Tomorrow's challenge in liver transplantation: diminishing the imbalance between donor organ availability and need.
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Humans↗
Biomedical subjects
E M Yoshida
Publications and source records attributed to E M Yoshida.
Selecting candidates for liver transplantation: a medical ethics perspective on the microallocation of a scarce and rationed resource.
Liver transplantation has evolved over the past 35 years from an experimental procedure with high perioperative mortality to an accepted form of treatment with an approximate 85% one-year and 80% three-year patient survival rate. Following the success and acceptance of transplantation in the treatment of end-stage liver disease, there has been a progressive increase in the number of patients seeking a limited supply of donor organs. The ethical focus, on a microallocation level, has therefore changed from that of the 1960s, when the question was whether the procedure should be offered at all, to that of the 1990s and beyond, when the focus is on the proper allocation of a scarce, life-saving resource. The ethical issues concerning fair allocation surrounding liver transplantation are explored, from both the referring physician's perspective and the perspective of the transplant physician. In particular, the contrasting viewpoints of bioethicists Nicholas Rescher and James Childress, with respect to nonmedical and social criteria in the selection of patients for scarce, life-saving therapies are explored. Lastly, some alternative ethical models for patients selection are reviewed.
British Columbia↗
Postliver transplant allograft reinfection with a lamivudine-resistant strain of hepatitis B virus: long-term follow-up.
Lamivudine is a nucleoside analogue with efficacy in the suppression of hepatitis B viral (HBV) replication. In a previously reported study, lamivudine was administered to patients with chronic, actively replicating HBV infection who subsequently underwent liver transplantation. Patients became serum HBV DNA-negative in response to lamivudine before transplantation, which was continued in the post-transplant period. Two of four patients surviving the immediate postoperative period developed allograft reinfection 240 and 409 days post-transplant. The strain of the reinfecting virus was analyzed, and a mutation in the YMDD region of the viral polymerase conferring resistance to lamivudine was discovered. The long term follow-up of these two patients is reported. The first patient developed ascites 16.5 months after allograft reinfection. A transjugular liver biopsy performed 18 months after the emergence of the lamivudine-resistant strain revealed cirrhosis and lobular hepatitis without rejection. The gradient between hepatic vein wedged and free pressures was 13 mmHg, consistent with portal hypertension. The second patient, 16 months after allograft reinfection with the lamivudine-resistant strain, is without clinical evidence of portal hypertension, although liver enzymes remain elevated. Both patients were given a trial of famciclovir, which did not significantly suppress HBV viremia. In conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an aggressive clinical course with rapid progression to cirrhosis. Famciclovir did not appear to be an effective rescue agent in these two patients.
2-Aminopurine↗
Primary induction with mycophenolate mofetil and corticosteroids in a liver transplant recipient with hepatorenal syndrome.
OBJECTIVE: To report the use of mycophenolate mofetil for primary induction in a liver transplant recipient to avoid the nephrotoxicity of cyclosporine/tacrolimus. CASE SUMMARY: A 47-year-old white man in a hepatic coma with anuric hepatorenal syndrome received a liver transplant, and was given mycophenolate mofetil and corticosteroids as primary induction immunosuppression with the addition of low-dose cyclosporine 13 days later. His renal function improved and he remains rejection-free after 13 months of follow-up. CONCLUSIONS: This case suggests that mycophenolate mofetil may be used as a primary induction agent in liver transplant recipients with renal failure to avoid the additional nephrotoxicity of the standard immunosuppressants, cyclosporine and tacrolimus. Low-dose cyclosporine/tacrolimus may be introduced later as the renal function improves.
Hepatic Encephalopathy↗
Issues in organ procurement: presumed consent, bioethical type II errors, and organ registries.
In an effort to alleviate the current imbalance between the many in need of an organ transplant and the limited number of organs procured, a policy of presumed consent has been recently debated. Presumed consent assumes that potential organ donors agree to donate their organs in the absence of known objections to the contrary. The authors examine the bioethical principles and consequences involved in such a policy and apply hypothesis testing, borrowed from clinical epidemiology, to a "bioethical test" of presumed consent in a hypothetical clinical scenario. A possible bioethical alternative to presumed consent, an organ donor registry of advanced directives as has been established in British Columbia, is also discussed.
Advance Directives↗
Outcomes after complete immunosuppression withdrawal in liver transplant recipients: rejection-free graft tolerance or late acute rejection?
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Follow-Up Studies↗
Alteration of the dismal natural history of fibrosing cholestatic hepatitis secondary to hepatitis B virus with the use of lamivudine.
BACKGROUND: Fibrosing cholestatic hepatitis (FCH) is a severe form of hepatitis B virus (HBV) infection occurring as either primary allograft reinfection after liver transplantation for HBV or as severe HBV reactivation induced by immunosuppression in patients with previously latent infection. Without treatment, FCH is universally fatal within a few months of diagnosis. Some improvement has been reported with long-term ganciclovir, with and without foscarnet, but an effective and easily available treatment has not yet been reported. METHODS: We report the prolonged survival of a renal transplant recipient who developed histologically confirmed FCH 6 months after transplantation and was treated with lamivudine. RESULTS: At the time of diagnosis, the patient had jaundice, ascites, and a serum HBV-DNA level of 3868 pg/ml. Lamivudine was instituted 2 months later, and after 6 months of treatment, the HBV-DNA level was undetectable with the serum bilirubin within the normal range. Twelve months after the diagnosis of FCH, the patient remains stable without progression of liver dysfunction. CONCLUSION: Our experience demonstrates that lamivudine therapy can improve the dismal natural history of FCH.
Antiviral Agents↗
Selection of patients for liver transplantation in 1997 and beyond.
Liver transplantation is now accepted as the standard surgical-medical treatment for end-stage liver disease, as well as replacement therapy for certain inborn errors of metabolism. While improvements in surgical methods and new immunosuppressive agents have improved survival, there remains a chronic shortage of available donor organs. This article offers guidelines for the physician, discussing indications for liver transplantation, controversial selection issues, contraindications, and finally, the future of liver transplantation.
Contraindications↗
Hyperammonemia after heart-lung transplantation.
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Adult↗
Idiopathic thrombocytopenic purpura in a liver transplant recipient with previous primary biliary cirrhosis.
The loss of immunotolerance has been implicated in the pathogenesis of both primary biliary cirrhosis (PBC) and idiopathic, immune-mediated thrombocytopenic purpura (ITP). An association between these two autoimmune diseases has been well described. We describe a 41-year-old woman in whom ITP developed 457 days after liver transplantation for PBC while receiving immunosuppressive medications sufficient to maintain allograft function. Our case report, the first to describe post-transplant ITP in association with PBC, demonstrates the persistence of the underlying immune dysregulation of PBC after transplantation. The practice of decreasing the dosage of immunosuppressive medication to maintenance levels after transplantation may unmask the effects of this defect in immunotolerance.
Adult↗
Massive bleeding from multiple gastric ulcerations in a patient with lymphocytic gastritis and celiac sprue.
Uncontrolled hemorrhage and multisystem organ failure developed in a patient with celiac sprue, lymphocytic gastritis, and diffuse gastric ulceration. A proximal small bowel biopsy showed villous atrophy and lymphoplasmacytic infiltration consistent with celiac sprue. At autopsy, there were no gross or histologic findings to suggest lymphoma. The intestinal lymphocytic infiltrate was not monoclonal, and gene rearrangements were not detected. Lymphocytic gastritis is a rare cause of upper gastrointestinal hemorrhage, which may be the result of sensitivity to gluten or other luminal antigens. This diagnosis should be considered in cases of diffuse gastric ulceration with bleeding in which the endoscopic appearances are not typical of peptic ulcer disease or drug-induced erosions. Ideally, biopsies of gastric and duodenal mucosa should be performed to establish the diagnosis.
Aged↗
Late recurrent post-transplant primary biliary cirrhosis in British Columbia.
Late recurrent primary biliary cirrhosis (PBC) following orthotopic liver transplant remains a controversial topic. The first documented case of recurrence occurring in 16 patients transplanted for PBC and followed at the authors' institution for longer than one year is presented. A 54-year-old man transplanted for PBC developed a cholestatic pattern of enzyme elevation on post-transplant day (PTD) 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to 1:400). A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis, focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC was diagnosed. At the time of orthotopic liver transplant this patient received induction immunosuppression with OKT3 crossed over to cyclosporine (CsA), azathioprine (AZA) and prednisone. AZA was discontinued early and maintenance CsA tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of hepatobiliary enzymes) were below target at 114 to 166 ng/mL. Of the 16 patients, all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough levels on target) and AZA; the other two, including the patient with recurrent PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC has been within the target range. The authors speculate that the underlying defect in immunoregulation in PBC persists post-transplant and that in the patient without recurrent PBC this defect was unmasked by lowered maintenance immunosuppression--allowing recurrence of PBC in a previously stable liver allograft.
Biopsy, Needle↗
Lung dysfunction and chronic liver disease.
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Humans↗
Human immunodeficiency virus infection, the acquired immunodeficiency syndrome, and inflammatory bowel disease.
The objective of this study was to determine the effect of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) on inflammatory bowel disease (IBD). A retrospective survey of the medical records of St. Paul's Hospital and its AIDS-care physicians/gastroenterologists searching for patients with both HIV/AIDS and IBD was conducted. Of 1,839 hospitalized patients (4,459 hospital admissions) from 1989 to 1993, two patients with AIDS/HIV and IBD were found. The physician survey revealed four patients for a total of six patients. Four patients developed de novo IBD--two ulcerative colitis (UC), one Crohn's disease (CrD), and one indeterminate colitis (IC)--after HIV infection. Two patients had UC predating HIV seroconversion. The absolute CD4 count of patients with de novo IBD was 210-700 cells/ml at the time of IBD. The patient with IC maintained quiescent IBD from a CD4 count of 190-30 cells/ml. The other had many relapses before HIV seropositivity. With CD4 count depletion, disease activity improved. IBD medications were discontinued at a CD4 count of 130 cells/ml. Diarrhea returned at a CD4 count of 20 cells/ml; however, sigmoidoscopy was unremarkable, and mucosal biopsy revealed cryptosporidiosis without active UC. No patient had an AIDS-related illness during active IBD. Two patients followed to CD4 counts of < 30 cells/ml suffered AIDS-related infections with quiescent IBD. With a progressive decline in CD4 count, IBD disease activity may improve and remit. The CD4 count at which remission occurs may reflect severe immunodeficiency such that risk for AIDS-related infection is high. Active IBD may occur with lesser degrees of immunodeficiency.
Acquired Immunodeficiency Syndrome↗
Case Report: a patient with primary biliary cirrhosis and autoimmune hemolytic anemia.
Diseases of an autoimmune nature are well recognized in association with primary biliary cirrhosis. Although autoimmune thyroiditis and many rheumatological conditions are well described in primary biliary cirrhosis, autoimmune haematological diseases have been less well reported. We report on a 66 year old North American Indian man with coincident primary biliary cirrhosis and warm antibody haemolytic anaemia. This case report supports the suggestion of an association between autoimmune haemolytic anaemia and primary biliary cirrhosis.
Aged↗
Late acute rejection occurring in liver allograft recipients.
To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR) in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA) trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1). Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2). LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant). Mean trough CsA levels were lower in patients with LAR compared with those without (224 +/- 66 ng/mL versus 233 +/- 49 ng/mL) but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5 +/- 1.6 mg/day versus 6.5 +/- 2.9 mg/day, P = 0.007) and CsA nadir values (129 +/- 60 ng/mL versus 186 +/- 40 ng/mL, P = 0.03) were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83%) of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8%) receiving prednisone 5 mg/day or more (P = 0.004). In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.
Acute Disease↗
AIDS-related extrapulmonary Pneumocystis carinii infection presenting as a solitary rectal ulcer.
Extrapulmonary infection with Pneumocystis carinii, although uncommon, is increasingly recognized. Use of aerosolized pentamidine versus a systemic medication is thought to be a contributing factor due to the low concentrations of drug that are incapable of suppressing systemic infection. Infection with P carinii has been reported in every organ system including the gastrointestinal system. A 28-year-old acquired immunodeficiency syndrome patient receiving prophylaxis with aerosolized pentamidine who presented with a solitary rectal ulcer is reported. Initial biopsy was characteristic of extrapulmonary P carinii infection, with numerous organisms present. Occasional cytomegalovirus inclusion bodies were noted which may have been a copathogen but which were not treated. Treatment with intravenous pentamidine resulted in documented eradication of P carinii and complete resolution of the ulcer. Although lower gastrointestinal pneumocystosis has been described without ulceration, this is the first description of rectal ulceration presenting as the initial manifestation of extrapulmonary pneumocystosis.
AIDS-Related Opportunistic Infections↗