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Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Jul 14, 2014; 20(26): 8325-8340
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8325
Table 1 Proteomic studies of non-alcoholic fatty liver disease
Protein categoriesProtein markersRef.YearFindingsImplications
Protein carrierApolipoproteinsChoe et al[21]2013Independent association between ApoB/ApoA1 ratio and NAFLDNAFLD is the hepatic manifestation of MetSApoB/ApoA1 ratio as a predictable marker of cardiovascular risk in NAFLD
CD5LGray et al[22]2009Identified a pattern of serum apolipoproteins and CD5L to distinguish between pre-cirrhotic NAFLD and cirrhotic NAFLDPossibility of different trigger factors for the progression of NAFLD, NASH to HCC
Metabolic pathwaysCPS1Rodríguez-Suárez et al[24]2010Identified CD5L as poor biomarkers for HCCDecreased in NASH compared to control patientsDown-regulation of CPS1 may lead to an increase of uric acid[31]
GRP78Rodríguez-Suárez et al[24]2010Decreased in NASH compared to control patientsIncreased de novo lipogenesis might play a role in NAFLD pathogenesis[27]
Uric AcidSirota et al[33]2013Association of increased serum uric acid level and severity of NAFLDMitochondrial oxidative damage could contribute to hepatic steatosis
Acute phase proteinhs-CRPYoneda et al[39]2007Increased hs-CRP serum level in advanced NASHAcute phase proteins may have an immediate role in hepatocytes injuries predictive markersSerum levels of acute phase proteins do not necessary reflect the severity of diseaseNAFLD progression has a more complex underlying protein mechanism
HaemoglobinYu et al[42]2012Association of elevated serum haemoglobin levels and prevalence of NAFLD
Fuc-HptKamada et al[44]2013Stepwise increased with increasing hepatocyte ballooning scores in biopsy-proven NAFLD patients
PTX-3Yoneda et al[47]2008A profound elevation of plasma PTX-3 level in NASH patients
Anti-inflammatory and anti-oxidantBilirubinKwak et al[49]2012An inverse relationship between total serum bilirubin level and the prevalence of NAFLDBilirubin has antioxidant, anti-inflammatory and anti-fibrogenic effects
Extracellular matrixHyaluronic acidKaneda et al[56]2006Association of increased serum concentration of ECM components and degree of fibrosis in NAFLDAn imbalance of ECM production and degradation could lead to fibrogenensis, but not specific to NAFLD
Type IV collagen 7SYoneda et al[59]2007
LamininGabrielli et al[60]1996
LumicanKrishnan et al[64]2012Over-expressed of Lumican with increasing severity of NAFLD and NASHUnregulated tissue remodelling and fibrogenesis could contribute to the progression of NAFLD
MMP-9D'Amico et al[72]2010An increase in serum MMP-9 levels in NASH and hepatitis C infected patientsDemonstrated a difference of immunolabelling patterns between NASH and hepatitis C infected liverPossibility of a different pathophysiological involvement of protease in the fibrogenesis of different liver etiology
Wanninger et al[67]2011Association of MMP-9 activity and hepatic inflammationA negative correlation of MMP-9 activity and serum adiponectinPossibility of peripheral adipocytes involvement in NAFLD progression
Immune cells and cytokinesCCL2/MCP1Haukeland et al[81]2006Demonstrated an increasing level of CCL2/MCP1, from healthy controls to NASHThe lipid accumulation from visceral tissue and hepatocellular could be responsible for the recruitment of immune cells
RBP4Bell et al[18]2010A decreased expression of RBP4 with increasing NAFLD severityRBP4 could contribute to the fibrogenesis pathway in NAFLD
Alkhouri et al[84]2009An inverse relationship between RBP4 levels and liver fibrosis
Graham et al[87]2006Association of increased serum RBP4 with T2DM and a decreased expression of glucose transporter 4RBP4 is associated with insulin resistance and T2DM
Christou et al[88]2012RBP4 has the ability to induce insulin resistance in the adipose tissueCirculating RBP4 can be influenced by non-metabolic conditions and interventionsThe association of RBP4 level and MetS is still not conclusive and should be interpret with caution