- CONDITION CENTERS
Dr. Grandinetti is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Rockville, Maryland. The views expressed are those of the author and not those of any government agency.
Genetically and clinically, hepatitis B and C are 2 distinct viruses. According to the World Health Organization, hepatitis B virus (HBV) infects an estimated 2 billion people worldwide and more than 350 million chronically. An estimated 1.25 million Americans are potentially infectious HBV carriers (those testing positive for hepatitis B surface antigen for more than 6 months); those who are hepatitis B e antigen (HBeAg)-positive have the highest degree of infectivity.1 Hepatitis C virus (HCV) infects approximately 30.9 million Americans and 130 million people worldwide, with most infected chronically.2
Acute HBV or HCV patients may be asymptomatic or have flu-like symptoms, anorexia, nausea, vomiting, abdominal pain, dark urine, and jaundice. Up to 90% of acute HBV cases resolve completely within a few weeks with lifelong immunity established; 9% progress to chronic infection, and 40% of these patients progress to cirrhosis, hepatic failure, or cancer.1,3 Unlike HBV, an estimated 85% of people infected with HCV develop chronic infection; cirrhosis occurs in approximately 30% of cases and hepatocellular cancer in 2%. Cirrhotic patients may develop ascites, jaundice, muscle wasting, hepatic encephalopathy, and esophageal varices. HCV is the most common indication for liver transplantation. 4,5
Both viruses are transmitted through direct exposure to blood and body fluids or by close person-to-person contact through open cuts or sores. HCV's perinatal, sexual, and needle-stick transmission risk is lower than for HBV. Differences may be due to HBV's more robust ability to survive outside the body and the 2- to 4-log higher blood concentration of the infected person.1,6
Treatment goals are to suppress viral replication, induce remission, maintain treatment adherence, and prevent complications (cirrhosis, hepatic failure, and hepatocellular cancer). Because treatment-related toxicities can significantly lessen quality of life and ability to function, minimizing adverse effects is another important treatment goal.1,4
For acute HBV patients, experts generally do not recommend antivirals, but they may benefit patients who are progressing to chronic infection. Conventional or pegylated (Peg) interferon (IFN) and nucleoside analogues (NAs)— such as lamivudine, adefovir dipivoxil, or entecavir—are standard HBV treatment options. PegIFN-alfa 2a (Pegasys) is the only pegylated formulation FDA approved for chronic HBV. IFNs are administered for predefined durations; whereas, NAs are given until specific end points are met (Table). HBeAg seroconversion, serum alanine aminotransferase (ALT) normalization, and a decrease in serum HBV DNA are used to assess treatment efficacy.8 Viral mutation and drug resistance are major concerns with long-term lamivudine therapy but less of a concern with adefovir and entecavir. Both are FDA approved for lamivudine-resistant HBV patients.1
Acute HCV patients may be treated with antivirals but only after sufficient time (within 6 months of exposure) has passed for spontaneous viral clearance.5 Standard treatment for chronic HCV is PegIFN plus ribavirin. PegIFN alone may be given to patients in whom ribavirin is contraindicated; however, ribavirin monotherapy is ineffective against HCV.4,9 Two PegIFN preparations are FDA approved for chro- nic HCV: PegIFN alfa-2a, administered as a fixed dose, and PegIFN alfa-2b (Peg-Intron), administered as a weight-based dose. No studies prove 1 formulation superior to the other.4 Medication selection, dose, and length of therapy depend on the HCV genotype (Table). Efficacy, defined as serum HCV RNA <50 IU/mL 6 months following completion of therapy, is monitored at baseline and periodically for up to 6 months after therapy by measuring HCV RNA and serum ALT levels.4,7
Conventional and Peg IFN have similar adverse-event profiles. The most troublesome adverse event is emotional lability, including depression and suicidal thoughts and attempts. Clinicians should assess patients for depression before and periodically during treatment. Serotonin reuptake inhibitors are often helpful for depression.1,4
NAs are generally well-tolerated. Lamivudine and entecavir have similar safety profiles, whereas nephrotoxicity is a major concern with adefovir Serum creatinine monitoring is necessary during adefovir therapy.1
Hemolytic anemia associated with worsening cardiac function is ribavirin's primary toxicity. Hemoglobin decreases usually occur during the first 2 to 4 weeks of therapy. During therapy, blood counts are monitored weekly, and patients with preexisting cardiac disease should receive baseline electrocardiograms and be monitored appropriately thereafter. The dose is often reduced or discontinued in patients with decreased hemoglobin concentrations.
Ribavirin is teratogenic and embryotoxic, and because of its long halflife, the risks are prolonged. Pregnancy tests are necessary before treatment and monthly for 6 months following therapy. Ribavirin is eliminated renally and not removed by hemodialysis; thus, it is contraindicated in patients with renal dysfunction (creatinine clearance <50 mL/min).4
Pharmacists can improve patient care by ensuring patients receive appropriate routine and follow-up tests, recommending therapies to minimize drug-related adverse events, monitoring patient adherence, and providing public and patient HBV and HCV education.