Non-alcoholic fatty liver disease is not a disease! The emperor’s new clothes
Alexander and colleagues deserve kudos for their most robustly designed study confirming that established cardiovascular risk factors are the cause of acute myocardial infarction or stroke, not fatty liver per se. (1,2)
Fatty liver is a symptom not a disease with, among a long list of causes, some total opposites as obesity and fasting. Moreover, there is no evidence yet that fatty liver per se can cause severe liver disease: a) in a series in 50 non selected subjects with morbid obesity, severe liver damage (16%) was constantly associated with alcohol intake or specific causes (3); b) no dose-response (a basis for causality), inflammation or fibrosis is not correlated with the amount of fat.
Alexander and colleagues showed that looking for fatty liver by combining imaging and blood tests (methods with major limitations as they highlighted) is useless. Indeed, the issue is about obvious unhealthy behaviours: smoking, obesity, low physical activity … Even alcohol should be a concern as use far above the low risk threshold --14 units/week or 6 glasses of wine, a unit being 8 g of pure alcohol (4) -- does not preclude diagnosis of non-alcoholic fatty liver disease by specialists! (5)
Alexander and colleagues' findings are in line with other studies. Even in patients with chronic hepatitis C, a more serious issue than fatty liver, more than half the excess mortality risk is due to health risk behaviours rather than chronic hepatitis C per se. (6)
Happily, life-style interventions (psycho-social) by trained multi-professional teams allow the achievement of healthy living, even in the long term: diet, physical activity, avoiding tobacco and alcohol. (7) However, dedicated care and lobbying for adequate public health policies seem less exciting than research for the magic bullet. In 2016 there were more than 100 drugs going through phase II and III clinical trials for a symptom whose market is estimated to be $1.6bn (£1.2bn; €1.4bn) by 2020.(8) First trials were published in the early 2000s but no magic bullet with clinically relevant effect (morbidity, mortality) yet.
1 Alexander M, Loomis AK, van der Lei J et al. Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ 2019;367:l5367.
2 Lazo M, Hernaez R, Bonekamp S et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011;343:d6891.
3 Braillon A, Capron JP, Hervé MA, Degoot C, Quénum C. Liver in obesity. Gut 1985;26:133-139.
4 Wise J. Cut drinking to reduce risk of cancer, says new guidance. BMJ 2016;352:i109
5 Braillon A Non-alcoholic fatty liver disease in alcohol users: an oxymoron? Gastroenterology 2018;154:1549-1550.
6 Innes H, McAuley A, Alavi M, Valerio H, Goldberg D, Hutchinson SJ. The contribution of health risk behaviours to excess mortality in American adults with chronic hepatitis C: a populationcohort-study. Hepatology 2018;67:97–107.
7 Baumann S, Toft U, Aadahl M, Jørgensen T, Pisinger C. The long-term effect of a population-based life-style intervention on smoking and alcohol consumption. The Inter99 Study--a randomized controlled trial. Addiction 2015;110:1853-60.
8 Braillon A. Non-Alcoholic Fatty Liver Disease and Disease Mongering. Am J Med 2019;132:e626.
Competing interests: No competing interests