What is the approach to a patient presenting with jaundice, considering their demographic, medical history, including previous liver disease, alcohol abuse, or gallstones?

Approach to a Patient with Jaundice

Begin with laboratory testing to differentiate unconjugated from conjugated hyperbilirubinemia, followed immediately by abdominal ultrasound as your first-line imaging study. 1

Initial Laboratory Workup

Order the following tests simultaneously:

• Total and fractionated (direct/indirect) bilirubin to categorize the hyperbilirubinemia type 1, 2
• Complete blood count to assess for hemolysis 1, 2
• Aspartate transaminase (AST) and alanine transaminase (ALT) 2
• Alkaline phosphatase and gamma-glutamyl transpeptidase (GGT) to identify cholestatic patterns 2, 3
• Albumin, prothrombin time, and INR to assess synthetic liver function 1, 2

The fractionated bilirubin result determines your entire diagnostic pathway. 1

Algorithmic Approach Based on Bilirubin Pattern

If Predominantly Unconjugated (Indirect) Hyperbilirubinemia:

Consider these etiologies in order of frequency:

• Hemolysis (2.5% of cases) - check CBC, reticulocyte count, Coombs test 4
• Gilbert syndrome (5.6% of cases) - benign, often triggered by fasting or illness 4
• Sepsis/shock (22-27% of severe jaundice) - creates mixed pattern but can present with unconjugated predominance initially 4

If Predominantly Conjugated (Direct) Hyperbilirubinemia:

Immediately obtain abdominal ultrasound to assess for biliary dilation and evaluate liver parenchyma. 1, 2

The most common causes in the United States are:

• Sepsis/shock (22-27% of cases) - most common overall 4
• Decompensated cirrhosis (20.5% of new-onset jaundice) - look for prior liver disease history 4
• Alcoholic liver disease (16% of cases) - alcoholic hepatitis often presents as first decompensation 4
• Choledocholithiasis (13-14% of cases) - multiple small stones (<5mm) carry 4-fold increased CBD migration risk 4
• Drug-induced liver injury (0.5-7% of cases) - review all medications and herbal supplements 4
• Malignancy (6.2% in U.S., higher in Europe) - pancreatic, cholangiocarcinoma, metastatic disease 4

Ultrasound Interpretation and Next Steps

Ultrasound has 65-95% sensitivity for cirrhosis and 32-100% sensitivity for biliary obstruction. 4

If Ultrasound Shows Biliary Dilation:

• Proceed to MRCP or CT with IV contrast to characterize the level and cause of obstruction 1
• ERCP is reserved for therapeutic intervention once obstruction is confirmed 1
• A normal CBD caliber has high negative predictive value for choledocholithiasis - if CBD is not dilated and patient has symptomatic gallstones, choledocholithiasis is unlikely 1

If Ultrasound Shows No Biliary Dilation but Parenchymal Changes:

• Consider intrahepatic cholestasis from medications, viral hepatitis, autoimmune hepatitis, or primary biliary cholangitis 1, 2
• Order hepatitis panel (A, B, C), autoimmune markers (ANA, ASMA, AMA), and immunoglobulins 2
• If diagnosis remains unclear after imaging and serologies, liver biopsy is required 2

Critical Historical and Physical Examination Details

Focus your history on:

• Alcohol consumption pattern - daily intake, duration, recent binge drinking 4
• All medications and supplements - prescription, over-the-counter, herbal products 4
• Prior liver disease - known cirrhosis, hepatitis, autoimmune conditions 4
• Gallstone history - prior cholecystectomy, biliary colic episodes 4
• Risk factors for viral hepatitis - IV drug use, transfusions, sexual exposure 2
• Recent weight loss or abdominal pain - suggests malignancy 4
• Fever and rigors - suggests cholangitis or sepsis 4

Physical examination priorities:

• Stigmata of chronic liver disease (spider angiomata, palmar erythema, ascites, splenomegaly) 2
• Right upper quadrant tenderness and Murphy's sign 2
• Palpable gallbladder (Courvoisier sign suggests malignant obstruction) 2

Common Pitfalls to Avoid

• Do not assume a nonvisualizing gallbladder on oral cholecystogram is a contraindication to workup - these patients can still have treatable disease 1
• However, if gallbladder nonvisualization develops during treatment, this predicts failure and therapy should be discontinued 1
• Markedly elevated transaminases (>1000 U/L) indicate hepatocellular injury, not obstruction - avoid unnecessary biliary procedures 3
• Viral hepatitis accounts for only 0.2% of severe jaundice cases - do not anchor on this diagnosis without supporting evidence 4
• Tissue harmonic imaging on ultrasound combined with elevated bilirubin, patient age, and CBD dilation increases sensitivity for CBD stones - request this technique specifically 1

When Diagnosis Remains Unclear

If laboratory testing and ultrasound do not establish a diagnosis, proceed systematically:

• CT with IV contrast or MRCP for better anatomic detail 1
• Consider ERCP if therapeutic intervention is likely needed 1
• Liver biopsy is the definitive diagnostic step when etiology remains unclear despite comprehensive workup 2