Nonalcoholic fatty liver disease: Evolving paradigms

Abstract

In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.

Keywords: Nonalcoholic fatty liver disease, Biomarkers, Clinical correlates, Diagnosis, Epidemiology, Genetics, Liver histology, Management, Metabolic Syndrome, Pathogenesis, Screening, Type 2 diabetes

Core tip: Nonalcoholic fatty liver disease (NAFLD) is a pandemic disease. Recent evidence highlights new concepts in clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. Other than the classical obese phenotype of NAFLD, a lean though metabolically abnormal variant has been recognized. Simple steatosis is no more considered a benign condition; insulin resistance is necessary but not sufficient for the disease progression, and NAFLD is not only a mere hepatic manifestation of metabolic syndrome, but may forerun the development of metabolic syndrome and cardio-renal complications. Several non-invasive diagnostic tests are now available and new drug treatment options are coming.