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PubMed2004

Distinguishing hepatitis B virus (HBV) genotype D from non-D by a simple PCR.

Different HBV genotypes have characteristic geographical distribution, which is important epidemiologically. HBV strains have been classified into eight different genotypes (A-H) on the basis of >8% differences in the entire genomic sequence. Genotypes A and D are predominant in Europe, Africa, and the USA, genotypes B and C are restricted to East Asia, genotype E is found in Africa, and genotype F is found in indigenous populations in Central and South America. Genotype D is prevalent in the Turkish population. HBV genotype D shows a 33-bp deletion in the pre-S1 region that accounts for their smaller genomic size (3182 bp). This deletion can be used to facilitate the identification of genotype D. A primer in the pre-S1 region was designed to discriminate genotype D from non-D by PCR. Sixty genotype D (40 acute and 20 chronic) and 4 genotype A sera identified by restriction fragment length polymorphism (RFLP) were included in the study. Using this simple PCR method, all genotype D sera were identified correctly and the test was able to detect HBV DNA at 1000 genomes per ml. An advantage of this method is that it can differentiate in a mixture of genotypes (genotype D from non-D) provided that one isn't present below 1 x 10(4) copies/ml. In conclusion this method is rapid (approximately 5h) and it will contribute to the epidemiological study of HBV in high prevalence areas of genotype D. It can also differentiate between genotype D from non-D in cases of co-infection.

DNA, Viral↗
PubMed2005

Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6.

Infection with hepatitis C virus (HCV) genotypes 4-6 (with the previously named genotypes 7-9 included as subtypes of genotype 6) is distributed and studied less widely than genotypes 1-3. However, genotypes 4-6 are very common in geographic areas where chronic hepatitis C is highly prevalent. In fact, the majority (87%) of the 169.7 million HCV-infected individuals worldwide are from western Pacific countries (62.2 million), southeast Asia (32.3 million), Africa (31.9 million), and eastern Mediterranean countries (21.3 million). It is among this large population outside of the Americas and Europe that these less well known genotypes are found: genotype 4 in Egypt and Africa, genotype 5 in South Africa, and genotype 6 in southeast Asia. The existing literature, although limited, suggests that patients with chronic hepatitis C genotypes 4-6 may exhibit different clinical courses and treatment outcomes. Ethnicity-related factors may contribute to the presence of more advanced disease in patients with genotype 4, who also tend to have a poor response to interferon-based therapy. HCV genotype 5 appears to be an easy-to-treat virus with response rates similar to those of genotypes 2 and 3 after a 48-week course of therapy. Response to treatment in patients with HCV genotype 6 may be at an intermediate level between that seen with genotype 1 and genotype 2 or 3. The optimal duration of treatment (24 vs 48 wk) for HCV genotype 6 is unclear and currently is under investigation.

Antiviral Agents↗
PubMed2000

Hepatitis C virus mixed genotype infection in patients on haemodialysis.

Hepatitis C virus (HCV) has been classified into different genotypes/subtypes with demonstrated clinical implications. Whether there is biological difference between genotypes is unknown. We determined HCV genotype in 120 anti-HCV-positive patients with end-stage renal disease and on haemodialysis, by both serological assay (which showed evidence of previous exposure) and by two molecular assays: restriction fragment length polymorphism (RFLP) and line-probe reverse hybridization (LiPA). In mixing experiments, RFLP and LiPA was able to detect the minor HCV genotypes (if present) in 5-30% and 1-2% of the viral population, respectively. Of the 120 patients studied, genotype-specific antibodies were detected in 50 (42%), and eight patients had reactivities to peptides derived from multiple genotypes (genotypes 1 and 2 and/or 3). Only genotype 1 infection was found by RFLP/LiPA in these eight patients with reactivities to multiple HCV genotypes. One-hundred and five of the 120 (88%) patients were positive for HCV RNA by reverse transcription-polymerase chain reaction (RT-PCR) analysis and 14 were found to have mixed genotype infection. Follow-up serum samples (4-21 months later) were available in five patients (genotype 1a with another genotype/subtype). All five patients had a reduced number of HCV genotypes detected during follow-up; four of the five patients still had detectable genotype 1a, and one patient lost genotype 1a and was positive for genotype 2b only. These data showed that HCV mixed infection can be reliably detected by molecular methods and, in patients with end-stage renal disease and mixed genotype infection, there is a trend that during follow-up, HCV genotype 1 may prevail, or 'take over' the genotype 2 and 3 infection.

Cloning, Molecular↗
PubMed1996

Response to interferon in chronic hepatitis C due to mixed genotype infection.

We examined the response to interferon (IFN) in patients with chronic hepatitis C (CHC) due to two different genotypes of hepatitis C virus (HCV) infection. Among 64 CHC patients studied, one (2%) had HCV-RNA genotype I, 36 (56%) had genotype II, 19 (30%) had genotype III, 2 (3%) had genotype IV and 6 (9%) had both genotypes II and III. There was no significant difference in age, sex, history of blood transfusion and liver histology among patients with genotypes II, III and II + III. The HCV-RNA titre of genotype II patients was significantly higher than that of genotype III patients (P < 0.05). However, there was no significant difference in the HCV-RNA titre between genotype II + III and the other groups. The complete response rate achieved with IFN therapy was significantly higher in genotype III patients (74%) than in genotype II patients (17%; P < 0.01). Of the six patients with genotype II + III, a complete response to IFN was only achieved by two patients (33%), both of whom had a low HCV-RNA titre ( < or = 10(4.5) copies/mL) and HCV serotype 2. The remaining four patients had HCV serotype 1 and three of the patients had a high HCV-RNA titre ( > or = 10(5) copies/mL). The HCV genotype III was lost in two patients after IFN therapy. These data suggest that HCV-RNA titre and HCV serotype are important factors for predicting the efficacy of IFN therapy in patients with mixed genotype infection and show direct evidence of higher susceptibility towards CHC of patients with genotype III than genotype II.

Adolescent↗
PubMed1998

Genotype-specific complementation of hepatitis delta virus RNA replication by hepatitis delta antigen.

Characterizations of genetic variations among hepatitis delta virus (HDV) isolates have focused principally on phylogenetic analysis of sequences, which vary by 30 to 40% among three genotypes and about 10 to 15% among isolates of the same genotype. The significance of the sequence differences has been unclear but could be responsible for pathogenic variations associated with the different genotypes. Studies of the mechanisms of HDV replication have been limited to cDNA clones from HDV genotype I, which is the most common. To perform a comparative analysis of HDV RNA replication in genotypes I and III, we have obtained a full-length cDNA clone from an HDV genotype III isolate. In transfected Huh-7 cells, the functional roles of the two forms of the viral protein, hepatitis delta antigen (HDAg), in HDV RNA replication are similar for both genotypes I and III; the short form is required for RNA replication, while the long form inhibits replication. For both genotypes, HDAg was able to support replication of RNAs of the same genotype that were mutated so as to be defective for HDAg production. Surprisingly, however, neither genotype I nor genotype III HDAg was able to support replication of such mutated RNAs of the other genotype. The inability of genotype III HDAg to support replication of genotype I RNA could have been due to a weak interaction between the RNA and HDAg. The clear genotype-specific activity of HDAg in supporting HDV RNA replication confirms the original categorization of HDV sequences in three genotypes and further suggests that these should be referred to as types (i.e., HDV-I and HDV-III) rather than genotypes.

Cloning, Molecular↗
PubMed2001

Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai, China.

OBJECTIVE: Hepatitis B virus (HBV) genotype distribution is still unclear in China, where a high prevalence of HBV infection exists, although it is well known that HBV can be classified into six genotypes based on intergroup divergence. The aim of this study was to investigate the epidemiological distribution of HBV genotypes and to clarify further the genotype-related differences in the pathogenicity of HBV. METHODS: Seminested PCR and restriction fragment length polymorphism analysis were conducted in 97 asymptomatic HBV carriers (ASC) and 46 chronic hepatitis (CH), 37 liver cirrhosis (LC) and 44 hepatocellular carcinoma (HCC) patients in Shanghai, China. RESULTS: Two hundred and twenty samples (98.2%) were positive for HBV DNA, and of these, 3 (1.4%), 38 (17.2%) and 179 (81.4%) were classified as genotype A, B and C, respectively. There was a statistically significant difference in the distribution of genotypes B and C among various categories of liver diseases (p < 0.01). The distribution of genotype C showed an increasing trend from ASC, CH and LC to the HCC group; in contrast, the distribution of genotype B showed a decreasing trend in the same order. HBeAg positivity was higher in genotype C than in genotype B in all the subjects or in the ASC group alone (p < 0.05, p < 0.01, respectively). More severe liver damage and a higher mean age were observed in genotype C than in genotype B (p < 0.01, p < 0.05, respectively). CONCLUSIONS: These results indicate the following: (1) genotypes A, B and C of HBV exist in Shanghai, China; (2) genotype C is the major genotype in this area; (3) genotype C is associated with the development of severe liver diseases, and (4) genotype B has a relatively good prognosis.

Adolescent↗
PubMed2004

Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii.

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS: Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by genetic methods. Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61 carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian, respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858). However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia with T-1858. In addition, two strains from Asian ethnicities were clustered with known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

Adult↗
PubMedDate not supplied

[Viral C hepatitis in patients with end stage renal disease. II. Viral genotypes].

BACKGROUND: The hepatitis C virus infection is highly prevalent in patients on chronic dialysis. There are more than 10 variants of the hepatitis C virus, with 55 to 72% of identity among them at the amino acid level. However, we do not know the specific genotype in dialysis patients in Mexico. Thus, the aim of the present study was to know the specific genotypes of the C virus in infected dialysis patients, to know the distribution of genotypes in the different dialysis techniques and to know the relation between genotype and hepatic disease stage. METHODS: We performed a prospective, transversal and comparative study in patients in dialysis in three hospital centers in the south of Mexico City. The presence of C-type hepatitis infection was assessed by ELISA II and qualitative RT-PCR in blood samples. The genotype of the hepatitis C virus was determined by analysis of the restriction pattern of the RT-PCR product using Mva I, Hinf I, BstU I and ScrF I restriction enzymes. Variables analyzed were: age, gender, etiology of renal failure, kind and time in substitutive therapy, transfusion and hepatitis history, liver function test, blood urea, serum creatinine and blood cell count. RESULTS: We studied 235 dialysis patients that were divided following their dialysis modality into: 132 in continue ambulatory peritoneal dialysis (CAPD), 17 in CAPD, but with history of hemodialysis (PD/HD) of at least one month and 86 on hemodialysis (HD). The hepatitis infection was detected in 24 of the 235 patients (CAPD = 4.5%, PD/HD = 41.1% and HD = 12.7%; p < 0.001). The most common genotype was 1B (12/24), followed by 1A and 2A (4/24 each one), and finally by 2B and 2C (2/24 each one). We detected no patients with genotypes 3 to 6. The patients with 2A genotype were older than those infected with 1A (p < 0.05). History of surgery, transfusions, and hepatitis was similar in all genotypes. Finally the time in dialysis was longer in patients with 2A genotype than others (2A = 60.5 +/- 71.5 months, vs. 1A = 11.5 +/- 11.3, 1B = 26 +/- 26.4 y 2B/C = 17.5 +/- 13.4), but the difference did not reach statistical significance. The genotype distribution between dialysis techniques showed that 1B genotype was the most frequent in all modalities. The 1A genotype was present in similar proportions in patients of the three dialysis groups, the 2C genotype was present only in patients with CAPD. Finally, the 2B was only found in hemodialysis patients. DISCUSSION: The assessment of viral genotype revealed that 1B is the most common genotype in patients on chronic dialysis in Mexico City. The fact that the 1B and 1A genotypes were the most common types in our dialysis population suggest that transmission was similar to the general population, that is, probably by blood transfusions.

Adult↗
PubMed2002

[Genotyping of hepatitis B virus and clinical investigation].

OBJECTIVE: To investigate the distribution of HBV genotypes in Changzhou area and to clarify the genotype-related difference in the liver function, the level of HBV DNA and the long-term effect of lamivudine in the pathogenicity of HBV. METHODS: Nested PCR and sequence analysis were conducted in 14 acute hepatitis (AH), 104 chronic hepatitis (CH), and 28 liver cirrhosis or hepatocellular carcinoma (LC/HCC) patients. RESULTS: One hundred and forty six samples were positive for HBV DNA, and 51 samples were classified as genotype B (34.9%), 95 samples were classified as genotype C, serum ALT value was 383.8 +/- 335.7 IU in patients with HBV genotypes B, and 364.3 +/- 333.7 IU in genotypes C, HBV DNA value was 10(7.795 +/- 1.22) copies/ml in genotypes B and 10(7.69 +/0- 1.19) copies/ml in genotypes C, and there were 36 and 64 HBeAg positive cases in patients with genotypes B and C; there were no significant difference on the level of ALT, HBV DNA and the expression of HBeAg (P>0.05), but genotype C in LC/HCC was higher than CH (P<0.01). Twenty three genotype B and forty five genotype C patients received lamivudine treatment, after 48 weeks, 18 genotype B and 14 genotype C patients had higher ALT or HBV DNA positive. CONCLUSIONS: These results indicate that genotype B and C existing Changzhou area; genotype C is associated with the development of severe liver disease and better therapeutic effect could be obtained in the patients with genotype C.

Adult↗
PubMed2004

[The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C].

OBJECTIVE: To investigate the influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C. METHODS: The genotypes of HCV virus were determined in the patients enrolled into the Randomized, opened and controlled trial of Peg-IFN alpha-2a (Pegasys) treatment, controlled with IFN-alpha-2a (Roferon-A), on chronic hepatitis C patients in China. The serum ALT levels and HCV RNA concentration of the patients were detected in the time of before treatment, the end of therapy and follow-up. The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C was analyzed in intention to treat (ITT) population. RESULTS: The HCV genotypes of 202 cases were determined. 158 (78.2%) cases infected with genotype 1 HCV and 44 (21.8%) cases with genotype non-1. For overall patients, the viral response at the end of treatment (ETVR) and sustained viral response (SVR) rates were 53.8% and 25.3% respectively in patients with genotype 1 HCV, but in genotype non-1 patients those was 61.4% and 43.2%, and the difference of SVR between genotype 1 and non-1 was significant (P=0.021). After grouped by the used drugs, in the patients given Pegasys treatment, the ETVR rates of patients with genotype 1 and non-1 HCV infection were 76.8% and 81.0%, the difference was not significant (P=0.686), but the difference of SVR rates, which were 35.4% and 66.7%, of the patients was significant (P=0.01). The viral relapse rate of genotype 1 was 55.6%; it was significant higher than that of genotype non-1 (23.5%) (P=0.02). In Roferon-A group, the ETVR and SVR rates of patients with genotype 1 HCV were 29.0% and 14.5%, which were lower, but not significant, than those of patients with genotype non-1 (43.5% and 21.7%). The viral relapse rate of genotype 1 was 72.7% and higher, but not significant, than that of genotype non-1 also (50.0%) (P=0.21). CONCLUSION: HCV genotype could affects the efficacies, mainly the sustained responses, of IFN treatment of patients with chronic hepatitis C, and the effects of IFN were related to the kinds of drugs and therapeutic course.

Antiviral Agents↗
PubMed2004

[Establishment of a new HBV genotyping method with PCR-RBD and its application].

OBJECTIVE: Using PCR-RDB to establish a new method for HBV genotyping, and to survey the distribution of HBV genotypes in the Foshan area. METHODS: Biotin-labeled primers for amplification of HBV region X (nt1550-1789) were used to amplify extracted HBV DNA. HBV was genotyped by hybridization of the PCR products with immobilized specific probes (genotype A to F) on C membrane. Color development was achieved by adding POD and TMB. A judgment was made according to color reactions. The reliability of this new method was verified by gene sequencing. 300 samples of HBV DNA-positive sera from the Foshan area were genotyped using this assay. RESULTS: Of the 300 sera genotyped by PCR-RBD, 147 (49.0%) cases were genotype B, 136 (45.3%) were genotype C, 1 (0.3%) genotype D, and 12 (4.0%) were mixtures of genotype B and C, and 4 (1.3%) were mixtures of genotype C and D. No genotype A, E or F were found. The results of PCR-RDB genotyping were consistent with the results obtained with sequence analysis. CONCLUSION: This newly established HBV genotyping system proved to be sensitive, specific, precise and economic, and should be suitable for clinical practice and epidemic study. The results of HBV genotyping show that genotype B and C are the predominant genotypes in the Foshan area.

DNA, Viral↗
PubMed2005

[Development and application of a new hepatitis C virus genotyping method with polymerase chain reaction-reverse blot dot technique].

OBJECTIVE: Using polymerase chain reaction-reverse blot dot (PCR-RDB) technique to establish a new method for hepatitis C virus (HCV) genotyping and to study the distribution of HCV genotypes in Foshan area. METHODS: HCV primers and probes were designed in 5'-untranslated region (nt-1-nt-299) of HCV. HCV RNA in serum was isolated and purified, and its cDNA was obtained by reversed transcription. Nested PCR using biotin-labelled primers, was done. PCR products were hybridized with immobilized specific probes (genotype 1a to 3b) on Biodyne C membrane to genotype HCV by color development while adding POD and TMB. A certain judgment could be made according to the position of color reaction. The reliability of this new method was verified by sequencing. HCV RNA levels in serum were determined by real time fluorescent quantitative (FQ)-PCR. 60 FQ-PCR-positive HCV sera from Foshan area were genotyped using this assay. RESULTS: All 60 sera could be successfully genotyped by PCR-RBD. 50 (83.3%) cases were found to be genotype 1b, 2 (3.3%) as genotype 1a and 2 (3.3%) as genotype 2a while 5 (8.0%) to be mixture of genotype 1a and 1b, and 1 (1.7%) to be mixture of genotypes 1b and 2a. No genotypes 2b, 3a and 3b were found. The results of PCR-RDB genotyping methods coincided with sequence analysis. CONCLUSION: Newly established HCV genotyping system was proved to be sensitive, specific, precise and economic, thus suitable for clinical and epidemiologic studies. The results of HCV genotyping showed that genotype 1b was the predominant genotype in Foshan area.

Genotype↗
PubMed2005

[The relation between virus genotypes and coexisting surface antigen and antibody in patients with hepatitis B, and the development of preS region deletions].

In recent years, there has been renewed interest in hepatitis B virus (HBV) genotypes. Our previous data have shown the importance of in-frame deletions in the preS region in cases of coexisting hepatitis B surface antigen (HBsAg) and anti-hepatitis B surface antibody (HBsAb). The aim of the present study was to investigate the relation between HBV genotypes and coexisting HBsAg and HBsAb, preS deletion mutants. We investigated the HBV genotypes in 9 patients with coexisting HBsAg and HBsAb. Viral DNA was extracted from the patients' sera and the HBV S gene region was amplified by polymerase chain reaction (PCR). HBV genotypes were then investigated by restriction fragment length polymorphism(RFLP) analysis. All 9 cases were found to have genotype C. This result clearly indicates that the unique finding of coexisting HBsAg and HBsAb depends on the HBV genotype. After genotypic screening was performed for HBV-positive samples from randomly selected 60 cases. The results of the 60 cases we investigated showed 26 cases of genotype B (43.3%), 31 cases of genotype C (51.7%), 1 case of coexisting genotype B and C (1.7%), and 2 cases of other genotypes (3.3%). Of the 60 cases, 45 cases consisting of 21 with genotype B and 24 with genotype C were subject to direct DNA sequencing of PCR products in the preS region to determine the presence or absence of preS deletion mutants. PreS deletion mutants were found in a total of 7 of the 45 HBV cases that underwent sequencing(7/45; 15.6%), and 6 of these had genotype C (6/24 cases, 25.0%), whereas only 1 had genotype B (1/21 cases, 4.8%). These results demonstrate a greater frequency of preS deletion mutants with genotype C. Interestingly, many preS deletion mutants showed deletions at the same point, namely the amino terminal side of the preS2 region. These results indicate that the HBV genotype is involved in the molecular pathogenesis of hepatitis B.

Adult↗
PubMed2006

Relationship between water use efficiency (WUE) and production of different wheat genotypes at soil water deficit.

Through 2-year field experiments, 7 wheat genotypes were better in their field yield. These 7 wheat genotypes and other 3 wheat species, which are being popularized on a large scale in different locations of China, were selected as experimental materials for the sake of measuring their difference in WUE and production and comparing their relationship at soil water deficits, future more, providing better drought resistance lines and theoretical guide for wheat production and practices and exploring anti-drought physiological mechanisms of different wheat genotypes. Under the condition of 3 soil-water-stress treatments (75% field capacity (FC), 55% FC, 45% FC, named level 1, level 2 and level 3, respectively), pot experiments for them were conducted and the related data were collected from their life circle. The main results were as followed: (1) according to the selected soil stress levels, water use efficiency (WUE) of 10 different wheat genotypes was divided into two groups (A and B); group A included genotypes 2, 3, 4, 5, 6, 7, 8, whose WUE decreased basically from level 1 to level 3 and reached individual peak of WUE at level 1; Group 2 included genotypes 1, 9, 10, whose WUE reached their individual peak at level 2; (2) based on total water consumption through all life circle, genotypes 1, 4, 8, 9 had lower water consumption (TWC) at level 1, genotypes 2, 3, 5, 6, 7 lower TWC at level 2, genotype 10 lower TWC at level 3; (3) at level 1, genotypes 2, 3, 4, 5, 6, 7, 8 had higher grain weight of single spike (GWSS), genotypes 1, 9, 10 better GWSS at level 2, which was in good line with individual WUE of different wheat genotypes; (4) by analyzing the indexes related to examining cultivars, it was found that genotypes 1, 2, 3, 4, 5, 6, 9, 10 had longer plant length (PL), spike length (SL), bigger grain number (GN) except genotypes 7 and 8 at level 1, RL was in better line with genotypes 1, 2, 3, 8, 9, 10, but not in the other genotypes at level 1.

Disasters↗
PubMed2005

Genotyping of hepatitis B virus in Malaysia based on the nucleotide sequence of preS and S genes.

Hepatitis B virus (HBV) has been classified into eight genotypes, designated A-H. These genotypes are known to have distinct geographic distributions. The clinical importance of genotype-related differences in the pathogenicity of HBV has been revealed recently. In Malaysia, the current distribution of HBV remains unclear. The aim of this study was to determine the genotypes and subtypes of HBV by using PCR, followed by DNA sequencing, as well as to analyse the mutations in the immunodominant region of preS and S proteins. The S gene sequence was determined from HBV DNA of four apparently healthy blood donors' sera and three sera from asymptomatic chronic hepatitis B carriers. Of this batch of sera, the preS gene sequence was obtained from HBV DNA from three out of the four blood donors and two out of the three chronic carriers. Due to insufficient sera, we had to resort to using sera from another blood donor to make up for the sixth DNA sequence of the preS gene. Based on the comparative analysis of the preS sequences with the reported sequences in the GenBank database, HBV DNA from two normal carriers was classified as genotype C. Genotype B was assigned to HBV from one blood donor and two hepatitis B chronic carriers, whereas HBV of one chronic carrier was of genotype D. Based on the S gene sequences, HBV from three blood donors was of genotype C, that of one blood donor and one chronic carrier was of genotype B, and the remaining, of genotype D. In the five cases where both preS and S gene sequences were determined, the genotypes assigned based on either the preS or S gene sequences were in concordance. The nature of the deduced amino acid (aa) sequences at positions 125, 127, 134, 143, 159, 161 and 168 of the S gene enabled the classification of these sequences into subtypes, namely, adrq+, adw2 and ayw2. The clustering of our DNA sequences into genotype groups corresponded to their respective subtype, that is, adw2 in genotype B, adrq in genotype C and ayw in genotype D. Analysis of the point mutations revealed that five of the sequences contained aa substitutions at immunodominant epitopes involved in B or/and T cell recognition. In conclusion, despite the low numbers of samples studied, due to budget constraints, these data are still worthwhile reporting, as it is important for the control of HBV infections. In addition, the genotype and mutational data obtained in this study may be useful for designing new treatment regimes for HBV patients.

Amino Acid Sequence↗
PubMed1999

Hepatitis C virus genotype does not affect patient survival among renal transplant candidates. The New England Organ Bank Hepatitis C Study Group.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk for infection with different hepatitis C virus (HCV) genotypes and multiple genotype infections. However, to date, the effect of the type and number of infecting HCV genotypes on survival among ESRD patients has not been carefully examined, and this was the objective of this study. METHODS: Sera from patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 were tested for anti-HCV using a third-generation enzyme-linked immunosorbent assay. All anti-HCV-positive serum samples were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction (PCR) with primers derived from the highly conserved 5'UTR region of the HCV genome. HCV genotypes were determined by restriction fragment length polymorphism of the 5'UTR PCR product. The duration of follow-up was calculated from the date of the first available serum specimen until death, loss to follow-up, or December 31, 1995, whichever occurred earlier. Two separate multivariate models were constructed: one to examine the impact of HCV genotype on mortality and the other to examine the impact of the single versus mixed infection on mortality. In both models, the independent variables were HCV genotype and transplantation. The HCV genotype was treated as a time-independent (baseline) variable. Transplantation was treated as a time-dependent variable in which the status changed after transplantation. RESULTS: HCV RNA was detected by PCR in 224 patients (81%) in whom sera were available. Complete clinical data on baseline covariates, subsequent transplantation, and mortality were available in 180 patients (80%), and these patients constituted the final study cohort. HCV genotypes 1a and 1b were the two most common genotypes encountered and were found in 60 and 24% of the patients, respectively. One hundred and sixty-two (90%) patients were infected with a single HCV single genotype, 16 patients (9%) with two genotypes, and two patients (1%) with three genotypes. Among the 180 patients in the final study cohort, 86 (48%) underwent transplantation, and 66 (37%) patients died during follow-up. Compared with patients infected with HCV genotype 1a, the relative risk (RR) of death from all causes was not significantly increased among patients infected with genotype 1b (RR = 1.02, 95% CI, 0.55 to 1.89) or other genotypes (RR = 1.08, 95% CI, 0.50 to 2.30). Likewise, compared with patients with a single infection, the RR of death among patients with mixed infection (RR = 1.18, 95% CI, 0.52 to 2.66) was not significantly increased. CONCLUSIONS: The results of this study suggest that the type and number of HCV genotypes may not have a significant impact on survival among ESRD patients.

Cohort Studies↗
PubMed2002

Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients.

BACKGROUND & AIMS: The aim of this study was to investigate if the variable outcome of chronic hepatitis B may be related to hepatitis B virus (HBV) genotype. METHODS: The clinical and virologic events observed over prolonged follow-up in 258 Spanish patients with chronic hepatitis B infected with different genotypes of HBV were compared. RESULTS: The prevalence of genotype A, D, and F was 52%, 35%, and 7%, respectively. Concomitant sustained biochemical remission and clearance of HBV DNA occurred at a higher rate in genotype A- than in genotype D- (log-rank, 14.2; P = 0.002) or genotype F-infected patients (log-rank, 4.2; P = 0.03). The rate of hepatitis B surface antigen (HBsAg) clearance was higher in genotype A than in genotype D hepatitis (log-rank, 4.6; P = 0.03). Sustained remission and clearance of HBsAg were associated with infection with genotype A by Cox regression analysis. Seroconversion to antibody to hepatitis B e antigen (anti-HBe) was unrelated to HBV genotype, but the rate of sustained remission after seroconversion was higher in genotype A than in genotype D hepatitis both in patients who seroconverted to anti-HBe during follow-up (log-rank, 4.5; P = 0.03) and in patients with positive anti-HBe at baseline (log-rank, 6.66; P = 0.009). Death related to liver disease was more frequent in genotype F than in genotype A (P = 0.02) or genotype D (P = 0.002) hepatitis. CONCLUSIONS: The long-term outcome of chronic hepatitis B is different in patients infected with HBV genotype A, D, or F.

Adult↗
PubMed2006

Genotypes and viremia of hepatitis B and D viruses are associated with outcomes of chronic hepatitis D patients.

BACKGROUND & AIMS: Genotypes and viremia of hepatitis D virus (HDV) and hepatitis B virus (HBV) may be associated with outcomes. This study evaluated the impact of viral genotypes and viremia on outcomes of dual HBV and HDV infection. METHODS: Viremia and viral genotypes were analyzed in 194 consecutive chronic hepatitis B patients with HDV superinfection and correlated with outcomes. RESULTS: The numbers of HBV genotype A, B, C, and nonclassified were 4, 57, 23, and 110, respectively. There were 51 genotype I HDV, 74 genotype II HDV, 8 genotype IV HDV, and 61 nonclassified HDV genotype. In a median follow-up of 135 months, 24 progressed to cirrhosis and 41 developed hepatocellular carcinoma. Patients infected with genotype I HDV had a lower remission rate (15.2% vs 40.2%; P = .007) and more adverse outcomes (cirrhosis, hepatocellular carcinoma, or mortality) (52.2% vs 25.0%; P= .005) than those with genotype II HDV. Patients infected with genotype C HBV had a lower remission rate (0 vs 32.1%; P = .005) and more adverse outcomes (70.0% vs 33.9%; P = .005) than those with genotype B HBV. The presence of HBV or HDV viremia was associated with lower remission rates compared with those negative for both (26.4% and 24.3% vs 69.2%; P < .001). In multivariate analysis, age, genotype C HBV, and genotype I HDV were independent factors associated with adverse outcomes. CONCLUSIONS: In chronic HBV and HDV dual infections, older age, genotype I HDV, and genotype C HBV correlated with adverse outcomes.

Adult↗