Jaundice

Jaundice is a clinical sign characterized by yellowish discoloration of the skin, sclerae, and mucous membranes due to elevated bilirubin in the bloodstream. It occurs across age groups and geographic regions and is encountered in settings from primary care clinics to tertiary Mayo Clinic and Johns Hopkins Hospital hepatology services. Recognition prompts evaluation for underlying disorders managed by specialists at institutions such as Cleveland Clinic and by public health agencies like the World Health Organization.

Signs and symptoms

Patients present with yellow discoloration of the sclera, skin, and oral mucosa accompanied variably by dark urine, pale stools, or pruritus. Associated systemic features may include fever, weight loss, abdominal pain or steatorrhea seen in referrals to centers like Massachusetts General Hospital and King's College Hospital. Physical findings that guide localization include hepatomegaly, splenomegaly, and ascites commonly assessed in clinics affiliated with University College London Hospitals and Charité – Universitätsmedizin Berlin. In neonates, clinicians at institutions such as Great Ormond Street Hospital and Boston Children's Hospital monitor feeding difficulty, lethargy, and kernicterus risk indicators during newborn screening and postnatal visits.

Causes and pathophysiology

Elevated bilirubin results from increased production, impaired conjugation, or obstructed excretion. Hemolytic states linked to disorders treated at centers like St Thomas' Hospital and Royal Victoria Hospital include autoimmune hemolysis, hereditary spherocytosis, and infections such as malaria diagnosed at London School of Hygiene & Tropical Medicine clinics. Genetic conjugation defects exemplified by conditions investigated at University of Oxford and Karolinska Institute include Gilbert syndrome and Crigler–Najjar syndrome. Hepatocellular injury from viral hepatitis strains managed by teams at Centers for Disease Control and Prevention, Osaka University Hospital, and All India Institute of Medical Sciences causes mixed hyperbilirubinemia. Cholestatic obstruction arises from gallstones, cholangiocarcinoma, and pancreatic head carcinoma referred to surgical units like Memorial Sloan Kettering Cancer Center and Royal Marsden Hospital, as well as from iatrogenic causes after procedures at Mayo Clinic Arizona. Neonatal physiologic jaundice relates to immature conjugation pathways studied in neonatal units such as Karolinska University Hospital and SickKids Hospital.

The underlying pathophysiology involves disrupted bilirubin metabolism: hemoglobin breakdown to unconjugated bilirubin bound to albumin, hepatic uptake and conjugation via UDP-glucuronosyltransferase enzymes characterized in research from National Institutes of Health and Institut Pasteur, and excretion into bile ducts. Obstruction elevates conjugated bilirubin and disrupts enterohepatic circulation, while hemolysis increases unconjugated bilirubin with potential for bilirubin encephalopathy if unbound bilirubin crosses the blood–brain barrier.

Diagnosis

Diagnosis integrates history, examination, laboratory tests, and imaging. Initial labs include serum total and direct bilirubin, liver transaminases (AST, ALT), alkaline phosphatase, gamma-glutamyl transferase, hemolysis markers (reticulocyte count, haptoglobin), and coagulation studies as performed in laboratories at Cleveland Clinic and Johns Hopkins University. Viral serologies for hepatitis A, B, C and autoimmune panels are ordered at centers such as Mayo Clinic and Vall d'Hebron University Hospital. Imaging modalities include abdominal ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography used by radiology departments at Mount Sinai Hospital, University Hospital Heidelberg, and Royal Infirmary of Edinburgh. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography are performed by interventional teams at Guy's and St Thomas' NHS Foundation Trust and Hospital of the University of Pennsylvania for diagnostic and therapeutic purposes. In neonates, transcutaneous bilirubinometry and serial total serum bilirubin measurements guide management per protocols from American Academy of Pediatrics and neonatal intensive care units like Neonatal Unit, King's College Hospital.

Management and treatment

Treatment targets the underlying cause and may be medical, endoscopic, radiologic, or surgical. Hemolysis is managed with transfusion, immunosuppression, or splenectomy in referral centers including Royal Free Hospital and University of Michigan Hospitals, while viral hepatitis receives antiviral therapy following guidelines from World Health Organization and European Association for the Study of the Liver. Obstructive causes are relieved by endoscopic stenting, stone extraction, or biliary surgery performed at specialized centers such as Johns Hopkins Hospital and Cleveland Clinic. In neonatal unconjugated hyperbilirubinemia, phototherapy and exchange transfusion protocols from American Academy of Pediatrics and units like Texas Children's Hospital reduce kernicterus risk. Cholestatic pruritus may be treated with ursodeoxycholic acid, rifampicin, or nasobiliary drainage utilized in tertiary hepatology centers including Queen Elizabeth Hospital Birmingham and Prince of Wales Hospital. Liver transplantation is considered for end-stage liver disease or acute liver failure in programs at King's College Hospital and UCLA Health.

Complications and prognosis

Complications vary with etiology: chronic liver disease, portal hypertension, and cirrhosis managed by hepatology services at Mount Sinai Hospital and Baylor St. Luke's Medical Center can lead to hepatic failure and need for transplantation. Malignant obstruction from cholangiocarcinoma or pancreatic cancer treated at Memorial Sloan Kettering Cancer Center often carries a poor prognosis. Hemolytic causes may result in iron overload or gallstone disease treated at surgical centers like Royal Sussex County Hospital. In neonates, untreated severe unconjugated hyperbilirubinemia risks irreversible neurologic damage known as kernicterus, with long-term sequelae addressed by pediatric neurology services at Great Ormond Street Hospital and Hospital for Sick Children, Toronto. Prognosis depends on reversibility of the underlying disorder, timely intervention at referral centers, and presence of comorbidities managed by multidisciplinary teams at institutions such as Cleveland Clinic and Johns Hopkins Hospital.

Category:Hepatology