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M65 is a highly sensitive marker of alcoholic steatohepatitis
Aim: The non-invasive assessment of disease activity in patients with non-alcoholic and alcoholic liver disease (NALD and ALD) is still unsettled but essential for the evaluation of disease progression. We here studied dependence of total (M65) and caspase-cleaved (M30) cytokeratin-18 fragments on histological subscores of inflammation, fibrosis and steatosis and the role of alcohol detoxication.
Methods: M30 and M65 (ELISA, Peviva, Sweden) were measured in patients with biopsy-proven ALD (n = 105) and NALD (n = 30). The natural course of M30 and M65 levels upon alcohol detoxication was studied in 40 patients.
Results: M65 was the best marker for histological signs of liver damage and inflammation such as balloning (0.65, P < 1E-9), Mallory-Denk bodies (0.554, P < 1E-6) and lobular inflammation (0.499, P < 1E-5). Its correlation surpassed that of M30 and GOT. However, M65 correlated less well with histological signs of cirrhosis (semiquantitative histological Chevallier score 0.320, P < 0.005) as compared to liver stiffness (0.8, P < 1E-19) or serum markers (hylaluronic acid (0.7, P < 1E-10). In contrast, M30 correlated better than M65 and any other parameter with steatosis as measured by histology (0.49, P < 1E-4) or ultrasound (0.39, P < 0.005). Compared to 30 patients with NALD and matched with regard to age, sex and fibrosis stage, levels of M30 and M65 were significantly higher in ALD while the presence of glycogenated nuclei, pigmented macrophages and haemoglobin were lower. During alcohol detoxication over a mean of 5.3 days, M30 increased from 408 to 553 U/L while M65 fell from 839 to 820 U/L. Both markers were significantly correlated with decreasing liver stiffness and GOT levels.
Conclusions: Our data suggest that M65 and M30 are highly sensitive and more significant markers of the histological degree of inflammation and liver damage clearly exceeding transaminase levels. Therefore, M30/65 could be especially useful in monitoring patients with severe alcoholic steatohepatitis.