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We read with great interest the article by Bartolotti et al. (Gut2005;54:852-857) regarding the shift in the predominance of hepatitis C genotype in 373 paediatric patients investigated between 1990 and 2002. The distribution of genotypes showed a major prevalence of HCV genotype 1, recorded in about 60% of children. The genotype 2, 3 and 4 were observed in 17, 15 and 5% of patients respectively. However...
We read with great interest the article by Bartolotti et al. (Gut2005;54:852-857) regarding the shift in the predominance of hepatitis C genotype in 373 paediatric patients investigated between 1990 and 2002. The distribution of genotypes showed a major prevalence of HCV genotype 1, recorded in about 60% of children. The genotype 2, 3 and 4 were observed in 17, 15 and 5% of patients respectively. However, the study after 1990 described a declining prevalence of genotypes 1b and 2 and by an increasing proportion of genotype 3 and 4.
We have conducted an analogous genotype determination in 1095 adults patients analyzed between 2000 to 2004. Subjects were been screening previously for anti-HCV antibodies for different reason, such as exposure to major risk factors, evidence of increased ALT, pregnancy and surgical procedures. Consequently, this population group was characterized by a rather homogenous representation of all age groups and included individuals independently of source of infection and liver disease. All patients were infected with HCV, as demonstrated by HCV-RNA detection obtained by a Polymerase Chain Reaction (PCR) assay, COBAS System Amplicor HCV monitor version 2.0 (Roche Diagnostics Systems Inc. Branchburg, NJ, USA). HCV genotyping/subtyping was done with a line-probe assay (INNO-LiPA HCV II, Innogenetics, Ghent, Belgium). The Simmonds classification was used.
The study population included 555 males and 540 females, in the age range of 15-102 years. 44 (4.0%) out of 1095 patients were younger than 30 years old; 179 (16.3% ) aged between 31 and 40; 189 (17.3%) between 41 and 50; 165 (15.1%) between 51 and 60; 304 (27.8%) between 61 and 70 and 190 (17.4%) between 71 and 80. Finally, 24 (2.3%) samples were obtained by patients older than 80 years. All the 1095 HCV-RNA positive samples included in the study were genotyped, and 1063 (97.1%) were also subtyped. The distribution of genotypes showed a major prevalence of HCV genotype 1 (49,3%). Three hundred seventy-one (33.9%) were infected with type 2 and 136 (12.4%) were suffering from genotype 3. HCV-4 was found in 52 (4.7%) persons. Type 5 could be detected only in one (0.1%) patient. The remaining 9 (0.8%) individuals were infected with more genotypes. The distribution of subtypes showed a major prevalence (39.7%) of subtype 1b. Three hundred thirty-one (30.2%) individuals were infected with subtypes 2a/2c and 122 (11.1%) were suffering from subtype 3a. Seventy-two (6.6%) samples were positive for serotype 1a. The serotype 2a and 4c/4d, were determinate only in 32 (2.9%) 36 (3.3%) patients, respectively. The subtypes 3b and 1a/1b were unusually recorded, (12 and 8 subjects respectively). Exceptional results appeared to be the infections with other subtypes and the co-infections (1-2 patients).
The data of subtype distribution according to age group demonstrates a notable variation in the profiles of the subtypes (Table). Subtype 1a was frequently detectable in young patients, was rarely found in old subjects and tended to disappear in the last age groups (p <0.0001). Subtype 1b appears to be more prevalent in individuals aged ≤30 years compared to patients 31-40 and 41-50 years old ( p 0.013). However, subjects in the age group older than 50 (near 50%) years had most frequent infections with subtypes 1b compared with patients 31-40 and 41-50 years old (p <0.0001). The profile of co-infection 2a/2c showed an evident and progressive increase of the prevalence with the increment of age (p <0.0001). Subtype 3a was described more frequently in the second and third age group compared with the first one (p 0.007). However, prevalence of this subtype declined according to increment of age and became irrelevant in the last age group(p <0.0001). An analogous profile was described for co-infection 4c/4d (p <0.0001).
Our data was in accordance with the predominance of genotype 1, and in particular of subtype 1b, observed previously in Italy and in most countries of Europe and of the Word. With respect to the genotype 2, almost completely represented by subtype 2a/2c, and for genotype 3 our results showed data analogous to those reported from other Italian and European studies. In our study genotype 4 was found in 4.1% of patients. HCV genotype 4 appears to be prevalent in North Africa and Middle East .[2-3] However, recent papers showed an high prevalence (4.5%) of HCV genotype 4 in Southern and Central Italy too.
Moreover, we have evaluated the shift in the predominance of HCV subtypes in age groups. Recently, this tendency for a shift in the prevalence of HCV subtypes was noted in Italian and international study.[5-6] A recent model of HCV spread, based on the coalescent theory, which showed that the circulation of subtype 1a continues to increase whereas the extent of infection with subtypes 1b tends to decrease. This is in line with our results on subtype 1a and probably with the epidemic behaviour of subtype 3a and co-infection 4c/4d.On the other hand, the high prevalence of subtype 1b that was observed in our patients younger than 30 years appears to suggest that the increase in rate of this variant has not yet achieved a plateau in Italy. Analogous data were obtained in an other Italian study conducted recently in North-East Italy.
In conclusion, our study has shown a shift of the epidemiological picture of HCV infection, with the diffusion of subtypes 1a, 3a and 4c/4d. These epidemiological changes reported in our patients reflected the shift in pattern of HCV genotypes described by Bartolotti (Gut2005;54:852-857) in children. These subtypes, prevalent in young adults, may represent the source of future infections transmitted mainly by injection drug use, perinatal, and sexual transmission, and it is expected that these subtypes will be distributed evenly in all cohorts.
1. 1 Simmonds P, McOmish F, Yap PL et al. Classification of hepatitis C virus into six major genotypes and series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993; 74: 2391-9.
2. Zein NN. Clinical significance of hepatitis C virus genotypes. Clin Microb Rew 2000; 13: 223-35.
3. Maertens G, Stuyver L. Genotypes and genetic variation of hepatitis C virus. In: Harrison TJ, Zuckerman AJ, editors. The Molecular Medicine of Viral Hepatitis. Wiley and Sons Ltd. Chichester, England, 1997: 183-233.
4. Matera G, Lamberti A, Quirino A et al. Changes in the prevalence of hepatitis C virus (HCV) genotype 4 in Calabria, Southern Italy. Diagn Microbiol Infect Dis 2002; 42: 169-73.
5. Ross RS, Viazov S, Renzing-Koholer K, Roggendorf M.. Changes in the epidemiology of hepatitis C infection in Germany: shift in the predominance of hepatitis C subtypes. J Med Virol 2000; 60: 122-5.
6. Dal Molin G, Ansaldi F, Biagi C et al. Changing molecular Epidemiology of hepatitis C virus infection in Northeast Italy. J Med Virol 2002; 68: 352-6.
Table: Prevalence of most frequent HCV-subtype in the different age groups