eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Hepatitis C: Differential Diagnoses & Workup

Author: Nicholas John Bennett, MBBCh, PhD, Staff Physician, Department of Pediatrics, State University of New York Upstate Medical University
Coauthor(s): Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University; Donald K Strickland, MD, National Liaison, Avastin, Genentech BioOncology
Contributor Information and Disclosures

Updated: Aug 12, 2008

Differential Diagnoses

Hepatitis A
Hepatitis B

Other Problems to Be Considered

Alcoholic liver disease
Drug toxicities
Opportunistic infections associated with HIV infection

Workup

Laboratory Studies

  • Both acute and chronic hepatitis C virus (HCV) infections are often asymptomatic; therefore, the diagnosis often relies on the identification of a potential risk factor and on subsequent screening for hepatitis C virus–directed antibodies.
  • Obtaining serum alanine aminotransferase (ALT) levels may be helpful.
    • Acute infections: The peak serum ALT level is less than 2000 IU/mL in most patients with acute hepatitis C virus infection, and 50% have a peak serum ALT level of less than 800 IU/mL. Overall, this peak is generally less than that of hepatitis A or hepatitis B infections.
    • Chronic infections: Many patients have normal serum ALT levels, although these levels may significantly fluctuate over time.
  • Hepatitis C virus–directed antibodies may be detected.
    • Acute infection: Antibodies are generally detectable approximately 6-8 weeks after exposure; however, as many as 5% of infected patients do not produce antibodies.
    • Chronic infection: Once present, antibodies generally persist.
    • Antibody screening using enzyme immunoassay (EIA) is inexpensive and reliable; generally, this is the screening test of choice for diagnosis. Recombinant immunoassay (RIBA) can then be used to confirm positive EIA results.
  • Hepatitis C virus RNA may be detected with the polymerase chain reaction (PCR) test. Several US Food and Drug Administration (FDA)–approved test kits that can be used for blood product screening or diagnostic testing are currently available. (Kits are not usually approved for both uses.)
    • Hepatitis C virus RNA is usually detectable within 1-2 weeks of exposure.
    • Quantitative assays are available, but hepatitis C viral load has not been definitively shown to be useful in predicting outcome (unlike HIV viral load).
    • PCR testing is useful to confirm positive EIA results in the setting of indeterminate RIBA test results and to distinguish between resolved and chronic hepatitis C virus infection in patients with positive EIA and RIBA results.
  • Other viral serologic tests may be useful in ruling out other causes of hepatitis, which can be present alone or in combination with hepatitis C virus.
    • Hepatitis A virus immunoglobulin M (IgM) and immunoglobulin G (IgG)
    • Hepatitis B virus surface antigen and antibody, core antibody
    • Cytomegalovirus (CMV) IgM and IgG (and/or CMV in urine cultures)
    • Epstein-Barr virus IgM and IgG
    • HIV IgG enzyme-linked immunoassay (ELISA)
  • Early work by one group suggests that alpha-fetoprotein may have a prognostic significance, at least for genotypes 1 and 4.2

Imaging Studies

  • These studies are not generally warranted to establish the etiology of hepatitis.
  • However, ultrasonography is useful to monitor for hepatitis C virus–related complications.

Procedures

  • Although liver biopsy is generally not used to diagnose hepatitis C virus, it is the most accurate method of evaluating the extent of hepatitis C virus–related liver disease.
  • Liver biopsy is recommended for all patients before they start antiviral therapy.

Histologic Findings

  • In patients with chronic hepatitis C virus infection, inflammatory cells accumulate in the portal tracts. They may also have foci of inflammation accompanied by necrosis in the parenchyma. Subsequently, the margins of the parenchyma and liver tracts become inflamed, and liver cell necrosis results.
  • Ultimately, if the infection progresses, inflammation and necrosis may lead to fibrosis.
    • Mild fibrosis is confined to the portal tracts and adjacent parenchyma, whereas severe fibrosis is associated with bridging between the portal tracts and hepatic veins.
    • Eventually, fibrosis can progress to cirrhosis, when the fibrous septa separate the liver into nodules.

More on Hepatitis C

Overview: Hepatitis C
Differential Diagnoses & Workup: Hepatitis C
Treatment & Medication: Hepatitis C
Follow-up: Hepatitis C
References
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References

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  2. Abdoul et al. Serum Alpha-Fetoprotein Predicts Treatment Outcome in Chronic Hepatitis C Patients Regardless of HCV Genotype. PLoS ONE. June 2008;3(6):[Medline]. [Full Text].

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  4. Arico M, Maggiore G, Silini E, et al. Hepatitis C virus infection in children treated for acute lymphoblastic leukemia. Blood. Nov 1 1994;84(9):2919-22. [Medline]. [Full Text].

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Further Reading

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Keywords

hepatitis C virus, HCV, HCV infection, infectious hepatitis, viral hepatitis, viral hepatitis type C, non-A/non-B hepatitis, Flaviviridae, portal hypertension, liver failure, hepatocellular carcinoma, HCC, cirrhosis, malaise, anorexia, jaundice, hepatomegaly, ascites, splenomegaly, spider nevi

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Contributor Information and Disclosures

Author

Nicholas John Bennett, MBBCh, PhD, Staff Physician, Department of Pediatrics, State University of New York Upstate Medical University
Nicholas John Bennett, MBBCh, PhD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University
Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Donald K Strickland, MD, National Liaison, Avastin, Genentech BioOncology
Donald K Strickland, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Leonard R Krilov, MD, Chief of Pediatric Infectious Diseases, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital
Leonard R Krilov, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Medimmune Grant/research funds Cliinical trials; Medimmune Honoraria Speaking and teaching; Medimmune Consulting fee Consulting

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota School of Medicine
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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