Recommendations are followed by quality of evidence ratings (Grades I, II-1, II-2, II-3, III), which are defined at the end of the "Major Recommendations" field.
Testing and Counseling
Testing
- Persons who should be tested for HCV infection (Grade III):
- Persons who have injected illicit drugs in the recent and remote past, including those who injected only once and do not consider themselves to be drug users
- Persons with conditions associated with a high prevalence of hepatitis C virus (HCV) infection, including:
- Persons with human immunodeficiency virus (HIV) infection
- Persons with hemophilia who received clotting factor concentrates before 1987
- Persons who were ever on hemodialysis
- Persons with unexplained abnormal aminotransferase levels
- Prior recipients of transfusions or organ transplants, including:
- Persons who were notified that they had received blood from a donor who later tested positive for HCV infection
- Persons who received a transfusion of blood or blood products before July 1992
- Persons who received an organ transplant before July 1992
- Children born to HCV-infected mothers
- Health care, emergency medical, and public safety workers after a needle stick injury or mucosal exposure to HCV-positive blood
- Current sexual partners of HCV-infected persons*
NOTE: Adapted from Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention MMWR Recomm Rep 1998;47(RR-19):1–39.
*Although the prevalence of infection is low, a negative test in the partner provides reassurance, making testing of sexual partners of benefit in clinical practice.
Counseling
- Persons infected with HCV should be counseled on how to avoid HCV transmission to others (refer to Table 3 in the original guideline document for more information) (Grade III).
Laboratory Testing
- Patients suspected of having chronic HCV infection should be tested for HCV antibodies (Grade II-2).
- HCV ribonucleic acid (RNA) testing should be performed in (a) patients with a positive anti-HCV test (Grade II-2); (b) patients for whom antiviral treatment is being considered, using a quantitative assay (Grade II-2); and (c) patients with unexplained liver disease whose anti-HCV test is negative and who are immune-compromised or suspected of having acute HCV infection (Grade II-2).
- HCV genotype should be determined in all HCV-infected persons prior to treatment in order to determine the duration of therapy and likelihood of response (Grade I).
- Regardless of the level of alanine aminotransferase (ALT), a liver biopsy should be done when the results will influence whether treatment is recommended, but a biopsy is not mandatory in order to initiate therapy (Grade III).
- A liver biopsy may be obtained to provide information on prognosis (Grade III).
Initial Treatment of HCV Infection
- The treatment of choice is pegylated interferon (peginterferon) plus ribavirin (Grade I).
- For patients for whom liver histology is available, treatment is indicated in those with more-than-portal fibrosis (Grade III).
- Treatment decisions should be individualized based on the severity of liver disease, the potential of serious side effects, the likelihood of treatment response, and the presence of comorbid conditions (Grade III).
Genotype-1 HCV Infection
- Treatment with peginterferon plus ribavirin should be planned for 48 weeks, using ribavirin doses of 1,000 mg for those <75 kg in weight and 1,200 mg for those more than 75 kg (Grade I).
- Quantitative serum HCV RNA should be performed at the initiation of, or shortly before, treatment and at week 12 of therapy (Grade I).
- Treatment may be discontinued in patients who do not achieve an early virologic response (EVR) at 12 weeks, although the decision should be individualized according to the tolerability of therapy, severity of underlying liver disease, and demonstration of some degree of biochemical and/or virologic response (Grades I, III).
- Persons whose treatment continues through 48 weeks, and whose qualitative measurement of HCV RNA at that time is negative, should be retested for HCV RNA 24 weeks later to document a sustained virologic response (SVR) (Grade II-1).
Genotype-2 or Genotype-3 HCV Infection
- Treatment with peginterferon plus ribavirin should be administered for 24 weeks, using a ribavirin dose of 800 mg (Grade I).
- Persons whose treatment continues for the full 24 weeks, and whose qualitative measurement of HCV RNA at that time is negative, should be retested for HCV RNA 24 weeks later to document an SVR (Grade II-1).
Retreatment of Persons Who Failed to Respond to Previous Treatment
- Retreatment with peginterferon plus ribavirin should be considered for nonresponders or relapsers who have significant fibrosis or cirrhosis and who have undergone previous regimens of treatment using nonpegylated interferon (Grade II-3).
- Retreatment with peginterferon plus ribavirin with the aim of eradicating HCV is not indicated in patients who have failed to respond to a prior course of peginterferon plus ribavirin, even if a different type of peginterferon is administered (Grade III).
Special Patient Groups
- Regardless of the serum aminotransferase levels, the decision to initiate therapy with interferon and ribavirin should be individualized based on the severity of liver disease by liver biopsy, the potential of serious side effects, the likelihood of response, and the presence of comorbid conditions (Grade III).
Diagnosis and Treatment of HCV-Infected Children
- Diagnosis and testing (including liver biopsy) of children suspected of having chronic HCV should proceed as with adults (Grade II-2).
- Because of the high rate of clearance of the HCV virus within the first year of life and the level of anxiety that may be caused by an early positive test, routine testing for HCV RNA in infants born to HCV-infected mothers is not recommended. Testing with anti-HCV may be performed at 18 months or later. If an earlier diagnosis is desired, PCR for HCV RNA may be performed at or after the infant's first well-child visit at 1 to 2 months (Grade I).
- Children aged 3-17 who are infected with hepatitis C and are considered appropriate candidates for treatment may receive therapy with interferon alfa-2b and ribavirin, administered by those experienced in treating children (Grades I, III).
- Treatment of children under the age of 3 years is contraindicated (Grade III).
Diagnosis, Natural History, and Treatment of Persons With HIV Coinfection
- Anti-HCV testing should be performed in all HIV-infected persons (Grade III).
- HCV RNA testing should be performed to confirm HCV infection in HIV-infected persons who are positive for anti-HCV, as well as in those who are negative and have evidence of unexplained liver disease (Grade III).
- Hepatitis C should be treated in the HIV/HCV-coinfected person in whom the likelihood of serious liver disease and a treatment response are judged to outweigh the risk of morbidity from the adverse effects of therapy (Grade III).
- Initial treatment of hepatitis C in most HIV-infected persons is peginterferon alfa plus ribavirin for 48 weeks (Grade III).
- Given the high likelihood of adverse events, HIV/HCV-coinfected patients on HCV treatment should be monitored closely (Grade III).
- Ribavirin should be used with caution in persons with limited myeloid reserves and in those taking zidovudine and stavudine. When possible, patients receiving didanosine should be switched to an equivalent antiretroviral before beginning therapy with ribavirin (Grade III).
- HIV-infected patients with decompensated liver disease may be candidates for orthotopic liver transplantation (Grade III).
Treatment of Persons With Renal Disease
- The decision to perform a liver biopsy in patients with renal disease should be individualized based on the clinical assessment of the need for therapy and the need to establish the severity of liver disease (Grade III).
- Eligible patients with renal insufficiency or end-stage renal disease and HCV may be treated with interferon (Grade II-2).
- Treatment with peginterferon alfa-2a monotherapy at a dose of 135 micrograms subcutaneously (SQ)/wk for patients on hemodialysis may be considered, with close monitoring for interferon toxicity. However, a firm recommendation regarding the use of peginterferon monotherapy must await results of ongoing controlled trials (Grade III).
- Patients with renal failure should not be treated with ribavirin (Grade II-2).
Treatment of Persons With Decompensated Cirrhosis
- Patients with clinically decompensated cirrhosis should be referred for consideration of liver transplantation (Grades I, III).
- Antiviral therapy may be initiated at a low dose in patients with mild degrees of hepatic compromise, as long as treatment is administered by experienced clinicians, with vigilant monitoring for adverse events, preferably in patients who have already been accepted as candidates for liver transplantation (Grade II-3).
- Growth factors can be used for treatment-associated anemia (epoetin) and leukopenia (G-CSF, GM-CSF) and may limit the need for antiviral dose reductions in patients with decompensated cirrhosis (Grade III).
Treatment of Patients After Solid Organ Transplantation
- Treatment of HCV-related disease following liver transplantation should be undertaken with caution because of the increased risk of adverse events and should be performed under the supervision of a physician experienced in transplantation (Grade II-2).
- Antiviral therapy is generally contraindicated in recipients of heart, lung, and kidney grafts (Grade III).
Treatment of Persons With Acute Hepatitis C
- The diagnosis of acute hepatitis C in patients with new-onset, unexplained liver disease should be confirmed by measuring HCV RNA in serum (Grade II-2).
- Although excellent results were achieved in reported uncontrolled studies using standard interferon monotherapy, it is appropriate to consider the use of peginterferon because of its improved ease of administration (Grade III).
- No recommendation can be made about the addition of ribavirin, and the decision will therefore need to be considered on a case-by-case basis (Grade III).
- In the absence of controlled study data, no definitive recommendations can be made about the timing of treatment initiation; however, it seems reasonable to delay treatment for 2 to 4 months after acute onset to allow for spontaneous resolution (Grade II-3).
- No definitive recommendation can be made about the duration of treatment needed to treat acute hepatitis C; however, it seems reasonable to continue treatment for at least 6 months (Grade II-3).
Treatment of Active Injection Drug Users
- Treatment of HCV infection should not be withheld from persons who currently use illicit drugs or who are on a methadone maintenance program, provided they wish to take HCV treatment and are able and willing to maintain close monitoring and practice contraception (Grade III).
- The decision of whether to treat should be made considering the anticipated risks and benefits for the individual (Grade III).
- Continued support from drug abuse and psychiatric counseling services is an important adjunct to treatment of HCV infection in persons who use illicit drugs (Grade III).
Definitions:
Quality of Evidence
Grade I: Randomized controlled trials
Grade II-1: Controlled trials without randomization
Grade II-2: Cohort or case-control analytic studies
Grade II-3: Multiple time series, dramatic uncontrolled experiments
Grade III: Opinions of respected authorities, descriptive epidemiology
