Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide, associated with epidemics of overweight and resulting metabolic syndrome (MetS). Around 20–30% of patients with NAFLD develop progressive liver fibrosis, which is the most important predictor of liver-related and overall morbidity and mortality. In contrast to classical understanding, no significant association has been demonstrated between the inflammatory component of NAFLD, i.e., nonalcoholic steatohepatitis (NASH), and the adverse clinical outcomes. Older age (>50 years) and presence of type 2 diabetes mellitus, in addition to some genetic variants, are most consistently reported indicators of increased risk of having liver fibrosis. However, critical driving force for the progression of fibrosis and risk factors for this have still not been fully elucidated. Apart from the genetic profile, gut dysbiosis, weight gain, worsening of insulin resistance, and worsening of liver steatosis represent candidate factors associated with unfavourable development of liver disease. Cardiovascular events, extrahepatic malignancies, and liver-related deaths are the leading causes of mortality in NAFLD. As patients with advanced fibrosis are under highest risk of adverse clinical outcomes, efforts should be made to recognize individuals under risk and rule out the presence of this stage of fibrosis, preferably by using simple noninvasive tools. This process should start at the primary care level by using validated biochemical tests, followed by direct serum tests for fibrosis or elastography in the remaining patients. Patients with advanced fibrosis should be referred to hepatologists for aggressive lifestyle modification and correction of the components of MetS, and cirrhotic patients should be screened for hepatocellular carcinoma and oesophageal varices.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is considered the most prevalent chronic liver disease (CLD) worldwide [1, 2]
NAFLD is defined as the presence of >5% of liver steatosis in the absence of other causes of steatosis and CLD in the absence of significant alcohol consumption (>21 drinks/week in men and >14 drinks/week in women) [2]. e presence of simple steatosis is defined as nonalcoholic fatty liver (NAFL), whereas nonalcoholic steatohepatitis (NASH) is a more aggressive form of NAFLD that includes a histological presentation of steatosis, ballooning, and lobular inflammation that leads to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) [2, 3]
Around 20–30% of patients with NAFLD are under risk of developing progressive liver fibrosis, which is the most important predictor of both liver-related and overall morbidity and mortality
Summary
Nonalcoholic fatty liver disease (NAFLD) is considered the most prevalent chronic liver disease (CLD) worldwide [1, 2]. E three most common causes of mortality for patients with NAFLD were cardiovascular diseases (30% to 61.5% of cases), followed by extrahepatic malignancies (19% to 28%) and liver-related deaths (7.7% to 19%) [11, 12] In both studies, when compared to the general population, mortality was significantly higher only in patients with NASH and not in those with isolated steatosis [11, 12]. Similar conclusions were reached by the authors of another study that analysed the survival of a cohort of 229 patients with NAFLD, followed for an average of 26.4 years In this cohort, significantly higher mortality relative to the general population was observed only in patients with F3 and F4 stages of liver fibrosis regardless of the presence of NASH, whereas mortality was not increased in patients with NASH who had lower stages (F0 to F1) of fibrosis [15]. The development of diabetes and a higher FIB-4 index during the follow-up period were identified as significant [31]
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