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

Abstract

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 ¼ 0.016), and was a predictor of the presence of portal hypertension (PHT) in regression analysis (P ¼ 0.010). Comparing normal versus portal hypertensive patients, waist circumference (117 ± 2 versus 128 ± 4 cm, P ¼ 0.005), waist-hip ratio (0.96 ± 0.06 versus 1.04 ± 0.03, P ¼ 0.003), visceral fat (229 ± 15 versus 292 ± 35 cm 2 , P ¼ 0.022), fasting insulin (15.4 ± 1.7 versus 21.8 ± 2.4 mU ml À1 , P ¼ 0.032), fasting c-peptide (1.22 ± 0.06 versus 1.49 ± 0.09 nmol l À1 , P ¼ 0.035) and homeostasis model assessment-insulin resistance (HOMA IR) (3.28 ± 0.29 versus 4.81 ± 0.57, P ¼ 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 ¼ 0.008) and HOMA IR (P ¼ 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.

Insulin resistance in patients with cirrhosis and portal hypertension

“…In addition, HOMA-2 index, together with prothrombin time, were the only independent predictors for the presence of CSPH. These findings suggest that IR may play a role in the progression of the chronic liver disease at the earlier stages, as it has already been suggested in patients with nonalcoholic fatty liver disease (16), where the presence of IR was associated with the presence of mild PH (in that study, all patients had HVPG Ͻ 10 mmHg). Interestingly, our data, including patients with more severe PH, show that, once CSPH has developed, the correlation between HOMA-2 index and HVPG is lost.…”

“…Thus it has been suggested that IR has a negative impact on the response rates to interferon-based therapy in chronic hepatitis C virus infection (19) and that IR could be a predictor of the presence of PH in patients with nonalcoholic fatty liver disease (16). Furthermore, a recent published clinical study has suggested that IR is able to independently predict the presence of gastroesophageal varices in cirrhosis (11).…”

The Symptoms of Gastroesophageal Reflux Disease Correlate with High Body Mass Index, the Aspartate Aminotransferase/Alanine Aminotransferase Ratio and Insulin Resistance in Japanese Patients with Non-alcoholic Fatty Liver Disease

“…Several studies in Western counties and Japan found that both the AST/ALT ratio and insulin resistance were important risk factors for the severity of NAFLD (20)(21)(22)(23)(24). Because the severity of NAFLD is apparently due to visceral fat accumulation (12,24), the negative correlations observed between the AST/ALT ratio and insulin resistance with the FSSG in the present study suggested that the relationship between the BMI and GERD symptoms may also be dependent on the visceral fat accumulation in subjects with NAFLD.…”

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients

“…Both cohorts enrolled bariatric surgery patients. The third cohort was sampled in Antwerp in Belgium, and enrolled patients presenting at the obesity clinic for an overweight problem [21]. In all three cohorts, patients were excluded if they were reported to consume more than 20 g of alcohol per day.…”