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A Patient With Jaundice and Malaise

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 58-year-old woman with a history of intravenous heroin use and chronic inactive hepatitis B virus (HBV) infection with a low serum HBV DNA value, normal liver enzyme values, and no evidence of cirrhosis presented to the emergency department with sudden onset of painless jaundice and 8 days of malaise. Her last intravenous heroin use occurred 9 days prior to presentation. She was not taking any prescription or herbal medications and had not been prescribed suppressive antiviral medication for chronic HBV infection. She reported no history of travel outside the US and no raw meat ingestion. Her vital signs, mentation, and physical examination were normal except for scleral icterus (Figure). Results of blood testing were negative for hepatitis C virus RNA, anti–hepatitis A IgM, and HIV antibody. Other selected laboratory values are shown in the Table. A liver ultrasound performed 6 months prior to presentation and a repeat liver ultrasound with Doppler revealed no abnormalities.

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Hepatitis D superinfection

D. Order testing for hepatitis delta virus (HDV) IgM and IgG antibodies and, if positive, test for HDV RNA

The key to the correct diagnosis is recognition that the most likely cause of sudden-onset jaundice and newly elevated aminotransferase and bilirubin levels in a patient with intravenous drug use and chronic HBV infection without acute hepatitis A or C virus infection is HDV. Choice A is incorrect because HIV does not typically cause this level of aminotransferase and bilirubin elevation. Hepatitis E (choice B) is unlikely because the patient has never traveled outside the US and has not eaten raw meat. Anti–smooth muscle antibody testing (choice C) is helpful to diagnose autoimmune hepatitis, but this is not the most likely diagnosis in a patient with chronic HBV infection and intravenous drug use.

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Article Information

Corresponding Author: Brian L. Pearlman, MD, Wellstar Atlanta Medical Center, Center for Hepatitis C, 285 Boulevard NE, Ste 525, Atlanta, GA 30312 (Brianpearlman3@hotmail.com).

Published Online: June 13, 2022. doi:10.1001/jama.2022.8384

Conflict of Interest Disclosures: Dr Pearlman reported serving on the speakers bureau and an advisory board of Gilead Sciences for viral hepatitis–related topics. Gilead has a nonapproved medication in clinical trials for delta hepatitis.

Additional Contributions: We thank the patient for providing permission to share her information.

References
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Urban  S , Neumann-Haefelin  C , Lampertico  P .  Hepatitis D virus in 2021.   Gut. 2021;70(9):1782-1794. doi:10.1136/gutjnl-2020-323888PubMedGoogle ScholarCrossref
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Cheung  A , Kwo  P .  Viral hepatitis other than A, B, and C: evaluation and management.   Clin Liver Dis. 2020;24(3):405-419. doi:10.1016/j.cld.2020.04.008PubMedGoogle ScholarCrossref
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Buti  M , Homs  M , Rodriguez-Frias  F ,  et al.  Clinical outcome of acute and chronic hepatitis delta over time.   J Viral Hepat. 2011;18(6):434-442. doi:10.1111/j.1365-2893.2010.01324.xPubMedGoogle ScholarCrossref
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Da  BL , Heller  T , Koh  C .  Hepatitis D infection.   Gastroenterol Rep (Oxf). 2019;7(4):231-245. doi:10.1093/gastro/goz023PubMedGoogle ScholarCrossref
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Brancaccio  G , Fasano  M , Grossi  A , Santantonio  TA , Gaeta  GB .  Clinical outcomes in patients with hepatitis D, cirrhosis and persistent hepatitis B virus replication, and receiving long-term tenofovir or entecavir.   Aliment Pharmacol Ther. 2019;49(8):1071-1076. doi:10.1111/apt.15188PubMedGoogle ScholarCrossref
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Chen  HY , Shen  DT , Ji  DZ ,  et al.  Prevalence and burden of hepatitis D virus infection in the global population.   Gut. 2019;68(3):512-521. doi:10.1136/gutjnl-2018-316601PubMedGoogle ScholarCrossref
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Miao  Z , Zhang  S , Ou  X ,  et al.  Estimating the global prevalence, disease progression, and clinical outcome of hepatitis delta virus infection.   J Infect Dis. 2020;221(10):1677-1687. doi:10.1093/infdis/jiz633PubMedGoogle ScholarCrossref
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Mahale  P , Aka  PV , Chen  X ,  et al.  Hepatitis D viremia among injection drug users in San Francisco.   J Infect Dis. 2018;217(12):1902-1906. doi:10.1093/infdis/jiy157PubMedGoogle ScholarCrossref
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Terrault  NA , Lok  ASF , McMahon  BJ ,  et al.  Update on prevention, diagnosis, and treatment of chronic hepatitis B.   Hepatology. 2018;67(4):1560-1599. doi:10.1002/hep.29800PubMedGoogle ScholarCrossref
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Lok  AS , Negro  F , Asselah  T , Farci  P , Rizzetto  M .  Endpoints and new options for treatment of chronic hepatitis D.   Hepatology. 2021;74(6):3479-3485. doi:10.1002/hep.32082PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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