Clinical Characteristics and Outcomes of Patients with Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is the upcoming liver disease of the twenty-first century. Prevalence rates range between 15 to 35% throughout the world. The metabolic syndrome, including obesity, hyperlipidemia, diabetes and arterial hypertension, is thought to be the triggering factor behind evolvement of NAFLD, however genetic and environmental factors have also been proposed. The natural history of NAFLD starts at simple hepatic steatosis which over time leads to non-alcoholic steatohepatitis (NASH) and finally fibrosis or even cirrhosis develops. In recent years a polymorphism in the patatin-like phospholipase domain containing 3(PNPLA3)-gene has been associated with an increased risk for NASH and advanced fibrosis, underlining the important mechanisms genetic predisposition might play in the natural history of the disease. Moreover several other polymorphisms have since then been published such as TM6SF2, MBOAT7 or HSD17B13, some of them however still needing a broader and more specific validation. Several studies have shown that advanced fibrosis (fibrosis stage 3) and cirrhosis (fibrosis stage 4) are the leading drivers of liver related decompensation and mortality in patients with NAFLD. Data suggests that around 10-20% of patients with NASH develop cirrhosis. In cirrhotic patients, irrespective of etiology, portal hypertension is the leading driver of hepatic decompensation and mortality. The hepatic venous pressure gradient (HVPG) is the gold-standard to quantify the severity of portal hypertension. Once portal pressure exceeds the HVPG-threshold of ≥10 mmHg (known as Clinically Significant Portal Hypertension (CSPH)) esophageal varices may develop and the risk of hepatic decompensation, such as variceal bleeding and ascites, and mortality increases rapidly. Management of those complications comprises pharmacological- (non-selective beta-blockers, diuretics) or interventional (endoscopic band ligation, paracentesis)-therapies. However, up-to-date data on profound clinical characteristics of patients with NASH-cirrhosis is scarce. Moreover longitudinal-data regarding response rates and clinical outcomes of patients on NSBB therapy are missing. Aim of this thesis is therefore to elucidate the clinical characteristics and phenotype of patients diagnosed with cirrhosis due to NAFLD and report longitudinal data regarding liver-related outcomes.
Methods and Skills:
Clinical studies; advanced statistics
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