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. 2025 Apr 1;120(4):816-826.
doi: 10.14309/ajg.0000000000002951. Epub 2024 Jul 17.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure

Ashish Kumar  1 , Anil Arora  1 , Ashok Choudhury  2 , Vinod Arora  2 , Mohamed Rela  3 , Dinesh Kumar Jothimani  3 , Mamun A Mahtab  4 , Harshad Devarbhavi  5 , Chundamanni 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  15 , Jinhua Hu  16 , Ajit Sood  17 , Omesh Goyal  17 , Vandana Midha  17 , Girish K Pati  18 , Ayaskant Singh  19 , Guan H Lee  20 , Sombat Treeprasertsuk  21 , Kessarin Thanapirom  21 , Ameet Mandot  22 , Ravikiran Maghade  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 , Fazal Karim  35 , Vivek A Saraswat  36 , Shahinul Alam  4 , Debashis Chowdhury  37 , Chandan K Kedarisetty  38 , Sanjiv Saigal  39 , Praveen Sharma  1 , Ghulam N Yattoo  40 , Abraham Koshy  41 , Ajay K Patwa  42 , Mohamed Elbasiony  43 , Pravin M Rathi  44 , Sudhir Maharshi  45 , Vishwa M Dayal  46 , Ashish K Jha  46 , Kemal F Kalista  47 , Rino A Gani  47 , Man F Yuen  48 , Virendra Singh  49 , Violeta A Sargsyan  50 , Chien H Huang  51 , Saurabh S Mukewar  52 , Shaojie Xin  53 , Ruveena B Rajaram  54 , Charles Panackel  55 , Sunil Dadhich  56 , Sanjeev Sachdeva  57 , Ajay Kumar  57 , Sanatan Behera  58 , Lubna Kamani  59 , Hemamala V Saithanyamurthi  60 , Babita Prasad  2 , Shiv K Sarin  2 ; APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party
Affiliations

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease-Related Acute-on-Chronic Liver Failure

Ashish Kumar et al. Am J Gastroenterol. .

Abstract

Introduction: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute-on-chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied.

Methods: Patients with MAFLD-ACLF were recruited from the Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC registry). The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease as MAFLD (or previous nomenclature such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, or non-alcoholic steatohepatitis-cirrhosis). Patients with coexisting other etiologies of chronic liver disease (such as alcohol, hepatitis B virus, hepatitis C virus, etc.) were excluded. Data were randomly split into derivation (n = 258) and validation (n = 111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered.

Results: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27% and hypertension in 29%. The dominant precipitants included viral hepatitis (hepatitis A virus and hepatitis E virus, 32%), drug-induced injury (drug-induced liver injury, 29%), and sepsis (23%). Model for End-Stage Liver Disease-Sodium (MELD-Na) and AARC scores on admission averaged 32 ± 6 and 10.4 ± 1.9. At 90 days, 51% survived. Nonviral precipitant, diabetes, bilirubin, international normalized ratio, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for nonviral precipitant), and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts.

Discussion: Almost half of patients with MAFLD-ACLF die within 90 days. Diabetes and nonviral precipitants such as drug-induced liver injury and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for patients with MAFLD-ACLF.

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