Diagnosis and Treatment of Non-alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting adults and children, leading to significant morbidity. It is often associated with the metabolic syndrome, although multiple pathogenetic mechanisms have been suggested. In the coming decades, it promises to be the leading cause of liver disease in industrial countries.
Aim: To provide a comprehensive, updated review of diagnosis and management of NAFLD and to appraise the evolution of new modalities in these areas.
Methods: An Ovid MEDLINE search was performed to identify pertinent original research and review articles. Selected references in these articles were also evaluated.
Results: The diagnosis of hepatic steatosis and steatohepatitis or non-alcoholic steatohepatitis (NASH) is not yet possible without liver biopsy. This is impractical given the large numbers affected by the condition. Current therapy has focused on improving insulin resistance and mediators of inflammation, factors probably associated with disease progression.
Conclusions: There are no proven non-invasive diagnostic modalities to distinguish NAFLD and NASH, but new biomarker panels are approximating the liver biopsy in accuracy. Therapeutic targets of drug development are in early stages, but a multifaceted approach will probably yield several treatment options in the years to come.

Introduction

Fatty liver disease is not a new condition, and indeed, alcohol-induced liver injury dates back thousands of years. The entity of non-alcoholic fatty liver disease (NAFLD) is also not a new condition, but was not appreciated in early reports. In the 1950s, livers consistent with non-alcoholic steatohepatitis (NASH) were described in obese individuals, but surreptitious alcohol use was suspected.^[1] In the now famous report of Ludwig et al. in 1980, the term NASH was coined.^[2] It was not until the 1990s, however, that the prevalence and increasing incidence of the condition brought it into the limelight. It was not coincidence that the recognition of NAFLD paralleled the alarming increase in body mass index (BMI) in the American population^[3] (Figure 1). The umbrella term of NAFLD embodies simple steatosis, NASH and advanced fibrosis or cirrhosis related to this pathological entity.