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

• Published in: The American journal of gastroenterology
• Main 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.
• Format: Journal Article
• Language: English
• Published: 17.07.2024
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.14309/ajg.0000000000002951

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.INTRODUCTIONThe 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.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.METHODSPatients 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.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.RESULTSThe 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.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.DISCUSSIONAlmost 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.