In memoriam: Hanns-Ulrich Marschall (1954-2023)

On August 1, 2023 Professor Hanns-Ulrich Marschall, Professor of Clinical Hepatology, Sahlgrenska Academy, University of Gothenburg, passed away from cancer. He was an outstanding physician, clinical scientist and educator. He was an internationally leading expert in bile acid metabolism and cholestasis and will be greatly missed by many colleagues around the world (Fig. 1). Hanns-Ulrich Marschall was born in 1954 in Ibbenbüren, Germany. He graduated in Medicine from the University of Aachen in 1981 and obtained a master’s degree in chemistry from the same university a year later. Following graduation, he worked as a physician in Tübingen and Aachen, and then in 1986 he studied for his PhD under the supervision of Professor Jan Sjövall at the Department of Medical Biochemistry, Karolinska Institute, Stockholm, whilst also working as Chief Physician in Gastrocentrum, Karolinska University Hospital, Huddinge. His thesis was entitled "Conjugation of Bile Acids with N-Acetylglucosamine" and was awarded in 1994. This enabled him to apply his expertise in chemistry to develop a deep understanding of bile acid biochemistry, resulting in him becoming a world-renowned expert in bile acid biochemistry. Throughout his career Hanns-Ulrich made a major research contribution to the understanding of the causes and consequences of cholestatic disorders. He built collaborations with many international colleagues, having been a Visiting Professor at the University of Graz from 2003-2017, and at King’s College London from 2014-2016. His incisive mind, detailed understanding of bile acid biochemistry and cholestasis, coupled with his infectious energy, resulted in these visits producing many fruitful collaborations. In parallel, he led a team of outstanding researchers first at the Karolinska Institute, and later at the Wallenberg Laboratory, Department of Medicine, Sahlgrenska Academy, University of Gothenburg. Hanns-Ulrich was mentor to many clinical and non-clinical scientists, consistently replying to requests for advice and his scientific opinion about research conundrums and complex clinical cases. Hanns-Ulrich Marschall’s Visiting Professorship at the Medical University Graz was an outstanding experience for all. He touched many with his loyalty and endurance, his unique ability to combine his constant thirst to generate new knowledge with thinking outside the box, creating new friendships across generations, and his curiosity to become acquainted with new areas. His constant input in the high-quality analysis and critical interpretation of bile acids in mouse models of cholestatic liver diseases and their extraintestinal manifestations enabled the team in Graz to develop a deepened understanding of their pathophysiological relevance, and to develop novel hypotheses about the therapeutic use of experimentally tested bile acids and their derivatives. Based on his amazing knowledge of bile acid biochemistry, Hanns-Ulrich represented a reliable lighthouse for the correct interpretation of data generated in mice and pivotal cues between mice and humans. His support and help were essential for the bench-to-bedside development of norucholic acid. His scientific seriousness coupled with a never-ending, almost childlike curiosity was inspiring for the younger scientists and empowering and comforting to the older faculty members. We all gratefully remember numerous fruitful bile acid conferences and scientific meetings, including the legendary Pichlschloss Transport Weekends hosted by Prof. Gustav Paumgartner, where he always generously shared his ideas. Hanns-Ulrich Marschall made a particular contribution to the understanding of intrahepatic cholestasis of pregnancy (ICP) throughout his career. This is the commonest liver disorder of pregnancy that affects just under 1% of all pregnant women and can cause distress due to severe itching and liver impairment in previously well women in addition to being complicated by preterm birth and stillbirth. Women with ICP have high total serum bile acids (TSBAs), and Hanns-Ulrich’s early work showed that there is a threshold concentration of TSBAs above which the pregnancy complications of stillbirth, preterm birth and fetal distress occur. He also led a highly impactful clinical trial that demonstrated a role for the drug ursodeoxycholic acid as a potential treatment for ICP, particularly for women with higher TSBA concentrations. Hanns-Ulrich worked closely with patient charities as well as clinical colleagues and was cited widely by the charity ICP Support as a leading internationally renowned researcher. He listened to patients and thought deeply about the impact of disease on their health. This led to his important studies demonstrating that women with a clinical diagnosis of ICP have an increased risk of hepatobiliary diseases later in life, including hepatic fibrosis, cholangitis and carcinoma. His work was highly novel and will have a major impact on the care and health of women with ICP during pregnancy and throughout their lives. In addition to leading important research, Hanns-Ulrich collaborated widely and was highly regarded as a collaborator in genomic studies on ICP, mechanistic experiments to understand the impact of reproductive hormone signalling in disease aetiology and recent clinical trials to evaluate rifampicin and ileal bile acid inhibitors. His advice was always insightful, intelligent and delivered with minimal delay. He became a popular member of the research team at King’s College London when he was a visiting professor and remained a friend and mentor to many members of the research team in London. In a similar way to his visits to Graz, he was inspirational to young and older researchers alike. After joining the Wallenberg Laboratory for metabolic and cardiovascular research at the University of Gothenburg, Hanns-Ulrich became a highly valued colleague contributing and sharing his knowledge on bile acid signalling, hepatology, and gastroenterology. Scientifically, he continued his work on bile acids with a focus on deciphering how the gut microbiota could metabolize bile acids as well as differences in bile acid metabolism between mice and humans. This work led to important findings, for example identification of tauro-conjugated betamuricholic acid as an FXR antagonist and the discovery of how fibre supplementation increases the production of 6alpha-hydroxylated bile acids leading to TGR5 activation and improvement in glucose metabolism. Accordingly, Hanns-Ulrich Marschall had a deep interest in determining how bile acids affected host metabolism, in particular through FXR signalling, which he explored both using mouse models as well as in human interventions. He was a principal investigator for several clinical investigations involving bile acid metabolism and signalling, resulting in important insights into bile acid biochemistry, while simultaneously showing deep consideration and care for study participants. Hanns-Ulrich Marshall was clinically responsible for patients with chronic liver diseases and co-authored several seminal studies within the field of cholestatic liver diseases. Finally, Hanns-Ulrich mentored 11 PhD students and acted as a role model for physician scientists. He was also deeply engaged in the careers of young scientists, introducing them to his professional network and providing highly appreciated career advice. Aside from his outstanding contribution as one of the great clinical scientists in bile acid biochemistry and cholestasis, Hanns-Ulrich was passionate about music, regularly attending both classical and rock concerts. He enjoyed architecture, fine food and art with friends from the international hepatology community, as well as with his friends and family in Sweden and Germany. We all miss him greatly as a friend, mentor and inspiring colleague who never lost his passion for science or medicine. It was a testimony to the high regard that Hanns-Ulrich’s colleagues had for him that the flags were flown at half-mast at the main building Academicum, at Medicinaregatan 16, and at Hälsovetarbacken on the day of his funeral. Hanns-Ulrich was a beloved husband, father, grandfather and brother. We send our condolences to his wife Susanne, his daughters Andrea and Hannah from his previous marriage, his granddaughter Inez and his sister Sabine. His death leaves a void in the world of hepatology and women’s health, and he is greatly missed as a colleague and friend.