Keratin 18 is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis
Department of Medicine, Division of Gastroenterology; Department of Population and Quantitative Health Sciences
Biological Factors | Diagnosis | Digestive System Diseases | Gastroenterology | Hepatology
BACKGROUND: and Aims: Acute alcoholic hepatitis (AAH) is a major cause of liver-related morbidity and mortality; there are no good blood biomarkers for diagnosis or determining magnitude of cell death. Keratin 18 (KRT18, also called K18), found in epithelial cells, is released from hepatocytes upon death. We investigated whether level of K18 is a better marker of hepatocyte death than standard biomarkers and might be used to identify patients with AAH at risk for death within 90 days.
METHODS: We analyzed data from 173 participants in a large trial performed at 4 medical centers. Participants with AAH were classified as severe (n=57, model for end-stage liver disease [MELD] scores above 20) or moderate (n=27, MELD scores from 12 to 19); 38 participants had alcohol use disorder with mild (n=28) or no liver injury (n=10); 34 participants had non-alcoholic steatohepatitis; and 17 participants were healthy (controls). We quantified serum levels of K18 using ELISAs and APOPTOSENSE kits.
RESULTS: Serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the ratio of AST:ALT did not correlate with MELD scores. Patients with alcohol use disorder had higher serum levels of ALT than patients with severe AAH. Levels of K18M65 and K18M30 had statistically significant increases as liver disease worsened, as did the degree of necrosis (ratio of K18 M65:M30). The ratio of K18M65:ALT was increased in serum from patients with AAH compared with controls. Serum levels of K18 identified patients who died within 90 days with greater accuracy than commonly used static biomarkers.
CONCLUSIONS: There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers (AST, ALT, and the AST:ALT ratio). The ratio of K18M65:M30 might be used as marker of mechanism of hepatocyte death, and the ratio of K18M65:ALT might be used to distinguish patients with AAH from patients with non-alcoholic steatohepatitis. Serum levels of K18 might be used to identify patients with severe AAH at risk for death.
NASH, hepatic, predictive, prognosis
DOI of Published Version
Clin Gastroenterol Hepatol. 2019 Dec 4. pii: S1542-3565(19)31390-4. doi: 10.1016/j.cgh.2019.11.050. [Epub ahead of print] Link to article on publisher's site
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
Vatsalya V, Cave MC, Kong M, Gobejishvili L, Falkner KC, Craycroft J, Mitchell M, Szabo G, McCullough A, Dasarathy S, Radaeva S, Barton BA, McClain CJ. (2019). Keratin 18 is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. Population and Quantitative Health Sciences Publications. https://doi.org/10.1016/j.cgh.2019.11.050. Retrieved from https://escholarship.umassmed.edu/qhs_pp/1327