LDH and the MELD-LDH in Severe Acute Liver Injury and Acute Liver Failure: Preliminary Confirmation of a Novel Prognostic Score for Risk Stratification.

BACKGROUND Acute liver failure (ALF) is a devastating condition with high mortality. Currently, liver transplantation is the only life-saving treatment, but the decision to transplant is difficult due to the rapid progression of ALF and persistent shortage of donor organs. Biomarkers that predict death better than current prognostics could help. To our surprise, proteomics recently revealed that lactate dehydrogenase (LDH) is prognostic in ALF by itself and in a novel form of the model for end-stage liver disease (MELD) score called the MELD-LDH. The purpose of this study was to confirm our proteomics results in a larger population. METHODS We reviewed laboratory data from 238 patients admitted to the University of Arkansas for Medical Sciences Medical Center with a diagnosis of ALF and biochemical evidence of acute liver failure over a 12-year period, as well as subset of 170 patients with encephalopathy. RESULTS LDH was strikingly elevated in the nonsurvivors at the time of peak injury. Receiver operating characteristic (ROC) curve analyses revealed that LDH by itself could discriminate between survivors and nonsurvivors on the first day of hospitalization, although not as well as the MELD and MELD-LDH scores that performed alike. Importantly, however, LDH by itself performed similarly to the MELD at the time of peak injury and the MELD-LDH score moderately outperformed both. The MELD-LDH score also had greater sensitivity and negative predictive value than the MELD and the King's College Criteria. CONCLUSIONS The results support our prior finding that LDH and the MELD-LDH score predict death and therefore transplant need in ALF patients.

[1]  A. Geerts,et al.  The utility of biomarkers in prognosis assessment of patients with acute liver failure , 2021, Hepatology research : the official journal of the Japan Society of Hepatology.

[2]  J. Verlander,et al.  Expression of Lactate Dehydrogenase A and B isoforms in the mouse kidney. , 2021, American journal of physiology. Renal physiology.

[3]  Y. Takikawa,et al.  Contrast‐Enhanced Ultrasonography–Based Hepatic Perfusion for Early Prediction of Prognosis in Acute Liver Failure , 2020, Hepatology.

[4]  P. Komolmit,et al.  The incidence, etiologies, outcomes, and predictors of mortality of acute liver failure in Thailand: a population-base study , 2019, BMC Gastroenterology.

[5]  William M. Lee,et al.  Acetaminophen‐induced Acute Liver Failure Is More Common and More Severe in Women , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[6]  William M. Lee,et al.  Elevated FABP1 serum levels are associated with poorer survival in acetaminophen‐induced acute liver failure , 2017, Hepatology.

[7]  Mitchell R. McGill The past and present of serum aminotransferases and the future of liver injury biomarkers , 2016, EXCLI journal.

[8]  Valerie Durkalski,et al.  Development of a Model to Predict Transplant-free Survival of Patients With Acute Liver Failure. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[9]  William M. Lee,et al.  Outcomes in Adults With Acute Liver Failure Between 1998 and 2013 , 2016, Annals of Internal Medicine.

[10]  J. Ryan,et al.  Blood alanine aminotransferase levels >1,000 IU/l - causes and outcomes. , 2015, Clinical medicine.

[11]  J. Yun,et al.  Binge alcohol promotes hypoxic liver injury through a CYP2E1-HIF-1α-dependent apoptosis pathway in mice and humans. , 2014, Free radical biology & medicine.

[12]  William M. Lee,et al.  Serum mitochondrial biomarkers and damage‐associated molecular patterns are higher in acetaminophen overdose patients with poor outcome , 2014, Hepatology.

[13]  William M. Lee,et al.  Development of an accurate index for predicting outcomes of patients with acute liver failure. , 2012, Gastroenterology.

[14]  Guozhong Tao,et al.  Wnt-β-catenin signaling protects against hepatic ischemia and reperfusion injury in mice. , 2011, Gastroenterology.

[15]  B. Copple,et al.  The Role of Hypoxia-Inducible Factor-1α in Acetaminophen Hepatotoxicity , 2011, Journal of Pharmacology and Experimental Therapeutics.

[16]  K. Kodys,et al.  Hepatocyte‐specific hypoxia‐inducible factor‐1α is a determinant of lipid accumulation and liver injury in alcohol‐induced steatosis in mice , 2011, Hepatology.

[17]  Pippa M Simpson,et al.  Acetaminophen hepatotoxicity and HIF-1α induction in acetaminophen toxicity in mice occurs without hypoxia. , 2011, Toxicology and applied pharmacology.

[18]  W. Kremers,et al.  MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure , 2007, Liver transplantation.

[19]  A. Qasim,et al.  MELD score as a prognostic model for listing acute liver failure patients for liver transplantation. , 2006, Transplantation proceedings.

[20]  L. James,et al.  Induction of the nuclear factor HIF-1alpha in acetaminophen toxicity: evidence for oxidative stress. , 2006, Biochemical and biophysical research communications.

[21]  P. Kamath,et al.  A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts , 2000, Hepatology.

[22]  G. Semenza,et al.  Hypoxia Response Elements in the Aldolase A, Enolase 1, and Lactate Dehydrogenase A Gene Promoters Contain Essential Binding Sites for Hypoxia-inducible Factor 1* , 1996, The Journal of Biological Chemistry.

[23]  B. Ebert,et al.  Hypoxic Regulation of Lactate Dehydrogenase A , 1995, The Journal of Biological Chemistry.

[24]  R Williams,et al.  Early indicators of prognosis in fulminant hepatic failure. , 1989, Gastroenterology.

[25]  OUP accepted manuscript , 2022, Toxicological Sciences.

[26]  H. Zimmerman,et al.  Computer analysis of liver function tests and their interrelationships in 347 cases of viral hepatitis. , 1970, Israel journal of medical sciences.