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

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.
 ...
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.
 ...
PMID:T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. 816 36

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.
 ...
PMID:Clinicopathologic features of late hepatic dysfunction in orthotopic liver transplants. 850 42

Hepatitis C virus (HCV) is the predominant cause of posttransplant non-A, non-B hepatitis among renal allograft recipients. Prior studies evaluating the impact of HCV in kidney transplantation have been retrospective in design and based largely on changes in serum transaminases. We studied a group of HCV-infected end-stage renal disease patients prospectively with pretransplant liver biopsies and close virologic and biochemical follow-up posttransplant. Fourteen patients have been followed a mean of 11.6 +/- 5.6 months posttransplant (range, 5-21 months). Six had changes of chronic hepatitis on pretransplant liver biopsy while 8 showed only mild histologic abnormalities. Circulating viral titers increased several-fold over baseline levels during posttransplant follow-up. Viral replication was particularly enhanced immediately following a course of antilymphocyte therapy. Although all patients showed a 2-3 fold increase in alanine aminotransferase (ALT) following transplantation, there were no association noted between pretransplant liver histology, the use of FK506 and/or cyclosporine-based immunosuppression, and the magnitude of ALT change posttransplant. The only clinical outcome found to differ significantly was a higher incidence of cytomegalovirus infection among patients with chronic hepatitis. All patients are alive with functioning grafts. There have been no episodes of fulmiinant or subfulminant liver failure. We conclude that HCV-infected patients can be safely transplanted with excellent short-term follow-up. Continued monitoring with sequential liver biopsies will be needed to define the long-term course of HCV infection in an immuno-suppressed population.
 ...
PMID:A prospective study of hepatitis C virus infection in renal allograft recipients. 862 54

Outcomes from 48 pregnancies in 34 female liver transplant recipients were analyzed. Data were collected via interviews, questionnaires, and hospital records. All recipients were treated with cyclosporine-based immunosuppression except 2 patients treated with FK506 and 2 treated with no immunosuppression. The age at conception was 26.1 +/- 5.9 years (mean +/- SD) with a transplant interval (time from transplantation to conception) of 2.9 +/- 2.5 years. There were 49 outcomes (1 set of twins): miscarriage 9 (18%), therapeutic abortion 4 (8%), and live birth 36 (74%). No stillbirths or ectopic pregnancies were reported. Of the 36 live births, the gestational age was 36.9 +/- 3.5 weeks, the birthweight was 2,604 +/- 698 grams, 39% were premature (< 37 weeks), and 31% had low birthweight (< 2,500 grams). No birth defects or neonatal deaths (< 28 days) were reported. The newborn complication rate was 17% (n = 6), 5% in premature infants. The incidence of drug-treated hypertension was 46%; pre-eclampsia 21%; infectious complications 26%; and Caesarean section 47%. Recipients with hypertension had a higher proportion of premature infants (71%) than normotensive patients (38%) (P = .04 by Fisher's exact test). Acute rejection was diagnosed in 6 pregnancies, 2 of which were ended by therapeutic abortion. Four recipients who continued their pregnancies were treated with increased immunosuppression for rejection, and all delivered livebirths. There were two grafts lost within 6 months of pregnancy. The only maternal death occurred in a patient who required retransplantation for recurrent C hepatitis 3 months afte therapeutic abortion and died 6 months later. The other recipient with graft loss was successfully retransplanted for chronic rejection 6 months after delivery. We draw the following conclusions: (1) female liver transplant recipients can safely undergo pregnancy, although there is a high rate of premature and low birthweight infants; (2) pregnancies in this population should be considered high-risk and require close monitoring of liver function; and (3) altered graft function during pregnancy should be thoroughly investigated.
 ...
PMID:National Transplantation Pregnancy Registry: analysis of pregnancy outcomes in female liver transplant recipients. 934 83

The optimal immunosuppressive regimen in patients transplanted for hepatitis C (HCV) is still under discussion. High immunosuppression may promote viral replication and recurrent graft hepatitis. But acute and chronic rejection frequently seen in conjunction with HCV recurrence may require some rescue therapy. One hundred and thirty-seven patients transplanted for HCV cirrhosis, who were HCV-RNA positive prior to transplantation, were analyzed. Seventy-nine patients received CSA-based immunosuppression and 58 patients FK506-based immunosuppression. One-month patient survival was 100% in both groups. Three month and 1-year survival rates and the cumulative 1-5-year patient survival was similar in CsA-treated [67/79 (84.8%)] and FK506-treated patients [50/58 (86.2%)]. Retransplantations for HCV recurrence were performed in 5.1% of CsA-treated patients and 6.9% of FK506-treated patients; it was successful in 50% and 75% of patients, respectively. Conversion from CsA to FK506 and vice versa was high with 25 out of 79 patients (31.6%) converting in the CsA group and 8 out of 58 patients (13.8%) converting in the FK506 group. Conversion to FK506 was performed due to acute and chronic rejection and to CsA because of toxicity and HCV recurrence. In both groups, 25% of converted patients died. Five patients of the CsA group and 9 of the FK506 group received OKT3; more than one-third of each group died. Five patients in the CsA group and 6 in the FK506 group received mycophenolate mofetil (MMF) for HCV recurrence or acute and chronic rejection in conjunction with HCV recurrence. All patients of this critical group are alive with good graft function. In conclusion, survival rates of HCV patients were similar to those seen for other indications. Conversion from CsA to FK506 and vice versa was high and reflects a critical group concerning patient survival. OKT3 treatment should be avoided. A promising therapeutic option for critical patients experiencing acute or chronic rejection in conjunction with HCV recurrence may be treatment with MMF.
 ...
PMID:Searching for the optimal management of hepatitis C patients after liver transplantation. 966 81

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.
 ...
PMID:Fibrosing cholestatic hepatitis after living related-donor renal transplantation. 987 Aug 1

Prednisone alone or in combination with azathioprine is the treatment of choice for severe type 1 autoimmune hepatitis. The combination regimen is preferred, especially in the elderly, because of a lower incidence of corticosteroid-related complications. Only patients with sustained severe laboratory abnormalities, bridging necrosis or multilobular necrosis on histological assessment, and/or incapacitating symptoms, have absolute indications for treatment based on controlled clinical trials. The institution of therapy must be individualised in other patients, based mainly on symptoms and disease behaviour. Serum aspartate aminotransferase and gamma-globulin levels are the most useful indices to monitor during therapy. Liver tissue examination is the best method of evaluating completeness of response. Most patients enter remission, but relapse occurs in 50 to 86% after drug withdrawal. Maintenance therapy with low dosages of prednisone or azathioprine can be used long term in patients who have relapsed repeatedly. Inability to achieve remission after 3 years (incomplete response), deterioration during therapy (treatment failure) and drug toxicity are unsatisfactory responses that warrant alternative strategies. Liver transplantation is effective in managing decompensated disease, but recurrence of autoimmune hepatitis after transplantation is possible. Tacrolimus and budesonide are promising new drugs.
 ...
PMID:Drug therapy in the management of type 1 autoimmune hepatitis. 995 51

We report the course of thrombotic thrombocytopenic purpura (TTP) in a patient receiving tacrolimus (FK506) immunosuppression for an ABO mismatched second liver graft. A Chinese woman with fulminant hepatitis-B reactivation failed a living-related orthotopic liver transplantation (OLT) due to portal vein thrombosis. An ABO mismatched cadaveric OLT (group A to O) was performed, with peri-operative plasmapheresis to reduce anti-A hemagglutinin titers. On day 30, she developed fever, hemolysis, thrombocytopenia and neurologic dulling. Prominent microangiopathic features in peripheral blood film, and characteristic brain lesions on magnetic resonance imaging confirmed TTP. She responded initially to intensive plasmapheresis with cryosupernatant replacement, and withdrawal of FK506. An attempted reintroduction of FK506 for threatened rejection led to TTP exacerbation. This was controlled with prolonged plasmapheresis and a ten-day infusion of prostacyclin. Immunosuppression was changed to mycophenolate mofetil. By day 53, the peripheral film and lactate dehydrogenase level had returned to baseline and plasmapheresis was stopped.
 ...
PMID:Tacrolimus (FK 506) induced thrombotic thrombocytopenic purpura after ABO mismatched second liver transplantation: salvage with plasmapheresis and prostacyclin. 1087 Jan 25

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.
 ...
PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48


<< Previous 1 2 3 4 5 6 Next >>