Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in Metabolic Dysfunction Associated Fatty Liver Disease–Related Acute-on-Chronic Liver Failure
Authors: Kumar Ashish , Arora Anil , Choudhury Ashok , Arora Vinod , Rela Mohamed , Jothimani Dinesh Kumar , Mahtab Mamun A. , Devarbhavi Harshad , Eapen Chundamanni E. , Goel Ashish , Yaghi Cesar , Ning Qin , Chen Tao , Jia Jidong , Zhongping Duan , Hamid Saeed S. , Butt Amna S. , Jafri Wasim , Shukla Akash , Tan Seok S. , Kim Dong J. , Saraya Anoop , Hu Jinhua , Sood Ajit , Goyal Omesh , Midha Vandana , Pati Girish K. , Singh Ayaskant , Lee Guan H. , Treeprasertsuk Sombat , Thanapirom Kessarin , Mandot Ameet , Maghade Ravikiran , Lesmana Rinaldi C. , Ghazinyan Hasmik , Mohan Prasad Virukalpatti G. , Dokmeci Abdul K. , Sollano Jose D. , Abbas Zaigham , Shrestha Ananta , Lau George K. , Payawal Diana A. , Shiha Gamal E. , Duseja Ajay , Taneja Sunil , Verma Nipun , Rao Padaki N. , Kulkarni Anand V. , Karim Fazal , Saraswat Vivek A. , Alam Shahinul , Chowdhury Debashis , Kedarisetty Chandan K. , Saigal Sanjiv , Sharma Praveen , Yattoo Ghulam N. , Koshy Abraham , Patwa Ajay K. , Elbasiony Mohamed , Rathi Pravin M. , Maharshi Sudhir , Dayal Vishwa M. , Jha Ashish K. , Kalista Kemal F. , Gani Rino A. , Yuen Man F. , Singh Virendra , Sargsyan Violeta A. , Huang Chien H. , Mukewar Saurabh S. , Xin Shaojie , Rajaram Ruveena B. , Panackel Charles , Dadhich Sunil , Sachdeva Sanjeev , Kumar Ajay , Behera Sanatan , Kamani Lubna , Saithanyamurthi Hemamala V. , Prasad Babita , Sarin Shiv K. ,   the APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party
Published: July 2024

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.