Total and High Molecular Weight Adiponectin and Hepatocellular Carcinoma with HCV Infection

Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades

Baseline clinical characteristics in case and control.

<p>Continuous variables presented as mean ± standard deviation.</p><p>Abbreviation: AST = aspartate aminotransferase; ALT = alanine aminotransferase;</p><p>APRI = aspartate aminotransferase-to-platelet ratio index; BMI = body mass index;</p><p>HMW = high molecular weigh.</p

Association between total and HMW adiponectin and histological grade in patients with hepatocellular carcinoma by multiple logistic regression analysis.

<p>Abbreviation: OR = odds ratio; 95% CI = confidence interval; HMW = high molecular weigh.</p><p>Model 1: adiponectin only.</p><p>Model 2: adiponectin and covariates in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026840#pone-0026840-t002" target="_blank">Table 2</a>.</p

Comparison of adiponectin levels according to histological grades in 97 cases.

<p>A. The serum total adiponectin levels in patients with moderately (<i>P</i> = 0.001) and poorly (<i>P</i><0.001) differentiated hepatocellular carcinoma (HCC) were significantly lower compared to those in patients with well-differentiated HCC. B. The serum high molecular weight (HMW) adiponectin levels in patients with moderately (<i>P</i><0.001) and poorly (<i>P</i><0.001) differentiated HCC were significantly lower compared to those in patients with well-differentiated HCC.</p

Association between clinical characteristics and histological grade in patients with hepatocellular carcinoma.

<p>Continuous variables presented as mean ± standard deviation.</p><p>Abbreviation: AST = aspartate aminotransferase; ALT = alanine aminotransferase;</p><p>APRI = aspartate aminotransferase-to-platelet ratio index; BMI = body mass index;</p><p>AFP = alpha-fetoprotein; DCP = des-gamma-carboxy prothrombin; HMW = high molecular weigh.</p>†<p>P<0.05 for Bonferroni corrected post hoc comparison with well-differentiated hepatocellular carcinoma.</p

Serum adiponectin levels and aspartate aminotransferase-to-platelet ratio index (APRI).

<p>A. Correlation between serum total adiponectin levels and APRI in controls (r = 0.482, <i>P</i><0.001). B. Correlation between serum high molecular adiponectin (HMW) adiponectin levels and APRI in controls (r = 0.476, <i>P</i><0.001). C. Correlation between serum total adiponectin levels and APRI in cases (r = 0.491, <i>P</i><0.001). D. Correlation between serum HMW adiponectin levels and APRI in cases (r = 0.485, <i>P</i><0.001).</p

Serum adiponectin levels and body mass index (BMI).

<p>A. Correlation between serum total adiponectin levels and BMI in controls (r = −0.142, <i>P</i> = 0.166). B. Correlation between serum high molecular adiponectin (HMW) adiponectin levels and BMI in controls (r = −0.144, <i>P</i> = 0.160). C. Correlation between serum total adiponectin levels and BMI in cases (r = −0.129, <i>P</i> = 0.208). D. Correlation between serum HMW adiponectin levels and BMI in cases (r = −0.131, <i>P</i> = 0.201).</p