Autoimmune liver diseases, like autoimmune hepatitis and primary sclerosing cholangitis, entail liver inflammation that occurs when the immune system attacks the liver or bile duct epithelial cells. If these conditions are left untreated, they can lead to liver failure. Other complications include liver cancer, enlarged veins in the esophagus and fluid build-up in the abdomen. Studying these conditions should provide better strategies for preventions and therapies so patients have lower risk of long-term complications.
My research delves into immune mechanisms driving liver inflammation and fibrosis in children with biliary atresia or autoimmune liver disease. My colleagues and I are also looking into the genetic causes of acute and chronic liver diseases and circulating and imaging biomarkers for liver inflammation or fibrosis so we can avoid an invasive procedure to monitor the disease.
Our research includes:
We have many translational studies at Cincinnati Children’s and are developing an infrastructure for a multi-center learning network to promote research and improve care for children with autoimmune liver disease across North America.
I started to pursue this area of research during my pediatric residency when I encountered infants with chronic liver disease from biliary atresia awaiting liver transplantation. The absence of medical therapies as an alternative to liver transplantation made me determined to discover new treatments. I’m grateful for my first research opportunities in Dr. Jorge Bezerra's laboratory during my residency and fellowship at Cincinnati Children’s, which helped me to develop independent research programs to find novel therapies for biliary atresia and autoimmune liver diseases.
There are many causes for liver disease in infants and children, including genetic, infectious or autoimmune etiologies. We still do not know enough about the mechanisms of various pediatric liver diseases, which impairs our ability to deliver safe, effective and targeted treatments. My research goal in pediatric hepatology is to find mechanisms through translational research that lead to new therapies. However, for more severe cases, the best way to save lives will be via liver transplantation. As the medical director of our liver transplant program, I lead the efforts of our team of physicians, nurses and care managers to maintain excellent transplant outcomes through innovative therapies and quality improvement sciences.
Some of the honors and awards I have received over the years include:
MD: Humboldt-University, Berlin, Germany, 2000.
Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2002-2004.
Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2005-2007.
Advanced Fellowship: Pediatric Transplant Hepatology, University of Cincinnati and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2009.
Certification: Pediatrics, 2005; Pediatric Gastroenterology, 2009; Pediatric Transplant Hepatology, 2010.
Pediatric liver disease including biliary atresia, inherited liver diseases, autoimmune hepatitis, and primary sclerosing cholangitis; gastrointestinal problems in children with bone marrow failure syndromes
Gastroenterology GI, Liver Care, Liver Transplant, Autoimmune Liver Disease, Liver Tumor
Immune mediated liver injury, specifically the role of regulatory T cells in biliary atresia and primary sclerosing cholangitis; genetic basis for intrahepatic cholestasis in children; acute liver failure in infants with mitochondrial disorders
Gastroenterology Hepatology and Nutrition, Fibrosis
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Longitudinal changes in quantitative magnetic resonance imaging metrics in children and young adults with autoimmune liver disease. Abdominal Radiology. 2023.
Serum biomarkers correlated with liver stiffness assessed in a multicenter study of pediatric cholestatic liver disease. Hepatology. 2023; 77:530-545.
Corrected T1 Mapping in Children and Young Adults With Autoimmune Liver Disease: Correlation With Histology. American Journal of Roentgenology. 2023.
Farnesoid X receptor antagonizes macrophage-dependent licensing of effector T lymphocytes and progression of sclerosing cholangitis. Science Translational Medicine. 2022; 14.
Customized postoperative therapy improves bile drainage in biliary atresia: A single center preliminary report. Journal of Pediatric Surgery. 2022.
Children undergoing early liver re-transplantation for primary non-function have improved survival. Pediatric Transplantation. 2022; 26.
Differential recruitment of monocyte-derived macrophages in control and stellate cell-depleted mice during recurrent carbon tetrachloride-induced acute liver injury. Journal of Cellular Physiology. 2022; 237:4215-4225.
Risk of variceal hemorrhage and pretransplant mortality in children with biliary atresia. Hepatology. 2022; 76:712-726.
Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study. Hepatology Communications. 2022; 6:2379-2390.
Impact of long-term administration of maralixibat on children with cholestasis secondary to Alagille syndrome. Hepatology Communications. 2022; 6:1922-1933.
Alexander G. Miethke, MD, Chunyue Yin, PhD3/23/2021
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