GLASGOW, SCOTLAND — Serum fibrosis markers—currently used as a research tool—have high sensitivity and specificity for diagnosing more severe forms of nonalcoholic fatty liver disease, according to a presentation at the Diabetes U.K. Annual Professional Conference.
Diagnosis of the most severe forms of nonalcoholic fatty liver disease (NAFLD), which include the onset of steatohepatitis and subsequent fibrosis and cirrhosis, requires measurement of the extent of inflammation and the presence of fibrosis. Currently, only liver biopsy can identify patients with these symptoms; such patients must be managed more aggressively than patients with less severe forms of the disease, particularly with respect to cardiovascular risk factors. However, biopsy is an expensive diagnostic procedure and is dangerous for the patient.
Dr. Christopher Byrne, head of the endocrinology and metabolism unit at the University of Southampton (England), said he believes that “in future, noninvasive serum markers might be better. Research is beginning to suggest that within NAFLD, a scoring system such as that using ELF [enhanced liver fibrosis assay, which looks at several serum biomarkers of fibrosis] might prove useful.” When combined with age as a risk factor, the three markers assessed by the ELF blood test—hyaluronic acid, procollagen III amino terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1)—have around 85% specificity and sensitivity for moderate to severe NAFLD, he noted.
Alanine aminotransferase (ALT) and GammaGT, plasma markers currently used to help guide diagnosis for NAFLD, are not very accurate, according to Dr. Byrne. “ALT is an extraordinarily poor proxy. Both GammaGT and ALT are in the normal range in patients who have quite extensive NAFLD when they get to biopsy,” he said.
NAFLD is one of the most common forms of chronic liver disease in developed countries, affecting 10%–24% of the general population, and it is especially common in people with type 2 diabetes. Liver damage in this condition is caused by accumulation of lipids, oxidative stress, and inflammation caused by release of proinflammatory cytokines. The associated marked insulin resistance in NAFLD has led some scientists to propose that it might be a malignant form of metabolic syndrome.
“Even adjusting for obesity, patients with NAFLD have marked increases in nonesterified fatty acid accumulation,” Dr. Byrne said. “So release of these from adipocyte depots into circulation is abnormal in these patients. But we don't know why [it is] associated with marked insulin resistance.”
He presented research showing that a group of 1,974 type 2 diabetes patients with NAFLD had a significantly higher prevalence of coronary, cerebral, and peripheral cardiovascular disease than a group of 418 type 2 diabetics without fatty livers. “NAFLD is associated with increased mortality, especially at the more severe end,” Dr. Byrne said. “In these patients, even adjusting for all conventional cardiovascular risk factors and features of the metabolic syndrome, NAFLD is an independent cardiovascular risk factor. If you find NAFLD, think accelerated cardiovascular risk and treat aggressively.”
Treatment recommendations include initial weight loss in obese patients; limited evidence suggests that therapy with glitazones also can be used to increase insulin sensitivity and decrease liver fat content. “Glitazones show promise,” Dr. Byrne said. “A new indication for glitazone therapy may prove to be NAFLD.”