Friday, August 21, 2009

Hepatitis Pandemics and its therapeutics!

Global7 the new Millennial Renaissance Vision for the Globe

Dear Patriotic global citizens and Friends of African Union and Ethiopia:

The Epidemiology of Hepatis Series of liver infections that range from A to E and more is not well celebrated inthe Infectious Disease or Global Public Health Expert communities like the most fashionable and rather exotic H1N1, HIV pandemics, Malaria and Tuberculosis epidemics and yet kills more people and is highly infectious.

The African and South East Asian Continents are the major targets of this fatal disease spectrum.

Please find attached what the experts say on how to treat one small variant the Hepatitis C infection.

Who knows some day, we might solve this tragic disease too.

Let me know if you appreciate such scientific communications that afflict a fairly high proproton of our populations

For the record, here is one such Expert Commentary!

Dr B

Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results.
Bacon BR, Shiffman ML, Mendes F, et al.
Hepatology. 2009;49:1838-1846.

Expert Commentary Capsule Summary

Consensus Interferon/Ribavirin Retreatment for Peginterferon/Ribavirin Nonresponders Beneficial for Select Group of Patients With Low Baseline Fibrosis Scores and Interferon Sensitivity

Richard K. Sterling, MD, MSc, FACP, FACG
Posting Date: May 01, 2009
Professor of Medicine
Associate Chair of Education and Training
Division of Gastroenterology, Hepatology, and Nutrition
Virginia Commonwealth University
Richmond, Virginia

Patients chronically infected with hepatitis C who fail to respond to first-line peginterferon/ribavirin therapy represent an underserved population, as optimal management of these individuals to prevent disease progression remains to be defined.

One of the many management strategies proposed for nonresponders is treatment with interferon alfacon-1 or consensus interferon

. The current study by Bacon and colleagues[1] tested the antiviral efficacy of consensus interferon plus ribavirin in nearly 500 previous peginterferon/ribavirin nonresponders (Capsule Summary).

Overall, sustained virologic response (SVR) rates in this trial were low, reaching only 7% for patients who received consensus interferon 9 µg/day and 11% for patients who received consensus interferon 15 µg/day.

These results are fairly disappointing, although not unexpected. The investigators enrolled a very difficult–to-treat population with several unfavorable treatment characteristics. For example, nearly 20% of the study population was black, approximately 25% had cirrhosis, more than 50% had steatosis, and nearly 80% had a < 2 log10 decline in HCV RNA in response to previous therapy—that is, a clearly defined group of previous peginterferon/ribavirin nonresponders.

The investigators conducted several subanalyses to tease apart various groups of nonresponders who may attain more benefit from consensus interferon/ribavirin retreatment than others.

As has been seen in other studies,[2] patients who had a partial response to previous peginterferon/ribavirin treatment (> 2 log10 IU/mL decrease in HCV RNA) were the most responsive to retreatment with consensus interferon/ribavirin.

In this population of patients, SVR rates for the 9-µg/day and 15-µg/day doses of consensus interferon were 11% and 23%, respectively. Although the numbers were small, those who achieved a complete response at Week 12 were more likely to achieve SVR (13/16 [81%] in the 9-µg/day group and 14/22 [64%] in the 15-µg/day group).

The investigators also found that patients with lower fibrosis scores responded better to treatment than those with higher fibrosis scores (SVR for fibrosis stage F0-F3 vs F4 with the 15-µg/day dose: 13.0% vs 4.5%).

This finding has been observed in other trials that included treatment-experienced patients.[3] When patients were classified according to fibrosis score and the level of response to previous peginterferon/ribavirin, the investigators found that patients with low fibrosis scores (F0-F3) and a previous reduction in HCV RNA > 2 log10 IU/mL attained SVR rates of 30% or greater with consensus interferon 15 µg/day.

The authors stated that 72% to 84% of patients received at least 80% of the cumulative consensus interferon dose, but adherence to ribavirin was not reported. It is important to note that the investigators had very strict criteria for ribavirin dose modification in response to anemia.
For patients who experienced a drop in hemoglobin < 10 g/dL, the dose of ribavirin was reduced from 1000-1200 mg/day to 600 mg/day, which probably represents the lower threshold of therapeutic efficacy.

No growth factor support was allowed. Therefore, depending on how many patients required ribavirin modification, this aspect of the treatment protocol may have attenuated the response rates that could have been achieved had smaller increments in ribavirin dose reduction been employed.

It is unclear what probability of response is sufficient or reasonable to warrant putting a patient through the expense, the adverse events, and the inconvenience of retreatment, and this should be considered on an individualized basis.

As such, the results of this study suggest that there may be specific subgroups of patients with a previous nonresponse to peginterferon/ribavirin who might benefit from retreatment with consensus interferon/ribavirin—namely, those who had a partial response to previous peginterferon/ribavirin and do not have cirrhosis.

Unfortunately, these are not the patients in dire need of such treatment. It is those individuals with unfavorable characteristics—cirrhosis, steatosis, high HCV RNA, and black race—for whom disease control is needed most urgently.

Preliminary results from studies of novel specifically targeted antiviral therapies for HCV (STAT-C) suggest that these agents may produce higher response rates than currently available options when used as part of a retreatment regimen.

1. Bacon BR, Shiffman ML, Mendes F, et al. Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology. 2009;49:1838-1846.

2. Jacobson IM, Gonzalez SA, Ahmed F, et al. A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C. Am J Gastroenterol. 2005;100:2453-2462.

3. Jensen DM, Marcellin P, Freilich B, et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med. 2009;150:528-540.

Link to the original abstract
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