| 1. |
- Bläckberg, Jonas, et al.
(författare)
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Genotypic differences in the hepatitis B virus core promoter and precore sequences during seroconversion from HBeAg to anti-HBe
- 2000
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Ingår i: Journal of Medical Virology. - 1096-9071. ; 60:2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) strains from anti-HBe positive patients often show specific mutations in the precore gene, the core promoter region, or both. The dynamics of seroconversion in relation to the appearance of these mutations has not been studied and compared between defined HBV genotypes. Samples from patients followed during seroconversion from HBeAg to anti-HBe were amplified by polymerase chain reaction (PCR), sequenced and genotyped. Among 16 sets of samples, 6 belonged to genotype A, 6 to genotype D, 2 to genotype B, 1 to genotype C, and 1 to genotype E. Whereas strains from genotypes B, C and E showed changes in the core promoter, precore codon 28 or both, genotype A and D strains displayed a different pattern. In 4 of 6 anti-HBe positive samples from genotype A, the precore had a wild-type sequence while the core promoter sequence showed a specific TGA mutation. In another genotype A strain a precore stop mutation was preceded by a mutation in codon 15, thus conserving base-pairing at the pregenomic RNA level in this region. In contrast, all genotype D strains showed wild-type sequences in both the core promoter and precore codon 28 in pre- and post-seroconversion samples. Thus, in 8 patients with a mean follow-up time of 17 months, wild-type sequences in both the core promoter and precore codon 28 were found after seroconversion to anti-HBe. This study also confirmed, for genotype D, that HBeAg seroconversion often occurs earlier than genomic conversion.
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| 2. |
- Bläckberg, Jonas
(författare)
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Hepatitis B virus infection and genomic changes from a long-term perspective
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hepatitis B virus is a non-cytopathic virus with a small, circular, partially double-stranded DNA of 3.2 kb. It causes acute and chronic inflammatory liver disease and hepatocellular carcinoma (HCC). Retesting of stored sera from an outbreak of acute hepatitis in 1969-72 allowed identification of 126 cases of acute hepatitis B. No chronic carriers expressing hepatitis B surface antigen (HBsAg) could be found among 100 patients at follow-up 25-30 years later. Sixteen patients with documented self-limited acute hepatitis were evaluated further. HBV DNA could not be detected by PCR in serum or PBMCs. However, HBV DNA could be detected in the liver specimens of two patients 30 years after having an acute hepatitis B infection. Both patients had histological signs of minor liver inflammation. When selected genomic sequences of the strains detected in the liver were compared with the primary infecting strains in serum collected 30 years earlier, they were identical. Mutations in the precore and core promoter (cp) regions of the HBV genome have been associated with a lack of detectable hepatitis B e antigen (HBeAg). The precore and cp regions of viral strains from 83 chronic HBV carriers, including 16 carriers sampled during HBeAg seroconversion, were sequenced. The development of precore and cp mutations appeared to be a separate event from the HBeAg seroconversion. Mutations in strains from 16 patients with HBV infection and HCC were analyzed. Sequencing of the preS, S, X, and precore regions showed a high prevalence (50%) of mutations affecting part of the preS2 region which codes for B and T cells epitopes.
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| 3. |
- Bläckberg, Jonas, et al.
(författare)
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Long-term outcome of acute hepatitis B and C in an outbreak of hepatitis in 1969-72
- 2000
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Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 19:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the epidemiology, etiology, and long-term outcome of an extended outbreak of acute hepatitis that occurred in an area of Sweden between 1969 and 1972. The outbreak was analyzed retrospectively by retesting stored frozen serum samples for the presence of hepatitis A, B and C markers. The results were compared with the diagnoses that had been determined during the outbreak. Of 180 patients, 29 (16%) had acute hepatitis A, 126 (70%) had acute hepatitis B, and eight (4.4%) had acute hepatitis C. The Australia antigen test used during the outbreak had failed to identify 21 patients with acute hepatitis B virus infection. Genotyping of the hepatitis B virus strains showed that genotype D was the most prevalent, irrespective of the transmission route. An attempt was made to follow up patients with unresolved hepatitis B virus infection, 25-27 years after the acute infection. None of the 100 patients with acute hepatitis B infection who were traced had become chronic carriers. In ten patients with hepatitis C virus infection, the follow-up showed considerable variation in the outcome, ranging from spontaneous resolution to death through liver cirrhosis. Intravenous drug users had a high prevalence of hepatitis C virus infection, with 52% testing positive for hepatitis C antibodies.
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| 4. |
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| 5. |
- Bläckberg, Jonas, et al.
(författare)
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Occult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation
- 2000
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Ingår i: Journal of Hepatology. - 0168-8278. ; 33:6, s. 992-997
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: After acute self-limited hepatitis B virus (HBV) infection, serological loss of viral antigens and appearance of anti-HBs is generally believed to signify viral clearance. Latent and occult HBV infection appearing decades after self-limited hepatitis B has not been reported, nor has the evolutionary rate of HBV DNA over the same observation period. METHODS: DNA from serum and leukocytes from 16 patients with acute self-limited hepatitis B 30 years earlier was tested by polymerase chain reaction and positive samples were sequenced. Liver tissue from four patients was also tested. Additionally, another 10 HBV strains isolated from acute HBV cases in 1969-72 were compared to 11 strains isolated from acute cases in 1998-99 in the same community. RESULTS: HBV DNA was detected in liver from two patients, but not in serum or leukocytes. The HBV strains detected in liver showed complete homology, in the sequences analyzed, to the strains originally infecting these patients. Ten strains from 1998-99 were identical in pre-S and core promoter/precore regions to strains from the same community isolated 30 years earlier. CONCLUSIONS: HBV can persist as an occult infection three decades after acute, apparently self-limited hepatitis B, and both the mutation and evolutionary rates of HBV DNA are low.
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| 6. |
- Kidd-Ljunggren, Karin, et al.
(författare)
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Clinical and serological variation between patients infected with different Hepatitis B virus genotypes.
- 2004
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 42:12, s. 5837-5841
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) has eight genotypes which have distinct geographical distributions. Studies comparing differences in the clinical outcomes of infections caused by strains with genotype-related variations in the HBV genome have largely compared genotypes B and C and genotypes A and D but not all four genotypes. The present study included 196 HBV-infected patients attending an infectious diseases outpatient clinic in Sweden. The age and geographic origin, liver function, HBeAg and anti-HBe status, and the presence or absence of HBV DNA were analyzed for each patient. HBV DNA was detected in 144 patients, and the HBV genotype and the core promoter and precore sequences were determined for the isolates from 101 of these patients. Among the patients who might be considered most likely to be nonviremic, namely, anti-HBe-positive HBV carriers with normal alanine aminotransferase (ALT) levels, 65% had detectable HBV DNA and were thus viremic. Among the viremic patients, HBeAg-positive patients were more likely to have elevated ALT levels than anti-HBe-positive patients. HBV genotypes A to F were represented in the study, and their distributions coincided accurately with the origin of the patient. A significantly higher number of genotype D-infected patients were anti-HBe positive and had elevated ALT levels (42% of genotype D-infected patients but 0% of patients infected with genotypes B and C). Genotype D strains with mutations in the core promoter and precore regions were significantly correlated with elevated ALT levels in the patients. The differences were not age related. Therefore, in this large-scale cross-sectional study, genotype D appears to be associated with more active disease.
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