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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of naturally occurring hepatitis B virus mutants that cannot synthesize the virus precore protein have been identified. Such mutants have been associated with more severe forms of hepatitis, including fulminant hepatitis. The most common mutation observed is a substitution of G to A in the distal precore gene that converts a codon specifying Trp (TGG) to a termination codon (TAG). Using oligonucleotide-directed mutagenesis, we have produced the same point mutation in the precore gene of an infectious clone of woodchuck hepatitis virus (WHV). Transfection of mutant WHV DNA into the livers of adult woodchucks resulted in replication of the mutant in three of three susceptible animals. Levels of virus replication and transient elevations in liver enzymes in serum were similar to those of adult animals infected with wild-type WHV. Virions, found to possess mutant precore genes by polymerase chain reaction amplification and DNA sequencing, were recovered from the serum of one of the animals and inoculated subcutaneously into neonatal woodchucks. They produced infection in all five animals studied. The level of virus replication in neonatal animals infected with this mutant virus was comparable to that found in neonatal woodchucks infected with wild-type WHV, but none of five woodchucks infected with the precore mutant virus as neonates became chronic virus carriers. It was concluded that the precore gene of the WHV genome is not essential for virus replication in the natural host but may be important for chronic infection.
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PMID:The precore gene of the woodchuck hepatitis virus genome is not essential for viral replication in the natural host. 150

The present study was undertaken to evaluate the ability of human hepatocytes to respond in culture to various mitotic agents including epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), or serum from patients with fulminant hepatitis. Human hepatocytes were maintained in culture on collagen-coated plates in a chemically and hormonally defined serum-free medium at low cell density. Twelve hours after plating, cultures were treated with increasing amounts of EGF (1-100 ng/mL), TGF-alpha (1-100 ng/mL), or human serum (1%-10%) for 0-96 hours. Proliferative response was assessed by determining against time the rate of DNA synthesis by [3H]thymidine incorporation in DNA, the labeling index, the expression of cyclin A, the amount of DNA, and the number of cells. The rate of DNA synthesis reached a maximum after 48 hours of treatment with 20 ng/mL EGF, 40 ng/mL TGF-alpha, or 5%-10% of human serum (fulminant hepatitis); the average increase with respect to untreated cells was 4.35 times with EGF, 5.4 times with TGF-alpha, and 4-6 times with serum from patients with fulminant hepatitis. The maximum expression of cyclin A coincided with the maximum of DNA synthesis. After 72 hours of treatment with EGF or human serum (fulminant hepatitis), the amount of DNA increased by 75%-100% (P less than 0.001) and the number of cells by 50% (P less than 0.001). These results show that adult human hepatocytes respond to mitogens, as expected from previous studies on animal hepatocytes, and provide experimental basis for future investigations in the field of human liver regeneration.
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PMID:Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor alpha, and human serum. 153 70

Enterically transmitted non-A, non-B hepatitis virus (HEV), the causative agent for sporadic and large epidemic outbreaks in developing countries, contains a positive-sense single-stranded RNA genome. The genome of the virus encodes three open reading frames (ORF1, ORF2, and ORF3). The gene segment corresponding to the small open reading frame (ORF3), overlapping between ORF1 and ORF2, was synthesized by reverse transcription-polymerase chain reaction (RT-PCR) from a number of previously identified HEV-positive clinical specimens. A DNA fragment of 166 bp was consistently obtained from all the clinical specimens. This small fragment was cloned, sequenced, and found to contain an open reading frame encoding only 41 amino acid residues. Comparison of our results with that of geographically related Burma HEV suggests a major inframe deletion of 246 bp in the ORF3 of Indian strain. The protein encoded by ORF3 does not appear to be useful for early serodiagnosis as a synthetic peptide deduced from the truncated ORF3 failed to show any demonstrable immunoreactivity against HEV-infected acute phase sera in an enzyme-linked immunosorbent assay.
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PMID:Indian hepatitis E virus shows a major deletion in the small open reading frame. 153 53

The hepatitis D virus (HDV) infection plays a major role in severe liver damage caused by hepatitis. To establish the prevalence of HDV infection in haemophilic patients and patients without haemophilia, 87 patients with chronic hepatitis B virus (HBV) infection were examined for serological evidence of delta hepatitis. In addition HBV, HDV and human immunodeficiency virus type 1 (HIV) infection markers were compared to clinical and histopathological outcome of hepatitis. Out of 46 haemophiliacs 30 (65%) were anti-HD-seropositive; 10 out of 30 anti-HD-positive patients (33%) had pathological liver function tests compared to 2 out of 16 anti-HD-negative haemophiliacs (13%). The rate of HIV infection did not differ between the HDV infected and the non-HDV infected individuals with haemophilia (17/27 anti-HD-positive patients versus 12/16 anti-HD-negative patients). Two haemophilic anti-HD-positive patients underwent liver biopsy, in both cases hepatitis D antigen (HDAg) was detected in the biopsies. Only 2 out of 41 patients without haemophilia were anti-HD-positive. Both had pathological liver function tests; chronic active hepatitis and cirrhosis, respectively, were diagnosed and HDAg was found in the liver biopsies. Out of 39 anti-HD-seronegative patients without haemophilia, 26 (67%) were hepatitis B e antigen positive; in the sera of 20 patients (51%) HBV-DNA was demonstrated, but only 6 patients (15%) had pathological liver function tests. In conclusion a high seroprevalence of HDV infection was found in haemophilic patients treated with non-pasteurized commercial clotting factor concentrates. An endemic spreading of HDV infection in patients without haemophilia with chronic HBV infection could not be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of hepatitis B virus, hepatitis D virus and human immunodeficiency virus type I infection markers in hepatitis B surface antigen positive haemophiliacs and patients without haemophilia with clinical and histopathological outcome of hepatitis. 153 69

To evaluate the factors determining the severity of chronic hepatitis B virus infection and the interactions of human immunodeficiency virus and hepatitis delta virus infections, we retrospectively analyzed 260 patients, 146 of whom were followed for a mean of 31.4 +/- 1.8 mo. Human immunodeficiency virus, hepatitis B virus, and hepatitis delta virus status and aminotransferase activities, histological activity index, alcohol consumption and the prevalence of cirrhosis were investigated. The patients included 54 homosexuals, 19 parenteral drug abusers and 187 subjects with other or unidentified risk factors for exposure to hepatitis B virus. Thirty-five patients (13%) were positive for antibody to human immunodeficiency virus; 27 were homosexual and 8 were drug abusers. The mean aminotransferase activities, histological activity index and the prevalence of cirrhosis were similar in the human immunodeficiency virus-positive and human immunodeficiency virus-negative subgroups. Actuarial survival was significantly lower in the human immunodeficiency virus-negative subgroups. Actuarial survival was significantly lower in the human immunodeficiency virus-positive group than in the human immunodeficiency virus-negative subjects (p = 0.004); the cause of death was clearly related to liver failure in four of the five human immunodeficiency virus-positive patients and two of the six human immunodeficiency virus-negative subjects who died. To evaluate the factors determining the severity of liver disease, we compared homogeneous subgroups of subjects. Among the homosexual patients, the prevalence of HBeAg and hepatitis B virus DNA, aminotransferase activities and the histological activity index did not differ according to human immunodeficiency virus antibody status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions between human immunodeficiency virus-1, hepatitis delta virus and hepatitis B virus infections in 260 chronic carriers of hepatitis B virus. 155 33

The polymerase chain reaction (PCR) was used to investigate the presence of hepatitis B virus (HBV)-related DNA sequences in blood from three blood donors and two transfusion recipients who developed posttransfusion non-A, non-B hepatitis (NANBH). In the first case, the sole donor was positive for antibody to hepatitis B surface (HBs) and core (HBc) antigens and had elevated alanine aminotransferase (ALT) levels, while the recipient had no HBV serologic markers. Both the donor and the recipient had serologic markers of hepatitis C virus (HCV) and were found positive for HBV DNA and HCV RNA sequences by PCR. The second case involved two donors and one recipient. Serologic tests for conventional HBV markers were negative in all three individuals, but one of the donors had elevated ALT. HBV DNA sequences were detected by PCR in the serum of the recipient and of the donor with high ALT, but not in the serum of the donor with normal ALT. Anti-HCV was detected in the serum of the recipient and of the suspect donor but not in that of the donor with normal ALT. The sequences amplified in the S region and determined after cloning of PCR products for both donor-recipient pairs were indistinguishable from each other and identical to the sequence of the major HBV subtype of adw in the first case and ayw in the second case. Furthermore, for the second case, an identical single-point mutation was found in both the donor and the recipient. These data confirm the transmission of conserved HBV sequences together with HCV in posttransfusion NANBH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transmission of serologically silent hepatitis B virus along with hepatitis C virus in two cases of posttransfusion hepatitis. 155 1

The reported case of an unsuccessful treatment with acyclovir of herpes simplex virus hepatitis in a young patient, during pregnancy, demonstrates the necessity of an early diagnosis with the consequence of an early therapy. If serum antibodies are not evident, the presumptive diagnosis is based upon the histological demonstration of inclusion bodies in liver biopsy specimens. With the DNA-in-situ hybridisation technique, differentiation of the type of virus infection is possible in a short time. Hence, consideration should be taken that a biopsy of the liver should be done before the coagulation system breaks down due to hepatic necrosis. The risk of the liver biopsy seems to be low compared with the high morbidity and mortality of mother and child in systemic herpes simplex virus hepatitis.
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PMID:[Liver dystrophy in disseminated herpes simplex infection in pregnancy]. 156 33

Hepatitis B virus DNA was determined in the sera of 198 chronic hepatitis B surface antigen (HBsAg) carriers by the spot hybridization technique. The results were correlated with hepatitis Be antigen (HBeAg) and antibody (anti-HBe), delta antibody (anti-HD) and liver histology. All subjects had a liver biopsy. The prevalence of HBV DNA was 63% in HBeAg-positive subjects and 8.8% in anti-HBe positives. HBV DNA was not found more frequently in chronic HBsAg carriers who had histological evidence of liver disease than in carriers without such evidence. Anti-HD was detected in 48.5% of subjects, with an increasing trend (p less than 0.001) according to the severity of liver disease. Among patients with more severe liver disease (CAH and cirrhosis), HBV DNA and HBeAg were detected less frequently in anti-HD-positive than in anti-HD-negative subjects (7% vs. 42.3%, p less than 0.001 and 7% vs. 34.4%, p less than 0.005, respectively). These findings indicate that HDV infection jointly affects both HBeAg status and HBV DNA.
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PMID:Hepatitis B virus DNA in chronic HBsAg carriers: correlation with HBeAg/anti-HBe status, anti-HD and liver histology. 156 10

A gene region encoding a segment of the major surface protein, HBsAg, of hepatitis B virus was analyzed from serum samples after orthotopic liver transplantation of three hepatitis B virus chronic carrier patients treated with a human anti-hepatitis B virus monoclonal antibody (SDZ OST 577). Each of these three patients became HBsAg negative after transplantation and therapy with the human anti-hepatitis B virus monoclonal antibody but returned to HBsAg positivity (first detected 143,251 and 252 days after the transplantation). Polymerase chain reaction DNA amplification was performed on DNA from serum samples showing low levels of recurrent HBsAg and reduced antigen reactivity with SDZ OST 577 antibody. Polymerase chain reaction DNA included a 230-bp highly conserved, major S gene region that was cloned into M13 bacteriophage; analysis of this DNA segment provided a consensus of DNA sequences for the serum samples exhibiting altered reactivity with the therapeutic monoclonal. Analysis of independent DNA clones from serum samples of patients exhibiting low but detectable recurrent serum levels of posttherapy HBsAg revealed the presence of S protein variant sequences when compared with polymerase chain reaction DNA derived from the original infected liver or pretherapy serum HBsAg. Genetic variation was predominant in a highly conserved peptide domain that has previously been implicated in antibody binding and neutralizing antibody epitopes. In independent patients infected with either adw or ayw hepatitis B virus subtypes, single nucleotide changes resulted in one to two amino acid differences for each variant allele (residues 124, 129, 131, 137, 140 and/or 145) when compared with pretherapy viral DNA. Administration of serum containing one of these variant viruses to a single hepatitis B-naive chimpanzee resulted in subclinical hepatitis and detectable levels of circulating anti-HBs and anti-HBc antibodies 49 and 70 days after virus administration, respectively. Hepatitis B virus DNA was recovered on liver biopsy between 6 and 8 wk after inoculation, although the animal remained persistently seronegative for HBsAg. DNA sequence analysis of both primate and patient liver hepatitis B virus confirmed the presence of the DNA encoding the S protein variant and associates this DNA with the predominant hepatotropic virus in liver infection.
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PMID:Genetic alterations in the gene encoding the major HBsAg: DNA and immunological analysis of recurrent HBsAg derived from monoclonal antibody-treated liver transplant patients. 156 15

Persistent infection with hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC) in humans. HCC has also been observed in animals chronically infected with two other hepadnaviruses: ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus (WHV). A distinctive feature of WHV is the early onset of woodchuck tumors, which may be correlated with a direct role of the virus as an insertional mutagen of myc genes: c-myc, N-myc, and predominantly the woodchuck N-myc2 retroposon. In the present study, we searched for integrated GSHV DNA and genetic alterations of myc genes in ground squirrel HCCs. Viral integration into host DNA was detected in only 3/14 squirrel tumors and did not result in insertional activation of myc genes, despite the presence of a squirrel locus homologous to the woodchuck N-myc2 gene. This suggests that GSHV may differ from WHV in its reduced ability to induce mutagenic integration events. However, the high frequency of c-myc amplification (6/14) observed in ground squirrel HCCs indicates that myc genes might be preferential effectors in the tumorigenic processes associated with rodent hepadnaviruses, a feature not reported so far in HBV-induced carcinogenesis. Together with previous observations, our results suggest that hepadnaviruses, despite close genetic and biological properties, may use different pathways in the genesis of liver cancer.
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PMID:Frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus. 157 Mar 7


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