Serum cytokeratin‐18 in the diagnosis of non‐alcoholic steatohepatitis: A meta‐analysis

Abstract

Identifying patients with non-alcoholic steatohepatitis (NASH), a more aggressive form with a worse prognosis than for simple steatosis, is highly important. Liver biopsy still remains the gold standard for diagnosing NASH, but with limitations. The diagnostic value of serum cytokeratin-18 (CK-18) in predicting NASH is still indefinite. We selected relevant studies by a literature search of the PubMed, Ovid Medline and Cochrane Library databases up to January 2012. A DerSimonian-Laird random effects model was used to compute the pooled estimates of sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR), and a summary receiver operating characteristic (SROC) curve was constructed. Stratified analysis was performed to explore the heterogeneity in test accuracy. Funnel plot and Egger's regression were performed to assess publication bias. A total of 10 studies with 838 patients were included (nine CK-18 fragments and five total CK-18 studies) in this meta-analysis. Among nine CK-18 fragment studies with a significant publication bias, the pooled results on SEN, SPE and DOR were 0.83 (95% CI, 0.80-0.86), 0.71 (95% CI, 0.66-0.76) and 11.90 (95% CI, 6.05-23.40), respectively, and age and body mass index were most strongly associated with the observed heterogeneity. Among five total CK-18 studies with homogeneity, the pooled results of SEN, SPE and DOR were 0.77% (95% CI, 0.70-0.83), 0.71 (95% CI, 0.65-0.77) and 7.99 (95% CI, 4.09-15.62), respectively. The area under the ROC curve (± SE) of CK-18 fragments and total CK-18 were 0.8445 (± 0.0306) and 0.8170 (± 0.0429), respectively. Both CK-18 fragments and total CK-18 have a clinically meaningful benefit in noninvasive diagnosing of NASH, though total CK-18 has a relatively low diagnostic accuracy. CK-18 fragments may be a useful biomarker for screening rather than identifying NASH.