Friday, June 4, 2010

Hepatitis C Treatment in an Urban Population

Hepatitis C Treatment in an Urban Population


CORRESPONDENCE
Hepatology Accepted Articles, Author's Proof
Early Print

ANNA CHRISTINA DELA CRUZ1, ELLEN ENGELSON2, GABRIEL IONESCU2, VERONIKA DUBROVSKAYA3, DONALD KOTLER2
1Department of Medicine Englewood Hospital Englewood, NJ
2Department of Medicine St. Luke's Roosevelt Hospital Center New York, NY 3Department of Medicine Health Science Center at Brooklyn State University of New York New York, NY

To the editor:

We read with interest the report by Feuerstadt et al.1 demonstrating limited effectiveness of Hepatitis C virus (HCV) therapy in an urban minority population. We evaluated 432 similar HCV mono-infected as well as 392 HIV/HCV co-infected patients and treated 45% and 21%, respectively. The baseline characteristics of our patients and theirs were similar, though more co-infected patients had advanced fibrosis (Table 1).

Low SVR Rates for Hispanics & African-Americans in Inner City Clinic in the Bronx NY - pdf attached - (03/31/10)

Sustained virologic response (SVR) was achieved in 21% of their subjects, 35% of our mono-infected, and 22% of our co-infected patients. In addition to the reported negative predictors of SVR, our co-infected patients had high mean HCV viral load and a 14% prevalence of diabetes. A previous study of co-infection from our institution found a 76% prevalence of HOMA-IR>3 (Homeostatic Model Assessment-Insulin Resistance). 2 Nasta et al. reported an 8% rapid viral response (RVR) rate in co-infected patients with high viral load and HOMA>3.3

Feuerstadt's study did not concentrate on race or gender effects on SVR. In our cohort, SVR rates in non-Caucasian genotype 1 co-infected men were strikingly low at 7.3% (3 of 41), compared to 27.3% in Caucasian genotype 1 men, and 36% in non-Caucasian genotype 1 women. It is unlikely that the results were due to poor adherence, as HIV control was well maintained in this subgroup, with a mean CD4 of 556 cells/mm3, undetectable HIV RNA in 67%, and a similar dropout rate (24%) compared to other subgroups (25%).

A polymorphism near the IL28B gene encoding IFN-λ-3 is the strongest predictor of SVR in genotype 1 patients and doubles the SVR, RVR and early viral response rates in patients of all ancestries.4,5 The CC genotype is more prevalent in Caucasians than in African Americans or Latinos in the Western Hemisphere, which helps explain ethnic disparities in treatment response. Rallon et al confirmed the association of the CC genotype with treatment response in Caucasian HIV/HCV co-infected patients.6 While IL28B polymorphisms have important implications for immune-modulating therapies, they also may modify the effectiveness of antiviral therapy. IL28B polymorphisms and amino acid substitution at the HCV core region predicted SVR to Telaprevir/Peg-interferon/Ribavirin.7

Amino acid substitution in HCV core region and genetic variation near IL28B gene predict viral response to telaprevir with peginterferon and ribavirin - (05/03/10)

Mehta et al. reported an SVR rate of 21% in treated patients in an urban HIV clinic, but only 0.7% of the full cohort, the latter due to a low referral rate.8 New treatment strategies are needed for HCV and HIV/HCV-coinfected patients in urban settings, given the low rates of SVR, particularly in non-Caucasian, genotype 1 HIV-infected men. If a larger series corroborates these results, maintaining the current standard of care in this subpopulation of HCV-infected individuals should be questioned.

IL28B genotyping to aid treatment decisions and deferring therapy pending the availability of new targeted therapies should be considered. Clinicians are being faced with the dilemma of whether to recommend immediate treatment or to "warehouse" the patient i.e., forego standard of care treatment in anticipation of novel therapies. Finally, when a clinician discusses the possible benefits and risks of hepatitis C therapy, the sobering, real-world treatment results should be made available to the patient.


References:

1. Feuerstadt, P, Bunim AL, Garcia H, Karlitz JJ, Massoumi H, Thosani AJ, et al. Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients. Hepatology 2010;51:1137-1143.

2. Kaplounov I, Engelson ES, Reka S, Kotler DP. Body composition and metabolic alterations in chronic hepatitis C (HCV) mono-infection and HIV/HCV co-infection. Gastroenterology. 2004;126:A745.

3. Nasta P, Gatti F, Puoti M, Cologni G, Bergamaschi V, Borghi F, et al Insulin resistance impairs rapid virologic response in HIV/hepatitis C virus co-infected patients on peginterferon-alfa-2a. AIDS 2008, 22: 857-861.

4. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399-401.

5. Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, et al. IL28B polymorphism improves viral kinetics and is the strongest pre-treatment predictor of SVR in HCV-1 patients. Gastroenterology. 2010 Apr 15. [Epub ahead of print]

6. Rallon NI, Naggie S, Benito JM, Medrano J, Restrepo C, Goldstein D, et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS. 2010 May 15;24:F23-29.

7. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, et al. Amino acid substitution in HCV core region and genetic variation near IL28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology. Accepted Article Online: Mar 26 2010

8. Mehta SH, Lucas GM, Mirel LB, Torbenson M, Higgins Y, Moore RD, et al. Limited Effectiveness of Antiviral Treatment for Hepatitis C in an Urban HIV clinic. AIDS 2006;20:2361-2369.

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    ReplyDelete
  3. HEPATITIS B DISEASE IS CURABLE!!!

    I will like to thank you for your weekly write-ups on health matters and help me to thanks Dr, EZIKE for the herbal remedy he render to me. I was diagnosed with hepatitis B virus in August 2009 and I thought the end had come because of what I had read about this disease.

    I read that there is no cure for it and that it is more deadly than HIV. I did a lot of tests in Hospital. I also read your write-ups about hepatitis B virus.
    one day as i was browsing on the internet i saw a post of a man called Alex testifying of how Dr EZIKE cure him from Hepatitis disease after 3yrs, i decide to give him a try then he prepare a herbal remedy for me and send it to me through. by His grace, last March, I went to two hospitals to do fresh tests on hepatitis B and the results were negative. Help tell the world that hepatitis B Virus is curable if they follow the advice of the doctors and believe God for healing. Thanks Dr EZIKE once again...
    Contact this great herbal man with his via email ID: drezikespellcasterhome@outlook.com or call (+2349052115217)

    ReplyDelete