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Randomized Controlled Trial
. 2022 May;42(5):1049-1057.
doi: 10.1111/liv.15218. Epub 2022 Mar 11.

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

Stephen Rahul Atkinson  1 , Mahmoud Aly  2   3 , Katharina Remih  2 , Luke David Tyson  1 , Nurdan Guldiken  2 , Robert Goldin  1 , Alberto Quaglia  4 , Mark Thursz  1 , Pavel Strnad  2
Affiliations
Randomized Controlled Trial

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

Stephen Rahul Atkinson et al. Liver Int. 2022 May.

Abstract

Background and aims: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: AH; K19; cytokeratin; liver disease; mortality.

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References

REFERENCES

    1. Liver EAftSot. EASL clinical practice guidelines: management of alcohol-related liver disease. J Hepatol. 2018;69(1):154-181.
    1. Szabo G, Kamath PS, Shah VH, Thursz M, Mathurin P. Alcohol-related liver disease: areas of consensus, unmet needs and opportunities for further study. Hepatology. 2019;69(5):2271-2283.
    1. Maddrey WC, Boitnott JK, Bedine MS, Weber FL Jr, Mezey E, White RI Jr. Corticosteroid therapy of alcoholic hepatitis. Gastroenterology. 1978;75(2):193-199.
    1. Sehrawat TS, Liu M, Shah VH. The knowns and unknowns of treatment for alcoholic hepatitis. Lancet Gastroenterol Hepatol. 2020;5(5):494-506.
    1. Forrest E, Evans C, Stewart S, et al. Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score. Gut. 2005;54(8):1174-1179.

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