My name is Fernando Florido and I am a GP in the United Kingdom. In today’s episode I go through a real-life case of a patient with abnormal Liver Function Tests and non- alcoholic fatty liver disease or NAFLD. I will describe a recommended approach to diagnose and manage them according to guidelines. 

I am not giving medical advice; this podcast is intended for health care professionals; it is only my interpretation of the guidelines and you must use your clinical judgement.  

There is a YouTube version of this and other videos that you can access here: 

·      The NICE GP YouTube Channel: NICE GP - YouTube 

The links to the websites that can calculate these scores are in the episode description:

·      The NAFLD Fibrosis Score (NFS) is available at https://www.thecalculator.co/health/NAFLD-Fibrosis-Score-Calculator-969.html 

·      The Fibrosis 4 (FIB-4) Score available at https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis 

You can download a summary of the episode here:  

·      Summary of NAFLD patient case: https://1drv.ms/b/s!AiVFJ_Uoigq0mBYIbok6DSu5vTnY?e=2W11Jd

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Transcript

Hello everyone and welcome. My name is Fernando and I am a GP in the United Kingdom. 

In today’s episode I go through a real-life case of a patient with abnormal Liver Function Tests and non- alcoholic fatty liver disease or NAFLD, describing the recommended approach for its diagnosis and management according to guidelines.

By the way, I am not giving medical advice; this is for health care professionals and it is only my interpretation of the various guidelines consulted so you must use your own clinical judgement.

If you want to download a summary of the episode, the link is in the episode description.

Remember that there is also a YouTube version of these episodes so have a look in the episode description. 

Right, so let’s get straight into it.

Our patient is a 55-year-old man of Hispanic family background who consults you following a routine blood test done one week earlier. This was a repeat blood test because 4 months previously he had been found to have a mildly raised alanine aminotransferase or ALT of 75 (NR 0-55).

The results of all his blood tests were normal with the exception of the ALT which was still high at 65.

His PMH includes:

·      Prediabetes

·      Hyperlipidaemia and

·      Overweight with a BMI of 27.8

His only medication is atorvastatin 20 mg daily for hyperlipidaemia.

He denies alcohol excess. In fact, he is teetotal and does not drink alcohol at all. He has otherwise no symptoms.

In the previous consultation he had been told that raised liver transaminase were not uncommon during the prescribing of statins but that statins need not be stopped for raised liver transaminase levels as long as they are less than 3 times the upper limit of normal.

However, as a result of that consultation, the patient decided to stop the statin of his own accord so he has not been taking it for the last 3 months.

So, in summary, we have a patient with a background of overweight, prediabetes and dyslipidaemia with a slightly elevated ALT for 3 months without an obvious cause.

What should we do?

When we face this situation, we should consider all the possible causes and investigate them fully. But we must primarily consider the most common reason for abnormal liver blood tests in the UK, which is non-alcoholic fatty liver disease, or NAFLD.

This condition happens when excess fat builds up in the liver. But for the diagnosis to be made, we must also exclude other secondary causes.

Let’s quickly remind ourselves that NAFLD has a spectrum that goes from simple hepatic steatosis, meaning that there's fat in the liver, but it's not causing any significant inflammation or damage, to something more serious called non-alcoholic steatohepatitis, or NASH which involves inflammation and injury to liver cells which can lead to liver fibrosis and cirrhosis.

Most people don't have any specific symptoms. However, some might experience fatigue, or mild abdominal discomfort.

In our patient's case, we know that he is overweight, which is typical. However, NAFLD can affect even non-obese individuals. Surprisingly, about 40% of all NAFLD cases worldwide are found in non-obese people, and around 20% in those who are lean.

We also know that NAFLD is closely tied to the metabolic syndrome, involving insulin resistance, obesity, impaired glucose regulation, and hypertension and our patient does have some of these factors. While the exact cause of NAFLD isn't fully clear, it is thought that both environment and genetics play a role.

The outlook for NAFLD depends on the stage of the disease:

• For those with simple steatosis, the outlook is generally positive.
• However, if someone has non-alcoholic steatohepatitis (NASH), they're at higher risk for cirrhosis, liver failure, and even liver cancer.

Complications of NAFLD can be serious. They include:

• Hepatic and metabolic complications and
• Above all, cardiovascular disease, which is the leading cause of death for people with NAFLD.

We should suspect that someone has NAFLD if:

• There are risk factors linked to the metabolic syndrome.
• There are high levels of alanine aminotransferase (ALT) for more than 3 months, and it's usually higher than another enzyme called aspartate aminotransferase (AST).
• They're not consuming excess alcohol, in which case it would be alcoholic fatty liver disease.
• An ultrasound scan reveals a fatty liver.
• They are nor on medication that can cause a fatty liver, e.g. tamoxifen or amiodarone.

So based on all this, we will suspect that our patient could have NAFLD.

How should we confirm the diagnosis?

Next, we'll arrange some more blood tests to get a clearer picture and exclude secondary causes. We will do:

• Liver function tests, to include AST as well as ALT.
• A full blood count, which can help detect low platelets, which is a sign of advanced fibrosis.
• A clotting screen, as it might be off in advanced fibrosis.
• Screening for viral hepatitis B and C, and test for auto-antibodies that could suggest autoimmune hepatitis.
• Ferritin and transferrin saturation to screen for haemochromatosis,
• Serum caeruloplasmin for Wilson's disease,
• Alpha-1-antitrypsin levels to screen for deficiency
• Immunoglobulin (IgA) tissue transglutaminase antibody (tTGA) as coeliac disease can present with cryptogenic liver disease.
• HbA1c, Lipid profile, ESR, CRP, Renal and thyroid function tests as general screening.

Additionally, we could request a liver USS to exclude any other structural issue that we could be missing.

Right, so we organise these tests and we see the patient a few weeks later to discuss the following:

An USS of the abdomen confirms that he has steatosis of the liver.

His blood tests showed that:

ALT has improved but it is still high at 59 (NR 0-55) and AST is also high at 49 (NR 5-34). The rest of his liver function tests were normal.

His FBC was normal with a platelet count of 219 (NR 150-400 10*9/L)

His HbA1c is in the prediabetes range at 43 or 6.1%.

He has normal clotting screen, ESR, CRP, renal and thyroid function tests.

And all other investigations for secondary causes were also normal: viral hepatitis serology, autoantibody screen, ferritin, transferrin saturation, caeruloplasmin, Alpha-1-antitrypsin levels and Immunoglobulin (IgA) tissue transglutaminase antibody (tTGA) as coeliac screen.

His cholesterol was slightly high at 5.1 with an HDL of 1, an LDL of 3.9 and TG of 1.5.

His BP was 147/82 and his CVD risk score using QRISK3 is 8%.

I summary, we have confirmed steatosis of the liver on USS and, given that we have not found secondary causes for the liver function test abnormality, we can conclude that this is indeed NAFLD.

As part of our consultation, we also do a thorough examination looking out for signs of advanced liver disease, of which he has none.

As the next step, we should estimate the level of fibrosis, or scarring of the liver, by using non-invasive tools. There are two simple tests that we can use in Primary care:

·      One, the Fibrosis-4 score or FIB-4, which uses the person's age, AST, ALT, and platelet count.

·      And two, the NAFLD Fibrosis Score (NFS) which measures age, body mass index, blood glucose, platelet count, albumin, and the AST to ALT ratio.

·      The Enhanced Liver Fibrosis (ELF) test is another option but this is really only available in secondary care because of the complexity of the parameters required.

The links to the websites that can calculate these scores are in the episode description:

·      The NAFLD Fibrosis Score (NFS) is available at https://www.thecalculator.co/health/NAFLD-Fibrosis-Score-Calculator-969.html 

·      The Fibrosis 4 (FIB-4) Score available at https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis

If the fibrosis score is low, we may be able to manage this patient in Primary Care.

We calculate the FIB4 score for this patient and it is 1.92. which means that further investigations are needed. The interpretation of the scores is as follows:

·      If FIB-4 is < 1.45: we can be reasonably confident that there is absence of cirrhosis

·      If FIB-4 is between 1.45 - 3.25:  the test is inconclusive and

·      If FIB-4 is > 3.25: we can be reasonably confident that there is cirrhosis

So let's move on to the management.

The Primary Care approach would be as follows:

• We will advise lifestyle changes including weight loss, if the person is overweight.
• We will recommend a Mediterranean diet, which can actually reduce liver fat even without weight loss.
• We will encourage moderate-intensity exercise.
• We will offer alcohol advice.
• We will optimise management of co-morbidities such as hypertension, hyperlipidaemia, or type 2 diabetes. In this case, we may revisit his statin therapy because he has two independent risk factors for CVD, prediabetes and NAFLD.
• We need to be aware that statins, if prescribed, don't pose additional liver risks for people with NAFLD. In fact, they can help improve various aspects of the condition.

So, in summary, the primary care approach to NAFLD involves empowering patients to make lifestyle changes, ensuring associated conditions are managed, and offering support and information along the way.

If a person has a working diagnosis of NAFLD and other liver disease causes have been ruled out, and if non-invasive tests indicate a low risk of advanced liver fibrosis (using NFS, FIB-4, or ELF), then primary care management is in order.

However, because his FIB4 score is inconclusive in this case, we will refer him to secondary care for a second opinion.

Other reasons to refer to a Specialist are:

• If there's a high risk of advanced liver fibrosis.
• If there are clear signs of advanced liver disease during examination.
• In cases where there's uncertainty about the diagnosis.

We also need to be aware that specialist management may involve amongst other things:

• Transient elastography, also known as fibroscan, which measures liver stiffness non-invasively, which correlates with the degree of liver fibrosis.
• Liver biopsy.
• In cases of non-alcoholic steato-hepatitis (NASH), pioglitazone, and Vitamin E supplementation might be considered.
• Bariatric surgery, has led to the resolution of steatosis in 66% and fibrosis in 40% of patients.
• Considering liver transplantation. However, NASH recurrence after transplantation is possible.

Finally, this patient should be reviewed regularly in Primary Care. Patients with NAFLD should have an annual review, more frequently if necessary, as per our clinical judgement:

During the review, we will:

• Identify any signs that might indicate liver disease.
• Measure blood pressure and BMI.
• Check liver and renal function, HbA1c and a lipid profile.
• Reassess the CVD risk
• And, every three years, reassess the risk of advanced liver fibrosis and refer if the person has a high risk of advanced liver fibrosis

But remember that this is only a summary and my interpretation of the guidelines.

We have come to the end of this episode. I hope that you have found it useful. Thank you for listening and good-bye