Diagnosis of hepatitis C virus infection in patients on dialysis
- Svetlozar Natov, MD
Svetlozar Natov, MD
- Assistant Professor of Medicine
- Tufts University School of Medicine
- Brian JG Pereira, MD
Brian JG Pereira, MD
- Professor of Medicine
- Tufts University School of Medicine
- Section Editors
- Jeffrey S Berns, MD
Jeffrey S Berns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Dialysis
- Professor of Medicine
- Perelman School of Medicine at the University of Pennsylvania
- Martin S Hirsch, MD
Martin S Hirsch, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Viral Infections
- Professor of Medicine
- Harvard Medical School
In 1989, the hepatitis C virus (HCV) was cloned and identified as the major cause of parenterally transmitted non-A, non-B hepatitis (NANBH) [1,2]. The transmission of HCV by transfusion of blood products and by sharing of needles among intravenous drug abusers has been unequivocally demonstrated. Horizontal transmission by sexual and/or household exposure and vertical transmission from mother to fetus have also been reported. Tests are now available that detect antibodies to multiple HCV antigens (anti-HCV), and the presence and titer of HCV RNA .
The basic biology of HCV, the limitations and types of methods used to detect the presence of the virus, and the clinical course of infected patients, with an emphasis on issues relevant to the patient with end-stage renal disease (ESRD), are reviewed here. Issues relating to HCV infection in patients on maintenance dialysis or receiving a renal transplant are discussed separately. (See "Hepatitis C virus infection in patients on maintenance dialysis" and "Hepatitis C virus infection in kidney donors".)
STRUCTURE OF HCV GENOME
The hepatitis C virus (HCV) is a small 40 to 60 nm virus with a lipid envelope and a single-stranded RNA viral genome comprising approximately 9500 nucleotides [1,4]. The N-terminus encodes the basic nucleocapsid (C), followed by two glycoprotein domains, the envelope (E1) and second envelope/non-structural-1 (E2/NS1) regions. Downstream to this region are the nonstructural genes NS2, NS3, NS4, and NS5, respectively.
Several HCV genotypes have been identified, and significant genetic heterogeneity has been observed over the entire viral genome. The regions encoding the E1 and E2/NS1 are the most variable sequences of the viral genome, while the 5' noncoding region (5'NCR) represents the most conserved one.
A universal system for the nomenclature of HCV genotypes has defined six major groups (1 to 6), designated as HCV types . Each major type consists of one or more closely related variants, designated as subtypes and named a, b, c, etc, in order of discovery. Finally, each subtype includes individual isolates. (See "Characteristics of the hepatitis C virus".)
- Choo QL, Kuo G, Weiner AJ, et al. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244:359.
- Kuo G, Choo QL, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 1989; 244:362.
- Fehr T, Ambühl PM. Chronic hepatitis virus infections in patients on renal replacement therapy. Nephrol Dial Transplant 2004; 19:1049.
- Houghton M, Weiner A, Han J, et al. Molecular biology of the hepatitis C viruses: implications for diagnosis, development and control of viral disease. Hepatology 1991; 14:381.
- Simmonds P, Alberti A, Alter HJ, et al. A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatology 1994; 19:1321.
- Fabrizi F, Poordad FF, Martin P. Diagnostic workup of hepatitis C and the patient on maintenance dialysis. Int J Artif Organs 2001; 24:843.
- Farci P, Alter HJ, Wong D, et al. A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. N Engl J Med 1991; 325:98.
- Weiner AJ, Kuo G, Bradley DW, et al. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 1990; 335:1.
- Podzorski RP. Molecular testing in the diagnosis and management of hepatitis C virus infection. Arch Pathol Lab Med 2002; 126:285.
- Busch MP, Wilber JC, Johnson P, et al. Impact of specimen handling and storage on detection of hepatitis C virus RNA. Transfusion 1992; 32:420.
- Grant PR, Kitchen A, Barbara JA, et al. Effects of handling and storage of blood on the stability of hepatitis C virus RNA: implications for NAT testing in transfusion practice. Vox Sang 2000; 78:137.
- Lau JY, Davis GL, Orito E, et al. Significance of antibody to the host cellular gene derived epitope GOR in chronic hepatitis C virus infection. J Hepatol 1993; 17:253.
- Hofgärtner WT, Kant JA, Weck KE. Hepatitis C virus quantitation: optimization of strategies for detecting low-level viremia. J Clin Microbiol 2000; 38:888.
- Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 1989; 339:237.
- Fabrizi F, Martin P, Quan S, et al. Serotyping strip immunoblot assay for assessing hepatitis C virus strains in dialysis patients. Am J Kidney Dis 2000; 35:832.
- Saab S, Brezina M, Gitnick G, et al. Hepatitis C screening strategies in hemodialysis patients. Am J Kidney Dis 2001; 38:91.
- Aach RD, Stevens CE, Hollinger FB, et al. Hepatitis C virus infection in post-transfusion hepatitis. An analysis with first- and second-generation assays. N Engl J Med 1991; 325:1325.
- Soffredini R, Rumi M, Lampertico P, et al. Increased detection of antibody to hepatitis C virus in renal transplant patients by third-generation assays. Am J Kidney Dis 1996; 28:437.
- Fabrizi F, Lunghi G, Raffaele L, et al. Serologic survey for control of hepatitis C in haemodialysis patients: third-generation assays and analysis of costs. Nephrol Dial Transplant 1997; 12:298.
- Busch MP, Korelitz JJ, Kleinman SH, et al. Declining value of alanine aminotransferase in screening of blood donors to prevent posttransfusion hepatitis B and C virus infection. The Retrovirus Epidemiology Donor Study. Transfusion 1995; 35:903.
- Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int Suppl 2008; :S1.
- Tanaka T, Lau JY, Mizokami M, et al. Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia. J Hepatol 1995; 23:742.
- Tanaka E, Ohue C, Aoyagi K, et al. Evaluation of a new enzyme immunoassay for hepatitis C virus (HCV) core antigen with clinical sensitivity approximating that of genomic amplification of HCV RNA. Hepatology 2000; 32:388.
- Aoyagi K, Ohue C, Iida K, et al. Development of a simple and highly sensitive enzyme immunoassay for hepatitis C virus core antigen. J Clin Microbiol 1999; 37:1802.
- Kurtz JB, Boxall E, Qusir N, et al. The diagnostic significance of an assay for 'total' hepatitis C core antigen. J Virol Methods 2001; 96:127.
- Seme K, Poljak M, Babic DZ, et al. The role of core antigen detection in management of hepatitis C: a critical review. J Clin Virol 2005; 32:92.
- Dentico P, Sacco R, Buongiorno R, et al. Hepatitis C virus-RNA, immunoglobulin M anti-HCV and risk factors in haemodialysis patients. Microbios 1999; 99:55.
- Natov SN, Pereira BJ. Hepatitis C in dialysis patients. Adv Ren Replace Ther 1996; 3:275.
- Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int 1997; 51:981.
- Galán F, Pérez-Gracia MT, Lozano A, et al. A 3-year follow-up of HCV-RNA viraemia in haemodialysis patients. Nephrol Dial Transplant 1998; 13:1211.
- Barril G, Castillo I, Arenas MD, et al. Occult hepatitis C virus infection among hemodialysis patients. J Am Soc Nephrol 2008; 19:2288.
- Umlauft F, Gruenewald K, Weiss G, et al. Patterns of hepatitis C viremia in patients receiving hemodialysis. Am J Gastroenterol 1997; 92:73.
- Alter MJ, Margolis HS, Krawczynski K, et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med 1992; 327:1899.
- al Meshari K, al Ahdal M, Alfurayh O, et al. New insights into hepatitis C virus infection of hemodialysis patients: the implications. Am J Kidney Dis 1995; 25:572.
- Pereira BJ, Milford EL, Kirkman RL, et al. Prevalence of hepatitis C virus RNA in organ donors positive for hepatitis C antibody and in the recipients of their organs. N Engl J Med 1992; 327:910.
- Kalantar-Zadeh K, Miller LG, Daar ES. Diagnostic discordance for hepatitis C virus infection in hemodialysis patients. Am J Kidney Dis 2005; 46:290.
- Martin P, Fabrizi F. Treatment of chronic hepatitis C infection in patients with renal failure. Clin Gastroenterol Hepatol 2005; 3:S113.
- Espinosa M, Martin-Malo A, Alvarez de Lara MA, et al. Natural history of acute HCV infection in hemodialysis patients. Clin Nephrol 2002; 58:143.
- Kiyosawa K, Sodeyama T, Tanaka E, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 1990; 12:671.
- Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 1995; 332:1463.
- Aeder MI, Shield CF, Tegtmeier GE, et al. Incidence and clinical impact of hepatitis C virus-positive donors in cadaveric transplantation. Transplant Proc 1993; 25:1469.
- Wolf PL, Williams D, Coplon N, Coulson AS. Low aspartate transaminase activity in serum of patients undergoing chronic hemodialysis. Clin Chem 1972; 18:567.
- Terrault NA, Adey DB. The kidney transplant recipient with hepatitis C infection: pre- and posttransplantation treatment. Clin J Am Soc Nephrol 2007; 2:563.
- Rao KV, Anderson WR, Kasiske BL, Dahl DC. Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients. Am J Med 1993; 94:241.
- Meyers CM, Seeff LB, Stehman-Breen CO, Hoofnagle JH. Hepatitis C and renal disease: an update. Am J Kidney Dis 2003; 42:631.
- STRUCTURE OF HCV GENOME
- TESTS FOR HCV RNA
- Qualitative polymerase chain reaction assay
- - False negatives
- - False positives
- Quantitative assays for HCV RNA
- Tests for genotypes
- TESTS FOR ANTIBODY TO HCV
- TESTS FOR HEPATITIS C CORE ANTIGEN
- DIFFICULTIES IN INTERPRETING HCV TESTS
- The anti-HCV-positive and HCV RNA-negative patient
- The anti-HCV-negative and HCV RNA-positive patient
- KDIGO GUIDELINES FOR HCV TESTING
- CLINICAL COURSE OF HCV INFECTION
- Relationship among serum ALT, HCV infection, and liver disease
- Liver biopsy
- SUMMARY AND RECOMMENDATIONS