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Acute variceal bleeding portends poor outcomes in patients with acute-on-chronic liver failure: a propensity score matched study from the APASL ACLF Research Consortium (AARC)

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Abstract

Background and aims

Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC).

Methods

Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB).

Results

Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age—46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27–40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age—44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24–40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00–28.00] vs. 17.00 [15.00–21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03–9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2–2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1–2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort.

Conclusion

Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF.

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Abbreviations

ACLF:

Acute on chronic liver failure

APASL:

Asia Pacific association for study of liver diseases

AVB:

Acute variceal bleeding

AARC:

APASL ACLF Research Consortium

HVPG:

Hepatic venous pressure gradient

MELD:

Model for end stage liver disease

PSM:

Propensity score matching

SOFA:

Sequential organ failure assessment

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Acknowledgements

APASL ACLF working Party Collaborators Detail: Shiv Kumar Sarin, Ashok Choudhury, Manoj K. Sharma, Rakhi Maiwall, Mamun Al Mahtab, Salimur Rahman, Sanjiv Saigal, Neeraj Saraf, A. S. Soin, Harshad Devarbhavi, Dong Joon Kim, R. K. Dhiman, Ajay Duseja, Sunil Taneja, C. E. Eapen, Ashish Goel, Q. Ning, Tao Chen, Ke Ma, Z. Duan, Chen Yu, Sombat Treeprasertsuk, S. S. Hamid, Amna S. Butt, Wasim Jafri, Akash Shukla, Vivek Saraswat, Soek Siam Tan, Ajit Sood, Vandana Midha, Omesh Goyal, Hasmik Ghazinyan, Anil Arora, Jinhua Hu, Manoj Sahu, P. N. Rao, Guan H. Lee, Seng G. Lim, Laurentius A. Lesmana, Cosmas Rinaldi Lesmana, Samir Shah, V. G. Mohan Prasad, Diana A. Payawal, Zaigham Abbas, A. Kadir Dokmeci, Jose D. Sollano, Gian Carpio, Ananta Shresta, G. K. Lau, Md. Fazal Karim, Gamal Shiha, Rino Gani, Kemal Fariz Fariz Kalista, Man-Fung Yuen, Seema Alam, Rajeev Khanna, Vikrant Sood, Bikrant Bihari Lal, Viniyendra Pamecha, Ankur Jindal, V. Rajan, Vinod Arora, Osamu Yokosuka, Madunil A. Niriella, Hai Li, Xiaolong Qi, Atsushi Tanaka, Satoshi Mochida, Dominic Ray Chaudhuri, Ed Gane, Khin Maung Win, Wei Ting Chen, Mohd Rela, Dharmesh Kapoor, Amit Rastogi, Pratibha Kale, Archana Rastogi, Chhagan Bihari Sharma, Meenu Bajpai, Virender Singh, Madhumita Premkumar, Sudhir Sudhir, A. Olithselvan, Cyriac Abby Philips, Anshu Srivastava, Surender K. Yachha, Zeeshan Ahmad Wani, B. R. Thapa, Anoop Saraya, Shalimar, Ashish Kumar, Manav Wadhawan, Subash Gupta, Kaushal Madan, Puja Sakhuja, Vivek Vij, Barjesh C. Sharma, Hitendra Garg, Vishal Garg, Chetan Kalal, Lovkesh Anand, Tanmay Vyas, Rajan P. Mathur, Guresh Kumar, Priyanka Jain, Samba Siva Rao Pasupuleti, Yogesh K. Chawla, Abhijit Chowdhury, Shahinul Alam, Do Seon Song, Jin Mo Yang.

Funding

Authors have nothing to declare for any funding.

Author information

Author notes

  1. Sanchit Sharma and Samagra Agarwal have equal contribution.

  2. Anoop Saraya and Shiv Kumar Sarin equal senior authors.

Authors and Affiliations

  1. Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110029, India

    Sanchit Sharma, Samagra Agarwal & Anoop Saraya

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

    Ashok Choudhury & Shiv Kumar Sarin

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

    Mamun Al Mahtab & Mohd. Shahinul Alam

  4. Department of Hepatology, Medanta The Medicity, Gurgaon, India

    Sanjiv Saigal

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

    Dong Joon Kim

  6. Department of Hepatology, Christan Medical College, Vellore, India

    C. E. Eapen & Ashish Goel

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

    Qin Ning

  8. Department of Hepatology, St Johns Medical College, Bangalore, India

    Harshad Devarbhavi

  9. 9Department of Hepatology, PGIMER, Chandigarh, India

    Virendra Singh

  10. LTMMC, Mumbai, India

    Akash Shukla

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

    Saeed Hamid

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

    Jinhua Hu

  13. Department of Medicine, Hospital Selayang, Bata Cabs, Selangor, Malaysia

    Soek-Siam Tan

  14. Department of Gastroenterology, Sir Ganga Ram Hospital and GRIPMER, Delhi, India

    Anil Arora

  15. Department of Hepatology, IMS and SUM Hospital, Bhubaneshwar, Odisha, India

    Manoj Kumar Sahu

  16. Department of Liver Transplant Surgery, Dr. Rela Institute and Medical Centre, Chennai, India

    Mohd. Rela & Dinesh Jothimani

  17. Asian Institute of Gastroenterology, Hyderabad, India

    P. N. Rao & Anand Kulkarni

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

    Hashmik Ghaznian

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

    Guan Huei Lee

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

    Duan Zhongping

  21. Department of Gastroenterology, Dayanand Medical College, Ludhiana, India

    Ajit Sood & Omesh Goyal

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

    Laurentius A. Lesmana & Rinaldi C. Lesmana

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

    Sombat Treeprasertsuk

  24. Hebei Medical University, Shijiazhuang, China

    Nan Yuemin

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

    Samir Shah

  26. Tianjin Institute of Hepatobiliary Disease, Tianjin, China

    Han Tao

  27. IGIMS, Patna, India

    V. M. Dayal

  28. Medical School of Chinese PLA, Beijing, China

    Xin Shaojie

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

    Fazal Karim

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

    Zaigham Abbas

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

    Jose D. Sollano

  32. Division of Hepetobiliary, Cipto Mangunkusuamo Hospital, University of Indonesia, Jakarta, Indonesia

    Kemal Fariz Kalista

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

    Ananta Shreshtha

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

    Diana Payawal

  35. Department of Hepatology, Yamanashi Central and Kita Hospitals, University of Tokyo, Tokyo, Japan

    Masao Omata

Authors
  1. Sanchit Sharma
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  2. Samagra Agarwal
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  3. Anoop Saraya
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  4. Ashok Choudhury
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  7. Sanjiv Saigal
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  8. Dong Joon Kim
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  44. Shiv Kumar Sarin
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Consortia

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

  • Shiv Kumar Sarin
  • , Ashok Choudhury
  • , Manoj K. Sharma
  • , Rakhi Maiwall
  • , Mamun Al Mahtab
  • , Salimur Rahman
  • , Sanjiv Saigal
  • , Neeraj Saraf
  • , A. S. Soin
  • , Harshad Devarbhavi
  • , Dong Joon Kim
  • , R. K. Dhiman
  • , Ajay Duseja
  • , Sunil Taneja
  • , C. E. Eapen
  • , Ashish Goel
  • , Q. Ning
  • , Tao Chen
  • , Ke Ma
  • , Z. Duan
  • , Chen Yu
  • , Sombat Treeprasertsuk
  • , S. S. Hamid
  • , Amna S. Butt
  • , Wasim Jafri
  • , Akash Shukla
  • , Vivek Saraswat
  • , Soek Siam Tan
  • , Ajit Sood
  • , Vandana Midha
  • , Omesh Goyal
  • , Hasmik Ghazinyan
  • , Anil Arora
  • , Jinhua Hu
  • , Manoj Sahu
  • , P. N. Rao
  • , Guan H. Lee
  • , Seng G. Lim
  • , Laurentius A. Lesmana
  • , Cosmas Rinaldi Lesmana
  • , Samir Shah
  • , V. G. Mohan Prasad
  • , Diana A. Payawal
  • , Zaigham Abbas
  • , A. Kadir Dokmeci
  • , Jose D. Sollano
  • , Gian Carpio
  • , Ananta Shresta
  • , G. K. Lau
  • , Md.Fazal Karim
  • , Gamal Shiha
  • , Rino Gani
  • , Kemal Fariz Fariz Kalista
  • , Man-Fung Yuen
  • , Seema Alam
  • , Rajeev Khanna
  • , Vikrant Sood
  • , Bikrant Bihari Lal
  • , Viniyendra Pamecha
  • , Ankur Jindal
  • , V. Rajan
  • , Vinod Arora
  • , Osamu Yokosuka
  • , Madunil A. Niriella
  • , Hai Li
  • , Xiaolong Qi
  • , Atsushi Tanaka
  • , Satoshi Mochida
  • , Dominic Ray Chaudhuri
  • , Ed Gane
  • , Khin Maung Win
  • , Wei Ting Chen
  • , Mohd Rela
  • , Dharmesh Kapoor
  • , Amit Rastogi
  • , Pratibha Kale
  • , Archana Rastogi
  • , Chhagan Bihari Sharma
  • , Meenu Bajpai
  • , Virender Singh
  • , Madhumita Premkumar
  • , Sudhir Sudhir
  • , A. Olithselvan
  • , Cyriac Abby Philips
  • , Anshu Srivastava
  • , Surender K. Yachha
  • , Zeeshan Ahmad Wani
  • , B. R. Thapa
  • , Anoop Saraya
  • ,  Shalimar
  • , Ashish Kumar
  • , Manav Wadhawan
  • , Subash Gupta
  • , Kaushal Madan
  • , Puja Sakhuja
  • , Vivek Vij
  • , Barjesh C. Sharma
  • , Hitendra Garg
  • , Vishal Garg
  • , Chetan Kalal
  • , Lovkesh Anand
  • , Tanmay Vyas
  • , Rajan P. Mathur
  • , Guresh Kumar
  • , Priyanka Jain
  • , Samba Siva Rao Pasupuleti
  • , Yogesh K. Chawla
  • , Abhijit Chowdhury
  • , Shahinul Alam
  • , Do Seon Song
  •  & Jin Mo Yang

Contributions

SS: conceptualisation, writing of original draft and revision. SA: conceptualisation, statistical analysis, revision of draft. AS: study design, conceptualisation and visualisation, study overview and critical revision of draft. AC: data collection and critical revision of the draft. MAM: data collection. MSA: data collection. SS: data collection. DJK: data collection. CEE: data collection. AG: data collection. QN team: data collection. HD: data collection. VS: data collection. AS: data collection. SH: Data collection. JH: data collection. S-ST: data collection. AA: data collection. MKS: data collection. MR: data collection. DJ: data collection. PNR: data collection. AK: data collection. HG: data collection. Guan Huei Lee: data collection. DZ: data collection. AS: data collection. OG: data collection. LAL: data collection. RCL: data collection. ST: data collection. NY: data collection. SS: data collection. HT: data collection. VMD: data collection. XS: data collection. FK: data collection. ZA: data collection. JDS: data collection. KFK: data collection. AS: data collection. DP: data collection. MO: data collection. SKS: study design, conceptualisation and visualisation, study overview and critical revision of draft.

Corresponding authors

Correspondence to Anoop Saraya or Shiv Kumar Sarin.

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Conflict of interest

Sanchit Sharma, Samagra Agarwal, Anoop Saraya, Ashok Choudhury, Mamun Al Mahtab, Mohd. Shahinul Alam, Sanjiv Saigal, Dong Joon Kim, C. E. Eapen, Ashish Goel, Qin Ning, Harshad Devarbhavi, Virendra Singh, Akash Shukla, Saeed Hamid, Jinhua Hu, Soek-Siam Tan, Anil Arora, Manoj Kumar Sahu, Mohd. Rela, Dinesh Jothimani, P. N. Rao, Anand Kulkarni, Hashmik Ghaznian, Guan Huei Lee, Duan Zhongping, Ajit Sood, Omesh Goyal, Laurentius A. Lesmana, Rinaldi C. Lesmana, Sombat Treeprasertsuk, Nan Yuemin, Samir Shah, Han Tao, V. M. Dayal, Xin Shaojie, Fazal Karim, Zaigham Abbas, Jose D. Sollano, Kemal Fariz Kalista, Ananta Shreshtha, Diana Payawal, Masao Omata, Shiv Kumar Sarin declare no competing interests.

Competing interests

None of the authors had any competing interests.

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None.

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None.

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None.

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Waived off.

Guarantor of the article

Shiv Kumar Sarin and Anoop Saraya.

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The members of the APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party are listed in Acknowledgements.

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Sharma, S., Agarwal, S., Saraya, A. et al. Acute variceal bleeding portends poor outcomes in patients with acute-on-chronic liver failure: a propensity score matched study from the APASL ACLF Research Consortium (AARC). Hepatol Int 16, 1234–1243 (2022). https://doi.org/10.1007/s12072-022-10372-1

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  • DOI: https://doi.org/10.1007/s12072-022-10372-1

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