The video version of this podcast can be found here:

·      https://youtu.be/lhtciu3O8tc

The video on raised bilirubin pattern can be found here:

·      https://youtu.be/ndAus37PfsE

The video on hepatitic pattern abnormal LFTs can be found here:

·      https://youtu.be/rIX46swVSfg

This episode refers to guidelines on the management of abnormal liver function tests by the British Society of Gastroenterology. Please note that the content on this channel reflects my professional interpretation/summary of the guidance and that I am in no way affiliated with, employed by or funded/sponsored by them.

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode I cover what to do when we encounter abnormal LFTs with a cholestatic pattern, always focusing on what is relevant in Primary Care only. 

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

Disclaimer:

The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.

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

Primary Care guidelines podcast:

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

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The resources consulted can be found here:

BSG- British Society of Gastroenterology:

·      bsg.org.uk/clinical-resource/guidelines-on-abnormal-liver-blood-tests

·      Guidelines on the management of abnormal liver blood tests (bsg.org.uk)

o  First published on:

o  BMJ article:

o  Guidelines on the management of abnormal liver blood tests | Gut (bmj.com)

Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I’m Fernando, a GP in the UK. Today we are going to cover what to do when we encounter abnormal LFTs with a cholestatic pattern, always focusing on what is relevant in Primary Care only.

This episode is based on the British Society of Gastroenterology guidelines on abnormal Liver function tests. A link to it is in the episode description.

Right, let’s jump into it.

And let’s start by remembering that there are three common patterns of abnormal liver function tests or LFTs:

1. A cholestatic pattern, normally showing a high ALP and GGT, which is what we will concentrate on today.
2.  An isolated raised bilirubin with otherwise normal liver tests.
3. And a hepatitic pattern, with a raised ALT and AST indicating hepatocellular injury. By the way, if you are interested in finding out more about the last two types, make sure to watch the corresponding episodes on this channel. The links are in the episode description.

As we have said, LFTs showing a cholestatic pattern normally present with a high ALP and GGT.

Alkaline phosphatase, or ALP, is produced mainly in the liver but is also found in bone, intestines, kidneys and the placenta. Levels are physiologically higher in childhood because of rapid bone growth, and in pregnancy due to placental production. Raised ALP can come from either hepatic or non-hepatic sources.

The main source of non-hepatic ALP is bone. ALP increases in bone disease because it is produced by osteoblasts, the cells responsible for forming new bone. Any condition that increases osteoblast activity or bone turnover—such as healing fractures, Paget’s disease, bone metastases, or vitamin D deficiency—causes osteoblasts to increase their activity, releasing more ALP into the circulation.

We should remember that the most common cause of an asymptomatic, non-hepatic raised ALP is vitamin D deficiency. And let’s remember that vitamin D deficiency increases bone turnover because low vitamin D reduces calcium absorption from the gut. To maintain normal calcium levels, parathyroid hormone rises and stimulates bone breakdown to release calcium. This increase in bone remodelling activates osteoblasts leading to a rise in ALP.

But as we are focusing on liver function tests, what is the source of a raised hepatic ALP? From a pathophysiological perspective, hepatic ALP rises when bile flow is impaired, also known as cholestasis. And, why does cholestasis cause a rise in ALP? It happens because alkaline phosphatase is found in high concentration in the cells lining the bile ducts. When bile flow is impaired, pressure builds up in the biliary system and the bile duct epithelium becomes irritated. This stimulates these cells to produce and release more ALP into the bloodstream. This is the reason why ALP rises in, for example, gallstone disease, strictures, or cholangitis.

On the other hand, γ-glutamyltransferase, or GGT, is found in the liver but not in bone. Therefore, when ALP is raised, measuring GGT helps determine whether the source is hepatic or non-hepatic. A raised ALP with a normal GGT suggests a bone-related cause, whereas a raised ALP with a raised GGT supports a hepatic origin and should prompt further assessment of cholestatic liver disease.

GGT rises in cholestasis because it is also highly concentrated in the cells lining the bile ducts. When pressure builds up in the biliary system, these cells release more GGT into the bloodstream. In addition, cholestasis causes oxidative stress because retained bile acids are toxic to liver cells. In response, the liver increases GGT production, as GGT is involved in antioxidant and detoxification pathways, leading to the characteristic rise in cholestatic liver disease.

A high GGT can also be due to obesity, excess alcohol, or medications. In obesity and NAFLD, fat accumulation within the liver creates oxidative stress, so the liver up-regulates GGT to protect hepatocytes from free radical damage. In this context, an elevated GGT reflects metabolic stress rather than structural cholestasis. In alcohol use, ethanol metabolism produces toxic intermediates that also generate oxidative stress, which further stimulates GGT production as part of the liver’s detoxification response.

We will not go into detail on how to proceed with an isolated raised ALP, that is, with a normal GGT, as today we are focusing on cases where there is clear hepatic involvement, meaning that both ALP and GGT are high in a true cholestatic pattern.

How should we investigate and manage these patients?

When we manage patients with any abnormal liver function tests, we must begin by recognising red flags that require urgent action. According to the British Society of Gastroenterology guidelines, if there are signs of synthetic liver failure – such as unexplained clinical jaundice, a low albumin, or a raised INR – or if there is a suspicion of malignancy, for example unexplained weight loss or marked cholestasis, then the patient should be urgently referred or admitted for specialist assessment.

If the pattern is cholestatic, we will proceed with a full liver screen. This is because cholestatic abnormalities are often related to structural biliary disease, autoimmune cholestatic conditions, or infiltrative disorders, and these require a broader diagnostic approach than simple repeat testing.

What tests should be done in a full liver screen?

A full liver screen should include an ultrasound scan of the liver and biliary tree, which is the first-line imaging test. Ultrasound helps identify biliary dilatation, gallstones, strictures, masses, or features of chronic liver disease. In addition to imaging, blood tests should include hepatitis B and C screening, an autoantibody screen, serum immunoglobulins, ferritin and transferrin saturation, and, often and where clinically appropriate, a coeliac screen, alpha-1 antitrypsin levels, and caeruloplasmin. These tests collectively help detect autoimmune cholestatic diseases such as primary biliary cholangitis, metabolic conditions such as haemochromatosis or Wilson’s disease, and chronic viral hepatitis.

It is also worth emphasising that this full liver screen is recommended not only for cholestatic abnormalities but also for patients who present with a hepatitic pattern, as the BSG guideline advises a comprehensive assessment irrespective of the pattern or the degree of derangement once initial red flags have been excluded.

The management in primary care is fairly simple, because the British Society of Gastroenterology recommends that once initial investigations have been completed, these patients should be referred to secondary care for further assessment. This applies both when a cholestatic picture come with abnormalities in the liver screen and also if the ALP and GGT remain persistently high even in the context of normal investigations.

Referral is indicated because persistent cholestatic abnormalities indicate underlying pathology that usually cannot be adequately diagnosed or managed in primary care and requires specialist input.

So that is it, a review of abnormal LFTs with a cholestatic pattern.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.