HEPATOLOGY HAEMATOLOGY

Liver function tests in primary care

Liver function tests (LFTs) are among the most commonly requested laboratory investigations in primary
care. However, as with all other laboratory tests, it is essential that clinicians consider whether LFTs are
being requested for the right patient at the right time, and have a firm understanding of how results will be
interpreted based on the specific clinical context. Given the diverse spectrum of liver disease and its potential
causes, navigating the ensuing diagnostic pathway can be a true test of any clinician’s investigative skillset.

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KEY PR AC TICE POINTS

A liver function test panel generally consists of around liver, preventing flow of bile from the liver (intrahepatic
seven individual biochemical analyses, including: cholestasis). This finding is more common in the context
– Enzymes associated with liver injury/hepatocyte necrosis of medicine use.
(alanine aminotransferase [ALT] and aspartate – Isolated bilirubin increases should be further evaluated
aminotransferase [AST]) by requesting a fractionated/split bilirubin test (i.e.
– Enzymes associated with liver or bile duct stimulation to estimate the proportion that is unconjugated/
(alkaline phosphatase [ALP] and γ-glutamyl- indirect) because this may be due to causes other than
transferase [GGT]) hepatocellular injury or cholestasis
– Proteins associated with liver synthetic function (e.g. Both acute and chronic liver disease can lead to the
albumin and prothrombin time/international development of complications of liver failure and portal
normalised ratio [INR]) hypertension
– Markers of biliary drainage (bilirubin) – Liver failure is associated with reduced liver synthesis
There are varied reasons for requesting LFTs, but this panel of proteins, such as albumin or coagulation factors
should only be used when specifically indicated by the (resulting in increased prothrombin time or INR).
clinical picture. Main indications are patients with risk Synthetic liver failure can be either acute or chronic
factors for viral hepatitis (particularly chronic hepatitis B or liver failure. Acute liver failure is usually caused by acute
C; see main text for further information), alcohol-related hepatitis (usually HBV infection), or medicine-induced
liver disease (i.e. excessive alcohol intake) or metabolic liver damage (especially paracetamol). Chronic liver
associated liver disease (e.g. obesity, type 2 diabetes, failure is usually caused by decompensated cirrhosis
hypertension, hyperlipidaemia), as well as monitoring the (any aetiology). This can occur in the context of either
effects of certain medicines (e.g. methotrexate). hepatocellular injury or cholestatic LFT patterns and
While LFTs are important to diagnose and monitor liver these patients require referral for urgent ultrasound or
damage, many markers are not direct measures of liver acute secondary care review.
function and abnormal results do not always indicate – Portal hypertension is associated with low platelet
liver-specific disease. Results must be interpreted in the counts, ultrasound findings of enlarged spleen, portal
context of patient-specific characteristics, current clinical vein and ascites or varices
situation, medical history and previous LFT results. Asymptomatic patients with borderline LFT abnormalities
There are two main patterns of LFT abnormalities that often do not require immediate follow-up testing,
can provide clues about the location or type of liver particularly if there is a likely modifiable cause present, e.g.
dysfunction: alcohol misuse, medicine changes or dose increases, acute
– 1. Hepatocellular injury – reflected by increased viral illness; consider repeating LFTs within three months
aminotransferase levels (ALT and AST). The AST:ALT ratio If the cause of LFT derangement is uncertain or if
may be helpful in determining both the aetiology and established liver disease is suspected, a tiered approach
the stage of liver disease (see main text). to subsequent laboratory testing and other investigations
– 2. Cholestasis – reflected by increased ALP and GGT is generally recommended, informed by the LFT pattern
levels and, if severe, elevated bilirubin level. This pattern and patient characteristics (see main text for specific
reflects conditions that reduce either the transport of recommendations)
bile from the hepatocyte into the canaliculi (intrahepatic Ultrasound imaging is a first-line investigation if cholestasis
cholestasis) or obstruction of flow of bile through the is suspected based on LFT results. If hepatocellular
extrahepatic bile ducts into the gut (extrahepatic biliary injury is suspected and the patient does not have
obstruction). concerning symptoms/features, ultrasound is a second-tier
– Mixed hepatocellular injury/cholestasis patterns are investigation after investigating the most likely causes
also possible, as severe hepatocellular injury causes liver (listed above).
swelling which blocks the small bile ductules within the

Contents:
3 The liver is a vital organ for supporting life 10 Consider whether a common LFT pattern is present
4 Liver function tests (LFTs): an overview 12 The pathophysiology of cholestasis
4 Indications for requesting LFTs 12 Other LFT changes to consider
6 Interpretation of LFT results should be individualised 14 Deciphering other isolated LFT marker abnormalities
6 Clues that could reveal a potential cause for 14 Referral criteria for patients with abnormal LFT
abnormal LFTs results
7 Always consider a possible pharmacological cause 15 Pregnancy-related LFT derangement/liver disease

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The liver is a vital organ for supporting life Except in instances of acute failure, liver disease usually
progresses silently over years or decades, with no obvious
When healthy, the liver mediates a wide range of essential signs or symptoms occurring until complications associated
bodily processes, including carbohydrate, protein (amino acid) with chronic failure develop.2, 3 In 2019, there were 158
and lipid metabolism and storage, waste product and ingested deaths caused by liver cirrhosis in New Zealand (3.3 deaths
toxin breakdown/excretion, red blood cell (RBC) storage, and per 100,000 people) and 188 deaths due to liver cancer (6.0
hormone and lymphatic fluid production.1 All other organs deaths per 100,000 people).4 Māori, Pacific and Asian peoples
in the body are dependent on the liver for optimal condition are considerably more likely to develop chronic liver disease
and performance, however, this high demand and functional compared with those of European/Other ethnicity.5 This is
interconnectedness also places it at increased risk of disease.1 likely to be related to a higher prevalence of associated risk
This includes potentially transient disturbances in function factors, e.g. metabolic syndrome, chronic viral hepatitis.
caused by acute injury (e.g. medicine exposure, acute viral Given that the liver is the only internal organ capable of
illness) through to established disease associated with substantial natural tissue regeneration to levels required for
progressive pathological changes (i.e. the spectrum of disease stable body system functioning,6 early identification of liver
leading from steatosis to cirrhosis; Figure 1). injury is an important clinical objective so that corrective
lifestyle changes or targeted interventions can be applied.

Liver cancer
Primary liver cancer – key risk
Co-morbidities Lifestyle factors factor: cirrhosis, particularly
E.g. Obesity, Alcohol misuse when associated with chronic
type 2 diabetes, HBV/HCV infection
Poor diet
dyslipidaemia, Secondary liver cancer – key
hypertension
risk factor: non-hepatic cancers
with metastatic potential

2 Steatosis Steatohepatitis
Abnormal fat retention Fatty liver
MASLD* or alcohol- inflammation
related liver disease MASH* or ASH
Healthy liver
1 3 4
Fibrosis / Cirrhosis

Medicines /toxins

5
Infection and immune
dysfunction
HBV infection
HCV infection Liver injury Liver failure
Primary biliary cholangitis ASH, alcoholic steatohepatitis; HBV, hepatitis B
Primary sclerosing virus; HCV, hepatitis C virus; MASLD, metabolic
cholangitis dysfunction-associated steatotic liver disease;
Reversible MASH, Metabolic dysfunction-associated
steatohepatitis.

* Nomenclature update (2023): The American Association for the Study of Liver Diseases (AASLD) has announced a new overarching term to
describe the various forms of steatosis influenced by metabolic processes. The previously used term non-alcoholic fatty liver disease (NAFLD) – which
is also referred to in the literature as metabolic dysfunction-associated fatty liver disease (MAFLD) – will now be labelled metabolic dysfunction-
associated steatotic liver disease (MASLD; pronounced ma-zuld). Metabolic dysfunction-associated steatohepatitis (MASH) is also now accepted
as the replacement term for non-alcoholic related steatohepatitis (NASH).
For further information see the online version of this article: bpac.org.nz/2022/LFTS.aspx

Figure 1. Physiological spectrum of progressive liver disease. Adapted from Tripathi et al, 2018.3

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Liver function tests (LFTs): an overview In general, the main indications for liver function testing
include:2, 12
Liver function tests (LFTs) involve a panel of laboratory analyses Risk factors for viral hepatitis (see: “A spotlight
performed on a single blood sample to assess the organ’s on the key causes of liver disease ” for a more
performance. Table 1 outlines the most common markers comprehensive list):
used in LFTs in New Zealand and their biological significance. Hepatitis C, e.g. injecting drug users, children
However, the combination of tests within a LFT panel may of mother with hepatitis C, immigrants from
differ between laboratories and regions. high-risk areas, recipients of blood transfusion
While the term “liver function test” is widely used, it is prior to 1992
potentially misleading in that many of the tests are not a direct Hepatitis B, e.g. Māori, Pacific or Asian people
measure of liver function and may be abnormal in patients born prior to 1990 (when universal neonatal
with an otherwise “healthy” or functional liver. This presents vaccination was introduced), high-risk sexual
a challenge for primary care clinicians, particularly given that practices especially in men who have sex with
elevated liver enzyme levels are estimated to occur in up to 9% men (MSM)
of asymptomatic people.7 Hepatitis A, e.g. travel to countries with poor
sanitation or a lack of safe water within last two
The clinical picture is further complicated by several other months, recent local outbreak, MSM
factors:8–10 Other rarer causes of viral hepatitis include
Some abnormalities are transient and self-resolve Epstein Barr virus and travel-related viruses
within several weeks, whereas others reflect a persistent
underlying issue Risk factors for metabolic dysfunction-
associated steatotic liver disease (MASLD;
Various non-hepatic diseases can influence LFT marker
previously known as non-alcoholic fatty liver
levels
disease [NAFLD] or metabolic associated fatty liver
Liver-specific causes of disease do not always correlate disease [MAFLD]), e.g. obesity, type 2 diabetes,
with a consistent LFT marker profile and some patients dyslipidaemia, hypertension
have LFT abnormalities earlier in the physiological
spectrum of disease than others (Figure 1) Risk factors for alcoholic liver disease, e.g.
There is a natural age-associated decline in liver excessive alcohol intake
functioning over time
Risk factors for immune-mediated liver diseases
(e.g. primary biliary cholangitis, primary sclerosing
Therefore, after identifying any LFT “abnormality” (see:
cholangitis, autoimmune hepatitis), including other
“Interpretation of LFT results should be individualised”), its
pre-existing autoimmune diseases or inflammatory
clinical significance must then be assessed in the context of
bowel disease
the patient’s characteristics, their current clinical situation,
medical history and previous test results. This information can Monitoring the effects of medicines that can
then provide clues to refine subsequent investigations. As such, affect liver function or that are hepatotoxic, e.g.
learning to recognise certain biochemical signatures in the methotrexate, sodium valproate
context of specific patient types becomes an important skill
that general practitioners develop over time. To exclude liver disease when a patient has a
pattern of persistent non-specific symptoms
Indications for requesting LFTs with no obvious identifiable cause or link or if
they have features such as jaundice or ascites on
Opportunistic liver function testing is not indicated for examination
asymptomatic people without risk factors.2, 12 As noted, healthy
people can have mildly abnormal LFT results, and unwarranted Family history of liver disease or co-morbidities
testing in response to isolated non-specific symptoms (such likely to influence liver function (see above)
as brief periods of fatigue) may prompt unnecessary patient
concern or investigation/treatment escalation if false positive For further information regarding the potential causes
results occur.13 underpinning these indications, see: “Clues that could reveal
a potential cause for abnormal LFTs”

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Table 1. Common markers used in liver function tests (LFTs)*.11

LFT marker
(results of tests with
matching colours Site of production Usual function Notes
often correlate with
each other)
Alanine Predominantly liver Intracellular enzymes involved Highly specific for liver injury
aminotransferase in glucose production and
(ALT)†• amino acid metabolism,
allowing them to be used for
Aspartate Liver, heart, skeletal Less sensitive and less specific compared
cellular energy production
aminotransferase muscle, kidney, brain, with ALT as it is also produced in other
(AST)†• RBCs organs and tissues
Alkaline Predominantly liver A group of enzymes that More specific than GGT for liver disease;
phosphatase and bone, also in bile co-ordinate various bodily ALP is induced by bile acids, and ALP
(ALP) • ducts, kidney, intestine, functions; in the liver ALP elevation indicates biliary obstruction.
placenta is associated with protein Levels are higher in childhood due to
breakdown bone turnover.
γ-Glutamyl- Liver and bile ducts, Enzyme present in cell Considered more sensitive than ALP;
transferase (GGT) • also present in cell membranes; catalyses transfer however mild elevations are non-specific,
membranes of multiple of amino acids across the and isolated increases are rarely
Common default laboratory LFT markers

other tissues, e.g. membrane and is involved indicative of liver disease

pancreas, kidneys in the metabolism of various
molecules
Bilirubin Bone marrow, liver Initial testing usually reports total bilirubin, which includes both
unconjugated/indirect and conjugated/direct fractions. The unconjugated
form is increased by RBC breakdown (e.g. haemolysis), if hepatic uptake
is reduced (e.g. medicine-induced or when hepatic blood flow decreases
[such as in heart failure]), or if hepatic conjugation is impaired due
to hereditary deficiency in the UGT enzyme (i.e. Gilbert’s syndrome,
which is found in approximately 5% of people). In contrast, conjugated
hyperbilirubinaemia is usually caused by impaired liver processing/bile
flow (e.g. hepatitis, medicine-induced cholestasis, or biliary obstruction
by gall stones or malignancy). For further information, see: “Isolated
hyperbilirubinaemia”. Page 13.
Serum albumin Exclusively produced A protein involved in Usually constitutes 50% of circulating
by the liver maintaining blood oncotic proteins. Levels may still be normal in
pressure (the pressure exerted patients with severe acute liver damage
by plasma proteins on capillary as the half-life of albumin in plasma is
walls); also functions as a ligand roughly 20 days.
transporter
Total protein Includes albumin immunoglobulins and other carrier Changes in the total protein are
proteins present in the blood; a variable proportion is non-specific as there may be increases
synthesised in the liver and decreases in different components,
e.g. chronic severe inflammatory liver
disease may cause low albumin and
other liver globulins but raised levels of
immunoglobulins
Prothrombin A reflection of liver synthesis of vitamin K dependent Outside the context of warfarin
time/International clotting factors II (prothrombin), VII, IX, X. A prothrombin monitoring, a raised INR may indicate
Additional

normalised ratio time test measures the time taken for clotting to occur decreased liver synthetic capacity or
(INR) in a sample, while the INR is a calculation based on the cholestasis with reduced vitamin K
prothrombin time results to ensure standardisation absorption. Levels rise quickly with acute
between laboratories. liver disturbance because of the short
half-life of the clotting factors.
* Community laboratories will provide reference ranges for LFT markers. For an example of LFT reference intervals stratified by sex and age, see:
www.labtests.co.nz/wp-content/uploads/sites/2/2019/11/Liver_Function.pdf.
† Sulfasalazine and sulfapyridine use may lead to false negative aminotransferase results. Some laboratories do not include AST in the initial LFT panel as
ALT is more specific.

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Interpretation of LFT results should be on the key causes of liver disease ” for more comprehensive lists
individualised of risk factors).

Reference ranges for LFTs will be provided by the community Medicine history and supplement use. Numerous medicines
laboratory performing the analysis. An “abnormal” LFT result is a are extensively metabolised within the liver, and some are
value that falls outside the range expected for 95% of a healthy directly hepatotoxic.1 In any patients with an abnormal LFT
reference population.8 This reference range can differ based on result(s), consider any medicines that have been recently
factors such as the patient’s sex and age. initiated or dosage changes. Also ask about use of any over-the-
counter (OTC) medicines or herbal or dietary supplements.1, 17
For an example of LFT reference intervals stratified by
See: “Always consider a possible pharmacological cause”.
sex and age, see: www.labtests.co.nz/wp-content/
uploads/sites/2/2019/11/Liver_Function.pdf Rare causes of abnormal LFTs
As a general guide, marker abnormalities are usually Family history of liver disease. Certain genetic conditions are
considered:7, 8 associated with liver damage, e.g. haemochromatosis, alpha-1
“Borderline” if they are < 2 times the upper limit of normal antitrypsin deficiency, Wilson’s disease (rare).2, 7
(ULN)
“Mild” if they are 2 – 5 times the ULN Exposure to hepatotoxic chemicals. If relevant, ask about
potential occupational or recreational exposure to hepatotoxic
The line that then separates “moderate” and “marked” LFT chemicals or industrial products, particularly in workers such
increases differs between international guidelines, with as painters, builders and factory workers. Some common
some labelling moderate as results between 5 – 10 times industrial solvents and epoxy resin hardeners are associated
the ULN,7, 8 whereas others consider the threshold to be > 15 with hepatocyte injury/cholestasis, e.g. dimethylformamide,
times the ULN.8, 14 In reality, this distinction is arbitrary, and dimethylacetamide, trichloroethylene.18
the magnitude of derangement in isolation is not a reliable
predictor of prognosis.2 Instead, the clinical significance of any How can symptoms and signs add to the clinical
change(s) should be interpreted in the context of (Figure 2): picture?
The specific patient’s characteristics, current clinical Acute liver disease symptoms. Acute hepatitis from any cause
situation, medical history and risk factors for liver disease is usually associated with non-specific symptoms of anorexia,
The overall pattern of LFT abnormality and any past fatigue and nausea. In severe cases, acute hepatitis can
results cause right upper quadrant abdominal discomfort, vomiting
and jaundice.2, 19 Acute cholangitis from any cause is usually
Clues that could reveal a potential cause for associated with the triad of (1) right upper quadrant abdominal
abnormal LFTs pain, (2) fever and (3) jaundice.

Common causes of abnormal LFTs Practice point: Cholecystitis is usually identified

Co-morbidities. Obesity, type 2 diabetes, dyslipidaemia and according to clinical presentation rather than LFT results
hypertension share similar lifestyle risk factors with liver disease and patients require acute referral and ultrasound if it
and promote its progression (see: “A spotlight on the key causes is suspected. The most common laboratory findings
of liver disease ”).2 In some cases the relationship is bidirectional, in patients with uncomplicated cholecystitis are
with liver disease also impacting on co-morbidity outcomes, e.g. leukocytosis and increased serum amylase levels.
type 2 diabetes.15 Other potential co-morbidities associated LFTs are often normal or associated with increased
with liver disease include autoimmune conditions (e.g. coeliac ALP levels. For further information, see: bpac.org.nz/
disease), inflammatory bowel disease or a history of cancer, i.e. bpj/2014/june/gallstones.aspx
metastases being deposited in hepatic tissue.
Chronic liver disease symptoms. In the early stages, most
Alcohol consumption. Consider past and present alcohol use people with chronic liver disease are either asymptomatic or
(see: “A spotlight on the key causes of liver disease ”). While even have mild non-specific symptoms such as fatigue.2 However,
short periods of alcohol misuse can cause liver damage, the risk in the advanced stages, symptoms can include weight loss
is highest in people who drink heavily over several years.16 (from malnutrition), weight gain with swollen legs (from fluid
retention), abdominal swelling (from ascites), gastrointestinal
Viral hepatitis. Review for risk factors of viral hepatitis (see: bleeding (from varices), sleep disturbance, drowsiness or
“Indications for requesting LFTs” in this article, or: “A spotlight confusion (from encephalopathy) or jaundice.19, 20

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 Referral for acute hepatology
Patient with an abnormal LFT assessment/urgent ultrasound at liver
Patient at risk of liver disease
finding(s) unit or gastroenterology department
(or emergency department)

Evaluate history for clues about the potential cause (if not already confirmed): Suspected synthetic liver failure
Co-morbidities, e.g. obesity, type 2 diabetes, Risk factors for hepatitis B and C infection  albumin + platelets and  prothrombin
dyslipidaemia, pregnancy Family history of liver disease time/INR (especially if jaundice is present)
Medicine history and supplement use Hepatotoxic chemical/substance exposure
Suspected malignancy e.g. weight loss and
Alcohol misuse (e.g. using AUDIT-C tool) Symptoms + physical examination findings Red marked cholestasis (see below)
flags
Suspected acute hepatitis/injury due to
If modifiable If it is a borderline abnormality and the patient is asymptomatic, address severe LFT increase/symptoms
cause is not any potential modifiable cause(s), such as:
apparent or LFT Change dose/substitute/discontinue medicine (if possible)
change is more Reduce/avoid alcohol consumption (if applicable or concerning)
significant

If the abnormal LFT finding(s) persists or worsens Repeat LFT within 3 months to see
if alteration persists and to inform
Is there a common clinical
subsequent action(s) required
pattern present?
Potential liver-related cause

Hepatocellular injury Acute: acute viral hepatitis, acute Consider the AST:ALT ratio
ischaemic injury, medicine-induced Yes < 1 = possible MASLD (no cirrhosis), chronic hepatitis B or C,
 ALT and/or
injury, acute autoimmune hepatitis acute injury
 AST
≥ 2 = possible alcohol- or medicine-injury, cirrhosis or malignancy
(compared with ALP) Chronic: Hepatitis B and C, alcohol-
≥ 5 = possible extra-hepatic cause if ALT low or normal
With/without  bilirubin related, MASLD, chronic autoimmune
Marked ALT or AST increases indicate acute hepatitis, or rare genetic causes, e.g.
or more severe injury haemochromatosis, Wilson disease
Apply a tiered approach to subsequent lab investigations according to
most likely causes + risk factors (see Table 2)

Cholestasis/cholestatic injury Acute: choledocholithiasis (gall

 ALP (often > 4× ULN) stones), acute cholangitis, medicine- Possible extra-hepatic causes: coeliac disease, heart failure, MI, skeletal
 GGT induced injury to bile ducts muscle injury, thyroid disorders, malnutrition, excessive exercise
(compared with ALT/AST) Chronic: primary biliary cholangitis,
With/without  bilirubin primary sclerosing cholangitis,
autoimmune cholangiopathy, bile
duct stricture, malignancy Yes Request ultrasound if suspected liver-related cause
Consider autoantibody/immunoglobulin testing if imaging is
negative

Possible extra-hepatic causes: bone disorders or metastases,

vitamin D deficiency, pregnancy-related, thyroid disorders

No

Manage according to underlying cause + consider

need for referral

Potential liver-related cause

Is there an isolated increase Request fractionated conjugated/direct bilirubin test and

Benign hereditary liver disorder such as
in bilirubin levels? i.e. Yes haemolytic screen (these are sometimes combined)
Gilbert’s syndrome (prevalence 5 – 8%)
normal ALT/AST and ALP/GGT If haemolysis negative and conjugated bilirubin is < 20% of
N.B. bilirubin can increase in addition to total bilirubin then Gilbert’s syndrome is likely
other LFT markers in most liver diseases Request ultrasound if conjugated bilirubin > 50% total

No If conjugated bilirubin ≥ 20% of total: can occur with either

acute hepatocellular or cholestatic injury, vanishing bile duct
syndrome, total parenteral nutrition, Rotor syndrome

Yes Reinforce general liver health advice

Repeat LFT within 3 months to see
Is there another isolated Consider need for other investigation(s) based
if alteration persists and to inform
abnormality? on specific LFT change (below) and any relevant
subsequent action(s) required
patient risk factors

 ALT Potential hepatocellular injury or extra-hepatic causes (as above)

Isolated AST increases may also indicate a extra-hepatic cause if ALT normal, e.g. cardiac or skeletal muscular injury
 AST
Fractionated isoenzyme testing may be useful to determine origin (e.g. liver or bone) if isolated increase persists > 6 months; however, this
 ALP
test is not readily available in community labs and is generally only requested after secondary care assessment
 GGT Rarely indicative of significant liver disease if raised in isolation; potentially caused by excess alcohol intake or medicine use
Test INR if not already available to assess for synthetic liver failure (see red flags above)
 Serum albumin
Other causes include cachexia, catabolic states such as sepsis or cancer, nephrotic syndrome and protein-losing enteropathy
Total protein comprises both albumin and globulins; isolated significant changes in patients with normal albumin may suggest an immune-
/ Total protein
related cause (e.g. active infection or autoimmune disease), malignancy

Abbreviations: ALP, alkaline phosphatase; ALT, Alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyl-transferase; INR, international normalised ratio; LFT, liver function test, MI, myocardial infarction;
MASLD, Metabolic dysfunction-associated steatotic liver disease.

Figure 2. A pathway for interpreting abnormal LFT results in primary care.2, 7–9
N.B. This algorithm is mostly applicable to stable patients with either no symptoms or mild symptoms. The presence of significant clinical features should
increase suspicion of acute or advanced liver disease or extra-hepatic conditions.

www.bpac.org.nz November 2022 7

 Always consider a possible pharmacological cause

While it is uncertain what proportion of abnormal LFT To assess whether a medicine undergoes significant
results are medicine-related in asymptomatic patients, at hepatic metabolism or can be used in patients with hepatic
least 20% of all acute liver failure events are associated impairment, refer to the New Zealand Formulary: nzf.org.nz
with medicine use.21 When reviewing the history of
patients with abnormal LFT findings, any newly initiated The investigation should not just be limited to prescribed
medicines should be considered a potential cause until medicines. Also consider:
proven otherwise (also see alternative medicines and OTC medicine use, particularly paracetamol or
other substances below). paracetamol-containing products (such as “cold and
flu” preparations) and NSAIDs
The patten of LFT derangement linked to
medicine use can vary; sometimes being Dietary supplements, e.g. turmeric, green tea
reflective of hepatocellular injury, cholestatic extract
injury or a combination of both (see below and Complementary and alternative medicines,
also “Consider whether a common LFT pattern including traditional Chinese medicines (e.g. Ba
is present”, Page 10)22 Jiao Lian [Dysosma pleianthum], Chi R Yun [Breynia
officinalis], Jin Bu Huan [Lycopodium serratum],
The time to liver toxicity can differ depending Ma Huang [Ephedra sinica], and Shou Wu Pian
on the medicine and patient; medicines with [Polygonum multiflorum]), Indian (ayurvedic)
dose-dependent effects can cause toxicity treatments, Polynesian traditional/herbal
within short periods of time (e.g. hours to days remedies and Rongoā Māori/Rākau preparations
of exposure), whereas those with idiosyncratic (e.g. those involving Usnea lichen)24
effects (dose-independent) may not cause Recreational drug use (especially ecstasy/MDMA
toxicity until weeks or months after exposure.22 and methamphetamine)

Frequently prescribed medicines in primary care that

If any potential pharmacological cause* is identified, the
influence liver function:1, 20, 22
subsequent action will depend on the medicine, balancing
Paracetamol. Hepatotoxicity is dose-dependent;
(1) its importance to the patient’s treatment and (2) the
scenarios include incorrect dosing, prolonged
magnitude of the LFT derangement or perceived clinical
use, inadvertent use of two different medicines
risk. Consider whether a medicine/supplement can be
containing paracetamol, intentional overdose.
withdrawn or a substitute can be used, particularly if the
Paracetamol-related liver injury typically involves
abnormality is severe and it is clinically reasonable to do
marked aminotransferase elevations (ALT and AST),
so.25 Alternatively, a dose reduction may be warranted for
which may be extreme in cases of acute overdose
essential medicines.25 Assuming the patient is stable and
(e.g. > 10,000 U/L).20
does not require secondary care review, repeat LFT testing
Antibiotics, e.g. amoxicillin + clavulanic acid, should be undertaken within three months to assess
flucloxacillin, erythromycin. Liver damage is often whether the abnormality has corrected.25
dose-independent and transient LFT changes can
* Some medicines have a specific detoxification protocol, e.g.
occur even with standard dosing.20 Sometimes
paracetamol overdose requires administration of intravenous
a course of antibiotics can cause abnormal LFTs acetylcysteine in patients at risk of hepatotoxicity (for further
several weeks/months after completion (in addition information, see: www.mja.com.au/journal/2020/212/4/updated-
to features such as persistent jaundice). guidelines-management-paracetamol-poisoning-australia-and-
Non-steroidal anti-inflammatory drugs (NSAIDs) new-zealand).

Anticonvulsant medicines, e.g. phenytoin,

carbamazepine, sodium valproate Practice point: report suspected medicine-
Immunomodulatory medicines, e.g. methotrexate, induced abnormal LFTs to the Centre for Adverse
azathioprine Reactions Monitoring (CARM)
Other medicines, including allopurinol, amiodarone,
isotretinoin, isoniazid

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Possible LFT patterns associated with specific medicines and supplements20, 23

Hepatocellular injury Cholestatic injury

Mixed pattern
( ALT and/or  AST ±  bilirubin) ( ALP and  GGT ±  bilirubin)

Paracetamol Oral contraceptives Carbamazepine

Allopurinol Amoxicillin + clavulanic acid Phenytoin
Sodium valproate Cephalosporins Lamotrigine
Disulfiram Erythromycin NSAIDs
Isoniazid Flucloxacillin
Green tea extract Rifampicin
Tricyclic antidepressants
Anabolic steroids

N.B. These are examples of medicines which cause more predictable LFT changes; other medicines can induce liver damage, but the associated LFT
derangement is variable.

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Physical examination. Physical examination findings are tissues (including skeletal, cardiac and smooth muscle), so
often normal in patients with LFT derangement; the presence isolated increases may indicate extra-hepatic conditions, e.g.
of abnormal findings should increase suspicion of more myocardial infarction or myositis.2
advanced or severe liver disease.8 For example:8, 14 A wide range of processes can damage liver cells, which
Hepatomegaly is more common in alcohol-related liver may become apparent through a review of the patient history
disease, haemochromatosis and primary biliary cirrhosis and risk factors, or after consideration of the AST:ALT ratio
than other liver diseases. Hepatomegaly may also be (see: “Consider the AST:ALT ratio”). Key causes of hepatocellular
caused by liver congestion (e.g. due to heart failure or injury include metabolic dysfunction-associated steatotic liver
hepatic venous obstruction) or malignant infiltration disease (MASLD), medicine or alcohol-induced liver damage
(particularly lymphoma and hepatocellular carcinoma). and viral hepatitis.7 Rarer causes include haemochromatosis,
Jaundice may indicate biliary obstruction, acute hepatitis autoimmune diseases and endocrine disorders.7
or advanced liver disease
Skin hyperpigmentation and arthralgias may be For further information, see: “A spotlight on the key causes
indicative of haemochromatosis of chronic liver disease”
Muscle wasting, spider telangiectases (also known as
spider naevus or spider angiomas), palmar erythema, If hepatocellular injury is suspected, a tiered approach to
gynaecomastia, testicular atrophy, ascites and subsequent testing is recommended, informed by patient-
splenomegaly may indicate cirrhosis specific characteristics (Figure 2 and Table 2).2, 7–9 For example,
if a patient has increased aminotransferases and risk factors for
Asterixis (hepatic flap/flapping tremor) is a distinctive
viral hepatitis, testing for hepatitis B surface antigen (HBsAg)
sign of hepatic encephalopathy
and anti-hepatitis C virus antibodies (anti-HCVAb) would be
Kayser-Fleischer rings and neurologic motor
key initial investigations as hepatitis B and C are the most
abnormalities are rare features of Wilson’s disease
common viral triggers. If these tests are negative, investigating
other potential viral causes could be considered (Table 2).2
Consider whether a common LFT pattern is
present Consider the AST:ALT ratio in patients
Individual LFT marker changes are not usually specific to with elevated aminotransferase levels;
a particular condition; instead, the pattern of LFT marker this can provide information on the likely
alteration is usually more informative if a review of the patient’s cause and stage of chronic liver disease and
history does not immediately reveal a likely underlying cause.2 inform the type of subsequent investigations
In many cases, this pattern will be one of the first pieces of required.
evidence to capture a clinician’s attention, which will then In general, an AST:ALT ratio of:8
guide subsequent investigations. While any liver disease can < 1 (i.e. AST is less than ALT) is generally
paint a complex biochemical picture, there are usually two key indicative of chronic viral hepatitis B or C, MASLD
patterns of LFT abnormality which reflect distinct types and without cirrhosis (see: “A spotlight on the key
locations of liver injury (Figure 2): hepatocellular injury and causes of chronic liver disease”) or an acute
cholestasis. hepatocellular injury
≥ 2 (i.e. AST is at least two times greater than
Pattern 1: Hepatocellular injury (increased
ALT) is generally found in patients with alcohol-
aminotransferases ± increased bilirubin)
related liver disease, drug-induced liver injury,
When liver cells are damaged by processes such as necrosis
cirrhosis of any cause, and primary liver cancer
or inflammation, their membranes become more permeable,
≥ 5 should prompt suspicion of a potential
which can lead to the release of intracellular enzymes into the
extrahepatic cause, particularly if ALT levels are
bloodstream.2 The most notable markers released through
minimally elevated or normal
this process are the aminotransferases (Table 1): alanine
aminotransferase (ALT) and aspartate aminotransferase
(AST).2 Disproportionate serum elevations for either enzyme Pattern 2: Cholestasis/cholestatic injury (increased
compared with ALP are the most common LFT abnormalities ALP and GGT ± increased bilirubin)
in this context; ALT and AST level changes frequently correlate Cholestasis refers to any condition that causes reduced bile
with each other.2 However, ALT is considered to be more production or flow through the bile ducts from the liver into
specific for liver dysfunction as this is the predominant site the duodenum.26 Patients with cholestasis are often clinically
of its production.2 AST is also abundant in other organs and asymptomatic, however, those with more severe disease may

10 November 2022 www.bpac.org.nz

Table 2. Recommendations for possible subsequent testing and interpretation of results in stable patients with elevated
aminotransferase levels (ALT or AST).2, 7–9

Test Abnormality Interpretation or potential cause

First tier

Full blood count (FBC) Macrocytosis* Possibly due to excessive alcohol intake,
particularly if GGT also raised

Thrombocytopenia* Portal hypertension (possible hypersplenism)

which may also be associated with
ultrasound findings of enlarged spleen,
portal vein and ascites or varices. Also
common in chronic liver disease.

HbA1c or fasting glucose Elevated (e.g. HbA1c > 41 mmol/mol or Indicates glucose intolerance conditions, e.g.
fasting glucose > 5.5 mmol/L) type 2 diabetes and pre-diabetes; MASLD is
common in these patient groups

Lipid profile Abnormal Contributor to fatty liver diseases, i.e. alcohol-

related liver disease or MASLD

Iron studies,* Elevated Possible haemochromatosis. Check

inc. ferritin and TSAT hereditary haemochromatosis (HFE)
genotype if repeat testing remains high in
fasting† and otherwise well patients

Hepatitis screening Positive Suggests hepatitis B or C infection. HCV

(HBsAg and anti-HCVAb) requires confirmation of infection by either
detection of HCV RNA or HCV Antigen

AUDIT-C screening Positive Suggests potential alcohol misuse; full AUDIT

(score ≥ 3 in female or ≥ 4 in male) tool assessment should then be undertaken

Second tier

Abdominal/ liver Echogenic liver, mass or dilated ducts Can be used to detect fatty liver, malignancy
ultrasound** or gall stones/obstruction

Testing for other causes Positive Suggests infection with corresponding

of viral hepatitis, e.g. virus; hepatitis A testing may be a first-tier
Hepatitis A, Epstein Barr investigation if the patient reports travel
virus, Cytomegalovirus to a country where infection is prevalent or
contact with local outbreak or MSM

Autoantibodies and Antimitochondrial antibody (AMA) positive, Diagnostic of primary biliary cirrhosis
Immunoglobulins increased IgM in combination with
cholestatic LFTs

Anti-smooth muscle antibody (SMA)/ Probable autoimmune hepatitis

anti-liver kidney microsomal (LKM)/anti-liver
soluble antigen (SLA)/anti-nuclear antibody
(ANA) positive, particularly with elevated IgG

Coeliac serology screen Positive Suggestive of coeliac disease-related liver

damage

Other tests dictated by clinical context or family history of liver disease, such as:
Checking alpha-1 antitrypsin levels in people with a family history of deficiency
Serum/urine copper and caeruloplasmin testing in patients with a family history of Wilson’s disease

* If these tests have been performed for other clinical reasons and an abnormality is found, then subsequent LFT testing is usually warranted
† A fasting sample may improve the accuracy of results if there is uncertainty about an abnormal result
** In patients where ultrasound does not identify any underlying cause and the diagnosis remains uncertain, consider referring for further assessment with
FibroScan, if needed (see: “FibroScan is an emerging alternative tool to liver biopsy”). Liver ultrasound is first tier investigation if cholestasis is suspected.

www.bpac.org.nz November 2022 11

 present with features such as intense pruritus, abdominal
The pathophysiology of cholestasis pain, jaundice and fatigue.26 For further information, see: “The
pathophysiology of cholestasis”.
Accurately diagnosing the underlying cause of cholestasis The hallmark LFT findings for cholestasis include elevated
is important to tailor subsequent management decisions; ALP and GGT results compared with aminotransferase levels
if left unresolved or ineffectively treated, chronic or severe (Figure 2).2, 26 While most other LFT markers are usually within
cases are associated with bile duct loss which inevitably a normal range, bilirubin levels can also be increased.26 If
leads to fibrosis and cirrhosis.26 cholestasis is suspected based on LFT results, a liver ultrasound
is recommended; this may help identify features such as
Cholestasis occurs when biliary constituents accumulate obstruction, biliary duct dilation, space-occupying lesions
beyond the normal limits of clearance. This process in turn (e.g. a cyst) or malignancy, which will then guide subsequent
contributes to direct cellular damage and accumulation management decisions.8 If there are no significant ultrasound
of noxious chemicals, including bile acids. Cholestasis findings, additional serologic blood tests may be helpful, e.g.
can be sub-classified as being intra-hepatic (e.g. due to antimitochondrial antibody positivity can indicate primary
hepatocyte injury, intra-hepatic bile duct or bile canaliculi biliary cholangitis as a potential cause.8
abnormalities) or extra-hepatic (e.g. abnormalities
associated with the extra-hepatic ducts, the common bile Fractionated ALP isoenzyme testing. GGT elevation
duct or common hepatic duct):26 in parallel with increased ALP levels is the strongest
Common causes of intrahepatic cholestasis LFT-based predictor of cholestasis. 26 However,
include acute hepatitis, drug-induced cholestasis cholestasis may also be associated with isolated
(e.g. amoxicillin + clavulanic acid, flucloxacillin). Rare ALP increases (i.e. GGT is normal or only borderline
causes include hereditary abnormalities in bilirubin elevated) which can be from either a hepatic or
transporters (Dubin-Johnson syndrome, Rotor extra-hepatic source (e.g. bone, intestine, placenta
syndrome, and progressive familial intrahepatic during pregnancy). A fractionated ALP isoenzyme
cholestasis). Severe sepsis may also cause canalicular test can help in this situation to distinguish whether
dysfunction which results in intrahepatic cholestasis. cholestasis is likely or whether other diagnoses should
Common causes of extrahepatic biliary be considered, e.g. bony metastases, Paget’s disease,
obstruction include gallstones and malignancy Vitamin D deficiency.2, 26 However, this test is not readily
– either intraductal obstruction from primary available in community laboratories in New Zealand
liver cancers (hepatocellular carcinoma or and is generally only requested after secondary care
cholangiocarcinoma), or extrinsic compression referral. ALP isoenzyme testing is most likely to be
from pancreatic cancer, lymphoma, or lymph node helpful for patients with a sustained increase in ALP
metastases from breast, colorectal cancers (> 6 months), and no other cause for the increase is
clinically apparent.
In cases not caused by obstruction, the heritable risk
of cholestasis is most notable during childhood, while
an autoimmune trigger (e.g. primary biliary cholangitis Other LFT changes to consider
and primary sclerosing cholangitis) is more likely in
Synthetic liver failure (decreased albumin and
adulthood.26
prolonged INR)
While the hepatocellular/cholestatic LFT patterns provide clues
regarding the location of dysfunction, overall liver performance
can also be estimated by its ability to produce albumin – a
protein exclusively synthesised in the liver.2 Particular attention
should be given to persistent decreases in albumin over time
when considering past test results. However, assessment of
this marker is complicated as serum albumin concentrations
are affected in other clinical circumstances, e.g. diabetic
nephropathy, malabsorption, sepsis, systemic inflammatory
conditions.2 In addition, albumin has a long half-life, meaning
levels may not be substantially reduced in instances of acute
liver injury.11

12 November 2022 www.bpac.org.nz

 Requesting an assessment of the patient’s INR (in those only report total bilirubin, i.e. both conjugated (direct) and
not taking warfarin) can be useful to more completely define unconjugated (indirect) forms. Therefore, a key follow-up
synthetic function if albumin levels have decreased.2 This investigation in patients with isolated hyperbilirubinaemia
provides information on whether pathways of coagulation is to request fractionated/split bilirubin testing to measure
are impaired; fibrinogen and most of the clotting factors used the conjugated/direct component (allowing for estimation of
in this investigation are produced in the liver, so an increased the unconjugated/indirect form). This approach can help to
INR further reflects hepatic deficiencies.7, 9 Other features that localise the potential source of marker abnormality:7, 8
should raise clinical suspicion of synthetic liver failure include Unconjugated hyperbilirubinaemia (conjugated form
low platelet levels and overt clinical signs of liver disease, is < 20% of total bilirubin) is more likely if production
such as jaundice.2 Vitamin K malabsorption (usually due to increases (e.g. haemolysis) or liver uptake/conjugation
cholestasis) can also increase INR, however, this usually resolves is impaired due to mutation in key processing enzymes
within 24 hours of parenteral vitamin K injection (not oral). (e.g. Gilbert’s syndrome)
Conjugated hyperbilirubinaemia (conjugated
Practice point: Given that synthetic liver failure
form is ≥ 20% of total bilirubin) can occur with either
reflects a loss of functioning liver mass, referral for
hepatocellular injury or cholestasis. Other conditions
urgent ultrasound or acute secondary care review is
associated with conjugated hyperbilirubinaemia include
generally recommended if there is clinical suspicion.
vanishing bile duct syndrome, the effects of total
Isolated hyperbilirubinaemia parenteral nutrition, and rare disorders such as Rotor
Serum bilirubin levels are not useful for distinguishing between syndrome and Dubin-Johnson Syndrome. Consider
hepatocellular injury or cholestasis as increases can occur ultrasound if the conjugated fraction is > 50% of the total.
with most types of liver damage.7 However, isolated bilirubin
increases in patients with otherwise normal LFT results may If unconjugated hyperbilirubinaemia is identified, haemolysis/
warrant further investigation as they can indicate several haemolytic anaemia should be ruled out by requesting a
different conditions of varying clinical significance, ranging haemolytic screen, assessing serum haemoglobin, haptoglobin
from benign inherited liver-related conditions (e.g. Gilbert’s levels, lactate dehydrogenase and reticulocyte count.2, 7 N.B.
syndrome), to haemolytic disorders or serious defects in liver Some laboratories may include the fractionated bilirubin test
processing/excretion. in the haemolytic screen. If these haemolytic tests are negative,
Red blood cell (haemoglobin) breakdown generates Gilbert’s syndrome is most likely the cause, which occurs in 5
unconjugated bilirubin, which is transported to the liver, – 8% of the population.2 This is generally considered a benign
processed into the conjugated form and excreted into condition, with at least one-third of all people being entirely
bile (Figure 3).2 However, standard LFT panels generally asymptomatic.2

Blood Liver

Red blood cell ~85%

breakdown
Unconjugated + Glucuronic acid
bilirubin
Ineffective Conjugated
Haem
erythropoiesis bilirubin

Haem- Biliverdin
containing tissue Bile duct

Small intestine
Conjugated
bilirubin Urobilinogen
Urine
Reabsorption

Kidneys Stool
Figure 3. An overview of bilirubin metabolism.2

www.bpac.org.nz November 2022 13

Deciphering other isolated LFT marker Non-acute hepatology referral should be considered in:2, 8
abnormalities Patients with persistent and unexplainable abnormal LFT
results, who have negative serology results and who lack
People with true liver dysfunction are most likely to have risk factors for MASLD or alcohol-related liver disease*
multiple abnormal LFT results rather than isolated marker Patients with suspected MASLD who have an elevated
derangement.2 All LFT marker levels can be affected by non- FIB 4 score (≥ 1.3 if aged ≤ 60 years or ≥ 2.0 if aged > 60
hepatic disease, modifiable risk factors or transiently fluctuate, years) AND a FibroScan reading > 8 KPa (see: “FibroScan
and therefore an isolated abnormality should increase clinical is an emerging alternative tool to liver biopsy”), as
suspicion of these various possibilities (although it does not this indicates they are likely to have progressed to
exclude the possibility of liver disease).2 steatohepatitis (MASH) and should be referred for
For borderline isolated LFT abnormalities (i.e. changes management
in individual markers < 2 times the ULN) in asymptomatic Patients with hepatitis B who have an elevated ALT level
patients, it is reasonable to deliver general liver health advice for at least three months† (N.B. this referral criterion was
(e.g. reducing alcohol intake, healthy eating and exercise, if previously six months)
applicable) and re-test LFTs within the next three months
Patients with hepatitis C if HCV RNA or antigen is still
(Figure 2). However, more significant changes in individual
detectable four weeks after Maviret treatment (N.B.
markers or a progressive increase from previous results may
the referral criterion was previously 12 weeks post-
prompt more immediate investigation.
treatment) or if they have cirrhosis†
Figure 2 details some causes of isolated marker increases
Patients with hereditary haemochromatosis (i.e.
and potential further actions. As an example, GGT is a very
HFE gene mutation) and abnormal LFT findings,
sensitive marker, and isolated mild increases commonly
hepatomegaly or ferritin > 1,000 micrograms/L**
occur due to alcohol consumption or medicine use; it does
not usually imply significant liver damage/disease unless the * For patients with suspected MASLD and alcohol-related liver disease
increase is marked. Likewise, given that GGT and ALP levels without suspicion of advanced fibrosis, it is reasonable to undertake
management and ongoing monitoring in primary care without referring
often correlate in the context of liver impairment, isolated
to secondary care.8 See the corresponding sections in “A spotlight on the
increases in ALP may be associated with deficiencies of bone
key causes of liver disease ” for more information.
origin rather than liver damage, and therefore fractionated
† For further information on:
isoenzyme testing may be indicated for persistent elevations, Managing hepatitis B infection, see: bpac.org.nz/2018/hepb.aspx
e.g. longer than six months (this may require secondary Managing hepatitis C infection, see: bpac.org.nz/2019/hepc/
care referral if not routinely available in local community overview.aspx
laboratory).2, 9 ** For further information on hereditary haemochromatosis, see: bpac.org.
In rare instances, enzymes tested for in LFT panels may nz/BT/2015/April/haemochromatosis.aspx

form macro-complexes with immunoglobulins (e.g. AST with

When should ultrasound be requested?
IgA), which reduces renal clearance and leads to elevated
results not associated with liver disease.27 Evaluation for LFT One of the more challenging decisions when investigating
macro-complexes can usually be arranged with community abnormal LFT results is deciding if and when an abdominal
laboratories, and this possibility could be considered in ultrasound should be requested in patients not being referred
patients with persistently elevated individual marker levels for gastroenterology review. Referral for community-based
with no identifiable cause. ultrasound is generally indicated in patients with abnormal
LFT results and:25, 28, 29

Referral criteria for patients with abnormal Suspected cholestasis (i.e. predominantly raised ALP/
LFT results GGT) or with jaundice where intra- or extra-hepatic
obstruction is suspected
While most liver problems can be managed in primary care, Persistently elevated aminotransferase levels which
referral for acute hepatology assessment is recommended cannot be explained by first tier investigations (Table 2)
in all patients with:2, 8
Suspected gallstone or pancreatic disease, e.g. associated
Any clinical, laboratory or imaging evidence of significant with persistent/recurrent right upper quadrant pain
fibrosis or cirrhosis
Clinical hepatomegaly
Any evidence of acute or chronic synthetic liver failure
Who are at risk of metastatic liver cancer
High suspicion of malignancy, e.g. weight loss and
Who require screening for primary hepatocellular
marked cholestasis
carcinoma due to existing cirrhosis

14 November 2022 www.bpac.org.nz

FibroScan is an emerging alternative tool to liver Detect disease progression or regression if serial
biopsy measurements are performed
Support management decisions and guide prognosis
Referral for consideration of liver biopsy is sometimes indicated
as the next step in patients with suspected liver disease but Over-estimation of fibrosis is possible in some cases, including
the diagnosis, prognosis and optimal management approach when patients have prominent liver inflammation, liver
remains uncertain based on laboratory tests, physical congestion (right heart failure, tricuspid regurgitation, fluid
examination and ultrasound.8 However, biopsy is an invasive overload from renal failure) cholestasis or malignancy.30 In
procedure that has several limitations, e.g. the potential for addition, accuracy may be reduced in patients with a high
sampling error, risk of complications and service availability.8 BMI (> 30 – 35 kg/m2) or older age.30 FibroScan is usually
unsuccessful (i.e. no readings can be obtained) in patients with
FibroScan is an emerging non-invasive tool in the liver ascites, or with morbid obesity.
diagnostic/prognostic toolkit, that uses transient elastography
to assess the stiffness of the liver which is an indirect Pregnancy-related LFT derangement/liver
measurement of liver fibrosis. FibroScan can diagnose the disease32–34
presence of severe fibrosis or cirrhosis of the liver but it cannot Intrahepatic cholestasis of pregnancy – while elevated
diagnose the underlying cause of the liver disease.30, 31 ALP levels are common during pregnancy due to an influx
of placental enzymes, transient LFT results indicative of
Intended as a complement to conventional cholestasis (i.e. both ALP and GGT increases) may also
ultrasound (if required) and not a replacement. sometimes occur, particularly during the third trimester. This
FibroScan does not inform on all aspects of structural is referred to as intrahepatic cholestasis of pregnancy (ICP) and
liver integrity, and ultrasound permits assessment of other the key symptom is pruritus, usually without a rash. The clinical
features, such as portal hypertension, abdominal varices, significance of ICP mostly relates to the potential for foetal risk,
recanalisation of the umbilical vein and splenomegaly.30 e.g. pre-term birth, intrauterine death. If a pregnant female
reports pruritus but has normal LFT findings, LFTs should be
Indications. FibroScan is recommended before repeated every 10 – 14 days while symptoms persist. If LFT
initiating Hepatitis C treatment in primary care.* results are abnormal, arrange a liver ultrasound and seek acute
FibroScan is also indicated whenever there is clinical obstetric advice (early induction of labour may be considered).
suspicion of advanced fibrosis/cirrhosis, regardless of the
underlying cause.30 Use of a relevant clinical scoring tool is Hyperemesis gravidarum – typically occurs during the first
often a pre-requisite to access, e.g. NFS, FIB-4 or APRI. trimester and involves nausea and intractable vomiting (more
* If FibroScan cannot be accessed, it is acceptable to calculate the patient’s severe than usual “morning sickness”), resulting in dehydration,
APRI score to estimate fibrosis risk before initiating treatment (see: “A ketosis and weight loss. While this is not a true liver disease
spotlight on the key causes of liver disease ”). For further information, per se, abnormal transaminase findings occur in approximately
see: bpac.org.nz/2019/hepc/pre-treatment.aspx half of patients with this condition. For further information
on management, see: bpac.org.nz/BPJ/2011/november/
Availability and referral criteria vary throughout pregnancy.aspx
the country. Clinicians are advised to contact
their local gastroenterology service to determine if Pre-eclampsia – defined as new onset hypertension occurring
FibroScan is available in their region, which patients should after 20 weeks of pregnancy, or when there is pre-existing
be referred for assessment and how this is done. In some areas, hypertension and new features of proteinuria, maternal
direct general practitioner referral is available for patients with organ dysfunction or uteroplacental dysfunction develop. LFT
Hepatitis C infection. abnormalities occur in 10% of females with pre-eclampsia and
may include mild increases in aminotransferase levels.
Transient elastography involves measuring the velocity
of vibration waves (“shear waves”) produced by a device HELLP syndrome – a variant of pre-eclampsia which usually
positioned on the skins surface.30 By determining the time occurs in the later stages of pregnancy (or soon after childbirth)
taken for waves to travel to a particular depth within the liver, and is characterised by haemolysis, elevated liver enzyme levels
stiffness caused by fibrosis or cirrhosis can be determined.30 (usually aminotransferase; typically more severe increases
This information can be used to:30 compared with pre-eclampsia) and low platelet counts (< 100
Estimate the current level of scarring-associated liver × 109/L). Increased blood pressure and proteinuria may also
damage be present. Risk factors include multiparity and advanced

www.bpac.org.nz November 2022 15

maternal age, and females typically present with fluctuating 7. Malakouti M, Kataria A, Ali SK, et al. Elevated liver enzymes in asymptomatic
patients – what should I do? J Clin Transl Hepatol 2017;5:1–10. doi:10.14218/
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25. Government of British Columbia. Practitioner and professional resources.
University of Auckland, Chief Hepatologist and Deputy Abnormal liver chemistries – evaluation and interpretation. 2011. Available
from: https://www2.gov.bc.ca/gov/content/health/practitioner-professional-
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Ltd and Roche Diagnostics NZ Ltd. The publication was 29. Ministry of Health. National criteria for access to community radiology.
independently written and Roche had no control over the 2015. Available from: https://www.health.govt.nz/system/files/documents/
publications/national-criteria-for-access-to-community-radiology-mar15-v2.
content. The views expressed in this publication are those
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