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Evaluation of Jaundice in Adults

Michelle Nelson, MD
Shaunak R. Mulani, MD
Aaron Saguil, MD, MPH

American Family Physician. 2025;111(1):25-30.

Author disclosure: No relevant financial relationships.

This clinical content conforms to AAFP criteria for CME.

Jaundice is an indication of hyperbilirubinemia and is caused by derangements in bilirubin metabolism. It is typically apparent when serum bilirubin levels exceed 3 mg/dL and can indicate serious underlying disease of the liver or biliary tract. A comprehensive medical history, review of systems, and physical examination are essential for differentiating potential causes such as alcoholic liver disease, biliary strictures, choledocholithiasis, drug-induced liver injury, hemolysis, or hepatitis. Initial laboratory evaluation should include assays for bilirubin (total and fractionated), a complete blood cell count, aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline phosphatase, albumin, prothrombin time, and international normalized ratio. Measuring fractionated bilirubin allows for determination of whether the hyperbilirubinemia is conjugated or unconjugated. Ultrasonography of the abdomen, computed tomography with intravenous contrast media, and magnetic resonance cholangiopancreatography are first-line options for patients presenting with jaundice, depending on the suspected underlying etiology. If the etiology of jaundice is unclear despite laboratory testing and imaging, liver biopsy may be required to establish the diagnosis, prognosis, and management of the disease.

Jaundice (ie, yellowing of the skin, sclera, and mucous membranes) is an indication of hyperbilirubinemia. An individual physician's ability to detect jaundice varies, but the condition is typically apparent when serum bilirubin levels exceed 3 mg/dL (51.3 mmol/L).1 Jaundice can indicate serious underlying disease of the liver or biliary tract and may be due to intra- or extrahepatic pathology.1,2 Figure 1 details a systematic approach for the evaluation of an adult with jaundice.3–7

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating Comments
Adults with jaundice should be evaluated for bilirubin (total and fractionated), complete blood cell count, aspartate transaminase, alanine transaminase, gamma-glutamyltransferase, alkaline phosphatase, albumin, prothrombin time, and international normalized ratio.4,5 C American College of Gastroenterology consensus guideline, expert opinion, and clinical review
Ultrasonography or computed tomography with contrast are typically preferred for initial evaluation of jaundice because of their noninvasive nature, lower cost, and convenience.6 C American College of Radiology Appropriateness Criteria
If the etiology of jaundice is unclear despite laboratory testing and imaging, liver biopsy can be used to establish the diagnosis, prognosis, and management of the disease.5,7 C Expert opinion from the American College of Gastroenterology consensus guideline, British Society of Gastroenterology, the Royal College of Radiologists, and the Royal College of Pathology Consensus Guideline

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

FIGURE 1.

Evaluation of jaundice in adults.

Information from references 3-7.

PATHOPHYSIOLOGY

Jaundice presents when impairment in bilirubin metabolism occurs. Bilirubin is formed by the destruction of the erythrocyte, which contains the heme molecule, inside the macrophages that phagocytose senescent blood cells.8 Heme is then converted to biliverdin and unconjugated bilirubin, which is water insoluble. Unconjugated bilirubin is then transported to the liver for conjugation by the bilirubin uridine diphosphateglucuronyl transferase (bilirubin-UGT) enzyme, which converts bilirubin into a water-soluble form. This conjugated bilirubin is then transferred to the biliary tract for storage in the gallbladder and secretion into the intestinal tract, where it is then excreted as urobilinogen in the urine and stercobilinogen in the stool.1,4 Any disruption in bilirubin metabolism may result in jaundice and may affect urine and stool coloration.

MICHELLE NELSON, MD, FAAFP, is a clinical assistant professor in the Department of Family Medicine and MSU/MyMichigan Medical Center Alma Family Medicine Residency at Michigan State University College of Human Medicine, Grand Rapids.

SHAUNAK R. MULANI, MD, is an assistant professor in the Department of Community Health and Family Medicine at the University of Florida College of Medicine, Gainesville.

AARON SAGUIL, MD, MPH, is a professor and chair in the Department of Community Health and Family Medicine at the University of Florida College of Medicine, Gainesville.

Address correspondence to Aaron Saguil, MD, MPH, at a.saguil@ufl.edu.

Author disclosure: No relevant financial relationships.

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