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

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.

Acamprosate may be safer than baclofen for the treatment of alcohol use disorder in patients with cirrhosis: a first description of use in real-world clinical practice.

OBJECTIVES: Patients with alcohol use disorder (AUD) and liver cirrhosis benefit from stopping alcohol intake. Baclofen has been trialled for AUD in cirrhosis and appears to be effective. However, in patients without cirrhosis acamprosate is safer and more efficacious. Acamprosate is rarely used in cirrhosis due to safety concerns: the only published report was for 24 h in a controlled setting. Our centre uses both medications off-label in cirrhotic patients. We performed an audit to pragmatically compare the safety of acamprosate to baclofen in these patients. METHODS: The electronic records of patients prescribed acamprosate or baclofen between 01/04/17 and 31/03/20 were retrospectively reviewed. Adverse events and abstinence at last follow-up were compared by Student's t-test, Mann-Whitney U or chi-square test. Confounding variables were evaluated by logistic regression. RESULTS: In total 48 cirrhotic patients taking acamprosate (median 84 days, range 2-524); 44 baclofen (247 days, 8-910) met inclusion criteria. At baseline, 41% had Childs-Pugh B or C cirrhosis. More patients taking baclofen had an unplanned hospital admission or attendance (23 vs 13; P = 0.013) and the mean number per patient was higher (1.6 vs 0.6; P = 0.032). Sub-group analysis revealed increased admissions in actively drinking patients prescribed baclofen to achieve abstinence (mean 2.4 vs 0.6; P = 0.020); acamprosate use was associated with a reduced chance of admission or attendance (OR, 0.284; 0.095-0.854; P = 0.025) independent of treatment length. No difference in efficacy was observed. CONCLUSIONS: In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns.