Jaundice and pruritus

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Jaundice becomes visible when bilirubin accumulates, but the route to diagnosis is pattern based. Unconjugated bilirubin rises with increased production, impaired uptake or conjugation, as in haemolysis or Gilbert syndrome, and is not excreted in urine. Conjugated bilirubin is water soluble and darkens urine when hepatocytes cannot excrete it normally or bile flow is blocked. Compare ALT and AST with alkaline phosphatase, using GGT or isoenzymes when the ALP source is uncertain. A cholestatic pattern suggests duct obstruction, drug injury, sepsis or autoimmune cholangiopathy; a hepatocellular pattern suggests viral, drug, ischaemic, autoimmune or metabolic injury. Mixed patterns require equal breadth.

History gives the urgency. Fever and pain suggest infected obstruction; painless progression and weight loss raise pancreatic, ampullary or cholangiocarcinoma; very high aminotransferases after hypotension, overdose or viral prodrome raises acute hepatocellular injury. Ask about prescribed and non-prescribed medicines, paracetamol timing, alcohol, travel, tattoos, injections, sexual and occupational exposure, pregnancy, surgery and family disease. Examine mental state, perfusion, scratching, xanthelasma, bruising, nodes, liver and spleen, ascites and a palpable gallbladder. Asterixis, hypoglycaemia and new coagulopathy indicate failing synthesis and detoxification rather than merely abnormal enzymes.

Ultrasound determines duct dilatation, gallstones and gross liver architecture. Dilated ducts direct urgent obstruction imaging and treatment; non-dilated ducts do not exclude early obstruction, primary sclerosing cholangitis or intrahepatic cholestasis. NICE recommends MRCP when ultrasound does not show a common-duct stone but the duct is dilated or liver tests are abnormal, with EUS when MRCP is non-diagnostic. ERCP carries pancreatitis, bleeding, infection and perforation risks and is used for drainage or therapy rather than as routine first diagnostic imaging. Pruritus care includes cool skin measures, emollient, sleep and excoriation management, but sustained relief depends on treating obstruction or cholangiopathy and using a monitored cholestatic-itch sequence.

Key points

Confirm jaundice in sclera and daylight, then determine whether bilirubin is predominantly conjugated or unconjugated and whether the biochemical pattern is cholestatic or hepatocellular.
Dark urine indicates water-soluble conjugated bilirubin; pale stool and generalised itch support impaired bile flow, but neither identifies whether obstruction is intrahepatic or extrahepatic.
Fever, right upper-quadrant pain and jaundice is the classic cholangitis triad, yet older or immunosuppressed patients may present mainly with hypotension, delirium or kidney injury.
Assess liver function separately from liver injury: INR, glucose, albumin, mental state and renal function determine severity, while ALT and ALP mainly describe pattern.
Medication and supplement timing is essential. Antibiotics, antiepileptics, anabolic agents, herbal products and many other drugs can cause hepatocellular, cholestatic or mixed injury.
Abdominal ultrasound is first-line for gallstones and bile-duct dilatation; MRCP or endoscopic ultrasound follows when common-duct stones remain suspected, while ERCP is primarily therapeutic.
Painless progressive jaundice, weight loss, new diabetes, palpable gallbladder or pancreatic or biliary imaging abnormality requires the current urgent cancer pathway.
Unconjugated bilirubin with normal other liver tests suggests haemolysis or Gilbert syndrome; check anaemia and haemolysis before arranging biliary procedures.
Cholestatic pruritus is not histamine driven. Cholestyramine is a common first pharmacological step, with specialist escalation when ineffective and careful spacing from other medicines.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Prehepatic bilirubin excess

Haemolysis and ineffective erythropoiesis increase unconjugated bilirubin production beyond hepatic uptake capacity without causing dark urine from bilirubin.

Hepatocellular dysfunction

Viral, autoimmune, metabolic, alcohol-related or drug-induced injury impairs bilirubin uptake, conjugation and excretion in varying proportions.

Intrahepatic or extrahepatic cholestasis

Gallstones, malignancy, biliary stricture, PBC, PSC and medicine-related cholestasis reduce bile flow and commonly cause dark urine, pale stool and itch.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Bilirubin production and handling
Haem breakdown generates unconjugated bilirubin, which hepatocytes take up, conjugate and normally secrete into bile through canalicular transport.
2
Systemic pigment accumulation
Excess production, hepatocyte failure or blocked excretion raises circulating bilirubin, producing scleral and skin discolouration once tissue deposition occurs.
3
Cholestatic pruritogen retention
Impaired bile flow allows bile-related mediators to accumulate and activate cutaneous-neural itch pathways, often without rash before scratching.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Acute ascending cholangitisRed flag

Jaundice with fever, right upper-quadrant pain, rigors, hypotension or confusion indicates infected biliary obstruction. Sepsis may progress rapidly and requires antibiotics plus prompt source control through biliary drainage.

Acute liver failureRed flag

Acute jaundice with new coagulopathy and encephalopathy in a person without established cirrhosis signals liver failure. Hypoglycaemia, acidosis, kidney injury and cerebral oedema risk require immediate liver-centre discussion.

Malignant obstruction

Painless progressive conjugated jaundice, pale stool, dark urine, pruritus, weight loss and a distended non-tender gallbladder supports pancreatic head, ampullary or biliary malignancy and urgent cross-sectional cancer assessment.

Gallstone obstruction

Episodic biliary pain, cholestatic liver tests and gallstones or duct dilatation support choledocholithiasis. Fever adds cholangitis; concurrent lipase elevation and pain can indicate gallstone pancreatitis.

Haemolytic unconjugated jaundice

Anaemia, reticulocytosis, raised LDH, low haptoglobin and predominantly unconjugated bilirubin support haemolysis. Dark urine from haemoglobin may occur, but bilirubinuria itself requires conjugated bilirubin.

Chronic autoimmune cholestasis

Persistent cholestatic tests and itch with antimitochondrial antibodies supports primary biliary cholangitis, while multifocal duct stricturing, IBD and cholangitis episodes raise primary sclerosing cholangitis. Both require specialist surveillance and treatment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Fractionated bilirubin and liver blood testsFirst step
Why
Separate conjugated from unconjugated hyperbilirubinaemia and classify hepatocellular, cholestatic or mixed injury.
Interpretation and limitations
Interpret magnitude relative to laboratory upper limits and trend. ALT and ALP describe injury pattern; albumin, INR, glucose and clinical state assess function and urgency.
02
INR, glucose, renal profile and blood gas
Why
Identify impaired synthesis, hypoglycaemia, kidney injury and metabolic severity in acute hepatic illness or sepsis.
Interpretation and limitations
New INR prolongation with encephalopathy is an acute liver-failure emergency. Lactate and acidosis can reflect shock or failing clearance and should trigger early critical-care and liver-centre discussion.
03
Full blood count and haemolysis screen
Why
Detect anaemia, infection, thrombocytopenia and haemolysis as an unconjugated bilirubin mechanism.
Interpretation and limitations
Reticulocytosis, raised LDH, reduced haptoglobin and blood-film findings support haemolysis; transfusion, liver disease and inflammation can complicate individual markers.
04
Abdominal ultrasound
Why
Identify gallstones, bile-duct dilatation, gallbladder inflammation, liver lesions, portal features and ascites as the first structural test.
Interpretation and limitations
Dilated ducts support extrahepatic obstruction; non-dilatation does not exclude early obstruction or intrahepatic cholangiopathy. Urgent sepsis care must proceed while imaging is obtained.
05
MRCP or endoscopic ultrasound
Why
Define duct stones, strictures and pancreaticobiliary anatomy when ultrasound and liver tests leave obstruction unresolved.
Interpretation and limitations
NICE uses MRCP after negative ultrasound when duct dilatation or abnormal liver tests sustain stone concern, with EUS if uncertainty remains. Findings direct therapeutic ERCP or cancer biopsy strategy.
06
Contrast CT pancreas and hepatobiliary tract
Why
Assess pancreatic, ampullary, biliary or hepatic malignancy, complications and resectability when obstruction or weight loss raises cancer concern.
Interpretation and limitations
Use the protocol selected with radiology before decompression when clinically safe because stents can affect interpretation. Cholangitis instability may require drainage before complete staging.
07
Viral, autoimmune and metabolic liver screen
Why
Identify treatable intrahepatic causes when imaging does not fully explain jaundice or the biochemical pattern is hepatocellular.
Interpretation and limitations
Select hepatitis serology, immunoglobulins, autoantibodies and metabolic tests from age, exposure and pattern. A positive autoantibody alone is not a diagnosis and requires hepatology interpretation.
08
Blood cultures
Why
Identify bloodstream infection in suspected cholangitis before antimicrobial treatment when this does not delay therapy.
Interpretation and limitations
Culture results guide narrowing but negative cultures do not exclude infected obstruction. Source control remains essential when sepsis persists.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Haemolysis or conjugation disorder

Anaemia, reticulocytosis, low haptoglobin or an isolated unconjugated rise suggests prehepatic disease rather than obstruction within the bilirubin pathway.

Acute hepatitis or liver failure

Marked hepatocellular enzymes, exposure history, coagulopathy, hypoglycaemia or encephalopathy directs urgent hepatic rather than solely biliary assessment.

Mechanical biliary obstruction

Duct dilatation, cholestatic tests, pain or a pancreaticobiliary lesion supports obstruction; fever or shock indicates superimposed cholangitis.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01CholangitisResuscitate and drain the sourceFirst stepJaundice accompanies fever, pain, rigors, hypotension or confusion.

1Begin sepsis ABCDE care, obtain cultures and urgent bloods, give locally recommended intravenous antimicrobials and correct fluid, glucose and electrolyte disturbance.
2Call gastroenterology, hepatobiliary surgery, anaesthesia and critical care early and obtain urgent ultrasound or cross-sectional imaging without delaying source-control planning.
3Arrange therapeutic biliary decompression, usually ERCP, on the urgency determined by sepsis and anatomy; use radiological or surgical drainage when endoscopy is unavailable or unsuccessful.
4DefinitiveAfter stabilisation, define stone, stricture or malignancy cause and arrange definitive clearance, surgery or cancer management.

02Acute liver failureRefer before decompensation completesAcute liver injury has coagulopathy, encephalopathy, hypoglycaemia or rapidly worsening organ function.

1Take an immediate paracetamol and toxin history, send urgent aetiology tests and begin cause-specific emergency treatment when indicated without waiting for all results.
2Discuss with a specialist liver or transplant centre immediately, manage glucose, airway, renal and cerebral risks in critical care and avoid sedatives that obscure encephalopathy where possible.
3Trend INR, lactate, glucose, creatinine and mental state frequently and coordinate transfer according to the receiving centre's criteria.

03Obstructive jaundiceImage ducts then interveneConjugated bilirubin and a cholestatic pattern suggest impaired bile flow without current septic shock.

1Perform ultrasound and review pain, fever, weight, gallstones and medicine history; apply urgent cancer referral for suspicious painless progressive disease.
2Use MRCP or EUS for unresolved common-duct stone or stricture and contrast CT for pancreaticobiliary malignancy according to the specific question.
3Reserve ERCP for planned therapy or tissue strategy after multidisciplinary discussion, balancing infection, bleeding, pancreatitis and procedural risks.
4Treat the underlying stone, stricture, cholangiopathy or tumour and monitor bilirubin, symptoms and stent or drainage function.

04Cholestatic pruritusTreat itch and its causeGeneralised itch accompanies cholestasis without an immediate drainable emergency.

1Check for obstruction and review medicines, skin disease, kidney, thyroid and haematological alternatives, then treat the hepatobiliary cause where possible.
2Offer cool bathing, emollient, nail and excoriation care and start cholestyramine when suitable, spacing it widely from other oral medicines.
3Second lineIf ineffective or intolerable, obtain hepatology input for monitored second-line therapy such as rifampicin and subsequent opioid-antagonist or serotonergic options.
4Track sleep, skin injury, adherence, liver tests and medicine toxicity, and consider advanced liver or transplant assessment for refractory severe cholestasis.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Treats bloodstream and biliary infection while urgent drainage provides definitive source control.

Empirical antimicrobials for acute cholangitis

Give the locally approved intravenous biliary-sepsis regimen promptly after cultures where feasible, adjusting for allergy, renal function, previous instrumentation and local resistance.

Antibiotics cannot relieve obstruction. Review cultures, C difficile and kidney risk and narrow or stop according to response and successful drainage under stewardship guidance.

Binds intestinal bile acids and is a common first pharmacological treatment for cholestatic itch after obstruction is assessed.

Cholestyramine for cholestatic pruritus

Start with the current BNF low-dose oral regimen and titrate to response, separating administration from all other oral medicines by the recommended interval.

Constipation, bloating, poor palatability, medicine binding and fat-soluble vitamin deficiency limit use. Schedule carefully and avoid assuming failure when doses were taken simultaneously with other drugs.

Can reduce cholestatic pruritus through hepatic enzyme and bile-acid handling effects when resin treatment is inadequate.

Rifampicin for refractory cholestatic itch

Use only through hepatology with the current BNF starting and titration regimen after first-line failure, supported by baseline and early repeat laboratory monitoring.

Hepatotoxicity, blood dyscrasia, kidney injury and extensive drug interactions can be serious. Stop and seek specialist review for biochemical or clinical toxicity.

Disease-modifying first-line therapy in primary biliary cholangitis rather than a generic treatment for undifferentiated jaundice.

Ursodeoxycholic acid for confirmed primary biliary cholangitis

Use the current weight-based BNF and BSG regimen after specialist confirmation, monitoring biochemical response at the guideline-defined interval.

Confirm diagnosis and adherence, review weight-based dosing and response, and refer inadequate biochemical response for specialist second-line consideration and surveillance.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cholangitis or acute liver failure

Obstructed infected bile causes sepsis, while extensive hepatocyte failure causes coagulopathy and encephalopathy; both require same-day escalation.

Fat and vitamin malabsorption

Prolonged cholestasis reduces intestinal bile salts, impairing fat and fat-soluble vitamin absorption and contributing to weight loss or coagulopathy.

Excoriation and sleep loss

Severe chronic itch causes skin damage, infection risk, insomnia, low mood and major functional impairment even when jaundice is modest.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Trend bilirubin, ALT, ALP, INR, glucose, creatinine, sodium and mental state at a frequency determined by cholangitis, obstruction or liver-failure severity.
In biliary sepsis, monitor temperature, blood pressure, lactate, urine output and antimicrobial response while tracking time to successful drainage.
After ERCP or drainage, watch for recurrent fever, pain, pancreatitis, bleeding and failure of bilirubin to improve, and verify stent follow-up or removal responsibility.
For cholestatic itch, record sleep, excoriation, quality-of-life impact and treatment timing, not just bilirubin, because itch intensity correlates poorly with biochemical severity.
During rifampicin or other specialist therapy, follow the specified liver, renal and blood-count schedule and check new medicine interactions at every review.
Track suspected cancer imaging, cytology or biopsy and multidisciplinary decisions to a named clinician; symptomatic improvement after drainage does not close diagnosis.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Enzymes are not function

Very high ALT reflects hepatocyte injury, while INR, glucose, encephalopathy and lactate reveal whether the organ is failing. Falling ALT during worsening failure can mean fewer viable hepatocytes, not recovery.

Urine bilirubin is conjugated

Only water-soluble conjugated bilirubin passes into urine. Dark urine therefore supports conjugated hyperbilirubinaemia, whereas isolated Gilbert syndrome does not cause bilirubinuria.

Duct calibre can lag

Early obstruction, intermittent stones and primary sclerosing cholangitis may not produce uniform ultrasound dilatation. Persistent cholestatic probability requires MRCP, EUS or specialist review despite a non-dilated duct.

ERCP is treatment first

MRCP and EUS define anatomy without instrumenting the papilla. ERCP is reserved mainly for drainage, stone removal, stenting or selected sampling because its complications are clinically important.

Itch does not track bilirubin

Severe cholestatic pruritus can occur with modest bilirubin and may fluctuate independently. Treatment response should therefore include sleep and skin injury rather than biochemical targets alone.

Antihistamine is indirect

Histamine is not the principal mediator of cholestatic itch. A sedating antihistamine may aid sleep in selected patients but does not treat the underlying pruritic mechanism and adds cognitive burden.

11Common pitfallsFrequent interpretation and management errors.

01
Waiting for Charcot's complete triad before treating an older delirious patient with cholestatic sepsis.
02
Equating aminotransferase height with liver function and overlooking INR, glucose and encephalopathy.
03
Using a non-dilated ultrasound bile duct to exclude early obstruction or sclerosing cholangitis categorically.
04
Requesting diagnostic ERCP before considering lower-risk MRCP or EUS when no immediate drainage is required.
05
Prescribing cholestyramine at the same time as essential oral medicines and causing treatment failure through binding.
06
Treating cholestatic itch with escalating sedating antihistamines while failing to investigate obstruction or monitor specialist therapy.
07
Assuming bilirubin improvement after stenting excludes pancreatic or biliary malignancy and losing tissue or MDT follow-up.