Diagnosis, management, and treatment of hepatitis C†

Abstract

HCV, hepatitis C virus; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HIV, human immunodeficiency virus; anti-HCV, HCV antibody; RNA, ribonucleic acid; PCR, polymerase chain reaction; TMA, transcription-mediated amplification; FDA, Food and Drug Administration; HCC, hepatocellular carcinoma; SVR, sustained virologic response; EVR, early virologic response; ETR, end of treatment response; peginterferon, pegylated interferon; G-CSF, granulocyte colony-stimulating factor; HAART, highly active antiretroviral therapy; ddI, didanosine; GM-CSF, granulocyte-macrophage colony-stimulating factor. These recommendations provide a data-supported approach. They are based on the following: (1) a formal review and analysis of the recently published world literature on the topic (Medline search); (2) the American College of Physicians' Manual for Assessing Health Practices and Designing Practice Guidelines1 ; (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 Guidelines2; the guideline procedures of the Infectious Diseases Society of America3; and (4) the experience of the authors in the specified topic. These recommendations are fully endorsed by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology. 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. In an attempt to characterize the quality of evidence supporting recommendations, the Practice Guidelines Committee of the AASLD requires a category to be assigned and reported with each recommendation (Table 1). The hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease. In the United States, the Centers for Disease Control and Prevention estimates that there are more than 2.7 million people with ongoing HCV infection.5 HCV is the leading cause of death from liver disease in the United States.6 The purpose of this article is to provide clinicians with approaches to the diagnosis, management, and prevention of HCV infection. The optimal methods of detecting HCV infection are to screen populations for history of risk and to test selected individuals with an identifiable risk factor. With careful questioning, an HCV risk factor can be identified in more than 90% of cases.7 The primary source of HCV transmission is HCV-infected blood or blood products. In the United States, injection drug use is the chief mode of transmission, and anyone who has ever injected illicit drugs should be tested.5, 7 Persons should also be tested if they received a blood or blood component transfusion or organ transplant before 1992, when sensitive tests were first used to screen donors for HCV antibodies. Since that time, HCV infection is rarely transmitted by transfusion.8 Other potential sources of HCV transmission include exposure to an infected sexual partner or multiple sexual partners, frequent exposure to infected blood among health care workers, and perinatal exposure.9-11 Although HCV prevalence rates are consistently higher in persons with multiple sexual partners, sexual transmission of HCV between monogamous partners is rare.7 Thus, while it is common to counsel HCV-infected persons to notify their current partners of their HCV status, they should be told that the risk of sexual transmission is sufficiently low12 that many authorities do not advise use of barrier precautions (i.e., latex condoms). Testing of sexual partners, therefore, is done chiefly for reassurance. There is no need to curtail ordinary household activities except those that might result in blood exposure, such as sharing a razor or toothbrush. HCV is not transmitted by hugging and the sharing of eating utensils. Although a monogamous sexual relationship carries a low risk of transmission of HCV infection, as noted above, the risk is higher in persons involved with multiple sexual partners. Persons with hemophilia should be tested for HCV infection if blood products were received before 1987, when viral inactivation procedures were implemented. It is also advisable to test persons for HCV infection if they have evidence of otherwise unexplained elevations of aminotransferase levels (alanine and/or aspartate aminotransferases; ALT /AST), have ever been on hemodialysis, or have human immunodeficiency virus (HIV) infection.10 Other situations that have been suggested to carry a risk for HCV transmission include certain folk medicine practices (acupuncture, ritual scarification), body piercing, tattooing, and even commercial bar