TABLE 49–7 Direct-acting antiviral combination regimens for the treatment of chronic hepatitis C infection in adult patients without cirrhosis.1 1 Regimens may differ in the presence of cirrhosis. 2 As an alternative regimen, elbasvir 50 mg/grazoprevir 100 mg once daily may be given in combination with weight-based ribavirin for 16 weeks. 3 Dose adjustment may be required if co-administered with a CYP 3A substrate.
the immunogenicity of the protein, resulting in a longer half-life and steadier plasma concentrations. Renal elimination of pegylated interferon alfa-2a and pegylated interferon alfa-2b accounts for about 30% of clearance; dose must be adjusted in renal insufficiency due to impaired clearance. The polyethylene glycol moiety is a nontoxic polymer that is readily excreted in the urine.
Pegylated interferon alfa-2a is licensed to treat chronic HBV and HCV infection; pegylated interferon alfa-2b is licensed to treat chronic HCV infection. However, the availability of newer and highly effective antiviral agents for HCV infection has greatly diminished the use of the interferons for this indication.
The adverse effects of interferon alfa include a flu-like syndrome (ie, headache, fevers, chills, myalgias, and malaise) that occurs within 6 hours after dosing in more than 30% of patients; it tends to resolve upon continued administration. Transient hepatic enzyme elevations may occur in the first 8–12 weeks of therapy and appear to be more common in responders. Potential adverse effects during chronic therapy include neurotoxicities (mood disorders, depression, somnolence, confusion, seizures), myelosuppression, profound fatigue, weight loss, rash, cough, myalgia, alopecia, tinnitus, reversible hearing loss, retinopathy, pneumonitis, and possibly cardiotoxicity. Induction of autoantibodies may occur, causing exacerbation or unmasking of autoimmune disease (particularly thyroiditis).
Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline and methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias.
No specific treatment is available for the treatment of acute hepatitis B infection, which most often resolves spontaneously.
The goals of chronic HBV therapy are the suppression of HBV DNA to undetectable levels, seroconversion of HBeAg (or more rarely, HBsAg) from positive to negative, and reduction in elevated serum aminotransferase levels. These endpoints are correlated with improvement in necroinflammatory disease, a decreased risk of hepatocellular carcinoma and cirrhosis, and a decreased need for liver transplantation. All of the currently licensed therapies achieve these goals. In contrast to the treatment of HCV infection (see below), cure is rare. In addition, because current therapies suppress HBV replication without eradicating the virus, initial responses may not be durable. The covalently closed circular (ccc) viral DNA exists in stable form indefinitely within the cell, serving as a reservoir for HBV throughout the life of the cell and resulting in the capacity to reactivate. Relapse is more common in patients co-infected with hepatitis D virus.