Chronic hepatitis C virus (HCV) infection affects an estimated 3 million persons in the United States, most of them younger than 50 years.1 Most of these infections are asymptomatic until advanced liver disease develops. HCV infection is one of the leading causes of chronic liver disease morbidity and mortality and the most common indication for liver transplantation. Specific populations at increased risk for infection have been defined, and reliable diagnostic tests exist. Treatment is available that eradicates the virus and eliminates or reduces liver inflammation and fibrosis in some patients. Counseling can be offered to all patients with HCV infection to modify or prevent the adverse effects of cofactors, such as alcohol consumption, on disease progression.
Various groups of experts generally agree on these characterizations of HCV infection.2–6 There is disagreement, however, on how this evidence should be translated into preventive interventions. Especially controversial are recommendations for identifying incidents of HCV infection by testing persons who are at high risk, for example, those who received blood transfusions before more sensitive testing of donors was implemented or those who injected illicit drugs. The details of this controversy have been published.7,8
One group of experts, the U.S. Preventive Services Task Force (USPSTF),9 found insufficient evidence to recommend for or against routine testing for HCV infection in high-risk asymptomatic adults because it found no studies that proved, directly or indirectly, that testing for HCV infection leads to a reduction in cases of HCV-related chronic disease and deaths. Other groups of experts, including the Centers for Disease Control and Prevention2; National Institutes of Health3; Veterans Health Administration4; and independent infectious-disease, hepatology, and public health organizations,5 have recommended or endorsed that testing be offered routinely to persons at high risk for HCV infection so that infected persons have the opportunity to seek medical evaluation to determine the severity of their disease, to consider treatment, and to make lifestyle changes that could reduce the likelihood of progression of their silent disease.
Different conclusions were reached by these groups of experts, not because their reviews or evaluations of the evidence varied, but because their definitions of “benefit” differed.7,8 As the USPSTF indicated, no data show that treatment of persons with HCV infection will prevent disease progression to HCV-related cirrhosis, liver cancer, and death, or that counseling against alcohol use will slow progression to liver disease. However, as the other groups of experts indicated, the expectation that current benefits will translate into long-term ones is supported by data that current antiviral therapies produce positive effects in a large subgroup of patients. These effects include virus elimination and normalization of liver enzyme levels that are maintained for at least 10 years. The magnitude of the combined adverse effects of alcohol use and HCV infection, and the potential to modify these effects, also cannot be ignored. Chronic HCV infection requires many years of follow-up to determine whether treatment or other interventions increase life expectancy or quality, and it seems inappropriate to wait several decades to measure the impact of early identification of HCV infection, particularly when most persons with chronic HCV infection are asymptomatic despite the presence of active disease. Symptoms do not develop reliably in these persons until cirrhosis is present, which is too late for therapy to have a major impact on survival.
Because practicing primary care physicians have limited time and resources to deliver a spectrum of preventive services, the USPSTF feels the highest priority should be given to services with evidence of substantial to moderate net health benefit.8 No amount of debate is going to change the fact that experts disagree on how benefit should be defined or what to do while waiting for direct evidence that testing will reduce HCV-related complications. Even if there were agreement on the issue of benefit, there would remain differences in opinion on the feasibility of ascertaining risk factor histories during patient visits. Most HCV-positive persons can be identified by asking about their histories of injection drug use and blood transfusion (occurring before 1992).10 Regardless, choosing between competing priorities is problematic in all areas of health care. As “experts,” we need to take some responsibility, in collaboration with clinical practice groups, for exploring innovative methods to implement our recommendations. For example, the Veterans Health Administration4 is developing an automated system, based on patients’ computerized medical record information, that will prompt physicians about several interventions, including which patients to test for HCV infection (M.O. Rigsby, personal communication, 2004). Such a system likely could be adapted to other large health care organizations to identify high-risk characteristics common to multiple diseases, such as smoking, obesity, and illicit drug use, and to provide reminders about appropriate immunizations. Similar algorithms might be developed for use by individual patients using computer-assisted technology. Based on the information provided, a computerized risk-assessment summary with corresponding recommended preventive services could be produced for each patient during the same visit.
There clearly is a need for further research on the long-term effectiveness of antiviral therapy and counseling to reduce HCV-related liver damage. However, the sheer number of relatively young persons with chronic HCV infection who may develop complications as they age emphasizes the need to identify strategies to efficiently integrate risk history screening and HCV testing into current clinical and public health prevention activities.