Abstract
BackgroundNon-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC). Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection.Methods2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1) pre-cirrhotic NAFLD (2) cirrhotic NAFLD and (3) cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis.ResultsFour of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L). By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease.ConclusionThis novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC.
Highlights
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies
There is presently no medical treatment to reverse the changes of cirrhosis, it is hoped that improved therapies introduced at lesser stages of disease may have an impact on their rate of progression to cirrhosis
Spot 2 in particular was reduced in cirrhotic individuals relative to those with pre-cirrhotic NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of over 20% in Western societies. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection Viral infections such as Hepatitis B (HBV) and Hepatitis C (HCV) are the principal causes of chronic liver injury, while in western nations steatohepatitis secondary to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) contribute significantly. NAFLD is the liver manifestation of the metabolic syndrome, characterised by central obesity, insulin resistance, hypertension and atherogenic dyslipidaemia. It is the commonest cause of chronic liver disease in western countries.[1] Whatever the insult, chronic injury generates a persistent wound healing response associated with a changing extracellular matrix (ECM) and the accumulation of fibrous, type I collagen rich, scar tissue. There is presently no medical treatment to reverse the changes of cirrhosis, it is hoped that improved therapies (eg. antiviral therapy or those targeting the metabolic syndrome and/or NAFLD) introduced at lesser stages of disease may have an impact on their rate of progression to cirrhosis
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