Treatment

In my practice, I often individualize decisions for treatment of chronic HC infection based on a clear understanding of (1) the natural history of chronic HC, (2) factors that influence treatment response and disease progression, (3) the required commitment for monitoring treatment adherence, tolerability, and response, and (4) the overall potential for side effects and poor outcomes. In general, my primary goal of treatment is to provide a safe and effective means to eradicate HCV infection. In addition, there are several secondary goals of treatment, including slowing disease progression, improving histology, reducing risk of HCC, and improving health-related quality of life.

The recent National Institutes of Health (NIH) Consensus Statement on the management of chronic HC emphasized that consideration of treatment should not be confined only to those patients who would have met the entry criteria of pivotal studies, but should be individualized for the goals of prevention of cirrhosis or its complications.

Interferons were among the first agents studied in the mid-1980s for treatment of viral hepatitis. The effects of interferons are multifactorial, and include induction of 2' 5' oligoadenylate synthetase; induction of RNA-dependent protein kinases; phosphorylation of EIF-2, a protein synthesis initiation factor; blocking viral replication; and cell membrane changes (ie, induction of HLA class I, and other immunomodulatory and antiproliferative effects). Pegylation of interferon involves a covalent attachment of polyethylene glycol (PEG), an inert, water-soluble, nontoxic substance, to the parent compound. The PEG chain size and configuration can differ (eg, straight or branched), and the various binding sites available result in mixtures of positional isomers. There are now two commercially approved peginterferons that have been approved by the US Food and Drug Administration (FDA). Peginterferon a-2b is a 12 kDa pegylated protein with a half-life of 22 to 60 hours and a specific activity approximately 28% of that of interferon a-2b. Peginterferon a-2a is a 40 kDa pegylated protein with a half-life of 60 to 80 hours and specific activity approximately 7% of that of interferon a-2a.

In 2002, the NIH Consensus Panel concluded that the combination of peginterferon and ribavirin is the most effective regimen for the treatment of chronic HC infection leading to sustained virologic responses in over 50% of treated patients. Currently FDA-approved dose regimens for peginterferons and ribavirin are as follows:

1. Peginterferon a-2a or Pegasys (monotherapy) 180 mcg (fixed dose) subcutaneously once a week

2. Peginterferon a-2a or Pegasys (combination therapy) 180 mcg (fixed dose) subcutaneously once a week along with i. Ribavirin (Weight < 75 kg): 1000 mg/d orally in 2 divided doses ii. Ribavirin (Weight > 75 kg): 1200 mg/d orally in 2 divided doses

3. Peginterferon a-2b or PegIntron (monotherapy): 1.0 mcg/kg (weight-based dose) subcutaneously once a week

4. Peginterferon a-2 b or PegIntron (combination therapy): 1.5 mcg/kg (weight-based dose) subcutaneously once a week along with i. Ribavirin 800 mg/d orally in 2 divided doses ii. Ribavirin at higher doses (weight-based, 10.6 mg/kg) is currently being evaluated in prospective trials.

The recommended duration of treatment in genotype 1 patients is 48 weeks; in genotype 2 or 3 patients it is 24 weeks.

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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