Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation.
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PMID:Changing perspectives on liver transplantation in 1988. 315 94

Cellular immune responses to hepatitis B virus (HBV) play an important role in the resolution of acute infection. They also influence the course of chronic infection and disease but are inadequate to completely clear the infection. Woodchuck hepatitis virus (WHV) infection of the woodchuck can provide a model to study these processes. Lymphocyte responses of woodchucks were assessed by in vitro proliferation and/or interleukin (IL)-2 assays using mitogen (Concanavalin A [ConA]), cytokine (IL-2), superantigen (Staphylococcus aureus enterotoxin B [SEB]), major histocompatibility complex (MHC) allo-antigen (mixed lymphocyte reaction [MLR]), and viral antigens (woodchuck hepatitis virus core antigen [WHcAg] and woodchuck hepatitis virus surface antigen [WHsAg]). ConA-stimulated woodchuck lymphocytes underwent cell division based on cell counting experiments and produced IL-2 as detected using an IL-2-dependent murine cell line but failed to incorporate sufficient tritiated thymidine; however, they did incorporate sufficient tritiated adenosine and deoxyadenosine to permit development of a meaningful proliferation assay. The IL-2 assay was sensitive and specific for detection of woodchuck IL-2 induced by mitogen, superantigen, and MLR, as shown by quantitative titration analysis and anti-body neutralization of ConA-supernatant activity. Cyclosporin A and FK506 specifically inhibited ConA- and SEB-induced IL-2 production by woodchuck lymphocytes. Positive two-way MLRs were detected by IL-2 production and proliferation assay between woodchucks from different geographic regions, thus indicating divergence among MHC molecules; however, occasional negative MLR reactions among indigenous pairs of woodchucks indicated that some woodchucks were mutually immunocompatible to some degree. The radioadenosine proliferation assay was sensitive for detecting peripheral blood lymphocyte responses to WHcAg and WHsAg in adult woodchucks with recently resolved acute infections. The above systems should facilitate the design of adoptive therapy and liver transplantation experiments in the woodchuck, and also enable modeling of immune responses that promote and maintain chronic hepadnavirus infection.
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PMID:In vitro activation of woodchuck lymphocytes measured by radiopurine incorporation and interleukin-2 production: implications for modeling immunity and therapy in hepatitis B virus infection. 754 55

Orthotopic liver transplantation (OLT) has been used with increasing frequency as a definitive treatment for end-stage liver disease. Whereas the spectrum of pathology in the early posttransplant period is well documented, the clinicopathologic features of patients with late hepatic dysfunction are less clearly defined. In a series of 100 OLTs we identified 12 patients with progressive liver dysfunction 4 months after transplantation. Four patients succumbed rapidly to fulminant hepatitis 4 to 6 months following transplantation, three of whom had recurrent hepatitis B infection. One patient lost two successive grafts owing to hepatitis C. Liver biopsies were diagnostic for hepatitis in all cases. The outcome of the remaining eight patients with late hepatic dysfunction was grim. Their clinical courses were notable for intractable and progressive cholestasis. Five patients died and two others required retransplantation. Only one patient responded to increased immunosuppression with FK506. Ductopenia was a common feature of liver biopsies in these cases, but severe ductopenia (vanishing bile duct syndrome) was seen in the liver biopsies of only four patients. In contrast, occlusive arteriopathy and secondary ischemic changes were ubiquitous. In summary, the liver biopsy is a useful adjunct in the diagnosis of late OLT dysfunction, particularly in distinguishing recurrent viral hepatitis from chronic graft rejection. Centrilobular ischemic changes occur frequently in chronic rejection, whereas ductopenia may be difficult to document consistently.
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PMID:Clinicopathologic features of late hepatic dysfunction in orthotopic liver transplants. 850 42

Recurrence of hepatitis B virus (HBV) in the graft is the major problem for patients with chronic HBV infection undergoing liver transplantation, which could be potentiated by the immunosuppression. In the present study, we used lymphocytes and hepatocytes isolated from patients with chronic HBV infection to investigate in vitro the effects of FK506 with and without methylprednisolone (25 ng/mL) on mitogen-induced lymphocyte proliferation, T-cell activation marker expression, and HBV replication in human hepatocytes. Increasing concentrations of FK506 (0.1, 0.5, and 5 ng/mL) resulted in a dose-dependent inhibition of lymphocyte proliferation with a reduction of the stimulation index by 9.2%, 39.0%, and 55.1%, respectively, with no difference between 25 chronic HBV carriers and normal controls. Methylprednisolone alone had no effect but potentiated the inhibitory effect of all three FK506 concentrations, such that the stimulation index was decreased by 20%, 56.2%, and 65.7%, respectively. FK506 (0.5 ng/ mL) reduced both the percentage of interleukin-2 receptor expressing T cells and the cell surface density of this receptor by 7.1% and 8.7% (P < .01), whereas it only reduced the proportion of HLA-DR expressing T cells by 6.8%. FK506 did not change significantly the intracellular HBV DNA or the hepatic expression of hepatitis B surface antigen (HBsAg) in short-term culture of human hepatocytes, whereas methylprednisolone increased the percentage of HBsAg-positive hepatocytes in all 5 patients with active viral replication. These results indicate that the effects of FK506 on T-cell activation in chronic HBV carriers are identical to normal subjects, resulting in marked suppression of T-lymphocyte function but only modest reduction in the expression of cell surface activation markers. The drug showed no direct stimulatory effect on viral replication, suggesting that FK506 can be a useful, steroid-sparing immunosuppressive agent for liver graft recipients with chronic HBV infection.
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PMID:FK506 in liver transplantation for chronic hepatitis B: in vitro studies on lymphocyte activation and virus replication. 934 13

A 43-year-old man underwent living related-donor renal transplantation because of chronic renal failure in 1991. During the transplant period, both donor and recipient were seronegative for hepatitis B surface antigen (HBsAg). The donor was seropositive for antibody to hepatitis B surface antigen (anti-HBs) due to hepatitis B virus (HBV) vaccination. After transplantation, FK506 and methylprednisolone had been administered to the patient as immunosuppressants. In 1993, HBsAg appeared in his serum. His alanine aminotransferase level elevated gradually during 1995 and then in 1996, general fatigue, ascites and jaundice developed. At this time his serum was positive for hepatitis B e antibody, contained more than 100000 Meq/mL HBV-DNA and 100% precore mutant. Despite subsequent intensive therapy, liver dysfunction progressed and this patient died of hepatic failure 2 months following admission. At autopsy, the liver exhibited cholestasis, fibrosis extending from the portal tracts, mild inflammation and hepatocytes with a ground-glass appearance. In addition, HBsAg and hepatitis B core antigens had accumulated in the hepatocytes. Consequently, the final diagnosis was fibrosing cholestatic hepatitis (FCH) due to precore mutant HBV infection contracted after renal transplantation. It is unclear when and where the recipient liver became HBV infected. Nevertheless, after renal transplantation, while receiving immunosuppressive drugs, HBV appeared to have the potential to cause hepatic failure and FCH may have been a fatal complication for the recipient.
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PMID:Fibrosing cholestatic hepatitis after living related-donor renal transplantation. 987 Aug 1

Post-transplant diabetes mellitus (PTDM) is a common complication after orthotopic liver transplantation (oLT). In our study, we investigated the prevalence and risk factors one year after transplantation in 618 patients who underwent oLT between 1990 and 1996 in a single center. The influence of steroid medication and hepatitis B or C (HBV/HCV) was also studied. Before oLT 66 of the 618 patients were diabetic. After transplantation 37 of these 66 (56%) patients showed no further signs of DM. Of the 552 patients without DM before transplantation 39 (7.2%) developed new onset PTDM. There was no influence of steroid medication on the presence of PTDM (steroids 10.4% PTDM, no steroids 12.5% PTDM). In addition we found no influence of HBV or HCV-infection on PTDM development. Analysis for risk factors showed no significant influence of the diagnosis leading to oLT, of FK506 or Cyclosorin A medication, age, gender or Child-Pugh class. Five year patient survival was not influenced by the presence of PTDM, especially patients with a preexisting DM showed no reduced survival. However, a subgroup of patients with new onset insulin-requiring PTDM showed significantly reduced 5 year survival (p<0.05). In conclusion we found new onset PTDM in 7.2% of patients undergoing oLT one year after the operation. On the other hand in more than 50% of patients with preexisting DM, the disease was no longer present post-transplant. This could be an indication that DM is dependent on liver function in these patients. Patients with preexisting DM should not be excluded from transplantation if indicated. Development of new onset insulin-requiring PTDM could be an important prognostic factor for patient survival after oLT. Further investigations are necessary to evaluate the prognostic meaning of PTDM and the pathophysiologic mechanisms.
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PMID:Liver transplantation and diabetes mellitus. 1102 53

Acute renal failure (ARF) is a frequent medical complication after liver transplantation (LT). We analyzed cadaveric related liver transplant recipients who had developed ARF early in the postoperative course. Between January 1982 and August 2003, a total of 67 patients underwent cadaveric related LT. Their mean age was 28.64 years at LT. The 67 recipients had the following indications: biliary atresia (n = 17), Wilson's disease (n = 15), hepatitis B-related liver cirrhosis (n = 14), hepatitis C-related liver cirrhosis (n = 4), primary biliary cirrhosis (n = 4), hepatitis B-related liver cirrhosis with hepatoma (n = 3), hepatitis C-related liver cirrhosis with hepatoma (n = 2), Budd-Chiari syndrome (n = 2), neonatal hepatitis (n = 1), choledochus cyst (n = 1), autoimmune cirrhosis (n = 1), neuroendocrine tumor (n = 1), and hemangioendothelioma (n = 1). Forty-nine patients received cyclosporine (CsA), azathioprine, and steroids and 18, a combination with tacrolimus (FK506). Eight (11.94%) patients developed ARF at a mean time of 17.25 days after LT. The mean peak serum creatinine was 2.24 mg%. Four of these patients had a diagnosis of hepatitis B-related liver cirrhosis; two, hepatitis C-related liver cirrhosis; one, primary biliary cirrhosis; and one, hepatitis B-related liver cirrhosis with hepatoma. The ARF etiology was multifactorial for the majority of patients. Eight ARF patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF. ARF treatment included fluid replacement, decreased or altered immunosuppressive agents, avoiding exposure to nephrotoxic drugs, and adjusting antibiotic dosages. The majority of patients returned to normal renal function at 1 to 3 weeks after the diagnosis of ARF. No patient required dialysis and/or experienced a mortality. We conclude that the incidence of ARF is relatively low and with good outcomes. ARF etiology was multifactorial for the majority of patients, but eight patients had a history of liver cirrhosis, which may be a risk factor for intraoperative ARF. We suggest that in the early postoperative period of LT cases diagnosis and treatment of ARF are important.
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PMID:Acute renal failure after cadaveric related liver transplantation. 1556 Dec 39

Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis.
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PMID:Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor region. 1692 12

Functional human hepatocytes xeno-engrafted in mouse liver can be used as a model system to study hepatitis virus infection and vaccine efficacy. Significant liver xeno-repopulation has been reported in two kinds of genetically modified mice that have both immune deficiency and liver injury-induced donor hepatocyte selection: the uPA/SCID mice and Fah(-/-) Rag2(-/-)Il2rg(-/-) mice. The lack of hardy breeding and the overly elaborated technique in these two models may hinder the potential future application of these models to hepatitis virus infection and vaccination studies. Improving the transplantation protocol for liver xeno-repopulation from human hepatocytes will increase the model efficiency and application. In this study, we successfully apply immunosuppressive drug treatments of anti-asialo GM1 and FK506 in Fah(-/-)Rag2(-/-) mice, resulting in significant liver xeno-repopulation from human hepatocytes and human fetal liver cells. This methodology decreases the risk of animal mortality during breeding and surgery. When infected with hepatitis B virus (HBV) sera, Fah(-/-)Rag2(-/-) mice with liver xeno-repopulation from human hepatocytes accumulate significant levels of HBV DNA and HBV proteins. Our new protocol for humanized liver could be applied in the study of human hepatitis virus infection in vivo, as well as the pharmacokinetics and efficacy of potential vaccines.
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PMID:Liver xeno-repopulation with human hepatocytes in Fah-/-Rag2-/- mice after pharmacological immunosuppression. 2065 Dec 38

To provide a basis for improved prevention and treatment of hepatitis B virus (HBV) re-infection after liver transplantation, variations in the S and P genes of HBV under immunosuppression in vitro and their association with patient prognosis were investigated. For the in vitro study, HepG2.2.15 hepatocellular carcinoma cells stably producing HBV particles were treated with the immunosuppressants methylprednisolone (MP) and tacrolimus (FK506) at doses found to be non-toxic by the methylthiazolyl tetrazolium (MTT) cell viability assay. MP dose-dependently inhibited HBV DNA expression in HepG2.2.15 cells, while FK506 did not, as determined by quantitative real-time PCR (qRT-PCR). By gene sequencing, both MP and FK506 were found to cause variations in HBV S, P, and S/P overlapping regions. MP- but not FK506-induced mutations were common in the glucocorticoid response element of the P region, while both immunosuppressants caused mutations outside the nucleoside analogue resistance sites. For the in vivo study, 14 patients with HBV-related end-stage liver disease re-infected after liver transplantation, and 20 cases without HBV re-infection as controls, were studied. Seventy-five percent of re-infected recipients showed multi-loci amino acid mutations at different sites besides lamivudine (LAM)-resistant loci in the P region, including in the glucocorticoid response element. Fifty percent of re-infected recipients had mutations in the "a" determinant region and flanking sequences. Re-infection was associated with negative serum hepatitis B immunoglobulin (HBIG), as measured by a microparticle capture enzyme immunoassay. Nucleotide mutations in the S region caused missense or synonymous mutations, which caused synonymous mutations in the overlapping P region. These results showed that effects of immunosuppressants on HBV genes in vitro were different from those in clinical recipients. Positive HBV DNA and gene mutations pre-transplantation were factors affecting re-infection post-transplantation. Multiple mutations found in the P and S genes suggest that the formation of quasispecies contributes to HBV re-infection after liver transplantation.
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PMID:Variations in the S and P regions of the hepatitis B virus genome under immunosuppression in vitro and in vivo. 2294 68


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