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Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure

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Abstract

Background

We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence.

Methods

ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted.

Results

Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I–II in 981 (74.6%) and grades III–IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III–IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients.

Conclusions

HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.

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Abbreviations

HE:

Hepatic encephalopathy

ACLF:

Acute-on-chronic liver failure

EASL:

European Association for the Study of the Liver

APASL:

Asian Pacific Association for the Study of Liver

DC:

Decompensated cirrhosis

ALF:

Acute liver failure

ICU:

Intensive Care Unit

AARC:

APASL ACLF Research Consortium

HVPG:

Hepatic venous pressure gradient

CTP:

Child-Turcotte-Pugh score

MELD:

Model for endstage liver disease

MELD-Na:

MELD-sodium

SOFA:

Sequential Organ Failure Assessment score

APACHE-II:

Acute Physiology and Chronic Health Evaluation-II

IQR:

Interquartile range

AUROC:

Area under receiver operating curve

SIRS:

Systemic inflammatory response syndrome

SHR:

Sub-distribution hazard ratio

CI:

Confidence interval

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Authors and Affiliations

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

    Nipun Verma, Sunil Taneja, Ajay Duseja & Virender Singh

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

    Radha Krishan Dhiman

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

    Ashok Choudhury & Shiv Kumar Sarin

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

    Mamun Al Mahtab

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

    Harshad Devarbhavi

  6. Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital, and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India

    Akash Shukla

  7. Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Q. Ning

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

    Saeed Sadiq Hamid, Amna Shubhan Butt & Wasim Jafri

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

    Soek Siam Tan

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

    Jinhua Hu

  11. Translational Hepatology Institute Capital Medical University, Beijing You’an Hospital, Beijing, China

    Duan Zhongping

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

    Sombat Treeprasertsuk

  13. Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore

    Guan H. Lee

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

    Hasmik Ghazinyan

  15. Digestive Disease and GI Oncology Centre, Medistra Hospital, Jakarta, Indonesia

    Laurentius A. Lesmana

  16. Department of Gastroenterology, DMC, Ludhiana, India

    Ajit Sood, Vandana Midha & Omesh Goyal

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

    Dong Joon Kim

  18. Department of Hepatology, CMC, Vellore, India

    C. E. Eapen & Ashish Goel

  19. Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, No. 83, Jintang Road, Hedong District, Tianjin, 300170, China

    Han Tao

  20. Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China

    Xin Shaojie

  21. Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China

    Nan Yuemin

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

    A. Kadir Dokmeci

  23. Department of Gastroenterology and Hepatology Sciences, IMS and SUM Hospital, Bhubaneswar, Odisha, India

    Manoj Sahu & Ayaskanta Singh

  24. Institute of Liver Gastroenterology and Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India

    Anil Arora & Ashish Kumar

  25. Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India

    Ramesh Kumar

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

    V. G. Mohan Prasad

  27. Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu, Nepal, India

    Ananta Shresta

  28. Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines

    Jose Sollano

  29. Fatima University Medical Center Manila, Manila, Philippines

    Diana Alcantara Payawal

  30. Global Hospitals, Mumbai, India

    Samir Shah

  31. Asian Institute of Gastroenterology, Hyderabad, India

    P. N. Rao & Anand Kulkarni

  32. Department of Medicine, Humanity, and Health Medical Group, Hong Kong, People’s Republic of China

    George K. Lau

Authors
  1. Nipun Verma
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  2. Radha Krishan Dhiman
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  3. Ashok Choudhury
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  4. Sunil Taneja
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  5. Ajay Duseja
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  6. Virender Singh
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  7. Mamun Al Mahtab
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  8. Harshad Devarbhavi
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  9. Akash Shukla
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  10. Q. Ning
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  11. Saeed Sadiq Hamid
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  12. Amna Shubhan Butt
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  13. Wasim Jafri
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  14. Soek Siam Tan
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  15. Jinhua Hu
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  16. Duan Zhongping
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  17. Sombat Treeprasertsuk
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  18. Guan H. Lee
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  19. Hasmik Ghazinyan
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  20. Laurentius A. Lesmana
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  21. Ajit Sood
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  22. Vandana Midha
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  23. Omesh Goyal
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  24. Dong Joon Kim
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  25. C. E. Eapen
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  26. Ashish Goel
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  27. Han Tao
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  28. Xin Shaojie
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  29. Nan Yuemin
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  30. A. Kadir Dokmeci
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  31. Manoj Sahu
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  32. Ayaskanta Singh
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  33. Anil Arora
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  34. Ashish Kumar
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  35. Ramesh Kumar
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  36. V. G. Mohan Prasad
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  37. Ananta Shresta
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  38. Jose Sollano
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  39. Diana Alcantara Payawal
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  40. Samir Shah
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  41. P. N. Rao
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  42. Anand Kulkarni
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  43. George K. Lau
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  44. Shiv Kumar Sarin
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Consortia

APASL ACLF Research Consortium (AARC) for 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.

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 center, i.e., ILBS New Delhi (vide letter no F/25/5/64/AC2013/912) and all the participating centres also had necessary approval from the respective ethical board.

Informed consent

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

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Verma, N., Dhiman, R.K., Choudhury, A. et al. Dynamic assessments of hepatic encephalopathy and ammonia levels predict mortality in acute-on-chronic liver failure. Hepatol Int 15, 970–982 (2021). https://doi.org/10.1007/s12072-021-10221-7

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  • DOI: https://doi.org/10.1007/s12072-021-10221-7

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