Researchers have identified a set of molecular signatures for biliary atresia that can help to identify the progression of disease after diagnosis, and then predict clinical outcomes.Cincinnati Children's Hospital Medical Center scientists examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective, observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years.Writing in the journal Genome Medicine, the authors point out that portoenterostomy at young age “has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis.”The study found 14 of 47 livers showed “predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes.“Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates.”The study found that the groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, whereas those with a fibrosis signature had decreased transplant-free survival.“This suggests that the molecular profile at diagnosis may determine the 'stage' of liver disease through specific biological pathways that are not easily distinguishable by standard approaches,” says Jorge A. Bezerra, MD, a pediatric gastroenterologist at Cincinnati Children's and senior author of the study. “Infants with inflammation were younger, indicating that inflammation may reflect an earlier stage of disease—particularly given that those with fibrosis had decreased survival without transplant.”See: Genome Med 2010;2:33. Available: http://genomemedicine.com/content/2/5/33. Researchers have identified a set of molecular signatures for biliary atresia that can help to identify the progression of disease after diagnosis, and then predict clinical outcomes. Cincinnati Children's Hospital Medical Center scientists examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective, observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Writing in the journal Genome Medicine, the authors point out that portoenterostomy at young age “has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis.” The study found 14 of 47 livers showed “predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. “Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates.” The study found that the groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, whereas those with a fibrosis signature had decreased transplant-free survival. “This suggests that the molecular profile at diagnosis may determine the 'stage' of liver disease through specific biological pathways that are not easily distinguishable by standard approaches,” says Jorge A. Bezerra, MD, a pediatric gastroenterologist at Cincinnati Children's and senior author of the study. “Infants with inflammation were younger, indicating that inflammation may reflect an earlier stage of disease—particularly given that those with fibrosis had decreased survival without transplant.” See: Genome Med 2010;2:33. Available: http://genomemedicine.com/content/2/5/33.