Dr. Karim Hamesch

Interplay of metabolic dysfunction and Pi*ZZ-related liver disease

Short summary:

Metabolic dysfunction such as obesity, diabetes mellitus, or dyslipidemia are important progression factors of chronic liver diseases. These metabolic risk factors were recently identified as modifying factors of Pi*ZZ-related liver fibrosis (scarring of the liver) in adults. Moreover, Pi*ZZ adults have increased liver steatosis (increased lipid content in the liver) and altered serum lipid markers indicating an underlying modified lipid metabolism. Hence, metabolic factors are likely a main cause for the heterogeneity of Pi*ZZ-related liver phenotypes. However, how metabolic dysfunction contributes to these phenotypes is still poorly understood.

In collaboration with patient advocacy groups, specialized lung centers and rare disease networks, the European Alpha-1 Liver Study Group (led by Aachen, Germany) prospectively analyzed >1600 adults in 11 European countries. Using this cohort, this pilot study’s objective is to assess the clinical associations and underlying mechanisms of metabolic dysfunction and altered lipid metabolism. The liver phenotypes (e.g., blood markers, elastography data, and liver histology) will be correlated with blood-based metabolic profile data, clinical data, and bioimpedance analysis. Based on these results, Pi*ZZ subjects with clinically relevant liver disease will be compared with matched Pi*ZZ subjects without liver disease to understand differences in lipid metabolism and underlying metabolic pathways. Furthermore, data of Pi*ZZ patients with clinically relevant liver disease will be compared with data from matched patients with metabolic dysfunction-associated fatty liver disease (MAFLD).

Altogether, Dr. Hamesch’s project aims to provide deeper insight into the metabolic alterations in Pi*ZZ adults in order to identify potential treatment targets for the complications of metabolic dysfunction on the liver and beyond. Despite the novel therapeutic options on the horizon, understanding the interplay of metabolic dysfunction with the Pi*ZZ-related liver phenotypes and how behavioral interventions (i.e., reducing metabolic risk factors) attenuate disease progression, or even help to induce regression of liver steatosis and/or fibrosis, are likely helpful for interdisciplinary patient management and counseling alike.


Short biography:

Dr. Karim Hamesch is a senior physician and clinician scientist at the Clinic for Gastroenterology, Metabolic Diseases and Intensive Care at RWTH Aachen University Hospital in Germany. He studied medicine at RWTH Aachen (Aachen, Germany), University College London (London, UK), and Brown University (Providence, RI, USA). He further broadened his clinical experience at Maastricht University Medical Center (Maastricht University; Maastricht, The Netherlands) and Brigham & Women’s Hospital (Harvard University; Boston, MA, USA). He earned his M.D. in experimental research (e.g., transgenic animal studies). Since 2015, he has been instrumental in establishing and expanding a multinational study group on liver disease in α1-antitrypsin deficiency (AATD; In 2021, he received the “Venia Legendi” for internal medicine (German term: “Habilitation”) for his work on characterizing the liver phenotypes in adults with the Pi*ZZ and Pi*MZ genotypes. His current clinical and research focusses are AATD, metabolic dysfunction-associated liver disease (MAFLD), and ultrasound.