Adiponectin as a modulator of hepatic fibrosis in chronic HCV-Infection

Adiponectin is a member of adipose tissue-secreted hormones, so-called adipokines, and has wide implications in glucose and lipid metabolism. It is also found in liver tissue and in NAFLD/NASH it provides protective features on liver tissue like antiinflammatory and antifibrotic effects. There are two specific receptors for adiponectin: AdipoR1 with abundant expression and AdipoR2 with expression especially on hepatocytes. Yet, little is known about the role of adiponectin in chronic HCV-infection. Recently, genetic studies of single nucleotide polymorphisms (SNP) of the adiponectin gene, e.g. +276G>T, have shown that genetic polymorphisms are implicated in altered protein function. Methods: From a total of 480 cases of chronic HCV-infection 99 paraffin-embedded, formalin fixed liver tissues including S0 (n=2), S1 (n=27), S2 (n=27), S3 (n=27) and S4 (n=16) were taken for immunohistological investigation of adiponectin. We performed immunostaining of adiponectin and counted positively stained portal tracts. For genetic analysis of SNP +276G>T in the adiponectin gene 183 cases of chronic HCV-infection, containing fibrosis stages S1, S2, S3 and S4, were examined by Real-Time PCR using SNP-specific TaqMan probes. Results: Immunofluorescent double-staining showed adiponectin reactivity in endothelial cells, especially, of portal vessels. In addition, moderate adiponectin immunostaining was observed in smooth muscle cells of portal arteries and in much lesser extend in sinusoidal cells. Nevertheless, adiponectin mRNA was not detectable in liver biopsies. In the panel of specimens with high grade fibrosis we found a slightly increasing number of adiponectin-positive portal tracts. Thus, we propose a modulating effect of adiponectin on the progression of liver fibrosis in chronic HCV-infection. Next we analyzed the SNP +276G>T, which is known to alter adiponectin function. We found the mutated T allele in position +276 to be more frequent in higher fibrosis stages. SUMMARY AND Conclusion: Adiponectin is mainly found in endothelial cells of the portal tract. In liver tissue with chronic HCV-infection showing progressive fibrosis adiponectin staining is slightly increased. Analysis of the SNP +276G>T of the adiponectin gene indicates that the 276T substitution might be involved in fibrosis progression and should be tested as a putative prognostic marker in chronic hepatitis C.