Cirrhotic patients with hereditary hemochromatosis (HHC) have an increased risk of primary liver cancer (PLC). The purpose of this study was to determine the prevalence of primary liver cancer in patients with HHC undergoing orthotopic liver transplantation (OLT). Five liver transplant centers were surveyed; clinical and pathological data on 37 patients with HHC undergoing OLT were retrospectively collected and analyzed. The diagnosis of HHC was established by a combination of serum transferrin-iron saturation, hepatic iron index (HII), and/or pattern of liver iron staining. The diagnosis of HHC had been unsuspected before OLT in 13 of 37 (35%). Primary liver cancer was found in the explants of 10 of 37 patients (27%) and was unsuspected in 7 of 10 (70%); 8 were hepatocellular carcinoma, and 2 were cholangiocarcinoma; foci of hepatocyte dysplasia were ereditary hemochromatosis (HHC) is the most H common genetic disease in Caucasians, with a prevalence of 3 to 5 per 1,000.' The complications of HHC result from the deposition of iron in multiple organs, leading to cirrhosis, cardiomyopathy, arthropathy, hypogonadism, and diabetes mellitus. There is a strong association between HHC and primary liver cancer (PLC), particularly in HHC patients with fibrosis or c i r r h o~i s .~,~ The reported prevalence of PLC in HHC ranges from 7.5% to 36%,4,5 and PLC is reported to be the cause of death in up to 45% of HHC patient^.^ However, there are no data on the prevalence of PLC among HHC patients undergoing orthotopic liver transplantation (OLT) or the frequency with which a definite diagnosis of HHC is established before OLT. Therefore, the primary purpose of this study was to examine the prevalence of known and incidental PLC in HHC patients undergoing OLT. Secondary goals were to examine 1-year survival rate following OLT in HHC patients, and to determine how often the diagnosis of HHC was established before OLT.found in 6 additional patients. Mean (GEM) hepatic iron content and HI1 in 20 patients without prior phlebotomy or bleeding were 17.2 mg/g dry weight (k2.9) and 5.5 (+0.8), respectively. The overall 1-year survival rate after OLT in the 37 HHC patients was 58% (v 55% for HHC patients with PLC). We draw the following conclusions: (1) the diagnosis of HHC is often unsuspected before OLT, and HHC should be evaluated pretransplantation by direct and indirect markers; (2) HHC patients undergoing OLT have a high prevalence of primary liver cancer, the majority being unsuspected; and (3) HHC patients have poorer than average survival after OLT, which cannot be explained solely by the presence of concomitant PLC.

Recent preliminary reports suggest a poor outcome of orthotopic liver transplantation for patients with hemochromatosis. We analyzed an institutional experience with orthotopic liver transplantation for hemochromatosis, focusing on factors contributing to increased morbidity and mortality. Between March 1988 and October 1992, nine of 249 adults (3.6%) undergoing orthotopic liver transplantation had hemochromatosis. Mean age was 53 yr (range, 42 to 62 yr), and eight of nine patients were men. The diagnosis of hemochromatosis was based on transferrin saturation > 62% and hepatic iron index > 2.0. Only two patients were known to have hemochromatosis before liver transplantation. All nine patients underwent standard cardiac evaluation before transplantation, and no patient had detectable pre-existing cardiac disease. One patient had a major operative cardiac complication as a result of pulmonary embolism and made a full recovery. Postoperatively, congestive heart failure developed in three patients and four patients had arrhythmias. One patient is undergoing phlebotomy for post-transplant cardiac complications from hemochromatosis. Two patients had primary hepatic tumors in the explant liver. There were four deaths caused by multiorgan failure with congestive heart failure (1), infection (2), and/or malignancy (2). Five patients are alive 3 to 25 mo post-transplant. The actuarial survival of the nine patients was 53% at 25 mo vs. 89% for 18 age- and sex-matched control transplant recipients (p = 0.1) and 81% for all other adult liver transplant recipients (p < 0.01). In five of seven patients, post-transplant liver biopsies revealed hepatic iron accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with hepatic iron overload who undergo orthotopic liver transplantation (OLT) have a worse 1-year survival than those who undergo transplantation for other indications; the long-term outcome in this population is unknown. The purpose of this study is to report long-term follow-up after OLT in a cohort of patients with hepatic iron overload. Five liver transplant centers in the United States reported follow-up data on 37 patients receiving a first liver transplant who had severe hepatic iron overload in their native livers. KaplanMeier 5-year survival among these patients was compared with survival data from all age-matched liver transplantations reported to the United Network for Organ Sharing (UNOS) over the same time period (1987 to 1993). The 5-year survival rate after OLT was 40% in the hepatic iron overload group compared with an overall survival rate of 62% for all patient groups from the UNOS registry (P ‫؍‬ .0009). Although sepsis was the cause of 53% of all deaths occurring within the first year after OLT, cardiac complications accounted for 50% of the late mortality in patients with hepatic iron overload. In conclusion, longterm survival after OLT is significantly decreased in patients with hepatic iron overload. Infectious and cardiac complications are the most common causes of death in these patients. Further studies are needed to define the relationship between hepatic iron overload and mortality and to examine the effect of iron depletion on outcome after OLT in this patient population.

Two patients with liver failure secondary to isoniazid hepatotoxicity were successfully treated with orthotopic liver transplantation. A 49-year-old man received isoniazid prophylaxis for a positive tuberculin test, and a 60-year-old woman was treated for active pulmonary tuberculosis with isoniazid, rifampin, and pyrazinamide. Both patients developed hepatic failure 4 and 1.5 months after initiation of antituberculous drug therapy, respectively. Liver transplantation was performed for progressive hepatic failure and was successful in both patients. The patient with active pulmonary tuberculosis was successfully treated with a modified antituberculous drug regimen while taking standard doses of immunosuppressive drugs after transplantation. In conclusion, liver transplantation is feasible and effective therapy for patients with isoniazid-induced hepatic failure, and active pulmonary tuberculosis may represent a relative rather than absolute contraindication to transplantation.

Comparisons of the oxygen-handling properties of calcined CeO,, CeO2-AI2O3, RhO,-CeO,, Rh0,-CeO2/AI,O3 and La,O,-CeO, materials are made on the basis of their experimentally observed abilities to bring about R,-type homophase oxygen isotope equilibration of an equimolar (1602 + 1802) mixture at room temperature, and/or to induce low onsettemperatures (ca. 550 K) for pairwise heterophase oxygen isotope-exchange between gas-phase 1802 and oxygen-1 6 species from the oxide. Those oxygen equilibration/exchange processes were enhanced over precalcined Rho,-CeO, materials prepared from chloride-free precursors, but not over La,03-CeO,. That difference contrasted with expectations for similar concentrations of dopant-related, anion vacancy creation in each material, based upon XRD observations of the incorporation of each dopant into a slightly expanded CeO, (fluorite) lattice. Consideration is given not only to conventional contribution to oxygen equilibration/exchange by residual Rho, species at the Rho,-CeO, surfaces, but also to ways in which bulk-incorporated, variable-valency rhodium ions can indirectly facilitate those processes.

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