| Key Question | Level and Type of Evidencea | Overall Evidence for the Linkb | Findings |
|---|---|---|---|
| 1. Does screening for HCV reduce the risk for or rate of harm and premature death and disability? | None. | N/A | No direct evidence regarding benefits of screening in the general population. |
| 2. Can clinical or demographic characteristics identify a subgroup of asymptomatic patients at higher risk for infection? | II-3. Cross-sectional studies |
Good for persons with intravenous drug use, high-risk sexual behaviors, and transfusions prior to 1992. Fair for other risk factors. |
Intravenous drug use is the most important risk factor for HCV infection. High-risk sexual behaviors are another important risk factor. Transfusions prior to 1992 remain a risk factor. Other risk factors have inconsistent associations with HCV infection. No prospective study has applied a screening strategy in the general population and measured what proportion of patients was identified correctly. |
| 3. What are the test characteristics of HCV antibody testing? | Studies of diagnostic test characteristics. | Fair | Using viremia as the reference standard, sensitivity of third-generation ELISA testing appears to be 94% or higher. Limited data found a specificity of 97% or greater using viremia as the reference standard. |
| 4. What is the predictive value of a positive screening test, and what are the harms associated with screening for HCV infection? | II-3. Cross-sectional studies. |
Good for positive predictive values. Poor for harms. |
Large population-based studies found that the positive predictive value for viremia of positive results on ELISA with confirmatory positive results on RIBA was 73%-86%. There are almost no data on the harms of screening. |
| 5a. What are the test characteristics of the work-up for treatable disease? | One good systematic review. | Fair | Blood tests have only modest value in predicting fibrosis on liver biopsy. |
| 5b. In patients found to be positive for HCV, what proportion of patients would qualify for antiviral treatment? | II-3. Cohort studies and cross-sectional studies. |
Fair | 30-40% of patients referred for treatment received treatment. |
| 6. What are the harms associated with the work-up for active HCV disease? | II-2. Cohort studies |
Fair | In the highest-quality trial, the risk of major complications (bleeding, death, perforation) from liver biopsy was approximately 1%-2%, with mortality less than 0.3%. The risks may be lower in patients undergoing liver biopsy specifically for evaluation of HCV infection. |
| 7a. How well does antiviral treatment reduce the rate of viremia, improve transaminase levels, and improve histology? | I. Well-designed randomized clinical trials. |
Good | Newer treatments have achieved sustained virologic response rates of 54-60%. (54-60% with pegylated interferon + ribavirin) compared with older treatments. Trials were performed in patients referred for treatment. |
| 7b. How well does antiviral treatment improve health outcomes in asymptomatic patients with HCV infection? | I, II-2. Cohort studies and clinical trials. |
Fair | Limited data, primarily from Japan, has found improved clinical outcomes in patients receiving antiviral treatment. Data on long-term quality of life outcomes is sparse. |
| 7c. How well do counseling and immunizations improve outcomes in asymptomatic patients with HCV infection or prevent spread of disease? | II-3. Case-control and cross-sectional studies. |
Poor | There is insufficient evidence to estimate the effects of counseling or immunizations on intermediate or clinical outcomes. |
| 8. What are the harms (including intolerance to treatment) associated with antiviral intervention? | I. Well-designed randomized clinical trials. |
Good | Common adverse events with interferon-based therapy are self-limited influenza-like symptoms, which occur in 50%-60%. Major complications occur in 1%-2% of patients. Withdrawals due to adverse events occurred in 14%-22% of patients on pegylated interferon plus ribavirin combination therapy. |
| 9. Have improvement in intermediate outcomes been shown to reduce the risk or rate of harm from HCV infection? | II-2. Fair-quality cohort studies and clinical trials. |
Fair | There is some evidence that intermediate outcomes are associated with improved clinical outcomes, but methodologic concerns limit interpretation of this data. |
* ELISA = enzyme-linked immunoassay; HCV = hepatitis C virus; NA = not applicable; RIBA = recombinant immunoblot assay a Evidence codes are based on study design categories.35 I = evidence obtained from at least one properly randomized, controlled trial; II-1 = evidence obtained from well-designed controlled trials without randomization; ll-2 = evidence obtained from well-designed cohort or case-control analytic studies; ll-3 = evidence obtained from multiple time series or dramatic uncontrolled experiments. | |||