Digestive Diseases and Sciences

, Volume 53, Issue 4, pp 1107–1113

Response of Combination Therapy on Viral Load and Disease Severity in Chronic Hepatitis C

  • Deepak Kumar
  • Abdul Malik
  • Mohammad Asim
  • Anita Chakravarti
  • Rakha H. Das
  • Premashis Kar
Original Paper


Influence of genotypes on viral kinetics and disease severity in chronic hepatitis C (CH-C) patients has been implicated, but requires further investigation. The 41 HCV patients were genotyped by restriction fragment length polymorphism and included for 48 weeks of combination therapy on the basis of clinical (alanine amino transferase ≥60 IU/l) and histological features (histological activity index ≥3). A significant number (30/41) of patients (6/9 of genotype 1, 23/30 of genotype 3 and 1/2 of mixed genotype) attain sustained virological response despite high viral load at baseline. More aggressive treatment was required in genotype 1 than in genotype 3 due to slow response rate. Significant (P < 0.05) difference in the viral load of sustained virological responder and non-responder (NR) was observed after 12 weeks of therapy. Severe course of liver disease was observed in 81.81% (9/11) of NR patients at baseline. Data indicate that genotype 1 was a slow responder compared to genotype 3 on combination therapy. Response to combination therapy was almost independent of baseline viral load. However, a positive correlation of viral load with disease severity was observed. The viral kinetics at 12 weeks is an important tool for determination of virological response.


Hepatitis C virus RFLP Virological response Interferon therapy Histological activity index 


  1. 1.
    Kim WR (2002) The burden of hepatitis C in the United States. Hepatol 36:S30–S34CrossRefGoogle Scholar
  2. 2.
    Panigrahi AK, Panda SK, Dixit RK, Rao KV, Acharya SK, Dasarathy S, Nanu A (1997) Magnitude of hepatitis C virus infection in India: prevalence in healthy blood donors, acute and chronic liver diseases. J Med Virol 51:167–174PubMedCrossRefGoogle Scholar
  3. 3.
    Hissar SS, Goyal A, Kumar M, Pandey C, Suneetha PV, Sood A, Midha V, Sakhuja P, Malhotra V, Sarin SK (2006) Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease. J Med Virol 78:452–458PubMedCrossRefGoogle Scholar
  4. 4.
    Rothman AL, Morishima C, Bonkovsky HL, Polyak SJ, Ray R, Di Bisceglie AM, Lindsay KL, Malet PF, Chang M, Gretch DR, Sullivan DG, Bhan AK, Wright EC, Koziel MJ, HALT-C Trial Group (2005) Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C. Hepatol 41:617–625CrossRefGoogle Scholar
  5. 5.
    Martinot-Peignoux M, Marcellin P, Pouteau M, Castelnau C, Boyer N, Poliquin M, Degott C, Descombes I, Le Breton V, Milotova V et al (1995) Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatol 22:1050–1056CrossRefGoogle Scholar
  6. 6.
    Dalgard O, Mangia A (2006) Short-term therapy for patients with hepatitis C virus genotype 2 or 3 infection. Drugs 66:1807–1815PubMedCrossRefGoogle Scholar
  7. 7.
    Hazari S, Panda SK, Gupta SD, Batra Y, Singh R, Acharya SK (2004) Treatment of hepatitis C virus infection in patients of northern India. J Gastroenterol Hepatol 19:1058–1065PubMedCrossRefGoogle Scholar
  8. 8.
    Davis GL, Esteban-Mur R, Rustgi V, Hoefs J, Gordon SC, Trepo C, Shiffman ML, Zeuzem S, Craxi A, Ling MH, Albrecht J (1998) Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. N Engl J Med 339:1493–1499PubMedCrossRefGoogle Scholar
  9. 9.
    Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J (1981) Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatol 1(5):431–435CrossRefGoogle Scholar
  10. 10.
    Chinchai T, Labout J, Noppornpanth S, Theamboonlers A, Haagmans BL, Osterhaus AD, Poovorawan Y (2003) Comparative study of different methods to genotype hepatitis C virus type 6 variants. J Virol Methods 109:195–201PubMedCrossRefGoogle Scholar
  11. 11.
    Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31:3497–3500PubMedCrossRefGoogle Scholar
  12. 12.
    Gerken G, Knolle P, Jakobs S, Meyer zum Buschenfelde KH (1997) Quantification and genotyping of serum HCV-RNA in patients with chronic hepatitis C undergoing interferon treatment. Arch Virol 142:459–464PubMedCrossRefGoogle Scholar
  13. 13.
    Legrand-Abravanel F, Sandres-Saune K, Barange K, Alric L, Moreau J, Desmorat P, Vinel JP, Izopet J (2004) Hepatitis C virus genotype 5: epidemiological characteristics and sensitivity to combination therapy with interferon-alpha plus ribavirin. J Infect Dis 189:1397–1400PubMedCrossRefGoogle Scholar
  14. 14.
    McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, Goodman ZD, Ling MH, Cort S, Albrecht JK (1998) Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 339:1485–1492PubMedCrossRefGoogle Scholar
  15. 15.
    Bukh J, Miller RH, Purcell RH (1995) Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Dis 15(1):41–63PubMedCrossRefGoogle Scholar
  16. 16.
    Zeuzem S (2004) Heterogeneous virological response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well? Ann Intern Med 140(5):370–381PubMedGoogle Scholar
  17. 17.
    Martins RM, Teles SA, Freitas NR, Motta-Castro AR, Souto FJ, Mussi A, Amorim RM, Martins CR (2006) Distribution of hepatitis C virus genotypes among blood donors from mid-west region of Brazil. Rev Inst Med Trop Sao Paulo 48(1):53–55PubMedGoogle Scholar
  18. 18.
    Stuyver L, Wyseur A, van Arnhem W, Lunel F, Laurent-Puig P, Pawlotsky JM, Kleter B, Bassit L, Nkengasong J, van Doorn LJ et al (1995) Hepatitis C virus genotyping by means of 5′-UR/core line probe assays and molecular analysis of untypeable samples. Virus Res 38:137–157PubMedCrossRefGoogle Scholar
  19. 19.
    Gracia-Samaniego J, Soriano V, Castill J, Braco R, Moreno A, Carbo J (1997) Influence of hepatitis C virus genotypes and HIV infection on histological severity of chronic hepatitis C. Am J Gasteroenterol 92:1130–1134Google Scholar
  20. 20.
    Khaja MN, Madhavi C, Thippavazzula R, Nafeesa F, Habib AM, Habibullah CM, Guntaka RV (2005) High prevalence of hepatitis C virus infection and genotype distribution among general population, blood donors and risk groups. Infect Genet Evol 6(3):198–204PubMedGoogle Scholar
  21. 21.
    Brechot C (1994) Hepatitis C virus genetic variability clinical implications. Am J Gastroenterol 89:S41–S47PubMedGoogle Scholar
  22. 22.
    De Moliner L, Pontisso P, De Salvo GL, Cavalletto L, Chemello L, Alberti A (1998) Serum and liver HCV RNA levels in patients with chronic hepatitis C: correlation with clinical and histological features. Gut 42(6):856–860PubMedCrossRefGoogle Scholar
  23. 23.
    Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347(13):975–982PubMedCrossRefGoogle Scholar
  24. 24.
    Missale G, Cariani E, Lamonaca V, Ravaggi A, Rossini A, Bertoni R, Houghton M, Matsuura Y, Miyamura T, Fiaccadori F, Ferrari C (1997) Effects of interferon treatment on the antiviral T-cell response in hepatitis C virus genotype 1b- and genotype 2c-infected patients. Hepatology 26(3):792–797PubMedCrossRefGoogle Scholar
  25. 25.
    Adinolfi LE, Utili R, Andreana A, Tripodi MF, Marracino M, Gambardella M, Giordano M, Ruggiero G (2001) Serum HCV RNA levels correlate with histological liver damage and concur with steatosis in progression of chronic hepatitis C. Dig Dis Sci 46(8):1677–1683PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Deepak Kumar
    • 1
    • 2
    • 3
  • Abdul Malik
    • 1
  • Mohammad Asim
    • 1
  • Anita Chakravarti
    • 2
  • Rakha H. Das
    • 3
  • Premashis Kar
    • 1
    • 4
  1. 1.Department of MedicineMaulana Azad Medical CollegeNew DelhiIndia
  2. 2.Department of MicrobiologyMaulana Azad Medical CollegeNew DelhiIndia
  3. 3.Comparative genomics UnitInstitute of Genomics and Integrative BiologyDelhiIndia
  4. 4.New DelhiIndia

Personalised recommendations