A photo of Alexander Miethke.

Alexander G. Miethke, MD


  • Medical Director, Liver Transplant Program
  • Associate Professor, UC Department of Pediatrics

About

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

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Publications

Risk of variceal hemorrhage and pretransplant mortality in children with biliary atresia. Bass, LM; Ye, W; Hawthorne, K; Leung, DH; Murray, KF; Molleston, JP; Romero, R; Karpen, S; Rosenthal, P; Loomes, KM; et al. Hepatology. 2022; 76:712-726.

Impact of long-term administration of maralixibat on children with cholestasis secondary to Alagille syndrome. Shneider, BL; Spino, CA; Kamath, BM; Magee, JC; Ignacio, RV; Huang, S; Horslen, SP; Molleston, JP; Miethke, AG; Kohli, R; et al. Hepatology Communications. 2022; 6:1922-1933.

Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center. Baker, EK; Ulm, EA; Belonis, A; Brightman, DS; Hallinan, BE; Leslie, ND; Miethke, AG; Vawter-Lee, M; Wu, Y; Pena, LD M. Frontiers in Genetics. 2022; 13.

Associations Between Quantitative MRI Metrics and Clinical Risk Scores in Children and Young Adults With Autoimmune Liver Disease. McCrary, J; Trout, AT; Mahalingam, N; Singh, R; Rojas, CC; Miethke, AG; Dillman, JR. American Journal of Roentgenology. 2022; 219:142-150.

Children undergoing early liver re-transplantation for primary non-function have improved survival. Rogers, ME; Delman, A; Campbell, K; Miethke, A; Tiao, G; Mullapudi, B; Bondoc, A. Pediatric Transplantation. 2022.

Pediatric Living Donor Liver Transplantation Outcomes-Is it Time for Outcome Optimization of Technical Aspects of Transplantation Using Learning Networks?. Bondoc, A; Barker, M; Mullapudi, B; Miethke, A; Tiao, G. Liver Transplantation and Surgery. 2022; 28:928-930.

Total pancreatectomy with islet autotransplantation in a child with pancreatic kaposiform hemangioendothelioma. Kaj-Carbaidwala, B; Bernieh, A; Russi, AE; Miethke, AG; Abu-El-Haija, M; Trout, AT; Gupta, A; Ricci, KW; Nathan, JD. Journal of Pediatric Surgery Case Reports. 2022; 81.

Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study. Loomes, KM; Squires, RH; Kelly, D; Rajwal, S; Soufi, N; Lachaux, A; Jankowska, I; Mack, C; Setchell, KD R; Karthikeyan, P; et al. Hepatology Communications. 2022.

Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency. Li, CZ; Ogawa, H; Ng, SS; Chen, X; Kishimoto, E; Sakabe, K; Fukami, A; Hu, YC; Mayhew, CN; Hellmann, J; et al. 2022; 4.

Sarcopenia is highly prevalent in children with autoimmune liver diseases and is linked to visceral fat and parent-perceived general health. Amevor, AA; Yodoshi, T; Trout, AT; Dillman, J; Singh, R; Jarvis, R; Fei, L; Liu, C; Taylor, A; Miethke, A; et al. Liver International. 2022; 42:394-401.

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