any mortality at the dose up to 5000 mg/kg. Conclusion CGAcould protect the liver againstCCI4-induced oxidative damage in rats, and the possible mechanism of the activity may be due to its free radical-scavenging and anti-oxidative activity.

Reabsorption of iron into acutely damaged rat liver:A role for ferritins

AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair.METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide(TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain(FTL), and ferritin heavy chain(FTH)was investigated in the liver by q RT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations.RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase(aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72 h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ(1 h) and IL-1β(3 h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter(96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes.CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.

Insight into the liver dysfunction in COVID-19 patients: Molecular mechanisms and possible therapeutic strategies

As of June 2022,more than 530 million people worldwide have become ill with coronavirus disease 2019(COVID-19).Although COVID-19 is most commonly associated with respiratory distress(severe acute respiratory syndrome),metaanalysis have indicated that liver dysfunction also occurs in patients with severe symptoms.Current studies revealed distinctive patterning in the receptors on the hepatic cells that helps in viral invasion through the expression of angiotensinconverting enzyme receptors.It has also been reported that in some patients with COVID-19,therapeutic strategies,including repurposed drugs(mitifovir,lopinavir/ritonavir,tocilizumab,etc.)triggered liver injury and cholestatic toxicity.Several proven indicators support cytokine storm-induced hepatic damage.Because there are 1.5 billion patients with chronic liver disease worldwide,it becomes imperative to critically evaluate the molecular mechanisms concerning hepatotropism of COVID-19 and identify new potential therapeutics.This review also designated a comprehensive outlook of comorbidities and the impact of lifestyle and genetics in managing patients with COVID-19.

Effects of Phentolamine on Hemorrheology and Hemodynamics in Dogs with Acute Liver Damage

The effects of phentolamine on hemorrheology and hemodynamics were studied in dogs with acute liver damage induced by acetaminophen. After 1 h of phentolamine application , the viscosity of plasma and whole blood was significantly diminished. The hematocrit readings followed the same pattern as the alterations in viscosity. The portal venous resistance and the value of K were remarkably decreased and the portal venous blood flow was obviously increased. It can be assumed , therefore , that the decrease in viscosity induced by phentolamine results from internal hemodilution and phentolamine may improve hepatic blood circulation through the decrease of portal venous resistance caused by the reduction of blood viscosity and the dilation of portal vascular beds.

Protective Effect of Dimethyl-4,4'-Dimethoxy-5,6,5',6'-Dimethylene Dioxybiphenyl-2,2'-Dicarboxylate (DDB) against Carcinogen-Induced Rat Liver Nuclear DNA Damage

The protective effect of DDB against carcinogen-induced DNA damage was examined in the present investigation. Preincubation of rat liver nuclei with DDB (1 mmol.L-1) resulted in 60% inhibition of binding of 3H-benzo (a) pyrene to nuclear DNA. Unscheduled DNA synthesis (UDS) induced by aflatoxin BI (10^(-7) mol.L-1) in freshly isolated rat hepatocytes was also inhibited by DDB (10^(-6)-10^(-3)mol.L-1). Oral administration of DDB at 200 mg.kg-1 once daily for 3 d induced a significant increase of liver cytosol glutathione-S-transferase and microsomal UDPG-transferase activity in mice. These results indicate that DDB is able to directly or indirectly antagonize certain carcinogen-induced DNA damages.

Antioxidant and hepatoprotective effects of Hypsizygus ulmarius polysaccharide on alcoholic liver injury in rats

Hypsizygus ulmarius polysaccharide(HUP)is a water-soluble polysaccharide obtained by hot water extraction,followed by precipitation and deproteinization.The characteristics of HUP,antioxidant activity and liver protection against alcohol-induced liver damage were studied.Structural characteristics indicate that the HUP is a pyran-type polysaccharide with a molecular weight of 2076 Da.In antioxidant scavenging assay,HUP showed moderate DMPD radical scavenging activity,cupric ion reducing antioxidant capacity and inhibitory effect against lipid peroxidation in a dose-dependent manner.Regarding in vivo hepatoprotective activity,compared with the ethanol induction group,pre-treatment of low and high doses of HUP signifi cantly reduced the behaviours of serum enzymes,lowered the levels of hepatic oxidative stress markers,restored the levels of biochemical constituents,enhanced the levels of liver and serum enzymatic antioxidants and non-enzymatic antioxidants,and improved the serum lipid levels of alcohol-intoxicated rats.The hepatoprotective effect of HUP was comparable to positive control silymarin.Besides,HUP pre-treatment signifi cantly normalized the histopathological changes induced by ethanol.The results indicate that HUP could be used as a functional food and may protect the biological system from oxidative stress through its antioxidant activity,thus having a signifi cant protective effect on acute alcoholic liver injury.

Mesona chinensis Benth polysaccharides alleviates liver injury by beneficial regulation of gut microbiota in cyclophosphamide-induced mice

There are a number of health benefits of Mesona chinensis Benth polysaccharide(MP),but little is known about its hepatoprotective effect and effect on gut microbiota composition in mice with liver damage induced by cyclophosphamide(CTX).This study indicated that MP supplementation effectively inhibited the production of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT),enhanced liver antioxidant capacity and repaired liver damage in mice caused by CTX.The release of inflammatory cytokines in liver and the concentration of lipopolysaccharide(LPS)in serum were decreased,and the level of short chain fatty acids(SCFAs)in colon was increased after MP administration.Those effects may be correlated with the regulation of the gut microbiota.Importantly,MP restrained liver inflammatory responses induced by CTX may via increasing the SCFAs-producing bacteria family Ruminococcaceae and reduced LPS-producing bacteria genus Bacteroides.In short,the prevention of CTX-induced liver injury by supplementing MP is achieved at least in part by regulating the community structure of the gut microbiota,and MP is expected to be a potential prebiotic to treat and prevent liver diseases.

Novel mechanism of hepatobiliary system damage and immunoglobulin G4 elevation caused by Clonorchis sinensis infection

Clonorchis sinensis infection is still a major public health problem.It is estimated that more than 15 million people worldwide are infected,especially in Northeast China,Taiwan,South Korea,and North Vietnam.The detection of Clonorchis sinensis eggs in feces and bile is still the only gold standard for the diagnosis of Clonorchis sinensis infection,and new detection methods are needed to improve the detection rate.After Clonorchis sinensis invades the human body,it mainly parasitizes the hepatobiliary tract.Therefore,it is closely related to hepatobiliary diseases such as cholangitis,bile duct stones,liver fibrosis,and cholangiocarcinoma.The increase in immunoglobulin G4(IgG4)caused by Clonorchis sinensis infection is rare and there are few reports about the relevant mechanism.It may be related to the inflammatory factors interleukin(IL)-4,IL-10,and IL-13 produced by human phagocytes,T cells,B cells,and other immune cells in the process of resisting the invasion of Clonorchis sinensis.However,this finding still needs further clarification and confirmation.This article reviews the epidemiology,clinical manifestations,serology,imaging,pathogenic mechanism,and control measures of Clonorchis sinensis infection to help establish the diagnostic process for Clonorchis sinensis.We report novel mechanisms of IgG4 elevation due to Clonorchis sinensis infection to provide more experience and a theoretical basis for clinical diagnosis and treatment of this infection.

Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19

patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.

Role of immune dysfunction in drug induced liver injury

Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has rendered the prediction and subsequent treatment intractable.Recent literature suggests that some drugs can alter the liver’s repair systems resulting in injury.The pathophysiology of DILI is complex,and immune dysfunction plays an important role in determining the course and severity of the disease.Immune dysfunction is influenced by the host response to drug toxicity.A deeper understanding of these processes may be beneficial in the management of DILI and aid in drug development.This review provides a structured framework presenting DILI in three progressive stages that summarize the interplay between drugs and the host defence networks.

Elevated liver enzymes portends a higher rate of complication and death in SARS-CoV-2

BACKGROUND Severe acute respiratory syndrome coronavirus 2,or coronavirus disease-2019(COVID-19),has infected millions worldwide since its discovery in Wuhan,China in December 2019,but little is still known about the disease process.Preliminary research in China notes liver function tests(LFTs)abnormalities are common in COVID-19 patients,suggesting decreased hepatic function,and that abnormalities in LFTs are related to complicated disease course and negative outcomes.However,there has been limited large-scale data assessing COVID-19’s association with liver dysfunction and negative outcomes.AIM To investigate how COVID-19 affects the liver function and disease course in patients infected with the virus treated at Henry Ford Hospital from March to September 2020.METHODS A total of 8028 patients infected with COVID-19 were identified and included in the study at a single academic center.Data from medical charts on laboratory testing including aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(AP),and bilirubin levels,past history of liver disease,and disease course indicators including hospital admission,intensive care unit(ICU)admission,intubation,and death were recorded and analyzed.Elevated liver enzymes were defined as ALT/AST greater than 60,AP greater than 150,or bilirubin greater than 1.5,super-elevated liver enzymes were defined as ALT/AST greater than 120,AP greater than 300,or bilirubin greater than 3.0.RESULTS A total of 8028 COVID-19 patients were identified and included in the study.Data from medical charts on LFTs(namely,AST,ALT,AP,and bilirubin levels),past history of liver disease,and disease course indicators(hospital/ICU admission,intubation,death)were recorded and analyzed.LFTs from 3937 patients were available for interpretation.45% were found to have elevated or super-elevated LFT.When compared to COVID-19 patients without elevated LFTs,this cohort was found to have significantly higher odds of hospital admittance,ICU admission,intubation,and death(all P<0.001).248(3.1%)had a history of liver disease.Those with elevated and super elevated LFTS had significantly higher odds of having a past history of liver disease(P<0.001).CONCLUSION The findings from this study suggest that in patients who have tested positive for COVID-19,those with elevated and super elevated liver enzyme levels have significantly higher odds of hospital admittance,ICU admittance,intubation and death in comparison to those COVID-19 patients without elevated liver enzyme levels.

An Experimental Study on the Disturbance of Liver Circulation and the Change

The changes of hepatic hemodynamics and hemorrheology were investigated in dogs with acute liver damage inducted by acetaminophen There were remarkable disturtance in liver circulation and hemorrheological abnormality occuring in both slight and severe liver damage.The study indicated that the degree of disturbance in liver circulation as well as in lemorheological change is positively correlated with the severity of livei damage For example,marked increase in blood viscosity linked with elevated fibrinogen level appeared in slight liver damage,whereas reduced blood viscosity associated with decreased plasma fibrinogen level and hematocrit occured in severe liver damage.This study also revealed that the inciease of portal venous resistance(PVR)and the disturbance of liver circulation in slight liver damage were chiefly related to the increase of blood viscosity and the increase of PVR in severe liver damage was mainly associated with the reduction of the radius of porta vein.