Diagnosis, management, and treatment of hepatitis C: An update # † ‡

Abstract

This document has been approved by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology. These recommendations provide a data-supported approach to establishing guidelines. They are based on the following: (1) a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2008); (2) the American College of Physicians' Manual for Assessing Health Practices and Designing Practice Guidelines;1 (3) guideline policies, including the American Association for the Study of Liver Diseases' (AASLD) Policy on the Development and Use of Practice Guidelines and the American Gastroenterological Association's Policy Statement on the Use of Medical Practice Guidelines;2 and (4) the experience of the authors in regard to hepatitis C. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the quality of evidence supporting recommendations, the Practice Guidelines Committee of the AASLD requires a Class (reflecting benefit versus risk) and Level (assessing strength or certainty) of Evidence to be assigned and reported with each recommendation (Table 1, adapted from the American College of Cardiology and the American Heart association Practice Guidelines).3, 4 AASLD, American Association for the Study of Liver Diseases; ALT, alanine aminotransferase; ANC, absolute neutrophil count; anti-HCV, antibody to HCV; AST, aspartate aminotransferase; CKD, chronic kidney disease; CTP, Child-Turcotte-Pugh; EIA, enzyme immunoassay; ETR, end-of-treatment response; EVR, early virological response; FDA, U.S. Food and Drug Administration; HCV, hepatitis C virus; HIV, human immunodeficiency virus; PCR, polymerase chain reaction; PEG, polyethylene glycol; RVR, rapid virological response; SVR, sustained virological response; ULN, upper limit of normal. The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease.5 An estimated 180 million people are infected worldwide.6 In the United States (U.S.), the prevalence of HCV infection between the years 1999 and 2002 was 1.6%, equating to about 4.1 million persons positive for antibody to hepatitis C (anti-HCV), 80% of whom are estimated to be viremic.7 Hepatitis C is the principal cause of death from liver disease and the leading indication for liver transplantation in the U.S.8 Some calculations suggest that mortality related to HCV infection (death from liver failure or hepatocellular carcinoma) will continue to increase over the next two decades.9 The purpose of this document is to provide clinicians with evidence-based approaches to the prevention, diagnosis, and management of HCV infection. The optimal approach to detecting HCV infection is to screen persons for a history of risk of exposure to the virus, and to test selected individuals who have an identifiable risk factor.10 Currently, injection drug use is the primary mode of HCV transmission in the U.S; thus, all persons who use or have used illicit injection drugs in the present or past, even if only once, as well as intranasal drug users who share paraphernalia, should be tested for HCV infection.7, 11, 12 Individuals who have received a blood or blood component transfusion or an organ transplant before 1992 should also be tested. With the introduction of sensitive tests to screen blood donors for HCV antibodies in 1992, transfusion-transmission of HCV has become rare.12, 13 Persons with hemophilia should be tested for HCV infection if blood products were received before 1987, after which time, viral inactivation procedures were implemented.14 Similarly, individuals with unexplained elevations of the aminotransferase levels (alanine and/or aspartate aminotransferase; ALT/AST), those ever on hemodialysis, children born to HCV-infected mothers, or those with human immunodeficiency virus (HIV) infection should be tested for the presence of HCV infection.15-17 Other potential sources of HCV transmission include exposure to an infected sexual partner or multiple sexual partners, exposure among health care workers to HCV-contaminated blood and blood products, and tattooing.12, 15, 18-23 The prevalence of HCV infection is consistently higher among persons with multiple sexual partners, whereas sexual transmission of HCV between monogamous partners is uncommon.11, 18 Thus, although it is prudent to counsel HCV-infected persons to notify their current partners of their HCV status, they should be informed that the risk of sexual transmission is sufficiently low19 that many authorities do not advise the use of barrier protection among monogamous couples.18 Nevertheless, between 1% and 5% of monogam