Fatty liver is commonly linked to high BMI individuals, sedentary lifestyles, metabolic syndrome, and/or type 2 diabetes to name a few co-factors.  But did you know that certain races or genetic make-ups are at risk of having fatty liver outside the expected population?  We say these folks have ‘lean NASH’ – people without the traditional risk factors but have fatty liver nonetheless.  Let’s look at lean NASH in greater detail.

What is lean NASH?

For starters, fatty liver and its advanced characteristics make up various phenotypes in the continuum.  Fatty liver starts out as something simple, a build-up of triglyceride in the individual hepatocytes, which we call non-alcoholic fatty liver disease or NAFLD.  Add in some lobular inflammation and some hepatocytes ballooning (a sign of liver cell stress), and you have the NASH triumvirate (NASH = non-alcoholic streatohepatitis, where steato- means fat or tallow and –hepatitis is, well, inflammation of the liver).  Add in fibrosis, and now you really have NASH which may progress to cirrhosis which puts you at risk of liver cancer.  The definitive diagnosis of NASH is based on liver biopsy, but who wants to get biopsied for this?

Common race values for body mass index (BMI) for Caucasians is 25 mg/m2 with Asians a little lower at 23 mg/m2, allowing us to define NASH or lean NASH on racial lines. We have not defined lean NASH to the extent as traditional NASH phenotypes, so we just consider this as non-obese NASH.  Looking specifically at the APAC countries, BMIs as (lean) NASH risk factor do vary:

  • 18.5-23 – China, India, Korea
  • ~25 – Japan, Taiwan, Sri Lanka, Hong Kong, Iran

Who’s at risk of having lean NASH?

We tend to focus on APAC people because they tend to have higher overall body fat in general, skin fold thickness, and more visceral fat than other races with similar age, sex, and BMI parameters.  Look for metabolic risk factors to be reduced in diagnosing lean NASH and the execution of clinical trials specifically in APAC countries.

How can I screen for the likelihood I have lean NASH?

In addition to anthropomorphic indicators and biochemical tests, the genetic marker of interest is the minor allele, PNPLA3 (rs738409, where G/G confers an increased NASH risk).  Non-invasive imaging techniques such as MRI-PDFF (various 1.5T and 3T systems with advanced liver imaging capabilities) and ultrasound controlled attenuation parameter (CAP) available on the FibroScan® system (Echosens, France).

The point is NASH is more than just BMI, and this people who think of themselves as healthy may still have fatty liver.  Adding waist circumference may not help either, as this can ignore the effects from subcutaneous vs. visceral fat distribution.  It’s the inflammatory factors from the visceral fat that contribute to the cardiovascular risk.  Watch for more validated genetic markers, too.  NAFLD/NASH is a silent disease after all – you may think you’re healthy, but your liver and fat may be hurting you.