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

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.

Acute liver failure secondary to yellow phosphorus rodenticide poisoning: Outcomes at a center with dedicated liver intensive care and transplant unit.

Accidental or suicidal poisoning with yellow phosphorus or metal phosphides (YPMP) such as aluminum (AlP) zinc phosphide (Zn3P2) commonly cause acute liver failure (ALF) and cardiotoxicity. These are used as household, agricultural and industrial rodenticides and in production of ammunitions, firecrackers and fertilizers. In absence of a clinically available laboratory test for diagnosis or toxin measurement or an antidote, managing their poisoning is challenging even at a tertiary care center with a dedicated liver intensive care unit (LICU) and liver transplant facility. PATIENTS AND METHODS: Patients with YPMP related ALF were monitored using standardized clinical, hemodynamic, biochemical, metabolic, neurological, electrocardiography (ECG) and SOFA score and managed using uniform intensive care, treatment and transplant protocols in LICU. Socio-demographic characteristics, clinical and biochemical parameters and scores were summarized and compared between 3 groups i.e. spontaneous survivors, transplanted patients and non-survivors. Predictors of spontaneous survival and the need for liver transplant are also evaluated. RESULTS: Nineteen patients with YPMP related ALF were about 32 years old (63.2% females) and presented to us at a median of 3 (0 - 10) days after poisoning. YPMP related cardiotoxicity was rapidly progressive and fatal whereas liver transplant was therapeutic for ALF. Spontaneous survivors had lower dose ingestion (<17.5 grams), absence of cardiotoxicity, < grade 3 HE, lactate < 5.8, SOFA score < 14.5, and increase in SOFA score by < 5.5. Patients with renal failure need for CVVHDF and KCC positivity on account of PT-INR > 6.5 had higher mortality risk. Patients undergoing liver transplant and with spontaneous recovery required longer ICU and hospital stay. At median follow-up of 3.4 (2.6 - 5.5) years, all spontaneous survivors and transplanted patients are well with normal liver function. CONCLUSIONS: Early transfer to a specialized center, pre-emptive close monitoring, and intensive care and organ support with ventilation, CVVHDF, plasmapheresis and others may maximize their chances of spontaneous recovery, allow accurate prognostication and a timely liver transplant.