Non-Alcoholic Fatty Liver Disease : Aspects on Diagnosis and Long-term Prognosis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease affecting approximately 25% of the global population. NAFLD is commonly recognized as the hepatic manifestation of the metabolic syndrome, i.e. abdominal adiposity, dyslipidaemia, hypertension, and type 2 diabetes mellitus (T2DM). Most individuals with NAFLD will develop T2DM, and vice versa-making the two conditions highly intertwined. The histological spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which is defined by hepatocellular injury and inflammation, with risk of developing fibrosis and subsequent cirrhosis and hepatocellular carcinoma. The gold standard for diagnosing NAFLD is liver biopsy. However, because of its invasive nature, liver biopsy entails some risk of adverse events and even death. Also, there is a high risk of sampling error, as well as intraand interobserver variability, making the results unreliable. Therefore, several non-invasive methods have been developed and validated in evaluating presence of fat and absence of fibrosis in patients with NAFLD. However, evaluation of inflammation and hepatocellular injury (i.e. NASH) or staging of fibrosis, still requires liver biopsy. Liver fat content can be assessed using various methods. The conventional histopathological method consists of a visual semiquantitative approach in which the pathologist uses a four-point scale: grade 0 corresponds to fat deposition in <5% of hepatocytes and corresponds (grade 1=5-33%, 2=34-66%, and 3=67-100%). A diagnosis of NAFLD requires that at least 5% of hepatocytes contain fat vacuoles. An alternate approach is to quantitatively assess steatosis using stereological point counting (SPC). Both the semiquantitative histological method and SPC rely on biopsies, however, in vivo proton magnetic resonance spectroscopy (1 H-MRS) is a reliable non-invasive method that can be used to quantitatively assess total hepatic lipid content, or proton density fat fraction (PDFF). In Paper I we compared the conventional semiquantitative histological method (grade 0-3) with SPC and 1 H-MRS. We found a strong positive correlation between 1 H-MRS and SPC, whereas the correlations between 1 H-MRS or SPC and histopathological grading were substantially weaker. Using the widely used cutoff participants were found to have steatosis (specificity 100%, sensitivity 53%). Reducing the cutoff cumbed to the workload. My boss and fellow skåning, Henrik Hjortswang, for teaching me that best patient care is given by seeking knowledge as a researcher, carrying it forward as a teacher and applying it as a clinician. Also, for giving me all opportunities to research, participate on courses and attend congresses on available time. My clinical tutor and mentor, Rikard Svernlöv, for helping me realize that there is a life outside of work, helping me cope with clinical dilemmas, and for being a role model in all things, big and small, in the role as a physician. I only have 40 years left until retirement, and then I prom...