eMedicine Specialties > Gastroenterology > Liver

Hepatitis C: Differential Diagnoses & Workup

Author: Sandeep Mukherjee, MB, BCh, MPH, FRCPC, Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center
Coauthor(s): Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Professor of Medicine, Charles Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Contributor Information and Disclosures

Updated: Jun 18, 2009

Differential Diagnoses

Autoimmune Hepatitis
Cholangitis
Hepatitis, Viral

Other Problems to Be Considered

Drug-induced hepatitis

Workup

Laboratory Studies

  • Alanine aminotransferase
    • Determining the alanine aminotransferase (ALT) level is useful for monitoring the effectiveness of therapy for HCV infection.
    • Because ALT levels can fluctuate, a single value in the reference range does not rule out active infection, progressive liver disease, or cirrhosis. ALT normalization with therapy is not proof of cure.
  • Hepatitis C antibody test
    • Anti-HCV serologic screening involves an enzyme immunoassay (EIA), including second- and third-generation EIAs. These assays are 97% specific but cannot distinguish acute from chronic infection.
    • The most recent third-generation EIA involves detecting antibodies against core protein and nonstructural proteins 3, 4, and 5 and can yield positive results an average of 8 weeks after the onset of infection.
    • False-negative results for the presence of HCV antibody can occur in persons with compromised immune systems, such as those with HIV type 1 infection, renal failure, or HCV-associated essential mixed cryoglobulinemia. False-positive EIA results can occur in persons without risk factors and in those without signs of liver disease, such as blood donors or health care workers.
  • Recombinant immunoblot assay
    • The recombinant immunoblot assay is used to confirm HCV infection. A positive immunoblot assay result is defined as the detection of antibodies against 2 or more antigens and an indeterminate assay result defined as the detection of antibodies against a single antigen.
    • A positive immunoblot assay result followed by 2 or more instances of undetectable HCV RNA suggests HCV infection has resolved. A positive anti-HCV immunoassay result followed by a negative immunoblot assay result represents a false-positive immunoassay, and no further testing is required.
    • The recombinant immunoblot assay has limited usefulness in clinical practice.
  • Qualitative and quantitative assays for HCV RNA
    • Qualitative assays can be used to test for HCV RNA. HCV RNA can be detected in blood using amplification techniques such as PCR or transcription-mediated amplification (TMA). The US Food and Drug Administration (FDA) has approved 2 PCR-based tests for qualitative HCV RNA detection.
      • Amplicor Hepatitis C Virus Test, version 2.0 (Roche Molecular Systems; Pleasanton, Calif) - PCR with a lower limit of detection of 50 IU/mL
      • Cobas Amplicor Hepatitis C Virus Test, version 2.0 (Roche Molecular Systems; Branchburg, NJ) - PCR with a lower limit of detection of 50 IU/mL
      • Versant HCV RNA Qualitative Assay, (Bayer HealthCare; Tarrytown, NY) - TMA with a lower limit of detection of 9.6 IU/mL
    • Quantitative assays ascertain HCV RNA quantity on blood using signal amplification (branched DNA assay) or target amplification techniques (PCR, TMA). The HCV RNA level in blood helps predict the likelihood of a response to treatment, and the change in HCV RNA level can also be used to monitor response. The same quantitative test should be used throughout therapy to avoid confusion, and results should be reported in international units to standardize data. The only FDA-approved quantitative test is Versant HCV RNA, version 3.0 (Bayer HealthCare; Tarrytown, NY). It is based on branched DNA technology and has a dynamic range of 615-7,700,000 IU/mL.
  • HCV genotyping
    • Genotyping is helpful for predicting the likelihood of response and duration of treatment. Patients with genotypes 1 and 4 are generally treated for 12 months, whereas 6 months of treatment is sufficient for other genotypes.
    • Genotyping can be performed by direct sequence analysis, reverse hybridization to genotype-specific oligonucleotide probes, or restriction fragment length polymorphisms.
    • Two tests are available; however, neither has been approved by the FDA. They are as follows:
      • Trugene HCV 5'NC Genotyping kit (Visible Genetics; Toronto, Canada) - Based on direct sequencing followed by comparison with a reference sequence database
      • Line Probe Assay (Inno LiPA HCVII, Innogenetics; Ghent, Belgium) - Based on reverse hybridization of PCR amplicon on a nitrocellulose strip coated with genotype-specific oligonucleotide probes
  • Diagnostic algorithm for the evaluation of hepatitis C - See Media file 4
  • Baseline investigations
    • Perform a CBC count with differential.
    • Perform liver function tests, including an ALT level determination.
    • Obtain the patient's thyrotropin level.
    • Order an anti-HCV antibody EIA.
    • Genotyping should be performed as an aid for guiding treatment.
    • Order a quantitative HCV RNA assay. Reverse transcriptase PCR is more sensitive than bDNA testing.
    • Stress testing may be necessary in appropriate patients.
    • Screen the patient for co-infection with HIV or hepatitis B virus (HBV).
    • Screen the patient for alcohol abuse, drug abuse, and/or depression.
    • An ophthalmological examination may be necessary.
  • Treatment toxicity
    • Patients should be closely monitored for treatment toxicity.
    • Tests to help monitor drug toxicity include CBC count with differential, renal function testing, liver function tests (including ALT level), and thyrotropin level.

Imaging Studies

  • Ultrasonography of the liver

Procedures

  • Liver biopsy: Liver biopsy is not considered mandatory before the initiation of treatment, but this may be helpful for assessing the activity and severity of HCV-related liver disease. However, some experts recommend biopsy only in the following situations:
    • The diagnosis is uncertain.
    • Other co-infections or disease may be present.
    • The patient being considered for treatment has normal liver enzyme levels and no extrahepatic manifestations.
    • The patient is immunocompromised.

Histologic Findings

Lymphocytic infiltration, moderate degrees of inflammation and necrosis, and portal or bridging fibrosis are noted. Regenerative nodules are seen in patients with cirrhosis. Some patients also may have findings indicative of HCC.

Most pathologists give separate measurements of disease activity (grade) and fibrosis (stage). Many trials use the Ishak (6-point scale) and Knodell histological activity index (18-point score); both are useful for assessing improvements in histology findings in studies but are impractical for clinical use because of interobserver disagreement. The METAVIR score was developed by the French METAVIR Cooperative Study Group and reported by Bedossa and Poynard in 1996; it is frequently used in European trials. It consists of a 3-point activity scale and 4-point fibrosis score, with good agreement among pathologists. In the United States, many pathologists use a scale described by Batts and Ludwig in 1995, which consists of an activity grade (0-4) and a fibrosis stage (0-4).

Noninvasive methods of assessing hepatic fibrosis are in development. Current serum assays are directed at measuring breakdown products of extracellular matrix constituents (eg, glycoproteins, propeptides) and their regulatory enzymes (eg, lysyl oxidase, lysyl hydroxylase, propyl hydroxylase).

More on Hepatitis C

Overview: Hepatitis C
Differential Diagnoses & Workup: Hepatitis C
Treatment & Medication: Hepatitis C
Follow-up: Hepatitis C
Multimedia: Hepatitis C
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Frank C, Mohamed MK, Strickland GT, Lavanchy D, Arthur RR, Magder LS, et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet. Mar 11 2000;355(9207):887-91. [Medline].

  2. Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC Jr, Perrillo RP, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. Nov 30 1989;321(22):1501-6. [Medline].

  3. Stramer SL, Glynn SA, Kleinman SH, Strong DM, Caglioti S, Wright DJ, et al. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing. N Engl J Med. Aug 19 2004;351(8):760-8. [Medline].

  4. Rischitelli G, Harris J, McCauley L, Gershon R, Guidotti T. The risk of acquiring hepatitis B or C among public safety workers: a systematic review. Am J Prev Med. May 2001;20(4):299-306. [Medline].

  5. Yeung LT, King SM, Roberts EA. Mother-to-infant transmission of hepatitis C virus. Hepatology. Aug 2001;34(2):223-9. [Medline].

  6. Alter MJ, Kruszon-Moran D, Nainan OV, McQuillan GM, Gao F, Moyer LA, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. Aug 19 1999;341(8):556-62. [Medline]. [Full Text].

  7. Niederau C, Lange S, Heintges T, Erhardt A, Buschkamp M, Hurter D, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. Dec 1998;28(6):1687-95. [Medline].

  8. Bellentani S, Pozzato G, Saccoccio G, Crovatto M, Crocè LS, Mazzoran L, et al. Clinical course and risk factors of hepatitis C virus related liver disease in the general population: report from the Dionysos study. Gut. Jun 1999;44(6):874-80. [Medline].

  9. El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med. Nov 18 2003;139(10):817-23. [Medline].

  10. Kim WR. The burden of hepatitis C in the United States. Hepatology. Nov 2002;36(5 Suppl 1):S30-4. [Medline].

  11. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. Sep 26 2002;347(13):975-82. [Medline].

  12. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology. May 2002;122(5):1303-13. [Medline].

  13. Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, Peters M, et al. Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med. Dec 18 1986;315(25):1575-8. [Medline].

  14. Di Bisceglie AM, Martin P, Kassianides C, Lisker-Melman M, Murray L, Waggoner J, et al. Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. N Engl J Med. Nov 30 1989;321(22):1506-10. [Medline].

  15. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med. Nov 19 1998;339(21):1485-92. [Medline]. [Full Text].

  16. Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. Nov 15 2001;345(20):1452-7. [Medline].

  17. Tong MJ, Reddy KR, Lee WM, Pockros PJ, Hoefs JC, Keeffe EB, et al. Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group. Hepatology. Sep 1997;26(3):747-54. [Medline].

  18. Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, et al. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med. Dec 7 2000;343(23):1666-72. [Medline].

  19. Heathcote EJ, Shiffman ML, Cooksley WG, Dusheiko GM, Lee SS, Balart L, et al. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis. N Engl J Med. Dec 7 2000;343(23):1673-80. [Medline].

  20. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. Sep 22 2001;358(9286):958-65. [Medline].

  21. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. Mar 2 2004;140(5):346-55. [Medline].

  22. Afdhal NH, Dieterich DT, Pockros PJ, Schiff ER, Shiffman ML, Sulkowski MS, et al. Epoetin alfa maintains ribavirin dose in HCV-infected patients: a prospective, double-blind, randomized controlled study. Gastroenterology. May 2004;126(5):1302-11. [Medline].

  23. Van Thiel DH, Faruki H, Friedlander L, Fagiuoli S, Caraceni P, Molloy PJ, et al. Combination treatment of advanced HCV associated liver disease with interferon and G-CSF. Hepatogastroenterology. Nov-Dec 1995;42(6):907-12. [Medline].

  24. Schaefer M, Engelbrecht MA, Gut O, Fiebich BL, Bauer J, Schmidt F, et al. Interferon alpha (IFNalpha) and psychiatric syndromes: a review. Prog Neuropsychopharmacol Biol Psychiatry. May 2002;26(4):731-46. [Medline].

  25. [Best Evidence] McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med. Apr 30 2009;360(18):1827-38. [Medline].

  26. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-García J, Lazzarin A, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. Jul 29 2004;351(5):438-50. [Medline].

  27. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. Jul 29 2004;351(5):451-9. [Medline].

  28. Laguno M, Murillas J, Blanco JL, Martínez E, Miquel R, Sánchez-Tapias JM, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. Sep 3 2004;18(13):F27-36. [Medline].

  29. Villa E, Grottola A, Buttafoco P, Colantoni A, Bagni A, Ferretti I, et al. High doses of alpha-interferon are required in chronic hepatitis due to coinfection with hepatitis B virus and hepatitis C virus: long term results of a prospective randomized trial. Am J Gastroenterol. Oct 2001;96(10):2973-7. [Medline].

  30. Liu CJ, Chen PJ, Lai MY, Kao JH, Jeng YM, Chen DS. Ribavirin and interferon is effective for hepatitis C virus clearance in hepatitis B and C dually infected patients. Hepatology. Mar 2003;37(3):568-76. [Medline].

  31. Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. May 27 2004;350(22):2265-71. [Medline].

  32. Hepburn MJ, Hepburn LM, Cantu NS, Lapeer MG, Lawitz EJ. Differences in treatment outcome for hepatitis C among ethnic groups. Am J Med. Aug 1 2004;117(3):163-8. [Medline].

  33. Fabrizi F, Dulai G, Dixit V, Bunnapradist S, Martin P. Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients. Aliment Pharmacol Ther. Dec 2003;18(11-12):1071-81. [Medline].

  34. Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR. The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology. Apr 2002;122(4):889-96. [Medline].

  35. Samuel D, Bizollon T, Feray C, Roche B, Ahmed SN, Lemonnier C, et al. Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study. Gastroenterology. Mar 2003;124(3):642-50. [Medline].

  36. Narayanan Menon KV, Poterucha JJ, El-Amin OM, Burgart LJ, Kremers WK, et al. Treatment of posttransplantation recurrence of hepatitis C with interferon and ribavirin: lessons on tolerability and efficacy. Liver Transpl. Jul 2002;8(7):623-9. [Medline].

  37. Mukherjee S, Rogge J, Weaver L, Schafer DF. Pilot study of pegylated interferon alfa-2b and ribavirin for recurrent hepatitis C after liver transplantation. Transplant Proc. Dec 2003;35(8):3042-4. [Medline].

  38. Rodriguez-Luna H, Khatib A, Sharma P, De Petris G, Williams JW, Ortiz J, et al. Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon alpha2b and ribavirin: an open-label series. Transplantation. Jan 27 2004;77(2):190-4. [Medline].

  39. Hui CK, Monto A, Belaye T, Lau E, Wright TL. Outcomes of interferon alpha and ribavirin treatment for chronic hepatitis C in patients with normal serum aminotransaminases. Gut. Nov 2003;52(11):1644-8. [Medline].

  40. Jacobson IM, Ahmed F, Russo MW, Lebovics E, Dieterich DT, Esposito SP, et al. Interferon alfa-2b [correction of alpha-2b]and ribavirin for patients with chronic hepatitis C and normal ALT. Am J Gastroenterol. Sep 2004;99(9):1700-5. [Medline].

  41. Crippin JS, McCashland T, Terrault N, Sheiner P, Charlton MR. A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation. Liver Transpl. Apr 2002;8(4):350-5. [Medline].

  42. Everson GT. Treatment of chronic hepatitis C in patients with decompensated cirrhosis. Rev Gastroenterol Disord. 2004;4 Suppl 1:S31-8. [Medline].

  43. Wiley TE, McCarthy M, Breidi L, McCarthy M, Layden TJ. Impact of alcohol on the histological and clinical progression of hepatitis C infection. Hepatology. Sep 1998;28(3):805-9. [Medline].

  44. Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology. Apr 2004;39(4):1147-71. [Medline].

  45. Hayashi N, Kasahara A. Interferon for decreasing the incidence of hepatocellular carcinoma in patients with chronic hepatitis C. Oncology. 2002;62 Suppl 1:87-93. [Medline].

  46. Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Shuto T, Kinoshita H. Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy. Br J Surg. Apr 2002;89(4):418-22. [Medline].

  47. Reiss G, Keeffe EB. Review article: hepatitis vaccination in patients with chronic liver disease. Aliment Pharmacol Ther. Apr 1 2004;19(7):715-27. [Medline].

  48. Ross AS, Bhan AK, Pascual M, Thiim M, Benedict Cosimi A, Chung RT. Pegylated interferon alpha-2b plus ribavirin in the treatment of post-liver transplant recurrent hepatitis C. Clin Transplant. Apr 2004;18(2):166-73. [Medline].

  49. Arenas JI, Vargas HE, Rakela J. The use of hepatitis C-infected grafts in liver transplantation. Liver Transpl. Nov 2003;9(11):S48-51. [Medline].

  50. Bacon BR, McHutchison JG. Into the light: strategies for battling hepatitis C. Am J Manag Care. Dec 2007;13 Suppl 12:S319-26. [Medline].

  51. Balderramo DC, García O, Colmenero J, Espinosa G, Forns X, Ginès P. Antiphospholipid syndrome during pegylated interferon alpha-2a therapy for chronic hepatitis C. Dig Liver Dis. Jan 31 2008;[Medline].

  52. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. Dec 1995;19(12):1409-17. [Medline].

  53. Beaulieu PL. Finger loop inhibitors of the HCV NS5B polymerase: discovery and prospects for new HCV therapy. Curr Opin Drug Discov Devel. Sep 2006;9(5):618-26. [Medline].

  54. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. Aug 1996;24(2):289-93. [Medline].

  55. Bruce MG, Bruden D, McMahon BJ, Christensen C, Homan C, Sullivan D, et al. Clinical significance of elevated alpha-fetoprotein in Alaskan Native patients with chronic hepatitis C. J Viral Hepat. Mar 2008;15(3):179-87. [Medline].

  56. Butt AA, Justice AC, Skanderson M. Rate and predictors of treatment prescription for hepatitis C. Gut. Sep 27 2006.

  57. Cameron AM, Ghobrial RM, Hiatt JR, Carmody IC, Gordon SA, Farmer DG. Effect of nonviral factors on hepatitis C recurrence after liver transplantation. Ann Surg. Oct 2006;244(4):563-71. [Medline].

  58. Chung RT, Gale M Jr, Polyak SJ, Lemon SM, Liang TJ, Hoofnagle JH. Mechanisms of action of interferon and ribavirin in chronic hepatitis C: Summary of a workshop. Hepatology. Jan 2008;47(1):306-20. [Medline].

  59. Ciesek S, Liermann H, Hadem J, Greten T, Tillmann HL, Cornberg M, et al. Impaired TRAIL-dependent cytotoxicity of CD1c-positive dendritic cells in chronic hepatitis C virus infection. J Viral Hepat. Mar 2008;15(3):200-11. [Medline].

  60. Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl. Apr 2003;9(4):331-8. [Medline].

  61. de Ledinghen V, Barreiro P, Foucher J, Labarga P, Castéra L, Vispo ME, et al. Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy. J Viral Hepat. Jun 2008;15(6):427-33. [Medline].

  62. Della Rossa A, Tavoni A, Baldini C, Bombardieri S. Mixed cryoglobulinemia and hepatitis C virus association: ten years later. Isr Med Assoc J. Jun 2001;3(6):430-4. [Medline].

  63. Dev A, Patel K, Conrad A, Blatt LM, McHutchison JG. Relationship of smoking and fibrosis in patients with chronic hepatitis C. Clin Gastroenterol Hepatol. Jun 2006;4(6):797-801. [Medline].

  64. Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology. Jan 2006;130(1):231-64; quiz 214-7. [Medline].

  65. Everson GT, Balart L, Lee SS, Reindollar RW, Shiffman ML, Minuk GY, et al. Histological benefits of virological response to peginterferon alfa-2a monotherapy in patients with hepatitis C and advanced fibrosis or compensated cirrhosis. Aliment Pharmacol Ther. Apr 1 2008;27(7):542-51. [Medline].

  66. Fabrizi F, Dixit V, Messa P, Martin P. Interferon monotherapy of chronic hepatitis C in dialysis patients: meta-analysis of clinical trials. J Viral Hepat. Feb 2008;15(2):79-88. [Medline].

  67. Fontana RJ, Goodman ZD, Dienstag JL, Bonkovsky HL, Naishadham D, Sterling RK, et al. Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C. Hepatology. Mar 2008;47(3):789-98. [Medline].

  68. Fontana RJ, Kleiner DE, Bilonick R, Terrault N, Afdhal N, Belle SH. Modeling hepatic fibrosis in African American and Caucasian American patients with chronic hepatitis C virus infection. Hepatology. Oct 2006;44(4):925-35. [Medline].

  69. Gigi E, Raptopoulou-Gigi M, Kalogeridis A, Masiou S, Orphanou E, Vrettou E, et al. Cytokine mRNA expression in hepatitis C virus infection: TH1 predominance in patients with chronic hepatitis C and TH1-TH2 cytokine profile in subjects with self-limited disease. J Viral Hepat. Feb 2008;15(2):145-54. [Medline].

  70. Goodman ZD, Makhlouf HR, Liu L, Balistreri W, Gonzalez-Peralta RP, Haber B, et al. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. Hepatology. Mar 2008;47(3):836-43. [Medline].

  71. [Best Evidence] Gordon CE, Uhlig K, Lau J, Schmid CH, Levey AS, Wong JB. Interferon treatment in hemodialysis patients with chronic hepatitis C virus infection: a systematic review of the literature and meta-analysis of treatment efficacy and harms. Am J Kidney Dis. Feb 2008;51(2):263-77. [Medline].

  72. Hourigan LF, Macdonald GA, Purdie D, Whitehall VH, Shorthouse C, Clouston A, et al. Fibrosis in chronic hepatitis C correlates significantly with body mass index and steatosis. Hepatology. Apr 1999;29(4):1215-9. [Medline].

  73. Hézode C, Zafrani ES, Roudot-Thoraval F, Costentin C, Hessami A, Bouvier-Alias M, et al. Daily cannabis use: a novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology. Feb 2008;134(2):432-9. [Medline].

  74. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. Jun 1995;22(6):696-9. [Medline].

  75. Kawamura H, Govindarajan S, Aswad F, Machida K, Lai MM, Sung VM. HCV core expression in hepatocytes protects against autoimmune liver injury and promotes liver regeneration in mice. Hepatology. Oct 2006;44(4):936-44. [Medline].

  76. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. Sep-Oct 1981;1(5):431-5. [Medline].

  77. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. Jul 5 2001;345(1):41-52. [Medline].

  78. Lindsay KL, Morishima C, Wright EC, Dienstag JL, Shiffman ML, Everson GT, et al. Blunted cytopenias and weight loss: new correlates of virologic null response to re-treatment of chronic hepatitis C. Clin Gastroenterol Hepatol. Feb 2008;6(2):234-41. [Medline].

  79. McHutchison JG, Bacon BR, Owens GS. Making it happen: managed care considerations in vanquishing hepatitis C. Am J Manag Care. Dec 2007;13 Suppl 12:S327-36; quiz S337-40. [Medline].

  80. McHutchison JG, Manns MP, Longo DL. Definition and management of anemia in patients infected with hepatitis C virus. Liver Int. May 2006;26(4):389-98. [Medline].

  81. Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. Feb 2008;134(2):416-23. [Medline].

  82. NIH Consensus Statement on Management of Hepatitis C: 2002. NIH Consens State Sci Statements. Jun 10-12 2002;19(3):1-46. [Medline].

  83. Patel K, Muir AJ, McHutchison JG. Diagnosis and treatment of chronic hepatitis C infection. BMJ. Apr 29 2006;332(7548):1013-7. [Medline].

  84. Patel K, Nelson DR, Rockey DC, Afdhal NH, Smith KM, Oh E, et al. Correlation of FIBROSpect II with histologic and morphometric evaluation of liver fibrosis in chronic hepatitis C. Clin Gastroenterol Hepatol. Feb 2008;6(2):242-7. [Medline].

  85. Pham TN, King D, Macparland SA, McGrath JS, Reddy SB, Bursey FR, et al. Hepatitis C virus replicates in the same immune cell subsets in chronic hepatitis C and occult infection. Gastroenterology. Mar 2008;134(3):812-22. [Medline].

  86. Pittaluga F, Allice T, Abate ML, Ciancio A, Cerutti F, Varetto S, et al. Clinical evaluation of the COBAS Ampliprep/COBAS TaqMan for HCV RNA quantitation in comparison with the branched-DNA assay. J Med Virol. Feb 2008;80(2):254-60. [Medline].

  87. Poordad F, Reddy KR, Martin P. Rapid virologic response: a new milestone in the management of chronic hepatitis C. Clin Infect Dis. Jan 1 2008;46(1):78-84. [Medline].

  88. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, et al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet. Oct 31 1998;352(9138):1426-32. [Medline].

  89. Pyrsopoulos NT, Reddy KR. Extrahepatic manifestations of chronic viral hepatitis. Curr Gastroenterol Rep. Feb 2001;3(1):71-8. [Medline].

  90. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm Rep. Oct 16 1998;47:1-39. [Medline]. [Full Text].

  91. Reddy KR, Govindarajan S, Marcellin P, Bernstein D, Dienstag JL, Bodenheimer H Jr, et al. Hepatic steatosis in chronic hepatitis C: baseline host and viral characteristics and influence on response to therapy with peginterferon alpha-2a plus ribavirin. J Viral Hepat. Feb 2008;15(2):129-36. [Medline].

  92. Rigamonti C, Donato MF, Fraquelli M, Agnelli F, Ronchi G, Casazza G, et al. Transient elastography predicts fibrosis progression in patients with recurrent hepatitis C after liver transplantation. Gut. Jun 2008;57(6):821-7. [Medline].

  93. Romero-Gomez M, Gomez-Gonzalez E, Madrazo A, Vera-Valencia M, Rodrigo L, Perez-Alvarez R, et al. Optical analysis of computed tomography images of the liver predicts fibrosis stage and distribution in chronic hepatitis C. Hepatology. Mar 2008;47(3):810-6. [Medline].

  94. Schäfer A, Wittchen HU, Seufert J, Kraus MR. Methodological approaches in the assessment of interferon-alfa-induced depression in patients with chronic hepatitis C - a critical review. Int J Methods Psychiatr Res. 2007;16(4):186-201. [Medline].

  95. Seeff LB, Curto TM, Szabo G, Everson GT, Bonkovsky HL, Dienstag JL, et al. Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology. Feb 2008;47(2):605-12. [Medline].

  96. Takaki S, Kawakami Y, Imamura M, Aikata H, Takahashi S, Ishihara H, et al. Eicosapentaenoic acid could permit maintenance of the original ribavirin dose in chronic hepatitis C virus patients during the first 12 weeks of combination therapy with pegylated interferon-alpha and ribavirin. A prospective randomized controlled trial. Intervirology. 2007;50(6):439-46. [Medline].

  97. [Best Evidence] Tang KH, Herrmann E, Pachiadakis I, Paulon E, Tatman N, Zeuzem S, et al. Clinical trial: individualized treatment duration for hepatitis C virus genotype 1 with peginterferon-alpha 2a plus ribavirin. Aliment Pharmacol Ther. May 2008;27(9):810-9. [Medline].

  98. Valenti L, Dongiovanni P, Fargion S, Fracanzani AL. Iron genes, dysmetabolism and fibrosis in chronic hepatitis C. J Hepatol. Mar 2008;48(3):513-4; author reply 514-5. [Medline].

  99. Vidali M, Tripodi MF, Ivaldi A, Zampino R, Occhino G, Restivo L, et al. Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C. J Hepatol. Mar 2008;48(3):399-406. [Medline].

  100. Villacres MC, Literat O, DeGiacomo M, Du W, Frederick T, Kovacs A. Defective response to Toll-like receptor 3 and 4 ligands by activated monocytes in chronic hepatitis C virus infection. J Viral Hepat. Feb 2008;15(2):137-44. [Medline].

  101. Wedemeyer H, Cornberg M, Wiegand J, Manns M. Treatment duration in acute hepatitis C: the issue is not solved yet. Hepatology. Oct 2006;44(4):1051; author reply 1051-2. [Medline].

  102. Yamashita N, Enjoji M, Kotoh K, Kato M, Ueda A, Horikawa Y, et al. Investigation of hyperuricemia during pegylated-interferon-alpha2b plus ribavirin combination therapy in patients with chronic hepatitis C. J Dig Dis. Feb 2008;9(1):27-31. [Medline].

  103. Younossi ZM, Nader FH, Bai C, Sjogren R, Ong JP, Collantes R, et al. A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment. J Viral Hepat. May 2008;15(5):370-8. [Medline].

  104. Yu ML, Huang CF, Dai CY, Huang JF, Chuang WL. Long-term effects of interferon-based therapy for chronic hepatitis C. Oncology. 2007;72 Suppl 1:16-23. [Medline].

  105. Zeuzem S, Alberti A, Rosenberg W, Marcellin P, Diago M, Negro F. Review article: management of patients with chronic hepatitis C virus infection and "normal" alanine aminotransferase activity. Aliment Pharmacol Ther. Oct 15 2006;24(8):1133-49. [Medline].

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Further Reading

Additional resources on asthma are available at Medscape’s Hepatitis C Resource Center.

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Keywords

hepatitis C virus, HCV, HCV infection, non-A non-B hepatitis, NANB hepatitis, acute hepatitis, hepatitis, virus infection, viral infection, virus, chronic liver disease, hepatocellular carcinoma, hepatoma, HCC, cirrhosis, orthotopic liver transplantation, OLT, quasispecies, interferon, IFN, sustained virologic response, sustained virological response, SVR, HIV-HCV coinfection, HIV-HCV co-infection, IFN therapy, interferon therapy, pegylated interferon therapy, PEG-IFN, pegylated interferon, hepatitis C viremia, hepatitis viremia

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Contributor Information and Disclosures

Author

Sandeep Mukherjee, MB, BCh, MPH, FRCPC, Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center
Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Coauthor(s)

Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Professor of Medicine, Charles Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Vinod K Dhawan, MD, FACP, FRCP(C) is a member of the following medical societies: American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Royal College of Physicians and Surgeons of Canada
Disclosure: Pfizer Inc None None

Medical Editor

George Y Wu, MD, PhD, Professor, Department of Medicine, Director, Hepatology Section, Herman Lopata Chair in Hepatitis Research, University of Connecticut School of Medicine
George Y Wu, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, American Medical Association, American Society for Clinical Investigation, and Association of American Physicians
Disclosure: Humana Press Consulting fee Consulting; Novartis Consulting fee Review panel membership

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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