The surface antigen (S) gene promoter, one of the major hepatitis B virus (HBV) promoters, directs the synthesis of a 2.1 kb mRNA which encodes the preS2 and S polypeptides. The preS2/S promoter does not contain a classical TATA box, and transcription regulation of the preS2/S gene has not been fully elucidated. We analysed two regions involved in preS2/S gene transcription of the HBV adw subtype: the diverged TATA box and a putative initiator element. We demonstrated sequence specific promoter activity of the putative TATA-like sequences in the preS2/S gene promoter (-25 to -32 bp). Using end labeled synthetic oligonucleotides we observed specific binding of nuclear extracts to the diverged TATA sequence, that was significantly reduced using a mutated oligonucleotide. Specific binding of yeast TBP to the diverged TATA sequence was shown which was increased in the mutant containing a classical TATA box. We analysed the proposed initiator (Inr) sequence of the preS2/S promoter region (-13 to -16 bp). Deletion of the inr element markedly reduced promoter activity as assessed by CAT expression. Gel shift assays showed specific binding of nuclear extracts to wild type but not to mutant Inr. Expression studies with double mutants of the diverged TATA and the Inr element established that both elements are active in transcription regulation.

Base Sequence↗

PubMed1997

Viral hepatitis in older adults.

The objective of this paper is to review the epidemiology, manifestations, therapy, and prevention of viral hepatitis in older people and to discuss issues of prevention and management. In developed countries a significant portion of the adult population is not immune to Hepatitis A virus (HAV). Morbidity and mortality from HAV infection increases with age. A safe and effective hepatitis A vaccine is available and health authorities should consider immunization early in life and for healthy adults as well as for potential high risk groups such as nursing home residents. Acute hepatitis due to Hepatitis B virus (HBV) is rare in older people and is usually a mild disease. Most older patients with chronic HBV infection who suffer from advanced liver disease have no evidence of ongoing viral replication. Therefore, they are not candidates for interferon therapy. Those with evidence of ongoing viral replication and compensated liver disease should be offered interferon or be included in clinical trials with new antiviral drugs such as lamivudine. Since the response rate to hepatitis B vaccination decreases with age, developing vaccines with greater immunogenicity is crucial. Hepatitis C virus (HCV) is the most frequent cause of acute viral hepatitis in older people. Acute hepatitis C is usually a mild disease in this age group. Because many older patients with chronic HCV infection have compensated liver disease, they could benefit from antiviral therapy. In light of the low response rate to interferon in older patients with chronic hepatitis C and the side effects of the drug, interferon therapy should be reserved for those with the best chance of response. "Combination" antiviral therapy should be on trial for older patients with chronic HCV infection who do not respond to interferon. The recently discovered RNA virus, Hepatitis G (HGV), has been associated with liver disease in older people. It's role in the pathogenesis of liver injury remains to be elucidated.

Adult↗

PubMed1997

Hepatitis C virus genotypes in patients with persistent infection--a preliminary report.

Hepatitis C virus (HCV) has nucleotide sequence diversity distributed throughout the viral genome, with variants showing even less than 70% homology. There is some evidence that sequence variation of HCV genotypes partly determines the course of infection and response to treatment with interferon. We studied the sera of 29 Israeli HCV patients, all suffering from chronic liver disease, and 34 patients with renal failure necessitating hemodialysis. HCV genotypes were detected using a reverse hybridization assay (LiPA), after reverse transcription polymerase chain reaction, using primers spanning the 5' UTR of the HCV genome. In this preliminary report the predominant HCV type detected was type 1, found in 65% of the chronic hepatitis patients and in 88% of the hemodialysis patients. Subtype 1b was the most prevalent and was detected in >40% of the chronic hepatitis patients and in >70%of the dialysis patients. Other types detected were 2a and 3, and in only two patients was type 4 found. More than 50% of patients with type 1 (1a or 1b) among patients with chronic hepatitis had received blood transfusion in the past, but only 16.6% of patients bearing subtype 2a HCV had such a history. Our preliminary evaluation revealed that patients bearing subtype 1b seemed to have a better response to interferon treatment, as compared with patients infected with subtypes 1a, 2a, who displayed a low response rate.

Adult↗

PubMed1997

New trends in liver transplantation for viral hepatitis.

Explore the source record for details and available documents.

Antiviral Agents↗

PubMed1996

[New trends in liver transplantation--lessons learned and future perspectives].

Explore the source record for details and available documents.

Animals↗

PubMed1996

Sanctuary of hepatitis B virus in bone-marrow cells of patients undergoing liver transplantation.

Hepatitis B virus (HBV) reinfection after liver transplantation is a major problem. HBV is mainly a hepatotrophic virus but replicates in many extrahepatic tissues. We present here two cases of infected patients who underwent liver transplantation. Both underwent bone marrow (BM) and liver biopsies after transplantation. Biopsy specimens were stained for hepatitis B surface antigen (HB-sAg), and bone marrow aspirates and were separated for all subsets of cells. In both cases, HBV DNA analysis detected DNA in all BM fractions after transplantation, but HBV recurrence was found only in one case. We suggest that graft reinfection after liver transplantation may be caused by active replication of HBV in extrahepatic tissues and that BM cells are probably one of the major sanctuaries. The use of immunoprophylaxis based on BM-HBV studies is discussed.

Bone Marrow Cells↗

PubMed1996

Beneficial effect of ribavirin on hepatitis C-associated cryoglobulinemia after liver transplantation.

Mixed cryoglobulinemia is a well-known complication after hepatitis C virus (HCV) infection. We report five cases in which cryoglobulinemia appeared or grossly exacerbated following orthotopic liver transplantation (OLT). Cryoglobulinemia and the associated clinical symptoms resolved or improved in two patients treated with ribavirin after liver transplantation, while plasmapheresis was ineffective in another patient. The mechanism involved in induction of cryoglobulinemia after liver transplantation is unknown. However, the effect of antiviral therapy observed in these patients suggests a correlation between cryoglobulinemia, HCV replication, and possibly hepatocellular disease activity. A larger-scale study is warranted to test the effect of ribavirin on post-OLT HCV-associated cryoglobulinemia.

Adult↗

PubMed1996

Hepatic failure associated with imipramine therapy.

Imipramine is an antidepressant drug that is rarely associated with mild liver function abnormalities. These are usually minor and transient liver enzyme elevations which return to normal levels upon discontinuation of the drug. We describe a 48-year-old male who developed subfulminant hepatic failure after imipramine usage, with complete recovery within three months after discontinuation of the drug.

Antidepressive Agents, Tricyclic↗

PubMed1996

Glomerulonephritis associated with acute hepatitis B.

Acute hepatitis B virus (HBV) infection has very rarely been associated with glomerulonephritis. We describe a case of post-infections glomerulonephritis associated with acute HBV infection. The kidney disease resolved concomitantly with the hepatitis, and the patient recovered from acute HBV infection.

Acute Disease↗

PubMed1995

Hepatitis C-associated cryoglobulinemia after liver transplantation.

Mixed cryoglobulinemia is well known to be associated with hepatitis C virus (HCV) infection. We report two cases in which cryoglobulinemia appeared or became grossly exacerbated after orthotopic liver transplantation. In both cases, there was co-appearance of cryoglobulinemia with the reinfection of the grafted liver with HCV. It is postulated that the cryoglobulinemia might be related to secondary HCV infection in these patients.

Adult↗