Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes?

Abstract

Fatty liver is present in over ten percentage of the world population and it is a growing public health problem. Nonalcoholic fatty liver disease (NAFLD) is not a single disease, but encompasses a spectrum of diseases of different etiologies. It is difficult to find highly specific and sensitive diagnostic biomarkers when a disease is very complex. Therefore, we should aim to find relevant prognostic markers rather than accurate diagnostic markers which will help to minimize the frequency of liver biopsies to evaluate disease progression. There are several biomarker panels commercially available, however, there is no clear evidence that more sophisticated panels are better compared to simple criteria such as, presence of diabetes over five years, metabolic syndrome, obesity, obstructive sleep apnea, aspartate transaminase/alanine transaminase (ALT) ratio > 0.8 or ferritin levels > 1.5 times normal in patients with over six month history of raised ALT and/or ultrasonological evidence of fat in the liver. Currently the biomarker panels are not a replacement for a liver biopsy. However the need and benefit of liver biopsy in NAFLD is questionable because there is no convincing evidence that biopsy and detailed staging of NAFLD improves the management of NAFLD and benefits the patient. After all there is no evidence based treatment for NAFLD other than management of lifestyle and components of "metabolic syndrome".

Risk factor compositions of nonalcoholic fatty liver disease change with body mass index in males and females

“…Together with the advancements in modern biomedical technologies and the awareness of the harm caused by NAFLD, research has progressed from risk factors to exploring a strategy to predict NAFLD and NASH [4, 23]. Much effort has focused on identifying biomarkers to predict NASH or NAFLD; however, these strategies have rarely benefited clinical practice in terms of NAFLD diagnosis or discrimination of the pathological development of NAFLD [23].…”

“…Much effort has focused on identifying biomarkers to predict NASH or NAFLD; however, these strategies have rarely benefited clinical practice in terms of NAFLD diagnosis or discrimination of the pathological development of NAFLD [23]. The performance of current noninvasive evaluations of NAFLD varies among patients, aetiologies, and disease stages [23]. Ultrasonography is a simple and effective tool for steatosis screening, and liver biopsy is the gold standard for diagnosis of NAFLD in clinical practice [21,26].…”

“…Many factors have been reported to be associated with NAFLD or NAFLD-related pathological processes, such as inflammation and NASH, including tumour necrosis factor-α [23], interleukin-6 [24], linoleic acid [25], miR-122 [26], miR-34a [26], and haptoglobin, apolipoprotein A1, tissue inhibitor of metalloproteinase 1 and chitinase-3-like protein 1 [21, 23]. However, these factors represented only the general pathophysiological processes of inflammation, repair, remodelling and fibrosis.…”

“…However, these factors represented only the general pathophysiological processes of inflammation, repair, remodelling and fibrosis. Distinguishing the pathophysiological processes of NAFLD from general processes is problematic [23]. In addition, other biomarkers/panels for NASH have been described [23].…”

“…Distinguishing the pathophysiological processes of NAFLD from general processes is problematic [23]. In addition, other biomarkers/panels for NASH have been described [23]. Age, sex, insulin resistance, systemic hypertension, TG, ALT, AST, GGT, AST/ALT ratio, α2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, fasting blood glucose and fibrosis-4 were found to be associated with NASH and have been used in various diagnostic panels [23, 27, 28].…”