This site is intended for UK healthcare professionals
Medscape UK Univadis Logo
Medscape UK Univadis Logo

Welcome to the new home of Guidelines in Practice

For Primary Care| Differential diagnosis

Jaundice: What's the Diagnosis?

Dr Jez Thompson Uses Case Studies to Explore Possible Causes of Jaundice and How They Should Be Diagnosed and Managed in Primary Care

Read This Article to Learn More About:
  • what jaundice is, and what causes it
  • investigation and management strategies based on the causes of jaundice
  • red flags for urgent referral.
Reflect on your learning and download our Reflection Record.

Jaundice, derived from the French word for yellow, jaune, can be a patient’s presenting symptom or a clinical sign identified by a clinician. It describes a yellow or sometimes greenish-yellow pigmentation of the skin, conjunctiva, and mucous membranes that is caused by raised plasma bilirubin.1 Jaundice usually becomes clinically apparent when a patient’s serum bilirubin concentration reaches 40–50 micromol/l.2

Jaundice can present at any age. It can be caused by a wide range of disorders that includes benign conditions, those that can result in permanent and irreversible liver damage, and those that are rapidly life threatening.1 Jaundice is the result of dysfunction in the bilirubin metabolism pathway, and its causes can be categorised as pre-hepatic (for example, excessive breakdown of red blood cells), intra-hepatic (for example, disease-related perturbation of liver function or intrahepatic anatomy), or post-hepatic (for example, obstruction of the bile ducts).1,2

Some of the common causes of jaundice in adults are summarised in Box 1.3

Box 1: Common Causes of Jaundice in Adults3
  • Causes of pre-hepatic jaundice include:
    • haemolytic anaemias
    • drugs
    • Gilbert’s syndrome
    • Crigler–Najjar syndrome
  • Causes of intra-hepatic jaundice include:
    • viral infection
    • alcohol
    • autoimmune liver disorders
    • metabolic causes of intra-hepatic jaundice
    • drugs
    • malignancy of the biliary system
  • Causes of post-hepatic or obstructive jaundice include:
    • gallstones
    • surgical strictures
    • extra-hepatic malignancy
    • pancreatitis
    • parasitic infections.
© NICE 2023. Jaundice in adults: causes. NICE Clinical Knowledge Summary. Available at:

All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See for further details.

In the neonatal period, more than half of healthy full-term babies develop jaundice as part of normal physiological processes4,5 and, in 2–15% of births, jaundice persists beyond 14 days.6 Outside the neonatal period, the incidence of jaundice has not been established; however, one prospective study looking at clinically overt jaundice (a serum bilirubin level in excess of 120 micromol/l) in Wales found an annual incidence of 56 cases per 100,000 people, approximating to one patient presenting with visible jaundice each year for a typical UK GP.7 

The challenge for the clinician is to establish the cause of jaundice and, as part of this, decide whether jaundice represents a benign and self-limiting condition or a serious underlying illness. Through the following case studies, this article aims to explore some common and important conditions that can present with jaundice, provide suggestions for first-line investigations and management in primary care, and offer guidance on when to consider specialist referral or admission.

Case 1 

A previously well man in his early 20s presents with a 1-week history of progressive fatigue, nausea, anorexia, low-grade fever, and flu-like symptoms followed by a 1-day history of yellowing of his eyes and skin. He has experienced no abdominal pain or itching, but admits to paler stools than usual and dark urine over the preceding 24 hours. 

The patient has reported no previous episodes of jaundice, and has no relevant medical history. Abdominal and general examinations are normal, apart from the presence of jaundice and a mild fever of 37.9°C. The patient is fully alert, and shows no signs of serious systemic illness. There are no red flags for a serious underlying condition.


The patient’s clinical presentation is suggestive of acute hepatitis. Differential diagnoses for hepatitis A are shown in Box 2.8

Box 2: Differential Diagnoses of Hepatitis A in Adults8

The differential diagnoses of hepatitis A include:

  • viral hepatitis caused by other viruses (such as hepatitis B, C, D, and E), Epstein–Barr virus (infectious mononucleosis), or cytomegalovirus (CMV)
  • alcohol-induced hepatitis—suspect if there is a history of alcohol misuse
  • drug-induced liver disease—suspect if there is a history of paracetamol overdose or therapeutic use of paracetamol in a person who misuses alcohol
  • acute HIV infection
  • autoimmune hepatitis—ninety percent of cases occur in women. Suspicion is raised by the presence of other autoimmune disorders 
  • hepatitis caused by bacterial infections such as leptospirosis and Coxiella burnetii
  • granulomatous disorders
  • Wilson's disease.
© NICE 2023. Hepatitis A: what else might it be? NICE Clinical Knowledge Summary. Available at:

All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See for further details.

Further history taking with this patient established that, 3 weeks previously, he returned from a 2-week holiday in a nonmalarial area in the Far East, where he got a tattoo. The patient drinks within recommended limits and, apart from smoking cannabis as a teenager, has not used illicit drugs and is a ‘never injector’. He has not taken any medications or remedies recently and has been abstinent from sex for the preceding 3 months, including while on holiday. He works in an office.

The patient underwent blood tests and, because there were no clinical features to suggest severe illness, was managed without specialist referral while waiting for the results. When the results returned, full blood count and urea and electrolytes were normal. Liver function tests (LFTs) showed a markedly raised alanine aminotransferase (ALT; 1012 IU/l) level and a significantly raised serum bilirubin concentration (82 micromol/l). Alkaline phosphatase (ALP) was only mildly raised, at around 1.5 times the upper end of the reference range. Prothrombin time and albumin level were normal. These results are consistent with a diagnosis of hepatitis with normal liver synthetic function.9

Because of the patient’s history of recent foreign travel and tattooing, serology testing was arranged for hepatitis A, B, and C, and HIV. Initial hepatitis B and C and HIV serology test results were negative, but hepatitis A serology tests yielded positive results for both hepatitis A virus immunoglobulin (Ig) M and IgG. A likely clinical diagnosis of acute hepatitis A infection was made and, in the absence of complications or signs of severe illness, it was decided that the patient should be managed in primary care. 


There is no specific treatment for hepatitis A, as it is generally a self-limiting condition; unless hospital admission is needed, treatment focuses on supportive symptomatic care.10 The patient was advised that he would likely feel more tired than normal, perhaps for several months, and that he should rest and stay hydrated. He was directed to take simple analgesia as required, and to avoid fatty foods and eat small, regular meals and snacks to help reduce nausea. He was also advised to avoid drinking alcohol while acutely unwell, to stay off work while he was infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice), and to use hygiene measures to reduce the risk of transmission to partners and contacts (see Box 3).10

Box 3: Measures to Minimise the Transmission of Hepatitis A Infection10

The person and all close contacts should:

  • ensure thorough hand washing after using the toilet, including supervising young children who may have difficulty with personal hygiene
  • wash their hands immediately after changing nappies or helping with child toileting (including handling a potty)
  • ensure good general personal hygiene
  • avoid handling food, if possible, or thorough hand washing before food preparation, for contacts of cases
  • avoid unprotected sexual intercourse, including oro-anal and oro-genital contact, until the person is no longer infectious (typically 7 days after the onset of jaundice, or 7 days after the onset of symptoms if there is no history of jaundice)
  • avoid sharing needles and other drug paraphernalia. 
© NICE 2023. Hepatitis A: scenario—managing hepatitis A infection. NICE Clinical Knowledge Summary. Available at:

All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See for further details.

The patient was ‘safety netted’ for worsening of any symptoms, and weekly telephone follow up was arranged while he was symptomatic. Repeat liver tests were booked at 4 weeks and, because of the ‘seroconversion window’ (the time after exposure during which an antibody response cannot be detected by routine testing methods), arrangements were made to recheck serology for hepatitis B at 6 months, hepatitis C at 3 months, and HIV at 3 months after his tattoo.11,12

The patient was made aware that his GP would seek specialist advice if LFTs became significantly worse (ALT levels greater than 2000 IU/l, bilirubin greater than 300 micromol/l, significantly abnormal prothrombin time), or if there were any other signs of deterioration of liver function.

Clinical Outcome

Follow-up calls showed that the patient made a fairly quick return to a symptom-free condition, and he went back to work after 2 weeks’ sick leave. 

ALT levels were normal after 4 weeks and liver monitoring was stopped, and other viral serology tests were normal when retested.

Case 2

A mother brings her 3-week-old baby to the GP. His delivery was uncomplicated, and he took to breastfeeding well, gaining weight normally for the first 2 weeks. He became mildly jaundiced at 1 week old, but the mother was reassured by her health visitor that this was most likely physiological, and that it should resolve by the time the baby was 2 weeks old. However, by the time of presentation, the jaundice has deepened rather than lightened, and the baby has become irritable and lost some weight. 

When asked, the mother said that she noticed that his stools have been pale for the last few days, which is confirmed using a stool colour chart, but that she is unsure about any change in urine colour. Apart from jaundice, there are no specific findings on clinical examination and no enlarged liver or spleen, although the baby seems abnormally irritable and looks unwell.


Although jaundice in neonates is common and normal, especially in breast-fed babies, both early jaundice (within the first week of life) and prolonged jaundice (jaundice persisting beyond the first 14 days) may be indicators of an underlying medical condition.5 In a child with prolonged jaundice, the clinician must always consider biliary atresia as a possible cause, and early diagnosis of this condition is crucial.13 If it is diagnosed promptly and the baby has surgical treatment early, the response to surgery and outlook are greatly improved;13 if surgery is delayed beyond 90 days after birth and the condition is untreated, it will typically progress to biliary cirrhosis with portal hypertension, end-stage liver disease, and death within the first 2 years of life.14 In this case, pale stool colour is another red flag for biliary cirrhosis, as would be persistent yellow or dark urine.15 A stool colour chart can be downloaded from


Because of his irritability and the fact that he appeared unwell, the baby was admitted to hospital for urgent investigations, which included measurement of conjugated and unconjugated bilirubin and abdominal ultrasound. 

The child’s conjugated bilirubin level was 29 micromol/l, ultrasound was consistent with biliary atresia and, after further investigation, he underwent an operative cholangiogram under general anaesthesia to establish the diagnosis. Biliary sclerosis was confirmed, and the cholangiogram was followed immediately by a Kasai procedure under the same anaesthetic to replace damaged bile ducts with a loop of the child’s intestine and restore bile drainage.13,16

For more information on the care of babies with prolonged jaundice, see Box 4.5

Box 4: Care of Babies with Prolonged Jaundice5

In babies with a gestational age of 37 weeks or more with jaundice lasting more than 14 days, and in babies with a gestational age of less than 37 weeks and jaundice lasting more than 21 days: 

  • look for pale chalky stools and/or dark urine that stains the nappy
  • measure the conjugated bilirubin
  • carry out a full blood count
  • carry out a blood group determination (mother and baby) and DAT (Coombs' test). Interpret the result taking account of the strength of reaction, and whether mother received prophylactic anti-D immunoglobulin during pregnancy
  • carry out a urine culture
  • ensure that routine metabolic screening (including screening for congenital hypothyroidism) has been performed.
Follow expert advice about care for babies with a conjugated bilirubin level greater than 25 micromol/litre because this may indicate serious liver disease.

DAT=direct antiglobulin test

© NICE 2023. Jaundice in newborn babies under 28 days. NICE Clinical Guideline 98. NICE, 2016. Available at:

All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication. See for further details.

Clinical Outcome

The child managed the surgery well and will be followed up long term in the hepatology clinic, as development of liver complications and cirrhosis at a later date remains a risk even when the Kasai procedure is performed early.17

Case 3

A GP processing the day’s pathology results spots a mildly raised bilirubin level of 28 micromol/l in the otherwise normal LFT panel of a 63-year-old man. Reviewing his notes, there had been two previous borderline or mildly elevated bilirubin readings with no other LFT abnormalities, and the tests had been filed as ‘satisfactory’ with no action taken. The patient has no history of liver disease, is a nondrinker, has no risk factors for viral hepatitis, and is taking a statin but no other medication.


The most likely cause of an isolated elevated bilirubin concentration (which may be visible or invisible to the naked eye) with otherwise normal LFT results is Gilbert’s syndrome.9,18 This is an inherited disorder in which reduced activity of the enzyme glucuronyl transferase causes impaired bilirubin conjugation.9 The condition affects 2–10% of the Caucasian population, and in most cases is inherited as an autosomal recessive condition (but may be dominant in some cases).18 As Gilbert’s syndrome is not associated with liver disease or ill health, and may actually be associated with a survival benefit, those diagnosed with it can be fully reassured.9,19


A full blood count was performed to exclude haemolytic anaemia, and LFTs repeated with measurement of conjugated and unconjugated bilirubin. 

Clinical Outcome

The full blood count was normal, and the hyperbilirubinaemia was confirmed to be unconjugated. Gilbert’s syndrome was diagnosed, the patient was informed and reassured, and he was able to continue living life as normal with no further follow up.

Case 4

A 72-year-old otherwise well woman presents with a 2-day history of upper abdominal pain, jaundice, vomiting, and fever. Before the presenting illness, she had been fit, well, and active for her age, and there are no red flags for malignant disease. She does, however, report a history of occasional grumbling ‘indigestion’ pain over the preceding 10 years.

Examination shows visible jaundice, marked right upper-quadrant tenderness, but no palpable liver or abdominal masses. She is pyrexial, with a temperature of 38.2°C, and looks dehydrated. The patient is admitted to hospital as an ‘acute abdomen’ with jaundice. 

Initial blood tests show a raised total white blood cell count (12.4 × 109/l), with an excess of neutrophils, elevated C-reactive protein (8.3 mg/dl), raised total bilirubin (79 micromol/l), raised ALP (893 IU/l), and raised ALT (178 IU/l). 


Jaundice with predominantly raised ALP and only moderately raised ALT suggests a cholestatic or post-hepatic picture, in which the biliary tree external to the liver is blocked.9 In adults, common causes of cholestatic jaundice comprise biliary obstruction by stones, strictures, and malignancy. Other causes include:9

  • primary biliary cholangitis
  • primary sclerosing cholangitis
  • hepatic congestion
  • drug-induced liver injury.


In this case, presentation was acute, and urgent admission was indicated. In less acute presentations, liver screening blood tests and ultrasound may be appropriate initial investigations in primary care, but urgent referral is indicated whenever there is any suspicion of hepatic or biliary malignancy.9

For this woman, urgent abdominal ultrasound demonstrated an atrophic gallbladder with stones, together with a large gallstone impacted in the common bile duct. The common and intrahepatic bile ducts were dilated. The hospital team proceeded to endoscopic retrograde cholangiopancreatography, and the stones were successfully removed. 

Clinical Outcome

The patient made an excellent postoperative recovery, and was soon back home.


There is a wide range of potential causes to consider in both infants and adults who present with jaundice. This article considers just a few of the potential diagnoses. 

For the jaundiced patient, careful and detailed history taking and examination should always be performed to elicit any red-flag symptoms and identify risk factors for liver disease, including alcohol misuse. Some cases of jaundice can be managed safely in primary care. However, emergency admission should be considered if the patient is systemically unwell in conjunction with jaundice, and any patient with marked derangement of liver blood tests, evidence of liver synthetic failure such as reduced albumin or prolonged prothrombin time, or clinical symptoms suspicious of malignancy or other serious underlying condition should be urgently referred.9 Nonurgent referral may be appropriate if there is diagnostic uncertainty.9

In neonates, a referral for urgent medical review should be made for babies with suspected or obvious jaundice in the first 24 hours of life to exclude pathological causes of jaundice.5 Babies with prolonged jaundice should be investigated in accordance with NICE guidance, and all babies with a conjugated bilirubin level greater than 25 micromol/l should be referred urgently to secondary care to assess for severe underlying liver disease.5

A useful summary of further investigation pathways following abnormal LFTs in adults is shown in Figure 1.9

Figure 1: British Society of Gastroenterology Response to Abnormal Liver Blood Tests Algorithm

This figure details the initial response to abnormal liver blood tests. Boxes in yellow indicate the initial evaluation of the clinical presentation. Patients with marked derangement of liver blood tests, synthetic failure and/or suspicious clinical symptoms/signs should be considered for urgent referral to secondary care (red box). For the remainder, a clinical history alongside evaluation of the pattern of liver blood test derangement will determine choice of pathway and is shown in the grey boxes. A grey box indicates all the tests that should be requested at that stage rather than a hierarchy within it. The presence of metabolic syndrome criteria should be sought to support a diagnosis of NAFLD. For children, the guideline should be consulted for modification of recommendation. Areas of diagnostic uncertainty are indicated in orange boxes and the decision for repeat testing or referral to secondary care will be influenced by the magnitude of enzyme elevation and clinical context. Green boxes indicate final/definitive outcomes for users of the pathway.

Abnormal USS may include extrahepatic biliary obstruction due to malignancy, which should result in urgent referral.

BMI=body mass index; ARLD=alcohol-related liver disease; ALT=alanine aminotransferase; AST=aspartate aminotransferase; INR=international normalised ratio; ALP=alkaline phosphatase; GGT=gamma-glutamyl transferase; FBC=full blood count; HbA1c=glycated haemoglobin; LDH=lactate dehydrogenase; NAFLD=nonalcoholic fatty liver disease; USS=ultrasound scan

Newsome P, Cramb R, Davison S et al. Guidelines on the management of abnormal liver blood tests. Gut 2018; 67 (1): 6–19. doi: 10.1136/gutjnl-2017-314924 Reproduced under the terms of the CC BY 4.0 licence.