Hepatitis C virus infection in chronic hepatitis B virus carriers.

One hundred eighty-four patients with hepatitis B surface antigen-positive chronic hepatitis were evaluated for antibodies to hepatitis C virus (anti-HCV). Only 11 (8%) of 136 patients with hepatitis B virus (HBV) replication (HBV-DNA-positive in serum) while 7 (35%) of 20 positive for antibody to hepatitis B e antigen (anti-HBe) but HBV-DNA-negative were positive for anti-HCV. By contrast, anti-HCV was never found in 30 anti-HBe-positive "healthy" carriers. Anti-HCV was more frequent in hepatitis D virus (HDV)-positive than in HDV-negative cases (32% vs. 12%). During 1-11 years of follow-up, anti-HCV persisted in 90% of cases, who showed continuing alanine aminotransferase elevation. Liver histology deteriorated in 2 of 4 anti-HCV-positive, anti-HBe-positive, HBV-DNA-negative patients. These results demonstrate the existence of a subgroup of patients with anti-HBe-positive, HBV-DNA-negative, HDV-negative chronic hepatitis B, where HCV may play a leading role in causing liver disease.     

Hepatitis B virus genotypes and clinical manifestation among hepatitis B carriers in Thailand

BACKGROUND: Hepatitis B virus (HBV) genotypes have distinct geographic distributions. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thailand. METHODS: Hepatitis B virus genotypes among 107 hepatitis B carriers residing in Thailand were evaluated using serologic and genetic methods. They were clinically classified into asymptomatic carriers with normal serum alanine transaminase (ALT) levels and patients with chronic liver disease, such as those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). RESULTS: Hepatitis B virus genotype distribution among the 107 patients was 25.2% for genotype B, 72.0% for genotype C and 2.8% for genotype D. The serum ALT levels, HBV-DNA and hepatitis B e antigen positivity were significantly higher in carriers infected with genotype C HBV than in those infected with genotype B (P < 0.05). The proportion of genotype B HBV was higher in asymptomatic carriers than in patients with CH and those who developed liver disease, such as LC and HCC (45.5, 16.9 and 25.0%, respectively; P < 0.05). In contrast, the proportion of genotype C HBV was higher in patients who developed liver disease and CH than in asymptomatic carriers (68.7, 83.0 and 50.0%, respectively; P < 0.05). Phylogenetic analysis based on entire genome sequences revealed three HBV isolates, which were classified into a subgroup of genotype C in isolates from South-East Asian countries. CONCLUSIONS: Genotypes B and C are the predominant types among hepatitis B carriers residing in Thailand and those genotypes influence the clinical manifestation in carriers with chronic hepatitis B infection.     

Hepatitis B virus genotypes and genome characteristics in China

AIM: To analyze the hepatitis B virus (HBV) characters in China, as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS: A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database (information including: genotype, territory and clinical status). HBV genotypes were classified by a direct reference from the Genbank sequence annotation, phylogenetic tree and online software analysis (http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi). The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software. HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods. Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms. Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages. The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software. Recombination analysis was performed by using Simplot software.RESULTS: In China, HBV genotype C was the predominant in Northeastern, genotype B was predominant in Central Southern areas, genotype B and C were both dominant in Southwestern areas, and the recombinant genotype C/D was predominant in Northwestern areas. C2 and B2 were identified as the two major sub-genotypes, {"type":"entrez-nucleotide","attrs":{"text":"FJ386674","term_id":"213495273","term_text":"FJ386674"}}FJ386674 might be a putative sub-genotype as B10. The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms. In addition to ATG, many other HBV initiation codons also exist. HBV has codon usage bias; the termination codon of X, C and P open reading frames (ORF) were TAA, TAG, and TGA, respectively. The major stop codons of S-ORF were TAA (96.45%) and TGA (83.60%) in B2 and C2 subtype, respectively.CONCLUSION: This study recapitulated the epidemiology of HBV in China, and the information might be meaningful critical for the future prevention and therapy of HBV infections.     

Nocardiosis in a tertiary care hospital on the island of Gran Canaria

Background: Nocardiosis is an uncommon but serious infection increasingly found in immunosuppressed persons. We describe 14 cases of nocardial infection seen at a tertiary hospital. Methods: All positive Nocardia cultures isolated from 1991 to 2002 were included. We analyzed predisposing factors, epidemiological and clinical features, laboratory and radiological findings, site(s) of infection, antimicrobial susceptibility pattern, treatment, and outcome. Factors related to mortality were analyzed. Results: Nineteen patients with a Nocardia isolate were identified and 14 were finally included. The most common predisposing factors included pulmonary diseases (71.4%), diabetes mellitus (35.7%), systemic diseases (28.6%) and immunosuppressive therapy (28.6%). The site of infection was pulmonary in 12 cases (85.71%), cutaneous or subcutaneous in one case (7.1%), and disseminated in another case (7.1%). The predominant clinical symptom was purulent expectoration (71.4%) while the predominant radiological pattern was a reticulonodular infiltrate (6/12, 50%). Relapse was observed in one case (7.7%) and death in three cases (23.1%). Diabetes mellitus was associated with the mortality rate (p=0.035). Treatment was highly individualized, but trimethoprim (TMP)-sulfamethoxazole (SMX) was the combination most often used. Conclusions: Nocardiosis should be part of the differential diagnosis for patients presenting with pulmonary symptoms, soft tissue infection, or brain abscess.     

Hepatitis B virus genotypes in children with chronic hepatitis B in Poland

OBJECTIVES: To analyse the distribution of HBV genotypes in Polish children with chronic hepatitis B, and to assess the relation between the viral genotype and the severity of liver damage. METHODS: Serum samples from children with chronic hepatitis B were used for biochemical and serological testing, and for determination of HBV genotypes by a nested-multiplex-polymerase chain reaction. Liver biopsies were obtained for histological assessment, which was performed according to the Batts and Ludwig scoring system of chronic hepatitis. RESULTS: Of 78 children with chronic hepatitis B, 74 had an identifiable HBV genotype: 86.5% were infected with genotype A, and 13.5% were carriers of genotype D. The frequency of HBeAg clearance and the levels of alanine aminotransferase and serum aspartate transaminase were comparable in both genotype groups. There was no correlation between the HBV genotype and either activity of liver inflammation or liver fibrosis. CONCLUSIONS: This study shows that the distribution of HBV genotypes in Polish children with chronic HBV infection reflects the general prevalence of HBV genotypes in Europe. The course of chronic hepatitis B in children is not significantly influenced by viral genotypes A or D.     

Hepatitis B virus genotypes in Europe

There are eight genotypes of hepatitis B virus (HBV). Most genotypes can be further divided into subgenotypes. HBV genotypes influence the course of disease and treatment, and show geographic preferences. In Europe, A and D are the main genotypes found. Genotype A is more prevalent in northern Europe, where genotype D is mainly found in countries surrounding the Mediterranean Sea and in Eastern Europe. Subgenotype A2 is the dominant subgenotype in Europe, but the geographic prevalence of the four subgenotypes found in genotype D is not yet clear. On treatment with interferon HBV, genotype A, compared to genotype D, showsbetter virological response and in a large proportion of patients, even development of anti-HBs. However, in the first year of treatment with lamivudine, higher rates of emergence of YMDD variants are observed in genotype A. This work summarizes the current knowledge on HBV genotypes in countries with low and intermediate HBV carriership from Europe.     

Hepatitis B virus taxonomy and hepatitis B virus genotypes

Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses).The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field,updates several recent reviews on HBV genotypes and subgenotypes.     

Hepatitis C virus genotypes: epidemiological and clinical associations

ABSTRACT— In a cohort of 292 chronic hepatitis C patients living in the Benelux countries the relationship between viral genotype and geographical origin, route of transmission, clinical characteristics and severity of liver disease was analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as 1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were predominantly infected with HCV subtype 1b (164/254, 65%, CI 58–70%), as were patients of Asian origin (7/13, 54%). Patients originating from Surinam (South America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational needle accident or tattoo in 11 (4%); no obvious source of infection was found in 93 (33%). In patients infected by blood transfusion, subtype 1b was predominant (70%, CI 61–77%), whereas subtypes 1a and 3 were predominant in those infected by IVDA (25% and 45%, respectively, p<0.001). Cirrhosis was observed in 68 (24%) patients; in multi-variate analysis, factors independently related to cirrhosis were: the duration of infection, age and prior hepatitis B. No significant relationship was found between the severity of fibrosis or liver inflammation and the HCV (sub)types. In summary, in this large cohort of patients in the Benelux countries the hepatitis C virus (sub)type present was clearly related to the country of origin and the route of transmission, but not to the severity of liver disease.     

黄石地区慢性无症状乙型肝炎病毒携带者的基因型分布

目的：了解湖北黄石地区慢性无症状乙型肝炎病毒（HBV）携带者HBV基因型的分布，及其与病毒复制水平、HBeAg表达的相关性。方法：选择黄石地区168例慢性无症状HBV携带者作为研究对象，HBV基因型采用PCR微板核酸杂交．ELISA方法检测；血清HBVDNA复制水平采用荧光定量PCR检测；HBV—M采用ELISA法检测。结果：168例慢性无症状HBV携带者中HBVDNA阳性者为114例（阳性率为67．9％），其基因型分布为B、C、D型以及这3种基因型组成的混合型，而未发现A、E、F基因型。其中以B型、C型为主，所占比例为62．6％和36．8％，D型及混合型比例均为5．3％。C基因型患者中，HBV DNA呈现高水平复制（10^7～10^8 Copies／ml）的患者比例为26．2％（11／42），B基因型为13．3％（8／60）（P〈0．05）。C基因型患者血清抗-HBe阳性率（40．5％）显著高于B基因型（15．0％）（P〈0．01）。结论：黄石地区存在HBV的B、C、D基因型，以及由它们组成的混合基因型；B基因型为优势基因型；C基因型与HBV高复制水平，以及基因变异相关。     

Hepatitis B virus genotypes identified by a Line Probe Assay (LiPA) among chronic carriers from Spain

Genotypes A and D of the hepatitis B virus were found to be prevalent among 278 chronic carriers residing in Spain, and genotypes B, C, E and F were detected with significant frequency (9%). Two genotype E infections corresponded to carriers born in Spain who had never traveled to Africa. These results indicate that genotype E is beginning to circulate in the Spanish population in the same way that genotype F did in the past.     

Hepatitis B virus genotypes and extrahepatic manifestations

BACKGROUND/AIMS: This study aimed at correlating the presence of extrahepatic manifestations with hepatitis B virus (HBV) genotypes in patients with chronic HBV infection. METHODS: This was a national (France), multicenter, retrospective, cross-sectional study. HBV genotypes were determined in 190 patients HBsAg-positive for at least 6 months and documented before any treatment. RESULTS: Patients were aged 42+/-15 years and mainly male (77%). Alcohol intake was high in 6% of them, ALT elevated in 73%; 27% were cirrhotic. All HBV genotypes were found, mainly A (24%), D (29%), C (11%), and E (10%). Thirty (16%) patients had clinical extrahepatic manifestations, mainly sensory-motor deficiency, sicca syndrome, myalgia, glomerulonephritis, and arthralgia-arthritis. Their presence was not related to any epidemiologic, viral (including genotypes) or hepatic factor, but to a higher platelet count (P=0.004). Twenty-nine (15%) patients had biological extrahepatic manifestations, mainly anti-smooth muscle, antinuclear, and anti-nucleosome antibodies. Their presence was related only to anti-HBe antibodies positivity (P=0.007) or elevated platelet count (P=0.003). Carrying precore mutant HBV increased by 2.8 folds the risk to have at least one extrahepatic biological manifestation. CONCLUSIONS: No relationships between HBV genotypes and the presence of extrahepatic manifestations were evidenced in patients with chronic HBV infection.     

Hepatitis B virus genotypes and subgenotypes in China

Eight Hepatitis B virus (HBV) genotypes (A to H) have been identified based on an intergenotype divergence of 8% or more in the entire nucleotide sequence. Subgenotypes have also been identified in different HBV genotypes. As a highly endemic area for HBV infection, the prevalence of chronic HBV infection in China is between 8 and 20% of the general population. Genotypes B and C were identified as the most common HBV strains and account for approximately 95% of Chinese patients. Further study confirmed all genotype B strains belong to subgenotype Ba. Two of genotype C subgenotypes, C1 (Cs) and C2 (Ce), were found in China and they showed different geographic distributions. Genotype A was very rarely found, while genotypes E, F, G and H have not beenreported until now. Two types of HBV C/Drecombinant viruses have been identified in west China and distinct geographic and ethnic distributions were observed. Significant differences were observed ( P  < 0.001) in the prevalence of A1896 and T1762/A1764 mutations among HBV Ba, C1 and C2 subgenotypes in Chinese patients. Accumulating evidence showed the response rate to antiviral therapy in Chinese patients is higher in genotype B than genotype C patients on interferon treatment, but no difference was observed on nucleoside/nucleotide analog treatment.     

广东省东莞地区慢性乙型肝炎患者HBV基因型分析

目的探讨东莞地区乙型肝炎患者HBV基因型的分布特点。方法采用PCR-微板核酸杂交-ELISA法检测HBVA—F基因型，采用荧光定量-聚合酶链反应法检测血清HBVDNA定量。结果在295例乙型肝炎患者中检出HBV基因型247例（83．7％），其中HBV基因C型占62．3％（154／247）、B型15．4％（38／247）、D型6．9％（17／247）、B／C混合型4．9％（12／247）、C／D混合型5．3％（13／247）、B／D混合型5．3％（13／247），48例未检出基因型；基因C型感染者之间无性别差异（x^2=0．043，P〉0．05）；各基因型患者血清HBVDNA水平无显著性相差，但与48例未检出基因型者比，后者HBVDNA水平明显降低（P〈0．01）。结论PCR-微板核酸杂交-ELISA法检测HBV基因型具有特异、敏感、简单和实用的特点，东莞地区乙型肝炎患者HBV基因型以C型为主，混合型比例相对较高，HBV复制强弱与病毒基因型无关。     

Hepatitis B virus: significance of genotypes

Hepatitis B Virus (HBV) genotypes have come of age. The concept that HBV genotypes may influence the course of disease and relevant biological differences has now been recognised. However, there are still major gaps in our knowledge. Most clinical data come from Asia and describe findings in patients infected with genotypes B and C. Large scale studies with genotypes A and D as found in Europe or A, D and E from Africa are urgently needed to broaden our understanding. Experimental data which explain in vivo findings in terms of differences in molecular biology in vitro are still in the beginning. The succeeding years will see many interesting studies which will aid our understanding of how variants and genotypes of HBV influence the spectrum of disease in people infected with HBV.     

Prevalence of the metabolic syndrome in the island of Gran Canaria: comparison of three major diagnostic proposals.

AIMS: The present study was conducted to estimate the prevalence of the metabolic syndrome in a Canarian population, and to compare its frequency as defined by the most commonly used working definitions. METHODS: Cross-sectional population-based study. One thousand and thirty adult subjects were randomly selected from the local census of Telde, a city located on the island of Gran Canaria. Participants completed a survey questionnaire and underwent physical examination, fasting blood analyses, and a 75-g standardized oral glucose tolerance test. The prevalence of the metabolic syndrome was estimated according to the definitions proposed by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR) and the National Cholesterol Education Program (NCEP), the latter with the original (6.1 mmol/l) and the revised criterion (5.6 mmol/l) for abnormal fasting glucose. RESULTS: The adjusted prevalence of the metabolic syndrome was 28.0, 15.9, 23.0 and 28.2%, using the WHO, EGIR, NCEP and revised NCEP criteria, respectively. The measure of agreement (kappa statistic) was 0.57 between the WHO and the original NCEP definitions, and 0.61 between the WHO and the revised NCEP definitions. After excluding diabetic subjects, the agreement between the EGIR and WHO proposals was fairly good (kappa=0.70), whereas concordance of the EGIR with the original and the revised NCEP definitions was moderate (kappa=0.47 and 0.46, respectively). CONCLUSIONS: Whichever the considered diagnostic criteria, the prevalence of the metabolic syndrome in this area of the Canary Islands is greater than that observed in most other European populations.     

经病理诊断的慢性乙型肝炎病毒携带者与慢性肝炎的临床分析

目的 比较病理学诊断为慢性HBV携带者与慢性肝炎患者的临床资料,为不同ALT水平的慢性HBV感染者的处理提供病理学依据.方法 对292例慢性HBV感染者进行肝活组织检查,按病理学诊断符合慢性HBV携带者标准(G0～G1且S0～S1)与慢性肝炎标准[G＞1和(或)S＞1]分为携带组和肝炎组,比较不同年龄分层及ALT水平分层与病理诊断的关系,同时比较其他可能与病理诊断相关的临床、生物化学及影像学指标,Logistic回归方程(后退法,极大似然法)进行多因素分析,确定病理学符合慢性HBV携带者诊断的独立影响因素.结果 292例患者中,病理诊断为慢性HBV携带者有140例,占47.9％;慢性肝炎152例,占52.1％.HBV携带组与慢性肝炎组在≤35岁与36～40岁、＞40岁比较,差异有统计学意义(x2=3.936,8.534;P=0.047,0.003); ALT水平在＜0.5×正常值上限(ULN)、(0.5～1.0)×ULN、(1.1～1.5)×ULN、(1.6～2.0)×ULN、＞2.0×ULN间比较差异有统计学意义(x2=55.314,P＜0.01),但ALT在(1.1～1.5)×ULN与＞2.0×ULN比较,差异无统计学意义(x2=3.810,P=0.051).多因素分析显示,病程、饮酒史、ALT分层、HBV DNA水平及超声检查肝表面是否光滑是病理学符合慢性HBV携带者诊断的独立影响因素(OR=0.995、0.224、0.516、1.308、0.270,P=0.005、0.007、0.000、0.025、0.001).结论 年龄35岁以上且ALT水平介于(1～2)×ULN的患者行肝活组织检查的临床意义更大.