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Genotype F prevails in HBV infected patients of hispanic origin in Central America and may carry the precore stop mutant.

The distribution of HBV genotypes and the presence of the precore stop mutation were investigated in HBV strains from Central America. 333 HBsAg positive sera from chronic HBsAg carriers and acute hepatitis B cases from five different countries (Costa Rica, Nicaragua, Honduras, EI Salvador and Guatemala) were tested for HBV DNA by nested PCR. Genotyping by limited sequencing within the S gene was performed on 90 strains, 66 from sera with a high level of HBV DNA, and another 24 from sera positive for HBV DNA only after nested PCR. 23 of the samples were anti-HBe positive. Genotype F was found in 71 (79%), A in 13 (14%), D in 5 (6%) and C in one of the 90 sera. 18 patients with genotype F infection had anti-HBe and HBV DNA in serum. Since the three published precore sequences of genotype F strains have a C1858, which is known to prevent the precore stop mutation from G to A at position 1896, the precore and part of the core genes were sequenced from 19 anti-HBe positive sera with HBV DNA, 17 with genotype F and 2 with genotype A. The A1896 mutation was found in 11 of the 17 genotype F strains. All these had a T1858, which was also present in 5 of the 6 genotype F strains with G1896. The precore region was therefore sequenced from genotype F strains from 5 HBeAg positive sera from the five different Central American countries. These also had a T1858, which thus is the wild type substitution in genotype F in Central America. A number of mutations were recorded between residues 57 and 68 in the core protein corresponding to a unique clustering region of the genotype F strains. The predominance of genotype F in Central American populations of Hispanic origin was not anticipated since this genotype is regarded as indigenous to the Amerindian populations of the New World.

Central America↗

Prevalence and clinical expression of HCV-genotypes in haemodialysis-patients of two geographically remote countries: Belgium and Saudi-Arabia.

Hepatitis C virus is the leading cause of acute and chronic liver disease in hemodialysis patients. There are at least six major HCV-genotypes, with a well documented geographical distribution in the general population. Moreover, HCV-genotype is one of the major determinants of the therapeutic response to Interferon Alpha in affected patients. Since the therapeutic outcome in HCV-positive hemodialysis patients, especially with regard to the different HCV-genotypes, is of interest, a multicentre epidemiologic study was performed in HCV-antibody positive hemodialysis patients of two geographically remote countries, i.e. in Flanders (Belgium) and in Saudi-Arabia. 184 chronic hemodialysis patients, with a positive second or third generation Elisa assay for HCV, were tested for HCV-viremia and HCV-genotype, using a 5' untranslated region (UR) nested PCR for the detection of HCV-RNA and subsequently type-specific probes to hybridize with HCV-RNA (Inno-Lipa). Additionally, clinical data were collected by means of a standardized questionnaire, thoroughly completed by the nephrologist in charge of each respective patient. Viremia was present in 79% of the patients (146 out of 184). The prevalence of HCV-genotypes differed significantly between Belgian and Saudi-Arabian dialysis-patients. In Belgian dialysis patients HCV-genotype 1b was most prevalent (i.e. 62%), while in Saudi-Arabian patients HCV-genotypes 4, 1b, and la were present in respectively 36,4%, 31,7%, and 25,8% of the HCV-PCR positive patients. Although there were significant differences between Belgian and Saudi-Arabian dialysis patients, no clinical data showed any significant correlation with the HCV-genotype. Transaminases, determined over a six months period, showed normal average values. Doubling of the transaminases, in at least one out of six measurements over a six monthly period, occurred only in 14% (alanine aminotransferase, ALT) and 10% (aspartate aminotransferase, AST) of the patients. In Belgian dialysis patients, HCV-genotype 4 (or HCV-genotype 5) significantly correlated with a more recent start of dialysis treatment. We conclude that there is a significant different geographical prevalence of HCV-genotypes in HCV-affected hemodialysis patients. None of the different HCV-genotypes shows any particular clinical expression. Transaminases are not a sensitive marker for ongoing HCV-replication in hemodialysis patients. In Belgian dialysis patients, a changing pattern of HCV-infection is suggested, with an increasing prevalence of HCV-genotype 4 (or HCV-genotype 5) in more recent years. These data suggest possible implications for the therapeutic strategy in dialysis patients.

Adult↗

[Clinical implications of hepatitis C virus genotype in human immunodeficiency virus infected patients with chronic liver disease].

OBJECTIVE: To know the prevalence of viral genotype in patients infected with hepatitis C virus (HCV) and coinfected with HIV and evaluate its clinical implications. PATIENTS AND METHODS: The genotype of the HVC was studied (INNO-LiPA HCV II, Imnogenetics, Belgium) in 40 patients coinfected with HIV; from 28 of these patients histologic data of chronic hepatitis were available. The most prevalent genotype was analyzed in this type of patients and its associations with different issues: risk behavior, histologic activity of liver disease and viremia level (quantitative PCR, Amplicor HCV, Roche Diagnostics). RESULTS: Genotype 1 was the most prevalent (55%), and subtype 1a predominated (36.3%). In most cases genotypes 1a and 3 were found (65%) and in four cases (10%) there was coinfection with two genotypes. The most common risk behavior was parenteral drug use (PDU) (34 cases), which might account for the higher prevalence of genotypes 1 and 3. A mild hepatic histologic activity was most frequently associated with genotype 3 compared with genotype 1 (63.6% versus 46.6%). The Knodell histologic activity index (HAI) was higher in the four patients with coinfection 1 + 3 versus the remaining patients (11.2 +/- 2.8 versus 7.8 +/- 3.6). The percentage of patients with genotype 1 with a viral load > 10(5) was higher than that of patients with genotype 3 (80% versus 7.6% [4]) (p < 0.05); in the two cases with subtype 1b viremia levels exceeded this limit. CONCLUSIONS: The prevalent HCV genotypes in patients coinfected with HIV in our environment seem to be 1a and 3, which is probably associated with the more common high risk behavior of PDU among these patients. Genotype 3 seems to be associated with a milder histologic liver damage and a lower viral load, and these two characteristics might be related. The HCV genotype should be considered in subjects coinfected with HIV to obtain a better clinical and prognostic evaluation of the chronic liver disease it causes.

Biopsy↗

Genotypes of hepatitis B virus among voluntary blood donors in northern Thailand.

There are distinct ethnogeographic variations for the distribution of various hepatitis B virus (HBV) genotypes, and pathogenic and therapeutic differences are also observed. In general, genotype B infection has a relatively better prognosis than genotype C. In Thailand, genotypes C and B were reported as the major genotypes; however, there were no previous reports of HBV genotyping in the north of the country. From 1998 to 2000, 216 HBsAg-positive serum samples (164 males and 52 females, aged 16-52 years), were screened and collected from voluntary blood donors in four provinces of northern Thailand. The method of Naito et al. was employed in this study, with the multiplex-PCR approach and genotype-specific primers to identify genotypes A-F. We found that the HBV genotype C was highly predominant in northern Thailand (89.3%), when compared with the previous reports of genotype C distribution among voluntary blood donors from other areas in the country (50-65%), followed by genotype B (7.4%), mixed infection of genotype B and C (1.9%) and genotype A (0.5%). Four samples (1.9%) were unclassifiable. There was no significant difference of genotype distribution among four northern Thai provinces or each age group.

Journal Article↗

Complete nucleotide sequence of genotype 4 hepatitis C viruses isolated from patients co-infected with human immunodeficiency virus type 1.

The hepatitis C virus (HCV) genotype 4 is spreading among southern European intravenous drug users, who are frequently co-infected with human immunodeficiency virus type 1 (HIV-1). Response to interferon (IFN) alpha-based therapies in HIV-1 positive patients co-infected with HCV genotype 4 is poor, similar to that obtained for HCV genotype 1 and much lower than for HCV genotypes 2 and 3. The lack of sequence data related to HCV of genotype 4 prompted us to sequence the complete genome of two genotype 4 variants isolated from two HIV-1 co-infected patients (24 and 25). Our aim was to investigate the evolutionary relationships of the former variants with other genotypes and/or genotype 4 subtypes. Sequence alignments and phylogenetic analysis from genomic regions 5'NC, core-E1 and NS5B revealed that the variants isolated from patients 24 and 25 (both subtyped 4c/4d by INNO-LIPA II HCV) belong to subtypes 4d and 4a, respectively. When looking at the complete genome sequence one of the variants showed a new genotype 4 subtype. Interestingly, sequence length differences in the interferon sensitivity determining region coding regions were observed when compared with sequences from other genotypes. Similarly, when the catalytic efficiency of the NS3/4 protease from patients 24 and 25 samples were determined, they displayed 70.6+/-7.7 and 23.5+/-3.4%, respectively, of the activity shown by genotype 1 NS3/4 proteases. Overall, pairwise comparison and phylogenetic analysis of nucleotide sequences of the complete genome or the different protein-encoding regions showed that genotype 4 sequences were more closely related to genotype 1 sequences. The description of new HCV genome variants may help our understanding of the HCV biology as well as the role of different genotypes in HCV treatment and therapy response.

Amino Acid Sequence↗

Different hepatitis B virus genotype distributions among asymptomatic carriers and patients with liver diseases in Nanning, southern China.

To determine the hepatitis B virus (HBV) genotype distribution among asymptomatic carriers and patients with liver diseases in Nanning, China, where the prevalence of HBV infection is high, the serum samples from 39 asymptomatic HBV carriers and 103 liver diseases patients were examined for the presence of HBV DNA by polymerase chain reaction and for genotypes by restriction fragment length polymorphism analysis. All patients were positive for HBV DNA and 135 (95.1%) patients were classified by RFLP, the remaining seven were classified by sequencing. Finally, six (4.2%), 20 (14.1%), 113 (78.9%) and two (1.4%) patients were identified with genotype A, B, C and D, respectively. One (0.7%) case was confirmed to be co-infected with both genotypes B and C. Genotype C was more frequently observed in cases with advanced liver diseases and relatively less frequently in case with mild liver diseases. In contrast, genotype B showed an opposite distribution pattern, although there was no statistically significant difference (P=0.05). The rate of positivity for anti-HBe was higher, but that for HBeAg was lower in chronic infection patients with genotype B than in those with genotype C, (P<0.05, P<0.05, respectively). Severe liver damage was observed in patients with genotype C compared with those with genotypes A or B (P<0.01, P<0.01, respectively). These results suggest that (1) genotype C is the predominant genotype in Nanning, China, (2) genotype C maybe more associated with development of severe liver diseases than genotype B.

Journal Article↗

Genotypic analysis of hepatitis B virus from patients with fulminant hepatitis: comparison with acute self-limited hepatitis.

AIM/BACKGROUND: There is an increasing evidence that certain hepatitis B virus (HBV) strains may contribute to the pathogenesis of fulminant hepatitis B (FHB). Recently, we reported that genotypes of HBV influence the clinical course of acute self-limited hepatitis B (AHB). In this study, we compared clinical features of FHB between different HBV genotypes and compared the prevalence of each genotype between FHB and AHB patients. METHODS: The subjects consisted of seven patients with FHB and 25 patients with AHB. The core promoter and precore region were directly sequenced following polymerase chain reaction, and genotype was determined by restriction fragment length polymorphism analysis of the S gene. RESULTS: Of the seven FHB patients, one had genotype A, one had genotype B, four had genotype C, and one had genotype D. Six of the seven FHB patients were infected by heterosexual contact; one FHB patient who was not infected by heterosexual contact had genotype C. All four FHB patients with genotype C had a short duration clinical course. In one patient with genotype A, the time from onset of hepatitis to hepatic coma was 30 days. These results are similar to those of the patients with AHB, in which clinical course was longer in patients with genotype A than in patients with genotype C. CONCLUSION: Viral genotype can be used to predict the clinical course of both FHB and AHB.

Journal Article↗

Genotyping of Actinobacillus actinomycetemcomitans serotype d isolates based on polymerase chain reaction.

The aims of the study were to determine the genetic diversity of the rare Actinobacillus actinomycetemcomitans serotype d and to compare the ability of the repetitive extragenic palindromic element (REP)-based polymerase chain reaction (PCR) with that of the arbitrarily primed (AP)-PCR to discriminate between and within A. actinomycetemcomitans serotypes. The material included 26 A. actinomycetemcomitans serotype d isolates, 3 reference strains, and 21 A. actinomycetemcomitans isolates, representing the previously described 17 AP-PCR genotypes from 4 serotypes (a, b, c and e). Among A. actinomycetemcomitans serotype d isolates (n = 26), the AP-PCR primer distinguished 2 genotypes, whereas the REP-primer pair (REP1R-I and REP2-I) and the (GACA)4 primer each produced one genotype. Among the total of 50 A. actinomycetemcomitans isolates, REP-primer pair distinguished 6 genotypes, the primer (GACA)4 7 genotypes, and the AP-PCR 19 genotypes. Among A. actinomycetemcomitans serotype a isolates (n = 6), REP-primer pair yielded 3 genotypes and (GACA)4 and AP-PCR primer 4 genotypes, and among serotype e isolates (n = 6) 3 genotypes. All serotype b isolates (n = 7), representing the AP-PCR genotypes 2, 9, 8, 12, 13, 16 and serotype c isolates (n = 5), AP-PCR genotypes 3, 4, 14, 15, belonged to the (REP1R-I and REP2-I)-PCR genotype 4 and to the (GACA)4-PCR genotype 4. In conclusion, based on both the AP-PCR method and the less discriminative REP-PCR methods, the present genotyping results indicated limited genetic diversity among serotype d isolates of A. actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans↗

VO2 max is associated with ACE genotype in postmenopausal women.

Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (VO2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE deletion/deletion (DD) genotype group after accounting for the effect of physical activity levels. The ACE II genotype group also had a 3.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE insertion/deletion (ID) genotype group. The ACE ID group tended to have a higher VO2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation in VO2 max among women after accounting for the effect of habitual physical activity levels. The entire difference in VO2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDO2). ACE genotype accounted for 17% of the variation in maximal a-vDO2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences in VO2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDO2 and not of maximal stroke volume and maximal cardiac output.

Body Composition↗

Genotypic differences in the hepatitis B virus core promoter and precore sequences during seroconversion from HBeAg to anti-HBe.

Hepatitis B virus (HBV) strains from anti-HBe positive patients often show specific mutations in the precore gene, the core promoter region, or both. The dynamics of seroconversion in relation to the appearance of these mutations has not been studied and compared between defined HBV genotypes. Samples from patients followed during seroconversion from HBeAg to anti-HBe were amplified by polymerase chain reaction (PCR), sequenced and genotyped. Among 16 sets of samples, 6 belonged to genotype A, 6 to genotype D, 2 to genotype B, 1 to genotype C, and 1 to genotype E. Whereas strains from genotypes B, C and E showed changes in the core promoter, precore codon 28 or both, genotype A and D strains displayed a different pattern. In 4 of 6 anti-HBe positive samples from genotype A, the precore had a wild-type sequence while the core promoter sequence showed a specific TGA mutation. In another genotype A strain a precore stop mutation was preceded by a mutation in codon 15, thus conserving base-pairing at the pregenomic RNA level in this region. In contrast, all genotype D strains showed wild-type sequences in both the core promoter and precore codon 28 in pre- and post-seroconversion samples. Thus, in 8 patients with a mean follow-up time of 17 months, wild-type sequences in both the core promoter and precore codon 28 were found after seroconversion to anti-HBe. This study also confirmed, for genotype D, that HBeAg seroconversion often occurs earlier than genomic conversion.

Adolescent↗

Hepatitis C virus genotypes and development of hepatocellular carcinoma.

BACKGROUND: Among several genotypes of hepatitis C virus (HCV), genotypes 1b (or II) and 2a (or III) are predominant in Japan. Although it has been shown that the efficacy of interferon treatment of patients with chronic hepatitis C varies with the HCV genotype, the relationship between HCV genotype and the development of hepatocellular carcinoma (HCC) has not been well described. METHODS: The genotypes and serum levels were determined for HCV-RNA in 72 patients with HCC and 131 patients without HCC, all of whom were positive for second-generation HCV antibody and HCV-RNA. In addition, clinical data from 34 patients with HCC who each had a history of blood transfusion were analyzed. RESULTS: Fifty-seven (79.2%) of 72 patients with HCC had genotype 1b HCV, whereas 101 (77.1%) of 131 patients without HCC had genotype 1b, indicating that there was no significant difference in the prevalence of genotype 1b HCV between the patients with and without HCC. Furthermore, comparison of patients with HCC with genotype 1b HCV with those with genotype 2a who had a history of blood transfusion did not differ significantly in the number of years from blood transfusion to diagnosis of HCC. Levels of HCV-RNA were not significantly different among patients with liver diseases of various stages. CONCLUSIONS: Hepatocellular carcinoma develops in patients with either genotype 2a HCV or genotype 1b HCV. A difference in genotype is not likely to be responsible for the difference in development of HCC.

Carcinoma, Hepatocellular↗

Bayesian trio models for association in the presence of genotyping errors.

Errors in genotyping can greatly affect family-based association studies. If a mendelian inconsistency is detected, the family is usually removed from the analysis. This reduces power, and may introduce bias. In addition, a large proportion of genotyping errors remain undetected, and these also reduce power. We present a Bayesian framework for performing association studies with SNP data on samples of trios consisting of parents with an affected offspring, while allowing for the presence of both detectable and undetectable genotyping errors. This framework also allows for the inclusion of missing genotypes. Associations between the SNP and disease were modelled in terms of the genotypic relative risks. The performances of the analysis methods were investigated under a variety of models for disease association and genotype error, looking at both power to detect association and precision of genotypic relative risk estimates. As expected, power to detect association decreased as genotyping error probability increased. Importantly, however, analyses allowing for genotyping error had similar power to standard analyses when applied to data without genotyping error. Furthermore, allowing for genotyping error yielded relative risk estimates that were approximately unbiased, together with 95% credible intervals giving approximately correct coverage. The methods were also applied to a real dataset: a sample of schizophrenia cases and their parents genotyped at SNPs in the dysbindin gene. The analysis methods presented here require no prior information on the genotyping error probabilities, and may be fitted in WinBUGS.

Alleles↗

Factors predisposing to the occurrence of cryoglobulinemia in two cohorts of Egyptian and Japanese patients with chronic hepatitis C infection: ethnic and genotypic influence.

The association between cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. However, the factors underlying its wide variation of occurrence have not yet been well identified. To investigate this, cryoglobulinemia was studied in four cohorts of Egyptian and Japanese patients. Fifty Egyptian patients with chronic hepatitis C, infected with genotype 4 (the predominant HCV genotype in Egypt), were compared with 50 age- and sex-matched Japanese patients, infected with HCV genotype 1b (the predominant HCV genotype in Japan). Thirty-two Egyptian and 30 age- and sex-matched Japanese patients with chronic hepatitis B were included as controls. All patients were noncirrhotic. Antinuclear antibody (ANA), immunoglobulins (Ig), and cryoglubulins were assessed. Results showed a significantly higher prevalence of cryoglobulinemia in chronic hepatitis C Japanese genotype 1b (40%) as compared with Egyptian genotype 4 (14%), P = 0.003, while no difference was found between Japanese (17%) and Egyptian chronic hepatitis B controls (13%). Symptomatic cryoglobulinemia was more prevalent in the Japanese than in the Egyptian chronic hepatitis C group (10% vs. 4%), but the difference was not statistically significant. Univariate analysis showed no association between cryoglobulinemia and either age, sex, alanine aminotransferase level, or HCV viral load in Japanese or Egyptian patients, while the mean IgM level was significantly higher in the cryoglobulin-positive than in the cryoglobulin-negative chronic hepatitis C patients in each group (P = 0.003 and 0.017, respectively). Cryoglobulinemia was found to be significantly associated with both high IgG level (P = 0.020), and positive ANA (P < 0.001) in Japanese patients with chronic hepatitis C, genotype 1b but not in Egyptians with genotype 4. Multivariate analysis showed that the only factors predisposing to cryoglobulinemia were Japanese ethnicity with HCV genotype1b (P = 0.002, OR = 2.56), high IgM level of >245 mg/dl (P = 0.018, OR = 2.05) and female gender (P = 0.040, OR = 1/0.66). In conclusion, cryoglobulinemia is prevalent in Japanese patients with chronic hepatitis C infected with genotype 1b, but cryoglobulinemia is not common in Egyptians with HCV genotype 4. Although it was not possible to evaluate ethnicity and HCV genotype separately in this study, HCV genotype 1b appears to predispose more to cryoglobulinemia than does genotype 4. Female gender and high serum IgM level were also related.

Asian People↗

Hepatitis B virus genotypes and HBsAg subtypes in refugees and injection drug users in the United States determined by LiPA and monoclonal EIA.

Hepatitis B virus (HBV) genotyping and hepatitis B surface antigen (HBsAg) subtyping were carried out on sera from 196 HBsAg-positive patients, including 151 refugees entering the United States and 45 injection drug users in Seattle. HBsAg subtyping was performed by enzyme immunoassay (EIA) using a panel of monoclonal antibodies and the HBV genotype was determined by polymerase chain reaction (PCR) followed by detection of amplified HBV DNA by a reverse-phase hybridization line probe assay (LiPA) using genotype-specific probes. HBV DNA was detected by PCR in 155 (79%) of the 196 sera and all 155 were genotyped by LiPA. Samples from Southeast Asia were predominantly genotype B/subtype ayw1 and genotype C/adr; samples from the former Soviet Union and eastern Europe were mostly genotype D/ayw2 and genotype D/ayw3; samples from east Africa were mainly genotype A/adw2 and genotype D/ayw2; and samples from injection drug users were mostly genotype D/ayw3 and genotype A/adw2. Some strains of ayw3 gave atypical monoclonal antibody reactivity patterns in the subtyping assay due to a Val/Ala instead of a Thr at amino acid residue 118 and a Thr instead of a Met at residue 125. A strain of ayw2 also gave an atypical monoclonal antibody reactivity pattern due to an Ala instead of a Thr at amino acid residue 123. LiPA genotyping and monoclonal EIA subtyping can provide useful information for epidemiological studies.

Africa, Eastern↗

African links and hepatitis B virus genotypes in the Republic of Yemen.

Hepatitis B virus (HBV) genotypes in three different communities in the Republic of Yemen with and without significant African links were studied. The subjects included indigenous Yemeni blood donors (n = 987), Africans who had settled down in Yemen for several generations (n = 97) and Soqotrans living on an island in the Indian Ocean close to the African coast (n = 99). Phylogenetic analysis of HBV surface region sequences showed the presence of two major genotypes; A and D: sequences from the blood donors were all genotype D (17/17); those from Africans residing in Yemen were predominantly genotype D (7/8) although one sequence was genotype A; whereas a mixture of genotype A and D was found among the Soqotrans (5/8 and 3/8 respectively). Genotype A sequences were associated with higher viral load, but the difference was not statistically significant. Human migration and international travel, may lead to an interaction between HBV genotypes. The Republic of Yemen is at a location where genotypes A and D meet. The results from this study suggest that genotype A is found only in communities with continuing African links and that genotype D remains the dominant genotype in settled populations. More studies are needed to examine possible long-term changes in HBV genotypes in this region.

Africa↗

Hepatitis B virus genotypes, core promoter variants, and precore stop codon variants in patients infected chronically in North-Eastern Italy.

The hepatitis B virus (HBV) genotypes distribution and the core promoter (CP)/precore (PC) variability were evaluated by a line probe assay in 272 patients infected chronically enrolled consecutively in an area of the North-Eastern Italy. Seven out of the eight genotypes were detected. Italian subjects (83% of the sample) were infected mainly by genotype D (73%) and A (26%); genotype F, and genotype H, were detected only in one subject. In foreigners, the genotype distribution reflected the distribution described for the areas of origin, that is, in Asia genotypes B, C, and D; in Africa genotypes A and E. CP and PC variants prevalence rates were 51% and 60%, respectively, and were significantly higher in Italian patients, probably in relation to their older age. In the analysis restricted to genotypes A and D, PC wild type was linked strongly to genotype A (OR = 4.08, 95% CI = 3.07-5.43, P < 0.0001). In genotype A-infected patients, only e seroconversion was associated significantly with CP variants. In genotype D-infected subjects, CP variants were linked significantly to older age and to a higher e seroconversion rate, while PC variants also showed a strong relationship with an ALT lower activity and a lower viral load. In multivariate analysis, HBeAg positivity was associated strongly and independently with younger age, genotype A and CP wild type. Independent determinants of higher viral loads were recognized by increasing age, in male gender and concomitant presence of HBeAg and the CP wild type virus.

Adult↗

Distribution of Epstein-Barr virus genotypes in throat washings, sera, peripheral blood lymphocytes and in EBV positive tumor biopsies from Slovenian patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignancy closely associated with Epstein-Barr virus (EBV). It is prevalent among the Chinese of Southern China, whereas outside China, the position seems to be different. The aim of this study was to determine the distribution of EBV genotypes in the patients with NPC in Slovenia, which is a nonendemic area. Detection of EBV was undertaken by testing the throat washes, sera, peripheral blood lymphocytes (PBLs), and biopsies of primary tumors of 48 patients with NPC in Slovenia. The sera of 20 patients with serologically confirmed primary EBV infection served as a control clinical material. The analysis of genotypes was carried out on three regions of EBV genome; BamHI WYH, BamHI I, and BamHI F, using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results show that, in Slovenia, the predominant combination of EBV genotypes based on the differences in the three genomic regions is ADF. This combination was found in 56 out of 103 different EBV positive clinical samples (throat washes, sera, PBLs, and tumor biopsies) of patients with NPC and in 15 out of 17 sera of patients with primary EBV infection. Very low number of genotypes C and f were detected, in spite of the fact that these two genotypes were considered to be associated with the development and/or maintenance of NPC in Southern China. Genotype f was found in only two tumor biopsies; in all other clinical samples (throat washes, sera and PBLs), genotype F was detected. Genotype C was proven in 31/103 clinical samples, with the highest percentage in tumor biopsies (37.5%). As in the NPC patients from other countries (Alaska is an exception), genotype A was predominant and was detected in 86/103 clinical samples. Genotype B was found in 15 clinical samples of patients with NPC and in 3 the two genotypes A and B were found. In comparison to China, these results show different EBV genotypes distribution. It seems that the genetic disposition of human population is an important factor that may contribute to different susceptibility for specific EBV genotypes.

Adolescent↗

Hepatitis C virus genotypes and quantitation of serum hepatitis C virus RNA in liver transplant recipients: relationship with severity of histological recurrence and implications in the pathogenesis of HCV infection.

The reasons for the wide variation of incidence and severity of recurrent hepatitis C after liver transplantation are not clear. We have studied liver transplant recipients to assess the impact of hepatitis C virus (HCV) genotype and HCV RNA quantification on HCV recurrence after transplantation. Twenty-two patients received transplants for HCV cirrhosis and were followed up with virological and histological assessments. Mean follow-up was 39 months. HCV genotype was determined with line probe assay (Inno-Lipa). HCV RNA quantity was determined in serum samples by use of polymerase chain reaction nested assay. HCV genotype 1 was detected in 13 patients and other genotypes in 9. Histological recurrence rates were 69% in patients with genotype 1 and 66% in patients with other genotypes. All cases of severe histological injury (chronic active hepatitis or cirrhosis) were observed in patients with genotype 1. HCV RNA quantity was significantly higher in patients with genotype 1 (mean, 2.023 x 10(3) copies/mL) than in patients with other genotypes (mean, 27,403 copies/mL). In conclusion, the severity of histological recurrence after liver transplantation for HCV disease was higher in patients infected by HCV genotype 1 than in those infected with other genotypes. The levels of viral replication were higher in patients with HCV genotype 1 than in those with other genotypes.

Adult↗