eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Hepatitis C: Treatment & Medication
Updated: Aug 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
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
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.
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.
Interferon alfa-2b (Intron A)
Protein 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
3 million IU SC 3 times/wk for 12 mo
Pediatric
3 million IU/m2 SC 3 times/wk administered with ribavirin (Rebetol)
Theophylline 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
Documented hypersensitivity; history of anaphylactic sensitivity to mouse IgG, egg protein, or neomycin; autoimmune hepatitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Acute 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
Ribavirin (Rebetol, Copegus)
Inhibits 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
Copegus: (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
Rebetol: (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)
Inhibits 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
Documented hypersensitivity; significant or unstable cardiac disease; autoimmune hepatitis; hemoglobinopathies (eg, thalassemia major, sickle-cell anemia)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution 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
Peginterferon alfa-2a (Pegasys) and alfa-2b (PEG-Intron)
Used 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
Alfa-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
Not established
Theophylline 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
Documented hypersensitivity; decompensated liver disease; significant preexisting psychiatric disease; autoimmune hepatitis; pancreatitis; colitis; ongoing or recent alcohol use; platelet count <70,000/µL
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Pregnancy 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
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| Overview: Hepatitis C |
| Differential Diagnoses & Workup: Hepatitis C |
 Treatment & Medication: Hepatitis C |
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References
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Further Reading
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
