It is estimated that 3 million to 5 million Americans are infected with the hepatitis C virus (HCV), which can lie silent in the liver for decades before erupting as cirrhosis, liver failure, or liver cancer. Infection with this virus is the leading indication for liver transplantation in the United States and Western Europe. Of those infected with HCV, some were exposed to contaminated blood in the years before the early 1990s, when a test for the virus was developed that enabled blood donors to be screened prior to transfusion. Other patients acquired the virus from intravenous or subcutaneous drug use. Sharing contaminated needles is the most common risk factor that has been identified, although sexual transmission also occurs in infected individuals. This last risk is increased in people with multiple sexual partners and in patients infected with HIV. In fact, up to 40% of Americans with HIV?300,000 to 400,000 people?are believed to be infected with HCV as well. Among some groups, primarily HIV-positive current and former intravenous drug users, the coinfection rate is thought to approach 90%. Because the extent of the problem has been recognized only recently, the appropriate treatment of people infected with both viruses is still in its infancy. Many health care professionals, however, now believe that the best strategy is to bring the HIV under control before treating the HCV. Of interest for future investigations, is that?although there are now more than a dozen medications that directly interfere with HIV enzymes?there are none that work that way for HCV.
Currently HCV is treated by the combination of pegylated interferon-alfa (an immune system protein secreted in response to the virus) and ri-bavirin (a synthetic nucleoside analog related to guanosine). A systematic review of the scientific literature published between January 1996 and March 2002 examined the efficacy and safety of this regimen for chronic hepatitis C in previously untreated patients and patients in selected subgroups, as well as treatment impact on long-term clinical outcomes, such as hepatocellu-lar carcinoma and death from liver failure. Results consistently showed that combination therapy with high-dose once-weekly pegylated interferon (peg-interferon; a new form of interferon) and daily ribavirin was more effective than 3-times-a-week standard interfer-on-alfa and daily ribavirin in the treatment of chronic hepatitis C in previously untreated individuals infected with the most treatment-resistant genotype, which is also the most commonly diagnosed type found in the United States. There appeared to be no difference in safety and tolerance when the 2 regimens were compared.
Peginterferon is interferon-alfa that has been modified chemically by the addition of a large inert molecule of polyethylene glycol. By protecting the protein against enzymatic degradation, pegylation (as the process is known) changes the uptake, distribution, and excretion of interferon, thus prolonging its half-life. Peginterferon can therefore be given once weekly, and it provides a constant level of interferon in the blood. Standard interferon, on the other hand, must be given 3 times weekly and provides intermittent and fluctuating serum levels. By suppressing the viral load over a longer period of time, pegin-terferon can more effectively decrease the viral replication rate, thereby reducing the risk of viral mutation and treatment resistance?a phenomenon that has been reported recently.
Unfortunately, the vast majority of trials that were reviewed either failed to include or specifically excluded patients who exhibited risk factors (eg, hemodialysis patients, hemophiliacs, individuals coinfected with HIV, Afri-can-American patients, and those with psychiatric disorders). The authors indicated that these understudied populations should be included in future trials.
The selection of patients for treatment must take into account a variety of factors, including the likelihood of response to therapy, the risk of disease progression without therapy, the toxicity of the therapeutic agents administered, and the motivation of the patient to adhere to therapy.
The primary goal of therapy is to eradicate the hepatitis C virus. Compliance with the recommended course of therapy (in many instances 48 weeks in duration) is critical in order to achieve this outcome. When using the combination of pegylated interferon and ribavirin, if patients take 80% of their prescribed doses for 80% of the recommended duration of therapy, then the chances of achieving a sustained virologic response?that is, the lack of detectable virus in the blood 6 months after treatment is completed?are far greater than if a patient is not adherent in this manner. This sustained virologic response confirms eradication of the virus in >99% of patients.
Pharmacists can play a critical role in counseling patients receiving combination therapy to treat chronic HCV infection. They can educate and encourage patients in all aspects of disease management, including proper administration of treatment and the availability of online information and support groups.
When dispensing pegylated interfer-on, pharmacists should refer patients to the guides provided by the drug manufacturers. Because the medication is administered once a week for 48 weeks, it is important that injection sites are rotated in a specific pattern that is continued throughout therapy. The pharmacist can provide a handout that can be used by the patient to chart this site rotation (Figure). The pharmacist also must discuss the proper preparation and disposal of each syringe.
In helping to ensure adherence, pharmacists should emphasize the long-term benefits that these medications can provide. They also can reassure patients about side effects that occur initially, but that are transient or can be readily treated, as well as those rare adverse events for which monitoring is necessary. Here the pharmacist can act as a gatekeeper, ensuring that proper laboratory tests are undertaken before the medications are dispensed.
Finally, because consumption of alcohol can adversely affect therapeutic response and can accelerate progression of the liver disease to cirrhosis and hepatocellular carcinoma, pharmacists should encourage patients to abstain from alcohol use during therapy.
As the concluding statement of theNational Institutes of Health Consensus Development Conference (published in November 2002 as a supplement to the journal Hepatology) indicated, in the 5 years since the previous conference was undertaken significant advances in the diagnosis and management of HCV infection have been reported. Pharmacists can help continue this momentum by educating the public about the disease and its treatment. They also can provide support to patients and offer information to other health care providers.
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