Non Alcoholic Fatty Liver Disease

Non Alcoholic Fatty Liver Disease (NAFLD), or “fatty liver” as it is commonly known, is one of those conditions that is synonymous with being Fat. The clue is in the name. But it turns out this conditions has a lot less to do with fat OR the liver than we originally thought it did…

Introduction to NAFLD

According to the National Institute for Clinical Excellence, Non Alcoholic Fatty Liver Disease (NAFLD) is characterised by excess fat accumulation in the liver (present in more than 5% of liver cells), that is NOT the result of excessive alcohol consumption or any other cause.

Almost all people with NAFLD have a diagnosis of “hepatic steatosis”, which means there is an “excess” of fat in the liver but no inflammation or damage. A small percentage of people will have “non-alcoholic steatohepatitis” or NASH. This means that inflammation is present. Inflammation can lead to scarring (fibrosis), which can potentially damage the liver’s ability to function properly. We call this cirrhosis of the liver, and it some cases it leads to liver failure.

No need to panic

This may sound scary, but it’s important to remember that it is extremely uncommon for people to develop cirrhosis of the liver without a history of excess alcohol consumption or an underlying condition (such as viral or autoimmune hepatitis). Later on, I’m going to tell you just how rare it is. 

The global prevalence of NAFLD is estimated to be around 20%. It’s higher in SWANA and South America. That being said, a 2018 study found that among over 17 million general practice records from Italy, Spain, the UK, and the Netherlands, less than 2% of people had been formally diagnosed.

We can stop blaming it on Fat

Still, NAFLD is the most common cause of abnormal liver blood test results in the UK, formal diagnosis or not! And despite its reputation, it is not a Fat person disease. In fact, around 40% of the global NAFLD population are lean and there is no evidence that weight loss prevents the development of NAFLD or NASH.

So what does cause it then?

Nobody knows for sure but we have some theories. Several genes have been identified so we know there is a genetic component. There has been some interesting research looking into gut biome, but nothing concrete. And then there’s insulin resistance. Plenty more on that later. 

What's in a name?

The term non-alcoholic was first coined back in 1980, to describe the liver histology associated with excess liver fat in the absence of significant alcohol consumption. We’ve since discovered that aside from superficial similarities under the microscope, liver disease caused by alcohol consumption has a very different pattern and prognosis to NAFLD.

Which is why, in early 2020, an international panel of experts created a new term; Metabolic dysfunction-associated fatty liver disease or MAFLD. As tempting as it is to laugh at the name change, experts are finally recognising that hepatic steatosis should not be diagnosed and treated the same way as other forms of liver disease. In fact, it appears to be less and less about the liver after all.

Sad times for hepatologists who are getting paid to do all those unnecessary liver biopsies, huh?

You say potato, I say po-tah-to

MAFLD has its own diagnostic criteria and diagnostic criteria. First, you must have hepatic steatosis or fatty infiltration of a minimum of 5% of your liver cells. Then you either have to be Fat, have type 2 diabetes, or have at least 2 out of the following 7 “metabolic risk abnormalities”:

  • Waist circumference >102/88 in Caucasian men and women, (or >90/80 cm in Asian men or women).
  • Blood pressure >130/85 mmHg or specific drug treatment.
  • Plasma triglycerides >150 mg/dL (>1.70 mmol/L) or specific drug treatment
  • Plasma HDL-cholesterol <40 mg/dL (<1.0 mmol/L) for men and <50 mg/dL (<1.3 mmol/L) for women or specific drug treatment
  • Prediabetes (i.e. fasting glucose levels 100-125 mg/dL (5.6-6.9 mmol/L) or 2-hour post-load glucose levels 140-199 mg/dL (7.8- 11.0 mmol/L) or HbA1c of 5.7-6.4% (39-47 mmol/mol)
  • Homeostasis model assessment of insulin resistance (HoMAIR) score >2.5
  • Plasma high-sensitivity C-reactive protein level >2 mg/L

 

This is starting to feel more and more like the “pre-diabetes” diagnosis that we’ve all been obsessed with since 2001. Anyone remember that story?

So it is NAFLD or MAFLD?

The answer is, I don’t know! On the one hand, I find it odd that “excess alcohol” is a recognised risk factor for NAFLD. Make that make sense!

I am also glad that we are finally acknowledging the link between hepatic steatosis and insulin resistance. I’m doubt many doctors will have been surprised to hear that one. It’s what we see in practice every day. 

I am concerned, however, that we are once again pathologizing something that does not need to be pathologized. What’s the point of defining a condition that is asymptomatic, is not known to cause any long term complications, and has no known effective treatment? Unless experts are looking for another excuse to sell weight loss? 🤔

Diagnosis and Prognosis

Let’s talk diagnosis. NAFLD is usually asymptomatic but it may cause fatigue, general malaise, and/or abdominal discomfort. It is usually picked up through blood test (persistently raised LFTs for longer than 3 months – NOT just a one-off) and/or an ultrasound scan.

It’s extremely common for liver function to be abnormal at the time of type 2 diabetes diagnosis, and this usually settles over a couple of years as treatment commences. Hardly surprising since NAFLD is linked to insulin resistance, and the mainstay of type 2 diabetes treatment is to reduce insulin resistance.

Management of NAFLD

So what should your doctor do if you have abnormal liver function tests for longer than 3 months? First, they should perform a liver screen looking for other underlying causes. Then they need to calculate your fibrosis score using your liver function test results.

If you are high risk, and ONLY if you are a high risk, you should be referred to a liver specialist for a biopsy and further treatment. It’s important, therefore, to ask your doctor what your risk is? Even better, you can calculate your FIB-4 score yourself.

Chances are, there’s not much more you’ll have to do. According to the National Institute of Health “Experts estimate about 24% of U.S. adults have NAFLD and about 1.5% to 6.5% of U.S. adults have NASH. NAFL typically does not progress to cause liver damage or complications”. (NIDDK)

Am I going to end up in liver failure?

According to the evidence, approximately 40% of people with NASH (less than 6.5% of people with NAFLD) have grade F3 and bridging fibrosis confirmed on biopsy. Bear in mind that this is only one study, but it’s the best we’ve got. Of those with F3 NASH, approximately 20% developed cirrhosis. And of those with cirrhosis, approximately 20% of people develop hepatic decompensation (signs of liver failure).

So let’s do the math for a moment. If you’re diagnosed with NAFLD today, the chances of you having grade F3 NASH with bridging fibrosis is between 0.6 – 2.6%. The chances of you developing cirrhosis is between 0.1 – 0.5%. The chances of you developing liver failure is between 0.02 – 0.1%.

To put that in context, according to the internet the lifetime odds of dying in a crash for a person born in the USA are 1 in 93 (1.1%). The lifetime odds of dying in a fall are 1 in 98. So worst case scenario, you are still 10 times more likely to die from a fall than you are to develop liver failure as a result of NAFLD.

Management of NAFLD

According to this recent literature review, “To date, there is no specific drug treatment for NAFLD, however it is believed that a combination of treatment goals (lifestyle adjustments, increasing physical activity and smoking/ alcohol cessation) can be beneficial”.

It is believed that lifestyle adjustments can be beneficial. So why does that get translated into lose weight? Is there any decent evidence to support this advice? Unsurprisingly, no.

Every single study I have come across that measures the impact of weight loss on NAFLD (including all the ones quoted in the aforementioned literature review) are flawed for a number of reasons:

  • Very low number of participants
  • The participants were not followed up for a sufficient amount of time
  • There was a focus on weight loss and liver function tests as primary outcomes as opposed to histological evidence
  • None of them consider the risks of weight loss

 

Weight loss CAUSES NAFLD!

Speaking of, did you know that rapid weight loss is a risk factor for NAFLD? Once again, this is not surprising. Weight loss worsens insulin resistance. Insulin resistance is linked to NAFLD. Simple!

You won’t be shocked to hear that most of the literature I found is extremely fatphobic. One article in the World Journal Of Gastroenterology claims that “patients with NAFLD consume high caloric diets, especially in the form of carbohydrate and fats, in comparison to control population.” It also claims that “NAFLD patients consume a larger quantity of soft drinks and meat than controls.”

And? Even if this were true (the evidence that they base this on is highly suspicious), what’s that got to do with anything? Are they trying to suggest that consuming fewer calories, or carbs, or fat, or meat, or soft drinks will prevent/treat NAFLD. Because the evidence doesn’t support this.

Can we trust the guidelines?

It’s this kind of nonsense that makes me want to tear my hair out. It’s the reason that guideline committees make stupid recommendations in spite of the glaringly absent evidence basis with which to do so. Take the NICE guidelines for example. They had the following to say about the evidence for weight loss in NAFLD:

“The GDG expressed reservations regarding the quality of some of the evidence, including the heterogeneity of means of diagnosing NAFLD, the small numbers of participants in certain included studies and the short follow-up time in other included studies. Most evidence was ranked as low or very low quality by GRADE criteria due to the high risk of bias found within the studies (detailed below) and the imprecision of the effect estimates. It was agreed that a stronger recommendation could not be made in the absence of high quality evidence and larger studies with a longer follow-up time.”

Apparently not

But that didn’t make a difference in the long term because when it came to their recommendations they say the following:

“While it can be difficult to pull apart the relative effectiveness of any one element of composite interventions, the GDG noted that weight loss achieved as part of a lifestyle modification strategy in adults with NAFLD appears to have a longer-term benefit in reducing NAFLD progression, even if the weight loss is maintained for a short time only (for example, ‘yo-yo’ dieters). As such, weight loss should be recognised as an important desirable outcome for lifestyle modification strategies in adults with NAFLD.”

Translation: Who care is there’s no decent evidence? We’ll recommend it anyway because it seems like the right thing to do.

Weight Loss Makes Things Worse

Where is the mention of the potential harms weight loss has on the liver? We’ve already touched on the impact of weight loss on insulin resistance. It’s not surprising, therefore, that rapid weight loss is actually a risk factor for new onset of NAFLD.

Worse still, studies have shown that “some patients undergoing bariatric and metabolic surgery develop NASH or suffer from aggravation of the disease (NAFLD/NASH/ live fibrosis) after bariatric surgery”.

Just so we’re clear; doctors are recommending weight loss surgery to managed NAFLD, even though there is no long term or good quality evidence to support this AND surgery may actually make things worse.

What about weight loss injections?

I only managed to find one study on Liraglutide (Victoza) in NASH. Bear in mind that Victoza is a diabetic medication and is neither licensed or used for weight loss. The sample size was small (only 52 participants) and they were only followed up for 48 weeks.

Most people (61%) didn’t see any improvement whilst on it, and most people (64%) didn’t have any progression in fibrosis without it. It also appeared that any positive impact on the liver appeared to be independent of weight loss and/or improvement in HbA1c.

So how should you manage your NAFLD

The most obvious option is to simply do nothing. The evidence suggests that you should avoid pursuing intentional weight loss since it has no proven benefits but does have several risks. Reducing insulin resistance sounds a lot easier than it is. To date there isn’t much evidence that treating insulin resistance will improve prognosis.

Remember that you should see a specialist ONLY if your Fib-4 score is high. There are no known treatments at this present time but if you do have NASH, you ought to speak to your specialist for the most up to date information in treatment.

If you enjoyed this blog post, then why not check out my NAFLD masterclass? Catch the replay, and get answers to all your questions, and learn more about the weight inclusive management of this condition. 

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