Liver Systems Medicine

striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research.

Welcome to the LiSyM Network

Liver Systems Medicine, or LiSyM, was a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examined the liver in its entirety. The Network officially adjourned in June 2021.

The successful LiSyM project is followed by the Systems medicine research network for the early detection and prevention of liver cancer “LiSyM- Cancer”: Please read more on the successive network at

In LiSyM the aim was to answer questions about the origin and progression of the metabolic liver disease non-alcoholic fatty liver disease (NAFLD). What initiates NAFLD? How does it develop? How can we improve diagnosis and treatment? More about the work here.

In LiSyM, 37 research groups at 23 scientific centers and institutions located around Germany joined forces to tackle some of the most complex problems of the human body. More about the groups here.

LiSyM Research

Research focuses on the four key, yet overlapping themes of the pillars. Four junior groups also address specific research topics.

Early Metabolic Injury

When does a fatty liver actually develop a disorder?

Chronic Liver Disease Progression

When connective tissue replaces functioning liver cells

Regeneration and Repair in Acute-on-Chronic Liver Failure (ACLF)

Liver failure after a long illness: Can it be prevented? Can the liver recover?

Liver Function Diagnostics

Develops computer-based diagnostic tools to help detect and assess changed liver functions early.


Standardized doses are suitable for only few people

30 June 2021 / Article
Patients metabolize drugs differently. Personalized physiologically based pharmacokinetic (PBPK) models improve precision dosing Read the article

Individual and combinations of health variables have a strong effect on NAFLD

15 March 2021 / Article
Ann-Kristin Becker’s Bayesian network assesses the risk of developing the liver disease more accurately than common clinical scores.
Read the article

Finding Important Relationships in Large Datasets

22 February 2021 / article
An interview with Ann-Kristin Becker, a PhD student at the Greifswald University Hospital, about how Bayesian networks can be used in systems biology to identify what variables are interdependent and to what degree
Read the article

PK-DB: pharmacokinetics database for individualized and stratified computational modeling

23 December 2020 / PUBLICATION
LiSyM researchers Matthias König and Jan Grzegorzewski together with international collaborators introduce their open database PK-DB for pharmacokinetics data from clinical trials with many unique features. PK-DB represents the first open resource for storing pharmacokinetics data and corresponding patient-specific metadata in accordance with the FAIR (Findable, Accessible, Interoperable, and Reproducible) principles.
The database PK-DB-v0.9.3 ( consists of 512 studies containing 1457 groups, 6308 individuals, 1408 interventions, 73 017 outputs, 3148 time-courses and 37 scatters related to acetaminophen, caffeine, codeine, diazepam, glucose, midazolam, morphine, oxazepam, simvastatin or torasemide. It provides curated information for patient cohorts in clinical trials on patient characteristics, drug therapies and pharmacokinetic parameters. The standardized and machine-readable data can assist analyses undertaken in physiologically based pharmacokinetic, pharmacokinetic/pharmacodynamic or populated pharmacokinetic modeling.
The authors envisage that PK-DB will encourage better reporting of pharmacokinetics studies by providing a means for data representation and integration. Providing access to PK data in a central database will improve reusability of pharmacokinetics data. PK-DB will also facilitate data integration between clinical studies and computational models.
Publication: Jan Grzegorzewski, Janosch Brandhorst, Kathleen Green, Dimitra Eleftheriadou, Yannick Duport, Florian Barthorscht, Adrian Köller, Danny Yu Jia Ke, Sara De Angelis, Matthias König, PK-DB: pharmacokinetics database for individualized and stratified computational modeling, Nucleic Acids Research, , gkaa990,

Mathematics as a Bridge from the Laboratory to the Clinic - Importance for Advancing Medicine

20 December 2020 / article
Many experimental results only reach patients through mathematical models. The computer scientist Dr. habil. Dirk Drasdo, an expert for simulations in the liver systems biology research network LiSyM, explains how models can contribute to medical advancements in acute and chronic liver disorders.
Read the article

Mathematics as a Bridge from the Laboratory to the Clinic - Developing Mathematical Models

20 December 2020 / article
Developing mathematical models of biological systems is very time consuming and challenging for scientists. Yet this is the only way for many experimental results to actually reach patients. The computer scientist Dr. habil. Dirk Drasdo from the systems biology research network LiSyM explains some of the technical issues involved when creating models. A simulations expert, Drasdo uses the liver model he has developed as an example to explain how chemistry, physics, biology, pharmacy, and medicine are transformed into mathematical equations and simulations.
Read the article

LiSyM Researches How Genes Impact NAFLD

27 October 2020 / Article
Genes have an effect on many diseases. According to Professor Dr. med. Frank Lammert, “The genetic profile plays an important role in NAFLD (nonalcoholic fatty liver disease).” Lammert, who is a member of the LiSyM research network, studies the gene variants that influence how susceptible people are to NAFLD. Other gene variants accelerate the course of the disease, or they increase the risk of complications. “How well therapies work also depends on genes,” Lammert explains, adding: “We need more large-scale clinical studies that combine patients’ clinical and molecular profiles with genetic data!” He believes this is the only way patients can benefit from the latest findings in genetic research.
Read the article

The Metabolic Liver Disease NAFLD: A Growing Health Problem

19 October 2020 / Article
The World Gastroenterology Organization WGO and other health care associations identify the metabolic liver disease, NAFLD (nonalcoholic fatty liver disease), as a “growing public health problem.” As many as one in four people worldwide has a nonalcoholic fatty liver today. The number is even as high as 40% in the US and Europe, according to estimates from the European Association for the Study of the Liver (EASL). The organization believes that 12 million are affected in Germany.
Read the article

New Insights into Bile Secretion in the Liver

6 August 2020 / Publication
In Germany, as many as five million people suffer from liver diseases. The liver is a resilient and complex organ, and currently we do not understand enough, not even about its most basic functions. In a study funded by the Federal Ministry of Education and Research (BMBF), LiSyM team members in Dortmund at IfADo (Leibniz Research Centre for Working Environment and Human Factors) provide fundamentally new insights into the production and transport of bile through 'canaliculi' in the liver. Their results show that the canaliculi contain a stagnant fluid, and bile constituents pass through this fluid by diffusion. These findings overturn long-standing assumptions about how the liver secretes bile. Their results have been published in Hepatology.

"Our new findings require a scientific debate in liver research, which will lead to an adjustment of the doctrine to the new observation. It is to be hoped that this will lead to long-term progress in the treatment of liver diseases", summarizes Dr. Nachiket Vartak, junior group leader in the LiSyM research program.

Press release (English):

Press release (German):

Explainer Video:

Publication: Vartak, N. et al.: Intravital dynamic and correlative imaging reveals diffusion-dominated canalicular and flow-augmented ductular bile flux. Hepatology 2020. doi: 10.1002/hep.31422

Loss of hepatic Mboat7 leads to liver fibrosis

July 2020 / Publication
LiSyM researchers find that deficiency in MBOAT7 causes liver fibrosis with no apparent inflammation
In collaboration with other key research partners, members of the LiSyM Network investigated the role played by MBOAT7 rs641738C>T – a variant of the MBOAT7 (membrane-bound O-acyltransferase domain containing 7) protein – in the origin and development of NAFLD (nonalcoholic fatty liver disease). They conclude that an MBOAT7 deficiency leads to the development of liver fibrosis without inflammation via a pathway that may be mediated by lipid signaling. Ultimately, this knowledge could lead to improved treatments of NAFLD.

Their study is based on the analysis of mice with hepatocyte-specific MBOAT7 deletion, of associations between the rs641738C>T genotype and liver inflammation and fibrosis in 846 NAFLD patients as well as genotype-specific liver lipidomes from 280 human biopsies.

See publication:

The Holy Grail of Systems Biology

19 February 2020 / article
LiSyM director Professor Dr. med. Peter Jansen believes that mathematical models are indispensable for the research of biological systems.
Human bodies are complex biological systems, with countless reactions taking place in every cell. These reactions are sometimes interconnected or have an impact on further processes. Furthermore, cells, tissue, and organs are closely connected. Professor Dr. med. Peter Jansen, director of the LiSyM research network, believes that the research of systems like these, which consist of multilayered processes, interactions, and dependencies, needs mathematical models.
Only models that simulate biological systems on computers make it possible to assemble the existing mass of heterogeneous data into dynamic reproductions in a meaningful way. Mathematical models enable systems researchers to deliver results more quickly and successfully. The idea that digital computers can play an essential role in this research is older than the machines themselves.
Read the article

Better diagnosis of NAFLD with 3D model of human liver tissue

11 December 2019
LiSyM researchers create geometrical and functional liver model for improved diagnosis of non-alcoholic fatty liver disease.
In collaboration with international researchers, members of the Liver Systems Medicine research network have developed the technology and knowledge to generate 3D geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease, NAFLD. With these high definition models, cellular and tissue markers can be quantified to define how far NAFLD has progressed in individual patients and thereby improve medical diagnoses markedly.
To press release

Research with liver tissue has a long tradition and has been the basis of the discipline of biochemistry. Over the years this research has yielded a wealth of stored quantifiable data. In Systems Medicine these data are re-used to integrate with new data as to develop multi-scale computational models that help in understanding the complexity of metabolism and its derangement in human diseases.
This should lead to a more personalised type of medicine, earlier diagnosis and new therapies

Peter Jansen