Nonalcoholic fatty liver disease (NAFLD) affects about 20%-30% of the general population, and its clinical relevance arises
from the fact that 20%-30% of these subjects develop non-alcoholic steatohepatitis (NASH), a condition at risk of cirrhosis progression.
In addition NAFLD, and in particular NASH patients, are also at high risk of cardiovascular alterations, suffering overall from an increased
liver and no liver-related events of risk and death. At the moment liver biopsy is the gold standard for a correct evaluation of
NASH and fibrosis among NAFLD patients. However, the high and increasing prevalence of NAFLD has triggered an intensive search
for alternative and non-invasive methods for evaluating disease severity. Specifically we can distinguish two main groups of non-invasive
methodologies, namely ‘serum markers’ that use clinical and/or biochemical variables, and methodologies derived from elaboration of
parameters arising from liver imaging techniques. All these tools showed encouraging results, even though their utility in clinical practice
in the individual patients is still under debate. Therefore further efforts are needed in order to generate non-invasive algorithms that correctly
assess liver damage in NAFLD patients. In particular, it should be interesting to perform gender-specific analysis, by combining
old and new tools, with the aim to generate more accurate scores. Finally we think that non-invasive scores should not only be able to
correctly classify the severity of liver disease in NAFLD patients, but also predict liver and non-liver related morbidity and mortality, further
acting as time-dependent markers of liver and systemic disease activity. This review summarizes the present knowledge on noninvasive
diagnosis in NAFLD patients, and suggest future directions for this complex research area.