A photo of Alexander Miethke.

Medical Director, Liver Transplant Program

Assistant Professor, UC Department of Pediatrics

513-636-8948

Board Certified

My Biography & Research

Biography

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:

  • The signaling molecules regulating liver inflammation and fibrosis in fibrosing cholangiopathies, which can be targeted with innovative treatments
  • Novel immune therapies based on what genes predispose patients to pediatric liver disease
  • Ways to detect and determine the various types of circulating and imaging biomarkers from liver injury and fibrosis in order to use them as surrogate endpoints in clinical trials for primary sclerosing cholangitis (PSC) and autoimmune hepatitis

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:

  • Director of the Center for Autoimmune Liver Disease (CALD) founded with extraordinary philanthropic support to find cures for PSC and autoimmune hepatitis
  • Holding the Robert and Sydney Anning Endowed Chair in Autoimmune Liver Disease at Cincinnati Children's Hospital since March 2020
  • NIH R01 level funding to study biliary atresia in animal models and human samples
  • Multiple research awards from the American Association for the Study of Liver Diseases (AASLD) to initiate my research

Additional Languages

German

Clinical Interests

Pediatric liver disease including biliary atresia, inherited liver diseases, autoimmune hepatitis, and primary sclerosing cholangitis; gastrointestinal problems in children with bone marrow failure syndromes

Research Interests

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

Academic Affiliation

Assistant Professor, UC Department of Pediatrics

Divisions

Gastroenterology GI, Liver Care, Liver Transplant, Autoimmune Liver Disease, Liver Tumor, Gastroenterology, Fibrosis

My Locations

My Education

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.

My Publications

Comparison of liver T1 relaxation times without and with iron correction in pediatric autoimmune liver disease. Dillman, JR; Serai, SD; Miethke, AG; Singh, R; Tkach, JA; Trout, AT. Pediatric Radiology: roentgenology, nuclear medicine, ultrasonics, CT, MRI. 2020; 50:935-942.

Evaluation of a change in cytomegalovirus prevention strategy following pediatric solid organ transplantation. Pangonis, S; Paulsen, G; Andersen, H; Flores, F; Miethke, A; Peters, A; Kocoshis, S; Lazear, D; Garr, B; Schecter, M; et al. Transplant Infectious Disease. 2020; 22.

Society of pediatric liver transplantation: Current registry status 2011-2018. Elisofon, SA; Magee, JC; Ng, VL; Horslen, SP; Fioravanti, V; Economides, J; Erinjeri, J; Anand, R; Mazariegos, GV; Dunn, S; et al. Pediatric Transplantation. 2020; 24.

Differentiating pediatric autoimmune liver diseases by quantitative magnetic resonance cholangiopancreatography. Gilligan, LA; Trout, AT; Lam, S; Singh, R; Tkach, JA; Serai, SD; Miethke, AG; Dillman, JR. Abdominal Radiology. 2020; 45:168-176.

Expanding and Underscoring the Hepato-Encephalopathic Phenotype of QIL1/MIC13. Russell, BE; Whaley, KG; Bove, KE; Labilloy, A; Lombardo, RC; Hopkin, RJ; Leslie, ND; Prada, C; Assouline, Z; Barcia, G; et al. Hepatology. 2019; 70:1066-1070.

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course. Deneau, M; Perito, E; Ricciuto, A; Gupta, N; Kamath, BM; Palle, S; Vitola, B; Smolka, V; Ferrari, F; Amir, AZ; et al. The Journal of Pediatrics. 2019; 209:92-96.e1.

Interleukin 2 Promotes Hepatic Regulatory T Cell Responses and Protects From Biliary Fibrosis in Murine Sclerosing Cholangitis. Taylor, AE; Carey, AN; Kudira, R; Lages, CS; Shi, T; Lam, S; Karns, R; Simmons, J; Shanmukhappa, K; Almanan, M; et al. Hepatology. 2018; 68:1905-1921.

Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome. Shneider, BL; Spino, C; Kamath, BM; Magee, JC; Bass, LM; Setchell, KD; Miethke, A; Molleston, JP; Mack, CL; Squires, RH; et al. Hepatology Communications. 2018; 2:1184-1198.

Putting it all together: established and emerging MRI techniques for detecting and measuring liver fibrosis. Serai, SD; Trout, AT; Miethke, A; Diaz, E; Xanthakos, SA; Dillman, JR. Pediatric Radiology: roentgenology, nuclear medicine, ultrasonics, CT, MRI. 2018; 48:1256-1272.

Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study. Ng, VL; Sorensen, LG; Alonso, EM; Fredericks, EM; Ye, W; Moore, J; Karpen, SJ; Shneider, BL; Molleston, JP; Bezerra, JA; et al. The Journal of Pediatrics. 2018; 196:139-147.e3.