I often write about fatty liver disease, a problem that is gaining mainstream recognition as published earlier this year in Newsweek. It is easy to assume that this is a problem just in the U.S., but data are coming in that highlight it as a global problem, as published in a recent article (1) and an accompanying editorial(2) in the journal Hepatology.
Younossi and his colleagues collected data on over 8.5 million people from 22 countries, using a method called meta-analysis which allows combining data from multiple studies. (I have described this method in a previous Perspective.) Rinella and Charlton nicely summarized the main findings of this very important study in their editorial.
Before I describe the main findings, I must define some terms. Non-alcoholic fatty liver disease, or NAFLD, refers to abnormal accumulation of fat in liver cells. In some individuals, NAFLD progresses to NASH, or non-alcoholic steatohepatitis. In NASH, the presence of inflammation and dying liver cells is added to the accumulation of fat in liver cells. Some individuals with NASH have progressive fibrosis, or scarring of the liver, which may ultimately lead to cirrhosis, complications of cirrhosis, the need for liver transplant, and death.
The first conclusion of the study is that approximately one in four people in the world are affected by NAFLD. There are geographical differences in the rates of NAFLD across the world, as shown in the figure below published in the editorial (the numbers represent the percent of people in that region who have NAFLD).
The color coding on this graph relates to the average caloric intake in the individual countries. While it is well known that obesity is associated with NAFLD, the relatively poor correlation with caloric intake with NAFLD rates suggests there are other factors involved. Some of these factors may include genetics (important in some regions), the type of food ingested, the composition of bacteria in the gut, and others.
The second major point taken from this study is that progression of fibrosis in NAFLD is slow and unusual. The editorial authors include an instructive figure to demonstrate this point. Out of 100 patients with NAFLD, only 5 will develop cirrhosis (the end stage of scarring) and only 1-2 patients will die as a result of that cirrhosis or require a liver transplant.
On face value, this seems like a small number of patients dying of their liver disease. However, when one considers the large number of people with NAFLD, those with cirrhosis represent a very significant problem. As stated by the authors, “Despite the low frequency of liver related mortality, the staggering denominator of over 1 billion adults with NAFLD coupled with a life-time risk of ~2% for liver-related mortality will eventually translate into ~20,000,000 liver-related deaths among patients currently alive with NAFLD.”
The final point is that NAFLD is, or will soon become, the most common cause of liver disease and liver-related death globally. The most important target for dealing with this enormous health problem is related to life-style changes to maintain a healthy liver, as I described in a previous Perspective. However, since there are currently no medicines available for this disease, we must also focus on those 20,000,000 people who are destined to die of NASH cirrhosis. This is the target for our Phase 2 clinical trial, NASH-CX, using our drug candidate GR-MD-02.
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Reference List
1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016 Jul;64(1):73-84.
2. Rinella M, Charlton M. The globalization of nonalcoholic fatty liver disease: Prevalence and impact on world health. Hepatology 2016 Jul;64(1):19-22.
