Serum keratin 19 (CYFRA21-1) is a prognostic biomarker in severe alcoholic hepatitis.

Stephen Rahul Atkinson, Mahmoud Aly, Katharina Remih, Luke David Tyson, Nurdan Guldiken, Robert Goldin, Alberto Quaglia, Mark Thursz, Pavel Strnad

Liver international : official journal of the International Association for the Study of the Liver 2022 May

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Up to 30% of patients with severe alcoholic hepatitis (sAH) die within 3 months of presentation. The degree of ductular reaction, characterized by accumulation of biliary and liver progenitor cells, confers a poor prognosis. Keratin fragments are established serological surrogates of liver injury and keratin 19 (K19) is a histological marker of the ductular reaction. We assessed the relationship between serum K19 levels (viz. CYFRA21-1), histology and outcome in patients with sAH. Serum CYFRA21-1 was quantified in pre-treatment serum samples from 824 patients enrolled in the STOPAH trial. The cohort was randomly divided into two groups to test mortality associations; histological analyses were performed using the 87 cases with suitable samples. CYFRA21-1 levels were elevated in sAH and strongly predicted alcoholic steatohepatitis (ASH) on biopsy (area under the receiver operated characteristic [AUROC] 0.785 [95% Confidence Interval 0.602-0.967]) and 90-day survival (AUROC 0.684/0.693). The predictive ability of CYFRA21-1 was comparable with the model of end-stage liver disease (MELD) score and was independently associated with survival in multivariable analysis. CYFRA21-1 moderately correlated with hepatocellular injury markers M30/M65 but displayed a more robust predictive ability. A combination of MELD and CYFRA21-1 conferred a modest improvement in the AUROC value (0.731/0.743). In sAH serum, CYFRA21-1 levels associate with the presence of ASH on biopsy and independently predict 90-day survival. As a single marker performance is comparable to established scoring systems. Therefore, CYFRA21-1, which is available in many clinical laboratories, may become a useful component of prognostic models. © 2022 The Authors. Liver International published by John Wiley & Sons Ltd.

Citation

Stephen Rahul Atkinson, Mahmoud Aly, Katharina Remih, Luke David Tyson, Nurdan Guldiken, Robert Goldin, Alberto Quaglia, Mark Thursz, Pavel Strnad. Serum keratin 19 (CYFRA21-1) is a prognostic biomarker in severe alcoholic hepatitis. Liver international : official journal of the International Association for the Study of the Liver. 2022 May;42(5):1049-1057