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. 2025 Oct 25.
doi: 10.1007/s12072-025-10914-3. Online ahead of print.

Diabetes mellitus is linked to higher mortality in alcohol-related acute-on-chronic liver failure

Ashish Kumar  1 , Anil Arora  1 , Praveen Sharma  1 , Rakhi Maiwall  2 , Ashok Choudhury  2 , Vinod Arora  2 , Mohamed Rela  3 , Dinesh Jothimani  3 , Mamun A Mahtab  4 , Harshad Devarbhavi  5 , Chundamannil E Eapen  6 , Ashish Goel  6 , Cesar Yaghi  7 , Qin Ning  8 , Tao Chen  9 , Jidong Jia  8 , Duan Zhongping  10 , Saeed S Hamid  11 , Amna S Butt  11 , Wasim Jafri  11 , Akash Shukla  12 , Seok S Tan  13 , Dong J Kim  14 , Anoop Saraya  2 , Jinhua Hu  15 , Ajit Sood  16 , Omesh Goyal  16 , Vandana Midha  16 , Manoj Sahu  17 , Guan H Lee  18 , Sombat Treeprasertsuk  19 , Kessarin Thanapirom  19 , Ameet Mandot  20 , Samir Shah  21 , Ravikiran Maghade  20 , Laurentius A Lesmana  22 , Rinaldi C Lesmana  23 , Hasmik Ghazinyan  24 , Virukalpatti G Mohan Prasad  25 , Abdul K Dokmeci  26 , Jose D Sollano  27 , Zaigham Abbas  28 , Ananta Shrestha  29 , George K Lau  30 , Diana A Payawal  31 , Gamal E Shiha  32 , Ajay Duseja  33 , Sunil Taneja  33 , Nipun Verma  33 , Padaki N Rao  34 , Anand V Kulkarni  34 , Mithun Sharma  34 , Fazal Karim  35 , Radha K Dhiman  36 , Ajay K Mishra  36 , Shahinul Alam  4 , Osamu Yokosuka  37 , Debashis Chowdhury  38 , Vivek A Saraswat  39 , Chandan K Kedarisetty  40 , Sanjiv Saigal  41 , Ghulam N Yattoo  42 , Abraham Koshy  43 , Ajay K Patwa  44 , Mohamed Elbasiony  45 , Pravin M Rathi  46 , Sudhir Maharshi  47 , Vishwa M Dayal  48 , Ashish K Jha  48 , Kemal F Kalista  49 , Rino A Gani  49 , Man F Yuen  50 , Virendra Singh  51 , Ayaskanta Singh  52 , Violeta A Sargsyan  53 , Chien H Huang  54 , Saurabh S Mukewar  55 , Shaojie Xin  56 , Ruveena B Rajaram  57 , Charles Panackel  58 , Sunil Dadhich  59 , Sanjeev Sachdeva  60 , Ajay Kumar  60 , Sanatan Behera  61 , Prabir Maji  62 , Lubna Kamani  63 , Hemamala V Saithanyamurthi  64 , Joy Varghese  65 , Pathik Parikh  66 , P Javed  67 , Neeraj Saraf  68 , Narendra S Choudhary  68 , Akash Roy  69 , Mahesh Goenka  69 , Chetan Kalal  70 , Krishnadas Devadas  71 , Gupse Adali  72 , Hithanadura J de Silva  73 , Shiv K Sarin  74 ; APASL ACLF Research Consortium (AARC) for APASL ACLF working Party
Affiliations

Diabetes mellitus is linked to higher mortality in alcohol-related acute-on-chronic liver failure

Ashish Kumar et al. Hepatol Int. .

Abstract

Background: Acute-on-chronic liver failure (ACLF) is a rapidly progressive syndrome marked by high short-term mortality. While diabetes mellitus (DM) is known to worsen liver-related outcomes, its specific impact on alcohol-related ACLF (ALD-ACLF) remains underexplored. This study aimed to assess the prognostic impact of DM on 90-day outcomes in ALD-ACLF using data from the APASL ACLF Research Consortium (AARC) database.

Methods: This observational study involved data from 5612 ACLF patients with documented 90-day outcomes. We identified 2096 patients with ALD-ACLF precipitated by alcoholic hepatitis. Patients with non-ALD etiologies, mixed etiologies, or non-alcoholic precipitants were excluded. Diabetic and non-diabetic patients were compared using 1:2 propensity score matching based on key baseline covariates. Survival outcomes were assessed using Kaplan-Meier analysis and multivariable Cox regression.

Results: After matching, 109 diabetic patients were compared with 218 well-matched non-diabetic controls. Diabetic patients had significantly lower overall survival (32 vs. 57%) and transplant-free survival (31 vs. 50%) compared to non-diabetics (log-rank p < 0.001). On multivariable Cox regression, DM was independently associated with increased 90-day mortality (HR 1.739, 95% CI 1.262-2.395, p < 0.001), along with elevated serum lactate (HR 1.187 per mmol/L, p < 0.001) and creatinine (HR 1.267 per mg/dL, p < 0.001).

Conclusion: Diabetes mellitus is a significant independent predictor of mortality in patients with ALD-ACLF. These findings highlight the need for early identification and integrated management of diabetes in ACLF care pathways to improve clinical outcomes.

Keywords: ALD-ACLF; Acute-on-chronic liver failure (ACLF); Alcoholic hepatitis; Alcoholic liver disease; Diabetes mellitus.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have not disclosed any competing interests.

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