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The Impact of Ethnicity on Hepatitis C Virus Treatment Decisions and Outcomes

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Abstract

Hepatitis C virus infection is a major public health concern. Approximately 4 million people are reported to be infected with the virus in the United States, and the annual death rate due to HCV-associated decompensated liver failure or hepatocellular carcinoma is estimated to be approximately 18,000 within the next decade. Therapeutic success, as measured by a sustained virologic response, is approximately 50 % in G1 patients with pegylated-interferon/ribavirin-based therapies. Independent studies have reported significant variation in response rates depending on the ethnicity or race of the patient, though the underlying reasons are not well understood. Historically, ethnic populations have been underrepresented in most large clinical trials of HCV therapies, even though these populations have disproportionately high rates of HCV infection. Recent clinical trials have investigated genetic variations in key biological pathways that may underlie the mechanisms responsible for the different rates of HCV clearance and treatment outcomes in ethnic populations treated with pegylated-interferon/ribavirin. However, as novel direct-acting antiviral drugs are added to, and eventually replace, existing treatment regimens, the role of the innate immune response in determining treatment outcomes will diminish. Socioeconomic and biological factors can impact rates of HCV infection, disease progression, and treatment outcomes in minority populations. Improved access to health care, novel antiviral treatments, and a better understanding of the host factors that contribute to disparities in treatment outcomes are expected to result in optimized treatment paradigms that directly target the virus, leading to improved outcomes for all patients.

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Abbreviations

BMI:

Body mass index

BOC:

Boceprevir

CHC:

Chronic hepatitis C

DAAs:

Direct-acting antivirals

GWAS:

Genome-wide association study

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HIV:

Human immunodeficiency virus

HLA:

Human leukocyte antigen

IDU:

Injection drug users

ISP:

Interferon signaling pathway

ISG:

Interferon signaling gene

LFT:

Liver function tests

MHC:

Major histocompatibility complex

MxA:

Myxovirus resistance-1

NASH:

Nonalcoholic steatohepatitis

OAS:

2-5-oligoadenylate synthetase 1

PKR:

Protein kinase

SNP:

Single nucleotide polymorphisms

SOC:

Standard of care

SVR:

Sustained virologic response

TPV:

Telaprevir

USA:

United States of America

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Acknowledgments

The authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and are fully responsible for all content and editorial decisions, and were involved at all stages of manuscript development. The authors would also like to personally thank Dr. Emmet B. Keeffe for his critical reading of this manuscript, and his many insightful comments. Financial support for writing assistance for this manuscript furnished by José L. Walewski, PhD, was provided by Genentech, Inc.

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Authors and Affiliations

  1. Hepatology Program, Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, 63110-1010, USA

    Mauricio Lisker-Melman

  2. Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, 650 West 168th Street, Room 1006, Box 57A, New York, NY, 10032, USA

    José L. Walewski

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  1. Mauricio Lisker-Melman
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  2. José L. Walewski
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Correspondence to Mauricio Lisker-Melman.

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In Memoriam

To Emmet B. Keeffe: Professor, Mentor, Colleague and Friend.

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Lisker-Melman, M., Walewski, J.L. The Impact of Ethnicity on Hepatitis C Virus Treatment Decisions and Outcomes. Dig Dis Sci 58, 621–629 (2013). https://doi.org/10.1007/s10620-012-2392-0

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