Molecular and cellular markers of subclinical graft fibrosis after pediatric liver transplantation and non-invasive assessment of liver fibrosis

Subclinical fibrosis and inflammation are common findings in pediatric hepatic diseases and in liver grafts after liver transplantation (LT). The mechanisms of these histopathological changes are unclear. Biomarkers that would precede these changes and non-invasive ways to assess fibrosis are needed. The aim of this thesis was to investigate the molecular and cellular markers of subclinical graft fibrosis and non-invasive methods to determine the stage of fibrosis and varices. Study I included 99 pediatric patients with chronic liver disease who underwent liver biopsy sampling for histology and transient elastography (TE) study for liver stiffness (LS) between January 2012 to March 2015. In addition, data on spleen size, platelet count, and aspartate aminotransferase to platelet ratio index (APRI) were collected. Esophagogastroduodenoscopy (EGD) was performed for 61 patients to assess varices. LS had the best accuracy in the prediction of liver fibrosis stage, compared to APRI, spleen size, and platelets to spleen size score. For moderate fibrosis (≥F2) and cirrhosis (F4) the area under receiver curve (AUROC) values for LS were 0.831 (95%CI: 0.745-0.981, p