Podcast - Understanding abnormal LFTs: the puzzle finally solved
16m | Mar 17, 2024Podcast description
The video version of this podcast can be found here:
https://youtu.be/IaId_nNbO-c?si=0FF7A5J7iPxocdBd
This episode refers to guidelines on the management of abnormal liver function tests by the British Society of Gastroenterology and a number of NHS organisations in the UK. 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 go through the interpretation of an abnormal liver function tests, 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 information consulted. You must always use your clinical judgement.
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
· Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK
· Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148
There is a YouTube version of this and other videos that you can access here:
- The Practical GP YouTube Channel:
https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk
My summary guide can be downloaded here:
· https://1drv.ms/b/s!AiVFJ_Uoigq0mQ8MRxaNYnA1_pzh?e=H2U7rS
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)
Southeast London pathway:
· Microsoft Word - Abnormal liver function test pathway-explanatory.docx (selondonccg.nhs.uk)
North and East Devon pathway:
· Management of Abnormal LFTs in Asymptomatic Adults - North & East (devonformularyguidance.nhs.uk)
North Bristol
West Hampshire:
· Liver Blood Test Pathway | GP Portal (westhampshireccg.nhs.uk)
Medscape:
· Liver Blood Tests: How to Interpret Abnormal Results (medscape.co.uk)
Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release]
- Music provided by Audio Library Plus
- Watch: https://youtu.be/aBGk6aJM3IU
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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 go through the interpretation of abnormal liver function tests or LFTs, including initial follow up management, always focusing on what is relevant in Primary Care only.
And for that I will summarise the British Society of Gastroenterology guidelines on LFTs. They were first published in the BMJ and the relevant links are in the episode description. Although the full guideline covers both adults and children, in today’s episode I will be focusing only on adults.
At the end, I will also tell you how to access my summary of the recommendations, which will be based not only on the BSG but also on a number of NHS bodies in the UK. The links to them are in the episode description and it’s worth having a look as they have flowcharts and other information that you may find useful.
Right, there is a lot of information to cover, so let’s jump into it.
The three the most common causes of liver disease are alcohol-related liver disease, non-alcoholic fatty liver disease and viral hepatitis, although autoimmune liver disease is also a significant cause.
Liver disease develops silently and at earlier stages liver enzymes may be normal. If they are high, the degree of abnormality is not necessarily related to the severity of the underlying condition and this is why many patients are not diagnosed until they have developed significant liver fibrosis.
In many cases if used in isolation, LFTs are neither very specific or sensitive and they are better at assessing liver fibrosis if incorporated into algorithms or ratios.
What constitute LFTs? Well, the LFTs standard panel can vary from hospital to hospital. Although we call them LFTs, not all the tests assess liver function. For example, high liver enzymes point towards liver injury; bilirubin, albumin and INR give information on liver function, while platelets can give information on the level of liver fibrosis.
So, let’s have a look at a number of these tests.
Bilirubin is the by-product of the breakdown of haemoglobin. It exists in two forms, unconjugated and conjugated. Bilirubin is transported to the liver as unconjugated bilirubin, where it is converted into conjugated bilirubin. A high unconjugated level is usually due to haemolysis or impaired conjugation whereas a high conjugated level is typically due to liver disease or biliary obstruction.
Many path labs will routinely report just total bilirubin, but they will give a breakdown if the level is abnormal or if specifically requested.
In normal circumstances, the majority of bilirubin should be conjugated. So, if the majority of the bilirubin is unconjugated, then, in the absence of haemolysis, the cause is almost always Gilbert’s syndrome where the enzyme that conjugates bilirubin has a reduced activity with a consequent rise in unconjugated bilirubin. it is not associated with liver disease or ill health, so patients should be fully reassured.
Albumin is a protein that is produced only in the liver and because of this, it is often considered as a marker of liver function. However, albumin can also be reduced in for example, sepsis, inflammatory disorders, and malabsorption.
Prothrombin time (PT) and INR can also be used to measure liver function, as the underlying clotting factors are made in the liver. Therefore, a high PT and INR can indicate liver dysfunction but it can also be caused by vitamin K deficiency as seen in fat malabsorption and chronic cholestasis.
A reduction in platelets, or thrombocytopenia, is an indicator of advanced liver disease. A low platelet count is caused by decreased production due to bone marrow suppression, splenic sequestration due to portal hypertension and increased platelet destruction due to shear stress, and fibrinolysis in liver cirrhosis or due to antiplatelet antibodies in autoimmune liver disease.
Alkaline phosphatase (ALP) is produced mainly in the liver but is also found in bone, intestines, kidneys and placenta. Levels are physiologically higher in childhood, because of bone growth, and in pregnancy due to placental production. High levels cab be due to bone disease (e.g., bone metastases and fractures) and cholestatic liver disease (like for example, in biliary obstruction).
γ-Glutamyltransferase (or GGT) is present in the liver but not in bone and therefore when the ALP s high, the measurement of GGT can indicate whether the ALP is of hepatic or non-hepatic origin. The most likely cause of a non-hepatic high ALP in someone asymptomatic is vitamin D deficiency. A high GGT can als be due to obesity, excess alcohol or drugs.
AST and ALT are enzymes present in the liver cells and the levels increase in response to cell injury or death. ALT is considered more liver-specific while AST is also present in skeletal, cardiac and smooth muscle and so may be elevated in patients with an MI or myositis.
An AST:ALT ratio of >1 is a non-invasive marker of advanced fibrosis. Although AST and ALT can be normal even in liver disease, the high AST:ALT ratio generally persists even if both values are normal.
When should LFTs be checked? We should do so when there are:
· Non-specific symptoms such as fatigue, nausea or anorexia.
· Symptoms or signs of advanced liver disease, like ascites, peripheral oedema, spider naevi and hepatosplenomegaly. In these cases, checking the INR would also help assess the synthetic liver function.
· Conditions which are associated with liver disease like autoimmune diseases, and inflammatory bowel disease.
· Hepatotoxic drugs like for example carbamazepine, macrolide antibiotics, statins, terbinafine, and methotrexate. And although statins can lead to drug-induced liver injury, this is very rare, and they are generally safe in patients with raised liver transaminase levels if they are less than 3 times the upper limit of normal.
· Family history of liver diseases such as haemochromatosis or Wilson’s disease.
· Suspected alcohol-related liver disease. And
· Suspected viral hepatitis.
So, what should we do when confronted by abnormal LFTs?
We often think that the extent of abnormality of the LFTs correlates with the severity, of the problem. However, this assumption is not supported by the evidence. Common conditions leading to chronic liver disease like NAFLD, and hepatitis C are frequently associated with only mild or moderate LFT abnormalities.
There is also the assumption that the duration of the abnormal LFTs is a reflection of clinical significance, so we often keep repeating the LFTs hoping that they will improve. And although LFTs can occasionally be high due to intercurrent illness, studies have shown that the vast majority still have abnormal LFTs after 2 years and therefore a strategy of simply repeating them can rarely be justified. Besides, in many chronic liver diseases such as hepatitis C and NAFLD, the LFTs returning to normal do not necessarily imply the resolution of the disease.
This has led to the BSG to recommend that patients with abnormal LFTs should have a full liver screen irrespective of level and duration of the abnormality.
And before moving on, let’s remember that there are three common patterns of abnormal LFTs:
1. An Isolated raised bilirubin with otherwise normal liver tests
2. A Cholestatic pattern: Normally showing a high ALP and GGT And
3. A Hepatitic pattern: with a raised ALT and AST indicating hepatocellular injury, like, for example, viral hepatitis, NAFLD, and ARLD.
The BSG has produced a flowchart to guide us through the process. You can access it in the episode description.
But, in summary, if there are signs of synthetic liver failure like unexplained clinical jaundice, a low albumin or a high INR or if there is suspicion of malignancy, for example because of weight loss or marked cholestasis, we should urgently refer or admit the patient.
If there is an isolated raised bilirubin but no clinical concerns, then:
1. We should request a FBC and repeat the LFTs on a fasting sample requesting the breakdown of conjugated and unconjugated bilirubin.
2. Fasting causes the unconjugated bilirubin to rise further in Gilbert’s syndrome so this is the likely diagnosis when this happens and there is no evidence of haemolysis, like anaemia.
3. If there is associated anaemia, we will have to consider haemolysis and we will request a reticulocyte count and LDH.
If the pattern is cholestatic or hepatitic we will do a liver screen. This should include an USS, hepatitis B and C screening, an autoantibody screen, serum immunoglobulins, both ferritin and transferrin saturation and, often, a coeliac screen, alpha-1-antitrypsin levels and caeruloplasmin.
If the patient has a cholestatic picture and the liver screen shows abnormalities or if the ALP and GGT remain high even in the context of normal investigations, we will refer the patient to secondary care.
If the patient has a hepatitic picture with a high ALT and AST, studies have shown that the majority will have NAFLD or ARLD and most will not need referral, but lifestyle advice and monitoring in primary care. The deciding factor is the level of liver fibrosis, which we can estimate using non-invasive fibrosis markers.
The BSG has also produced a specific flowchart for when NAFLD is suspected following a liver USS. You can also access it in the episode description.
In summary, it says that for patients with NAFLD or liver disease of unknown cause, the next step is to estimate the risk of fibrosis using the FIB4 or NAFLD fibrosis score.
Values <1.3 and ≤-1.455, respectively, represent a low risk of advanced fibrosis. Higher cut-off points, <2.0 and <0.12 respectively, should be used for patients over 65. In these cases, we will just manage the risk factors in Primary Care and reassess periodically, generally every 2 to 5 years.
FIB4 or NAFLD fibrosis score values >1.3 and >-1.455, respectively, should have second-line tests such as an enhanced liver fibrosis blood test, also known as an ELF tests or imaging such as a FibroScan or elastography.
However, patients with a very high FIB-4 score >3.25 or a NFS >0.675 should be referred without waiting to do an ELF test, Fibroscan or elastography.
Those with intermediate FIB-4 score (that is between 1.3 and 3.25) or NFS (that is, between -1.455 and 0.625), should have an ELF test or a Fibroscan. If the result is 9.5 or less or 7.8 or less respectively, we will manage them in primary care and we will refer if the result is above those limits
In primary care, the treatment for NAFLD is weight loss, alcohol advice, the reduction of cardiovascular risk and the management of co-morbidities.
Next, the BSG has also produced a specific flowchart to guide us if ARLD is suspected. I have also put a link to it in the episode description.
And in summary, those drinking ≥35 units/week for women and ≥50 units/week for men, will need referral to both alcohol services and hepatology for further assessment with a Fibroscan or elastography. For all other patients, the AUDIT C questionnaire alongside brief intervention is recommended initially. If the AUDIT C is 5 or more, we will need to give them the full AUDIT questionnaire.
For patients with an AUDIT score of >19, we will also need to refer them to both alcohol services and hepatology for further assessment with a Fibroscan or elastography. For those with an AUDIT score of between 8 and 19 we should check the GGT and if it is >100 we should refer them as for the higher-risk group. Otherwise, we could monitor them and refer to alcohol services if excessive drinking persists.
The treatment of ARLD is to stop drinking harmfully, and for many this usually means complete abstinence. Weight loss sometimes also helps because there is a synergy between alcohol and obesity. For example, when the BMI is >35, the risk of liver disease doubles for any given alcohol intake.
But, finally, what should we do if the patient has a hepatitic pattern with a high ALT and AST without an obvious cause, that is, when the liver screen is normal and there is no evidence of NAFLD on USS or excess alcohol?
In those cases, we will need to re-examine the history to exclude potential drug-induced causes. Also, ultrasound is only sensitive for steatosis when hepatocytes are more than 30% steatotic so patients with milder steatosis might have a normal USS. So, if these patients are obese or have metabolic risk factors and we suspect that they may still have NAFLD despite the normal USS, we should assess them in accordance with the NAFLD flowchart. As I mentioned earlier, we should follow it for patients with NAFLD or liver disease of unknown cause.
Well, this is the end of the BSG guideline itself. I have created a quick reference guide which contain the various BSG flowcharts as well as information found in the NHS pathways from Southeast London, North and East Devon, North Bristol, and West Hampshire. Links to their information and flowcharts are in the episode description. They all had similar advice to the BSG guideline but there were also some other elements which would be useful from a practical perspective. Where there was a discrepancy between their guidance, I have generally opted for the most conservative approach. If you are in any doubt, please consult the original guidance or seek local specialist advice. You will be able to find a link to download my summary in the episode description.
We have come to the end of this episode. Remember that this is not medical advice and it is only my summary and my interpretation of the guidelines. You must always use your clinical judgement.
Thank you for listening and goodbye.
