Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantation.

BACKGROUND: Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post-mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. AIMS: To assess the results of testing for iron overload in liver transplant candidates at our institution. METHODS: Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation ≥50% and ferritin ≥250 ng/mL underwent liver biopsy graded for iron. Patients with 3-4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. RESULTS: Eight hundred and fifty-six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty-seven patients (34%) had transferrin saturation ≥50% and ferritin ≥250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty-three patients underwent liver biopsy. Twenty-six patients (17%) had 3-4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. CONCLUSIONS: Non-HFE-related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation.

Improvement in dilated cardiomyopathy after bariatric surgery.

BACKGROUND: Young severely obese patients with advanced heart failure may not be suitable candidates for cardiac transplantation because of surgical morbidity and availability of adequately sized donor hearts. METHODS AND RESULTS: We report 2 patients with severe systolic dysfunction and Class IV heart failure despite maximal medical therapy who were considered for cardiac transplantation. Because of their severe obesity, transplantation was not considered an optimal therapy, and both were referred for bariatric surgery. The individuals had nonischemic cardiomyopathy. Both underwent laparoscopic vertical gastrectomy, minimizing surgical risk while providing definitive reduction in gastric volume. They experienced substantial weight loss and resolution of dyspnea. Inotrope infusion was discontinued in 1 dobutamine-dependent individual. They achieved weight reduction of 46 to 52 kg after the surgery. End-systolic volume index improved from 64 to 49 mL/m(2) and from 66 to 39 mL/m(2). Left ventricular ejection fraction improved from 20% to 45% and from 25% to 39%. They remain symptom-free and are no longer listed for transplant at 2 years' follow-up. CONCLUSIONS: Bariatric surgery may lead to improvement in left ventricular systolic dysfunction in young morbidly obese individuals with nonischemic cardiomyopathy. Potential explanations for the improvement in left ventricular function include reduced direct toxic effects of adiposity on cardiomyocytes and improved hemodynamics after weight loss. The potential for bariatric surgery to provide an alternative to heart transplantation in extreme obesity merits further study.

Weight loss composition: the effects of exercise following obesity surgery as measured by bioelectrical impedance analysis.

BACKGROUND: Sudden weight loss following bariatric operations for morbid obesity, such as the duodenal switch (DS), can result in a concurrent decrease in lean body mass. Several methods for tracking body composition, such as bioelectrical impedance analysis (BIA), are available to monitor these changes. One method to offset the negative effects of sudden weight loss on body mass composition may be exercise. METHODS: 100 patients who had undergone the DS operation for morbid obesity were classified as exercisers and non-exercisers based on self-reporting. Their body mass compositions were measured using BIA preoperatively and at 0.75, 1.5, 3, 6, 9, 12, and 18 months postoperatively. RESULTS: At no study interval did postoperative percent changes in weight loss differ between the exercise and non-exercise groups. At 18 months postoperatively, the exercise group showed a 28% higher loss of fat mass and an 8% higher gain in lean body mass than the non-exercise group. CONCLUSION: Exercise positively influences body mass composition following the DS. BIA can be successfully employed to monitor changes, diagnose deficiencies, and formulate treatment recommendations.

Nutritional markers following duodenal switch for morbid obesity.

BACKGROUND: Laparoscopic duodenal switch with gastric reduction (LapDS) is a minimally invasive hybrid operation combining moderate intake restriction with moderate malabsorption for treatment of morbid obesity. In LapDS, both the quantity of food ingested and the efficiency of digestion are reduced. METHODS: A cohort of 589 sequential LapDS patients had laboratory studies drawn annually. Serum markers for calcium, iron and protein metabolism and for hepatic function were analyzed using SAS statistical software. RESULTS: There were 95 men and 494 women. Mean age was 44 years, mean BMI 50 kg/m(2) and mean preoperative weight 142 kg. Although mean hemoglobin decreased below reference and mean parathyroid hormone (PTH) increased above reference, similar to abnormal values reported after Roux-en-y gastric bypass, both hemoglobin and calcium in LapDS readily returned to within the reference range following supplementation with iron and calcium respectively. Mean iron, corrected calcium, alkaline phosphatase, albumin, total protein, aspartate aminotransferase (AST), alanine transaminase (ALT), and bilirubin remained within the normal range. CONCLUSION: LapDS is not associated with broad nutritional deficiencies. Annual laboratory studies, which are required following any type of bariatric operation, appear to be sufficient to identify unfavorable trends. In selected patients, additional iron and calcium supplementation are effective when indicated.

Laparoscopic technique for performing duodenal switch with gastric reduction.

BACKGROUND: The duodenal switch procedure with gastric reduction (DS) is a hybrid procedure for morbid obesity that combines moderate intake restriction with moderate malabsorption. This report describes the laparoscopic hand-assisted technique for the duodenal switch procedure (LapDS). METHODS: Restriction is achieved via a greater curvature gastrectomy, reducing gastric capacity to 120 ml. The malabsorptive component is constructed by dividing the duodenum 4 cm distal to the pylorus and anastomosing the proximal duodenum to the distal 250 cm of ileum. The biliopancreatic limb is anastomosed to create a 100 cm common channel. Laparoscopic cholecystectomy, cholangiogram, liver biopsy and appendectomy are performed in conjunction with DS. RESULTS: 345 LapDS procedures (27 lap-assisted; 318 hand-assisted) were performed between September 1999 and February 2002. There were 299 women and 46 men with a mean age of 43 years (range 19-67 years). Mean BMI was 50 (range 36-118 kg/m(2)). Mean operating time was 201 minutes (range 105-480). The median length of hospital stay was 3.0 days (range 2-22 days, excluding one outlier). There were 7 conversions to open laparotomy, 14 reoperations, and 21 readmissions. There were 3 pulmonary emboli, 2 deep venous thromboses, and 4 perioperative proximal anastomotic strictures. There were no deaths. Mean percent excess weight loss at 6, 18, and 24 months was 51%, 89%, and 91%, respectively. CONCLUSION: Laparoscopic assisted duodenal switch procedure can be performed safely with acceptable operative times and without excess morbidity or mortality.

Immunosuppression impact on long-term cardiovascular complications after liver transplantation.

BACKGROUND: With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed. OBJECTIVE: The objective of this study is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation. METHODS: Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were >/=18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx. RESULTS: At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group. CONCLUSION: Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease.

Thoracic radiology in kidney and liver transplantation.

Renal transplantation accounts for more than half of all solid organ transplants performed in the U.S., and the liver is the second most commonly transplanted solid organ. Although abdominal imaging procedures are commonplace in these patients, there has been relatively little attention paid to thoracic imaging applications. Preoperative imaging is crucial to aid in the exclusion of infectious or malignant disease. In the perioperative time period, thoracic imaging focuses both on standard intensive care unit care, including monitoring devices and their complications, and on the early infections that can occur. Postoperative management is divided into three time periods, and the principles governing the occurrence of infections and malignancies are reviewed. Anatomic and pathologic aspects unique to kidney and liver transplantation patients are also discussed.

Retransplantation for hepatic allograft failure: prognostic modeling and ethical considerations.

Retransplantation already accounts for 10% of all liver transplants performed, and this percentage is likely to increase as patients live long enough to develop graft failure from recurrent disease. Overall, retransplantation is associated with significantly diminished survival and increased costs. This review summarizes the current causes of graft failure after primary liver transplant, prognostic models that can identify the subset of patients for retransplantation with outcomes comparable to primary transplantation, and ethical considerations in this setting, i.e., outcomes-based versus urgency-based approaches.

Graft failure from severe recurrent primary sclerosing cholangitis following orthotopic liver transplantation.

UNLABELLED: Speculation that primary sclerosing cholangitis (PSC) may recur in the transplanted liver is based on the relative increase in frequency of biliary abnormalities and histologic evidence of periportal fibrosis without other causes. A recent study demonstrated almost 9% of patients undergoing liver transplantation (OLT) for primary sclerosing cholangitis (PSC) develop recurrent sclerosing cholangitis although the patient and graft survival is not different from those in whom recurrence does not develop. Most reports of PSC recurrence post-OLT estimate rates of 1% to 14%, but to date, no center has reported rapidly progressive fibro-obliterative cholangitis leading to graft failure. CASE REPORT: DV was a 39-year-old white man with ulcerative colitis, since age 21, who developed jaundice and pruritus in 1992. ERCP and liver biopsy were consistent with PSC, and he developed thrombocytopenia and bleeding esophageal varices. He underwent an uneventful OLT in May 1994 with an ABO-compatible organ and normal ischemic times. There was no evidence of postoperative cytomegalovirus infection, hepatic artery thrombosis, or rejection. In October 1994, mild abnormalities of liver function tests (LFTs) led to liver biopsy that revealed inflammatory infiltrate in triad with spillover into lobules and mild periportal fibrosis. LFTs normalized without any treatment, but in February 1995 repeat liver biopsy for increased LFTs revealed moderate periportal fibrosis with inflammatory cells in triads and lobules. Viral shell and CMV titers were negative. No evidence of infectious etiology or rejection was noted. The patient was started on ursodeoxycholic acid at that time and percutaneous transhepatic cholangiogram (PTC) revealed marked narrowing of the intrahepatic ducts. Esophagogastroduodenoscopy (EGD) revealed esophageal varices. Hepatic arteriogram and Doppler ultrasound were negative. He developed progressive graft failure, and died at home while awaiting re-transplant. CONCLUSIONS: Although most series report mild recurrence of PSC following OLT, this case illustrates that early, severe recurrence of PSC may occur, leading to graft failure and need for re-transplantation.

Comparative analysis of outcome following liver transplantation in US veterans.

The purpose of this study was to evaluate whether there was a difference in mortality following orthotopic liver transplantation (OLT) in a US veteran (VA) population (n = 149) compared to a non-VA (university) population (n = 285) and what factors could explain this difference. Survival following OLT for 149 VA patients was compared with that of 285 university patients. By Kaplan-Meier survival analysis, VA patients had higher mortality than university patients with respective 1-year, 3-year, and 5-year survival of 82%, 75%, and 68% vs. 87%, 82%, and 78% (p = 0.006). Gender, etiology of end-stage liver disease (ESLD) and donor age (i.e. older than 34 years) also significantly influenced survival. However, when donor and recipient age, gender, model for end-stage liver disease (MELD) score, and etiology of liver disease were included with hospital status in a multivariate Cox proportional hazards model, the VA population did not have higher mortality. A final model to predict mortality following transplantation was derived for all 434 patients where individuals were assigned risk scores based on the equation R = 0.219 (gender) + 0.018 (donor age) + 0.032 (recipient age) + 0.021 (MELD), where recipient age, donor age, and MELD score are the respective continuous variables and gender = 1 (men) and 0 for women (c-statistic = 0.71).

Tumor necrosis factor-alpha promoter polymorphisms and the risk of rejection after liver transplantation: a case control analysis of 210 donor-recipient pairs.

After orthotopic liver transplantation (OLT), allograft rejection remains an important problem and is the major reason that immunosuppressive therapy must be administered. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory mediator that is central to the immune response, and intragraft expression of this cytokine is increased during acute cellular rejection (ACR). Polymorphisms within the TNF promoter have been identified and correlated with alterations in production. The aims of this study were to determine if an individual patient's propensity to develop ACR is related to the presence of these genetic polymorphisms (either alone or in combination) within donor and recipient tissue and to determine if these polymorphisms affect patient survival after OLT. The study group consisted of 210 patients who underwent OLT between 1989 and 1999 with at least 6 months survival, including 42 cases who had evidence of acute cellular rejection (biopsy-proven, elevated enzymes, and response to increased immunosuppression) and were matched 4:1 to controls (n = 168) with similar age, gender, underlying liver disease, date of transplant, and baseline immunosuppression. The underlying liver diseases were hepatisis C virus (HCV)/alcohol (70), HCV alone (50), alcohol (30), primary biliary cirrhosis (15), primary sclerosing cholangitis (15), autoimmune hepatitis/cirrhosis (10), cryptogenic (15), and hepatitis B virus (HBV) (5). DNA was extracted from paraffin-embedded donor and recipient liver tissue (total 420 samples), amplified, and sequenced for TNF single-nucleotide polymorphisms (TNFA-308 A/G and TNFA-238 A/G). We found no differences between the TNF allelic distributions among donors without liver disease (presumably representative of a normal control population) and patients with end-stage liver disease undergoing OLT. Multivariate analysis revealed no association with TNF polymorphisms (within donor or recipient tissue) and rejection risk or patient survival after transplantation. In this large case control analysis of patients undergoing liver transplantation for diverse etiologies, TNF promoter polymorphisms were not independently associated with rejection or survival.

Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure.

OBJECTIVE: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. METHODS: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. RESULTS: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). CONCLUSIONS: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.