Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection
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摘要
BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.
BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.
BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.
引文
1 Zhang S,Wang F,Zhang Z.Current advances in the elimination of hepatitis B in China by 2030.Front Med 2017;11:490-501[PMID:29170919 DOI:10.1007/s11684-017-0598-4]
2 European Association for the Study of the Liver.Electronic address:easloffice@easloffice.eu.;European Association for the Study of the Liver.EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.J Hepatol 2017;67:370-398[PMID:28427875 DOI:10.1016/j.jhep.2017.03.021]
3 Chang ML,Liaw YF.Hepatitis B flares in chronic hepatitis B:Pathogenesis,natural course,and management.J Hepatol 2014;61:1407-1417[PMID:25178562 DOI:10.1016/j.jhep.2014.08.033]
4 Hoofnagle JH.Reactivation of hepatitis B.Hepatology 2009;49:S156-S165[PMID:19399803 DOI:10.1002/hep.22945]
5 Kumar M,Chauhan R,Gupta N,Hissar S,Sakhuja P,Sarin SK.Spontaneous increases in alanine aminotransferase levels in asymptomatic chronic hepatitis B virus-infected patients.Gastroenterology2009;136:1272-1280[PMID:19208347 DOI:10.1053/j.gastro.2009.01.011]
6 Wong VW,Chan HL.Severe acute exacerbation of chronic hepatitis B:A unique presentation of a common disease.J Gastroenterol Hepatol 2009;24:1179-1186[PMID:19682192 DOI:10.1111/j.1440-1746.2009.05924.x]
7 Tsai WL,Sun WC,Cheng JS.Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation.Int JMol Sci 2015;16:28126-28145[PMID:26703566 DOI:10.3390/ijms161226087]
8 Liaw YF,Tai DI,Chu CM,Pao CC,Chen TJ.Acute exacerbation in chronic type B hepatitis:Comparison between HBe Ag and antibody-positive patients.Hepatology 1987;7:20-23[PMID:2433203 DOI:10.1002/hep.1840070106]
9 Liaw YF,Chen JJ,Chen TJ.Acute exacerbation in patients with liver cirrhosis:A clinicopathological study.Liver 1990;10:177-184[PMID:1696678 DOI:10.1111/j.1600-0676.1990.tb00455.x]
10 Fattovich G,Brollo L,Alberti A,Realdi G,Pontisso P,Giustina G,Ruol A.Spontaneous reactivation of hepatitis B virus infection in patients with chronic type B hepatitis.Liver 1990;10:141-146[PMID:2385155 DOI:10.1111/j.1600-0676.1990.tb00449.x]
11 Moreau R,Jalan R,Gines P,Pavesi M,Angeli P,Cordoba J,Durand F,Gustot T,Saliba F,Domenicali M,Gerbes A,Wendon J,Alessandria C,Laleman W,Zeuzem S,Trebicka J,Bernardi M,Arroyo V;CANONIC Study Investigators of the EASL-CLIF Consortium.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology 2013;144:1426-1437,1437.e1-1437.e9[PMID:23474284 DOI:10.1053/j.gastro.2013.02.042]
12 Sarin SK,Kedarisetty CK,Abbas Z,Amarapurkar D,Bihari C,Chan AC,Chawla YK,Dokmeci AK,Garg H,Ghazinyan H,Hamid S,Kim DJ,Komolmit P,Lata S,Lee GH,Lesmana LA,Mahtab M,Maiwall R,Moreau R,Ning Q,Pamecha V,Payawal DA,Rastogi A,Rahman S,Rela M,Saraya A,Samuel D,Saraswat V,Shah S,Shiha G,Sharma BC,Sharma MK,Sharma K,Butt AS,Tan SS,Vashishtha C,Wani ZA,Yuen MF,Yokosuka O;APASL ACLF Working Party.Acute-on-chronic liver failure:Consensus recommendations of the Asian Pacific Association for the Study of the Liver(APASL)2014.Hepatol Int2014;8:453-471[PMID:26202751 DOI:10.1007/s12072-014-9580-2]
13 Wu T,Li J,Shao L,Xin J,Jiang L,Zhou Q,Shi D,Jiang J,Sun S,Jin L,Ye P,Yang L,Lu Y,Li T,Huang J,Xu X,Chen J,Hao S,Chen Y,Xin S,Gao Z,Duan Z,Han T,Wang Y,Gan J,Feng T,Pan C,Chen Y,Li H,Huang Y,Xie Q,Lin S,Li L,Li J;Chinese Group on the Study of Severe Hepatitis B(COSSH).Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-onchronic liver failure.Gut 2018;67:2181-2191[PMID:28928275 DOI:10.1136/gutjnl-2017-314641]
14 Gustot T,Moreau R.Acute-on-chronic liver failure vs.traditional acute decompensation of cirrhosis.JHepatol 2018;69:1384-1393[PMID:30195459 DOI:10.1016/j.jhep.2018.08.024]
15 Nakayama N,Uemura H,Uchida Y,Tomiya T,Ido A,Inoue K,Genda T,Takikawa Y,Sakaida I,Terai S,Yokosuka O,Shimizu M,Takikawa H,Mochida S.A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan.Hepatol Res 2018;48:303-312[PMID:29341357 DOI:10.1111/hepr.13064]
16 Chen EQ,Zeng F,Zhou LY,Tang H.Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure.World J Gastroenterol 2015;21:11964-11973[PMID:26576085 DOI:10.3748/wjg.v21.i42.11964]
17 Hsu YC,Wu CY,Chang CY,Tai CM,Tseng CH,Perng DS,Mo LR,Lin JT.Pretreatment viral DNAstratifies mortality risk in patients receiving antiviral therapy for severe acute exacerbation of chronic hepatitis B.Antivir Ther 2013;18:221-228[PMID:23128388 DOI:10.3851/IMP2435]
18 Tsang SW,Chan HL,Leung NW,Chau TN,Lai ST,Chan FK,Sung JJ.Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection.Aliment Pharmacol Ther 2001;15:1737-1744[PMID:11683687 DOI:10.1046/j.1365-2036.2001.01107.x]
19 Ren Y,Liu L,Li Y,Yang F,He Y,Zhu Y,Hu X,Lin S.Development and validation of a scoring system to predict progression to acute-on-chronic liver failure in patients with acute exacerbation of chronic hepatitis B.Hepatol Res 2018;48:692-700[PMID:29336092 DOI:10.1111/hepr.13062]
20 Tsubota A,Arase Y,Suzuki Y,Suzuki F,Sezaki H,Hosaka T,Akuta N,Someya T,Kobayashi M,Saitoh S,Ikeda K,Kumada H.Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B.J Gastroenterol Hepatol 2005;20:426-432[PMID:15740488 DOI:10.1111/j.1440-1746.2004.03534.x]
21 Wong VW,Wong GL,Yiu KK,Chim AM,Chu SH,Chan HY,Sung JJ,Chan HL.Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B.J Hepatol 2011;54:236-242[PMID:21030105 DOI:10.1016/j.jhep.2010.06.043]
22 European Association for the Study of the Liver.Electronic address:easloffice@easloffice.eu.;European Association for the Study of the Liver.EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.J Hepatol 2018;69:406-460[PMID:29653741 DOI:10.1016/j.jhep.2018.03.024]
23 Mochida S,Nakayama N,Ido A,Inoue K,Genda T,Takikawa Y,Sakaida I,Terai S,Yokosuka O,Shimizu M,Takikawa H.Proposed diagnostic criteria for acute-on-chronic liver failure in Japan.Hepatol Res 2018;48:219-224[PMID:29361652 DOI:10.1111/hepr.13066]
24 Shi Y,Yang Y,Hu Y,Wu W,Yang Q,Zheng M,Zhang S,Xu Z,Wu Y,Yan H,Chen Z.Acute-onchronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults.Hepatology 2015;62:232-242[PMID:25800029 DOI:10.1002/hep.27795]
25 Fukui H,Saito H,Ueno Y,Uto H,Obara K,Sakaida I,Shibuya A,Seike M,Nagoshi S,Segawa M,Tsubouchi H,Moriwaki H,Kato A,Hashimoto E,Michitaka K,Murawaki T,Sugano K,Watanabe M,Shimosegawa T.Evidence-based clinical practice guidelines for liver cirrhosis 2015.J Gastroenterol2016;51:629-650[PMID:27246107 DOI:10.1007/s00535-016-1216-y]
26 Clària J,Stauber RE,Coenraad MJ,Moreau R,Jalan R,Pavesi M,Amorósà,Titos E,Alcaraz-Quiles J,Oettl K,Morales-Ruiz M,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,Ginès P,Bernardi M,Arroyo V,Arroyo V.CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure(EF-CLIF).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]
27 Zhang Q,Han T,Li Y,Nie C,Liu H.Predictors of progression into acute-on-chronic liver failure from acute deterioration of pre-existing chronic liver disease.Hepatol Res 2016;46:320-328[PMID:26234788DOI:10.1111/hepr.12567]
28 Gao FY,Liu Y,Li XS,Ye XQ,Sun L,Geng MF,Wang R,Liu HM,Zhou XB,Gu LL,Liu YM,Wan G,Wang XB.Score model for predicting acute-on-chronic liver failure risk in chronic hepatitis B.World JGastroenterol 2015;21:8373-8381[PMID:26217089 DOI:10.3748/wjg.v21.i27.8373]
29 Yuen MF,Sablon E,Hui CK,Li TM,Yuan HJ,Wong DK,Doutreloigne J,Bogaerts V,Wong BC,Fan ST,Lai CL.Prognostic factors in severe exacerbation of chronic hepatitis B.Clin Infect Dis 2003;36:979-984[PMID:12684909 DOI:10.1086/374226]
30 Terrault NA,Lok ASF,Mc Mahon BJ,Chang KM,Hwang JP,Jonas MM,Brown RS,Bzowej NH,Wong JB.Update on prevention,diagnosis,and treatment of chronic hepatitis B:AASLD 2018 hepatitis Bguidance.Hepatology 2018;67:1560-1599[PMID:29405329 DOI:10.1002/hep.29800]
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37 Singal AK,Kamath PS.Model for End-stage Liver Disease.J Clin Exp Hepatol 2013;3:50-60[PMID:25755471 DOI:10.1016/j.jceh.2012.11.002]
38 Lee TY,Chen CY,Lia HC,Hsu YC,Yang SS.The ultra-short virological dynamics in response to entecavir or lamivudine during chronic hepatitis B with spontaneous severe acute exacerbation.Antivir Ther 2018;23:77-85[PMID:28671553 DOI:10.3851/IMP3183]
2 European Association for the Study of the Liver.Electronic address:easloffice@easloffice.eu.;European Association for the Study of the Liver.EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.J Hepatol 2017;67:370-398[PMID:28427875 DOI:10.1016/j.jhep.2017.03.021]
3 Chang ML,Liaw YF.Hepatitis B flares in chronic hepatitis B:Pathogenesis,natural course,and management.J Hepatol 2014;61:1407-1417[PMID:25178562 DOI:10.1016/j.jhep.2014.08.033]
4 Hoofnagle JH.Reactivation of hepatitis B.Hepatology 2009;49:S156-S165[PMID:19399803 DOI:10.1002/hep.22945]
5 Kumar M,Chauhan R,Gupta N,Hissar S,Sakhuja P,Sarin SK.Spontaneous increases in alanine aminotransferase levels in asymptomatic chronic hepatitis B virus-infected patients.Gastroenterology2009;136:1272-1280[PMID:19208347 DOI:10.1053/j.gastro.2009.01.011]
6 Wong VW,Chan HL.Severe acute exacerbation of chronic hepatitis B:A unique presentation of a common disease.J Gastroenterol Hepatol 2009;24:1179-1186[PMID:19682192 DOI:10.1111/j.1440-1746.2009.05924.x]
7 Tsai WL,Sun WC,Cheng JS.Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation.Int JMol Sci 2015;16:28126-28145[PMID:26703566 DOI:10.3390/ijms161226087]
8 Liaw YF,Tai DI,Chu CM,Pao CC,Chen TJ.Acute exacerbation in chronic type B hepatitis:Comparison between HBe Ag and antibody-positive patients.Hepatology 1987;7:20-23[PMID:2433203 DOI:10.1002/hep.1840070106]
9 Liaw YF,Chen JJ,Chen TJ.Acute exacerbation in patients with liver cirrhosis:A clinicopathological study.Liver 1990;10:177-184[PMID:1696678 DOI:10.1111/j.1600-0676.1990.tb00455.x]
10 Fattovich G,Brollo L,Alberti A,Realdi G,Pontisso P,Giustina G,Ruol A.Spontaneous reactivation of hepatitis B virus infection in patients with chronic type B hepatitis.Liver 1990;10:141-146[PMID:2385155 DOI:10.1111/j.1600-0676.1990.tb00449.x]
11 Moreau R,Jalan R,Gines P,Pavesi M,Angeli P,Cordoba J,Durand F,Gustot T,Saliba F,Domenicali M,Gerbes A,Wendon J,Alessandria C,Laleman W,Zeuzem S,Trebicka J,Bernardi M,Arroyo V;CANONIC Study Investigators of the EASL-CLIF Consortium.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology 2013;144:1426-1437,1437.e1-1437.e9[PMID:23474284 DOI:10.1053/j.gastro.2013.02.042]
12 Sarin SK,Kedarisetty CK,Abbas Z,Amarapurkar D,Bihari C,Chan AC,Chawla YK,Dokmeci AK,Garg H,Ghazinyan H,Hamid S,Kim DJ,Komolmit P,Lata S,Lee GH,Lesmana LA,Mahtab M,Maiwall R,Moreau R,Ning Q,Pamecha V,Payawal DA,Rastogi A,Rahman S,Rela M,Saraya A,Samuel D,Saraswat V,Shah S,Shiha G,Sharma BC,Sharma MK,Sharma K,Butt AS,Tan SS,Vashishtha C,Wani ZA,Yuen MF,Yokosuka O;APASL ACLF Working Party.Acute-on-chronic liver failure:Consensus recommendations of the Asian Pacific Association for the Study of the Liver(APASL)2014.Hepatol Int2014;8:453-471[PMID:26202751 DOI:10.1007/s12072-014-9580-2]
13 Wu T,Li J,Shao L,Xin J,Jiang L,Zhou Q,Shi D,Jiang J,Sun S,Jin L,Ye P,Yang L,Lu Y,Li T,Huang J,Xu X,Chen J,Hao S,Chen Y,Xin S,Gao Z,Duan Z,Han T,Wang Y,Gan J,Feng T,Pan C,Chen Y,Li H,Huang Y,Xie Q,Lin S,Li L,Li J;Chinese Group on the Study of Severe Hepatitis B(COSSH).Development of diagnostic criteria and a prognostic score for hepatitis B virus-related acute-onchronic liver failure.Gut 2018;67:2181-2191[PMID:28928275 DOI:10.1136/gutjnl-2017-314641]
14 Gustot T,Moreau R.Acute-on-chronic liver failure vs.traditional acute decompensation of cirrhosis.JHepatol 2018;69:1384-1393[PMID:30195459 DOI:10.1016/j.jhep.2018.08.024]
15 Nakayama N,Uemura H,Uchida Y,Tomiya T,Ido A,Inoue K,Genda T,Takikawa Y,Sakaida I,Terai S,Yokosuka O,Shimizu M,Takikawa H,Mochida S.A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan.Hepatol Res 2018;48:303-312[PMID:29341357 DOI:10.1111/hepr.13064]
16 Chen EQ,Zeng F,Zhou LY,Tang H.Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure.World J Gastroenterol 2015;21:11964-11973[PMID:26576085 DOI:10.3748/wjg.v21.i42.11964]
17 Hsu YC,Wu CY,Chang CY,Tai CM,Tseng CH,Perng DS,Mo LR,Lin JT.Pretreatment viral DNAstratifies mortality risk in patients receiving antiviral therapy for severe acute exacerbation of chronic hepatitis B.Antivir Ther 2013;18:221-228[PMID:23128388 DOI:10.3851/IMP2435]
18 Tsang SW,Chan HL,Leung NW,Chau TN,Lai ST,Chan FK,Sung JJ.Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection.Aliment Pharmacol Ther 2001;15:1737-1744[PMID:11683687 DOI:10.1046/j.1365-2036.2001.01107.x]
19 Ren Y,Liu L,Li Y,Yang F,He Y,Zhu Y,Hu X,Lin S.Development and validation of a scoring system to predict progression to acute-on-chronic liver failure in patients with acute exacerbation of chronic hepatitis B.Hepatol Res 2018;48:692-700[PMID:29336092 DOI:10.1111/hepr.13062]
20 Tsubota A,Arase Y,Suzuki Y,Suzuki F,Sezaki H,Hosaka T,Akuta N,Someya T,Kobayashi M,Saitoh S,Ikeda K,Kumada H.Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B.J Gastroenterol Hepatol 2005;20:426-432[PMID:15740488 DOI:10.1111/j.1440-1746.2004.03534.x]
21 Wong VW,Wong GL,Yiu KK,Chim AM,Chu SH,Chan HY,Sung JJ,Chan HL.Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B.J Hepatol 2011;54:236-242[PMID:21030105 DOI:10.1016/j.jhep.2010.06.043]
22 European Association for the Study of the Liver.Electronic address:easloffice@easloffice.eu.;European Association for the Study of the Liver.EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.J Hepatol 2018;69:406-460[PMID:29653741 DOI:10.1016/j.jhep.2018.03.024]
23 Mochida S,Nakayama N,Ido A,Inoue K,Genda T,Takikawa Y,Sakaida I,Terai S,Yokosuka O,Shimizu M,Takikawa H.Proposed diagnostic criteria for acute-on-chronic liver failure in Japan.Hepatol Res 2018;48:219-224[PMID:29361652 DOI:10.1111/hepr.13066]
24 Shi Y,Yang Y,Hu Y,Wu W,Yang Q,Zheng M,Zhang S,Xu Z,Wu Y,Yan H,Chen Z.Acute-onchronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults.Hepatology 2015;62:232-242[PMID:25800029 DOI:10.1002/hep.27795]
25 Fukui H,Saito H,Ueno Y,Uto H,Obara K,Sakaida I,Shibuya A,Seike M,Nagoshi S,Segawa M,Tsubouchi H,Moriwaki H,Kato A,Hashimoto E,Michitaka K,Murawaki T,Sugano K,Watanabe M,Shimosegawa T.Evidence-based clinical practice guidelines for liver cirrhosis 2015.J Gastroenterol2016;51:629-650[PMID:27246107 DOI:10.1007/s00535-016-1216-y]
26 Clària J,Stauber RE,Coenraad MJ,Moreau R,Jalan R,Pavesi M,Amorósà,Titos E,Alcaraz-Quiles J,Oettl K,Morales-Ruiz M,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,Ginès P,Bernardi M,Arroyo V,Arroyo V.CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure(EF-CLIF).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]
27 Zhang Q,Han T,Li Y,Nie C,Liu H.Predictors of progression into acute-on-chronic liver failure from acute deterioration of pre-existing chronic liver disease.Hepatol Res 2016;46:320-328[PMID:26234788DOI:10.1111/hepr.12567]
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