Antiviral Therapy for Treatment Naive Patients with Hepatitis C Virus

aDepartment of Medicine, Harvard Medical School, 25 Shattack Street, Boston, MA 02115, USA hThe Liver Center, Beth Israel Deaconess Medical Center, 110 Francis Street, Suite 8E, Boston, MA 02215, USA

Chronic hepatitis C virus (HCV) infection is recognized as a global health problem, with 170 to 200 million people estimated to be infected worldwide. In the United States, chronic HCV is the most common cause of end-stage liver disease, hepatocellular cancer, and the most frequent indication for liver transplantation [1]. Data from the third National Health and Nutrition Examination Survey (NHANES III) estimated that 2.7 million Americans have active HCV infection [2]. This figure probably underestimates the true prevalence of chronic HCV infection, however, as the study excluded high-risk groups such as prisoners and homeless people. HCV infection generally is regarded as ''a disease of decades,'' as the most significant clinical consequences occur 20 to 30 years after the initial exposure. Approximately 10,000 HCV related deaths occur each year, mostly resulting from end-stage liver disease and development of hepatocellular carcinoma (HCC) [3]. The NHANES study also revealed that HCV prevalence was the highest in persons 30 to 49 years of age. Because of its slowly progressive natural history, the Centers for Disease Control and Prevention (CDC) predict that HCV-associated mortality might double or triple over the next 10 to 20 years [4]. Davis et al estimated that the need for liver transplantation will increase by 528%, and liver-related death might increase by 223% by 2008 [5]. One logical solution is early detection and aggressive antiviral treatment to eradicate HCV or to halt disease progression.

A version of this article originally appeared in the 33:3 issue of Gastroenterology Clinics of North America.

* Corresponding author.

E-mail address: [email protected] (N.H. Afdhal).

0891-5520/06/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.idc.2006.01.007

This article focuses on the most recent therapies for patients with HCV who are naive to therapy. The primary end point for the treatment of nai've HCV patients is viral eradication or a sustained virological response (SVR), which is defined as the absence of HCV in the serum, as detected by a sensitive polymerase chain reaction (PCR) test, 24 weeks after stopping antiviral therapy. Recent data suggest that an SVR can be equated with a biochemical, virological, and histological response that is sustained for up to 5 years and is conceptually a cure of HCV in 90% of patients [6]. Some patients fail to clear HCV by PCR while on treatment, and these are classified as nonre-sponders (NR). Additionally, there is a final group of relapsers, who are able to clear HCV on treatment, but in whom HCV reappears within 24 weeks of stopping treatment. These definitions of patient responses are used in the clinical trials discussed in this article.

Patient selection

The indications for therapy for naive patients have undergone many revisions over the last 10 years (Box 1). Patients who are HCV-positive by PCR test with an elevated alanine aminotransferase (ALT) and necro-

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