We have undertaken a comprehensive study of hepatitis C virus (HCV) genotype and its clinical significance in haemophilic patients. 189 HCV RNA positive patients were typed, using the Simmonds classification scheme, by restriction fragment length polymorphism (RFLP) in an amplified segment of the 5 non-coding region of the HCV genome. Type 1 was found in 121 (64.0%), type 2 in 23 (12.2%), type 3 in 36 (19.0%), type 4 in 3 (1.6%), type 5 in 2 (1.1%) and mixed infection in 3 (1.6%). There were no type 6 infections and one patient (0.5%) could not be typed. Genotype was not associated with diagnosis, age, or with HIV infection. Type I was associated with higher serum HCV RNA levels, and with a poor response to interferon. Progression to hepatic decompensation has been seen less frequently in those with type 3 compared to type 1 infection (p = 0.07). Three out of eleven patients studied over a longer time course showed a change in genotype, the remainder were persistently infected with HCV type 1. In conclusion, HCV genotype has clinical relevance in the management of haemophilic patients. Those with type 1 are probably more likely to develop serious liver disease and since they respond poorly to inter- feron-α, should be considered for new treatment strategies aimed at sustained clearance of HCV RNA.
References
1
Makris M,
Preston FE,
Triger DR,
Underwood JC,
Choo QL,
Kuo G.
Hepatitis C antibody and chronic liver disease in haemophilia (see comments). Lancet 1990; 335: 1117-1119
4
Davis G,
Balart L,
Schiff ER,
Lindsay K,
Bodenheimer HC,
Perrillo RP,
Carey W,
Jacobson IM,
Payne J,
Dienstag JL,
Van Thiel DH,
Tamburro C,
Lefkowitch J,
Albrecht J,
Meschievitz C,
Ortego TJ.
Gibas A and the hepatitis interventional therapy group. Treatment of chronic hepatitis C infection with recombinant-interferon alfa N Engl J Med 1989; 321: 1501-1506
5
Simmonds P,
Alberti A,
Alter HJ,
Bonino F,
Bradley DW,
Brechot C,
Brouwer JT,
Chan SW,
Chayama K,
Chen DS,
Choo QL,
Colombo M,
Cuy- pers HT M,
Date T,
Dusheiko M,
Esteban JI,
Fay O,
Hadziyannis SJ,
Han J,
Hatzakis A,
Holmes EC,
Hotta H,
Houghton M,
Irvine B,
Kohara M,
Kolberg JA,
Kuo G,
Lau JY N,
Lelie PN,
Maertens G,
Mcomish F,
Miyamura T,
Mizokami M,
Nomoto A,
Prince AM,
Reesink HW,
Rice C,
Roggendorf M,
Schalm SW,
Shikata T,
Shimotohno K,
Stuyver L,
Trepo C,
Weiner A,
Yap PL,
Urdea MS.
A proposed system for the nomenclature of hepatitis C viral genotypes. Hepatol 1994; 19 (05) 1321-1324
6
Pozzato G,
Moretti M,
Franzin F,
Croce LS,
Tiribelli C,
Masayu T,
Kaneko S,
Unoura M,
Kobayashi K.
Severity of liver disease with different hepatitis C viral clones. Lancet 1991; 338: 509
8
Pasi KJ,
Hill FG H.
In vitro and in vivo inhibition of monocyte phagocyticfunction by factor VIII concentrates. Correlation withconcentrate purity BrJ Haematol 1990; 76: 88-93
9
Telfer P,
Sabin C,
Devereux H,
Scott F,
Dusheiko G,
Lee C.
The progression of HCV-associated liver disease in a cohort of haemophilic patients. Br J Haematol 1994; 87 (03) 555-561
10
Telfer PT,
Devereux H,
Colvin B,
Dusheiko G,
Lee CA.
The treatment of hepatitis C infection with alpha Interferon in haemophilic patients. Haemophilia 1995; 1: 54-58
13
Savage K,
Dhillon AP,
Schmilovitz-Weiss H,
El-Batonony M,
Brown D,
Dusheiko G,
Scheuer P.
Detection of HCV-RNA in paraffin-embedded liver biopsies from patients with autoimmune hepatitis. J Hepatol 1995; 22: 27-34
16
Nousbaum JB,
Pol S,
Nalpas B,
Landais P,
Berthelot P,
Brechot C.
Hepatitis C virus type lb (II) infection in France and Italy. Collaborative Study Group (see comments) Ann Int Med 1995; 122 (03) 161-168
17
Garson JA,
Tuke PW,
Makris M,
Briggs M,
Machin SJ,
Preston FE,
Tedder RS.
Demonstration of viraemia patterns in haemophiliacs treated with hepatitis C virus contaminated factor VIII concentrates. Lancet 1990; 336: 1022-1025
19
Dusheiko G,
Schmilovitz-Weiss H,
Brown D,
McOmish F,
Yap PL,
Sherlock S,
McIntyre N,
Simmonds P.
Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatol 1994; 19 (01) 13-18
20
Chan SW,
Simmonds P,
McOmish F,
Yap PL,
Mitchell R,
Dow B,
Follett E.
Serological responses to infection with three different types of hepatitis C virus (letter) (see comments). Lancet 1991; 338 8779 1391
21
Matsumoto A,
Tanaka E,
Suzuki T,
Ogata H,
Kiyosawa K.
Viral and host factors that contribute to efficacy of interferon-2a therapy in patients with chronic hepatitis C. Diges Dis Scien 1994; 39: 1273-1280
22
Hino K,
Sainokami S,
Shimoda K,
lino S,
Wang Y,
Okamoto H,
Miyakawa Y,
Mayumi M.
Genotypes and titers of hepatitis C virus for predicting response to interferon in patients with chronic hepatitis C. J Med Virol 1994; 42 (03) 299-305
23
Detmer J,
Kolberg J,
Joh M,
Collins M,
Zayati C,
Irvine B,
Urdea M.
Comparison of HCV genotypes with characterized and quantified HCV RNA transcripts in the Quantiplex™ HCV RNA assay. International Conference on hepatitis C and related viruses San Diego; California: 1994. Abstract 267
24
Yamada M,
Kakumu S,
Yoshioka K,
Higashi Y,
Tanaka K,
Ishikawa T,
Takayanagi M.
Hepatitis C virus genotypes are not responsible for development of serious liver disease. Dig Dis Scien 1994; 39 (02) 234-239
25
Preston FE,
Jarvis LM,
Makris M,
Philp L,
Underwood JC E,
Ludlam CA,
Simmonds P.
Heterogeneity of hepatitis C virus genotypes in haemophilia: Relationship with chronic liver disease. Blood 1995; 85: 1259-1262
26
Tsubota A,
Chayama K,
Ikeda K,
Yasuji A,
Koida I,
Saitoh S,
Hashimoto M,
Iwasaki S,
Kobayashi M,
Hiromitsu K.
Factors predictive of response to interferon-therapy in hepatitis C infection. Hepatol 1993; 19: 1088-1094
