Comparative Accuracy of Clinical Fibrosis Markers, Hepascore and Fibroscan® to Detect Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. METHODS: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3-4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. RESULTS: In 271 NAFLD patients, 83 (31%) had F3-4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). CONCLUSIONS: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals.

Non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. The prevalence of NAFLD is up to 30% in developed countries and nearly 10% in developing nations, making NAFLD the most common liver condition in the world. The pathogenesis of NAFLD is related to insulin resistance and, thus, it is frequently found in individuals who have central obesity or diabetes. Insulin resistance and excess adiposity are associated with increased lipid influx into the liver and increased de novo hepatic lipogenesis, promoting hepatic triglyceride accumulation. Defects in lipid utilization via mitochondrial oxidation and lipid export may also contribute to hepatic lipid build-up. Adipocytokine alterations, lipotoxicity from saturated fatty acids and fructose have been all been implicated in causing hepatocyte injury in NAFLD through pathways involving oxidative and endoplasmic reticulum stress. Clinically, NAFLD is commonly asymptomatic and frequently detected incidentally by blood liver function tests or imaging performed for other reasons. Subjects with NAFLD have a higher mortality rate than the general population and are at increased risk of developing cardiovascular disease and diabetes in the future. Histologically, NAFLD occurs as a spectrum from mild hepatic steatosis only, to non-alcoholic steatohepatitis (NASH) characterized by hepatocellular injury and inflammation, to cirrhosis. A diagnosis of NASH with associated fibrosis heralds a more significant prognosis as it is more likely to progressive to cirrhosis with complications of hepatic failure and hepatocellular carcinoma. Currently, the diagnosis of NASH requires a liver biopsy, however, serum based markers of hepatocyte apoptosis such as cytokeratin-18 fragments offer promise as accurate non-invasive diagnostic tests. Treatment of NAFLD revolves around addressing concomitant metabolic risk factors and improving insulin resistance through weight loss measures and exercise. Insulin sensitizing agents such as pioglitazone and anti-oxidant agents such as vitamin E show some promise in improving liver histology in patients with NASH, however, the long-term benefit of these medications has not been demonstrated.

Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist as they share the pathogenic abnormalities of excess adiposity and insulin resistance. Although type 1 diabetes mellitus (T1DM) is due to a relative lack of insulin, an increased prevalence of obesity and insulin resistance in this population means that NAFLD also commonly coexists with this condition. Both T2DM and NAFLD are associated with adverse outcomes of the other; T2DM is a risk factor for progressive liver disease and liver-related death in patients with NAFLD, whereas NAFLD may be a marker of cardiovascular risk and mortality in individuals with T2DM. Nonalcoholic steatohepatitis-a histological subtype of NAFLD characterized by hepatocyte injury and inflammation-is present in approximately 10% of patients with T2DM and is associated with an increased risk for the development of cirrhosis and liver-related death. Current treatment strategies aim to improve insulin resistance via weight loss and exercise, improve insulin sensitivity by the use of insulin-sensitizing agents (for example, pioglitazone) and reduce oxidative stress by the use of antioxidants, such as vitamin E. Pioglitazone and vitamin E supplementation show the most promise in improving hepatic steatosis and inflammation but have not yet been demonstrated to improve fibrosis, and concern remains regarding the toxicity of long-term use of both of these agents.