Budd-Chiari syndrome with portal, splenic, and superior mesenteric vein thrombosis treated with TIPS: who dares wins.
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Biomedical subjects
Publications and source records attributed to A K Burroughs.
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BACKGROUND & AIMS: Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). METHODS: One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. RESULTS: The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). CONCLUSIONS: In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.
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Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.
BACKGROUND: The effect of the type of immunosuppression on the course of posttransplant hepatitis C virus (HCV) infection is unclear. The aim of this study was to evaluate the histological outcome of posttransplant HCV infection with respect to initial immunosuppressive therapy in a cohort of 59 of 65 HCV positive transplant patients who survived at least 12 months. METHODS: Initial immunosuppressive therapy was triple (cyclosporine or tacrolimus and azathioprine and prednisolone) in 41, double (cyclosporine and prednisolone) in 5, and single (cyclosporine or tacrolimus) in 13 patients. There was blinded histological evaluation, based on necroinflammatory activity (grading score:0-18) and fibrosis (staging score: 0-6). The median histological follow-up was 36 (12-72) months. RESULTS: In the last liver biopsy, high necroinflammatory activity indicating chronic hepatitis (grading score > or =4) was found in 42 (71%) and severe fibrosis or cirrhosis (staging score > or =4) in 18 (30.5%) patients. High necroinflammatory activity was associated significantly with absence of pretransplant alcohol abuse (P=0.01) and relatively with occurrence of posttransplant acute lobular hepatitis C (P=0.055). Development of severe fibrosis or cirrhosis was significantly associated only with the type of initial immunosuppressive therapy. In particular, severe fibrosis or cirrhosis developed significantly more frequently in patients treated with triple or double (17/46 or 37%) than with single initial immunosuppressive therapy (1/13 or 7.7%) (adjusted for biopsy time: P=0.045). CONCLUSIONS: Severe fibrosis or cirrhosis appears to develop in 30% of HCV transplant patients in a median of 3 years and to be associated with heavier initial immunosuppression.
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The effects of the immunocompromised state after liver transplantation on the frequency of cytomegalovirus-specific cytotoxic T lymphocytes (CTL) were investigated in 93 patients by using HLA class I tetrameric complexes corresponding to HLA-A*0201, HLA-B*0702, HLA-B*0801, and HLA-B*3501 refolded with peptides from the ppUL83 matrix protein. ppUL83 CTL frequencies were suppressed during the first 6 months after transplantation. Patients with >1 HLA-restricted response detected had high correlation among ppUL83 CD8(+) CTL frequencies restricted by different HLA haplotypes (Spearman's rho=.67; P<.0001). There was an inverse correlation among levels of the calcineurin inhibitor, tacrolimus, and ppUL83 CD8(+) CTL frequencies (r=-.31; P=.005), which is consistent with the presence of a large proportion (70%) of activated (CD38(+)) ppUL83 CD8(+) CTL within the population of HLA class I tetramer-positive cells.
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BACKGROUND/AIMS: We describe the histological patterns of rejection in liver transplant recipients using induction therapies with cyclosporine and tacrolimus monotherapy compared with standard triple therapy as historical control. METHODS: Patients formed part of the initial cohort in an open-labelled, randomised pilot study and were selected consecutively if they had histological rejection and no other confounding diagnoses. There were 13 patients in the cyclosporine monotherapy group (CsA), 11 in the tacrolimus monotherapy group and 13 in the triple therapy group (CAP). The histology of liver biopsies was reassessed blindly and the severity of rejection was recorded. RESULTS: The total Royal Free Hospital (RFH) rejection scores as well as other histological features (zone 3 haemorrhage, apoptosis in zones 1 and 3, steatosis, cholestasis, nuclear vacuolation, lymphoblasts and ballooning) were comparable in the three groups. There was no difference in individual components of the histological features comprising the diagnosis of rejection, except that the portal inflammation score was significantly lower in the tacrolimus group when compared with the CsA group (p=0.04). There was no significant difference in the number of patients with moderate/severe rejection between the three groups. Overall, there was no significant increase in histological severity of rejection in the monotherapy groups. CONCLUSIONS: The results suggest that the monotherapy may be as effective as the triple therapy in the initial post-transplant phase and that no particular graft histological changes were associated with the type of treatment.
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Hepatitis C virus (HCV) reinfection is almost universal in patients transplanted for HCV-related cirrhosis. The medium-term survival after orthotopic liver transplantation (OLT) is similar to other transplanted patients, but the long-term survival remains uncertain. The prevention and an effective treatment of progressive liver disease are the primary aims in HCV recurrence. Interferon and ribavirin, as monotherapy or in combination, have been tried to treat or prevent HCV recurrence. Preliminary studies suggest a better chance of initial HCV clearance and better results in preventing HCV recurrence with combination therapy. IFN or ribavirin, as monotherapy, may normalize liver enzymes, but only gives rise to a transient virological response, without histological improvement. Combination IFN and ribavirin may be able to prevent progression of HCV-related graft disease, but indications and duration of treatment need further evaluation. No clear association between type and dose of immunosuppressive and outcome of post-transplant HCV recurrence has been found. Strategies to minimize the effects of immunosuppressive drugs include dose reduction of all agents and the selective discontinuation of individual agents. Initial immunosuppression with a single drug may inhibit or delay the severe fibrosis, and further investigation with a single immunosuppressive regimen to evaluate the outcome of recurrent hepatitis C should be performed. The recent evidence that mycophenolate may have an antiviral effect needs a clinical confirmation. Retransplantation survival is better with early retransplantation, and for indications not directly related to viral recurrence.
Hepatic artery thrombosis (HAT) is one of the principal causes of morbidity and graft loss following liver transplantation. There are several risk factors for the development of HAT; technical aspects of the arterial anastomosis are important particularly for early thrombosis, but the improvement of surgical technique has lessened this problem. Apart from technical causes, other risk factors include a variety of conditions such as low donor/recipient age ratio, immunologic factors, clotting abnormalities, tobacco use, and infections. In particular, cytomegalovirus (CMV) infection of endothelial cells has been recently suggested as an infective cause of HAT, as it is known to be followed by a rapid procoagulant response. Thus, latent CMV in an allograft may become activated and promote or contribute to vascular thrombosis. This review evaluates these aspects, focusing on data relating CMV infection or viremia to HAT following liver transplantation.
A frequent complication in patients with end-stage liver disease is portal vein thrombosis (PVT). Although PVT is not considered an absolute contraindication to orthotopic liver transplantation (OLT), more complex surgery is required and patients have more postoperative complications and greater mortality rates. We describe 2 patients who experienced complete PVT either while waiting for liver transplantation or during the workup, resulting in acute deterioration of liver function. Recanalization of the portal vein was successfully performed in both patients using transjugular intrahepatic portosystemic stent shunt (TIPS), and patency was maintained by the addition of anticoagulation therapy. They subsequently underwent successful OLTs and remain well. In conclusion, we believe that TIPS placement can be performed safely in patients with recent PVT, ensuring the patency of the portal vein until OLT.
This case report describes fulminant hepatic failure in a 53-year-old female caused by inadvertent rechallenging with diclofenac, treated by orthotopic liver transplantation. The case also illustrates the hazards of using both generic and non-generic drug prescribing, with drugs that are known to be toxic. The literature on non-steroidal anti-inflammatory drugs and hepatoxicity is reviewed.