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Introduction The liver is frequently involved in systemic AL amyloidosis in association with B-cell dyscrasias, and some of the hereditary forms mainly apolipoprotein ApoAI amyloidosis. Extensive hepatic amyloid infiltrate can lead to liver failure. We report here the features, disease course, management and outcome of 28 patients with end-stage hepatic amyloidosis. Methods Twenty-eight patients with amyloid related liver failure, median age 53 (28–70) years. All patients had hepatomegaly, 14 (50%) had jaundice, ten had ascites, four patients had encephalopathy, and three were in renal failure. The amyloid type was determined by immunohistochemistry, serum/urine electrophoresis and DNA analysis. All patients had comprehensive systemic, cardiac and neurological evaluation. Results 22 patients had AL amyloidosis due to B-cell dyscrasias; none were eligible for chemotherapy. Six cases had hereditary amyloid due to variant fibrinogen A α chain, AFib (1) and apolipoprotein ApoAI (5). Extrahepatic amyloid deposits were present in all cases. 11/22 patients with AL liver failure were listed for liver transplantation (LT). All six patients with ApoAI or AFib amyloidosis who had liver and renal failure were considered for combined liver/kidney transplant (LKT). Nine AL patients received LT as a rescue procedure and two died with complications of hepatic rupture or multi-organ failure on the waiting list. The remaining 11 AL cases all died within 2–16 weeks with progressive cholestasis and subacute liver failure. Actuarial 1-year survival post LT in AL was 75%, 2-year 50%. Early mortality post LT was due to septic episodes, nephrotic syndrome and renal failure, and medium-term due to progressive amyloidosis and multiple organ falure. Only two AL patients exhibited over 5 year survival. Both had predominantly liver and splenic amyloid with no cardiac or renal involvement and were treated with stem cell transplant (SCT) after LT. Three ApoAI cases had successful LKT but two died with complications of liver failure on the wait list. The AFib patient has normal graft function at 13 years post LKT (cumulative LKT survival for ApoAI and AFib 100%). Conclusion LT is life saving for liver failure due to AL amyloidosis, but the outcome is ultimately determined by severity of systemic disease at the time of LT and eligibility for efficient treatment for AL after LT. Sequential SCT was associated with long-term remission in two LT recipients. The excellent outcome of LT in both ApoAI and AFib hereditary systemic amyloidosis strongly supports its use for these indications.

Results: Overall, 160 (41.5%) patients achieved successful downstaging of HCC to within the Milan criteria. During the follow-up, 82 eventually dropped off the waiting list for LT due to tumor progression, with estimated dropout rates at 1, 2, and 5 years of 46.7%, 70.2%, and 84.6%, respectively. Thirty-seven patients ultimately underwent LT. The overall post-transplant survival rates at 1, 2, and 5 years were 89.2%, 70.3%, and 54.6%, while the corresponding rates for recurrence-free survival were 74.7%, 71.8%, and 66.3%, respectively. Multivariate analysis indentified alpha-fetoprotein (AFP) levels 100 ng/ml at LT (P = 0.003), maximum tumor size 7 cm (P = 0.002), and the lack of complete necrosis by TACL (P = 0.048) as independent predictors of HCC recurrence after LT. Patients with none of these risk factors had an excellent post-transplant outcome, with an 87.5% probability of recurrence-free survival up to 6 years. Conclusions: These long-term results may contribute to the database for optimizing management of LT candidates with downstaged HCC. Although overall outcome of downstaged patients falls short of that of those initially meeting the Milan criteria, carefully selected patients can have long-term survival post-LT. Based on our data, patients with a maximum tumor size

A 62-year-old man with a history of chronic hepatitis B cirrhosis presented with deteriorating liver function. The serum α fetoprotein (AFP) level was 253 kU/l (normal upper limit

Non-Myeloablative Preparative Regimen in Children with Severe Organ Dysfunction Undergoing Bone Marrow Transplantation

Between January 1989 and June 1993, a total of 470 liver transplantations were performed at King's College Hospital. Thirty-seven transplantations were performed in 34 patients with liver-based metabolic disease. There were 16 females and 18 males with a median age of 19 years (range 1 month to 62 years). There were 14 patients under 16 years of age. The indications for liver transplantation were Wilson's disease (n = 16), alpha 1-antitrypsin deficiency (n = 10), tyrosinaemia (n = 2), primary hyperoxaluria type 1 (PH1; n = 2), congenital haemochromatosis (n = 1), familial amyloidotic polyneuropathy (FAP; n = 1, familial hypercholesterolaemia) (n = 1) and Crigler-Najjar syndrome type I (CNS1; n = 1). These included two patients who received combined heart-liver grafts for familial hypercholesterolaemia and FAP, respectively. Two patients received combined liver-kidney transplants for PH1. There were four deaths: from sepsis (n = 2), acute hepatic vein obstruction in a left lateral segment graft (n = 1) and portal vein thrombosis with liver necrosis (n = 1). Three patients were retransplanted, one for chronic rejection and two for hepatic artery thrombosis, giving an overall graft survival of 81% and patient survival of 88% (30/34), at a mean follow-up of 34 months (range 10-64 months).

BACKGROUND: Experience of liver transplantation in haemophiliacs with end stage hepatitis C liver disease is limited and particularly difficult questions are raised when there is also HIV infection. AIMS: This is the first report in Great Britain to describe the operative replacement therapy and initial outcome in four haemophiliacs with end stage HCV cirrhosis. PATIENTS: Two patients had factor VIII, one had factor IX, and one had factor X deficiency. One patient had also contracted HIV infection from factor replacement but had no AIDS defining illnesses. METHODS: Intraoperatively patients were given either factor VIII infusions, factor IX bolus, or fresh frozen plasma, according to formulae devised to calculate exact clotting factor requirements. Baseline preoperative coagulation studies included prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and factor VIII, IX, and X concentrations. Factor concentrations were then assayed at 12, 24, 48, and 72 hours postoperatively. RESULTS: Postoperatively all patients had coagulation factor concentrations sustained within the normal ranges by 72 hours unsupported (137, 125, 95, 104 IU/dl), representing de novo synthesis by the graft. Transfusion requirements during the operative and immediate post-transplant period were no greater than those of patients without clotting disorders. Two patients had episodes of bleeding postoperatively, one of which was fatal, occurring at the site of a previous untreated subdural bleed. In both instances the bleeding occurred in the presence of normal concentrations of clotting factor. The remaining three patients are at 6, 6, and 12 months post-transplant and remarkably improved clinically with sustained factor concentrations. One patient has evidence of graft dysfunction from HCV recurrence and all have evidence of recurrent viraemia with HCV on polymerase chain reaction studies. CONCLUSIONS: Orthotopic liver transplantation should be considered in haemophiliac patients with end stage liver disease from hepatitis C infection with or without concomitant HIV infection. Their clinical condition is likely to be greatly improved by orthotopic liver transplantation and the haemophilia cured with only a small risk of severe graft dysfunction from recurrent HCV infection.