Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure
Authors: Thanapirom Kessarin , Teerasarntipan Tongluk , Treeprasertsuk Sombat , Choudhury Ashok , Sahu Manoj K. , Maiwall Rakhi , Pamecha Viniyendra , Moreau Richard , Al Mahtab Mamun , Chawla Yogesh Kumar , Devarbhavi Harshad , Yu Chen , Ning Qin , Amarapurkar Deepak , Eapen Chundamannil E. , Hamid Saeed Sadiq , Butt Amna Subhan , Kim Dong Joon , Lee Guan H. , Sood Ajit , Lesmana Laurentious A. , Abbas Zaigham , Shiha Gamal , Payawal Diana A. , Yuen Man-Fung , Chan Albert , Lau George , Jia Jidong , Rahman Salimur , Sharma Barjesh C. , Yokosuka Osamu , Sarin Shiv Kumar ,   The APASL ACLF Working Party, Sarin Shiv Kumar , Choudhury Ashok , Sharma Manoj K. , Maiwall Rakhi , Mahtab Mamun Al , Rahman Salimur , Saigal Sanjiv , Saraf Neeraj , Soin A. S. , Devarbhavi Harshad , Kim Dong Joon , Dhiman R. K. , Duseja Ajay , Taneja Sunil , Eapen C. E. , Goel Ashish , Ning Q. , Chen Tao , Ma Ke , Duan Z. , Yu Chen , Treeprasertsuk Sombat , Hamid S. S. , Butt Amna S. , Jafri Wasim , Shukla Akash , Saraswat Vivek , Tan Soek Siam , Sood Ajit , Midha Vandana , Goyal Omesh , Ghazinyan Hasmik , Arora Anil , Hu Jinhua , Sahu Manoj , Rao P. N. , Lee Guan H. , Lim Seng G. , Lesmana Laurentius A. , Lesmana Cosmas Rinaldi , Shah Samir , Mohan Prasad V. G. , Payawal Diana A. , Abbas Zaigham , Kadir Dokmeci A. , Sollano Jose D. , Carpio Gian , Shresta Ananta , Lau G. K. , Fazal Karim Md. , Shiha Gamal , Gani Rino , Kalista Kemal Fariz Fariz , Yuen Man-Fung , Alam Seema , Khanna Rajeev , Sood Vikrant , Lal Bikrant Bihari , Pamecha Viniyendra , Jindal Ankur , Rajan V. , Arora Vinod , Yokosuka Osamu , Niriella Madunil A. , Li Hai , Qi Xiaolong , Tanaka Atsushi , Mochida Satoshi , Chaudhuri Dominic Ray , Gane Ed , Win Khin Maung , Chen Wei Ting , Rela Mohd , Kapoor Dharmesh , Rastogi Amit , Kale Pratibha , Rastogi Archana , Sharma Chhagan Bihari , Bajpai Meenu , Singh Virender , Premkumar Madhumita , Sudhir Sudhir , Olithselvan A. , Philips Cyriac Abby , Srivastava Anshu , Yachha Surender K. , Wani Zeeshan Ahmad , Thapa B. R. , Saraya Anoop , Shalimar  , Kumar Ashish , Wadhawan Manav , Gupta Subash , Madan Kaushal , Sakhuja Puja , Vij Vivek , Sharma Barjesh C. , Garg Hitendra , Garg Vishal , Kalal Chetan , Anand Lovkesh , Vyas Tanmay , Mathur Rajan P. , Kumar Guresh , Jain Priyanka , Pasupuleti Samba Siva Rao , Chawla Yogesh K. , Chowdhury Abhijit , Alam Shahinul , Song Do Seon , Yang Jin Mo 
Published: November 2021

Abstract
Background and aims
Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database.

Methods
A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis.

Results
Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36–0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43–0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred.

Conclusions
The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.