Roles of hepatic stellate cells in acute liver failure: From the perspective of inflammation and fibrosis
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摘要
Acute liver failure(ALF) usually results in hepatocellular dysfunction and coagulopathy and carries a high mortality rate. Hepatic stellate cells(HSCs) are famous for their role in liver fibrosis. Although some recent studies revealed that HSCs might participate in the pathogenesis of ALF, the accurate mechanism is still not fully understood. This review focuses on the recent advances in understanding the functions of HSCs in ALF and revealed both protective and promotive roles during the pathogenesis of ALF: HSC activation participates in the maintenance of cell attachment and the architecture of liver tissue via extracellular matrix production and assists liver regeneration by producing growth factors; and HSC inflammation plays a role in relaying inflammation signaling from sinusoids to parenchyma via secretion of inflammatory cytokines.A better understanding of roles of HSCs in the pathogenesis of ALF may lead to improvements and novel strategies for treating ALF patients.
Acute liver failure(ALF) usually results in hepatocellular dysfunction and coagulopathy and carries a high mortality rate. Hepatic stellate cells(HSCs) are famous for their role in liver fibrosis. Although some recent studies revealed that HSCs might participate in the pathogenesis of ALF, the accurate mechanism is still not fully understood. This review focuses on the recent advances in understanding the functions of HSCs in ALF and revealed both protective and promotive roles during the pathogenesis of ALF: HSC activation participates in the maintenance of cell attachment and the architecture of liver tissue via extracellular matrix production and assists liver regeneration by producing growth factors; and HSC inflammation plays a role in relaying inflammation signaling from sinusoids to parenchyma via secretion of inflammatory cytokines.A better understanding of roles of HSCs in the pathogenesis of ALF may lead to improvements and novel strategies for treating ALF patients.
Acute liver failure(ALF) usually results in hepatocellular dysfunction and coagulopathy and carries a high mortality rate. Hepatic stellate cells(HSCs) are famous for their role in liver fibrosis. Although some recent studies revealed that HSCs might participate in the pathogenesis of ALF, the accurate mechanism is still not fully understood. This review focuses on the recent advances in understanding the functions of HSCs in ALF and revealed both protective and promotive roles during the pathogenesis of ALF: HSC activation participates in the maintenance of cell attachment and the architecture of liver tissue via extracellular matrix production and assists liver regeneration by producing growth factors; and HSC inflammation plays a role in relaying inflammation signaling from sinusoids to parenchyma via secretion of inflammatory cytokines.A better understanding of roles of HSCs in the pathogenesis of ALF may lead to improvements and novel strategies for treating ALF patients.
引文
1 Liver Failure and Artificial Liver Group;Chinese Society of Infectious Diseases;Chinese Medical Association;Severe Liver Disease and Artificial Liver Group;Chinese Society of Hepatology;Chinese Medical Association.Guideline for diagnosis and treatment of liver failure.Zhonghua Gan Zang Bing Za Zhi 2019;27:18-26[PMID:30685919 DOI:10.3760/cma.j.issn.1007-3418.2019.01.006]
2 Bernal W.Acute Liver Failure:Review and Update.Int Anesthesiol Clin 2017;55:92-106[PMID:28288031 DOI:10.1097/AIA.0000000000000141]
3 Tsuchida T,Friedman SL.Mechanisms of hepatic stellate cell activation.Nat Rev Gastroenterol Hepatol2017;14:397-411[PMID:28487545 DOI:10.1038/nrgastro.2017.38]
4 Schumacher JD,Guo GL.Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors.Biomed Res Int 2016;2016:8323747[PMID:27699175 DOI:10.1155/2016/8323747]
5 Shen K,Chang W,Gao X,Wang H,Niu W,Song L,Qin X.Depletion of activated hepatic stellate cell correlates with severe liver damage and abnormal liver regeneration in acetaminophen-induced liver injury.Acta Biochim Biophys Sin(Shanghai)2011;43:307-315[PMID:21335335 DOI:10.1093/abbs/gmr005]
6 Fujita T,Narumiya S.Roles of hepatic stellate cells in liver inflammation:a new perspective.Inflamm Regen 2016;36:1[PMID:29259674 DOI:10.1186/s41232-016-0005-6]
7 Xiang DM,Sun W,Ning BF,Zhou TF,Li XF,Zhong W,Cheng Z,Xia MY,Wang X,Deng X,Wang W,Li HY,Cui XL,Li SC,Wu B,Xie WF,Wang HY,Ding J.The HLF/IL-6/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis.Gut 2018;67:1704-1715[PMID:28754776DOI:10.1136/gutjnl-2016-313392]
8 Fujita T,Soontrapa K,Ito Y,Iwaisako K,Moniaga CS,Asagiri M,Majima M,Narumiya S.Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immunemediated hepatitis.Hepatology 2016;63:1325-1339[PMID:26248612 DOI:10.1002/hep.28112]
9 Harvey SA,Dangi A,Tandon A,Gandhi CR.The transcriptomic response of rat hepatic stellate cells to endotoxin:implications for hepatic inflammation and immune regulation.PLoS One 2013;8:e82159[PMID:24349206 DOI:10.1371/journal.pone.0082159]
10 Sowa JP,Gerken G,Canbay A.Acute Liver Failure-It's Just a Matter of Cell Death.Dig Dis 2016;34:423-428[PMID:27170397 DOI:10.1159/000444557]
11 Bantel H,Schulze-Osthoff K.Mechanisms of cell death in acute liver failure.Front Physiol 2012;3:79[PMID:22485095 DOI:10.3389/fphys.2012.00079]
12 Weng HL,Cai X,Yuan X,Liebe R,Dooley S,Li H,Wang TL.Two sides of one coin:massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.Front Physiol 2015;6:178[PMID:26136687 DOI:10.3389/fphys.2015.00178]
13 Macdonald S,Andreola F,Bachtiger P,Amoros A,Pavesi M,Mookerjee R,Zheng YB,Gronbaek H,Gerbes AL,Sola E,Caraceni P,Moreau R,Gines P,Arroyo V,Jalan R.Cell death markers in patients with cirrhosis and acute decompensation.Hepatology 2018;67:989-1002[PMID:29023872 DOI:10.1002/hep.29581]
14 Best J,DolléL,Manka P,Coombes J,van Grunsven LA,Syn WK.Role of liver progenitors in acute liver injury.Front Physiol 2013;4:258[PMID:24133449 DOI:10.3389/fphys.2013.00258]
15 Preziosi ME,Monga SP.Update on the Mechanisms of Liver Regeneration.Semin Liver Dis 2017;37:141-151[PMID:28564722 DOI:10.1055/s-0037-1601351]
16 Sang JF,Shi XL,Han B,Huang T,Huang X,Ren HZ,Ding YT.Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis.Hepatobiliary Pancreat Dis Int 2016;15:602-611[PMID:27919849]
17 CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure(EF-CLIF);Stauber RE,Coenraad MJ,Moreau R,Jalan R,Pavesi M,Titos E,Oettl K,Angeli P,Domenicali M,Alessandria C,Gerbes A,Wendon J,Nevens F,Trebicka J,Laleman W,Saliba F,Welzel TM,Albillos A,Gustot T,Benten D,Durand F,Bernardi M,Arroyo V,Clària J,Amorósà,Ginès P,Morales-Ruiz M,Alcaraz-Quiles J.Systemic inflammation in decompensated cirrhosis:Characterization and role in acute-on-chronic liver failure.Hepatology 2016;64:1249-1264[PMID:27483394 DOI:10.1002/hep.28740]
18 Wang LK,Wang LW,Li X,Han XQ,Gong ZJ.Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure.Hepatobiliary Pancreat Dis Int 2013;12:180-188[PMID:23558073]
19 Zhong W,Qian K,Xiong J,Ma K,Wang A,Zou Y.Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κBrelated signaling.Biomed Pharmacother 2016;83:302-313[PMID:27393927 DOI:10.1016/j.biopha.2016.06.036]
20 Donnelly MC,Hayes PC,Simpson KJ.Role of inflammation and infection in the pathogenesis of human acute liver failure:Clinical implications for monitoring and therapy.World J Gastroenterol 2016;22:5958-5970[PMID:27468190 DOI:10.3748/wjg.v22.i26.5958]
21 Fischer J,Silva TE,Soares E Silva PE,Colombo BS,Silva MC,Wildner LM,Bazzo ML,Rateke EC,Frode TS,Mello SV,Rosa JS,Dantas-Correa EB,Narciso-Schiavon JL,Schiavon LL.From stable disease to acute-on-chronic liver failure:Circulating cytokines are related to prognosis in different stages of cirrhosis.Cytokine 2017;91:162-169[PMID:28082235 DOI:10.1016/j.cyto.2016.12.017]
22 Yang X,Chen Y,Zhang J,Tang T,Kong Y,Ye F,Zhang X,Liu X,Lin S.Thymosinα1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure.Exp Ther Med 2018;15:3231-3238[PMID:29545840 DOI:10.3892/etm.2018.5843]
23 Liang DY,Liu LM,Ye CG,Zhao L,Yu FP,Gao DY,Wang YY,Yang ZW,Wang YY.Inhibition of UII/UTR system relieves acute inflammation of liver through preventing activation of NF-κB pathway in ALF mice.PLoS One 2013;8:e64895[PMID:23755157 DOI:10.1371/journal.pone.0064895]
24 Lee UE,Friedman SL.Mechanisms of hepatic fibrogenesis.Best Pract Res Clin Gastroenterol 2011;25:195-206[PMID:21497738 DOI:10.1016/j.bpg.2011.02.005]
25 Lunova M,Goehring C,Kuscuoglu D,Mueller K,Chen Y,Walther P,Deschemin JC,Vaulont S,Haybaeck J,Lackner C,Trautwein C,Strnad P.Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload.J Hepatol 2014;61:633-641[PMID:24816174 DOI:10.1016/j.jhep.2014.04.034]
26 McGill MR,Jaeschke H.Apoptosis or necrosis in acetaminophen-induced acute liver failure?New insights from mechanistic biomarkers.Crit Care Med 2013;41:2653-2654[PMID:24162681 DOI:10.1097/CCM.0b013e31829caf67]
27 Bourbonnais E,Raymond VA,Ethier C,Nguyen BN,El-Leil MS,Meloche S,Bilodeau M.Liver fibrosis protects mice from acute hepatocellular injury.Gastroenterology 2012;142:130-139.e4[PMID:21945831DOI:10.1053/j.gastro.2011.09.033]
28 Zhan SS,Jiang JX,Wu J,Halsted C,Friedman SL,Zern MA,Torok NJ.Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo.Hepatology2006;43:435-443[PMID:16496318 DOI:10.1002/hep.21093]
29 Dechêne A,Sowa JP,Gieseler RK,Jochum C,Bechmann LP,El Fouly A,Schlattjan M,Saner F,Baba HA,Paul A,Dries V,Odenthal M,Gerken G,Friedman SL,Canbay A.Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation.Hepatology 2010;52:1008-1016[PMID:20684020 DOI:10.1002/hep.23754]
30 He Y,Jin L,Wang J,Yan Z,Chen T,Zhao Y.Mechanisms of fibrosis in acute liver failure.Liver Int2015;35:1877-1885[PMID:25388426 DOI:10.1111/liv.12731]
31 Chalasani N,Aljadhey H,Kesterson J,Murray MD,Hall SD.Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity.Gastroenterology 2004;126:1287-1292[PMID:15131789]
32 Teschke R,Danan G.Drug-induced liver injury:Is chronic liver disease a risk factor and a clinical issue?Expert Opin Drug Metab Toxicol 2017;13:425-438[PMID:27822971 DOI:10.1080/17425255.2017.1252749]
33 Osawa Y,Hannun YA,Proia RL,Brenner DA.Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver.Hepatology 2005;42:1320-1328[PMID:16317686 DOI:10.1002/hep.20967]
34 Gkretsi V,Bowen WC,Yang Y,Wu C,Michalopoulos GK.Integrin-linked kinase is involved in matrixinduced hepatocyte differentiation.Biochem Biophys Res Commun 2007;353:638-643[PMID:17194454DOI:10.1016/j.bbrc.2006.12.091]
35 Yan C,Zhou L,Han YP.Contribution of hepatic stellate cells and matrix metalloproteinase 9 in acute liver failure.Liver Int 2008;28:959-971[PMID:18507761 DOI:10.1111/j.1478-3231.2008.01775.x]
36 Michalopoulos GK.Advances in liver regeneration.Expert Rev Gastroenterol Hepatol 2014;8:897-907[PMID:24964729 DOI:10.1586/17474124.2014.934358]
37 Kwon YJ,Lee KG,Choi D.Clinical implications of advances in liver regeneration.Clin Mol Hepatol2015;21:7-13[PMID:25834796 DOI:10.3350/cmh.2015.21.1.7]
38 Yin C,Evason KJ,Asahina K,Stainier DY.Hepatic stellate cells in liver development,regeneration,and cancer.J Clin Invest 2013;123:1902-1910[PMID:23635788 DOI:10.1172/JCI66369]
39 Williams MJ,Clouston AD,Forbes SJ.Links between hepatic fibrosis,ductular reaction,and progenitor cell expansion.Gastroenterology 2014;146:349-356[PMID:24315991 DOI:10.1053/j.gastro.2013.11.034]
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43 Wen YA,Liu D,Zhou QY,Huang SF,Luo P,Xiang Y,Sun S,Luo D,Dong YF,Zhang LP.Biliary intervention aggravates cholestatic liver injury,and induces hepatic inflammation,proliferation and fibrogenesis in BDL mice.Exp Toxicol Pathol 2011;63:277-284[PMID:20149605 DOI:10.1016/j.etp.2010.01.006]
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47 Chen Y,Wu Z,Yuan B,Dong Y,Zhang L,Zeng Z.MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate cell activation and hepatocyte apoptosis through inhibition of TLR4pathway.Cell Death Dis 2018;9:22[PMID:29348414 DOI:10.1038/s41419-017-0038-z]
48 Wang W,Wu L,Li Q,Zhang Z,Xu L,Lin C,Gao L,Zhao K,Liang F,Zhang Q,Zhou M,Jiang W.Madecassoside prevents acute liver failure in LPS/D-GalN-induced mice by inhibiting p38/NF-κB and activating Nrf2/HO-1 signaling.Biomed Pharmacother 2018;103:1137-1145[PMID:29715757 DOI:10.1016/j.biopha.2018.04.162]
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52 Gong X,Yang Y,Huang L,Zhang Q,Wan RZ,Zhang P,Zhang B.Antioxidation,anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice.Int Immunopharmacol 2017;46:124-132[PMID:28282576 DOI:10.1016/j.intimp.2017.03.003]
2 Bernal W.Acute Liver Failure:Review and Update.Int Anesthesiol Clin 2017;55:92-106[PMID:28288031 DOI:10.1097/AIA.0000000000000141]
3 Tsuchida T,Friedman SL.Mechanisms of hepatic stellate cell activation.Nat Rev Gastroenterol Hepatol2017;14:397-411[PMID:28487545 DOI:10.1038/nrgastro.2017.38]
4 Schumacher JD,Guo GL.Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors.Biomed Res Int 2016;2016:8323747[PMID:27699175 DOI:10.1155/2016/8323747]
5 Shen K,Chang W,Gao X,Wang H,Niu W,Song L,Qin X.Depletion of activated hepatic stellate cell correlates with severe liver damage and abnormal liver regeneration in acetaminophen-induced liver injury.Acta Biochim Biophys Sin(Shanghai)2011;43:307-315[PMID:21335335 DOI:10.1093/abbs/gmr005]
6 Fujita T,Narumiya S.Roles of hepatic stellate cells in liver inflammation:a new perspective.Inflamm Regen 2016;36:1[PMID:29259674 DOI:10.1186/s41232-016-0005-6]
7 Xiang DM,Sun W,Ning BF,Zhou TF,Li XF,Zhong W,Cheng Z,Xia MY,Wang X,Deng X,Wang W,Li HY,Cui XL,Li SC,Wu B,Xie WF,Wang HY,Ding J.The HLF/IL-6/STAT3 feedforward circuit drives hepatic stellate cell activation to promote liver fibrosis.Gut 2018;67:1704-1715[PMID:28754776DOI:10.1136/gutjnl-2016-313392]
8 Fujita T,Soontrapa K,Ito Y,Iwaisako K,Moniaga CS,Asagiri M,Majima M,Narumiya S.Hepatic stellate cells relay inflammation signaling from sinusoids to parenchyma in mouse models of immunemediated hepatitis.Hepatology 2016;63:1325-1339[PMID:26248612 DOI:10.1002/hep.28112]
9 Harvey SA,Dangi A,Tandon A,Gandhi CR.The transcriptomic response of rat hepatic stellate cells to endotoxin:implications for hepatic inflammation and immune regulation.PLoS One 2013;8:e82159[PMID:24349206 DOI:10.1371/journal.pone.0082159]
10 Sowa JP,Gerken G,Canbay A.Acute Liver Failure-It's Just a Matter of Cell Death.Dig Dis 2016;34:423-428[PMID:27170397 DOI:10.1159/000444557]
11 Bantel H,Schulze-Osthoff K.Mechanisms of cell death in acute liver failure.Front Physiol 2012;3:79[PMID:22485095 DOI:10.3389/fphys.2012.00079]
12 Weng HL,Cai X,Yuan X,Liebe R,Dooley S,Li H,Wang TL.Two sides of one coin:massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.Front Physiol 2015;6:178[PMID:26136687 DOI:10.3389/fphys.2015.00178]
13 Macdonald S,Andreola F,Bachtiger P,Amoros A,Pavesi M,Mookerjee R,Zheng YB,Gronbaek H,Gerbes AL,Sola E,Caraceni P,Moreau R,Gines P,Arroyo V,Jalan R.Cell death markers in patients with cirrhosis and acute decompensation.Hepatology 2018;67:989-1002[PMID:29023872 DOI:10.1002/hep.29581]
14 Best J,DolléL,Manka P,Coombes J,van Grunsven LA,Syn WK.Role of liver progenitors in acute liver injury.Front Physiol 2013;4:258[PMID:24133449 DOI:10.3389/fphys.2013.00258]
15 Preziosi ME,Monga SP.Update on the Mechanisms of Liver Regeneration.Semin Liver Dis 2017;37:141-151[PMID:28564722 DOI:10.1055/s-0037-1601351]
16 Sang JF,Shi XL,Han B,Huang T,Huang X,Ren HZ,Ding YT.Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis.Hepatobiliary Pancreat Dis Int 2016;15:602-611[PMID:27919849]
17 CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure(EF-CLIF);Stauber RE,Coenraad MJ,Moreau R,Jalan R,Pavesi M,Titos E,Oettl K,Angeli P,Domenicali M,Alessandria C,Gerbes A,Wendon J,Nevens F,Trebicka J,Laleman W,Saliba F,Welzel TM,Albillos A,Gustot T,Benten D,Durand F,Bernardi M,Arroyo V,Clària J,Amorósà,Ginès P,Morales-Ruiz M,Alcaraz-Quiles J.Systemic inflammation in decompensated cirrhosis:Characterization and role in acute-on-chronic liver failure.Hepatology 2016;64:1249-1264[PMID:27483394 DOI:10.1002/hep.28740]
18 Wang LK,Wang LW,Li X,Han XQ,Gong ZJ.Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure.Hepatobiliary Pancreat Dis Int 2013;12:180-188[PMID:23558073]
19 Zhong W,Qian K,Xiong J,Ma K,Wang A,Zou Y.Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κBrelated signaling.Biomed Pharmacother 2016;83:302-313[PMID:27393927 DOI:10.1016/j.biopha.2016.06.036]
20 Donnelly MC,Hayes PC,Simpson KJ.Role of inflammation and infection in the pathogenesis of human acute liver failure:Clinical implications for monitoring and therapy.World J Gastroenterol 2016;22:5958-5970[PMID:27468190 DOI:10.3748/wjg.v22.i26.5958]
21 Fischer J,Silva TE,Soares E Silva PE,Colombo BS,Silva MC,Wildner LM,Bazzo ML,Rateke EC,Frode TS,Mello SV,Rosa JS,Dantas-Correa EB,Narciso-Schiavon JL,Schiavon LL.From stable disease to acute-on-chronic liver failure:Circulating cytokines are related to prognosis in different stages of cirrhosis.Cytokine 2017;91:162-169[PMID:28082235 DOI:10.1016/j.cyto.2016.12.017]
22 Yang X,Chen Y,Zhang J,Tang T,Kong Y,Ye F,Zhang X,Liu X,Lin S.Thymosinα1 treatment reduces hepatic inflammation and inhibits hepatocyte apoptosis in rats with acute liver failure.Exp Ther Med 2018;15:3231-3238[PMID:29545840 DOI:10.3892/etm.2018.5843]
23 Liang DY,Liu LM,Ye CG,Zhao L,Yu FP,Gao DY,Wang YY,Yang ZW,Wang YY.Inhibition of UII/UTR system relieves acute inflammation of liver through preventing activation of NF-κB pathway in ALF mice.PLoS One 2013;8:e64895[PMID:23755157 DOI:10.1371/journal.pone.0064895]
24 Lee UE,Friedman SL.Mechanisms of hepatic fibrogenesis.Best Pract Res Clin Gastroenterol 2011;25:195-206[PMID:21497738 DOI:10.1016/j.bpg.2011.02.005]
25 Lunova M,Goehring C,Kuscuoglu D,Mueller K,Chen Y,Walther P,Deschemin JC,Vaulont S,Haybaeck J,Lackner C,Trautwein C,Strnad P.Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload.J Hepatol 2014;61:633-641[PMID:24816174 DOI:10.1016/j.jhep.2014.04.034]
26 McGill MR,Jaeschke H.Apoptosis or necrosis in acetaminophen-induced acute liver failure?New insights from mechanistic biomarkers.Crit Care Med 2013;41:2653-2654[PMID:24162681 DOI:10.1097/CCM.0b013e31829caf67]
27 Bourbonnais E,Raymond VA,Ethier C,Nguyen BN,El-Leil MS,Meloche S,Bilodeau M.Liver fibrosis protects mice from acute hepatocellular injury.Gastroenterology 2012;142:130-139.e4[PMID:21945831DOI:10.1053/j.gastro.2011.09.033]
28 Zhan SS,Jiang JX,Wu J,Halsted C,Friedman SL,Zern MA,Torok NJ.Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo.Hepatology2006;43:435-443[PMID:16496318 DOI:10.1002/hep.21093]
29 Dechêne A,Sowa JP,Gieseler RK,Jochum C,Bechmann LP,El Fouly A,Schlattjan M,Saner F,Baba HA,Paul A,Dries V,Odenthal M,Gerken G,Friedman SL,Canbay A.Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation.Hepatology 2010;52:1008-1016[PMID:20684020 DOI:10.1002/hep.23754]
30 He Y,Jin L,Wang J,Yan Z,Chen T,Zhao Y.Mechanisms of fibrosis in acute liver failure.Liver Int2015;35:1877-1885[PMID:25388426 DOI:10.1111/liv.12731]
31 Chalasani N,Aljadhey H,Kesterson J,Murray MD,Hall SD.Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity.Gastroenterology 2004;126:1287-1292[PMID:15131789]
32 Teschke R,Danan G.Drug-induced liver injury:Is chronic liver disease a risk factor and a clinical issue?Expert Opin Drug Metab Toxicol 2017;13:425-438[PMID:27822971 DOI:10.1080/17425255.2017.1252749]
33 Osawa Y,Hannun YA,Proia RL,Brenner DA.Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver.Hepatology 2005;42:1320-1328[PMID:16317686 DOI:10.1002/hep.20967]
34 Gkretsi V,Bowen WC,Yang Y,Wu C,Michalopoulos GK.Integrin-linked kinase is involved in matrixinduced hepatocyte differentiation.Biochem Biophys Res Commun 2007;353:638-643[PMID:17194454DOI:10.1016/j.bbrc.2006.12.091]
35 Yan C,Zhou L,Han YP.Contribution of hepatic stellate cells and matrix metalloproteinase 9 in acute liver failure.Liver Int 2008;28:959-971[PMID:18507761 DOI:10.1111/j.1478-3231.2008.01775.x]
36 Michalopoulos GK.Advances in liver regeneration.Expert Rev Gastroenterol Hepatol 2014;8:897-907[PMID:24964729 DOI:10.1586/17474124.2014.934358]
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