Roger Chou, M.D.;a, b, c Elizabeth C. Clark, M.D., M.P.H.;a, c Mark Helfand, M.D., M.P.H.a, d, e, f
The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Address correspondence to: Roger Chou, M.D., 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239; E-mail: chour@ohsu.edu.
Select for copyright information. The USPSTF recommendations based on this review are online.
The summaries of the evidence briefly present evidence of effectiveness for preventive health services used in primary care clinical settings, including screening tests, counseling, and chemoprevention. They summarize the more detailed Systematic Evidence Reviews, which are used by the U.S. Preventive Services Task Force (USPSTF) to make recommendations.
Abstract
Introduction
Methods
Results
Discussion
Acknowledgments
References
Notes
Appendix
Background: Hepatitis C virus (HCV) is the most common bloodborne pathogen in the United States and is an important cause of patient morbidity and mortality, but it is unclear whether screening to identify asymptomatic infected persons is appropriate.
Purpose: To synthesize the evidence on risks and benefits of screening for HCV infection.
Data Sources: MEDLINE® (through February 2003), Cochrane Clinical Trials Registry (2002, Issue 2), reference lists, and experts.
Study Selection: Controlled studies of screening and antiviral therapy and observational studies on other interventions, risk factors, accuracy of antibody testing, work-up, harms of biopsy, and outcomes.
Data Extraction: Using preset criteria, the authors assessed the quality of included studies and abstracted information about settings, patients, interventions, and outcomes.
Data Synthesis: There are no published trials of screening for HCV infection. Approximately 2 percent of U.S. adults have HCV antibodies, with the majority having chronic infection. Risk factor assessment could identify adults at substantially higher risk. Antiviral treatment can result in a sustained virologic response rate of 54 percent to 56 percent, but no trials have been done specifically in asymptomatic patients likely to be identified by screening. Data are insufficient to determine whether treatment improves long-term outcomes. There are no data to estimate the benefit from counseling or immunizations. Although risks of biopsy and treatment appear minimal or self-limited, data on other adverse effects of screening, such as labeling or anxiety, are sparse.
Conclusions: Antiviral treatment can successfully eradicate HCV, but data on long-term outcomes in populations likely to be identified by screening are lacking. Although the yield from targeted screening, particularly in intravenous drug users, would be substantially higher than in the general population, data are inadequate to accurately weigh the overall benefits and risks of screening in otherwise healthy, asymptomatic adults.
Hepatitis C virus (HCV), the most common chronic bloodborne pathogen in the United States, is acquired primarily by large or repeated percutaneous exposures to blood.1 In the United States, approximately 2.3 percent of adults 20 years of age or older are positive for anti-HCV-antibody. Between 55 percent and 84 percent of these have chronic infection,1-6 but only 5 percent to 50 percent of infected adults are thought to know their status.7-9
In the United States, HCV is associated with approximately 40 percent of cases of chronic liver disease and 8,000 to 10,000 deaths each year.1 Chronic HCV infection can also cause fatigue and decreased quality of life in the absence of cirrhosis or other complications.5,10,11
The natural course of chronic HCV infection varies. Some patients never develop histologic evidence of liver disease even after decades of infection.12,13 In a meta-analysis of community-based cohort studies, 7 percent of patients with chronic HCV infection developed cirrhosis after 20 years.14 Factors that may be associated with a more progressive course include older age at acquisition;14,15 comorbid medical conditions, such as heavy alcohol use,14,16-21 HIV infection,22-24 and other chronic liver disease;25-27 male gender;14 and longer duration of infection. Mode of acquisition, viral load, aminotransferase levels, and viral genotype have not been consistently established as predictors of disease progression.28-31 The effects of ethnicity on the course of HCV infection have not been well studied in the United States.32
In this systematic review, commissioned by the USPSTF, we focus on whether it is useful to test for anti-HCV antibodies in asymptomatic adults who have no history of liver disease.
The analytic framework, definitions used, key questions, literature search, and data extraction methods are described in detail in the Appendix (available at www.annals.org). Briefly, relevant studies were identified from searches of MEDLINE® (1989 through February 2003) and the Cochrane Clinical Trials Registry (2002, Issue 2) and from the reference list of a recent evidence report commissioned by the National Institutes of Health.33 Reference lists of retrieved articles, periodic hand searches of relevant journals, and suggestions from experts supplemented the electronic searches.
Two readers reviewed all English-language abstracts. We selected studies that provided direct evidence on the benefits of screening and studies on risk factors for HCV infection and the performance of third-generation HCV enzyme-linked immunoassay (ELISA) alone or followed by confirmatory recombinant immunoblot assay (RIBA). We focused on third-generation ELISAs because they are thought to be slightly more sensitive than second-generation tests, but included data on second-generation ELISAs from large, good-quality observational studies.34 We also selected studies evaluating noninvasive methods to evaluate active HCV infection and the harms associated with biopsy. For treatment, we focused on trials of pegylated interferon with ribavirin but included studies that examined the effect of other interferon-based treatment regimens on long-term clinical outcomes. We also reviewed studies evaluating effects of counseling on high-risk behaviors and benefits of immunizations. Good-quality meta-analyses were reviewed when available.
We excluded studies of pregnant patients; children; and patients with occupational exposures, end-stage renal disease, or HIV infection, as well as studies focusing on patients who had already developed complications of chronic HCV infection.
We used predefined criteria developed by the USPSTF, described in detail elsewhere,35 to assess the internal validity of included studies, which we rated as "good," "fair," or "poor." We also rated the applicability of each study to the population likely to be identified by screening. We rated the overall body of evidence for each key question using the system developed by the USPSTF.35
This research was funded by the Agency for Healthcare Research and Quality under a contract to support the work of the USPSTF. Agency staff and Task Force members participated in the initial design of the study and reviewed interim analyses and the final manuscript. Additional reports were distributed for review to content experts and revised accordingly.36 Agency approval was required before this manuscript could be submitted for publication, but the authors are solely responsible for the content and the decision to submit it.
We identified no randomized trials or longitudinal cohort studies comparing outcomes between patients in the general adult population who were screened and not screened for HCV infection.
The identification of risk factors for the presence of HCV infection could aid in the development of selective screening strategies.8 We identified 4 large population-based studies from the United States and Europe that evaluated rates of HCV infection and risk factors associated with HCV status.2,3,37,38 Among these, the National Health and Nutrition Examination Survey III (NHANES III), a good-quality nationwide sample of U.S. households that was conducted from 1988 to 1994 and had 21,241 participants, found that the prevalence of positivity for anti-HCV antibodies was 1.8 percent overall, and 2.3 percent in adults older than 20 years of age.3 Although NHANES III provides the most reliable estimate of prevalence of HCV infection in U.S. households, it probably underestimates the overall prevalence of disease because it excluded persons without addresses, institutionalized persons, and those in military service.
Independent risk factors for HCV infection found in the 4 large population-based studies are shown in Table 1.2,3,37,38 Intravenous drug use was the strongest independent risk factor (adjusted odds ratios, 18.4-29.2) in 3 of these studies. The fourth study, NHANES III, did not assess for intravenous drug use. However, it found that cocaine and marijuana use were associated with HCV infection, perhaps because they are surrogate markers for intravenous drug use (Table 1).3 Many other smaller cross-sectional studies in a variety of specific populations support the strong association between HCV infection and intravenous drug use.39-51 Cross-sectional studies in intravenous drug users have reported prevalence rates ranging from 50 percent to more than 90 percent.52-56
All 4 large population-based studies also found an independent association between HCV infection and high-risk sexual behaviors (variably defined, but usually considered sex with multiple partners or sex with an HCV-infected person). In most settings with a low prevalence of intravenous drug use, high-risk sexual behaviors are the strongest risk factor for HCV infection.56-60 It is not clear whether this association is due to a high rate of sexual transmission in specific situations61-66 or because high-risk sexual behaviors are a marker for unacknowledged drug use.
Since 1992, transfusions have not been an important mode of HCV transmission.56,67,68 There is insufficient evidence to determine the importance of tattoos, body piercings, shared razors, and acupuncture as risk factors.2,67,69-75 Non-percutaneous risk factors such as gender, ethnicity, and socioeconomic status have inconsistent or weak associations with the prevalence of HCV infection.3,38,76
In large U.S. cross-sectional studies, between 33 percent and 81 percent of patients with HCV infection reported intravenous drug use.38-40,77 Other retrospective studies have found that 53 percent to 88 percent of infected patients had identifiable risk factors.78,79 Sample differences, varying stringency of risk factor ascertainment, or variation in the risk factors examined could explain some of the discrepancies between studies.79 No study has prospectively applied a selective screening strategy and determined how many patients were correctly identified by it.
The terminology and interpretation of tests used to diagnose HCV infection are reviewed in the Appendix.
A recent fair-quality systematic review of third-generation ELISA (7 studies) and RIBA (3 studies) found that only 10 of 150 studies used appropriate methods for evaluating a diagnostic test.80 We applied the USPSTF quality criteria to 9 of these 10 studies and found that all 9 had at least 1 important flaw: inclusion of a narrow patient spectrum, failure to perform a reference standard test in all samples, or lack of clarity about whether the reference standard test was interpreted independently of the screening test.81-86 The tenth study, a study of RIBA in 51 patients receiving hemodialysis, was not referenced in the systematic review and we could not find it.
Of 7 studies that evaluated the sensitivity of third-generation ELISA and involved 4,674 patients, sensitivity ranged from 97.2 percent to 100 percent compared with the results of polymerease chain reaction (PCR) (a reference standard for active infection) or RIBA (a reference standard for exposure). We identified 3 additional studies of the sensitivity of third-generation ELISA using PCR as the reference standard (Table 2).87-89 One of these was a good-quality study that found a sensitivity of 94 percent (107 of 114).87 The specificity was 97 percent (946 of 976) and the positive predictive value (prevalence 10 percent) was 78 percent (107 of 137). Second-generation ELISAs are thought to be slightly less sensitive than third-generation tests, but may be more specific.34 In data collected by the Centers for Disease Control and Prevention in 24,012 lower-prevalence (2 percent) patients, the positive predictive value of current second- and third-generation ELISAs without confirmatory RIBA was 42 percent using PCR as the reference standard.90
To minimize false-positive results in low-prevalence populations, positive ELISA tests are usually followed by confirmatory RIBA tests.90 Patients with positive results on both tests are considered to have confirmed evidence of HCV exposure, although they may not have active infection. In 4 large population-based studies (prevalence 1.2 percent to 3.2 percent), the proportion of patients with positive results on ELISA confirmed by RIBA who were found to have viremia was 73 percent to 86 percent using second- or third-generation ELISAs.2,3,37,91
False-positive screening tests could result in harms that are difficult to measure (for example, labeling, anxiety, detrimental effects on close relationships). There are few data regarding harms in patients who have false-positive tests or HCV-positive patients who do not receive treatment, though 1 fair-quality observational study suggests worse quality of life in patients who are aware of their status.92 We found no studies investigating whether harms associated with learning HCV status could be reduced by effective patient education and counseling. However, data from 1 small trial of 34 patients found that a counseling program improved sense of well-being in women with HCV.93
In addition to viral load and aminotransferase testing, the National Institutes of Health currently recommends pretreatment liver biopsy.67 Several blood tests have been proposed as noninvasive methods of predicting biopsy findings, but in a recent good-quality systematic review, no blood test predicted liver biopsy findings accurately, particularly for intermediate stages of fibrosis.94
In clinical practice, the number of referred patients who receive antiviral treatment depends on the degree of liver damage, the presence of serious co-morbid conditions, and patient preferences regarding treatment. Antiviral therapy is recommended for patients with chronic HCV infection who are at the greatest risk for progression to cirrhosis. These persons have HCV viremia, persistently elevated aminotransferase levels, or liver biopsy findings showing significant fibrosis or inflammation and necrosis.1,67,95-98 In patients with minimal or no biopsy abnormalities, the benefits of treatment are not clear, and decisions about therapy are individualized.67,69,98,99 Many patients identified by screening are likely to be in this category. In 3 community-based cohort studies, the rate of chronic hepatitis of minimal grade or with no inflammation was 43 percent to 61 percent.4-6 Patients with cirrhosis or serious comorbid medical or psychiatric conditions also must have the risks and benefits of antiviral treatment carefully weighed.
We identified 3 fair-quality observational studies in referral centers (involving 100, 327 and 557 patients, respectively) that evaluated the number of patients referred for HCV infection who received treatment.100-102 In these studies, 30 percent to 40 percent of evaluated patients received treatment. Common reasons for ineligibility were ongoing substance abuse (13 percent to 44 percent) and serious co-morbid medical or psychiatric conditions (12 percent to 34 percent). Non-adherence to the protocol (37 percent) and declining to receive therapy (10 percent) were also reported in one study.102
In the work-up of patients with chronic HCV infection, percutaneous liver biopsy is associated with the highest risk for complications. The most common complication of liver biopsy is pain; approximately 30 percent of patients require strong analgesic medications.103 More serious but less common complications include bleeding (the most frequent major complication), biliary rupture, intestinal perforation, vasovagal hypotension, or infection.
Most data on risks of percutaneous liver biopsy come from large, fair-quality series of patients undergoing liver biopsy for a variety of reasons.104-109 The study of highest quality (independent assessment, standard assessment form) evaluated consecutive percutaneous liver biopsies in a nationwide sample in the United Kingdom.107 A bleeding rate of 26 of 1,500 (1.7 percent) was found, with 11 of 1,500 (0.7 percent) requiring transfusion. Death was definitely associated with biopsy in 2 of 1,500 patients and was possibly associated with biopsy in another 3, yielding a mortality rate of 0.13 percent to 0.33 percent. Because a substantial proportion of patients in this study had malignant disease, patients with chronic HCV infection may have been overestimated.109 The rates of major complications in other large series were 0 percent to 3.7 percent (mortality rates typically <0.1 percent).104,106,110 In large series, the material obtained was inadequate for diagnosis in 1.5 percent to 5 percent of cases.107,108
Two small studies involving 126 and 166 patients, respectively, reported complication rates from percutaneous biopsy in patients specifically with HCV infection.111,112 In both studies, which included patients with known or suspected cirrhosis, no major complications were reported.
Small studies suggest that ultrasound-guided biopsies may be associated with fewer complications than blind biopsies.110,112-115 Increased experience of the person performing the liver biopsy has also been associated with fewer complications.105,107,108
Because of the large number of patients and long duration required to demonstrate improvements in long-term clinical outcomes, intermediate outcomes have been the most common measure of treatment benefit. Sustained virologic response rates (absence of viremia 6 months after completion of a treatment course) are currently considered the best indication of successful treatment.116
Antiviral treatment began in 1986 with the use of interferon-alpha.117 Meta-analyses of interferon trials report sustained virologic response rates of 6 percent to 21 percent for interferon monotherapy, compared to about 2 percent in untreated controls.118-121 Combination interferon plus ribavirin was approved in 1998 and was found in 3 good-quality systematic reviews to be superior (sustained virologic response, 33 percent to 41 percent) to interferon monotherapy.119-121 Treatment with pegylated interferon, alone or in combination with ribavirin, has been used for only a few years. For all interferon-based regimens, factors associated with successful treatment include genotypes other than 1, lower baseline viral load, less serious biopsy findings, and less body surface area or lower weight.67
We reviewed 3 randomized controlled trials of pegylated interferon plus ribavirin versus pegylated interferon alone for 24 to 48 weeks (Table 3). Two trials122,123 were large, multi-center, good-quality randomized controlled trials involving 1,121 and 1,530 patients, and the other was a small, fair-quality study involving 72 patients.124
The 2 good-quality trials found that 54 percent to 56 percent of all patients achieved a sustained virologic response with pegylated interferon plus ribavirin versus 44 percent to 47 percent with pegylated interferon monotherapy (P<0.01).122,123 One of these trials also found a higher sustained virologic response rate with pegylated interferon plus ribavirin compared with non-pegylated interferon plus ribavirin (56 percent vs. 44 percent; P<0.001).122 Table 4 summarizes the relative effects of each interferon-based regimen, with estimated numbers needed to treat for benefit.
Treatment studies may not be directly applicable to the population that would be identified by screening because they evaluate patients who probably have more serious disease. In addition, a significant proportion of patients identified by screening would not meet inclusion criteria used by antiviral trials. For example, 6122,123,125-128 out of 7124 trials of pegylated interferon used elevated aminotransferase levels as an inclusion criterion. In large, population-based studies, 46 percent to 67 percent of patients with viremia had normal aminotransferase levels.2,37,91
The long duration for important complications to develop and the relatively short time period that treatments have been available complicate our ability to assess the long-term benefits of antiviral treatment. There are no data on long-term benefits after treatment with pegylated interferon alone, pegylated interferon combined with ribavirin, or non-pegylated interferon combined with ribavirin.119
One recent good quality systematic review of 3 randomized controlled trials and 13 cohort studies evaluated the long-term effects (viremia or clinical outcomes) of non-pegylated interferon monotherapy.120 The studies were heterogeneous in design, had some methodological limitations, and did not consistently show that treated patients had better long-term clinical outcomes than untreated patients.
We independently reviewed the 2 randomized controlled trials that reported long-term clinical outcomes after treatment with interferon (Table 5). In an unblinded, fair-quality Japanese trial, 90 patients were randomly assigned to interferon-alpha for 24 weeks or symptomatic treatment. After 8.7 years, rates of hepatocellular carcinoma (27 percent vs. 73 percent; P<0.0001) and mortality (11 percent vs. 58 percent; P<0.001) were significantly reduced in the interferon-treated patients.129 The relative risk for progressing to Child B cirrhosis was 0.250 (95 percent CI, 0.124 to 0.505) in the treatment group versus the control group. In a fair-quality Italian randomized controlled trial, no significant differences in long-term outcomes were found up to 5 years after randomization to interferon-beta or placebo (hepatocellular cancer 5.3 percent vs. 4.3 percent).130
The single randomized, controlled trial and many of the cohort studies showing significantly improved long-term outcomes after interferon monotherapy were conducted in Japan, and may not be applicable to settings in the United States. Some evidence shows that chronic HCV infection in Japan is associated with substantially higher rates of serious complications.33,129,131,132
Quality of life has generally been evaluated by comparing results in patients who achieved a sustained viral response and those who did not. We identified only 1 randomized controlled trial that analyzed quality-of-life outcomes according to whether patients received antiviral treatment or placebo.133 This study was rated as poor quality because results were available for only 53 of 106 patients randomly assigned to interferon, baseline quality-of-life scores appeared significantly different between groups, and it was unclear whether patients were blinded to markers of response to treatment. Patients randomly assigned to interferon had no significant change in total Sickness Impact Profile score compared with baseline.
Counseling asymptomatic patients found to have HCV infection might help prevent spread of disease or decrease the likelihood of progressive disease.70 Specifically, patients could be counseled to obtain immunizations for hepatitis A virus or hepatitis B virus, avoid excess alcohol, or avoid sharing needles or engaging in other risky practices.134
Hepatitis A and hepatitis B vaccinations in patients with HCV infection have been found to be immunogenic and safe.135 We identified no studies evaluating the effect of vaccinations after diagnosis of HCV on subsequent clinical outcomes. Although a widely-publicized Italian study136 reported high rates of fulminant (7 of 17) and fatal (6 of 17) hepatitis in patients with HCV infection who acquired hepatitis A infection, other studies137,138 have reported much lower rates. According to data from the Centers for Disease Control and Prevention, mortality rates from hepatitis A virus infection are higher in patients with underlying chronic liver disease (4.6 percent [107 of 2,311]) than those without it (0.2 percent [247 of 113, 009]), but it is not clear how many of these deaths were associated with HCV infection.135
We identified no studies evaluating the effect of postdiagnosis counseling regarding alcohol consumption or other high-risk behaviors on subsequent clinical outcomes or spread of disease. We also did not identify any studies that estimated rates of spread of disease in patients aware of their status compared with those who were unaware. One poor-quality French observational study found less "excessive" alcohol consumption after diagnosis of HCV infection, but the results may have been affected by recall bias or patients' unwillingness to admit to current heavy alcohol use.139 One small U.S. study found no significant differences in behaviors in young injection drug users aware of their HCV status compared with those who were unaware.140
Interferon-based treatments are commonly associated with self-limited adverse events. The most common adverse event is an influenza-like syndrome involving myalgias, fevers, and fatigue. A good-quality systematic review found that serious or life-threatening side effects occurred in 1 percent to 2 percent of patients receiving interferon monotherapy.118 Patients with significant comorbid conditions were generally excluded from randomized controlled trials. Because of the long duration (6 months) of interferon regimens, adverse effects of treatment can have significant (although usually self-limited) effects on quality of life.
Three randomized controlled trials provided data about adverse effects associated with combination therapy with pegylated interferon plus ribavirin or pegylated interferon monotherapy (Table 3).122-124 In all of the studies, rates of adverse events were similar in both groups (50 percent to 60 percent). No serious complications or deaths from treatment were reported. In addition to dose-related influenza-like symptoms, psychiatric, gastrointestinal, dermatologic, and mild self-limited hematologic adverse effects were also common. Withdrawal rates in the pegylated interferon plus ribavirin group in 2 good-quality studies122,123 were 14 percent and 22 percent, compared with 13 percent to 32 percent in the nonpegylated interferon plus ribavirin group. Two good-quality systematic reviews found withdrawal rates of 8 percent to 9 percent in trials of patients receiving non-pegylated interferon monotherapy.119,121
In 5 uncontrolled retrospective and prospective studies of patients who received antiviral treatment, complete responders (sustained virologic response and sustained biologic response) had a moderately decreased risk for hepatocellular cancer and cirrhosis compared with those who had relapses or those who did not respond.33,120,141 However, these studies did not consistently find a decreased risk for hepatocellular cancer in nonresponders compared with untreated controls. These studies were heterogeneous in design and had some methodologic limitations. Specifically, this body of literature does not exclude the possibility that favorable, unknown underlying prognostic factors led to a better response to treatment and better long-term outcomes.
In 4 clinical trials of treatment-naïve patients with HCV infection, 3 of which were fair quality142-144 and 1 of which was poor quality (133), a sustained virologic response was associated with better functional status 24 weeks after treatment (Table 6).142-144 The 3 fair-quality studies found that sustained responders had better scores than nonresponders on the 36-Item Short-Form Health Survey (SF36) in 5 to 8 of 8 domains. In all of these studies, patients could have been aware of the results of biochemical or virologic testing before SF-36 testing was repeated.
The results of the evidence review are summarized in Table 7. No direct evidence shows benefits of screening for HCV infection in the general adult population. There are inadequate data to accurately weigh the benefits and risks of screening for HCV in the otherwise healthy, asymptomatic adults. Although screening can accurately detect chronic HCV infection and antiviral treatment can successfully eradicate viremia, there are inadequate data to estimate benefits of treatment for long-term clinical outcomes such as death, cirrhosis, hepatocellular cancer, and quality of life. There are also no data to estimate benefits from vaccinations or counseling about alcohol use and high-risk behaviors.
Clinical trials of antiviral treatment have been performed in referred patients, who generally have more serious and progressive disease than patients followed in community-based cohorts. Even if treatment is equally effective for virology end points in patients identified by screening and those studied in clinical trials, the overall clinical benefit would be expected to be smaller since the underlying progression rate is lower. Although the proportion of screened patients found to have chronic HCV in selected high-risk populations, particularly intravenous drug users, would be substantially higher than in the general population, there are also no data to accurately weigh the risks and benefits of selective screening. Table 8 estimates the yield from screening in hypothetical cohorts of 1,000 adults in the general population and 1,000 intravenous drug users.
Important gaps remain in our understanding of the natural history of untreated patients with HCV infection who are likely to be identified by screening. If untreated chronic HCV infection causes important morbidity in the absence of cirrhosis, there may be other important goals to be obtained from treatment, but few studies have adequately assessed the impact of treatment on quality of life or symptoms. Additional studies are needed to define the progression from asymptomatic to symptomatic HCV infection and how long symptomatic patients remain unidentified without screening.
Many studies showing improvement in long-term clinical outcomes have been conducted in Japan. Chronic HCV infection appears to follow a substantially more aggressive course in Japan than in the United States. Although lead-time bias could explain some of the observed differences in disease progression rates, the case for screening would be greatly strengthened by data showing that treatment in earlier, asymptomatic stages of disease in western countries is associated with improved outcomes compared to treatment reserved for patients who have become symptomatic and could be identified without screening. Studies demonstrating important individual or public health benefits from counseling, immunizations, and behavioral changes after a diagnosis of HCV would also greatly strengthen the case for screening. Little is known about the benefits and risks of treatment in patients typically excluded from or under-represented in randomized trials, such as those with ongoing substance abuse, those with co-morbid conditions, elderly persons, and persons of non-white ethnicity).145
No studies have adequately assessed the potential harmful effects of screening for HCV infection, such as anxiety, labeling, or damage to close relationships, and whether these factors can be minimized by appropriate counseling. Additional studies on the long-term effects of antiviral treatment in nonresponders are important because studies have not consistently found an improved outcome in this group compared with untreated controls.
Reasonable screening strategies might be to screen adults with established risk factors, adults in settings with a high prevalence of HCV, or all adults in the general population. Studies that adequately assess the usefulness of risk factor assessment to guide selective screening strategies and the harms and benefits of selective versus universal screening are needed. A potential barrier to screening patients on the basis of risk factors is the difficulty in obtaining accurate histories of intravenous drug use or high-risk sexual behaviors. Little is known about patient preferences for screening. There are no data to estimate risks and benefits of 1-time screening versus other screening strategies.
Complications from chronic HCV present an enormous health burden that is expected to increase 2- to 4-fold over the next 2 to 4 decades. Further research to more accurately determine the benefits and harms of screening is of paramount importance.
The authors thank Susan Wingenfeld and Kathryn Pyle Krages, A.M.L.S., M.A., for their administrative support, and Heidi Nelson, M.D., M.P.H., for reviewing the manuscript.
This study was conducted by the Oregon Evidence-based Practice Center for the Agency for Healthcare Research and Quality, Contract No. 290-97-0018, Task Order 2 for the U.S. Preventive Services Task Force.