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Prospective biopsy‐controlled evaluation of cell death biomarkers for prediction of liver fibrosis and nonalcoholic steatohepatitis
Author(s) -
Joka Diana,
Wahl Kristin,
Moeller Sarah,
Schlue Jerome,
Vaske Bernhard,
Bahr Matthias J.,
Manns Michael P.,
SchulzeOsthoff Klaus,
Bantel Heike
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24734
Subject(s) - steatosis , fibrosis , steatohepatitis , medicine , liver biopsy , nonalcoholic fatty liver disease , pathology , gastroenterology , biopsy , fatty liver , disease
Fibrosis and steatosis are major histopathological alterations in chronic liver diseases. Despite various shortcomings, disease severity is generally determined by liver biopsy, emphasizing the need for simple noninvasive methods for assessing disease activity. Because hepatocyte cell death is considered a crucial pathogenic factor, we prospectively evaluated the utility of serum biomarkers of cell death to predict different stages of fibrosis and steatosis in 121 patients with chronic liver disease. We compared the M30 enzyme‐linked immunosorbent assay (ELISA), which detects a caspase‐cleaved cytokeratin‐18 (CK‐18) fragment and thereby apoptotic cell death, with the M65 ELISA, which detects both caspase‐cleaved and uncleaved CK‐18 and thereby overall cell death. Both biomarkers significantly discriminated patients with different fibrosis stages from healthy controls. However, whereas both markers differentiated low or moderate from advanced fibrosis, only the M65 antigen could discriminate even lower stages of fibrosis. The M65 assay also performed better in distinguishing low (≤10%) and higher (>10%) grades of steatosis. In a subgroup of patients, we evaluated the biomarkers for their power to predict nonalcoholic steatohepatitis (NASH). Importantly, both markers accurately differentiated healthy controls or simple steatosis from NASH. However, only serum levels of M65 antigen could differentiate simple steatosis from healthy controls. Conclusion: Cell death biomarkers are potentially useful to predict fibrosis, steatosis, or NASH. Compared with the widely used apoptosis marker M30, the M65 assay had a better diagnostic performance and even differentiated between lower fibrosis stages as well as between healthy individuals and patients with simple steatosis. (H EPATOLOGY 2012)