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Comparative accuracy of prognostic models for short-term mortality in acute-on-chronic liver failure patients: CAP-ACLF

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Abstract

Background

Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.

Methods

Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-R2, relative prediction errors, and odds ratios.

Results

Thirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p < 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, R2 0.609 and lower prediction errors by 10–50%. Day-7 NACSELD-ACLF-binary was the simple model (minimum AIC/BIC 12/17) with the highest odds (8.859) and sensitivity (100%) but with a lower PPV (70%) for mortality. Patients with day-7 AARC score > 12 had the lowest 30-day survival (5.7%).

Conclusions

APASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score > 12 may be used as a futility criterion in APASL-ACLF patients.

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Abbreviations

ACLF:

Acute-on-chronic liver failure

MELD:

Model for end-stage liver disease

APASL:

Asian Pacific Association for the Study of the Liver

AARC:

APASL ACLF Research Consortium

INR:

International normalized ratio

LA:

Lactate

OFs:

Organ failures

CLIF-C:

Chronic Liver Failure Consortium

NACSELD:

North American Consortium for the Study of End-Stage Liver Disease

MELD-Na:

Model for end-stage liver disease-sodium

CTP:

Child–Turcotte–Pugh

SOFA:

Sequential organ failure assessment

APACHE-II:

Acute physiology and chronic health evaluation

C-index:

Concordance index

PPV:

Positive predictive value

AIC:

Akaike information criteria

BIC:

Bayesian information criteria

OR:

Odds ratio

SD:

Standard deviation

IQR:

Interquartile range

CANONIC:

Chronic liver failure acute-on-chronic liver failure in cirrhosis

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Acknowledgements

This work was presented as an oral presentation at the 29th Asian Pacific Association for the Study of the Liver (APASL) 2020 in Bali, Indonesia.

Funding

None.

Author information

Author notes

  1. Radha Krishan Dhiman’s affiliation was Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India during the conduct of this study.

Authors and Affiliations

  1. Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Nipun Verma, Virendra Singh, Ajay Duseja & Sunil Taneja

  2. Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India

    Radha Krishan Dhiman

  3. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India

    Ashok Choudhury, Manoj Kumar Sharma & Shiv Kumar Sarin

  4. Department of Hepatology, CMC, Vellore, India

    C. E. Eapen

  5. Department of Hepatology, St John Medical College, Bangalore, India

    Harshad Devarbhavi

  6. Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

    Mamun Al Mahtab

  7. Department of Hepatology, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India

    Akash Shukla

  8. Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan

    Saeed Sadiq Hamid, Wasim Jafri & Amna Shubhan Butt

  9. Department of Medicine, Tongji Hospital, Tongji Medical College, Wuhan, China

    Qin Ning & Tao Chen

  10. Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia

    Soek Siam Tan

  11. Department of Medicine, Medistra Hospital, Jakarta, Indonesia

    Laurentius A. Lesmana & Cosmas Rinaldi A. Lesmana

  12. Department of Hepatology, IMS and SUM Hospital, Bhubaneswar, Odisha, India

    Manoj K. Sahu

  13. Department of Medicine, 302 Military Hospital, Beijing, China

    Jinhua Hu

  14. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Guan Huei Lee

  15. Department of Gastroenterology, DMC, Ludhiana, India

    Ajit Sood, Vandana Midha & Omesh Goyal

  16. Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia

    Hasmik Ghazinian

  17. Department of Internal Medicine, Hallym University College of Medicine, Seoul, Korea

    Dong Joon Kim

  18. Department of Medicine, Chulalongkorn University, Bangkok, Thailand

    Sombat Treeprasertsuk

  19. Department of Gastroenterology, VGM Hospital, Coimbatore, India

    V. G. Mohan Prasad

  20. Department of Medicine, Ankara University School of Medicine, Ankara, Turkey

    Abdul Kadir Dokmeci

  21. Department of Medicine, University of Santo Tomas, Manila, Philippines

    Jose D. Sollano

  22. Global Hospitals, Mumbai, India

    Samir Shah

  23. Department of Medicine, Cardinal Santos Medical Center, Metro Manila, Philippines

    Diana Alcantara Payawal

  24. Asian Institute of Gastroenterology, Hyderabad, India

    P. N. Rao & Anand Kulkarni

  25. Department of Medicine, Humanity, and Health Medical Group, Hong Kong, China

    George K. Lau

  26. Beijing You’anmen Hospital, Translational Hepatology Institute Capital Medical University, Beijing, China

    Zhongping Duan & Yu Chen

  27. Chiba University, Chiba, Japan

    Osamu Yokosuka

  28. Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan

    Zaigham Abbas

  29. CMOSH Medical College, Agrabad, Chittagong, Bangladesh

    Fazal Karim

  30. Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh

    Debashish Chowdhury

  31. Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu, Nepal

    Ananta Shrestha Prasad

Authors
  1. Nipun Verma
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  2. Radha Krishan Dhiman
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  3. Virendra Singh
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  4. Ajay Duseja
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  5. Sunil Taneja
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  6. Ashok Choudhury
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  7. Manoj Kumar Sharma
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  8. C. E. Eapen
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  15. Qin Ning
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  16. Tao Chen
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  17. Soek Siam Tan
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  18. Laurentius A. Lesmana
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  19. Cosmas Rinaldi A. Lesmana
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  20. Manoj K. Sahu
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  21. Jinhua Hu
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  28. Sombat Treeprasertsuk
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  29. V. G. Mohan Prasad
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  30. Abdul Kadir Dokmeci
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  31. Jose D. Sollano
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  32. Samir Shah
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  33. Diana Alcantara Payawal
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  34. P. N. Rao
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  35. Anand Kulkarni
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  36. George K. Lau
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  37. Zhongping Duan
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  38. Yu Chen
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  39. Osamu Yokosuka
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  40. Zaigham Abbas
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  41. Fazal Karim
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  42. Debashish Chowdhury
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  43. Ananta Shrestha Prasad
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  44. Shiv Kumar Sarin
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Consortia

APASL ACLF Working Party

Corresponding author

Correspondence to Radha Krishan Dhiman.

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Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants or legally acceptable representative of the participant included in the study.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki 1975, as revised in 2008. The AARC registry for ACLF was approved by the Institutional Ethical Review board at the nodal centre i.e. ILBS New Delhi (vide letter no F/25/5/64/AC2013/912) and all the participating centers also had necessary approval from respective ethical board.

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Verma, N., Dhiman, R.K., Singh, V. et al. Comparative accuracy of prognostic models for short-term mortality in acute-on-chronic liver failure patients: CAP-ACLF. Hepatol Int 15, 753–765 (2021). https://doi.org/10.1007/s12072-021-10175-w

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