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‘First week’ is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure

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Abstract

Background and aims

Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

Methods

Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.

Results

The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01).

Conclusions

ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. ‘Emergent LT’ should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.

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Abbreviations

AARC:

APASL ACLF Research Consortium (AARC).

ACLF:

Acute-on-chronic liver failure

AKI:

Acute kidney injury

CSE:

Conditional survival estimate

DDLT:

Deceased donor liver transplant

HE:

Hepatic encephalopathy

LT:

Deceased donor liver transplant

LDLT:

Living donor liver transplant

MOF:

Multi-organ failure

OF:

Organ failure

MELD:

Model for end-stage liver disease

CTP:

Child Turcot Pugh

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Funding

The project under the APASL ACLF working party with a research grant from APASL as a project to APASL ACLF Research Consortium (AARC).

Author information

Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India

    Ashok Choudhury, Rajan Vijayaraghavan, Rakhi Maiwall, Manoj Kumar, Vinod Arora & Shiv K. Sarin

  2. Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India

    Ashok Choudhury, Rajan Vijayaraghavan, Rakhi Maiwall, Manoj Kumar, Vinod Arora & Shiv K. Sarin

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

    Zhongping Duan & Chen Yu

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

    Saeed Sadiq Hamid, Wasim Jafri & Amna Subhan Butt

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

    Harshad Devarbhavi

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

    Qin Ning & Ke Ma

  7. Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia

    Soek-Siam Tan

  8. Department of Hepatology, KEM Hospital and Seth GSMC, Mumbai, India

    Akash Shukla

  9. Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Radhakrishna Dhiman, Ajay Duseja & Sunil Taneja

  10. Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India

    C. E. Eapen & Ashish Goel

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

    Sombat Treeprasertsuk

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

    Mamun Al-Mahtab

  13. Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia

    Hasmik Ghazinyan

  14. Centre for Liver and Digestive Diseases, Gangwon-Do, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea

    Dong Joon Kim

  15. Department of Gastroenterology and Biliary Sciences, IMS and SUM Hospital, Bhubaneswar, Odisha, India

    Manoj K. Sahu

  16. Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore

    Guan Huei Lee

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

    Laurentius A. Lesmana & Rinaldi Cosmas Lesmana

  18. Department of Hepatology, Global Hospital, Mumbai, India

    Samir Shah

  19. Department of Hepatogastroenterology, Ziauddin University, Karachi, Pakistan

    Zaigham Abbas

  20. Department of Hepatology, Cardinal Santos Medical Centre, Manila, Philippines

    Jose D. Sollano

  21. Asian Institute of Gastroenterology, Hyderabad, India

    P. N. Rao & Anand Kulkarni

  22. Department of Internal Medicine, Egyptian Liver Research Institute and Hospital, Cairo, Egypt

    Gamal Shiha

  23. Liver Foundation Nepal Sitapaila Height, Kathmandu, Nepal

    Ananta Shrestha

  24. Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey

    AKadir Dokmeci

  25. Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China

    Man Fung Yuen

  26. Department of Hepatology, Cardinal Santos Medical Center, Manila, Philippines

    Diana Alcantara Payawal

  27. Division of Hepatobiliary Cipto Mangunkusuamo Hospital, University of Indonesia, Jakarta, Indonesia

    Kemal Fariz Kalista

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

    V. G. Mohan Prasad

  29. Department of Gastroenterology, Humanity and Health Medical Centre, Hong Kong, China

    George K. Lau

  30. Department of Hepatology, Sir Salimullah Medical College, Dhaka, Bangladesh

    Fazal Karim

  31. Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India

    Priyanka Jain & Guresh Kumar

  32. Department of Hepatobiliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India

    Viniyendra Pamecha & Piyush Sinha

  33. Department of Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India

    Viniyendra Pamecha & Piyush Sinha

Authors
  1. Ashok Choudhury
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  2. Rajan Vijayaraghavan
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  3. Rakhi Maiwall
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  4. Manoj Kumar
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  5. Zhongping Duan
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  6. Chen Yu
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  7. Saeed Sadiq Hamid
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  8. Wasim Jafri
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  9. Amna Subhan Butt
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  10. Harshad Devarbhavi
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  11. Qin Ning
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  12. Ke Ma
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  13. Soek-Siam Tan
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  14. Akash Shukla
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  15. Radhakrishna Dhiman
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  16. Ajay Duseja
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  17. Sunil Taneja
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  18. C. E. Eapen
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  19. Ashish Goel
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  20. Sombat Treeprasertsuk
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  21. Mamun Al-Mahtab
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  22. Hasmik Ghazinyan
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  23. Dong Joon Kim
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  24. Manoj K. Sahu
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  25. Guan Huei Lee
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  26. Laurentius A. Lesmana
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  27. Rinaldi Cosmas Lesmana
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  28. Samir Shah
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  29. Zaigham Abbas
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  30. Jose D. Sollano
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  31. P. N. Rao
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  32. Anand Kulkarni
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  33. Gamal Shiha
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  34. Ananta Shrestha
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  35. AKadir Dokmeci
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  36. Man Fung Yuen
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  37. Diana Alcantara Payawal
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  38. Kemal Fariz Kalista
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  39. V. G. Mohan Prasad
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  40. George K. Lau
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  41. Fazal Karim
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  42. Priyanka Jain
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  43. Guresh Kumar
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  44. Vinod Arora
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  45. Viniyendra Pamecha
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  46. Piyush Sinha
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  47. Shiv K. Sarin
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Consortia

APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party

Contributions

AC and SKS conceptualised the research design, AC prepared the manuscript, PJ, GK done the data compiling and statistical analysis, rest of the authors contributed the data and suggested modification, SKS did the final proof reading and provided all the logistic support.

Corresponding author

Correspondence to Shiv K. Sarin.

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Conflict of interest

Ashok Choudhury, Rajan Vijayaraghavan, Rakhi Maiwall, Manoj Kumar, Zhongping Duan, Chen Yu, Saeed Sadiq Hamid, Wasim Jafri, Amna Subhan Butt, Harshad Devarbhavi, Qin Ning, Ke Ma, Soek-Siam Tan, Akash Shukla, Radhakrishna Dhiman, Ajay Duseja, Sunil Taneja, C. E. Eapen, Ashish Goel, Sombat Treeprasertsuk, Mamun Al-Mahtab, Hasmik Ghazinyan, Dong Joon Kim, Manoj K. Sahu, Guan Huei Lee, Laurentius A. Lesmana, Rinaldi Cosmas Lesmana, Samir Shah, Zaigham Abbas, Jose D. Sollano, P. N. Rao, Anand Kulkarni, Gamal Shiha, Ananta Shrestha, A. Kadir Dokmeci, Man Fung Yuen, Diana Alcantara Payawal, Kemal Fariz Kalista, V. G. Mohan Prasad, George K. Lau, Fazal Karim, Priyanka Jain, Guresh Kumar, Vinod Arora, Viniyendra Pamecha, Piyush Sinha, Shiv K. Sarin declare no conflicts of interest.

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Supplementary Information

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12072_2021_10206_MOESM1_ESM.tiff

Supplementary file1Supple Fig -1: Cumulative Mortality and Dynamicity in absence of a transplant. A) MELD Na based B) Liver Failure based (TIFF 1521 kb)

12072_2021_10206_MOESM2_ESM.tiff

Supplementary file2Suppl Figure-2: Implication of various organ failures on 90 days outcome HR by Cox regression (TIFF 1521 kb)

Supplementary file3 (DOCX 50 kb)

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Choudhury, A., Vijayaraghavan, R., Maiwall, R. et al. ‘First week’ is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure. Hepatol Int 15, 1376–1388 (2021). https://doi.org/10.1007/s12072-021-10206-6

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