Fatty liver disease encompasses a spectrum of diseases, including alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), one type of which is non-alcoholic steatohepatitis (NASH). However, it is increasingly recognised that a large number of patients have both harmful alcohol consumption and metabolic risk factors, such as obesity, diabetes, and dyslipidaemia.
Independent of which aetiology predominates, there is a possibility of disease progression to advanced liver disease, cirrhosis, or hepatocellular carcinoma (HCC). The only distinction between ALD and NAFLD is daily alcohol consumption of <30 g for men and <20 g for women. Alcohol consumption above these limits represents ALD.1 Harmful alcohol consumption is a major burden to an individual’s health in general, and particularly for the liver. According to the World Health Organization (WHO) noncommunicable diseases 2014 report,2 an estimated 3.3 million deaths, or 5.9% of total deaths worldwide, were attributable to alcohol consumption in 2012. Approximately half a million of these were as a result of liver cirrhosis, which represents 0.9% of total deaths, 10.4% of alcohol-attributable deaths, and 0.6% of all disability adjusted life-years. Data from the European Union (EU) have shown that 41% of liver-related deaths, excluding primary liver cancer, are attributable to alcohol and 46% are of unknown aetiology. However, as recently reviewed by Sheron,3 it is possible that a large percentage of the undisclosed causes are ALD and that around 60–80% of liver-related deaths in Europe are, in fact, due to excess alcohol consumption.
Although the disease has a slow progression, usually >10 years, patients tend to present with symptoms in the later stages of disease, when they already have complications such as ascites, jaundice, infections, gastro-intestinal bleeding, and HCC. In fact, HCC is one of the more serious consequences of alcoholic liver disease, and it was recently reported that alcohol is the second leading cause of HCC, being responsible for about one-third of all HCC.4 NAFLD is an umbrella term for several different fatty liver diseases, including steatosis, NASH, and cirrhosis. For many years, there has been a dichotomy between steatosis and NASH; steatosis is characterised by either pure steatosis or steatosis and mild lobular inflammation, whereas NASH is defined by hepatocyte ballooning plus lobular inflammation. Recently, this distinction with regard to diagnosis does not seem so important, since the major prognostic factor in long-term follow-up is the presence and degree of fibrosis.5,6
The prevalence of NAFLD worldwide is estimated to be 25.2%, the highest being in the Middle East and the lowest being in Africa, which could be related to the nutritional and physical activity status in these areas.7 NAFLD incidence is more frequent in males, increases with age, and increases in the presence of a metabolic syndrome, such as hypertension, obesity, or dyslipidemia.8 However, a certain degree of discrepancy between excessive caloric intake and NAFLD in areas such as Asia and South America suggests that ethnicity and genetic factors also play a significant role in the development of NAFLD. Recently, two variants of the genes PNPLA3 and TM6SF2 were found to have a strong effect on the risk and severity of NAFLD and ALD. Additionally, a variant of the MBOAT7 gene was also associated with ALD; however, its association with NAFLD is still to be proven.9 NAFLD is linked to an increased risk of cardiovascular disease; several studies have demonstrated that the major cause of death in patients with NAFLD is cardiovascular related, including a recent meta-analysis of 8 studies, as well as a 26-year long-term study that reported 43% of deaths of NAFLD patients was due to cardiovascular disease.10