Volume 2, Number 3
Decline in post-transfusion HCV infection (1965-1997) |
(Washington) In a decision of far-reaching importance, the U.S. Secretary of Health and Human Services (HHS), Donna E. Shalala, has approved the nation's first program to directly notify recipients of transfusions from donors who later tested positive for hepatitis C. Under the program, often called "targeted HCV lookback,"thousands of hospital workers will begin combing through records of transfusions given as far back as 1987, searching for people who received blood from donors who subsequently tested positive for HCV on confirmed second-generation screening tests. As many as 250,000 Americans could receive notification letters. The total cost of the program could reach over $200 million.
Shalala's move marks a turning point in federal blood policy and culminates nine years of debate about HCV lookback in the public health and blood banking communities. HHS staff and blood bankers had argued for years that lookback was a poor use of resources and would benefit only a tiny portion of HCV-infected persons in the United States. But, bending to the recommendations of a Congressional subcommittee and an HHS advisory panel, Shalala decided that persons exposed to HCV through blood transfusions had a right to know of their exposure, and must be notified.
HCV is America's most common bloodborne pathogen. About 3.9 million people in the U.S. have been infected with HCV. Of these, 290,000 (7%) acquired their infections from transfusions, mostly before blood screening for anti-HCV was instituted in 1990. Many infected persons are unaware of their infections. The program announced by Shalala aims to find as many of these people as possible and alert them to the availability of treatment and preventive measures.
Blood donors in the United States have been screened for hepatitis C (previously called post-transfusion non-A, non-B hepatitis) since 1988. The first tests, ALT and anti-HBc, were surrogate markers for HCV infection. An enzyme immunoassay for anti-HCV was first introduced in 1990 and a better, second-generation immunoassay was introduced in 1992. A confirmatory test, the recombinant immunoblot assay or RIBA, became available in 1993. A third generation anti-HCV test followed in 1996.
Screening has dramatically reduced the risk of post-transfusion hepatitis C. From 1988 to 1992, the rate of post-transfusion hepatitis C dropped from about 1 in 50 to 1 in 5,000. The current risk is even lower - 1 in 103,000, according to one recent study (Schreiber et al., NEJM 1996;334:1685-90).
But even screened blood occasionally transmits HCV when the donor is in the early "window period"of HCV infection. The window period refers to the earliest stages of the infection, when HCV is present in blood but antibodies are not yet detectable by screening tests. With current tests, the HCV window period lasts for about the first 12 weeks of infection. To understand how targeted lookback will work, consider a donor who gave blood only twice, once in 1987 and once in 1993. In 1993, his blood tested positive for anti-HCV using a second generation test, which was confirmed with RIBA. His 1993 donation was discarded, he was told that he could never donate blood again, and he was referred to his physician. But what about his 1987 donation? It is possible that the donor was infected at that time, and the recipient of his blood may have acquired an HCV infection that is still undiagnosed. Under Shalala's decision, blood banks and transfusion services will attempt to find such recipients, notify them that they may have been exposed to HCV, and suggest that they see a physician for counseling and testing.
The disturbing problem of hepatitis C
In the last fifteen years, hepatitis C has become recognized as a serious bloodborne infection. Of those infected, chronic hepatitis develops in 60% to 70%, and, of those, 20% may develop cirrhosis over 20 to 30 years. The liver disease caused by HCV is often asymptomatic. CDC estimates that HCV causes 8,000 to 10,000 deaths annually in the U.S. The yearly cost of the disease exceeds $500 million.
The first treatment for HCV infection, interferon alfa-2b, was licensed by FDA in 1991. But it was only at a 1997 NIH conference that clinicians reached consensus on exactly which HCV-infected patients should be treated. In general, the drug is indicated for patients with persistent ALT elevations and detectable HCV RNA in serum. The sustained response rate to interferon therapy, however, is abysmally low - only 15% to 25% after one year of treatment. Although antiviral treatment is not very effective, persons infected with HCV can take steps to slow the progression of the disease and avoid transmitting it to others. For example, patients with chronic hepatitis C should not drink alcohol. They should also receive hepatitis A vaccination, because, if they are infected with hepatitis A virus, they face a higher risk of fulminant hepatitis and death (see Vento et al. NEJM 1998;338:286-90). HCV-infected patients can also be warned that the virus is readily transmitted through the sharing of needles used to inject illegal drugs. Additionally, although the risk of sexual transmission is believed to be low, safer sex practices can be be recommended for patients with multiple sexual partners.
New committees, new policy
Shalala's decision came after an HHS committee, the Advisory Committee on Blood Safety and Availability (ACBSA), considered the issue in 1997. ACBSA was formed in 1995 in response to a report from the Academy of Science's Institute of Medicine (IOM) that harshly criticized FDA's management of blood safety issues.
Before 1995, HHS's main blood safety committee was the Blood Products Advisory Committee (BPAC), a longstanding panel within FDA. Between 1989 and 1994, BPAC considered the HCV lookback question several times. In 1993, the members of BPAC actually voted 5 to 4 to recommend HCV lookback.
But the recommendation was never implemented, in part because BPAC was headed for a major change in its role. In its 1995 report, IOM chastised BPAC and FDA for their failure to adequately protect the nation's blood supply against HIV in the early 1980s. IOM also said that BPAC was overly influenced by members from the blood and blood products industries. This prompted FDA Commissioner David Kessler to reconstitute BPAC in 1995 to include more members who were independent of industry. At that point, BPAC became a group reserved for technical advice, and FDA began to look elsewhere for broad policy guidance on blood safety. Another committee within HHS had also been examining HCV lookback for several years, the Interagency Working Group on Blood Safety and Availability.
It included members from FDA, CDC and NIH. In 1991, the Working Group concluded that targeted lookback would be less effective than broader programs aimed at educating providers and consumers about the need for HCV testing.
Congress jumps in
In early 1995, the safety of the nation's blood supply attracted the attention of a member of Congress, Christopher Shays, Republican of Connecticut. Shays, a former businessman, educator and realtor from Stamford, Connecticut, told a staffer, Anne Marie Finley, to look into blood safety. The House subcommittee that Shays chairs, the Subcommittee on Human Resources and Intergovernmental Relations (HRIR) of the Government Reform and Oversight Committee, held hearings on blood safety in October and November of 1995.
Shays' approach to analyzing HCV lookback was much different from the approach taken by the federal committees. Over the previous six years, BPAC and the Interagency Working Group had examined the issue using traditional methods of public health analysis, such as balancing risks versus benefits, weighing costs and effectiveness against available resources. Shays, in contrast, approached HCV lookback as an issue of individual rights.
Shays' subcommittee issued its report in August 1996. It left HHS with little room for interpretation: "HHS should take steps to ensure that the estimated 300,000 living recipients of blood and blood products who were infected with hepatitis C virus before 1990 are notified of their potential infection so that they might seek diagnosis and treatment."But HHS moved glacially on the issue, prompting Shays to publicly criticize the Department's inaction in early 1997.
Meanwhile, in 1996, the Interagency Working Group again evaluated targeted HCV lookback. The group again recommended that HHS not pursue lookback, but emphasized that the Department should conduct programs to notify potentially infected persons through physician outreach and public information campaigns. The group's main concern about targeted lookback was its inability to benefit any substantial proportion of persons in the U.S. who are infected with HCV.
According to the Working Group's analysis, only about 7% of persons infected with HCV, or 290,000, acquired the virus from transfusion. Of these, perhaps 55,000 would be still alive and would respond to lookback notification by going to their doctors and seeking a blood test. Of those who did seek a test, only about 800 to 1,600 persons would receive interferon and have a sustained therapeutic response. As the group said, "intensive efforts put into targeted lookback would benefit only 0.1% of all persons chronically infected with this agent."
Ethics drove Advisory Committee
ACBSA finally met in April 1997, under the chairmanship of Arthur Caplan, Ph.D., director of bioethics at the University of Pennsylvania, and a popular ethics commentator. As promised to Congressman Shays, HCV lookback was the Committee's first order of business. ACBSA was charged with considering not just the scientific and technical issues around HCV notification (as BPAC had already done), but also the ethical, legal, social and economic issues.
ACBSA took the position that it should not involve itself in implementation issues, including funding. Its job was only to say what ought to be done. As stated by Chairman Caplan, "I am perfectly willing to say that [targeted lookback] ought to happen, and that we urge the White House, the agencies, Congress, to make it happen, but in all honesty, we will not sort out who is going to pay for this, and we should not."
On August 12, 1997, the Committee voted unanimously, with one abstention, to recommend targeted lookback to Shalala. The vote was won mainly by the principle that if specific information exits about a particular recipient's exposure to HCV through transfusion, such as a record of the donor later seroconverting, then there is an ethical duty to inform the recipient. 1987 was chosen as the furthest back that the lookback should go, based mainly on the availability of transfusion records.
In summarizing the Committee's findings, one member said, "weähave to be prepared to answer the question, why are you making us look, if the yield is low, if the costs are high, if the records stink, why don't you do it some other way? Well, I think the American people will probably want to know that, if we knew that some of them were exposed to infected blood, that we did what we could to tell them. I personally am going to find it hard to say, I knew you were exposed, even in a probabilistic way, and I did not tell you."
Additionally, the Committee felt that lookback was now justified by new information that had not been available to previous committees considering the issue: the emergence of new reliable tests to detect the presence of anti-HCV and HCV, better information about the epidemiology and risk of transmission, more data on the natural history and epidemiology of the disease, new knowledge about how lifestyle, especially alcohol consumption, can affect the course of the disease, and especially the crystallization of views on therapy at the 1997 NIH consensus conference.
Wringing their hands, the blood bankers concurred
HCV lookback will consist of several tasks: the identification of past donations and notification of transfusion services, the identification of recipients, retrieval of medical records, ascertainment of responsible physicians, preparation of notifications, and physicians' actual attempts to locate and contact recipients. Blood bankers at the ACBSA proceedings expressed concern about the logistics and multi-million dollar cost of HCV lookback. One called the effort "a labor intensive exercise that actually masquerades as a public health measure."
Much of the workload will fall on transfusion services, and it is still unclear how many services will have the needed medical records, as far back as 1987, to carry out notifications.
Many questions remain: When will lookback start? How long will it take? Who will bear the cost of notification? The cost of testing? The cost of medical evaluation and treatment? How many lawsuits will be generated by the notifications and how will the legal costs be absorbed by blood banks, transfusion services, and hospitals?
"A comprehensive plan"
In addition to targeted lookback, Shalala also approved an educational effort directed at those who received blood before the second generation screening test became available. This educational effort, she said, will benefit all Americans at risk for hepatitis C, regardless of the source of their risk. HHS's educational efforts will supplement existing programs sponsored by groups such as the American Liver Foundation and Hepatitis Foundation International.
Shalala also said that the announced steps were only the first phase of a comprehensive plan to address the problem of HCV infection acquired through earlier transfusions. Further details about these new programs will be announced by the Department in the future, and guidance documents implementing the HCV lookback program will be issued by FDA in the coming weeks.