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AUTHOR AND EDITOR INFORMATION

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Author: Nicholas John Bennett, MBBCh, PhD, Staff Physician, Department of Pediatrics, State University of New York Upstate Medical University

Nicholas John Bennett is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics

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

Editors: Leonard R Krilov, MD, Chief of Pediatric Infectious Diseases, Vice Chair, Department of Pediatrics, Professor of Pediatrics, Winthrop University Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine; 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; 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; 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

Author and Editor Disclosure

Synonyms and related 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


INTRODUCTION

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Background

Hepatitis C virus (HCV) is one of 6 viruses (along with hepatitis A, B, D, E, and G viruses) that cause viral hepatitis. Prior to identification of the virus, it was termed non-A/non-B hepatitis to distinguish it from the viral causes of nonalcoholic hepatitis that were known at the time.

Several distinct genotypes of hepatitis C virus have been identified, and genotyping has proven to be a useful clinical tool because the response to therapy and prognosis is influenced by the viral genotype. Genotype 1 is less than half as likely as other genotypes to respond to therapy, and the combination therapy regimens vary depending on the different genotypes (see Medication).

Unfortunately, most patients have chronic infection and are at risk for progressive liver disease. Furthermore, diagnosis primarily relies on identifying the risk factors of transmission because infected individuals typically have few or no symptoms. Once hepatitis C virus infection is diagnosed, current treatment options for eradication are limited and often result in significant adverse effects.

Although hepatitis C virus infection is uncommon in the pediatric population, the caregiver should be familiar with the basic concepts. For example, patients transfused as recently as July 1992 may have been exposed to the virus. Furthermore, vertical transmission of hepatitis C virus is possible. Most studies performed to further delineate the natural history have involved adult cohorts; therefore, further research on the ultimate outcome of infection during childhood is clearly needed.

Pathophysiology

Hepatitis C virus is a member of the Flaviviridae family of RNA-containing viruses; thus, it is not integrated into the host genome. Although the liver is the primary target of infection, studies to better define the steps of hepatitis C virus infection are greatly hampered by the lack of a suitable animal model for such studies (the only animal known to be susceptible to hepatitis C virus is the chimpanzee). A tissue-culture system using recombinant DNA technology was recently developed and has advanced the scientific knowledge base considerably, including early forays into vaccine development.

The primary immune response to hepatitis C virus is mounted by cytotoxic T lymphocytes. Unfortunately, this process fails to eradicate infection in most people; in fact, it may contribute to liver inflammation and, ultimately, tissue necrosis. The ability of hepatitis C virus to escape immune surveillance is the subject of much speculation. One likely means of viral persistence relies on the presence of closely related but heterogeneous populations of viral genomes. Further studies of these quasi-species enable classification of several genotypes and subtypes, which may have clinical implications.

Frequency

United States

An estimated 30,000 new infections occur annually, although only 25-30% are diagnosed. Since the 1980s, acute infections have declined by more than 80%. Nearly 4 million Americans, or about 2% of the US population, are infected with hepatitis C virus.

International

Although the worldwide prevalence varies considerably by geographic region, more than 3% of the global population is infected.

Mortality/Morbidity

  • Acute fulminate infection is rare. More than 80% of acutely infected patients have chronic hepatitis C virus. Annually, it accounts for 8,000-10,000 deaths in the United States.
  • In more than 20% of adults with chronic infection, progression to cirrhosis occurs an average of 20 years after initial infection. Patients with this condition have a secondary risk of portal hypertension, liver failure, and other complications. Hepatitis C is now the leading reason for liver transplantation in the United States.
  • In 1-5% of patients, most of whom have underlying cirrhosis, hepatocellular carcinoma (HCC) is diagnosed an average of 30 years after initial hepatitis C virus infection.

Race

  • With respect to the frequency of infection worldwide, significant racial differences are observed.
  • In the United States, infection is more common among members of minority populations than in other groups.
  • The effect of ethnic background on the risk of significant liver disease is undefined.

Sex

  • Hepatitis C virus infection is far more common in males than in females.
  • Females have been reported to have a higher rate of infection from blood product transfusions and a lower rate of intravenous drug and alcohol abuse compared with males.
  • Females may have less evidence of liver damage (liver enzyme levels, fibrosis) and high rates of spontaneous viral clearance.1

Age

  • In the United States, the highest incidence is among individuals aged 20-39 years, and the highest prevalence is among those aged 30-49 years.
  • The age at time of initial infection likely has important implications on the natural history of infection because individuals who are infected at a younger age tend to have a decreased risk of progression to cirrhosis and HCC.


CLINICAL

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History

  • The incubation period widely varies, with a mean of 7-10 weeks and a range of 2-20 weeks.
  • Infections are often inapparent or subclinical. Only 25-35% of patients have nonspecific symptoms such as weakness, malaise, and anorexia; likewise, patients with chronic hepatitis C virus (HCV) often have few or no symptoms. Fatigue is reported most often.

Physical

  • Approximately 25% of patients with acute infection have jaundice, whereas less than one third have hepatomegaly.
  • Some patients with chronic infection have findings consistent with chronic liver disease; these include hepatomegaly, ascites, splenomegaly, and spider nevi.

Causes

  • Direct percutaneous exposure is the primary means of transmission.
  • Blood transfusions are another means of transmission.
    • Historically, most hepatitis C virus infections result from blood transfusions.
    • The risk of transfusion-borne hepatitis C virus began to decline in 1986, when surrogate-marker screening of blood donors started.
    • Further declines were noted after the introduction of hepatitis C virus–directed antibody screening in 1990 (first generation) and 1992 (second generation).
    • The current risk of transfusion-derived hepatitis C virus is estimated to be 1 case in every 100,000 units transfused.
  • Currently, the use of injected drugs is the most important epidemiologic risk factor, probably accounting for around 50% of both acute and chronic infections.
  • Other parenteral routes may be involved.
    • Hemodialysis is a possible cause of hepatitis C virus infection.
    • Health care employees may be accidentally exposed.
    • Tattooing, body piercing, and acupuncture with unsterile equipment are possible routes of infection.
  • The risk of sexual transmission appears to be low, even among individuals with multiple sex partners; however, the presence of coexisting sexually transmitted diseases (eg, human immunodeficiency virus [HIV] infection) appears to increase the risk.
  • Vertical transmission may occur.
    • Perinatal transmission is possible and affects an estimated 5% of babies born to mothers with hepatitis C virus infection.
    • The risk is higher for babies born to mothers who are co-infected with hepatitis C virus and HIV.
    • Breastfeeding is not contraindicated for mothers with hepatitis C virus infection.
  • Approximately 10% of adults with hepatitis C virus infection have no identified risk factor for infection; this frequency is probably higher among pediatric patients.


DIFFERENTIALS

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Hepatitis A
Hepatitis B

Other Problems to be Considered

Alcoholic liver disease
Drug toxicities
Opportunistic infections associated with HIV infection


WORKUP

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Lab 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.


TREATMENT

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Medical Care

  • Acute infection
    • Supportive care is the mainstay of treatment.
    • Early initiation of antiviral therapy is not defined.
  • Chronic infection
    • The goal is to identify complications and suitable candidates for antiviral therapy.
    • The purpose is to ameliorate symptoms and reduce the risk of progressive liver disease.
    • Long-term monitoring is essential because the risk of liver cancer is still high, even in sustained virologic responders.3

Surgical Care

  • Consider liver transplantation in patients with advanced liver disease.
  • Surgical intervention may be necessary for complications such as portal hypertension and HCC.

Consultations

  • Consultation with a gastroenterologist may be indicated.

Diet

  • No special diet is required; however, instruct the patient to avoid alcohol use.

Activity

  • No activity modifications are required.


MEDICATION

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Alpha interferon (IFN) results in a sustained response in fewer than 20% of patients, and adverse effects are often problematic. More recently, the addition of oral ribavirin to IFN therapy has improved the sustained response rate to 40-50%. Some research suggests that the dose of interferon might be lowered in genotypes 2 and 3, if ribavarin is used in combination. However, adverse effects remain a problem, and the response rate is lower for individuals infected with genotype 1, the most common genotype that causes infection, and the less common genotype 4.

Pegylated IFN (the addition of polyethylene glycol to the drug) results in significantly higher rates of response, especially with non–genotype 1 hepatitis C virus (HCV) infections.

Drug Category: Antiviral agents

IFNs are synthetically derived from a class of proteins that is produced and released by cells after viral invasion. They stimulate the production of another protein that inhibits viral replication. The nucleoside analogue ribavirin has some antiviral activity against hepatitis C virus, although improvements are not typically sustained after monotherapy is discontinued. However, the use of ribavirin in combination with IFN alpha is more effective than either drug alone and provides sustained responses.

Drug NameInterferon alfa-2b (Intron A)
DescriptionProtein product manufactured with recombinant DNA technology. Mechanism of antiviral activity is not clearly understood. However, modulation of host immune responses enhances cytolytic T-cell activity; stimulates natural killer cell activity and amplifies HLA class I protein on infected cells. Direct antiviral activity activates viral ribonucleases, inhibits viral entry to cells, and inhibits viral replication. Direct antifibrotic effect has been postulated.
Prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cells, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 4 mo, discontinue treatment. If a response occurs (as measured by clinical improvement, a reduction in HCV viral load, or histologic improvement on liver biopsy), continue treatment until no further improvement is observed. Whether continued treatment after that time is beneficial remains unknown. Some studies have some salvage regimens with PEG-IFN to be of benefit.
Adult Dose3 million IU SC 3 times/wk for 12 mo
Pediatric Dose3 million IU/m2 SC 3 times/wk administered with ribavirin (Rebetol)
ContraindicationsDocumented hypersensitivity; history of anaphylactic sensitivity to mouse IgG, egg protein, or neomycin; autoimmune hepatitis
InteractionsTheophylline may increase IFN alpha toxicity by reducing its clearance; cimetidine may increase the antitumor effects of IFN alpha; zidovudine and vinblastine may increase IFN alpha toxicity
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAcute hypersensitivity reactions are rare; may exacerbate psoriasis; do not use different brands in one treatment regimen; may exacerbate preexisting psychiatric conditions, particularly major depression; rare GI hemorrhage (may be severe); bone marrow suppression; before initiating therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor patient periodically (eg, monthly) during treatment to determine response to treatment

Drug NameRibavirin (Rebetol, Copegus)
DescriptionInhibits viral replication by inhibiting DNA and RNA synthesis. Administer as combination therapy with IFN alpha-2b. Ribavirin may potentiate the effects of IFN alpha, improving sustained-response rates with HCV. Rebetron is a kit that contains ribavirin and IFN alpha-2b for the treatment of HCV.
Adult DoseCopegus: (administer with peginterferon alfa-2a)
Note: Dose based on genotype
Genotype 1/4:
<75 kg: 1000 mg/d PO divided bid with meals for 48 wk
>75 kg: 1200 mg/d PO divided bid with meals for 48 wk
Genotype 2/3: 800 mg/d PO divided bid with meals for 24 wk

Rebetol: (administered with peginterferon alfa-2b)
400 mg PO bid with meals
Rebetol: (administered with IFN alfa-2b)
<75 kg: 400 mg PO every am and 600 mg PO every pm
>75 kg: 600 mg PO bid

Pediatric DoseRebetol: (administer with IFN alfa-2b)
<3 years: Not established
>3 years:
<25 kg and unable to swallow capsules: 15 mg/kg/d PO divided bid with meals
25-36 kg: 200 mg PO bid
37-49 kg: 200 mg PO every am and 400 mg PO every PM
50-61 kg: 400 mg PO bid
>61 kg: Administer as in adults 
Treatment duration is 24 wk (genotype 2/3 virus) or 48 wk (genotype 1 virus)
ContraindicationsDocumented hypersensitivity; significant or unstable cardiac disease; autoimmune hepatitis; hemoglobinopathies (eg, thalassemia major, sickle-cell anemia)
InteractionsInhibits stavudine and zidovudine phosphorylation, thereby decreasing effect; coadministration with didanosine is not recommended because of reports of fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactemia and lactic acidosis
PregnancyX - Contraindicated; benefit does not outweigh risk
PrecautionsCaution in preexisting anemia, bone marrow suppression, renal failure, ischemic heart disease, cerebral vascular disease; decrease dose with hemoglobin <10 g/dL or decrease of 2 g/dL within 4 wk; discontinue with hemoglobin <8.5 g/dL or CrCl <50 mL/min

Drug NamePeginterferon alfa-2a (Pegasys) and alfa-2b (PEG-Intron)
DescriptionUsed in combination with ribavirin to treat patients with chronic HCV infection who have compensated liver disease and have not previously received IFN alfa. Consists of IFN alfa-2a attached to a 40-kD branched PEG molecule (alfa-2b has a smaller 12-kD PEG molecule and is made from IFN alpha-2b). Predominantly metabolized by the liver.
Several recent small clinical trials have shown that PEG-IFN used in combination with ribavirin is superior to standard IFN therapy. Which populations these recommendations can be extended to (the trials involved mostly HIV/HCV co-infected individuals) and whether alfa-2a is better than alfa-2b or vice versa is not yet clear.
Adult DoseAlfa-2a (Pegasys): 180 mcg SC qwk for monotherapy or combined with ribavirin
Alfa-2b (PEG-Intron):
Monotherapy: 1 mcg/kg/wk SC for 1 y
Combined with oral ribavirin: 1.5 mcg/kg/wk SC for 1 y
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; decompensated liver disease; significant preexisting psychiatric disease; autoimmune hepatitis; pancreatitis; colitis; ongoing or recent alcohol use; platelet count <70,000/µL
InteractionsTheophylline may increase toxicity by reducing clearance; cimetidine may increase the antitumor effects; zidovudine and vinblastine may increase toxicity; concurrent administration with interleukin-2 may increase nephrotoxicity
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsPregnancy category X when combined with ribavirin
Alfa-2a: Insomnia; mental dysfunction (eg, mood dysfunction, depression, psychosis, aggressive behavior, hallucinations, violent behavior, suicidal ideation, suicide attempt, suicide, homicidal ideation [rare]), even without previous history of psychiatric illness; flulike symptoms; rash and pruritus; anorexia; neutropenia; thrombocytopenia; thyroid dysfunction; retinal abnormalities
Alfa-2b: Considered to have abortifacient potential; reduce starting dose by 50% or discontinue if serious adverse reactions develop during course of treatment (may reinitiate treatment if adverse reaction abates or decreases in severity); fatal and nonfatal pancreatitis or ulcerative and hemorrhagic colitis reported; life-threatening or fatal neuropsychiatric events may occur; severe suppression of bone marrow function may occur, which occasionally results in severe cytopenias; may cause headache and flulike symptoms and myelosuppressive, pulmonary, thyroid, cardiovascular, or infectious disorders


FOLLOW-UP

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Further Inpatient Care

  • Usually, inpatient care is necessary only if complications of chronic hepatitis C virus (HCV) infection, such as portal hypertension and HCC, are present.

Further Outpatient Care

  • Perform ongoing studies to monitor the status of hepatitis C virus infection.
    • Serum ALT levels have no consistent relationship to liver histologic findings.
    • Longitudinal assessment of hepatitis C virus RNA provides a strong correlation with liver histologic results but is a weaker predictor of rate of progression.
    • The prothrombin time is useful for assessing liver function.
    • The serum alpha-fetoprotein assay is a potential screening test for HCC.
    • Ultrasonography is potentially useful to monitor for hepatitis C virus–related complications such as portal hypertension and HCC.
  • Identify suitable candidates for antiviral therapy, although all patients with chronic infection are potential candidates.
    • Treatment is recommended for patients with chronic infection who have a persistently elevated serum ALT level, portal or bridging fibrosis, and at least moderate inflammation and necrosis at liver biopsy.
    • Consider treatment for other patients on an individual basis. Do not treat patients with decompensated cirrhosis by using antiviral therapy.
  • Perform immunization against hepatitis A virus and hepatitis B virus.

Deterrence/Prevention

  • No vaccine has been developed for hepatitis C virus.
  • Discourage users of intravenous drugs from sharing needles.
  • Adhere to universal precautions.
  • Infected patients with multiple partners should use barrier protection during sex. No special precautions are needed for monogamous relationships.
  • Instruct the patient not to share personal care articles such as toothbrushes or razors.
  • Blood, organ, or sperm donation from patients with hepatitis C virus infection is not permitted.

Complications

  • Fulminant hepatitis (rare)
  • Cirrhosis, which may result in portal hypertension and liver failure
  • Hepatocellular carcinoma
  • Extrahepatic manifestations
    • Porphyria cutanea tarda
    • Sialadenitis resembling Sjögren syndrome
    • Mooren corneal ulcers, a form of chronic ulcerative keratitis
    • Type II cryoglobulinemia
    • Membranoproliferative glomerulonephritis
    • Non-Hodgkin lymphoma

Prognosis

  • Most patients chronically infected with hepatitis C virus remain asymptomatic and do not have significant liver disease.
  • The prognosis is guarded for those who have hepatitis C virus–related complications such as HCC and liver failure.

Patient Education


MISCELLANEOUS

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Special Concerns

  • For individuals exposed to hepatitis C virus (HCV), passive immunization is not recommended.
  • Screen patients for hepatitis C virus infection if any of the following applies:
    • History of illegal injected drug use
    • Transfusion with clotting factor concentrates before 1987
    • Use of blood or blood components or organ transplants before July 1992
    • Use of hepatitis C virus–contaminated blood from a donor
    • Individuals on long-term hemodialysis or those who have persistently abnormal serum ALT levels
    • Needle sticks, accidents with sharps, or mucosal exposures to hepatitis C virus–positive blood
  • Considering hepatitis C virus testing in patients with HIV may be prudent, especially in those who acquired HIV through intravenous drug use. Hepatitis C virus is more easily transmitted than HIV, and the 2 viruses are often co-infections.


REFERENCES

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  1. Narciso-Schiavon et al. Anti-hepatitis C virus-positive blood donors: are women any different?. Transfus Med. Jun 2008;18(3):175-83. [Medline].
  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].
  3. Scherzer et al. Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C. J Viral Hepat. Jul 2008;[Medline].
  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].
  5. Cesaro S, Petris MG, Rossetti F, et al. Chronic hepatitis C virus infection after treatment for pediatric malignancy. Blood. Aug 1 1997;90(3):1315-20. [Medline]. [Full Text].
  6. Conry-Cantilena C, VanRaden M, Gibble J, et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med. Jun 27 1996;334(26):1691-6. [Medline]. [Full Text].
  7. Donahue JG, Munoz A, Ness PM, et al. The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med. Aug 6 1992;327(6):369-73. [Medline].
  8. Elmowalid GA, Qiao M, Jeong SH, Borg BB, Baumert TF, Sapp RK, et al. Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. Proc Natl Acad Sci. May 2007;e-pub ahead of print:[Medline]. [Full Text].
  9. FDA. Donor Screening Assays for Infectious Agents and HIV Diagnostic Assays (Includes serologic and nucleotide tests for screening, diagnosis and quantitative analysis). FDA. Available at http://www.fda.gov/cber/products/testkits.htm.
  10. Hartman C, Berkowitz D, Rimon N, Shamir R. The effect of early treatment in children with chronic hepatitis. J Pediatr Gastroenterol Nutr. Sep 2003;37(3):252-7. [Medline].
  11. Heller T, Saito S, Auerbach J, et al. An in vitro model of hepatitis C virion production. Proc Natl Acad Sci U S A. Feb 15 2005;102(7):2579-83. [Medline]. [Full Text].
  12. Jacobson IM, Gonzalez SA, Ahmed F, et al. A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C. Am J Gastroenterol. Nov 2005;100(11):2453-62. [Medline]. [Full Text].
  13. Locasciulli A, Testa M, Pontisso P, et al. Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia. Blood. Dec 1 1997;90(11):4628-33. [Medline].
  14. Lucidarme D, Dumas F, Arpurt JP, et al. [Rapid progress of cirrhosis in hepatitis C: the role of age at the time of viral contamination]. Presse Med. Apr 4 1998;27(13):608-11. [Medline].
  15. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C: Hepatitis Interventional Therapy Group. N Engl J Med. Nov 19 1998;339(21):1485-92. [Medline]. [Full Text].
  16. NIH. Management of hepatitis C. NIH Consens Statement. Mar 24-26 1997;15(3):1-41. [Medline].
  17. Paul IM, Sanders J, Ruggiero F, et al. Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease. Blood. Jun 1 1999;93(11):3672-7. [Medline]. [Full Text].
  18. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. Mar 22 1997;349(9055):825-32. [Medline].
  19. Shepherd J, Brodin H, Cave C, et al. Pegylated interferon alpha-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation. Health Technol Assess. Oct 2004;8(39):iii-iv, 1-125. [Medline]. [Full Text].
  20. Sook-Hyang Jeong, Ming Qiao, Michelina Nascimbeni, Zongyi Hu, Barbara Rehermann, Krishna Murthy, et al. Immunization with Hepatitis C Virus-Like Particles Induces Humoral and Cellular Immune Responses in Nonhuman Primates. J Virol. July 2004;78(13):6995-7003. [Medline]. [Full Text].
  21. Villano SA, Vlahov D, Nelson KE, et al. Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology. Mar 1999;29(3):908-14. [Medline].
  22. Vogt M, Lang T, Frosner G, et al. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med. Sep 16 1999;341(12):866-70. [Medline]. [Full Text].
  23. WHO. Hepatitis C: global prevalence. Wkly Epidemiol Rec. Nov 14 1997;72(46):341-4. [Medline].

Hepatitis C excerpt

Article Last Updated: Aug 12, 2008