Chronic Hepatitis C Virus Infection in Haemophilic Patients: Clinical Significance of Viral Genotype

Abstract

SummaryWe 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.

The natural history of chronic hepatitis C in a cohort of HIV-negative Italian patients with hereditary bleeding disorders

“…If there are no doubts about the association between the duration of HCV infection and severity of liver disease, [16][17][18]23,26 more uncertainties exist as to the role of HCV genotype 1 on liver disease progression. [37][38][39][40][41][42][43][44] Our study also confirms for hemophiliacs the observations in non-hemophilic patients 15,18,44 about the greater virulence of genotype 1.…”

“…HCV genotype distribution in our cohort of patients is similar to that observed generally in the Italian population 35 and in other studies on hemophiliacs from the same Italian regions, 36,37 but it is quite different from data coming from trials on hemophiliacs in other countries. [38][39][40][41][42][43][44] Furthermore, as hemophiliacs have been exposed to clotting factor concentrates prepared from thousands of donors, some of them have been infected by multiple HCV genotypes. In our study the prevalence of mixed infection is 7% which is similar to that reported in literature.…”

“…In our study the prevalence of mixed infection is 7% which is similar to that reported in literature. [36][37][38][39][40][41][42][43][44] On analyzing the epidemiologic, clinical, and virologic features of the 88 HCV-RNA-positive patients (Tables 2,3) we observed that a more advanced liver disease was associated with HCV genotype 1, a higher age at evaluation, and a more severe congenital bleeding disorder. As in other studies, 23,26 we also identified the duration of infection as an important variable of progression of liver disease: The longer the exposure to HCV, the more severe the liver disease.…”

Hepatitis C virus infection among Brazilian hemophiliacs: a virological, clinical and epidemiological study

“…It has been suggested that genotype may influence progression of chronic liver disease. Some studies have indicated that HCV genotype 1 is associated with more aggressive liver disease (6,7), but this has not been a consistent finding. In addition to clinical differences, the various genotypes have distinct geographical distributions.…”

Prevalence and Changes in Hepatitis C Virus Genotypes among Multitransfused Persons with Hemophilia

“…On the basis of nucleotide-sequence homology, the majority of isolates can be classified into 6 major genotypes and a variable number of subtypes [16]. HCV genotype has been shown to be related to responsiveness to interferon [17][18][19] and may have clinical implications with respect to pathogenicity [14,18,[20][21][22].…”