Cholestasis Workup

  • Author: Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H; Chief Editor: Carmen Cuffari, MD   more...
 
Updated: Mar 9, 2010
 

Laboratory Studies

  • Serum bilirubin levels are elevated in virtually all patients with cholestasis.
  • Serum direct or conjugated bilirubin levels are elevated in virtually all cholestatic diseases and not in other diseases causing hyperbilirubinemia.
  • Total serum bile salt concentration levels are elevated in virtually all cholestatic diseases.
  • Qualitative serum and urine bile acids by mass spectroscopy are used to identify genetically determined errors in bile acid synthesis.
  • The total serum cholesterol level is elevated in virtually all obstructive cholestatic diseases, whereas the high-density lipoprotein (HDL) level is within the reference range or low. Total cholesterol is within the reference range in certain hepatocellular cholestatic diseases, whereas the HDL level is within the reference range or low.
  • Serum lipoprotein-X levels are elevated in virtually all obstructive cholestatic diseases.
  • Serum alkaline phosphatase levels are elevated in virtually all obstructive cholestatic diseases and most hepatocellular cholestatic diseases.
  • Serum 5'-nucleotidase levels are elevated in virtually all obstructive cholestatic diseases and most hepatocellular cholestatic diseases.
  • Serum gamma-glutamyl transferase (GGT) levels are elevated in virtually all obstructive cholestatic diseases and many hepatocellular cholestatic diseases. A small number of hepatocellular cholestatic diseases occur in which the GGT level is within the reference range or low (eg, progressive familial intrahepatic cholestasis, inborn errors of bile acid synthesis).
  • Fecal fat levels are elevated in virtually all cholestatic diseases.
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Imaging Studies

  • Ultrasonography of liver and bile ducts is used to identify anatomic causes of obstructive cholestasis (eg, choledochal cyst, gallstones).
  • Abdominal CT scanning is used to identify anatomic causes of obstructive cholestasis (eg, choledochal cyst, gallstones).
  • Biliary nuclear medicine study (ie, hepatoiminodiacetic acid [HIDA] scanning) is used to identify anatomic causes of obstructive cholestasis (eg, choledochal cyst, gallstones) and to differentiate between obstructive and hepatocellular cholestasis (ie, biliary atresia versus neonatal hepatitis).
  • Endoscopic retrograde cholangiography is used to identify anatomic causes of obstructive cholestasis (eg, choledochal cyst, gallstones).
  • Percutaneous transhepatic cholangiography is used to identify anatomic causes of obstructive cholestasis (eg, choledochal cyst, gallstones).
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Procedures

  • Liver biopsy is the single most useful test to determine the cause of cholestasis but requires a high degree of expertise in interpretation.
  • Exploratory surgery is a very useful tool for diagnosing neonatal cholestasis. Older literature suggested that exploratory surgery placed patients with neonatal hepatitis at risk, but this is not the case with modern anesthesia and surgical techniques.
    • If surgical disease is in question, initiate exploratory surgery to provide a definitive demonstration of bile duct anatomy.
    • In institutions with less experience and expertise, perform exploratory surgery more frequently, rather than less so.
  • Operative cholangiography is simple, straightforward, time-efficient, and definitive.
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Histologic Findings

  • Many histologic findings are disease specific; therefore, refer to articles about disease states (see Causes). The typical histopathologic features of hepatocellular cholestasis include the presence of bile within hepatocytes and canalicular spaces, in association with generalized cholate injury. Typical of obstructive cholestasis is bile plugging of the interlobular bile ducts, portal expansion, and bile duct proliferation in association with centrilobular cholate injury.
  • Differentiating between idiopathic neonatal hepatitis and biliary atresia is a diagnostic challenge. With expert evaluation, nothing contributes as much to that differential diagnosis as the findings on percutaneous liver biopsy.
  • The landmark 1974 paper of Brough and Bernstein demonstrated the diagnostic usefulness of the percutaneous liver biopsy.[6] In this study of 158 patients, the authors compared the original pathologic diagnosis to the ultimate diagnosis that included surgical findings and long-term follow-up. The original diagnosis was an error in 10 patients (6.3%), which makes biopsy an excellent diagnostic procedure. The type of error observed in these 10 patients was more important. In 9 of 10 misdiagnoses, the pathologic diagnosis was obstructive disease when the patient actually had neonatal hepatitis or alpha1-antitrypsin deficiency. This error led to exploratory surgery to confirm the diagnosis, which was of little harm to the patient. In only 1 patient with biliary atresia was the pathologic diagnosis that of hepatitis, which led to delay in the diagnosis of this surgical obstructive disease. Thus, in only 1 of 158 patients (0.6%) did a diagnostic error lead to meaningful clinical consequences.
  • Liver biopsy, therefore, has a very high sensitivity and specificity for the diagnosis of biliary atresia, with somewhat less specificity for the diagnosis of neonatal hepatitis.
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Contributor Information and Disclosures
Author

Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H  Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan

Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H is a member of the following medical societies: Royal College of Paediatrics and Child Health, Royal College of Physicians, Royal College of Surgeons in Ireland, Royal College of Surgeons of Edinburgh, and Royal Society of Tropical Medicine and Hygiene

Disclosure: Nothing to disclose.

Specialty Editor Board

Jayant Deodhar, MD  Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD  Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References

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Eruptive xanthomas. Courtesy of Duke University Medical Center.
 
 
 
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