Skip to main content

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models

Abstract

Background and aims

Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.

Methods

A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).

Results

The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5–15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5–7; II: 8–10; and III: 11–15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).

Conclusions

The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3

Abbreviations

AARC:

APASL ACLF research consortium

ACLF:

Acute-on-chronic liver failure

HAV:

Hepatitis A virus

HCC:

Hepato-cellular carcinoma

HEV:

Hepatitis E virus

HBV:

Hepatitis B virus

SAH:

Severe alcoholic hepatitis

TJLB:

Trans-jugular liver biopsy

References

  1. 1.

    Sarin SK, Choudhury A. Acute-on-chronic liver failure: terminology, mechanisms and management. Nat Rev Gastroenterol Hepatol 2016;13(3):131–149

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, For CANONIC Study Investigators of the EASL–CLIF Consortium, et al. Acute on chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144:1426–1437

    Article  PubMed  Google Scholar 

  3. 3.

    Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, For APASL ACLF Working Party, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2014;8:453–471

    Article  PubMed  Google Scholar 

  4. 4.

    Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Ginès P, Levesque E, Durand F, For CANONIC study investigators of the EASL-CLIF Consortium, et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014;61(5):1038–1047

    Article  PubMed  Google Scholar 

  5. 5.

    Garg H, Kumar A, Garg V, Sharma P, Sharma BC, Sarin SK. Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure. Dig Liver Dis 2012;44(2):166–171

    Article  PubMed  Google Scholar 

  6. 6.

    Agrawal S, Duseja A, Gupta T, Dhiman RK, Chawla Y. Simple organ failure count versus CANONIC grading system for predicting mortality in acute-on-chronic liver failure. J Gastroenterol Hepatol 2015;30(3):575–581

    Article  PubMed  Google Scholar 

  7. 7.

    Sarin SK, Choudhury A. Acute-on-chronic liver failure. CurrGastroenterol Rep 2016;18(12):61 (Review)

    Article  Google Scholar 

  8. 8.

    Wang ZX, Yan LN, Wang WT, Xu MQ, Yang JY. Impact of pretransplant MELD score on post transplant outcome in orthotropic liver transplantation for patients with acute-on-chronic hepatitis B liver failure. Transplant Proc 2007;39:15011504

    Google Scholar 

  9. 9.

    Jalan R, Pavesi M, Saliba F, Amorós A, Fernandez J, Holland-Fischer P, For CANONIC Study Investigators; EASL-CLIF Consortium, et al. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015;62(4):831–840

    Article  PubMed  Google Scholar 

  10. 10.

    Yang WB, Chen EQ, Bi HX, Bai L, Chen XB, Feng P, Tang H. Different models in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure. Ann Hepatol 2012;11(3):311–319

    PubMed  Google Scholar 

  11. 11.

    Cordoba J, Ventura-Cots M, Simón-Talero M, Amorós À, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Ginés P, Bernardi M, Arroyo V, CANONIC Study Investigators of EASL-CLIF Consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014;60(2):275–281

    Article  PubMed  Google Scholar 

  12. 12.

    Levesque E, Winter A, Noorah Z, Daurès JP, Landais P, Feray C, Azoulay D. Impact of acute-on-chronic liver failure on 90-day mortality following a first liver transplantation. Liver Int 2017;. doi:10.1111/liv.13355

    PubMed  Google Scholar 

  13. 13.

    Jeppesen JB, Mortensen C, Bendtsen F, Møller S. Lactate metabolism in chronic liver disease. Scand J Clin Lab Invest 2013;73(4):293–299

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Cardoso NM, Silva T, Basile-Filho A, Mente ED, Castro-e-Silva O. A new formula as a predictive score of post-liver transplantation outcome: postoperative MELD-lactate. Transplant Proc 2014;46(5):1407–1412

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Huo TI, Lin HC, Wu JC, Lee FY, Hou MC, Lee PC, Chang FY, et al. Proposal of a modified Child-Turcotte-Pugh scoring system and comparison with the model for end-stage liver disease for outcome prediction in patients with cirrhosis. Liver Transplant 2006;12(1):65–71

    Article  Google Scholar 

  16. 16.

    Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015;62(1):232–242

    Article  PubMed  Google Scholar 

  17. 17.

    Moon DB, Lee SG, Kang WH, Song GW, Jung DH, Park GC, Cho HD, et al. Adult living donor liver transplantation for acute-on-chronic liver failure in high- model for end-stage liver disease score patients. Am J Transplant. 2017;17(7):1833–1842.

    Article  PubMed  Google Scholar 

  18. 18.

    Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, Laleman W, For CANONIC Study Investigators of the EASL-CLIF Consortium, et al. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 2015;62(1):243–252

    Article  PubMed  Google Scholar 

  19. 19.

    Zheng MH, Wu SJ, Shi KQ, Yan HD, Li H, Zhu GQ, Xie YY et al. Conditional survival estimate of acute-on-chronic hepatitis B liver failure: a dynamic prediction based on a multicenter cohort. Oncotarget 2015;6(27):23261–2371

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Zabor EC, Gonen M, Chapman PB, Panageas KS. Dynamic prognostication using conditional survival estimates. Cancer 2013;119:3589–3592

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Consortia

Corresponding author

Correspondence to S. K. Sarin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Approval of the institutional ethics committees was obtained.

Informed consent

Informed consent was taken from the patient or the next of kin.

Financial disclosures

None.

Electronic supplementary material

Appendix

Appendix

The study was approved by institute ethical committee vide letter no F/25/5/64/AC2013/912 and the respective centers also had their own ethical board approval for the study to be carried out. The centers, investigators and the number of patients contibuted are listed as follows:

Center no. Name Country/center Total patients
1 Dr. Shiv K Sarin ILBS, India 1286
5 Dr. Mamun-Al Mahtab Bangladesh 145
6 Dr. Yogesh Chawala Chandigarh 128
9 Dr. Tan SS Malaysia 109
3 Dr. Harshad Devarbhavi Bangalore 103
2 Dr. Zhongping Duan Beijing 98
21 Dr. Qin Ning, Jidong Jia, China 96
14 Dr. Deepak Naryan Bombay Hospital 76
4 Dr. Eapen Vellore 72
8 Dr. Saeed Hamid Karachi, Pakistan 69
22 Dr. Kim et.al.  Republic of Korea 68
13 Dr. Hasmik Armenia 50
10 Dr. Guan Huei Lee Singapore 39
7 Dr. Ajit sood Ludhiana, India 34
12 Dr. Laurentius A. Lesmana Indonesia 28
17 Dr. Zaigham Abbas Pakistan 25
23 Dr. Gamal Shiha Egypt 25
11 Dr. Diana Alcantara-Payawal Philippines 21
20 Dr. A. Kadir Dokmeci Turkey 19
16 Dr. Jose Philippines 12
24 Dr. Man-Fung Yuen Hong Kong 12
15 Dr. George K Lau China 10
18 Dr. Fazal Karim Bangladesh 6
19 Dr. P N Rao Hyderabad, India 4
Total    2535
Complete data for analysis 1402

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Choudhury, A., Jindal, A., Maiwall, R. et al. Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models. Hepatol Int 11, 461–471 (2017). https://doi.org/10.1007/s12072-017-9816-z

Download citation

Keywords

  • Cirrhosis
  • ACLF
  • AARC score
  • Organ failure
  • Liver failure