Hepatitis B Virus Gene Mutation and Its Clinical Significance in Human Liver Diseases
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Purpose: The study was designed to 1. Detect and characterize mutations in the precore/core and surface genes using PCR-SSCP of the hepatitis B virus and finally confirming by direct sequencing. 2. To study the clinical and biochemical profile and the final outcome of patients harboring mutant forms of the HBV virus and that of the wild type. Methods: The study included a total of 331 patients (Acute Viral Hepatitis: 115), (Fulminant Hepatitis: 40), (Chronic Hepatitis: 116), (Liver Cirrhosis: 30), (Hepatocellular carcinoma: 30) who were admitted in the wards of Lok Nayak Hospital, New Delhi, India. Surface, Pre-core and Core regions of the viral genome were amplified with the help of PCR. Surface, Pre-core and Core regions of the viral genome were screened for the presence or absence of mutations by SSCP. Ligase chain reaction was performed specifically for the presence or absence of W28 stop codon mutation. Purified products were sequenced with respect to the forward and reverse primers in an automated DNA sequencer. The obtained sequences of the above described regions of the viral genome were compared with reference strain from the Gene bank. Results: Precore, core and surface mutations accounted for 20% (23/115), 8.6% (10/115) and 9.5% (11/115) respectively in patients of acute viral hepatitis. Precore and core mutations accounted for 47.5% (19/40) of the fulminant hepatitis cases. Precore and core mutations accounted for 13.7% (16/116) while surface mutations accounted for 8.6% (10/116) of the cases of chronic hepatitis B. Precore and core mutations were observed in 46.6% (14/30) of the cases of HCC. Stop codon mutations were observed in all the categories. A clear association of genotype D and genotype A was documented in this particular study but the frequency of genotype D (70%) was higher compared to genotype A (30%) with response to the different types of liver diseases evaluated. Conclusion: 1) the study suggested that the prevalence of Precore mutation was significantly higher in fulminant hepatitis cases compared to acute viral hepatitis and chronic hepatitis. 2) the prevalence of Precore stop codon G1896 (W28 stop) was seen in all clinical categories and therefore it rules out its association with any particular spectrum of liver disease. 3) The study revealed that HBeAg does not necessarily associate with W28 stop mutations. 4) G1896 Precore mutation was specifically associated with genotype D. 5) Core gene mutations were found to have no genotype specificity. 6) Prevalence of genotype D was seen in 70% of the cases of different type of liver diseases while 30% were constituted by genotype A. 7) A118 and A128 surface mutants was specifically associated with genotype D.Keywords:
Fulminant hepatitis
Viral Hepatitis
Objective To detect hepatitis B virus core promoter (CP) mutations in patients with fulminant hepatitis.Methods Polymerase chain reaction amplified serum HBV DNA fragments were directly sequenced. Results There were 2 12 nucleotide substitutions in CP region in the 7 subacute fulminant hepatitis patients studied. An 11 bp nucleotides insertion was found in one patient. Mutations in CP were usually seen in the first and the second A T rich regions. The A to T mutation at nt 1 762 and G to A mutation at nt 1 764 were found in 4 cases, 3 of them were HBeAg negative. The third A T rich region was kept intact in all the 7 patients, so did the initial site of HBV replication (DR1) and the intial site of mRNA transcription (1 783/1784 or 1 790±1 for precore mRNA and 1818 for pregenome C/P mRNA).Conclusion CP mutations in patients with fulminant hepatitis are common, most of the CP variations occur in the first and the second A T rich regions, and these mutations may impede the transcription of precore mRNA and affect the expression of HBeAg.
Fulminant hepatitis
HBeAg
Fulminant
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Hepatitis B
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The fulminant hepatic failure is a dramatic complication of acute viral hepatitis. Despite therapeutical efforts, the mortality of these forms of acute hepatitis is rated in most studies from 60 to 90%.We made a retrospective study that included 2014 patients hospitalized at the Bacau County Hospital from January 1996 to December 2005 with the diagnosis of acute viral hepatitis. Among these, 72 patients presented severe forms of hepatitis.13 patients presented fulminant hepatic failure. In most cases, etiology was represented by the B-type virus (66.7%). Defining for the fulminant form of hepatitis are the Quick index under 50%, the increase of total serum bilirubine and the leucocitosis associated with neutrophilia.Mortality in fulminant forms of hepatitis was of 61.5%, respectively 75% in the case of the B-type viral hepatitis. Key words: SEVERE
Fulminant hepatitis
Fulminant hepatic failure
Viral Hepatitis
Fulminant
Etiology
Acute hepatitis
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To detect mutations in precore region of hepatitis B virus of HBeAg negative- patients with fulminant hepatitis and to determine the effect of T1862 mutants on synthesis of precursor of hepatitis B e antigen.The entire precore and core region were amplified from sera of nine HBeAg negative-patients with fulminant hepatitis B by polymerase chain reaction (PCR). PCR products were cloned into plasmid pUC18, and sequencing for analysis of precore mutations. Precore and core sequence of T1862 variant were also cloned into expression plasmid pGEMT for in vitro transcription and translation study on synthesis and procession of e antigen.Three variants, A1896, A1899 and T1862, whose nucleotide mutation led to amino acids substitutions, were detected in patients with fulminant hepatitis. T1862 variant didn't effect the synthesis of precursor of e antigen. Also there was no variant detected in precore region of hepatitis B virus in two patients.The causes for negative of e antigen in fulminant hepatitis patients may be partially explained by precore mutation of A1896 and T1862, and the latter variant may effect the process of precursor of e antigen, rather than the synthesis of precursor protein.
Fulminant hepatitis
HBeAg
Hepatitis B
Fulminant
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To detect hepatitis B virus core promoter (CP) mutations in patients with fulminant hepatitis.Polymerase chain reaction amplified serum HBV DNA fragments were directly sequenced.There were 2-12 nucleotide substitutions in CP region in the 7 subacute fulminant hepatitis patients studied. An 11 bp nucleotides insertion was found in one patient. Mutations in CP were usually seen in the first and the second A T rich regions. The A to T mutation at nt 1,762 and G to A mutation at nt 1,764 were found in 4 cases, 3 of them were HBeAg negative. The third A T rich region was kept intact in all the 7 patients, so did the initial site of HBV replication (DR1) and the initial site of mRNA transcription (1,783/1784 or 1,790 +/- 1 for precore mRNA and 1818 for pregenome-C/P mRNA).CP mutations in patients with fulminant hepatitis are common, most of the CP variations occur in the first and the second A T rich regions, and these mutations may impede the transcription of precore mRNA and affect the expression of HBeAg.
Fulminant hepatitis
HBeAg
Fulminant
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Background. A nosocomial outbreak of fulminant hepatitis B occurred in five patients in Haifa, Israel. Previous investigations identified the suspected source as a carrier of hepatitis B surface antigen who was positive for antibodies to hepatitis B e antigen and had chronic liver disease. We examined the strain of hepatitis B virus (HBV) that caused this epidemic, in order to identify specific mutations in the precore or core region. Methods. The presence of HBV was identified by polymerase-chain-reaction amplification of viral DNA in serum from the source patient, the five patients with fulminant hepatitis B, and five controls with acute, self-limited hepatitis B. The amplified viral HBV DNA samples were then cloned and sequenced. Results. Sequence analysis of viral DNA established that the same HBV mutant with two mutations in the precore region was present in the source patient and the five patients with fulminant hepatic failure. This HBV mutant had significant sequence divergence from other known HBV subtypes in the X, precore, and core regions. Cloned HBV DNA derived from a hospitalized patient who had subclinical hepatitis B at the same time as the outbreak and from four other control subjects with acute, self-limited hepatitis B all contained the wild-type sequence in the precore region. Conclusions. In the outbreak we studied, a mutant hepatitis B viral strain was transmitted from a common source to five patients who subsequently died of fulminant hepatitis B infection. Naturally occurring viral mutations in the HBV genome may predispose the infected host to more severe liver injury. Background. The presence of the hepatitis B e antigen (HBeAg) in serum is known to be a marker of a high degree of viral infectivity. However, fulminant hepatitis may occur in persons who are negative for HBeAg. A single point mutation has been reported to produce a stop codon in the precore region of hepatitis B virus DNA and prevent the formation of the precore protein required to make HBeAg. To determine whether a precore-mutant virus is causally related to severe liver injury, we analyzed the entire precore region in viral strains isolated from patients with fatal cases and uncomplicated cases of hepatitis B. Methods. Serum was obtained from 9 patients with fatal hepatitis B (5 with fulminant and 4 with severe exacerbations of chronic hepatitis) and 10 patients with acute, self-limited hepatitis B. Serum samples from a sex partner implicated as the source of the virus in one case of fulminant hepatitis were also studied. The 87 nucleotides in the precore region of the hepatitis B virus were amplified by the polymerase chain reaction and then directly sequenced. Results. Of the nine patients with fatal hepatitis, seven had retrievable hepatitis B DNA. In all seven there was a point mutation from G to A at nucleotide 1896 of the precore region, converting tryptophan (TGG) to a stop codon (TAG). In contrast, this mutation was not found in the 10 patients with acute, self-limited hepatitis B. The hepatitis B DNA from the implicated source contained a sequence with the stop-codon mutation that was identical to the sequence in her partner, who had fulminant hepatitis. Conclusions. The presence of a mutant viral strain is associated with and may be involved in the pathogenesis of fulminant hepatitis B and severe exacerbations of chronic hepatitis B.
Fulminant hepatitis
Fulminant
Hepatitis B
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In this paper,in order to provide some check methods for the fulminant viral hepatitis (FVH)to the doctors and advancing its treatmental effection the development of the diagnosis and treatment on the fulminant viral hepatitis are discussed.
Fulminant
Fulminant hepatitis
Viral Hepatitis
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Genome-wide sequences of hepatitis B virus strain associated with type B fulminant hepatitis have not been compared with those of acute self-limited hepatitis. We carried out full-length sequencing analysis of viral strains derived from patients with type B acute liver injury.Nine acute self-limited hepatitis and 6 fulminant hepatitis patients were the subjects of this study. Full-length sequencing analysis of viral DNA was done by PCR-direct sequencing.Higher frequencies in fulminant hepatitis strains compared with acute hepatitis ones were observed in the T1762/A1764 (p < 0.05), A1896 (p = 0.09) and M1753 (M = C or A) (p = 0.09) mutations. Viruses related to fulminant hepatitis possessed the higher number of nucleotide substitutions than those related to acute hepatitis in the whole virus genome (p < 0.01) and various regions including preS/S gene (p < 0.05), precore/core gene (p < 0.01), polymerase gene (p < 0.05) and basic core promoter/core upstream regulatory sequence (p < 0.01). The high number of nucleotide substitutions in viruses related to fulminant hepatitis was predominantly non-synonymous in the preS/S and precore/core genes.Development of type B fulminant hepatitis may be associated with a highly mutated hepatitis B virus strain.
Fulminant hepatitis
Fulminant
Hepatitis B
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Acute viral hepatitis (AVH) is a major public health problem and is an important cause of morbidity and mortality in India. A study to examine the clinical – epidemiological profile of acute viral hepatitis was carried in Aligarh, Uttar Pradesh. It was found that in a total of 90 serologically positive acute viral hepatitis patients, Hepatitis E was the most prevalent and with most fatalities in pregnant women. Hepatitis B had the most fulminant course followed by hepatitis E. The disease was statistically insignificantly distributed among different age groups, sex and residency rural or urban. The individual courses of the different types of acute viral hepatitis were thereby studied and discussed.
Viral Hepatitis
Fulminant hepatitis
Acute hepatitis
Indian subcontinent
Fulminant
Uttar pradesh
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Viral Hepatitis
Fulminant hepatitis
Fulminant
Acute hepatitis
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