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Comparison and application of a novel genotyping method, semiautomated primer-specific and mispair extension analysis, and four other genotyping assays for detection of hepatitis C virus mixed-genotype infections.

To date the true prevalence of hepatitis C virus (HCV) mixed-genotype infections has not been established mainly because currently available methods are not suitable for the detection of mixed genotypes in a viral population. A novel semiautomated genotyping method, primer-specific and mispair extension analysis (S-PSMEA), which is more reliable than other genotyping assays was developed for detection of HCV mixed-genotype infections. A genotype present at levels as low as 0.8% in a defined mix of HCV genotypes was detected, showing a 20-fold increase in sensitivity over that of direct DNA sequencing. A total of 434 HCV isolates were genotyped and analyzed for a comparative study of the accuracy between S-PSMEA and four current genotyping methods. The results showed that viruses in approximately 40% of the samples from this group determined to be infected with mixed genotypes by S-PSMEA were undetected by direct DNA sequencing due to its low sensitivity. Type-specific PCR, line probe assay, and restriction fragment length polymorphism analysis performed poorly, being able to identify only 38.5, 16.1, and 15.4% of mixed-genotype infections, respectively, that were detected by direct DNA sequencing. The prevalence of mixed-genotype infections detected by S-PSMEA was 7.9% (12 of 152 donors) among HCV-infected blood donors, 14.3% (15 of 105) among patients with chronic hepatitis C, and 17.1% (6 of 36) among thalassemia patients who had received multiple transfusions. The data lead us to conclude that HCV mixed-genotype infections are more common than previously estimated and that S-PSMEA may be the method of choice when detection of genotypes present at low levels in mixed-genotype infections is required due to its higher level of sensitivity.

Base Pair Mismatch↗

Genotype distribution in Nagoya and new genotype (genotype 3a) in Japanese patients with hepatitis C virus.

We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b + 2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japanese isolates, we should take more care because genotype 3a is not determined by current typing systems.

Amino Acid Sequence↗

Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D.

BACKGROUND AND AIMS: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated. PATIENTS AND METHODS: HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases. RESULTS: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as independent positive predictive parameters of IFN response. CONCLUSIONS: The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.

Adult↗

Presence of multiple genotype-specific antibodies in patients with persistent infection with hepatitis C virus (HCV) of a single genotype: evidence for transient or occult superinfection with HCV of different genotypes.

OBJECTIVE: We investigated the significance of multiple genotype-specific antibodies in patients with persistent infection with hepatitis C virus (HCV) of a single genotype. METHODS: Titers of genotype-specific antibodies to group 1 and 2 HCV polypeptides in the NS4 region of HCV were measured in 53 hemophiliacs and 58 nonhemophiliacs who were persistently infected with HCV of a single genotype. In addition, sequence variability in hypervariable region 1 (HVR1) of HCV was evaluated in these patients. RESULTS: The presence of antibodies to both group 1 and 2 polypeptides, reflecting a mixture of serotypes, was more frequent in hemophiliacs (11 of 53 patients, 20.8%) than in nonhemophiliacs (two of 58 patients, 3.4%; p = 0.01). HVR1 sequence variability in 13 patients with mixed serotypes was higher than in 87 patients with a single serotype (21.1 +/- 4.3% vs 8.5 +/- 6.3%; p < 0.01). CONCLUSIONS: A mixture of HCV serotypes was more common in hemophiliacs with persistent HCV infection of a single genotype who were at high risk of exposure to HCV than in nonhemophiliacs, and the sequence variability of the infecting strains was high in these patients. These data are suggestive of the effects of superinfection with HCV of different genotypes. The presence of multiple genotype-specific antibodies to HCV may be evidence of transient or occult superinfection with HCV of different genotypes in patients with persistent infection by HCV of a single genotype.

Adolescent↗

Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System.

In this review we describe the principles, protocols, and applications of two commercially available SNP genotyping platforms, the TaqMan SNP Genotyping Assays and the SNPlex Genotyping System. Combined, these two technologies meet the requirements of multiple SNP applications in genetics research and pharmacogenetics. We also describe a set of SNP selection tools and validated assay resources which we developed to accelerate the cycle of experimentation on these platforms. Criteria for selecting the more appropriate of these two genotyping technologies are presented: the genetic architecture of the trait of interest, the throughput required, and the number of SNPs and samples needed for a successful study. Overall, the TaqMan assay format is suitable for low- to mid-throughput applications in which a high assay conversion rate, simple assay workflow, and low cost of automation are desirable. The SNPlex Genotyping System, on the other hand, is well suited for SNP applications in which throughput and cost-efficiency are essential, e.g., applications requiring either the testing of large numbers of SNPs and samples, or the flexibility to select various SNP subsets.

Gene Frequency↗

Genotype-by-environment interaction with broiler genotypes differing in growth rate. 1. The effects of high ambient temperature and naked-neck genotype on lines differing in genetic background.

High ambient temperature (AT) significantly depresses growth rate and meat yield of commercial broilers, thus making it a major factor hindering poultry meat production, especially in hot climates. The effects of high AT were variably moderated when feather coverage was reduced by the naked-neck gene (Na). In this study, the effects of high AT and Na were investigated in broiler progeny of hens from a sire line and two dam lines, differing in growth rate and meat yield due to different breeding histories. Heterozygous naked-neck (Na/na) males were mated with normally feathered (na/na) hens from the three lines. The 500 progeny were segregated for Na/na and na/na genotypes. After brooding, chicks of each maternal background, Na genotype, and sex were equally divided to two similar chambers and were reared on litter to 53 d of age. One chamber was set to normal AT, averaging 25 C; the second chamber was set to high AT, averaging 30 C. The high AT treatment reduced growth and meat yield in the progeny of all three groups. This reduction increased with age and was highest in the broilers produced by hens from a sire line bred for high growth rate and breast meat yield. The two other groups, produced by hens from selected and relaxed dam lines, differed in growth rate but were similarly affected by the high AT. It is suggested that the magnitude of the high AT effect depends not only on differences in potential growth rate but also on differences in overall genetic background. It was also shown that broiler performance in the final weeks could be improved by introducing the Na gene into commercial flocks. The advantage of the Na/na genotype was much more pronounced at high AT and in broilers with genetically higher growth rate and breast meat yield.

Animals↗

[Distribution of hepatitis B virus genotype in 5 cities of Fujian province and the clinical implications of HBV genotype].

OBJECTIVE: To study the prevalence of hepatitis B virus (HBV) genotype in 5 cities of Fujian province and the clinical implications of distinct genotypes in HBV-related liver diseases. METHODS: HBV genotype was determined by the restriction fragment length polymorphism analysis in patients with chronic HBV infection in 5 cities of Fujian province. The relationship between HBV genotype and its clinical implications was studied by multinomal logistic regression and correspondence analysis. RESULTS: Of the 431 HBV DNA positive patients detected by PCR, 275 (63.8%) belonged to HBV genotype B, 100 (23.2%) to genotype C, 51 (11.8%) to genotype D and D-mixed genotype. Genotype A, E and F were not found. Multinomal logistic regression showed that genotype B was more prevalent in Quanzhou and Sanming cities than in Fuzhou (P = 0.002, P = 0.006), and genotype B appeared significantly more common in asymptomatic carriers (ASC), chronic hepatitis B (CHB) and severe hepatitis (SH). Genotype C was most prevalent in patients with liver cirrhosis (LC) (47.0%) than in those with ASC (14.5%) and SH (14.7%) (P = 0.009, P < 0.001). The positive rate of hepatitis B e antigen was higher in patients with genotype C than in those with genotype B and genotype D (56.0% vs. 52.4%, P = 0.008, and 56.0% vs. 30.8%, P = 0.051, respectively). By correspondence analysis, genotype D and D-mixed genotype seemed to be correlated with hepatocellular carcinoma (HCC). CONCLUSIONS: (1) The major popular genotypes of HBV were B, C and D in Fujian. (2) Data of our study suggested that the geographic distribution of genotype B and C might be different in some cities of Fujian. (3) Genotype B might have a tendency to lead to SH in younger patients with chronic hepatitis B and the development of LC might be associated with genotype C among the elder patients. (4) Genotype D appeared to associate with development of HCC, which called for further study to confirm.

Adolescent↗

Genotypic dominance and novel recombinations in HBV genotype B and C co-infected intravenous drug users.

Pathogenic differences among hepatitis B virus (HBV) genotypes have been documented. However, the interaction between different HBV genotypes remains unclear. Herein, we chose HBV genotypes B (HBV/B) and C (HBV/C) co-infected intravenous drug users to study this issue. HBV genotype was determined in 40 HBsAg, anti-HCV, and anti-HDV co-positive intravenous drug users by using genotype-specific primers. The distribution of HBV genotype was as follows: HBV genotype B alone in 29 (72.5%); HBV genotype C alone in 4 (10.0%); and mixed HBV genotype B and HBV genotype C in 7 (17.5%). The interaction between HBV genotype B and HBV genotype C within the same individual was further studied in the seven intravenous drug users with HBV genotype B and HBV genotype C co-infection. By direct sequencing of the pre-S region, only HBV genotype B was detected. When 10-21 clones of the pre-S region were propagated from each intravenous drug user and sequenced, most of the clones were HBV genotype B. Novel recombinations between HBV genotype B and HBV genotype C occurred in four clones (M7-5, M1-10, M1-21, and M1-24) from two intravenous drug users (M7 and M1). The recombination breakpoints were estimated at nucleotide 3120-3171 for M7-5, at nucleotide 3060-3191 for M1-10, and at nucleotide 2910-2950 for M1-21 and M1-24 by SimPlot program. The recombination sites of these HBV/pre-S C-B and B-C recombinants may be within the pre-S1 region. The results in this study suggest that HBV/B is the dominant strain in HBV genotypes B and C co-infected intravenous drug users in Taiwan, and recombinations between different HBV genotype are not unusual. The impact of recombination on the evolution of HBV and their clinical significance remains to be studied.

Adult↗

Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam.

Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV-infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A-G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication-phenotype of single genotypes compared to genotype-mixtures suggest that co-infection with different HBV-genotypes is associated with altered pathogenesis and clinical outcome.

Adult↗

Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d'Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E.

The characteristics of hepatitis B virus (HBV) genotype E are not well known because only a few studies have been carried out by complete genome analysis. The aim of this study was to elucidate the distribution of HBV genotypes in Cote d'Ivoire, and to clarify the genotype-related characteristics of genotype E. The distribution of HBV genotypes among 48 HBV carriers in Cote d'Ivoire was determined using serological and genetic methods. The characteristics of genotype E were evaluated by complete genome sequences, and further investigations of small S gene, basic core promoter (BCP) mutation, and precore mutation were undertaken. HBV genotype distribution among the 48 carriers was 6.3% for genotype A, 6.3% for genotype D, and 87.4% for genotype E. Complete genomes of two genotype E strains were sequenced, and found to have 98.2% to 99.2% homology at the nucleotide level when compared with genotype E strains reported previously. In 24 genotype E carriers, the precore mutation was detected in 75% of the patients without HBeAg, in contrast to only 25% of the patients with HBeAg (P < 0.05). All 24 strains have T at nucleotide 1858 in the precore region. In contrast, BCP double mutation was detected in 17% of the patients with HBeAg, and 33% of the patients without HBeAg. These results indicated as the following: (1) genotypes A, D, and E of HBV exist in Cote d'Ivoire and genotype E is the most prevalent; (2) genotype E spread with low genetic diversity over the complete genome in West Africa; (3) HBV precore and/or BCP double variants were common among the patients with genotype E infections.

Amino Acid Sequence↗

[Relation between genotype of HBV and its clinical manifestation by PCR with genotype-specific primers].

OBJECTIVE: To determine the relation between genotype of HBV and its clinical manifestation. METHODS: Sera of 220 patients from Hunan Province of China, infected chronically with asymptomatic, mild, moderate, severe and fulminant hepatitis hepatitis B, were genotyped by PCR with genotype-specific primers. The results were statistically analyzed. RESULTS: Only genotype B (86.4%) and C (13.6%) were found. With the aggravations of patients' condition, genotype C was found more often (P < 0.05). The levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and HBV-DNA of genotype C was higher than those of genotype B, but there was no statistical difference. However, the ALT elevation rates of genotype C (96.7%) were significantly higher than those of genotype B (75.2%) (P < 0.05). There was no statistical difference in HBeAg rate between genotype B and C in general, but in patients with chronic fulminant hepatitis or aged 21 approximately 30, the HBeAg rates of genotype C (35.0% and 50.0%) were significantly higher than those of genotype B (14.4% and 24.5%) (P < 0.05). CONCLUSION: The dominant genotype of HBV in Hunan Province of China is genotype B and C. Genotype of HBV correlates with its clinical manifestation and genotype C of HBV can lead to more severe hepatitis than genotype B of HBV.

Adolescent↗

Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America.

The complete genomes were sequenced for ten hepatitis B virus (HBV) strains. Two of them, from Spain and Sweden, were most similar to genotype D, although encoding d specificity. Five of them were from Central America and belonged to genotype F. Two strains from Nicaragua and one from Los Angeles, USA, showed divergences of 3.1-4.1% within the small S gene from genotype F strains and were recognized previously as a divergent clade within genotype F. The complete genomes of the two genotype D strains were found to differ from published genotype D strains by 2.8-4.6%. Their S genes encoded Lys(122), Thr(127) and Lys(160), corresponding to the putative new subtype adw3 within this genotype, previously known to specify ayw2, ayw3 or, rarely, ayw4. The complete genomes of the three divergent strains diverged by 0.8-2.5% from each other, 7.2-10.2% from genotype F strains and 13.2-15.7% from other HBV strains. Since pairwise comparisons of 82 complete HBV genomes of intratypic and intertypic divergences ranged from 0.1 to 7.4% and 6.8 to 17.1%, respectively, the three sequenced strains should represent a new HBV genotype, for which the designation H is proposed. In the polymerase region, the three strains had 16 unique conserved amino acid residues not present in genotype F strains. So far, genotype H has been encountered in Nicaragua, Mexico and California. Phylogenetic analysis of the complete genomes and subgenomes of the three strains showed them clustering with genotype F but forming a separate branch supported by 100% bootstrap. Being most similar to genotype F, known to be an Amerindian genotype, genotype H has most likely split off from genotype F within the New World.

Asian People↗

Superinfection of chimpanzees carrying hepatitis C virus of genotype II/1b with that of genotype III/2a or I/1a.

Three chimpanzees persistently infected with hepatitis C virus of genotype II/1b were challenged with hepatitis C virus of genotype III/2a and 6 wk later with hepatitis C virus of genotype I/1a. They were tested for titers of total and genotype-specific hepatitis C virus RNA, as well as for serum transaminase levels, until 52 wk after the first challenge. One chimpanzee (CH489) with intermittent low hepatitis C virus RNA titers of genotype II/1b in serum was superinfected with hepatitis C virus of genotype III/2a between wk 1 and 7 after the challenge; superinfection was accompanied by fluctuating high transaminase levels. Later, the animal was superinfected with hepatitis C virus of genotype I/1a. Superinfection was accompanied by persistently high transaminase levels immediately after the challenge. Hepatitis C virus of genotype I/1a persisted, whereas hepatitis C virus of genotype II/1b was undetectable 22 wk after the challenge and thereafter. In another chimpanzee (CH353) with intermittent low hepatitis C virus RNA titers of genotype II/1b, hepatitis C virus of genotype III/2a induced fluctuating high levels of serum transaminases without revealing itself in serum. Then, HCV of genotype I/1a superinfected her, induced persistently high transaminase levels and took over HCV of genotype II/1b at 22 wk after the challenge and thereafter. The third chimpanzee (CH451) with persistently high HCV RNA titers of genotype II/1b did not reveal HCV RNA of genotype III/2a in serum after the challenge, although transaminases sharply increased. Low-titered HCV RNA of genotype I/1a was detected at 18 wk after the challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Global identification of three major genotypes of varicella-zoster virus: longitudinal clustering and strategies for genotyping.

By analysis of a single, variable, and short DNA sequence of 447 bp located within open reading frame 22 (ORF22), we discriminated three major varicella-zoster virus (VZV) genotypes. VZV isolates from all six inhabited continents that showed nearly complete homology to ORF22 of the European reference strain Dumas were assigned to the European (E) genotype. All Japanese isolates, defined as the Japanese (J) genotype, were identical in the respective genomic region and proved the most divergent from the E strains, carrying four distinct variations. The remaining isolates carried a combination of E- and J-specific variations in the target sequence and thus were collectively termed the mosaic (M) genotype. Three hundred twenty-six isolates collected in 27 countries were genotyped. A distinctive longitudinal distribution of VZV genotypes supports this approach. Among 111 isolates collected from European patients, 96.4% were genotype E. Consistent with this observation, approximately 80% of the VZV strains from the United States were also genotype E. Similarly, genotype E viruses were dominant in the Asian part of Russia and in eastern Australia. M genotype viruses were strongly dominant in tropical regions of Africa, Indochina, and Central America, and they were common in western Australia. However, genotype M viruses were also identified as a minority in several countries worldwide. Two major intertypic variations of genotype M strains were identified, suggesting that the M genotype can be further differentiated into subgenotypes. These data highlight the direction for future VZV genotyping efforts. This approach provides the first simple genotyping method for VZV strains in clinical samples.

Cluster Analysis↗

Difference in prognosis between patients infected with hepatitis B virus with genotype B and those with genotype C in the Okinawa Islands: a prospective study.

The factors contributing to the prognosis of hepatitis B virus (HBV)- related chronic liver disease were assessed prospectively in 72 patients with chronic hepatitis B confirmed clinically and pathologically. A comparative study was undertaken between patients infected with genotype B and those with genotype C. During the follow-up period, 13 (81.3%) of 16 patients with genotype B who were initially hepatitis B e antigen (HBeAg) positive became HBeAg negative and 14 (51.9%) of 27 with genotype C became HBeAg negative. HBeAg had been cleared in 8 (61.5%) of 13 patients with genotype B within the first 2 years of the follow-up, but in only one (7.1%) of 14 with genotype C (P < 0.05). Four (11.4%) of 35 patients with genotype B had progressed to cirrhosis, whereas, 12 (32.4%) of 37 patients with genotype C progressed to cirrhosis, including two patients with hepatocellular carcinoma. Multivariate analysis showed that difference in HBV genotype influenced significantly either the clearance of HBeAg or the development of cirrhosis. In conclusion, HBeAg was cleared from sera more frequently and earlier in patients with genotype B compared with those with genotype C, and development of cirrhosis occurred less frequently in patients with genotype B compared with those with genotype C. Thus, HBV genotypes may influence the prognosis of HBV-related chronic liver disease.

Adolescent↗

TRUGENE sequencing versus INNO-LiPA for sub-genotyping of HCV genotype-4.

Hepatitis C virus genotypes and subtypes determination is an important factor for understanding the epidemiology of the virus, in the pre-treatment evaluation of the patients and in defining better treatment strategies. In the present study, we compared two commercially available assays for HCV genotyping: the reverse hybridization based Innogenetics INNO-LiPA HCV II and the direct sequencing by TRUGENE assay. The study included 31 HCV-RNA positive Egyptian patients; 18 patients with chronic active hepatitis, 8 with HCC, and 5 with cirrhosis. Using the TRUGENE genotyping test, all the samples had genotype 4 (100%) and subtyped as 4a in 18/31(58%), 4c in 10/31 (32%), 4e in 1/31 (3%), 4a/c in 1/31 (3%), and 4g in 1/31 (3%). Using the INNO-LiPA assay, 30 samples had genotype 4 (97%), and 1 sample had genotype 1e (3%). One sample showed mixed infection with type 4f and type 1. Only six samples were subtypable by INNO-LiPA, three were genotype 4c/d, and the other three were 4f, 4e, and 1e. Seven samples gave reactivity in the INNO-LiPA of lines 5, 6, 16, 17, 18, which are considered untypable by the interpretation chart but considered to be a rare HCV genotype 4 by the manufacturer. At the genotype level, there was a 97% concordance between TRUGENE sequencing and INNO-LiPA, but at the subtype level the concordance rate was 3% only. We conclude that the TRUGENE genotyping assay is a reliable test for HCV genotyping for the detection of major types and subtypes detection, while INNO-LiPA is a good test at the genotype level but unreliable for subtyping especially in the Egyptian population. This is mainly due to the high diversity of genotype 4, which is the most prevalent genotype in Egypt.

Adult↗

Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: a longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline.

BACKGROUND/AIMS: Longitudinal studies on the relationship between hepatitis B virus (HBV) genotypes and reactivation of hepatitis B and progression to cirrhosis were very rare. METHODS: Liver biochemistry, virological markers and ultrasound were monitored in 202 hepatitis B e antigen (HBeAg)-positive patients with normal alanine aminotransferase (ALT) at baseline for 3-20 (average 10.8) years, and the outcome was correlated with HBV genotypes. RESULTS: There were 150 genotype B and 52 genotype C patients. Hepatitis activity during the HBeAg-positive phase showed no significant difference. However, genotype B was associated with a significantly earlier and higher rate of HBeAg seroconversion. HBeAg seroconversion correlated with age at entry for genotype B and with ALT levels for genotype C. Reactivation of hepatitis B was significantly more common in genotype C patients. Five genotype B and 10 genotype C patients progressed to cirrhosis. Multivariate analysis revealed that genotype C (P = 0.03) and reactivation of hepatitis B (P = 0.0004) were independent factor predictive of cirrhosis. CONCLUSIONS: Rate and factors of HBeAg seroconversion, and rate of reactivation of hepatitis B differed between genotype B and genotype C patients. Genotype C and reactivation of hepatitis B were associated with increased risk of cirrhosis.

Adult↗

Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C.

BACKGROUND & AIMS: Recent studies suggest that hepatitis B virus (HBV) genotype B is associated with less active liver disease than HBV genotype C. The aim of our study was to determine if HBV genotype B is associated with higher rates of spontaneous hepatitis B e antigen (HBeAg) seroconversion compared with genotype C. METHODS: A retrospective study using stored sera from 332 Chinese patients with chronic HBV infection followed for a mean of 48 months (range, 12-98) were tested for HBV genotype using a line-probe assay. RESULTS: HBV DNA was detected in 273 patients, 122 had HBV genotype B and 147 genotype C. Patients with genotype B had a significantly lower prevalence of HBeAg at presentation and significantly higher rates of spontaneous HBeAg seroconversion during follow-up. HBV genotype B patients who were HBeAg positive were significantly younger, and spontaneous HBeAg seroconversion occurred approximately 1 decade earlier compared with HBV genotype C patients. Multivariate analyses identified high alanine aminotransferase (baseline and follow-up), age >30 years, and genotype B as independent factors associated with spontaneous HBeAg seroconversion. CONCLUSIONS: HBV genotype B is associated with earlier HBeAg seroconversion than genotype C. This finding may explain the less active/progressive liver disease in patients with genotype B.

Adolescent↗