Hepatology. 2003 Sep;38(3):645-652.  Related Articles, Links 

 
Early virologic response to treatment with peginterferon alfa-2b
plus ribavirin in patients with chronic hepatitis C.

Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J.

Division of Hepatology, Baylor University Medical Center, Dallas,
TX; Division of Clinical Decision Making, Department of Medicine,
Tufts/New England Medical Center, Boston, MA; Duke Clinical Research
Institute, Duke University Medical Center, Durham, NC; Medizinische
Hochschule Hannover, Division of Gastroenterology and Hepatology,
Hannover, Germany; and Schering-Plough Research Institute,
Kenilworth, NJ.

Interferon-based regimens for the treatment of chronic hepatitis C
have become increasingly effective and are able to eradicate virus
in more than one half of cases. Early identification of patients who
will not respond is desirable because treatment might be stopped,
thereby avoiding the expense and inconvenience of unnecessary
therapy. We examined the accuracy of different degrees of viral
inhibition during the early weeks of treatment (early virologic
response [EVR]) with pegylated interferon alfa-2b and ribavirin
(PEG/R) in identifying patients who would not respond to therapy.
The best definition of EVR was a reduction in hepatitis C virus
(HCV) RNA by at least 2 logs after the first 12 weeks of treatment
compared with baseline. Between 69% and 76% of patients achieved
this threshold, depending on the treatment regimen, and sustained
virologic response (SVR) occurred in 67% to 80% of these patients.
Patients who did not reach EVR did not respond to further therapy.
If treatment had been stopped in patients without EVR, drug costs
would have been reduced by more than 20%. In conclusion, early
confirmation of viral reduction following initiation of antiviral
therapy for chronic hepatitis C is worthwhile. It provides a goal to
motivate adherence during the first months of therapy and a milepost
at which to reassess the need for continued treatment. Most patients
who are able to complete the first 12 weeks of therapy achieve EVR
and have a high probability of SVR. Patients who fail to achieve EVR
will not clear virus even if an additional 9 months of therapy is
received. Therapy can be confidently discontinued in those cases.

PMID: 12939591 [PubMed - as supplied by publisher]
 

Treatment options for chronic HCV infection have evolved significantly over the last few years, and current therapy with pegylated interferon and ribavirin is effective in 50% to 60% of patients with previously untreated infection.

Although there is some encouraging progress in new antiviral drug development for hepatitis C, it will be several years before any of these novel compounds are available in clinical practice.

In the interim, pegylated interferon and ribavirin remain the cornerstone of therapy. Healthcare providers have an important role in educating and selecting appropriate patients for therapy, recognizing common side effects, establishing a team approach to the management of chronic HCV infection, and keeping abreast of changes in treatment guidelines.

Following are brief excerpts on approaches to the treatment and management of chronic HCV from an article by Drs. Keyur Patel and John G. McHutchison.

Before initiating therapy, ensure there are no contraindications to interferon alfa (or peginterferon) and ribavirin. These include

         For Interferon  Alfa or Peginterferon Alfa

·         Decompensated liver disease
 

·         Autoimmune hepatitis

·         Severe neuropsychiatric illness

·         Unstable coronary artery disease

·         Unstable epilepsy

·         Poorly controlled diabetes

         For Ribavirin

·         * Anemia (hemoglobin, <11 g/dL)

·         Hemoglobinopathies (thalassemia major, sickle cell disease)

·         Ischemic heart disease

·         Cerebrovascular disease

·         Pregnancy

·         Refusal to practice barrier contraception

·         Chronic renal impairment (creatinine clearance, <50 mL/min)

There are 10 steps with which patient and physician should move forward:

1. Ensure there are no contraindications to therapy.

2. Assess carefully for comorbid conditions (including depression, hypothyroidism, cardiac disease, and diabetes) that should be evaluated and controlled before starting antiviral therapy.

3. Determine HCV genotype and HCV RNA level.

4. Obtain liver biopsy to assess disease severity.

5. Discuss with the patient the side effects and possible treatment outcomes.

6. If appropriate, start therapy with pegylated interferon and ribavirin.
        a) Determine dose of ribavirin according to genotype and weight.
        b) Continue treatment for 24 or 48 weeks, according to genotype.

7. Perform laboratory monitoring.* (see Table 1).

8. Carefully perform a clinical evaluation monthly (or more often) for depression and other side effects; assess treatment adherence.

9. For genotype 1 infection, measure HCV RNA level at week 12.
        a) Continue treatment for another 36 weeks if the patient has an early
            virologic response.
        b) Consider terminating therapy if there is no early virologic response.

10. Measure HCV RNA level at end of treatment. If HCV RNA is still not present at 6 months post-therapy (a sustained response), long-term eradication is likely to have occurred.

Table 1. A proposed laboratory monitoring schedule during combination therapy monitoring schedule during combination therapy for chronic hepatitis C

09/05/03

Reference
K Patel and JG McHutchison. Drug combination achieves sustained response in more than half of patients. Postgraduate Medicine 114(1): July 2003.