ReviewCardiovascular risk, lipidemic phenotype and steatosis. A comparative analysis of cirrhotic and non-cirrhotic liver disease due to varying etiology
Section snippets
Background and aims
Liver, a major regulator of lipid metabolism through the synthesis of apoprotein and lipoprotein and de novo lipogenesis [1], is also a chief modifier of cardiovascular risk (CVR). This occurs through the synthesis of atherogenic apoprotein-B (Apo-B), and the remodeling of HDL and apoB containing lipoproteins by action of Cholesterol Ester Transfer Protein (CETP) and liver-X receptor (LXR) [2], [3]. The activation of CETP gene expression by LXR is deemed to be pro-atherogenic [3], and certain
Alcoholic liver disease
Excess alcohol intake is a common cause of non-familial hyperlipidemia [12], [13]. Alcoholic hyperlipidemia, which follows binge drinking and is often associated with alcoholic fatty liver (AFL) and steatohepatitis (ASH), rarely occurs in established cirrhosis and is characterized by elevated plasma TG resulting from VLDL accumulation or, rarely, by superimposed (fasting) hyperchylomicronemia [14], [15], [16]. Such a VLDL increase depends on the amount of ingested alcohol and patient features
NAFLD
NAFLD displays a powerful atherogenic lipoprotein profile; serum TG, LDL-CH, and Apo-B are increased, while HDL-CH and LDL buoyancy are decreased [52], [53], [54].
A recent large multi-ethnic study demonstrated that NAFLD, diagnosed through the Liver/Spleen ratio, although unassociated with total CH or LDL-CH, was indeed associated with higher fasting serum TG, lower serum HDL-CH, LDL particle concentration, and negatively associated with LDL particle size. Such lipoprotein abnormalities
Chronic hepatitis B
The interaction of hepatitis B virus (HBV) vital cycle with the host lipid metabolism is not characterized as fully as is the case for HCV infection.
Acute hepatitis B is associated with transient hypertriglyceridemia [86], [87]. The biological basis underlying this reversible dyslipidemia, however, remains poorly characterized and given its transient course, it is probably of scarce concern for CVR.
Chronic HBV infection is associated with reduced TG, total CH and HDL-CH and with significantly
Chronic hepatitis C
Chronic HCV infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide [103], [104].
An altered metabolic profile is a peculiar extra-hepatic feature in HCV infection, acknowledged to be a “systemic disease” [105]. It includes IR, steatosis, hypocholesterolemia and visceral fat hypertrophy. This unique cluster of dysmetabolic conditions named HCV-associated dysmetabolic syndrome differs from the “typical” MS on the grounds of reduced plasma lipids levels [11], [106],
Cirrhosis
Cirrhosis represents the stereotyped end-stage histologic lesion resulting from unopposed chronic action of a variety of liver injuring agents. ALD, HCV infection and NASH are the most common causes of cirrhosis in Europe and North America, whereas HBV infection is the prevailing cause in most parts of Asia and sub-Saharan Africa [128].
Liver cirrhosis is characterized by an abnormal plasma lipid and lipoprotein profile due to impaired liver biosynthetic capacity. In non-cholestatic
Primary biliary cirrhosis
As part of chronic cholestatic liver diseases, primary biliary cirrhosis (PBC) is often associated with mixed hyperlipidemia (hypercholesterolemia with markedly elevated TG, LDL and HDL serum concentrations) [164]. Reduced plasma LCAT activity, biliary lipids secretion and functional LDL receptors in hepatocytes, as well as increased hepatic CH synthesis are all deemed to concur to the development of the altered lipid profile [165], [166]. Two different patterns of serum lipoproteins are
Hepatocellular carcinoma
HCC frequently arises from cirrhosis and, much more rarely, from chronic, viral or metabolic, hepatitis [81]. While these predisposing conditions per se are often associated with deranged plasma lipid and lipoprotein profile [135], HCC patients will typically display slightly to significantly decreased TG, CH, free FA, HDL, LDL, Lp(a), Apo-AI and Apo-B plasma levels, which mirror a poorer prognosis [190], [191].
Lipid and lipoprotein metabolism is regulated by cytokines; HCC is associated with
Conclusions
Liver diseases due to various etiologies are associated with varying serum lipid and lipoprotein phenotypes. Noteworthy, the two major hepatotropic viruses, HBV and HCV, display different lipid profiles.
At variance with what observed in the general population, patients with liver disease fail to display the strict and proportional association between increasing (total and LDL-) CH and TG levels and cardiovascular morbidity, suggesting that other factors, such as steatosis and IR, further to
Acknowledgment
The Institutions of the Authors of this review are recipient of funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under agreement no. HEALTH-F2-2009-241762 for the project FLIP.
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