Jaundice in Adults Algorithm

Safety

Red Flags — Exclude Life-Threatening Causes First

Done

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

Suspected acute liver failure Acute liver injury with prolonged INR plus new encephalopathy (confusion, drowsiness, asterixis), hypoglycaemia, acidosis, rapidly worsening jaundice or multiorgan dysfunction → 999 + urgent liver/critical-care discussion

Ascending cholangitis Fever/rigors + RUQ pain + jaundice → same-day hospital; 999 if hypotension, confusion, severe sepsis, hypoxia or instability

Haemodynamic instability Hypotension, poor perfusion or altered consciousness — judged on the whole picture → 999

Paracetamol overdose Any suspected overdose → ED now (999 if unwell) + TOXBASE/NPIS advice. Do not delay acetylcysteine for bloods if late, uncertain-timing or staggered — staggered ingestion is not plotted on the nomogram

Jaundice at 40 or over Suspected cancer: pancreatic Suspected cancer pathway referral whether or not there is weight loss (NICE NG12); weight loss, pale stools, itch or a palpable gallbladder (Courvoisier — suggestive, not diagnostic) add concern

Pruritus + pale stools + dark urine Obstructive pattern → urgent USS/HPB assessment; at 40+ the jaundice itself meets the NG12 pancreatic criterion → Suspected cancer

Coagulopathy / bleeding Raised INR needs urgent interpretation (exclude warfarin/DOAC, vitamin K deficiency, chronic disease); spontaneous bruising or GI bleed → Same-day ED (999 if bleeding actively)

Pregnant patient Jaundice in pregnancy → urgent same-day obstetric/medical; 999 if unstable, confused, hypotensive, bleeding, severely unwell or suspected acute liver failure/HELLP/AFLP

Acute liver failure is a medical emergency. Ascending cholangitis (Charcot's triad) progresses to Reynold's pentad (septic shock + confusion) rapidly. Pancreatic head cancer causes obstructive jaundice and has a poor prognosis — an early suspected cancer pathway referral may enable surgical resection. Paracetamol toxicity must be identified within the window for N-acetylcysteine to be effective. AFLP is life-threatening if missed.

Diagnose

Confirm Jaundice — Pattern Recognition and History

Done

Confirm true jaundice (scleral icterus usually visible when bilirubin is above about 40 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 is common. 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 suggests obstructive jaundice, although hepatocellular disease can also cause dark urine and pale stools. 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 is a common 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 ↑; LFTs usually normal (secondary changes or coexisting liver disease possible); dark urine absent; anaemia, splenomegaly. Causes: haemolytic anaemia, sickle cell, G6PD, Gilbert's

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

Describe the predominant pattern by the relative rise of ALT vs ALP; for suspected DILI use the R-ratio (ALT/ULN ÷ ALP/ULN: ≥5 hepatocellular, 2–5 mixed, ≤2 cholestatic). GGT with ALP suggests a biliary (not bone) source. Conjugated bilirubin is not synonymous with obstruction

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. LFTs are 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

Fever + jaundice raises concern for cholangitis — same-day hospital. 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 raises suspicion of malignant obstruction (not diagnostic) → urgent imaging; at 40+ the jaundice meets the NG12 pathway

Stigmata of CLD

Spider naevi, 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

A palpable non-tender gallbladder with jaundice (Courvoisier's sign) raises suspicion of malignant obstruction but is not diagnostic — arrange urgent imaging and referral; at 40 or over the jaundice itself meets the NG12 pancreatic criterion. Stigmata of chronic liver disease (such as spider naevi) suggest portal hypertension and require hepatology involvement. A positive Murphy's sign with fever warrants same-day surgical assessment. Asterixis is a critical finding indicating Grade II+ encephalopathy requiring emergency hospital admission.

Diagnose

Investigations — Bloods and Imaging

Done

Initial bloods for all new jaundice; imaging urgency set by sepsis, rate of rise, pain, duct dilatation and malignancy concern.

First-line bloods All

Bilirubin (fractionated), ALT, AST, ALP, GGT, albumin, PT/INR, FBC + platelets, U&E, glucose; CRP if infection suspected; TFTs, calcium, CK by the picture

BSG standard aetiology screen All unexplained

Liver USS, HBsAg, HCV antibody (RNA/core antigen if positive), ferritin + transferrin saturation, AMA, ANA, ASMA, immunoglobulins. Acute hepatitis: hep A IgM and hep E (even without travel); EBV/CMV selectively. HBsAg positive → specialist referral and HBV staging

Autoimmune screen Hepatitic/cholestatic

ANA, ASMA, AMA, IgG (in the standard screen at any age) ± LKM-1; a positive antibody alone does not establish autoimmune disease

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; urgency by clinical picture and local access. Suspected cholangitis → hospital, not outpatient USS

MRCP

Via the specialist/HPB pathway if USS is non-diagnostic but obstruction, PSC or stricture remains 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 needs prompt abdominal USS (clinical practice); jaundice at age 40 or over meets the NICE NG12 (updated April 2026) suspected cancer pathway criterion for pancreatic cancer. INR/PT is the most sensitive marker of acute hepatic synthetic function — a raised INR in a jaundiced patient needs urgent interpretation but is not automatically acute liver failure — consider anticoagulants, vitamin K deficiency and chronic liver disease. Autoimmune hepatitis is eminently treatable with steroids but missed if screen not requested — include the autoimmune markers in the standard screen. 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

Suspected acute liver failure (encephalopathy, hypoglycaemia); cholangitis with sepsis or instability; shock; active GI bleeding; unwell after overdose; pregnancy with systemic illness

Same-day ED

New jaundice with coagulopathy, renal dysfunction, fever, significant pain, rapidly rising bilirubin, inability to maintain intake or suspected decompensation; suspected paracetamol overdose → ED now, not later in the day; suspected alcoholic hepatitis (steroids for Maddrey DF ≥32 are specialist-only) — no single bilirubin or INR number decides

Suspected cancer: pancreatic / upper GI

Jaundice at 40 or over (with or without weight loss) → pancreatic suspected cancer pathway (NG12) — do not wait for imaging, and a normal ultrasound does not exclude pancreatic cancer; obstruction or duct dilatation → urgent HPB assessment, suspected cancer pathway referral if criteria met or imaging suggests malignancy. NICE NG85: pancreatic-protocol CT before biliary drainage unless drainage is urgent

Urgent (1–2 weeks)

Cholestatic LFTs + normal USS (PSC/PBC suspected); HBsAg or HCV RNA positive; positive autoantibodies supported by pattern, raised IgG or persistent derangement

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 bilirubin, normal ALT/ALP/GGT/albumin/INR, haemolysis excluded); fatty liver without jaundice and with low fibrosis risk — new jaundice from suspected alcoholic hepatitis needs urgent specialist assessment

The Maddrey discriminant function (4.6 × [PT - control PT] + bilirubin µmol/L ÷ 17) predicts 30-day mortality in alcoholic hepatitis — a score ≥32 identifies severe disease needing hospital and specialist consideration of prednisolone consideration. PSC carries an increased lifetime risk of cholangiocarcinoma and needs specialist-led surveillance. 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

Confirm isolated unconjugated hyperbilirubinaemia (FBC/retic/LDH if haemolysis possible; not with abnormal ALT, ALP, GGT, albumin or INR). No treatment or routine monitoring once confirmed.

Suspected Alcoholic Hepatitis

Urgent specialist assessment

New jaundice → urgent hospital/hepatology, especially with coagulopathy, renal dysfunction, infection or encephalopathy. Corticosteroids are specialist-only after infection, GI bleeding and renal impairment are addressed. Thiamine if at risk (IV Pabrinex in hospital if Wernicke's suspected); no abrupt cessation in dependence without assisted withdrawal; alcohol services.

Drug-Induced Liver Injury

Review the suspected drug

Stop a suspected non-essential drug after weighing indication and withdrawal risk (specialist advice for essential medicines). Monitor by severity and trend — jaundice, coagulopathy, renal dysfunction, encephalopathy or worsening → urgent specialist. A diagnosis of exclusion; Yellow Card.

Pruritus (cholestatic)

Colestyramine 4–8 g daily (SPC)

First-line for cholestatic itch; give other medicines well apart, as the SPC directs. Rifampicin only on specialist advice (hepatotoxicity, interactions). Antihistamines do not treat the cholestatic mechanism, though sedating ones may aid sleep.

PBCSuspected on a persistent cholestatic pattern, compatible imaging and AMA/specialist serology → hepatology. UDCA (about 13–15 mg/kg/day) is usually specialist-initiated; second-line treatment is specialist-led (obeticholic acid carries MHRA liver-injury warnings).

Hep CDirect-acting antivirals via the hepatology/ODN pathway — regimen and duration depend on cirrhosis, prior treatment, renal function, interactions and commissioning. Screen for hepatitis B first (reactivation risk).

Hep BHBsAg positive → specialist referral and HBV staging; any antiviral choice is specialist-led (HBV DNA, ALT, fibrosis, pregnancy, renal and bone health). Vaccinate household contacts; notify per local public-health rules.

HaemochromatosisConfirm iron overload and genotype via hepatology; venesection targets and frequency are specialist-set. Primary care: avoid iron supplements, address alcohol and comorbid liver disease; offer family testing (HFE C282Y).

Next steps: see Gilbert's syndrome · Fatty liver (MASLD) · Cholecystitis and gallstones · Harmful drinking and alcohol dependence

UDCA for PBC improves transplant-free survival; assessment of treatment response and second-line therapy are specialist-led. 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 Complete abstinence in established alcohol-related liver disease or cirrhosis — but no abrupt stopping in dependence without an assisted-withdrawal plan. Refer to alcohol services; relapse-prevention drugs per specialist advice (naltrexone generally avoided in significant liver disease).

Weight management Gradual, sustained weight loss where overweight, with physical activity and cardiovascular-risk management.

Dietary hepatoprotection Mediterranean-style diet; limit sugary processed foods. Coffee may be discussed but is not a treatment.

Vaccination Offer Hep A + Hep B vaccines to all patients with chronic liver disease. Flu and pneumococcal vaccination per the current Green Book. Check immunity before commencing immunosuppressants.

Medication review Avoid hepatotoxic drugs: NSAIDs, sedatives (precipitate encephalopathy); tailor paracetamol dose to severity, weight, nutrition and alcohol; statins are usually continued unless specialist-advised. 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: moderate no-added-salt diet with specialist dietary advice.

Infection vigilance Cirrhosis raises infection risk: prompt treatment of infections; SBP prophylaxis only per hepatology criteria (not routine for all ascites — NG50).

NAFLD is common and a 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, international).

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 in selected stable patients — not instead of urgent assessment or referral. 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: falling is reassuring but does not exclude malignancy, chronic disease or persistent obstruction. Static/rising = escalate. NAFLD without advanced fibrosis: retest for advanced fibrosis every 3 years (NICE NG49); hepatology if fibrosis markers raised (FIB-4 / ELF)

Cirrhosis

Cirrhosis: liver USS every 6 months ± AFP per cause and hepatology protocol — never substitute annual AFP for imaging (NG50). Variceal screening per hepatology

FIB-4 score

Age × AST ÷ (platelet × √ALT). <1.3 low risk under 65 (about 2.0 if over 65); intermediate → ELF/elastography; high (BSG commonly >3.25) → specialist — follow the local hepatology thresholds. 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 widely used first-line (clinical practice); NICE NG49 (NAFLD/MASLD) recommends considering the ELF test to assess for advanced fibrosis. USS surveillance for HCC every 6 months is recommended in cirrhosis (NICE NG50). 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.