Jaundice in Adults Algorithm

The full reasoning pathway — split the bilirubin and localise pre- / intra- / post-hepatic, exclude cholangitis and liver failure, run the liver screen, then treat by cause and pull the NICE NG12 pancreatic/biliary 2WW for any painless obstructive jaundice.StartDecisionInvestigateActionReferStop / Admit

PresentationJaundice / raised bilirubin

Pale stools + dark urine (obstructive), pain vs painless, weight loss, alcohol, drugs, travel/risk factors, itch. Request a split (conjugated/unconjugated) bilirubin, full LFTs, FBC, clotting and urgent USS.

Step 1 · Safety — screen the emergenciesCholangitis or liver failure?

Ascending cholangitis — Charcot's triad (fever + RUQ pain + jaundice) ± Reynolds' pentad (+ hypotension + confusion)
Acute liver failure — encephalopathy, coagulopathy (↑INR), hypoglycaemia
Paracetamol overdose or new drug-induced liver injury
Sepsis / haemodynamic instability

YES — emergency

Stop · admitEmergency admission

Cholangitis → IV fluids + antibiotics + urgent biliary decompression (ERCP). Acute liver failure / paracetamol → 999, NAC, hepatology. Don't wait for outpatient imaging.

NO — stable

Step 2 · InvestigateSplit bilirubin + LFT pattern + USS

Use the conjugated fraction + ALT-vs-ALP ratio to localise; USS liver/biliary tree for duct dilatation; full liver screen (viral serology, autoantibodies, ferritin, caeruloplasmin, immunoglobulins) as for abnormal LFTs.

Step 3 · where is the block?

Pre-hepatic

Unconjugated, normal LFTs

Haemolysis (↑retic, ↑LDH, ↓haptoglobin, +DAT) or Gilbert's (isolated mild ↑bilirubin, worse when fasting/unwell). No dark urine.

Hepatic

Hepatocellular (↑↑ALT)

Viral hepatitis (A–E), alcoholic/drug-induced (incl. paracetamol), autoimmune hepatitis, decompensated cirrhosis, Wilson's, haemochromatosis.

Post-hepatic

Obstructive (↑↑ALP/GGT, conjugated)

Pale stools, dark urine, itch. Gallstones (painful), stricture, PSC, pancreatic / cholangiocarcinoma. Painless = malignancy until proven.

Step 7 · treat by cause

Step 7 · Action — cause-directed treatmentTreat the level, support the liver

Pre-hepatic: Gilbert's — reassure, no treatment. Haemolysis — find & treat the cause (haematology).
Hepatic: stop hepatotoxins & alcohol; antivirals for hepatitis B/C; immunosuppression for autoimmune hepatitis; manage cirrhosis complications; NAC for paracetamol.
Post-hepatic benign: ERCP stone extraction → cholecystectomy; stricture dilatation/stenting.
Post-hepatic malignant: urgent staging CT + hepatobiliary MDT; biliary stenting for relief; symptom control (itch — colestyramine), nutrition.

Step 6 · escalation thresholds

Step 6 · ReferEscalation thresholds

Emergency cholangitis, acute liver failure, decompensated cirrhosis, suspected paracetamol toxicity.
2WW · NICE NG12 adults aged ≥40 with jaundice → urgent direct-access CT (or USS) for suspected pancreatic cancer / urgent suspected-cancer referral. Painless obstructive jaundice always takes the urgent pathway, regardless of LFT detail.
Hepatology / gastro unexplained hepatocellular jaundice, suspected autoimmune/inherited liver disease, PSC. Haematology haemolysis.

Step 8 · modify & protect

Step 8 · Lifestyle & liver protectionReduce ongoing injury

Alcohol cessation and brief intervention · review and stop hepatotoxic drugs/supplements · weight loss for fatty liver · hepatitis A/B vaccination in chronic liver disease · avoid further paracetamol above safe limits · safe-sex/needle advice for viral hepatitis · pruritus measures.

Step 9 · monitor & safety-net

Step 9 · Monitoring & safety-netWhen to come back

999 / same-day if fever + rigors + RUQ pain (cholangitis), confusion/drowsiness, bruising/bleeding, or vomiting blood. Review: chase USS/CT and 2WW outcomes; repeat LFTs to track trend; re-image if obstruction suspected but first scan normal. Safety-net that a normal USS does not exclude a small pancreatic tumour — escalate to CT if jaundice persists.

⚠️ Painless jaundice is a red flag: in an adult aged ≥40 it is pancreatic or biliary cancer until proven otherwise — arrange urgent CT on the suspected-cancer pathway, and never wait out a normal ultrasound.

Safety

Red Flags — Exclude Life-Threatening Causes First

Done

Jaundice is a symptom, not a diagnosis. Always exclude emergency and malignant causes before proceeding.

Acute liver failure Confusion, coagulopathy, rapidly deepening jaundice, encephalopathy → 999

Ascending cholangitis Charcot's triad: fever, RUQ pain, jaundice. Sepsis signs → 999

Haemodynamic instability SBP <90, HR >100, altered GCS — any cause → 999

Paracetamol overdose Known or suspected ingestion within 24h; any LFT derangement → 999

Painless jaundice + weight loss Courvoisier's sign — pancreatic head malignancy until proven otherwise → 2WW Upper GI

Pruritus + pale stools + dark urine Obstructive pattern in patient >40 without obvious benign cause → 2WW Upper GI

Coagulopathy / bleeding INR >1.5, spontaneous bruising, GI bleed — suggests severe hepatic dysfunction → Same-day ED

Pregnant patient Any jaundice in pregnancy — AFLP, obstetric cholestasis, HELLP — emergency obstetric review → 999 / Same-day

Neonate-like picture Rapidly progressive; bili >300 µmol/L; any neonatal jaundice >14 days → Same-day paeds

Acute liver failure carries 30-day mortality >50% without transplant. Ascending cholangitis (Charcot's triad) progresses to Reynold's pentad (septic shock + confusion) rapidly. Pancreatic head cancer causes obstructive jaundice and has a median survival of 6 months — early 2WW may enable surgical resection. Paracetamol toxicity must be identified within the window for N-acetylcysteine to be effective. AFLP has a maternal mortality of 12-18% if missed.

Diagnose

Confirm Jaundice — Pattern Recognition and History

Done

Confirm true jaundice (scleral icterus visible when bilirubin >35 µmol/L), then use history to direct the differential.

Confirm jaundice

Scleral icterus (best seen in natural light); check palms, skin. Pseudo-jaundice (hypercarotenaemia) spares sclera

Onset and speed

Sudden onset suggests haemolysis or acute hepatitis; gradual onset suggests obstruction or chronic liver disease

Dark urine + pale stools

Conjugated hyperbilirubinaemia → obstructive or hepatocellular. Absent in prehepatic (haemolytic) jaundice

Pain character

Colicky RUQ = gallstone; Constant epigastric/back = pancreatic; No pain = malignancy, cholestasis, haemolysis

Drug and OTC history

DILI in up to 10% of jaundice cases. Ask: statins, antibiotics (co-amox, nitrofurantoin), herbal remedies, supplements, new medications in last 3 months

Alcohol history

Units/week; CAGE score; pattern (binge vs daily). Alcoholic hepatitis can present acutely

Travel + exposure

Hep A/E — recent foreign travel, shellfish, water. Hep B/C — IVDU, sexual contacts, tattoos, healthcare worker

Family history

Gilbert's syndrome (benign, fasting-precipitated); haemolytic anaemias; haemochromatosis; Wilson's disease

Systemic features

Weight loss, anorexia, fatigue → malignancy. Fever → infection/cholangitis. Arthralgia → autoimmune hepatitis

History directs the differential more than any single test. The triad of dark urine, pale stools, and pruritis strongly predicts obstructive jaundice (LR+ ~10). Drug-induced liver injury is the most commonly missed cause of jaundice — always take a full drug history including OTCs, herbal remedies, and supplements. Gilbert's syndrome affects ~5% of the population and is a benign cause precipitated by fasting, illness, or exercise — important to recognise to avoid unnecessary investigation.

Diagnose

Classify Jaundice Type — Pre-hepatic / Hepatic / Post-hepatic

Done

Classify into one of three mechanistic categories to direct investigation and referral.

Pre-hepatic (haemolytic)

Unconjugated bilirubin ↑; normal LFTs; dark urine absent; anaemia, splenomegaly. Causes: haemolytic anaemia, sickle cell, G6PD, Gilbert's, neonatal

Hepatic (hepatocellular)

Mixed bilirubin ↑; raised AST/ALT (often >10× ULN in acute); ALP mildly raised. Causes: viral hepatitis, alcoholic hepatitis, DILI, autoimmune, cirrhosis, acute liver failure

Post-hepatic (obstructive)

Conjugated bilirubin ↑; ALP/GGT markedly raised; AST/ALT mildly raised; dark urine + pale stools + pruritus. Causes: gallstones, cholangiocarcinoma, pancreatic cancer, primary sclerosing cholangitis

LFT pattern guide

Hepatitic: ALT >3× ULN, ALP <3× ULN. Cholestatic: ALP >3× ULN, ALT <3× ULN. Mixed: both elevated. Gilbert's: isolated unconjugated bilirubin, normal LFTs

Key discriminator

ALP:ALT ratio >2 favours cholestatic; ratio <0.5 favours hepatitic. GGT elevation with ALP suggests biliary (not bone) source

Classification is essential because management pathways diverge completely. Hepatocellular jaundice rarely requires imaging as first-line — virology and autoimmune screen drive diagnosis. Cholestatic jaundice almost always requires urgent USS. Haemolytic jaundice needs haematological workup. Getting the pattern right from LFTs saves time and prevents over-investigation. NICE CG32 recommends LFTs as the first investigation for all new jaundice presentations.

Diagnose

Targeted Examination

Done

Examination should take <3 minutes and directly modifies the differential and urgency of referral.

Vital signs

Temp ≥38°C + jaundice = ascending cholangitis until proven otherwise. HR/BP for haemodynamic stability. SaO₂ if unwell

Scleral icterus

Confirm jaundice. Yellow tinge to conjunctiva. Best seen in natural light or with bright examination light

Abdomen

RUQ tenderness = biliary/hepatic pathology. Murphy's sign (cholecystitis). Epigastric mass = pancreatic cancer. Hepatomegaly (smooth = congestion/hepatitis; nodular = cirrhosis/metastases). Splenomegaly = portal hypertension / haemolysis

Courvoisier's sign

Palpable non-tender gallbladder + jaundice = pancreatic head obstruction (malignancy) until proven otherwise → 2WW

Stigmata of CLD

Spider naevi (>5 = significant), palmar erythema, leukonychia, Dupuytren's, parotid enlargement, gynaecomastia, caput medusae, testicular atrophy → suggests chronic liver disease/cirrhosis

Lymphadenopathy

Supraclavicular (Virchow's), axillary — haematological malignancy or metastatic disease

Skin

Scratch marks = cholestatic pruritus. Xanthelasma = chronic cholestasis (PBC). Tattoos/tracks = hepatitis risk

Mental state

Asterixis (liver flap), confusion, drowsiness → hepatic encephalopathy → acute liver failure → 999

Courvoisier's law has a positive predictive value of ~55% for malignant obstruction — a palpable gallbladder with painless jaundice mandates urgent 2WW referral regardless of LFTs. Stigmata of chronic liver disease (especially >5 spider naevi) suggest portal hypertension and require hepatology involvement. Murphy's sign has a sensitivity of 65% and specificity of 87% for acute cholecystitis — positive Murphy's with fever mandates same-day surgical assessment. Asterixis is a critical finding indicating Grade II+ encephalopathy requiring emergency hospital admission.

Diagnose

Investigations — Bloods and Imaging

Done

First-line bloods are mandatory for all new jaundice. Image within 24h if obstruction suspected.

First-line bloods All

LFTs (ALT, AST, ALP, GGT, bilirubin total + conjugated), albumin, INR/PT, FBC, U&E, CRP, glucose, TFTs

Viral screen Hepatitic pattern

Hep A IgM, Hep B sAg + core Ab, Hep C Ab, Hep E IgM (if travel/pregnancy), EBV/CMV IgM if young patient

Autoimmune screen Hepatitic/cholestatic

ANA, ASMA (anti-smooth muscle), LKM-1, AMA (anti-mitochondrial — PBC), serum IgG. Request if viral screen negative and <50 years

Metabolic screen

Ferritin + transferrin saturation (haemochromatosis); serum caeruloplasmin if <40 (Wilson's disease); alpha-1-antitrypsin if <50 with no obvious cause

USS abdomen Cholestatic pattern

First-line imaging for suspected obstruction. Dilated bile ducts, gallstones, mass lesions. Arrange within 24h if obstructive pattern on LFTs

MRCP

Arrange via gastroenterology if USS non-diagnostic but obstruction still suspected. Better than USS for CBD stones and biliary strictures

Haemolytic screen Pre-hepatic

Blood film, reticulocyte count, haptoglobin (low = haemolysis), LDH (raised), Coombs' test if immune haemolysis suspected

Do NOT routinely order

CA 19-9 without imaging evidence of malignancy (high false positive rate). CEA, AFP without specialist guidance. Random biopsy without diagnosis

LFT pattern guides the investigation pathway — ALP-predominant pattern requires USS within 24 hours per NICE guidance (NG12 updated). INR/PT is the most sensitive marker of acute hepatic synthetic function — INR >1.5 is a criterion for acute liver failure and warrants same-day hospital referral. Autoimmune hepatitis is eminently treatable with steroids but missed if screen not requested — it accounts for 20% of jaundice without obvious cause. Haemochromatosis is the most common genetic liver condition in the UK (1 in 200 homozygous) and is highly treatable with venesection.

Refer

Referral Criteria — Urgency and Destination

Done

Almost all new jaundice in adults requires specialist input. The key decision is urgency of referral.

999

Acute liver failure (encephalopathy + coagulopathy); ascending cholangitis; haemodynamic compromise; paracetamol OD; jaundice in pregnancy with systemic illness

Same-day ED

INR >1.5; bilirubin >200 µmol/L; febrile with obstructive LFTs; unable to tolerate oral fluids; alcoholic hepatitis with discriminant function >32

2WW Gastro/UGI

Painless jaundice + weight loss; Courvoisier's sign; biliary obstruction on USS (dilated ducts, mass); age >40 with cholestatic pattern and no benign cause

Urgent (1–2 weeks)

Cholestatic LFTs + normal USS (PSC/PBC suspected); active viral hepatitis (Hep B/C) needing antiviral treatment; autoimmune hepatitis screen positive

Routine Hepatology

Chronic viral hepatitis (stable); haemochromatosis; Wilson's disease; PBC (stable); cirrhosis monitoring; unexplained persistent LFT derangement >6 months

Primary care manage

Gilbert's syndrome (isolated unconjugated bili, normal LFTs, precipitant identified); mild alcoholic fatty liver (no fibrosis markers, stable, engaging with change)

The Maddrey discriminant function (4.6 × [PT - control PT] + bilirubin µmol/L ÷ 17) predicts 30-day mortality in alcoholic hepatitis — score >32 indicates 50% mortality and need for hospital admission for prednisolone consideration. PSC carries a 10–15% lifetime risk of cholangiocarcinoma and requires regular surveillance (MRCP + CA 19-9 6-12 monthly). PBC has excellent outcomes with UDCA if treated early. Hepatitis C is now curable in 8–12 weeks with direct-acting antivirals — urgent hepatology referral is essential.

Treat

Treatment Pathway by Cause

Done

Treatment is cause-specific. Most definitive treatments are secondary care — primary care role is stabilisation and specific manageable conditions.

Gilbert's Syndrome

Reassurance Benign

No treatment needed. Explain fasting, illness, exercise precipitate episodes. Written information. No monitoring required.

Alcoholic Hepatitis (mild)

Alcohol cessation + nutrition

Thiamine 300 mg OD (Pabrinex if IV access needed). High protein diet. AUDIT-C. Refer to alcohol services. Discriminant function if available.

Drug-Induced Liver Injury

Stop causative drug immediately

Identify and stop offending drug. Monitor LFTs every 2–4 weeks. Alert to Yellow Card. Seek hepatology advice if persistent.

Pruritus (cholestatic)

Cholestyramine 4 g TDS

First-line for cholestatic itch. Allow 2–4 weeks for response. If inadequate: rifampicin 150 mg OD–BD (hepatology guidance). Avoid antihistamines (ineffective for cholestatic itch).

PBCUrsodeoxycholic acid (UDCA) 13–15 mg/kg/day — hepatology initiates. Reduces progression to cirrhosis by 30–40%. Monitor LFTs 3-monthly. Alkaline phosphatase target: <1.67× ULN (Paris II criteria).

Hep CDirect-acting antivirals (sofosbuvir/ledipasvir or glecaprevir/pibrentasvir) — hepatology prescribes. 8–12 week course. Cure rate >95%. Refer urgently.

Hep BTenofovir 245 mg OD or entecavir 0.5 mg OD — hepatology prescribes. Suppress viral load. HBsAg carriers: vaccinate household contacts. Notify Public Health.

HaemochromatosisVenesection 1 unit/week until ferritin <50 µg/L, then maintenance. Target: Hb ≥120 g/L before each session. Screen first-degree relatives with genetic testing (HFE C282Y).

UDCA for PBC improves transplant-free survival — those who achieve Paris II response criteria have near-normal life expectancy. Hepatitis C is now a curable disease; failure to refer is a significant clinical governance issue. Rifampicin for cholestatic pruritus is off-label but supported by BSG guidelines when first-line fails — requires hepatology oversight due to hepatotoxicity risk. Venesection in haemochromatosis, if started before cirrhosis, normalises life expectancy. In DILI, rechallenge is generally contraindicated due to risk of severe reaction.

Lifestyle

Non-Pharmacological Interventions — Essential Adjuncts

Done

Lifestyle interventions are treatment, not optional add-ons. In alcoholic and NAFLD-related disease, lifestyle may be the only effective intervention.

Alcohol cessation Absolute abstinence if alcoholic liver disease. Reduces 5-year mortality from 50% to <10% in those without cirrhosis. Refer to structured alcohol programme. Consider acamprosate or naltrexone.

Weight management In NAFLD: 7–10% weight loss reduces hepatic steatosis by up to 50% and can resolve NASH. Target BMI <25. Low carbohydrate diets show best liver-specific benefit.

Dietary hepatoprotection Mediterranean diet reduces liver inflammation markers. Avoid fructose-heavy processed foods (drive de novo lipogenesis). Coffee: 2–3 cups/day associated with 40% lower risk of cirrhosis.

Vaccination Offer Hep A + Hep B vaccines to all patients with chronic liver disease. Flu and pneumococcal vaccination reduces decompensation risk. Check immunity before commencing immunosuppressants.

Medication review Avoid hepatotoxic drugs: statins (relative CI in active hepatitis), NSAIDs, paracetamol >2 g/day in liver disease, sedatives (precipitate encephalopathy). Review and document all supplements.

Exercise 150 minutes moderate aerobic/week reduces hepatic fat. Resistance training improves insulin sensitivity. Reduces NAFLD progression independent of weight loss.

Salt restriction If ascites or portal hypertension: restrict sodium to <90 mmol/day (no added salt diet). Reduces need for spironolactone dose escalation.

Infection vigilance Cirrhotic patients have 40× increased risk of spontaneous bacterial peritonitis. Advise on food hygiene, prompt treatment of infections, prophylactic antibiotics if indicated by hepatology.

NAFLD affects 25% of the UK population and is now the leading cause of cirrhosis referral — lifestyle intervention is the primary treatment as no licenced pharmacotherapy exists for NASH. The impact of alcohol cessation on liver disease is dramatic — even compensated cirrhosis can show hepatic functional recovery. Coffee consumption is one of the most consistent lifestyle hepatoprotective factors in the literature, with data across multiple prospective cohorts. Salt restriction in decompensated cirrhosis reduces readmission rates and diuretic requirements (EASL guidelines 2018).

Safety

Follow-Up, Monitoring and Safety-Netting

Done

All patients with new jaundice need structured follow-up. The interval depends on cause and severity.

1–2 weeks

Repeat LFTs + FBC if initial results abnormal. Check response to any stopped drug (DILI). Confirm specialist appointment made. Review alcohol intake

4 weeks

LFTs improving? If not, escalate urgency of referral. Check medication side effects (cholestyramine constipation/malabsorption)

3 months

LFT trend: downward = reassuring. Static/rising = escalate. NAFLD: repeat USS at 3 years if normal; annually if fibrosis markers present (FIB-4 score)

Annual

Stable chronic liver disease: LFTs, AFP (hepatocellular carcinoma screen if cirrhosis), USS 6-monthly if cirrhotic. Variceal screening per hepatology

FIB-4 score

Age × AST ÷ (platelet × √ALT). <1.3 = low fibrosis risk; >2.67 = advanced fibrosis → hepatology referral. Use to triage NAFLD/AFLD monitoring in primary care

Safety-net 999

Confusion / drowsiness (encephalopathy); haematemesis or melaena; severe abdominal pain; marked pallor; collapse

Safety-net same-day

Deepening jaundice; new fever; inability to eat/drink; bruising without injury; worsening abdominal distension (ascites)

Patient information

Provide written safety-net advice. Alcohol advice leaflet if relevant. NAFLD patient information. BSG / EASL patient info links

The FIB-4 score is validated for risk-stratification of liver fibrosis in primary care (AUC 0.86 for advanced fibrosis) and is incorporated into NICE guidance on NAFLD (NG49 updated). USS surveillance for HCC is associated with a 37% mortality reduction in cirrhotic patients when performed 6-monthly. Spontaneous bacterial peritonitis (SBP) presents with subtle signs in cirrhosis — any unexplained deterioration should prompt same-day assessment. Hepatic encephalopathy progresses from Grade I (mild confusion) to Grade IV (coma) rapidly and should always be treated as emergency.