CLINICAL STUDY Serum markers of liver fibrogenesis, and liver histology findings in patients with chronic liver diseases Holoman J, Glasa J, Galbavy S, Danis D, Molnarova A, Kazar J, Bednarova A, Misianik J Bratisl Lek Listy 2002; 103 (2): 70-75 Department of Clinical Pharmacology, Slovak Postgraduate Academy of Medicine; Institute of Pathology, Faculty of Medicine, Comenius Uni- versity; Department of Pathology, Slovak Postgraduate Academy of Medicine and Faculty Dérers Hospital; Department of Internal Medici- ne, Slovak Postgraduate Academy of Medicine; Department of Viral Hepatitis, Institute of Preventive and Clinical Medicine; Department of Radioimmunology, St. Elisabeth Hospital; Bratislava, Slovakia Address for correspondence: J. Holoman, MD, PhD, Dept of Clinical Pharmacology, Slovak Postgraduate Academy of Medicine, Limbova 12, SK-833 03 Bratislava 37, Slovakia. Phone: +421.2.59369505 Fax: +421.2.54773906 Department of Clinical Pharmacology, Slovak Postgraduate Academy of Medicine, Bratislava, Slovakia.holoman@upkm.sk Abstract Aim of the study: Investigation of the relationships between the grade and stage of chronic liver dis- eases irrespective of their etiology using some novel serum markers of liver fibrogenesis, the classi- cal serum markers of liver necro-inflammatory injury (such as transaminases), and the histo- morphological evaluation of liver biopsies. Methods: Markers of liver fibrogenesis: serum metalloproteinase 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1), and N-terminal propeptide of the procollagen III (PIIINP); liver function tests (LFTs): bilirubin, transaminases ALT, AST; ALP, GMT; and liver morphology findings: necro-inflammatory activity, fibrosis; were studied in the series of 32 naive, i.e. yet untreated patients (women/men  11/21) with various CLDs: chronic viral hepatitis B or C 13 (CHB 3, CHC 10), non-alcoholic steatohepatitis 9, liver steatosis 4, primary biliary cirrhosis 5, drug-induced hepatitis. The diagnoses were based on the clinical, laboratory and liver imaging (ultrasonography) findings and confirmed by the liver biopsy. Conclusions: Investigation of liver fibrogenesis serum markers (PIIINP, MMP-1, TIMP-1) in patients with various CLDs has shown statistically significant correlations of these parameters with classical serum markers of liver necro-inflammation (ALT, AST) and the results of histomorphological evalua- tion of the necro-inflammatory activity (parameters NAI, MEF) and fibrosis (parameter FI) in liver biopsies. (Tab. 4, Ref. 31.) Key words: chronic liver disease, liver fibrosis, serum metalloproteinase 1 (MMP-1), tissue inhibitor of serum metalloproteinase 1 (TIMP-1), N-terminal propeptide of the procollagen III (PIIINP), liver biopsy, histomorphology, morphometry. 70 Liver fibrosis, together with other necro-inflammatory and proliferative changes, are a major determinants of the clinical course and prognosis in chronic liver diseases (CLDs) (1, 3, 7). Because of various limitations in liver biopsy (4, 6, 10, 19), nov- el markers of fibrosis as well as those of complex fibro-produc- tive/-lytic processes are sought to enable the non-invasive eval- uation and monitoring in clinical practice (12, 13, 14, 15, 21, 22). Several molecules, either elements or regulators of the met- abolic pathways of the connective tissue extracellular matrix components, are being considered as potential candidates (25, 26, 27, 28, 30, 31). More precise data on their clinical signifi- cance, relationship to the liver biopsy findings and other classi- cal liver serum parameters are still rather scarce. To study the relationships between the stage and grade of CLD irrespective of their etiology using some novel serum mar- kers of liver fibrogenesis (PIIINP, MMP-1, and TIMP-1), the classical serum markers of liver necro-inflammatory injury (such as transaminases ALT, AST), and the histomorphological evaluation of liver biopsies. Material and methods The series of 32 naive (i.e. yet untreated) consecutive pa- tients (women/men  11/21) with various CLDs  chronic viral