The online version of this article (doi:10.1186/1471-230X-14-27) contains supplementary material, which is available to authorized users.
HT holds endowed faculty positions in research for HGF tissue repair and regenerative medicine and has received funds from Eisai Co., Ltd.
KM and HU: principal investigator, data collection, subject evaluation and manuscript preparation. SM, AI, YY and TN: subject evaluation and statistical analysis. KO and KT: subject recruitment and subject evaluation. KK, TT, AM, MO, YS, MH and SE: subject recruitment and data collection. HU and HT: guarantor of the article. All authors read and approved the final manuscript.
Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients.
Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated.
A serum AIM level of ≥1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103–28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ≥8.6 ng/ml was independently associated with the presence of hepatic steatosis (≥5%) (OR, 6.195; 95% CI, 1.409–27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively.
High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism.
Hu KQ, Currie SL, Shen H, Cheung RC, Ho SB, Bini EJ, McCracken JD, Morgan T, Bräu N, Schmidt WN, Jeffers L, Wright TL, VA HCV-001 Study Group: Clinical implications of hepatic steatosis in patients with chronic hepatitis C: a multicenter study of U.S. veterans. Dig Dis Sci. 2007, 52: 570-578. 10.1007/s10620-006-9418-4. CrossRefPubMed
Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, Sobesky R, Martinot-Peignoux M, Maylin S, Nicolas-Chanoine MH, Paradis V, Vidaud M, Valla D, Bedossa P, Marcellin P: Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008, 134: 416-423. 10.1053/j.gastro.2007.11.010. CrossRefPubMed
Miyazaki T, Hirokami Y, Matsuhashi N, Takatsuka H, Naito M: Increased susceptibility of thymocytes to apotosis in mice lacking AIM, a novel murine macrophage-derived soluble factor belonging to the scavenger receptor cysteine-rich domain superfamily. J Exp Med. 1999, 189: 413-422. 10.1084/jem.189.2.413. CrossRefPubMedPubMedCentral
Kurokawa J, Nagano H, Ohara O, Kubota N, Kadowaki T, Arai S, Miyazaki T: Apoptosis inhibitor of macrophage (AIM) is required for obesity-associated recruitment of inflammatory macrophages into adipose tissue. Proc Natl Acad Sce USA. 2011, 108: 12072-12077. 10.1073/pnas.1101841108. CrossRef
Tsochatzis E, Papatheodoridis GV, Hadziyannis E, Georgiou A, Kafiri G, Tiniakos DG, Manesis EK, Archimandritis AJ: Serum adipokine levels in chronic liver diseases: association of resistin levels with fibrosis severity. Scand J Gastroenterol. 2008, 43: 1128-1136. 10.1080/00365520802085387. CrossRefPubMed
Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, Adinolfi LE, Asselah T, Jonsson JR, Smedile A, Terrault N, Pazienza V, Giordani MT, Giostra E, Sonzogni A, Ruggiero G, Marcellin P, Powell EE, George J, Negro F, HCV Meta-Analysis (on) Individual Patients' Data Study Group: Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology. 2006, 130: 1636-1642. 10.1053/j.gastro.2006.03.014. CrossRefPubMed
Gray J, Chattopadhyay D, Beale GS, Patman GL, Miele L, King BP, Stewart S, Hudson M, Day CP, Manas DM, Reeves HL: A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease. BMC Cancer. 2009, 9: 271-10.1186/1471-2407-9-271. CrossRefPubMedPubMedCentral
Haruta I, Kato Y, Hashimoto E, Minjares C, Kennedy S, Uto H, Yamauchi K, Kobayashi M, Yusa S, Müller U, Hayashi N, Miyazaki T: Association of AIM, a novel apoptosis inhibitory factor, with hepatitis via supporting macrophage survival and enhancing phagocytotic function of macrophages. J Biol Chem. 2001, 276: 22910-22914. 10.1074/jbc.M100324200. CrossRefPubMed
Dolganiuc A, Norkina O, Kodys K, Catalano D, Bakis G, Marshall C, Mandrekar P, Szabo G: Viral and host factors induce macrophage activation and loss of toll-like receptor tolerance in chronic HCV infection. Gastroenterology. 2007, 133: 1627-1636. 10.1053/j.gastro.2007.08.003. CrossRefPubMedPubMedCentral
Novo E, Marra F, Zamara E, Valfrè Di Bonzo L, Monitillo L, Cannito S, Petrai I, Mazzocca A, Bonacchi A, De Franco RS, Colombatto S, Autelli R, Pinzani M, Parola M: Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans. Gut. 2006, 55: 1174-1182. CrossRefPubMedPubMedCentral
Muzzi A, Leandro G, Rubbia Brandt L, James R, Keiser O, Malinverni R, Dufour JF, Helbling B, Hadengue A, Gonvers JJ, Müllhaupt B, Cerny A, Mondelli MU, Negro F, Swiss Hepatitis C Cohort Study: Inrulin resistance is associated with liver fibrosis in non-diabetic chronic hepatitis C patients. J Hepatol. 2005, 42: 41-46. 10.1016/j.jhep.2004.09.022. CrossRefPubMed
Baig NA, Herrine SK, Rubin R: Liver disease and diabetes mellitus. Clin Lab Med. 2001, 21: 193-207. PubMed
Svegliati-Baroni G, Ridolfi F, Di Sario A, Casini A, Marucci L, Gaggiotti G, Orlandoni P, Macarri G, Perego L, Benedetti A, Folli F: Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology. 1999, 29: 1743-1751. 10.1002/hep.510290632. CrossRefPubMed
Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, Conti M, Huet S, Ba N, Buffet C, Bedossa P: High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology. 2001, 34: 738-744. 10.1053/jhep.2001.28055. CrossRefPubMed
Piche T, Vandenbos F, Abakar-Mahamat A, Vanbiervliet G, Barjoan EM, Calle G, Giudicelli J, Ferrua B, Laffont C, Benzaken S, Tran A: The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C. J Viral Hepat. 2004, 11: 91-96. 10.1046/j.1365-2893.2003.00483.x. CrossRefPubMed
Itoh Y, Nishimura T, Yamaguchi K, Yokomizo C, Fujii H, Minami M, Nagao Y, Sumida Y, Hashimoto H, Umemura A, Shima T, Okanoue T, Yoshikawa T: Hepatic steatosis in chronic hepatitis C patients infected with genotype 2 is associated with insulin resistance, hepatic fibrosis and affects cumulative positivity of serum hepatitis C virus RNA in peginterferon and ribavirin combination therapy. Hepatol Res. 2011, 41: 1145-1152. 10.1111/j.1872-034X.2011.00886.x. CrossRefPubMed
Ohnishi M, Tsuge M, Kohno T, Zhang Y, Abe H, Hyogo H, Kimura Y, Miki D, Hiraga N, Imamura M, Takahashi S, Ochi H, Hayes CN, Tanaka S, Arihiro K, Chayama K: IL28B polymorphism is associated with fatty change in the liver of chronic hepatitis C patients. J Gastroenterol. 2012, 47: 834-844. 10.1007/s00535-012-0550-y. CrossRefPubMed
- Serum levels of apoptosis inhibitor of macrophage are associated with hepatic fibrosis in patients with chronic hepatitis C
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