Published:
[Erscheinungsort nicht ermittelbar]: University of Groningen, 2022
Language:
English
Identifier:
Origination:
University thesis:
Dissertation, University of Groningen, 2022
Footnote:
Description:
In this thesis, we examined the epidemiology of MAFLD, its concomitant comorbidities and mediators, environmental and metabolic determinants, genetic factors and outcomes. This thesis describes that MAFLD is highly frequent in the general population, where it coexists with high prevalence of comorbid diseases such as MetS, T2D and CVD and is influenced by BCAAs and higher sodium intake. It is known that MAFLD is a manifestation of a common cardio-metabolic multisystem disorder with highly increased cardiovascular risk, likely mediated at least in part by coexisting plasma lipoprotein abnormalities. This thesis described several additional mechanisms of lipoprotein abnormalities in MAFLD, concerning elevated triglycerides, LDL cholesterol, VLDL, apoB dyslipoproteinemias and apoE levels, and on the other hand lower HDL cholesterol levels with impaired HDL function, which could all contribute to increased atherosclerosis susceptibility. Furthermore, this thesis describes that MAFLD populations could highly benefit from adequate LDL cholesterol lowering treatment by statins, to at least partially treat and prevent specific dyslipoproteinemias, such as high LDL cholesterol. Additionally, in this thesis we described that lipid homeostasis is also influenced by thyroid hormones. In MAFLD there is also a considerable genetic influence on hepatic fat content and two novel genetic candidate loci for MAFLD were revealed in this thesis. Furthermore, different steatosis phenotypes for MAFLD GWASs were compared and showed that the FLI is an easy and reliable approach to study MAFLD at the population level, since a substantial similar genetic architecture in comparison with MRI-PDFF defined MAFLD was shown. At last, as NASH cirrhosis is emerging as the most common indication for liver transplantation, this thesis describes that obese and cirrhotic NASH patients, experience more short term perioperative minor complications, but fortunately do not experience more short-term major morbidity or mortality. Overall, the results of this thesis support the contention that the presence of (suspected) MAFLD coincides with a series of metabolic abnormalities that are not sufficiently captured by obesity phenotypes; i.e., elevated BMI, waist or waist/hip ratio, as such.