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)

Rapamycin (Rapa), one of the newer immunosuppressants has been found to control and prevent autoimmune features in animal models. This is the first report describing the successful control of post-transplant autoimmune hepatitis (AIH) with Rapa. Post-transplant AIH is diagnosed in the presence of raised transaminases, elevated immunoglobulin G, presence of autoantibodies and histologic changes consistent with AIH on liver biopsy. It may represent a recurrence of the original AIH that led to transplantation or present as a de novo AIH after liver transplant. Post-transplant AIH has conventionally been treated with Prednisolone (Pred) and Azathioprine (AZA). In this report, tailoring of immunosuppression after diagnosis of post-transplant AIH is described with special emphasis on those treated successfully with Rapa. Fifteen of 21 patients responded to treatment with an increase in dose of Pred and addition of AZA or Mycophenolate Mofetil (MMF) to calcineurin inhibitor. Five non-responders and one other patient with post-transplant AIH were treated with addition of Rapa. All six responded to treatment but drug was withdrawn in one patient. Adverse events were minimal. Rapa may prove to be an important addition in the control of autoimmune liver disease.
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PMID:Rapamycin successfully treats post-transplant autoimmune hepatitis. 1581 90

The choice of immunosuppressive regime used after liver transplantation depends on many factors, which should include the effect of disease recurrence; recurrence of disease after liver transplantation may be affected by the degree and type of immunosuppression used and recurrent disease may affect patient and graft survival. For autoimmune diseases, recurrence of primary biliary cirrhosis develops sooner and more rapidly in those on tacrolimus compared with cyclosporine, but graft loss from recurrent disease is uncommon; recurrence rates of primary sclerosing cholangitis is unaffected by immunosuppressive regimes and recurrence of autoimmune hepatitis may be reduced by prescription of corticosteroids. Whether the immunosuppressive regime affects the pattern of hepatocellular carcinoma recurrence is uncertain. It is probable that the use of calcineurin inhibitor does not have a significant effect and inhibitors of TOR may have an anti-cancer effect, but this still has to be shown clinically. Most metabolic diseases are not affected by the choice of immunosuppression, although recurrence of sarcoidosis may be prevented by corticosteroids.
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PMID:Long-term immunosuppression for prevention of nonviral disease recurrence. 1591 26

The severity of recurrent hepatitis C virus (HCV) is likely related to several factors. Controversial results have been reported regarding the effect of specific calcineurin-inhibitors. The aim of this research was to determine whether there are differences on posttransplantation outcome in HCV-infected patients based on initial immunosuppression. Prospective randomized trial comparing tacrolimus vs. cyclosporine-based immunosuppression in a cohort of patients undergoing primary orthotopic liver transplantation between 2001 and 2003 was used. Yearly biopsies were performed. Patients with at least 1 protocol biopsy and those with very severe recurrence despite a follow-up of less than 1 yr (cholestatic hepatitis, progression to bridging fibrosis/cirrhosis) were included. Baseline characteristics (demographics, liver function at transplantation, genotype distribution, donor, surgery, immunosuppression except for the type of calcineurin inhibitor) did not differ between the 2 groups. Severe disease (defined as bridging fibrosis, cirrhosis, cholestatic hepatitis, and/or death due to recurrent disease in the first year) was present in 27 in 90 (30%), and was equally distributed in the cyclosporine and tacrolimus groups (15/46 vs. 12/44, respectively). A total of 33 in 90 (37%) patients had no fibrosis in the first year biopsy with no difference between the cyclosporine and tacrolimus groups (36.5 vs. 37%). The percentage of patients developing recurrent acute hepatitis was also similar (32% vs 35%); time to acute hepatitis though was shorter in the tacrolimus group (59 days [35-185] vs. 92 days [39-343] in the cyclosporin group; P = 0.02). Cholestatic hepatitis was observed in 4 of 44 and 5 of 46 patients under cyclosporine and tacrolimus, respectively (P = not significant). In conclusions, the short-term posttransplantation course of hepatitis C is not related to the calcineurin inhibitor used.
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PMID:Effect of calcineurin inhibitors on survival and histologic disease severity in HCV-infected liver transplant recipients. 1662 96

The use of sirolimus as the main immunosuppressant in a calcineurin inhibitor-free regimen in the early postoperative period of liver transplantation (LT), when the incidence of rejection is the highest, has seldom been reported. We report six patients who received sirolimus in association with steroids only, at a median time of 10 days after LT (range 3-23). Tacrolimus, initially given as the standard immunosuppressant, was discontinued because of nephrotoxicity in three of these patients and neurotoxicity in the other three. Resolution of the neurological symptoms was observed in all cases and a marked improvement of the renal function in two of three patients. Two patients died, one of sepsis and the other of recurrent hepatitis C virus hepatitis, after 47 and 143 days respectively. Three patients developed acute rejection which responded to intravenous steroids. In this cohort of patients, the use of sirolimus appeared safe and provided an adequate prophylaxis against rejection, even though the drug was administered in the immediate postoperative period after LT.
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PMID:Sirolimus as the main immunosuppressant in the early postoperative period following liver transplantation: a report of six cases and review of the literature. 1708 Dec 33

Choice of calcineurin inhibitor may be a contributing factor to deteriorating patient and graft survival following liver transplantation for hepatitis C virus (HCV). In our multicenter, open-label LIS2T study, de novo liver transplant patients stratified by HCV status were randomized to cyclosporine or tacrolimus. Follow-up data were obtained in an observational study of 95 patients. Mean follow-up was 34 and 37 months, respectively, for cyclosporine-treated (n = 47) and tacrolimus-treated (n = 48) patients. In patients not receiving antiviral therapy, 22 of 31 given cyclosporine (72%) and 24 of 29 given tacrolimus (83%) had biochemical recurrence of HCV. In 68 patients with at least one biopsy, histological evidence of HCV-related hepatitis was present in 27 of 31 (87%) cyclosporine-treated patients and 37 of 37 (100%) tacrolimus-treated patients (P = .02, chi-square test). Three-year actuarial risk of fibrosis stage 2 was 66% with cyclosporine and 90% with tacrolimus; for fibrosis stage 3 or 4 it was 46% and 80%, respectively. Three graft losses were attributed to HCV recurrence in cyclosporine-treated patients and six in tacrolimus-treated patients. Tacrolimus may be associated with increased risk of histological HCV disease recurrence compared to cyclosporine.
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PMID:Long-term outcomes in liver transplant patients with hepatic C infection receiving tacrolimus or cyclosporine. 1711 75

A controversy exists over whether the outcome of a hepatitis C virus (HCV)-infection-related liver transplant differs based on the calcineurin inhibitor (CNI) used. We have performed a systematic review and a subsequent meta-analysis evaluating tacrolimus (Tac)-based vs. cyclosporine A-based immunosuppression in HCV-infected liver transplant recipients. Searches were conducted to locate randomized controlled trials comparing Tac vs. cyclosporine A. Data on HCV liver transplant recipients were obtained, independently of whether the study was specifically designed for patients with this disease or not. A fixed effects model was used for statistical pooling of the relative risks (RR) for the different outcomes. A total of 5 articles (366 patients) fulfilled the inclusion criteria. Statistically significant differences between Tac-based vs. cyclosporine A-based therapies were not found for mortality (P = 0.11; RR = 0.72; 95% confidence interval [CI], 0.49-1.08), graft survival (P = 0.37; RR = 0.86; 95% CI, 0.61-1.21), biopsy-proven acute rejection (P = 0.65; RR = 0.91; 95% CI, 0.61-1.36), corticoresistant acute rejection (P = 0.26; RR = 2.25; 95% CI, 0.55-9.29), and fibrosing cholestatic hepatitis (P = 0.92; RR = 0.96; 95% CI, 0.41-2.26). In 1 study, no differences were detected regarding severe fibrosis at 1 yr. In conclusion, patient and graft survivals in HCV-positive liver transplant patients are similar independently of the CNI selected as basic immunosuppressant. Unfortunately, data on the severity of recurrence and effect on viremia are scarce. Well-designed randomized prospective studies are needed to determine whether there are differences between the 2 CNIs regarding these specific variables.
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PMID:Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV recurrence after liver transplantation: results of a meta-analysis. 1719 6

De novo autoimmune hepatitis has been described in both pediatric and adult liver transplantation (LT) recipients. Studies of small numbers of patients have proposed it to be an alloimmune hepatitis or form of chronic rejection. We have recently noted an increasing number of patients with post-LT recurrent hepatitis C virus (HCV) developing this, with an apparent negative impact on outcome and survival. We term this entity posttransplant plasma cell hepatitis (PCH). A search of our institution's pathology database was performed with the terms "plasma cell(s)," "lymphoplasmacytic infiltrate," and "liver allograft." A histological scoring system was devised to more reliably diagnose PCH in the setting of recurrent HCV. Thirty-eight patients were identified, and their clinical data were analyzed. Sixty percent had a negative outcome as defined by the development of cirrhosis, need for retransplantation, or death. Eighty-two percent had recent lowering of immunosuppression or subtherapeutic calcineurin inhibitor levels; 58% developed PCH within 2 years post-LT. Histologic resolution of PCH was associated with good outcome (P < 0.001). Patients not receiving treatment had a negative outcome (P = 0.007) as did patients receiving corticosteroids as therapy (P = 0.02). Persistence (P = 0.007) or recurrence of PCH was associated with negative outcome. In conclusion, PCH is a histologic variant of rejection. On liver biopsy, PCH can at times be difficult to diagnose, and the use of a standardized scoring system is recommended to differentiate it from other forms of allograft dysfunction. Treatment by optimization of immunosuppression without the use of corticosteroids appears effective. The development of PCH in the setting of recurrent HCV is a negative prognostic factor for patient outcome and allograft failure.
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PMID:Posttransplant plasma cell hepatitis (de novo autoimmune hepatitis) is a variant of rejection and may lead to a negative outcome in patients with hepatitis C virus. 1850 66

As outcomes from liver transplantation have improved, attention has focused on long-term outcomes: patient and graft survival is affected by many factors, including the consequences of both overimmunosuppression (eg, renal failure and cancer) and underimmunosuppression (eg, rejection). The use of protocol (rather than event-driven) biopsies of the liver allograft, except for those grafted for HCV infection, has been largely abandoned. The aim of this study was to determine if protocol biopsies can improve the management of liver allograft recipients. A retrospective analysis of liver allograft recipients who had undergone protocol liver biopsies between 2000 and 2006 was performed. One hundred seventy-eight patients with normal liver tests (alcoholic liver disease, 49; autoimmune hepatitis, 20; and primary biliary cirrhosis, 107) who had undergone 235 protocol biopsies were identified. No significant complication from the biopsy was recorded. Liver histology was reported as normal or nearly normal in only 57 (24%). Chronic hepatitis (not obviously related to disease recurrence) was present in 78 (33%). Interpreted in the light of the calculated creatinine clearance, the biopsy findings indicated that overall immunosuppression (IMS) should be maintained or increased with standard calcineurin inhibitor (CNI)-based IMS in 25% of cases, that overall IMS should be reduced in 15% of cases, and that overall IMS should be maintained or increased by the substitution of non-nephrotoxic agents for CNIs in 9% of cases. The histological findings led to a documented change in IMS in 76 (32%) (increased IMS, 11; decreased IMS, 58; and switch from CNI, 7). In conclusion, protocol liver biopsy provides important histological information about graft function that is not available from standard liver tests and safely allows modification of IMS to ensure that long-term side effects of drug therapy (eg, renal failure) are minimized while graft function is sustained. Liver Transpl 15:931-938, 2009. (c) 2009 AASLD.
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PMID:Late protocol liver biopsies in the liver allograft: a neglected investigation? 1964 26

Liver transplantation is the only curative treatment in patients with end-stage liver disease. Neurological complications (NC) are increasingly reported to occur in patients after cadaveric liver transplantation. This retrospective cohort study aims to evaluate the incidence and causes of NC in living donor liver transplant (LDLT) patients in our transplant center. Between August 1998 and December 2005, 121 adult LDLT patients were recruited into our study. 17% of patients experienced NC, and it occurred significantly more frequently in patients with alcoholic cirrhosis (42%) and autoimmune hepatitis (43%) as compared with patients with hepatitis B or C (9/10%, P = 0.013). The most common NC was encephalopathy (47.6%) followed by seizures (9.5%). The choice of immunosuppression by calcineurin inhibitor (Tacrolimus or Cyclosporin A) showed no significant difference in the incidence of NC (19 vs. 17%). The occurrence of NC did not influence the clinical outcome, since mortality rate, median ICU stay and length of hospital stay were similar between the two groups. Most patients who survived showed a nearly complete recovery of their NC. NCs occur in approximately 1 in 6 patients after LDLT and seem to be predominantly transient in nature, without major impact on clinical outcome.
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PMID:Neurologic complications in adult living donor liver transplant patients: an underestimated factor? 1972 99

In 2004, we defined the genetic mismatch in the glutathione S-transferase T1 (GSTT1) gene positive donor/null recipient as a risk factor to develop de novo immune hepatitis (IH) after liver transplant (LT), which is always associated with production of donor-specific anti-GSTT1 antibodies. However, there are several unresolved questions, such as why some of these patients produce antibodies, why others do not and why not all of the patients with antibodies develop the disease. The aim of this study was to evaluate the influence of several variables in the production of anti-GSTT1 antibodies and/or de novo IH. The study group included 35 liver-transplanted patients. The number of patients not producing antibodies was significantly higher in the group treated with Tac-based immunosuppression compared with the CsA-based group (94.1% vs. 5.9%, p = 0.001). Additionally, a protective effect of the Tac-based therapy vs. the CsA-based therapy was observed with regard to development of de novo IH (80.8% vs. 19.2%, p = 0.003). In conclusion, the choice of calcineurin inhibitor may influence the development of de novo IH mediated by anti-GSTT1 antibodies.
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PMID:Choice of calcineurin inhibitor may influence the development of de novo immune hepatitis associated with anti-GSTT1 antibodies after liver transplantation. 2023 32


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