The study was supported by National Natural Science Foundation of China (NSFC), grant number: 30770962, 30971333, 81170421, 81470869 and Chinese High Technology “863” programme, grant number: 2006AA02A411 (Hai.Li); The CLIF
Consortium Data Management Center is supported by an unrestricted grant from Grifols

Amoros, A

Arroyo, V

Chen, L-Y

Dusheiko, G

Foster, GR

Gines, P

Hua, J

Jalan, R

Li, H

Li, S-T

Ma, X

Mookerjee, RP

Moreau, R

Pavesi, M

Qiu, D-K

Sheng, L

Xia, Q

Xie, Q

Xue, F

Zeng, B

Zhang, N-N

Scientific Reports

PubMed

AbstractThe diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p &lt; 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles.</jats:p

Hai Li

Liu-Ying Chen

Nan-nan Zhang

Shu-Ting Li

Bo Zeng

Marco Pavesi

Àlex Amorós

Rajeshwar P Mookerjee

Qian Xia

Feng Xue

Xiong Ma

Jing Hua

Li Sheng

De-kai Qiu

Qing Xie

Graham R Foster

Geoffrey Dusheiko

Richard Moreau

Pere Gines

Vicente Arroyo

Rajiv Jalan

Crossref

Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles

UCL Discovery

1  Supplementary Appendix  Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.  Hai Li, Liu-Ying Chen, Nan-nan Zhang, Shu-Ting Li, Bo Zeng, Marco Pavesi, Àlex  Navarro, Rajeshwar P Mookerjee, Qian Xia, Feng Xue, Xiong Ma, Jing Hua, Li Sheng, De-kai Qiu, Qing Xie, Graham R Foster, Geoffrey Dusheiko, Richard Moreau, Pere Gines, Vicente Arroyo, Rajiv Jalan.  2   Table of Contents  Table/Figure Title Page Supplementary Table S1 Characteristics of Patients at hospital admission. 3-5 Supplementary Table S2 Characteristics and prognosis of patients with ACLF with and without prior history of AD. 6-8 Supplementary Table S3 Clinical characteristics and mortality according to the presence/absence or type of precipitating events in patients with ACLF 9-10 Supplementary Figure S1 The CLIF-Organ Failure score system. 11 3   Supplementary Table S1. Characteristics of Patients at hospital admission.  Age(y) 50.0±11.2 Male sex 683(76.7) Cause of cirrhosis  HBValone 807(90.7) HBV+Alcohol 55(6.2) HBV+other hepatitis virus 17(1.9) HBV+schistosomiasis 11(1.2) HBV-DNA level(IU/ml)  ≤100 157(17.6) >100-2x104 435(48.9) >2x104-2x106 244(27.4) >2x106 54(6.1) Treatment with NUCs* 209(23.5) Cause of hospitalization at enrolment  Ascites 506(56.9) Hepatic Encephalopathy 103(11.8) Bacterial infections 40(4.4) GI-bleeding 237(26.5) Other cause 4(0.4) Potential precipitating events(PE) of ACLF  No PE’s 402(45.2) At least one PE 389(43.7) >1PE 99(11.1) Bacterial infection 94(10.6) 4  Gastrointestinal hemorrhage 67(7.5) Active alcoholism** 64(7.2) HBV reactivation 41(4.6) others 151(16.9) Previous decompensation  No 400(44.9) Yes 490(55.1) Site of hospitalization at enrolment  Intensive care unit 0(0.0) Ward 890(100.0) Laboratory data  Hematocrit(%) 30±7 Platelet count(x 109/L) 78±59 Serum bilirubin(mg/dL) 11.8±14.9 International normalized ratio 2.0±1.2 Alanine aminotransferase(U/L) 156±394 Aspartate aminotransferase(U/L) 139±293 γ-Glutamyltransferase(U/L) 64±79 Serum creatinine(mg/dL) 1.0±0.9 Serum sodium(mmol/L) 134±9 Leukocyte count(x109/L) 6.4±4.9 MELD score at enrolment 20.2±9.4 MELD na score at enrolment 22.6±9.3 Liver failure 268(30.1) Kidney failure 89(10.0) Cerebral failure 46(5.2) Coagulation failure 232(26.1) 5  Respiration failure 11(1.2) Circulation failure 21(2.4) No organ ailure 510(57.3) 1 organ failure 180(20.2) >1 organ failure 200(22.5) Renal dysfunction 46(5.3) Cerebral dysfunction 74(8.3) ACLF 243(27.3) GradeI 45(5.1) GradeII 132(14.8) GradeIII 66(7.4)   Data are mean±Standard Deviation or n(%) *within 6months prior to enrolment **within 3 months prior to hospitalization                    6  Supplementary Table S2. Characteristics and prognosis of patients with ACLF with and without prior history of AD.  Characteristics Any prior AD (n=143) No prior AD (n=157) p-value Age(y) 46.9±10.4 46.1±12.0 0.518 Male sex 102(71.3) 131(83.4) 0.012 Ascites 110(76.9) 119(76.3) 0.896 Cause of cirrhosis   0.243 HBV alone 120(86.3) 143(91.1)  HBV+Alcohol 13(9.4) 6(3.8)  HBV+other hepatitis virus 4(2.9) 4(2.6)  HBV+schistosomiasis 2(1.4) 4(2.6)  HBV-DNA level(IU/ml)    ≤100 27(18.9) 33(21.0) 0.899 >100-2x104 74(51.7) 83(52.9)  >2x104-2x106 35(24.5) 33(21.0)  >2x106 7(4.9) 8(5.1)  Treatment with NUCs* 46(32.2) 49(31.2) 0.859 Potential precipitating events of ACLF    Bacterial infection 31(21.7) 28(18.0) 0.418 Gastrointestinal haemorrhage 19(13.3) 4(2.6) <0.001 Active alcoholism** 14(9.8) 16(10.2) 0.908 HBV reactivation 19(13.3) 8(5.1) 0.013 others 20(14) 20(14) 1.000 No precipitating events 51(35.7) 84(53.5) 0.005 At least one precipitating event 71(49.7) 61(38.9)  7  >1 precipitating events 21(14.7) 12(7.6)  Organ failures    Liver 102(72.3) 131(84.5) 0.011 Kidney 44(31.0) 41(26.5) 0.388 Cerebral 37(25.9) 34(21.7) 0.391 Coagulation 91(64.1) 112(72.3) 0.130 Circulation 35(24.5) 22(14.0) 0.021 Lungs 21(14.7) 22(11.4) 0.868 Renal dysfunction 21(15.1) 23(15.1) 0.996 Cerebral dysfunction 28(19.6) 29(18.5) 0.807 ACLF   0.197 GradeI 25(18.1) 20(13.4)  GradeII 55(38.5 77(49.0)  GradeIII 31(22.5) 35(22.3)  Laboratory data    Leukocyte count(x109/L) 10.4±7.7 10.3±6.0 0.879 Platelet count(x109/L) 81±68 88±58.8 0.335 Serum bilirubin(mg/dL) 23.6±15.9 29.2±16.3 0.003 International normalized ratio 3.1±1.9 3.3±2.2 0.322 Alanine aminotransferase(U/L) 241±501 382±653 0.036 Aspartate aminotransferase(U/L) 240±505 266±398 0.627 γ-Glutamyltransferase(U/L) 54±54 83±122 0.007 Serum creatinine(mg/dL) 1.6±1.7 1.5±1.3 0.007 Mortality    28 days 66(46.2) 66(42.0) 0.473 90 days 74(51.8) 76(48.4) 0.563 180 days 77(53.9) 76(48.4) 0.347 8  365 days 78(54.6) 77(49.0) 0.341   Data are mean±Standard Deviation or n(%) *within 6 months prior to enrolment **within 3 months prior to hospitalization                                   9  Supplementary Table S3. Clinical characteristics and mortality according to the presence/absence or type of precipitating events in patients with ACLF  Characteristics HBV reactivation Other Precipitating event No Precipitating event but HBV DNA>500 No Precipitating event and HBV DNA ≤500 p-value  N=27 N=81 N=155 N=37  Age(y) 41.5±8.6 48.3±10.7 45.7±11.5 49.1±12.3 0.018 Male sex 21(77.8) 65(80.3) 117(75.5) 30(81.1) 0.805 Previous decompensation     0.037 No 8(29.6) 39(48.2) 87(56.1) 23(62.2)  Yes 19(70.4) 42(51.9) 68(43.9) 14(37.8)  Ascites 22(81.5) 61(75.3) 136(87.7) 29(78.4) 0.096 Mean arterial pressure(mmHg) 95±15 85±15 85±13 88.7±14.9 0.002 Organ failures      Liver 25(92.6) 51(63.0) 121(78.1) 25(67.6) 0.007 Kidney 6(22.2) 32(39.5) 41(26.5) 10(27.0) 0.147 Cerebral 4(14.8) 5(6.2) 22(14.2) 12(32.4) 0.003 Coagulation 19(70.4) 42(51.9) 90(58.1) 23(62.2) 0.360 Circulation 2(7.4) 9(11.1) 7(4.5) 1(2.7) 0.183 Lungs 1(3.7) 3(3.7) 4(2.6) 3(8.1) 0.460 Renal dysfunction 3(11.5) 13(16.9) 24(15.8) 4(11.1) 0.813 Cerebral dysfunction 9(33.3) 20(24.7) 24(15.5) 4(10.8) 0.043 Laboratory data      Hematocrit(%) 36±7 29±7 29±8 31±9 0.001 Leucocytes 10.5±5.9 10.6±6.9 8.7±4.9 10.7±5.5 0.037 Platelet count(×109/L) 86±42 91±74 86±60 86±60 0.937 Serum bilirubin(mg/dL) 28±10 23±17 27±17 20±13 0.040 International normalized ratio 3.3±1.3 2.6±1.1 2.9±1.4 3.7±3.1 0.008 Alanine aminotransferase(U/L) 508±412 223±497 336±669 272±423 0.149 Aspartate aminotransferase(U/L) 368±386 204±399 234±447 257±416 0.403 γ-Glutamyltransferase(U/L) 86±84 83±122 64±81 51±47 0.234 Serum creatinine(mg/dL) 1.6±2.8 1.5±1.2 1.3±1.3 1.6±1.4 0.561 10  Serum sodium(mmol/L) 130±7 131±8 129±7 131±7.7 0.105 ACLF grades:     0.047 ACLF-I 5(18.5) 17(21.0) 28(18.1) 5(13.5)  ACLF-II 16(59.3) 31(38.3) 86(55.5) 14(37.8)  ACLF-III 6(22.2) 33(40.7) 41(26.5) 18(48.7)  Mortality      28 days 12(44.4) 39(48.2) 56(36.1) 22(59.5) 0.047 90 days 13(48.2) 46(56.8) 69(44.5) 23(62.2) 0.134 180 days 13(48.2) 47(58.0) 71(45.8) 23(62.2) 0.158 365 days 13(48.2) 47(58.0) 73(47.1) 23(62.2) 0.225   Data are mean±Standard Deviation or n(%)  11     

Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B

The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were 'hepatic' and 'coagulation'. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles

Li, Hai

Chen, Liu-Ying

Zhang, Nan-nan

Li, Shu-Ting

Zeng, Bo

Pavesi, Marco

Amorós, Àlex

Mookerjee, Rajeshwar P.

Xia, Qian

Xue, Feng

Ma, Xiong

Hua, Jing

Qiu, De-kai

Xie, Qing

Foster, Graham R.

Dusheiko, Geoffrey

Moreau, Richard

Ginès i Gibert, Pere

Arroyo, Vicente

Jalan, Rajiv

Sheng, Li

Diposit Digital de la Universitat de Barcelona

Queen Mary Research Online

https://qmro.qmul.ac.uk/xmlui/bitstream/handle/123456789/15327/Foster%20Characteristics%2c%20Diagnosis%20and%20Prognosis%20of%20Acute-on-Chronic%20Liver%20Failure%202016%20Published.pdf?sequence=1

Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B

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UCL Discovery

Diposit Digital de la Universitat de Barcelona

Queen Mary Research Online