Non‐alcoholic fatty liver disease: Confronting the global epidemic requires better awareness

A paper in this issue of the Journal of Gastroenterology and Hepatology reports a study from Hong Kong, where 83% of the general population had never come across the term non-alcoholic fatty liver disease (NAFLD), and among those that had, there were many misconceptions regarding the condition.1 Hong Kong is a developed country with a relatively well-informed, highly literate society, so that levels of awareness regarding NAFLD are likely to be much worse among less well-off populations with lower literacy rates. This is worrying, given the magnitude of public health problems posed by NAFLD. NAFLD is one of the commonest, if not the commonest, liver diseases in Western populations, affecting at least 24–42% of adults.2 It is strongly associated with insulin resistance and metabolic syndrome. Parallel to rapidly increasing rates of obesity and type 2 diabetes, NAFLD is being increasingly diagnosed in the Asia–Pacific region, and prevalence rates of 5–40% have been reported.2 As obesity among children becomes increasingly common,3 similar trends are being observed in the pediatric population; NAFLD has been reported to occur in 3% of the general pediatric population and in 53% of obese children.4,5 There are even disturbing reports of NAFLD with advanced fibrosis and cirrhosis in young children, and NAFLD in toddlers.6,7 NAFLD is now probably the most common cause of liver disease in the pre-adolescent and adolescent age groups.8 NAFLD includes a spectrum of liver disease ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and advanced hepatic fibrosis and cirrhosis. Approximately 12–24% of patients with simple steatosis go on to develop NASH with early fibrosis after 8–13 years, and depending on the degree of fibrosis at baseline, 15–25% of patients with NASH develop cirrhosis over a similar period of time.9,10 There is now mounting evidence to suggest that a significant proportion of patients diagnosed as having cryptogenic cirrhosis have NASH-related cirrhosis. Approximately 7% of patients with NASH-associated cirrhosis develop hepatocellular carcinoma (HCC) within 10 years.11,12 Older age and even social alcohol consumption have recently been found to be risk factors for the development of HCC among patients with NASH-related cirrhosis.13 The long-term prognosis of NASH-related cirrhosis is no better than that of hepatitis C cirrhosis, and the majority of patients with NASH-related cirrhosis succumb to liver related causes. In addition, people with NAFLD, even in the absence of cirrhosis, have a high morbidity because of associated cardiovascular disease and type 2 diabetes. In short, NAFLD is already a major public health problem in Western countries, and is fast becoming one in other parts of the world. Although some NASH patients progress to cirrhosis, others will not, and some even improve histologically. Histological progression is associated with increasing age, obesity and type 2 diabetes. Guidelines on the management of diabetes, while giving detailed instructions on screening patients for microvascular and macrovascular complications, do not emphasize screening for NAFLD. Here, we could be losing the opportunity to screen a population at high risk of NAFLD; for instance, a NAFLD prevalence of 70% has been reported among Italian type 2 diabetics.14 Family studies and ethnic variations in susceptibility suggest that genetic factors can also play an important role in determining disease risk.15 However, genetic associations with advanced NAFLD have yet to be convincingly demonstrated, but raise questions as to whether family members of patients diagnosed with NAFLD or cryptogenic cirrhosis should be screened for NAFLD. Strong associations have also been shown between NAFLD and polycystic ovarysyndrome16 and obstructive sleep apnea,17 suggesting that patients with these conditions require hepatic evaluation. Ultrasound is currently the most widely used screening test to detect NAFLD.18 Imaging with ultrasound, computed tomography and magnetic resonance imaging can detect steatosis only when more than one-third of the liver is affected. NASH or fibrosis cannot be detected, and newer techniques, such as transient elastography and proton magnetic resonance spectroscopy, are still being evaluated. Liver biopsy is mainly indicated for staging when advanced disease is suspected, and is not required for diagnosis in a patient with typical features of NAFLD.18 Several scoring systems (e.g. The NAFLD Fibrosis Score) and serum fibrosis markers (e.g. European Liver Fibrosis Panel) have been shown to accurately predict advanced fibrosis in NAFLD,19,20 but require further validation before they can be recommended for use in routine clinical practice.21 There are no large randomized controlled studies on which to establish evidence-based treatment recommendations for NAFLD.22 Given the pathophysiological association of NASH with insulin resistance and metabolic syndrome, treatment strategies should aim to improve insulin sensitivity, modify metabolic risk factors and protect the liver from oxidative stress and other insults. These measures would also greatly reduce cardiovascular risk, which is an important concern in patients with NAFLD.23 Lifestyle changes should include nutritional counseling and regular aerobic exercise. However, although lifestyle changeslead to weight loss, the effect is usually short lived, and long-term data on histological improvement in the liver are lacking. Recently, very promising results have been reported on liver histology in patients undergoing bariatric surgery for extreme obesity.24 Another unresolved issue is the effect of a moderate alcohol intake on NAFLD. Obesity increases the risk of cirrhosis in heavy drinkers. A recent study has shown lower transaminase levels in people who drank moderate amounts of alcohol than in abstainers.25 However, a study from Sweden has showed that even a moderate alcohol consumption was associated with progression of fibrosis in patients with NAFLD.26 The effect was more pronounced in episodic heavy drinkers. Whether or not patients with NAFLD should be advised to abstain from alcohol is still unclear. With regards to pharmacological therapy, well-powered, randomized, placebo controlled trials of therapeutic agents showing a clear benefit in NAFLD and NASH are still being anticipated. In the absence of a definitive treatment for NAFLD, the current emphasis should be on prevention. For any preventive program to succeed, competent primary care doctors and a motivated public are required. This brings us back to the subject of the paper from Hong Kong.1 Both public awareness regarding NAFLD and knowledge and treatment practices relating to NAFLD among doctors have been poorly studied. The few, like the Hong Kong study, that have addressed these issues have found disappointing results. A recent study from Italy found GPs' knowledge and practices regarding NAFLD to be “barely adequate”, although significant improvements were seen after an educational intervention.27 Another study from the USA found that a significant proportion of primary care physicians were unaware of guidelines on viral hepatitis B and C and NAFLD, but those aware of the guidelines were more likely to screen appropriately and avoid unnecessary testing.28 These findings indicate that more needs to be done to assess awareness and the implementation of guidelines in hepatology. If we are to effectively tackle the NAFLD-related public health problem, primary care doctors should be required to have a basic knowledge of the pathophysiology of NAFLD and NASH, and know who, when and how to screen, be able to identify those most likely to have advanced disease so that they can be referred for specialist opinion or liver biopsy and know how to manage and monitor patients with milder forms of NAFLD. For instance, monitoring cardiovascular risk factors and glucose tolerance are key issues in most patients with metabolic syndrome, the underlying pathophysiology of NAFLD and NASH. There is currently a declining prevalence of metabolic diseases among the higher socioeconomic strata of the Western world. This encouraging observation is most likely to be because of the increased awareness of the benefits of a healthier lifestyle, but also because of the application of potent lipid-lowering drugs, antihypertensives and other pharmacotherapy under the supervision of primary care physicians. Population-based educational campaigns on metabolic syndrome and NAFLD would thus seem worthwhile, as would school-based programs to educate children on the value of a healthy lifestyle, because satisfactory community participation can only be expected from a public that is well informed regarding NAFLD and its potential complications.