Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the last four years, 551 liver transplantations have been performed at the Paul Brousse center, for a total of 840 liver transplantations performed from 1984 to 1992. Several changes have been observed in the field of liver transplantation in the past years. The field of immunosuppression was marked mainly by the advent of FK506 as a preventive treatment of rejection and as a treatment of cortico-resistant rejection. Results are still under analysis. From the surgical viewpoint, the main modification was the advent of UW solution, which extends cold ischemic time. However, our policy was to maintain the cold ischemic time at less than 12 hours. Primary indications for liver transplantations have changed with an increase in the rate of patients transplanted for cirrhosis related to hepatitis virus infection: from 24% in the period 1984-1988 to 42% in the period 1989-1992. The difference was due mainly to HCV-related cirrhosis, which increased from 8% to 20%. Alcoholic cirrhosis was a rare indication in the period 1989-1992 (3.4%); however, it was an increasing indication in the last 2 years. In order to improve the long-term results, major attention was given to the recurrence of initial liver disease. In patients transplanted for HBsAg-positive liver disease, long-term passive anti-HBs immunoprophylaxis was administered, which reduced the rate of HBV recurrence in patients without HBV replication before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The Paul Brousse liver transplant series 1989 to 1992: new trends in the last four years. 133 27

The effect of conversion from cyclosporine-steroid immunosuppression to the new agent FK506 was studied in 96 liver allograft recipients who were experiencing graft dysfunction or cyclosporine toxicity. Patients were stratified according to the cause of graft dysfunction that ultimately led to conversion to FK506. Response to FK506 introduction was monitored pathologically and biochemically. The outcome of a switch from CsA to FK506 was highly favorable in patients experiencing acute and the early stages of chronic rejection, despite optimal conventional therapy. Patients with later stages of chronic rejection did not respond to conversion to FK506 and most eventually lost their liver grafts in this process. Patients in whom we had difficulty separating chronic rejection from chronic persistent or low-grade chronic active hepatitis were mostly unaffected by conversion to FK506. Active hepatitis was a poor indication for conversion, because most of the patients experienced graft failure or died from liver failure. As a group, there was no statistically significant change in renal function 180 days after conversion to FK506. These findings expand the experience with FK506 in human liver allograft recipients.
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PMID:Conversion of liver allograft recipients from cyclosporine to FK506 immunosuppressive therapy--a clinicopathologic study of 96 patients. 137 44

Twenty-three pediatric liver transplant recipients (median age 3.9 years) were converted from cyclosporine A-based immunosuppression to FK506 for uncontrollable acute rejection (AR; n = 16), chronic rejection (n = 4), or predominantly nonspecific hepatitis (n = 3). Of these, 19 had received poly- or monoclonal anti-T lymphocyte antibodies either for AR prophylaxis or therapy before FK506 conversion. Full clinical and histologic responses to FK506 therapy were observed in 11/16 cases of AR compared with 0/7 cases of non-AR indications (P = 0.006). Acute FK506 toxicity included renal dysfunction in 12/23 children (52%), neurological disorders in 7/23 (30%), and isolated hyperkalemia in 2/23 (9%), with a poor correlation with the corresponding FK506 trough plasma level. Moreover, a significant impairment of glomerular filtration rate was recorded in the 12 children who received FK506 treatment for more than 6 months (P = 0.002). FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n = 4; persistent tremor: n = 1; reason unrelated to FK506: n = 1). Five children developed a lymphoproliferative syndrome (LPS), leading to death in 3 cases despite cessation of the immunosuppressive therapy; in the other 2 patients, LPS was controlled, and the children were successfully retransplanted for chronic rejection under FK506. The occurrence of Epstein-Barr virus primary infection under FK506 therapy was found to constitute a significant risk factor for LPS (P = 0.027). In summary, full response to FK506 conversion was observed in 69% of uncontrollable AR cases; however, 74% and 22% of this probably over-immunosuppressed population experienced major adverse events and LPS under FK506 therapy, respectively.
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PMID:Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric liver allografts. Efficacy, toxicity, and dose regimen in 23 children. 750 72

We reviewed 37 living related liver transplantations (LRLT) performed by our department during the last 27 months on children with end-stage liver disease. The patients were 15 boys and 22 girls aged 7 months to 15 years with biliary atresia (27), cryptogenic cirrhosis (3), Budd-Chiari syndrome (2), progressive intrahepatic cholestasis (2), protoporphyria (1), Wilson's disease (1), and fulminant hepatitis (1). The donors were 14 fathers and 23 mothers. Grafts were made from the left lateral segment (19), left lateral segment with partial S4 (11), left lobe (6), and right lobe (1). After graft harvesting all donors resumed normal liver function and normal life. The recipient underwent total hepatectomy with preservation of the inferior vena cava. FK506 and low-dose steroids were used for immunosuppression. The survival rate was 90% (27/30) in elective cases and 57% (4/7) in emergency cases. Six recipients had functioning grafts but died of extrahepatic complications. Hepatic vein stenosis occurred in 3 cases at 3 months after LRLT and was successfully treated by balloon dilatation. Portal vein stenosis occurred in 1 case at 8 months after LRLT and was also safely dilated. We incurred no hepatic artery thrombosis after introducing microsurgery techniques. Among 12 viral, 5 bacterial, and 3 fungal postoperative infections, 1 Candida pneumonia and 1 EBV-associated lymphoma were lethal. Three patients with ABO-blood group compatible grafts and one with an incompatible graft developed acute rejection, which was controlled in evey case by steroid bolus and/or increasing the dose of FK506. There were no definite episodes of rejection in ABO-identical cases. Children with moderate growth retardation (> or = -1.5 SD of normal growth) caught up in growth soon after LRLT, but those with severe retardation (<-1.5 SD) were slow to attain age-normal height. Appropriate timing, meticulous surgical procedures, and comprehensive management of complications are crucial for successful outcome with LRLT. LRLT is a promising option for alleviating the shortage of livers for pediatric transplantation and may be regarded as an independent modality to supplement cadaver donation.
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PMID:Living related liver transplantation in children. 751 49

This prospective study characterizes the incidence, etiology, timing, risk factors, and outcome of the infectious complications after 88 consecutive liver transplantations in 79 patients receiving tacrolimus (FK506) as primary immunosuppression with a median follow-up of 880 days. Infections occurred in 59% (47/79) of the patients, and 39% had major infections. Of the major infections, 55% were bacterial, 22% were viral, and 22% were fungal. Bacteremia accounted for 30% of major bacterial infections. Sixty percent of bacteremias occurring within the first 3 months were catheter related, while 75% of those occurring more than 3 months after transplant were of a biliary source. Patients with recurrent hepatitis C virus hepatitis and patients requiring dialysis after transplant had a significantly higher rate of infections as compared with other patients. Overall mortality was 18%, and 29% of all deaths were associated with infection. Only invasive aspergillosis was associated with infectious mortality. Our data suggest that the potent immunosuppressive agent FK506 is not associated with a higher incidence of infectious complications as compared with previous studies using CsA.
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PMID:Infectious complications in liver transplant recipients on tacrolimus. Prospective analysis of 88 consecutive liver transplants. 752 4

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

From more than 900 articles in the medical literature, published between August 1, 1991 and July 31, 1992, 46 were selected for review. During the year of review, major international symposiums were held on a new drug, FK506, and intestinal transplantation. In addition, at least one new attempt at a unifying hypothesis regarding graft adaptation was proposed. Other studies included living related donor transplantation, results with transplantation for alcoholics, and the controversy regarding the role of liver transplantation for the treatment of Budd-Chiari syndrome. Concerns regarding the recurrence of both hepatitis and primary hepatic malignancy following liver transplantation were also addressed. Two innovative approaches to the treatment of acute liver failure offer exciting promise for the future. Other subjects include histologic evaluation of renal dysfunction in patients with liver disease, quality of life after transplantation, and the proper distribution of precious donor livers.
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PMID:Liver transplantation. 758 80

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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PMID:Weaning of immunosuppression in long-term liver transplant recipients. 783 42

An analysis of the first 740 liver transplants performed at Baylor is presented, including all cases to the end of calendar 1992. Kaplan-Meier curves are extended to nine years posttransplant. Our focus on outcome analysis has led us to review our experience with diabetics, with elderly patients, causes and patterns of late graft loss, long-term renal function. Quality of life data tracked for 2 years posttransplant is outlined. Clinical correlates to whole blood and plasma assays of FK506 are reviewed. Concerns remain over the disappointing results of liver transplantation for cholangiocarcinoma and those of patients with hepatitis-B antigenemia under current protocols.
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PMID:Baylor update: outcome analysis in liver transplantation. 791 48

This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB/c mice were given a single intravenous injection of concanavalin A (Con A) (> or = 0.3 mg/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB/c nu/nu mice or BALB/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.
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PMID:T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. 816 36


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