Visceral adiposity and insulin resistance are independent predictors of the presence of non-cirrhotic NAFLD-related portal hypertension

Introduction: We previously demonstrated in an animal model that steatosis, in the absence of fibrosis, induces a significant rise in portal pressure, indicating substantial changes in liver hemodynamics. As assessment of portal pressure is an invasive procedure, non-invasive parameters are needed to identify patients at risk. Aims: To study the portal pressure in nonalcoholic fatty liver disease patients and to identify factors that are possibly related to steatosis-induced changes in liver hemodynamics. Materials and methods: Patients presenting with a problem of overweight or obesity, and in whom non-invasive investigations showed signs of liver involvement, were proposed for transjugular hepatic vein catheterization and liver biopsy. The biopsy was scored according to the Nonalcoholic Steatohepatitis Clinical Research Network Scoring System. Results: A total of 50 consecutive patients were studied. Their mean age was 47.9 +/- 1.8 years; 31 (62%) were female. Hepatic venous pressure gradient was normal in 36 (72%) and elevated in 14 (28%) patients. The degree of steatosis was the only histological parameter that differed significantly between the two groups (P = 0.016), and was a predictor of the presence of portal hypertension (PHT) in regression analysis (P = 0.010). Comparing normal versus portal hypertensive patients, waist circumference (117 +/- 2 versus 128 +/- 4 cm, P = 0.005), waist-hip ratio (0.96 +/- 0.06 versus 1.04 +/- 0.03, P = 0.003), visceral fat (229 +/- 15 versus 292 +/- 35cm(2), P = 0.022), fasting insulin (15.4 +/- 1.7 versus 21.8 +/- 2.4 mu U ml(-1), P = 0.032), fasting c-peptide (1.22 +/- 0.06 versus 1.49 +/- 0.09 nmol l(-1), P = 0.035) and homeostasis model assessment-insulin resistance (HOMA IR) (3.28 +/- 0.29 versus 4.81 +/- 0.57, P = 0.019) were significantly higher. Age, gender, liver enzymes, ferritin and high-sensitive C-reactive protein were not significantly different. In regression analysis, waist circumference (P = 0.008) and HOMA IR (P = 0.043) were independent predictors of PHT. Conclusions: Estimates of both visceral adiposity and IR are predictors for the presence of PHT, related to the degree of steatosis, and may help in identifying patients who are at risk of developing steatosis-related complications. International Journal of Obesity (2011) 35, 270-278; doi: 10.1038/ijo.2010.134; published online 27 July 2010