Liver Fibrosis Biomarker Evaluation

The study protocol was approved by the local ethics committee (ethics committee of University Hospital Aachen, RWTH Aachen), and written informed consent was obtained from each patient. The study was conducted according to the principles expressed in the Declaration of Helsinki. Inclusion criteria were either any CLD with a predisposition to liver fibrosis or an already established liver fibrosis/cirrhosis of any origin. Established cirrhosis (in contrast to non-cirrhotic CLD) was defined, if imaging (ultrasound, CT or MRI scan), biopsy or laparoscopy indicated liver cirrhosis or if cirrhosis-related complications were present. Patients with established liver cirrhosis were staged according to Child-Pugh's criteria [32] (link). Patients with acute liver failure or acute hepatitis B or C were not included. Exclusion criteria were conditions known to directly affect monocyte subset distributions in humans, specifically ongoing bacterial infections (procalcitonin concentration above normal value [<0.5 µg/L]), HIV-infection, systemic steroid medication (prednisolone >7.5 mg/d or equivalent doses) and malignant tumor(s) except hepatocellular or cholangiocellular carcinoma. Furthermore, patients were excluded in case of systemic inflammatory response syndrome (SIRS) or sepsis criteria [33] (link). The etiologies of liver diseases comprised viral hepatitis (n = 89, 39.4%; HBV n = 38, HCV n = 51), biliary or autoimmune disease (n = 27, 11.9%; autoimmune hepatitis n = 10, primary biliary cirrhosis n = 8, primary sclerosing cholangitis n = 9), alcoholic liver disease (n = 65, 28.7%) and other liver diseases (n = 45, 20%, e.g. non-alcoholic steatohepatitis n = 7, hemochromatosis n = 4, cryptogenic n = 23). Grading and staging of liver samples (biopsies and explants) were performed according to Desmet-Scheuer score by one experienced pathologist, who was fully blinded to any experimental data [34] (link).
As a control group, 181 healthy volunteers were recruited from the local blood transfusion institute that had normal aminotransferase activities, no history of liver disease or alcohol abuse and tested negative for HBV, HCV and HIV infections.