Growth hormone and hepatocellular carcinoma

Development of hepatocellular carcinoma (HCC) is a function of activation or inhibition of several molecular pathways where important protein, cytokine, and interleukin synthesis and destruction can be changed. An alteration in the secretion pattern of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) has been described in chronic liver diseases. Reduction of the hepatocyte mass and impaired synthesis capacity of the damaged hepatocytes leads to a decrease in IGF-1 synthesis with subsequent negative feedback regulation and increased GH levels. We previously reported an association between IGF-1 level and HCC risk and prognosis. The current population study aimed to assess the association between GH and HCC risk and prognosis. With approval from The University of Texas MD Anderson Cancer Center Institutional Review Board, 763 patients with HCC were prospectively enrolled in our ongoing population study. Circulating plasma levels of GH were determined in patients with HCC with cirrhosis (n=489), HCC without cirrhosis (n=274), healthy controls (n=200), and non-HCC cirrhotic patients (n=75). On the basis of Mayo clinic values of GH in men and women, we classified HCC patients as having high GH values (women, >3.67 μg/L; men, >.9 μg/L) or low GH values (women, ≤3.67 μg/L; men, ≤.9 μg/L). To identify independent risk factors for HCC with high GH, we estimated the odds ratio (OR) using logistic regression analy ses. In addition, hazard ratios (HR) were calculated using Cox proportional hazards models to assess the role of GH in HCC prognosis. For both OR and HR, 95% confidence intervals (CI) were determined. We observed higher mean (±standard error [SE]) baseline GH in patients with HCC with cirrhosis (3.5±0.2) or without cirrhosis (2.2±0.2) than in healthy controls (0.4±0.1; P<.001). The increase was also observed among non-HCC cirrhotic patients (3.3±.5). Restricted analysis in the non-cirrhotic HCC population and healthy controls showed that those with high GH had an approximately 7-fold increased risk of HCC development compared with those with low GH (OR 6.8, 95% CI 1.3-36.4, P=.001). In addition, high GH was an independent risk factor for mortality; the adjusted HR for overall survival in patients with high GH was approximately two times higher than in patients with low GH (HR 1.8, 95% CI 1.3-2.4, P≤.001). In conclusion, high GH may predict HCC risk and prognosis, especially in the absence of underlying chronic liver disease. Further validation of the IGF-1/GH axis in HCC risk and prognosis in independent populations is highly warranted.