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Genetic background of liver cirrhosis complications
Šenkeříková, Renáta ; Špičák, Julius (advisor) ; Brůha, Radan (referee) ; Husová, Libuše (referee)
Liver cirrhosis represents the end stage of most chronic liver diseases. The course of the disease and its complications can be significantly influenced by host genetic factors and the severity of portal hypertension (PH). The aim of the study was to describe the role of genetic factors influencing the progression and complications of liver disease and to determine the role of non-invasive assessment of the stage of liver fibrosis and severity of PH and their correlation with portosystemic gradient (HVPG) measurements. We first focused on the role of allelic variants in TLR4 signalling pathway genes in the risk of occurrence of severe bacterial infections in patients with advanced liver cirrhosis, liver transplant (LT) candidates. We found that the TNFA c.-238G/A promoter variant significantly reduced the risk of bacterial infections and was associated with a decreased mortality rate. We further investigated the role of the variant G allele in PNPLA3 gene in the progression of chronic liver failure and the need for LT in patients with liver cirrhosis due to HCV infection. As a result, we found that the carriage of the variant G allele led to a faster progression of chronic liver failure and the need for LT at a younger age. Third, we investigated whether the efficacy of triple combination treatment...
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Metabolic and genetic risks of development of non-alcoholic fatty liver disease in patients after liver transplantation and its impact on patient and graft survival
Míková, Irena ; Trunečka, Pavel (advisor) ; Červinková, Zuzana (referee) ; Brůha, Radan (referee)
Nonalcoholic fatty liver disease (NAFLD) occurs frequently not only in the general population, but also in liver transplant (LT) recipients. The data about prevalence, evolution, causes and significance of steatosis in patients after LT are limited. In a large retrospective study in LT recipients with histological evaluation of steatosis, we found high prevalence of steatosis (56,4 %) and steatohepatitis (10,4 %), the prevalence of steatosis increased after LT. Pretransplant predictors of steatosis included alcoholic cirrhosis and high BMI, whereas increased alkaline phosphatase and mycophenolate mofetil given initially were protective. Posttransplant predictors of steatosis included BMI, serum triglycerides, alcohol consumption and presence of type 2 diabetes mellitus, whereas increased serum creatinine was protective. Presence of significant steatosis/steatohepatitis was not associated with increased grade of fibrosis. There was no difference between the occurrence of steatosis in surviving and lost grafts. Survival of patients with/without significant steatosis was similar with a trend to higher long-term mortality of patients with significant steatosis. In the evaluation of the impact of TM6SF2 rs58542926 and PNPLA3 rs738409 genotypes of the donor and recipient on pathophysiology of steatosis...
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