Previous changes

November 2020 — reviewed. A literature search was conducted in November 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

August 2015 to February 2016 — new topic. A literature search was conducted in August 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 June 2025.

HTAs (Health Technology Assessments)

No new HTAs since 1 June 2025.

Economic appraisals

No new economic appraisals relevant to England since 1 June 2025.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 June 2025.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 June 2025.

New policies

No new national policies or guidelines since 1 June 2025.

New safety alerts

No new safety alerts since 1 June 2025.

Changes in product availability

No changes in product availability since 1 June 2025.

Haemolytic anaemias

• Haemolytic anaemias result from increased haemolysis of abnormal red blood cells due to conditions such as:
  • Homozygous sickle cell disease and thalassemia major which are inherited disorders that produce defects in haemoglobin structure. See the CKS topic on Sickle cell disease for further information.
  • Hereditary spherocytosis, which causes membrane abnormalities.
  • Glucose-6-phosphate dehydrogenase deficiency, which is due to enzyme abnormalities.
  • Vitamin B12 deficiency (pernicious anaemia), which can cause ineffective erythropoiesis of the bone marrow, leading to mildly elevated bilirubin levels — see the CKS topic on Anaemia - B12 and folate deficiency for further information.
  • Autoimmune disorders, including systemic lupus erythematosus, which can cause anaemia of chronic disease, but may also impair erythropoietin function.

 [Beckingham, 2001; Fargo, 2017; Pavlovic Markovic, 2022; Nelson, 2025]

Drugs

• Drug-induced liver injury (DILI) may be:
  • Direct, when liver injury is dose-dependent and predictable. Some drugs, for example, paracetamol, will cause liver injury in almost any person if taken at a high enough dose.
  • Idiosyncratic, when injury is not related to dose or duration, but occurs variably during or after administration. Examples include amoxicillin-clavulanate, cephalosporins, isoniazid and nitrofurantoin. Risk of an idiosyncratic DILI varies with a number of factors including age, gender, ethnicity, dose and comorbidity.
  • Indirect, when the drug affects the immune system, leading to a secondary type of liver injury. This may occur with some drugs used for immunotherapy, such as immune checkpoint inhibitors.
• Drugs can cause jaundice through:
  • Haemolysis of red blood cells (for example, methyldopa and sulfasalazine).
  • Hepatitis (for example, paracetamol overdose, diclofenac, nitrofurantoin, pyrazinamide, rifampicin, and isoniazid).
  • Cholestasis (for example, amoxicillin-clavulanate, cephalosporins, erythromycin, flucloxacillin, sulfonamides, terbinafine, oral contraceptives, hormone replacement therapy, chlorpromazine, and corticosteroids).
  • Mixed causes (for example, carbamazepine, lamotrigine, phenytoin, sulfonamides).
• Antibiotics and central nervous system and anti-inflammatory agents are the most commonly reported drugs causing DILI.
• Non-prescribed drugs, such as herbal medicines, or dietary supplements, such as green tea extract, turmeric and anabolic corticosteroids, have been documented as causing DILI and can lead to acute liver failure. Over-the-counter drugs (particularly paracetamol and paracetamol-containing products such as cold and flu remedies) and some recreational drugs, such as ecstasy and methamphetamine, may also cause liver damage.
• There is a wide variety in when DILI may occur, from within hours to days after exposure to months post-exposure.

[Beckingham, 2001; Ryder, 2001; BSG, 2022; BPAC NZ, 2023; Fontana, 2023]

Gilbert's syndrome

• At least 3% of the adult population has Gilbert’s syndrome.
• It is an inherited metabolic disorder that causes excess unconjugated bilirubin due to defective conjugating enzymes in the hepatocytes.
• Typically, it presents as an incidental finding on blood tests, with slightly raised serum bilirubin levels, while other routine liver function tests and reticulocyte count remain within normal limits.
• Plasma bilirubin concentrations can rise in people with Gilbert’s syndrome during intercurrent illness, periods of stress, when dehydrated or fasting, or during menstruation. Frank jaundice may occur.
• No treatment is required.
• See the CKS topic on Gilbert's syndrome for further information.

 [Beckingham, 2001; Fargo, 2017; Pavlovic Markovic, 2022; Nelson, 2025]

Crigler-Najjar syndrome

• Crigler-Najjar syndrome is a very rare inherited disorder causing defects in the hepatic bilirubin conjugating enzyme leading to unconjugated hyperbilirubinaemia.
  • Type 1 Crigler-Najjar syndrome presents in neonates with progressive jaundice in the first few days of life. If untreated, it leads to bilirubin encephalopathy (kernicterus) and death.
  • Type 2 Crigler-Najjar syndrome is less severe, and brain damage is rare.
• Bilirubin encephalopathy may occur in later life with intercurrent infection, ingestion of drugs that displace unconjugated bilirubin from albumin (sulphonamides, salicylates, or penicillin), or stress.

  [Pavlovic Markovic, 2022; Bhandari, 2024; Nelson, 2025]

Viral infection

• Viral hepatitis (hepatitis A, B, C, D, and E) can cause jaundice through intra-hepatic inflammation leading to disruption in the transport of conjugated bilirubin.
  • Hepatitis A is usually self-limiting and presents with acute jaundice — see the CKS topic on Hepatitis A for further information.
  • Hepatitis B and C infections may not cause jaundice in the initial phase of infection but can lead to progressive jaundice when chronic infection leads to cirrhosis — see the CKS topics on Hepatitis B and Hepatitis C for further information.
  • Hepatitis D only causes clinically significant disease when co-infection with hepatitis B is present.
  • Hepatitis E occurs worldwide, particularly in regions where sanitation is poor. It is spread predominantly by the faeco-oral route. It usually produces a mild disease but some groups such as pregnant women and the immunocompromised are at risk of more severe disease. For information on diagnosis and management, please see the Public Health England (PHE) document Hepatitis E: symptoms, transmission, treatment and prevention.
• Epstein-Barr virus infection occasionally causes transient hepatitis and jaundice — see the CKS topic on Glandular fever (infectious mononucleosis) for further information.
• HIV infection can cause jaundice through extra-hepatic obstruction due to AIDS cholangiopathy — see the CKS topic on HIV infection and AIDS for further information.

[Mehta, 2024; Nelson, 2025]

Alcohol

• Alcohol-related liver disease is the most common cause of liver-related ill health and death in the UK.
• In England, there were 27,085 admissions to hospital where the primary diagnosis was alcoholic liver disease in the financial year ending 2023.
• In England, the rate of premature deaths from alcoholic liver disease in 2022 was 11.6 per 100,000 population under 75 years of age (5776 deaths). The number of premature deaths from alcoholic liver disease increased by 61% in England over the twenty years up to 2022, and the rates by 36%.
• Jaundice can occur due to:
  
  • Alcoholic hepatitis. This typically presents with jaundice, malaise and liver decompensation in a person who has a history of chronic alcohol misuse. Typically, those with alcoholic hepatitis have been having more than 7 to 10 units of alcohol per day, and 70% go on to develop cirrhosis.
  • Disruption of bile uptake and secretion results in cholestasis.
  • Development of fatty liver (steatosis) and cirrhosis with jaundice from chronic alcohol misuse.
  • Decompensated chronic liver disease, when there is a deterioration in liver function in a person with cirrhosis (due to developing alcoholic hepatitis, infection or variceal haemorrhage, for example). This may present with symptoms such as jaundice, encephalopathy, ascites and gastrointestinal bleeds.

  [Fargo, 2017; Parker, 2023; BSG, 2024; OHID, 2024]

Metabolic dysfunction-associated steatotic liver disease (MASLD)

• Metabolic dysfunction-associated steatotic liver disease (MASLD) was formerly known as non-alcoholic fatty liver disease (NAFLD).
• It is a common cause of chronic liver disease, with rapidly escalating global prevalence.
• It refers to excessive fat accumulation (steatosis) in the hepatocytes in a person with cardiometabolic risk factors, such as obesity, hyperglycaemia or insulin resistance, hypertension and hyperlipidaemia.
• Steatosis can be associated with hepatocellular injury, inflammation, and may progress to advanced liver fibrosis and cirrhosis. In North America and Europe, it has become one of the leading causes of cirrhosis.
• MASLD represents the liver component of a multisystem disorder. The exact cause is complex, but insulin resistance, bile acid metabolism disorders, gut microbiota imbalances, and hyperuricaemia may all contribute. 
• It may be asymptomatic and picked up incidentally in early stages, but early symptoms may be mild and non-specific, such as minor fatigue and reduced appetite. There may be features of metabolic syndrome, such as obesity, dyslipidaemia and hypertension, and there is a strong association with type 2 diabetes.
• See the CKS topic Non-alcoholic fatty liver disease (NAFLD) for more information.

[BPAC NZ, 2023; Rinella, 2024; Gan, 2025]

Autoimmune liver disorders

• Primary biliary cholangitis (previously primary biliary cirrhosis) (PBC)
  • PBC is a rare progressive liver disorder typically presenting in middle-aged and older women. Prevalence in Europe is around 14.6 per 100,000.
  • It may be asymptomatic initially. In 65 to 85% of patients, symptoms include fatigue and itch. Jaundice develops as the disease progresses.
  • It is often associated with other autoimmune conditions.
  • 95% of people with PBC have high titres of anti-mitochondrial antibodies.
• Primary sclerosing cholangitis (PSC)
  • PSC is an immune-mediated, chronic, progressive inflammatory condition that affects the intra- and extra-hepatic bile ducts, leading to fibrosis and stricture formation.
  • PSC is more common in men, particularly young men. Prevalence in the UK is around 7.4 per 100,000.
  • Symptoms often include itch and jaundice, as well as fatigue and right upper quadrant pain.
  • Around 65% of people with PSC also have inflammatory bowel disease (particularly ulcerative colitis), and it is associated with increased risk of cholangiocarcinoma and colorectal cancer.
  • Serum perinuclear antinuclear cytoplasmic antibody is present in 33 to 88% of people with PSC but is not specific.
• Autoimmune hepatitis (AIH)
  • AIH is a chronic inflammatory liver disease that can lead to cirrhosis, liver failure, and death if untreated.
  • It is thought to be immune in origin as it is associated with other autoimmune conditions, specific human leucocyte antigen (HLA) alleles, non-organ-specific serum autoantibodies and hyperglobulinaemia. It occurs when genetically predisposed individuals encounter environmental risk factors (such as medication, infections, vaccinations, and smoking).
  • AIH is rare, with an annual incidence in the UK of 2 per 100,000 population and a prevalence of 19 - 34 per 100,000. It is around three times more common in females.
  • AIH may present as an ‘acute hepatitis’ with jaundice preceded by anorexia, nausea, and flu-like symptoms, or more insidiously with non-specific symptoms such as fatigue, malaise, nausea, anorexia, weight loss, amenorrhoea, and joint pains. Acute liver failure may also be the presentation in a few cases.
  • 12 to 39% of people with AIH are asymptomatic at diagnosis, which may occur following incidental findings of abnormal liver function tests.
  • Bloods tests may reveal markedly raised serum alanine and aspartate transaminase (ALT and AST) with normal or mildly raised alkaline phosphatase (marked elevation suggests PBC or PSC), immunoglobulins, and autoantibodies (such as smooth muscle antibodies, antinuclear antibody) in the absence of viral hepatitis.
  • AIH variant syndrome refers to co-existence of features of AIH with either PBC or PSC.

  [Fargo, 2017; Chapman, 2019; Gan, 2025; Gleeson, 2025]

Hereditary metabolic causes of intra-hepatic jaundice

• Alpha-1-antitrypsin deficiency
  • This is a genetic condition affecting the lungs and the liver, and has a number of genetic variations.
  • It may cause cirrhosis as well as young-onset emphysema.
  • The most prevalent variation in people of European descent occurs at a rate of around 1 in 2000 to 1 in 4000.
• Dubin-Johnson and Rotor’s syndromes
  • These are rare hereditary metabolic conditions that disrupt the transport of conjugated bilirubin from the liver cells.
• Haemochromatosis
  • Is the most common inherited liver disease in the UK, affecting 1 in 200 of the population.
  • It leads to iron overload, and people usually present with skin pigmentation (80%), cirrhosis (70%), or diabetes (55%) due to excessive iron deposits in the liver and pancreas.
  • Jaundice occurs in decompensated disease in those with cirrhosis.
• Wilson’s disease 
  • Is a rare autosomal recessive disorder that causes liver disease through excess deposition of copper in the hepatocytes. It also affects the basal ganglia and eyes.

[Ryder, 2001; Gan, 2025; Nelson, 2025]

Malignancy of the liver and biliary system

Tumours may cause jaundice through intra-hepatic damage, or cholestasis, which may be intra- or extra-hepatic.

• Hepatocellular carcinoma
  • Hepatocellular carcinoma is the most common primary liver tumour worldwide.
  • Risk is increased in men, with advancing age, and in people with cirrhosis – especially due to excessive alcohol use, and hepatitis B and C infection.
  • Obesity, diabetes, and family history are also associated with increased risk.
  • It is often diagnosed late, and survival rates are poor, with only 3 in 10 patients surviving for a year or more after diagnosis.
  • In 2018, incidence in the UK was 6.2 and 14.3 per 100,000 women and men, respectively.
• Cholangiocarcinoma
  • Cholangiocarcinoma is the second most common primary liver tumour worldwide after hepatocellular carcinoma.
  • Primary sclerosing cholangitis is the most commonly known predisposing factor for cholangiocarcinoma in the Western world but most cases are sporadic.
  • Cholangiocarcinoma may arise in various sites which may be intra-hepatic or parts of the biliary system external to the liver. Those which are extra-hepatic usually present with symptoms of obstructive jaundice, whereas those arising within the liver usually present with non-specific features such as weight loss, anorexia, abdominal discomfort, nausea and malaise.
  • There is a high mortality rate due to late presentation.
• Metastases in the liver
  • The liver is a common site of cancer metastasis, particularly from colorectal cancers, but also from other cancers, including breast and pancreatic cancers.
• Gallbladder cancer
  • Gallbladder cancer is rare but is the most common biliary tract malignancy.
  • Gallbladder cancer typically presents with jaundice, hepatomegaly, and a mass in the right upper quadrant (Courvoisier's sign).

[Rushbrook, 2023; Gan, 2025; Suddle, 2024; Nelson, 2025]

Gallstones

• A gallstone (cholelithiasis) is a solid deposit that forms within the gallbladder or bile duct.
• Prevalence varies between 5–25%, with a higher prevalence in women, those from Western countries, and with increasing age.
• Most people with gallstone disease are asymptomatic but gallstones can cause obstruction of the flow of bile within the biliary duct system and lead to complications such as:
  • Biliary colic — this describes pain in the epigastrium or right upper quadrant that is usually persistent, lasting from 15 minutes up to several hours. Pain lasting more than 24 hours or accompanied by fever suggests acute cholecystitis.
  • Nausea and vomiting.
  • Jaundice — this can occur when a gallstone causes obstruction within the biliary system.
  • Cholecystitis is inflammation or infection of the gallbladder with pain similar to biliary colic along with fever and tenderness in the right upper quadrant.
  • Cholangitis (inflammation or infection of the common bile duct) is classically diagnosed by the symptoms of Charcot’s triad fever, pain, and jaundice. It most often occurs because of an impacted gallstone and can be life-threatening.
  • Gallstone pancreatitis can present with sudden onset of pain in the epigastrium or left upper quadrant and may radiate into the back. Acute pancreatitis has a 3–20% mortality after a first acute attack.
• See the CKS topic on Gallstones for further information.

 [Gurusamy, 2014; Fargo, 2017]

Surgical strictures

• Biliary strictures and infection should be considered in people with post-operative jaundice.
• Biliary strictures can occur following operations such as cholecystectomy, liver transplantation. and the Whipple and Billroth procedures.
• Complications associated with biliary strictures include chronic cholestasis, recurrent cholangitis, and secondary biliary cirrhosis.

 [Fargo, 2017; Pavlovic Markovic, 2022]

Extra-hepatic malignancy

• Pancreatic cancer
  • Pancreatic cancer can present with jaundice due to obstruction of the lower common bile duct.
  • In 2017 - 2019, pancreatic cancer was the tenth most common cancer in the UK and the fifth most common cause of cancer death.
  • Incidence increases with age, with nearly half of pancreatic cancers in the UK being diagnosed in people aged 75 or more.
  • Only 7 to 8% of people diagnosed with pancreatic cancer in England and Wales survive for 5 years or more.
  • It is estimated that 60% of pancreatic cancers cause obstructive jaundice.
  • A systematic review of eight studies with a collective total of 3,438,363 patients found that the only high-risk feature of pancreatic cancer in primary care was jaundice, with a positive predictive value of 4.1% in people aged over 40 years. (The guideline on recognition and referral of suspected cancer from the National Institute for Health and Care Excellence (NICE) recommends that people over the age of 40 presenting with jaundice should be referred to a suspected cancer pathway.)
  • For more information, see the CKS topic on Gastrointestinal tract (upper) cancers - recognition and referral.
• Other extra-hepatic malignancies
  • Jaundice associated with lymphoma or metastatic cancers, such as breast or bowel cancer, can be due to intra-hepatic cholestasis from infiltration of the liver or obstruction of the biliary ductal system.

[Schmidt-Hansen, 2016; Fargo, 2017; CRUK, 2020; Nelson, 2025; NICE, 2025]

Pancreatitis

• Pancreatitis typically presents with sudden onset of severe pain in the epigastrium or left upper quadrant radiating into the back.
• The most common causes of pancreatitis are alcohol misuse and gallstones.
• Pancreatitis can lead to jaundice from pancreatic oedema or from fibrosis and strictures.
• For further information, see the CKS topic on Pancreatitis - acute.

[Fargo, 2017; Pavlovic Markovic, 2022]

Parasitic infection

• Severe malaria infection may cause jaundice, through haemolysis of infected red blood cells, by disseminated intravascular coagulation or through malarial hepatitis/hepatopathy.
  • The incidence of jaundice in malaria has been reported as being between 2.6 and 62%. It is usually a marker of severe disease.
  • Recent studies suggest that the high unconjugated bilirubin levels causing jaundice may be a protective mechanism, preventing more serious consequences of malaria.
• In addition to malaria, infection with other parasites can cause jaundice, and should be considered in the differential diagnosis of people with jaundice who have travelled to endemic areas.
  • Fasciola is a liver fluke common in sheep and cattle in many areas of the world.
    • Human infection occurs when Fasciola larvae are ingested in contaminated water or on water plants such as raw watercress.
    • After ingestion, the parasites migrate from the intestines to the liver and then settle in the bile ducts.
    • In the biliary system, the parasites can cause inflammation and blockage.
  • Clonorchis is a liver fluke (worm) found across parts of Asia.
    • Infection occurs when the larvae are ingested in raw or undercooked fish, crabs, or crayfish.
    • The juvenile parasites migrate from the duodenum to the biliary tract where they mature to adult flukes and can cause inflammation and intermittent obstruction.
    • Jaundice may be due to a number of mechanisms, including recurrent pyogenic cholecystitis, chronic biliary inflammation, biliary strictures, and possibly increased risk of cholangiocarcinoma.
  • Opisthorchiasis spp are also hepatobiliary flukes mainly found in Southeast Asia and Eastern Europe.
    • Infection is through the ingestion of undercooked freshwater fish containing Opisthorchiasis larvae.
    • These then migrate into the bile ducts and mature into adult worms.
    • Jaundice may be due to a number of mechanisms, including recurrent pyogenic cholecystitis, chronic biliary inflammation, biliary strictures, and possibly increased risk of cholangiocarcinoma.
  • Schistosomiasis is caused by flukes of the genus Schistosoma.
    • Humans are infected through freshwater exposure.
    • Presentation is with acute onset of fever, myalgia and lethargy, with lymphadenopathy, hepatomegaly being common.
    • Jaundice may occur where advanced fibrosis of the liver and portal hypertension develop.
  • Echinococcosis is caused by Echinococcus spp.
    • Hepatic involvement is common, and symptoms occur when hepatic cysts become large enough to cause symptoms.
    • Cholestatic jaundice occasionally results from bile duct compression from a large cyst.
  • Entamoeba histolytica may cause liver abscesses, which typically present with right upper quadrant pain, fever, as well as jaundice in some cases, through multiple mechanisms.
    
    • Infective cysts are transmitted through contaminated food and water.
  • Ascariasis caused by Ascaris lumbricoides is a common helminth infection worldwide.
    • Infection is through ingestion of eggs in the soil, contaminating food and water.
    • Jaundice can occur, usually due to biliary obstruction, also from pancreatitis and liver abscess formation.

[Chan, 2012; CDC, 2025; Figueiredo, 2025; Gan, 2025]

What should I ask a person with jaundice?

• Take a history including:
  • Duration, speed of onset and previous episodes of jaundice. 
  • Colour of urine and stools, including any evidence of tarry/bloody stools suggesting melaena. (Dark urine and pale stools are a feature of obstructive jaundice, although they may also occur transiently in acute hepatic illness.)
  • Pain, including the site, severity, and radiation. (Viral hepatitis is usually painless, whereas upper abdominal pain may suggest gallstones, or cancer of the pancreas or pancreatitis, particularly if the pain radiates to the back.)
  • Itching (pruritus). Pruritus may suggest biliary obstruction or primary biliary cholangitis if long-lasting.
  • Systemic features such as anorexia, weight loss, fever, rigors, arthralgia, myalgia, rash, fatigue, nausea, and vomiting. Consider features which may suggest infection such as viral hepatitis or parasitic infection. Be alert for the presence of any red flags that suggest a serious underlying condition such as malignancy. 
  • Alcohol intake in units — see the CKS topic on Alcohol - problem drinking for further information.
  • Travel abroad to areas endemic for viral hepatitis and parasites (such as Clonorchis) that can cause jaundice.
  • Other risk factors for viral hepatitis — intravenous drug use, tattoos, body piercings, blood transfusion, multiple sexual partners, sex between men or with sex workers.
  • Past medical history of biliary surgery, gallstones, hepatitis, autoimmune liver disease, thyroid disease, or non-alcoholic fatty liver disease.
  • Co-morbidities such as inflammatory bowel disease (which can increase the risk of primary sclerosing cholangitis), obesity, diabetes, and metabolic syndrome (associated with an increased risk of metabolic dysfunction-associated steatotic liver disease).
  • Drugs — prescribed and over-the-counter, including herbal medications and dietary supplements. Always ask about potential paracetamol overdose.
  • Occupation — exposure to viral hepatitis, HIV, or hepatotoxic chemicals.
  • Family history of inherited anaemias or haemoglobinopathies.
  • Possibility of pregnancy. Jaundice associated with pregnancy should prompt urgent same-day obstetric or secondary care assessment. See the CKS topic on Itch in pregnancy for further information.

How should I examine a person with jaundice?

• Carry out an examination looking for:
  • Signs of sepsis — fever, tachycardia, and hypotension.
  • Signs of chronic liver disease:
    • Palmar erythema and spider naevi — up to five spider naevi can be normal in women, but in men, any number of spider naevi suggests chronic liver disease.
    • Fingernail clubbing — associated with liver cirrhosis.
    • Leukonychia (white nails) — due to hypoalbuminaemia.
    • Dupuytren’s contractures (contracture of the palmar fascia) — associated with chronic liver disease due to alcohol misuse, but can also be familial or due to other causes such as diabetes mellitus. See the CKS topic on Dupuytren's disease for further information.
    • Gynaecomastia (breast enlargement in men), with loss of body hair and testicular atrophy — due to reduced oestrogen breakdown.
    • Visible veins on the skin of the abdomen, such as around the umbilicus (caput medusae).
  • Signs of liver failure:
    • Altered neuromuscular function such as ataxia, nystagmus, or asterixis (coarse flapping tremor) can occur with hepatic encephalopathy.
    • Altered mental state such as drowsiness, confusion, disorientation, or coma.
    • Bruising, petechiae, or purpura.
  • Lymphadenopathy:
    • Enlargement of the left supraclavicular lymph nodes (Troisier’s sign) can be caused by malignancy, including metastatic pancreatic and gastric cancer.
    • More widespread lymphadenopathy with hepatosplenomegaly can indicate lymphoma.
  • Masses such as:
    • Hepatomegaly can be due to many causes, including chronic parenchymal liver disease such as alcoholic liver disease or viral hepatitis; malignancy such as primary hepatocellular cancer or secondary metastatic cancer; or haematological disease such as lymphoma or myelofibrosis.
    • Splenomegaly can be due to haematological disorders such as lymphoma or haemolytic anaemia; portal hypertension; infections such as glandular fever; or rheumatological conditions such as systemic lupus erythematosus.
    • Palpable gallbladder (Courvoisier’s sign) — a palpable gallbladder in a jaundiced person is likely to be due to extra-hepatic obstruction, such as from pancreatic cancer.
  • Abdominal tenderness:
    • Localized tenderness in the right upper quadrant below the costal margin on deep inspiration (Murphy’s sign) may indicate acute cholecystitis.
    • Widespread abdominal tenderness may indicate pancreatitis or peritonitis.
  • Ascites — indicates underlying causes such as intra-abdominal malignancy, chronic liver disease, or severe heart failure.

What investigations should I consider in a person with jaundice?

• If the person is well and does not need immediate admission, arrange blood and urine tests. Note — while the results of some of these tests may influence the referral pathway for a person with jaundice, do not delay referral while waiting for test results if the person is unwell.
• Carry out the following tests:
  • A full blood count — to identify haemolysis or infection, and to look for thrombocytopaenia, which may be a feature of chronic liver disease, and macrocytosis, which may suggest excessive alcohol intake.
  • Urea and electrolytes — to identify associated renal impairment.
  • Liver function tests (LFTs) — see the section on liver function tests for further information on interpretation of LFTs.
  • Initial LFT investigations should include bilirubin, albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and Gamma glutamyltransferase(GGT). 
    • Request a split bilirubin (both conjugated and unconjugated forms). In adults, the majority of measurable bilirubin is normally conjugated. Where there is unconjugated hyperbilirubinaemia, likely diagnoses are Gilbert's syndrome or haemolysis, or other pre-hepatic causes. Conjugated hyperbilirubinaemia can occur with hepatocellular injury or cholestasis.
  • Clotting screen — Prothrombin time and INR, which reflect liver function. Abnormal clotting can occur in both biliary obstruction and parenchymal liver disease.
  • Amylase if pancreatitis is suspected.
  • Hepatitis A, B, and C, if risk factors are present.
  • Urine dipstick — if positive for bilirubin this indicates increased levels of conjugated bilirubin in the serum.
• Depending on the results of the initial tests, arrange additional investigations as appropriate:
  • If LFTs show an obstructive picture — see the section on Who should I refer?.
  • If LFTs show a non-obstructive picture — carry out a full liver screen, if not already arranged, to include in addition to the liver tests above, aspartate aminotransferase (AST) level, and any of the above not previously tested. Consider the following additional tests:
    • Viral hepatitis screen — hepatitis A, B, and C.
    • Immunoglobulins — serum globulins increase in chronic hepatitis and cirrhosis. High levels of IgM are characteristic of primary biliary cirrhosis, and high levels of IgG indicate chronic active hepatitis.
    • Auto-antibody profile — to detect autoimmune liver disease.
    • Ferritin (and transferrin saturation if ferritin is raised) — to screen for hereditary haemochromatosis.
    • Alpha-1-antitrypsin and caeruloplasmin, with or without urinary copper — to detect the hereditary metabolic liver diseases alpha-1-antitrypsin deficiency and Wilson's disease, particularly where there is a positive family history. (Check caeruloplasmin in people under 40 only.)
    • HBA1c — Pre-diabetes and diabetes may contribute to metabolic dysfunction-associated steatotic liver disease (MASLD).
    • Lipid profile. (Abnormal lipids may contribute to steatotic liver diseases.)
  • Abdominal ultrasound scan.
    • Ultrasound scan can identify gallbladder stones, dilated bile ducts (indicating extra-hepatic obstruction), steatotic liver, liver cysts and tumours, and pancreatic masses. Visualization can be impaired by overlying bowel gas and body habitus.

Interpretation of liver function tests

The pattern of abnormality on liver function tests (LFTs) varies depending on the underlying disease process.

• Isolated raised bilirubin
  • This is most often due to Gilbert's syndrome.
    • Repeat LFTs, with split bilirubin and full blood count when clinically appropriate to ensure there is no evidence of anaemia or haemolysis.
• Cholestatic picture
  • Raised alkaline phosphatase (ALP) is the predominant feature, along with a raised gamma-glutamyl transferase (GGT). Common causes include primary biliary cholangitis, primary sclerosing cholangitis, biliary obstruction (stones, strictures, tumours), liver congestion, and drug-induced liver injury.
  • Bony disease such as Paget's disease as well as Vitamin D deficiency can also cause raised ALP and complicate interpretation of LFTs.
    • Repeat the LFTs, the urgency depending on clinical judgement, and add GGT to help confirm a liver cause if not already included.
• Hepatitic picture
  • Predominantly raised alanine transaminase (ALT) and/or aspartate transaminase (AST).
  • ALP may also be raised, although less so in comparison.
  • Caused by hepatocellular liver injury secondary to viral hepatitis, metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease, autoimmune hepatitis, or drug-induced liver injury.
  • Acute viral hepatitis can cause ALT to rise to over one thousand units per litre (U/L).
  • Acute liver injury from drugs (such as paracetamol overdose) or ischaemia can produce ALT levels greater than 10,000 U/L.
  • Acute alcoholic hepatitis can cause AST and ALT to rise to several hundred U/L.
  • Hepatocyte damage caused by alcohol, drugs, cirrhosis and malignancy usually results in an AST to ALT ratio of 2 or more, whereas chronic infection causes ALT to rise more than AST.
  • AST and ALT are not usually raised in obstructive jaundice unless complicated by cholangitis.

• Mixed picture
  • Occasionally LFTs may indicate both cholestasis and hepatocyte damage, and this is usually due to cholangitis associated with stones in the common bile duct.
• Albumin
  • Low serum albumin may suggest chronic liver disease, but also occurs in other clinical situations, such as sepsis, systemic inflammatory disorders, nephrotic syndrome, malabsorption, cachexia, and gastrointestinal protein loss.
• Clotting
  • Increased prothrombin time or INR are suggestive of significant liver injury which may be acute or chronic.
• Apparent jaundice with normal bilirubin level (pseudojaundice).
  • Consider other causes for skin discolouration, such as carotenaemia, tanning products, Addison's disease, anorexia nervosa.

Basis for recommendation

These recommendations are based on British Society of Gastroenterology Guidelines on the management of abnormal liver blood tests [Newsome, 2018], information from the Best Practice Advocacy Centre New Zealand (BPAC NZ) on Liver function tests in primary care [BPAC NZ, 2023], and expert opinion in the review articles ABC of diseases of the liver, pancreas and biliary system. Investigation of liver and biliary disease [Beckingham, 2001], Evaluation of jaundice in adults [Nelson, 2025], Jaundice as a diagnostic and therapeutic problem: A general practitioner's approach [Pavlovic Markovic, 2022], and Evaluation of jaundice in adults [Fargo, 2017].

Who should I admit?

Arrange emergency or urgent referral for same-day secondary care assessment and probable admission (route of referral depending on clinical judgement and local referral pathways) if a person with jaundice:

• Is exhibiting red flag signs and symptoms needing immediate assessment, including: 
  • Signs associated with hepatic encephalopathy such as:
    • Confusion or alteration in mental state.
    • Altered neuromuscular function such as poor co-ordination, ataxia, asterixis, and nystagmus.
  • Signs associated with severe hepatic dysfunction such as:
    • Bruising, purpura, or petechiae.
  • Signs of gastrointestinal blood loss such as:
    • Haematemesis or melaena (black or tarry stools).
  • Signs associated with sepsis such as:
    • Fever, hypotension, and tachycardia.
    • Cyanosis, or a mottled, ashen appearance.
    • Acute alteration of mental state.
    • See the CKS topic Sepsis for more information.
  • Signs associated with ascending cholangitis:
    • Fever and right upper quadrant pain (associated with jaundice, known as 'Charcot's triad').
    • See the CKS topic Gallstones for more information.
  • Signs of dehydration such as:
    • Reduced urine output.
    • Dry mucous membranes.
  • Marked abdominal tenderness or pain.
    • See the CKS topics Cholecystitis - acute and Pancreatitis - acute for more information.
  • Vomiting.
  • Appears to be systemically unwell.
• Has a bilirubin level greater than 100 micromol/L.
• Has an abnormal clotting profile or shows signs of coagulopathy.
• Is suspected of having taken a paracetamol overdose.
• Is frail or has significant co-morbidities.
• Is pregnant.

Who should I refer?

• Be alert for the presence of red flag symptoms and signs that require admission.
• Jaundice is not a common presentation in primary care but is usually indicative of serious illness that requires urgent investigation and treatment. All people with unexplained jaundice should therefore be referred immediately.
• Where locally available and depending on local referral pathways,  a rapid access jaundice assessment clinic or an ambulatory emergency care unit may be the point of referral for people with painless jaundice to receive any required investigations, and appropriate onward referral. Otherwise:
  • Refer people aged 40 years and over, using a suspected cancer pathway (for an appointment within 2 weeks) to exclude pancreatic cancer.
  • Refer people with a cholestatic or obstructive picture on liver function tests (LFTs) to an upper gastrointestinal surgeon, gastroenterologist, or liver clinic (depending on the suspected diagnosis), the urgency depending on clinical judgement.
  • Refer people with a hepatitic picture on LFTs urgently to a liver clinic or gastroenterologist.
  • Refer people with suspected alcohol-related liver disease to a specialist experienced in the management of alcohol-related liver disease, the urgency depending on clinical judgement.
  • Refer people with suspected inherited liver disease, such as haemochromatosis or Wilson's disease, to a gastroenterologist, the urgency depending on clinical judgement.

Who should I manage in primary care?

• Most people presenting with jaundice should be admitted or referred to secondary care.
  • Although jaundice is not a particularly common presentation in primary care, it is usually indicative of a serious underlying cause (such as malignancy) and prompt admission or referral, where appropriate, is essential.
• People who are well and have been diagnosed with Gilbert's syndrome or hepatitis A can be managed in primary care.
  • Gilbert's syndrome
    • For information on the management of people with Gilbert's syndrome in primary care, see the CKS topic on Gilbert's syndrome.
  • Hepatitis A
    • Hepatitis A must be serologically confirmed in a well person for management in primary care — if the person is acutely unwell with vomiting dehydration or signs of hepatic decompensation they should be admitted.
    • For information on the management of hepatitis A infection in primary care, see the CKS topic on Hepatitis A.