The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the hig...The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.展开更多
AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in sout...AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.展开更多
AIM： To characterize the clinical, serologic and virologic features of hepatitis B virus （HBV） infection in Iranian patients with different stages of liver disease.METHODS： Sixty two patients comprising of 12 inac...AIM： To characterize the clinical, serologic and virologic features of hepatitis B virus （HBV） infection in Iranian patients with different stages of liver disease.METHODS： Sixty two patients comprising of 12 inactive carriers, 30 chronic hepatitis patients, 13 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma （HCC） were enrolled in the study. The HBV S, C and basal core promoter （BCP） regions were amplified and sequenced, and the clinical, serologic, phylogenetic and virologic characteristics were investigated.RESULTS： The study group consisted of 16 HBeAgpositive and 46 HBeAg-negative patients. Anti-HBepositive patients were older and had higher levels of ALT, ASL and bilirubin compared to HBeAg-positive patients. Phylogenetic analysis revealed that all patients were infected with genotype D （mostly ayw2）. The G1896A precore （PC） mutant was detected in 58.1% patients. HBeAg-negative patients showed a higher rate of PC mutant compared to HBeAg-positive patients （2,2 = 9.682, P = 0.003）. The majority of patients with HCC were HBeAg-negative and were infected with PC mutant variants. There was no significant difference in the occurrence of BCP mutation between the two groups, while the rate of BCP plus PC mutants was higher in HBeAg-negative patients （2,2 = 4.308, P = 0.04）. In the HBV S region, the genetic variability was low, and the marked substitution was P120T/S, with a rate of 9.7% （n = 6）.CONCLUSION： In conclusion, HBV/D is the predominant genotype in Iran, and the nucleotide variability in the BCP and PC regions may play a role in HBV disease outcome in HBeAg-negative patients.展开更多
基金Supported by Mahmoud Reza Pourkarim is supported by a postdoctoral grant from the''Fonds voor Wetenschappelijk Onderzoek Vlaanderen''
文摘The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
文摘AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.
基金A grant from the Nanotechnology committee of the Ministry of Science, Research and Technology, Iran, No. 31.1895 on 05.03.2004 to Majid Sadeghizadeh
文摘AIM： To characterize the clinical, serologic and virologic features of hepatitis B virus （HBV） infection in Iranian patients with different stages of liver disease.METHODS： Sixty two patients comprising of 12 inactive carriers, 30 chronic hepatitis patients, 13 patients with liver cirrhosis and 7 patients with hepatocellular carcinoma （HCC） were enrolled in the study. The HBV S, C and basal core promoter （BCP） regions were amplified and sequenced, and the clinical, serologic, phylogenetic and virologic characteristics were investigated.RESULTS： The study group consisted of 16 HBeAgpositive and 46 HBeAg-negative patients. Anti-HBepositive patients were older and had higher levels of ALT, ASL and bilirubin compared to HBeAg-positive patients. Phylogenetic analysis revealed that all patients were infected with genotype D （mostly ayw2）. The G1896A precore （PC） mutant was detected in 58.1% patients. HBeAg-negative patients showed a higher rate of PC mutant compared to HBeAg-positive patients （2,2 = 9.682, P = 0.003）. The majority of patients with HCC were HBeAg-negative and were infected with PC mutant variants. There was no significant difference in the occurrence of BCP mutation between the two groups, while the rate of BCP plus PC mutants was higher in HBeAg-negative patients （2,2 = 4.308, P = 0.04）. In the HBV S region, the genetic variability was low, and the marked substitution was P120T/S, with a rate of 9.7% （n = 6）.CONCLUSION： In conclusion, HBV/D is the predominant genotype in Iran, and the nucleotide variability in the BCP and PC regions may play a role in HBV disease outcome in HBeAg-negative patients.
