BACKGROUND The outcomes of kidney transplantation and immunosuppression in people infected with human immunodeficiency virus (HIV) are incompletely understood. METHODS We undertook a prospective, nonrandomized trial of kidney transplantation in HIV-infected candidates who had CD4+ T-cell counts of at least 200 per cubic millimeter and undetectable plasma HIV type 1 (HIV-1) RNA levels while being treated with a stable antiretroviral regimen. Post-transplantation management was provided in accordance with study protocols that defined prophylaxis against opportunistic infection, indications for biopsy, and acceptable approaches to immunosuppression, management of rejection, and antiretroviral therapy. RESULTS Between November 2003 and June 2009, a total of 150 patients underwent kidney transplantation; survivors were followed for a median period of 1.7 years. Patient survival rates (±SD) at 1 year and 3 years were 94.6±2.0% and 88.2±3.8%, respectively, and the corresponding mean graft-survival rates were 90.4% and 73.7%. In general, these rates fall somewhere between those reported in the national database for older kidney-transplant recipients (≥65 years) and those reported for all kidney-transplant recipients. A multivariate proportional-hazards analysis showed that the risk of graft loss was increased among patients treated for rejection (hazard ratio, 2.8; 95% confidence interval [CI], 1.2 to 6.6; P = 0.02) and those receiving antithymocyte globulin induction therapy (hazard ratio, 2.5; 95% CI, 1.1 to 5.6; P = 0.03); living-donor transplants were protective (hazard ratio, 0.2; 95% CI, 0.04 to 0.8; P = 0.02). A higher-than-expected rejection rate was observed, with 1-year and 3-year estimates of 31% (95% CI, 24 to 40) and 41% (95% CI, 32 to 52), respectively. HIV infection remained well controlled, with stable CD4+ T-cell counts and few HIV-associated complications. CONCLUSIONS In this cohort of carefully selected HIV-infected patients, both patient- and graft-survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection. The unexpectedly high rejection rates are of serious concern and indicate the need for better immunotherapy.

BACKGROUND Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in HIV-infected patients due to reportedly poor outcomes. METHODS This prospective U.S. multicenter cohort study compared patient and graft survival in 89 HCV-HIV coinfected versus 2 different controls groups: 235 HCV monoinfected LT controls and all U.S. transplant recipients ≥65 years. RESULTS The 3-year patient and graft survival rates (95% CI) were 60% (47–71%) and 53% (40–64%) in HCV-HIV versus 79% (72–84%) and 74% (66–79%) in HCV recipients (both p<0.001) and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among HCV-HIV patients, older donor age (HR=1.3 per decade), combined kidney-LT (HR=3.8), HCV-positive donor (HR=2.5), and body mass index (BMI) less than 21 kg/m2 (HR=3.2) were independent predictors of graft loss. In patients without these latter 3 factors, patient and graft survival were similar to those in U.S. LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher in HCV-HIV versus HCV (log rank p=0.02) but cumulative incidence of severe HCV disease (29% versus 23% at 3 years, respectively) were not significantly different (p=0.21). CONCLUSIONS Patient and graft survival are lower in HCV-HIV compared to HCV alone LT patients. Importantly, rates of treated acute rejection but not HCV disease severity are significantly higher in HCV-HIV compared to HCV recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients but recipient and donor selection as well as management of acute rejection strongly influence outcomes.

GP73 is an accurate serum marker for the detection of HCC and its recurrence after surgery, with higher sensitivity and specificity than AFP. Clinical implementation of serum GP73 measurement as a standard test for HCC is recommended.

ObjectiveTo assess the long-term incidence of venous complications, including portal vein and hepatic vein stenoses, in both whole cadaveric and reduced-size cadaveric and living related liver transplants in a pediatric population, and to assess the therapeutic modalities in the treatment of these lesions. Summary Background DataA shortage in appropriate-sized liver grafts for pediatric patients led to the use of segmental liver grafts, which became the predominant graft used in 325 of 600 (54%) transplants at the authors' institution. To assess the long-term impact of this strategy, the authors examined the incidence of late (Ͼ90 days) venous complications and the efficacy of all therapeutic interventions. MethodsSix hundred pediatric liver transplants were performed in 325 patients, with reduced-size or split (RSS; n ϭ 207), living related (LRD; n ϭ 118), or full-size cadaveric grafts (FS; n ϭ 275) from 1988 to 2000. All transplants identified with late portal vein or vena caval stenoses or thromboses from a cohort of 524 grafts with survival greater than 90 days were reviewed for demographics, symptoms, therapeutic intervention, recurrence, morbidity, and mortality. ResultsFifty lesions were identified in 49 patients (38 portal vein and 12 hepatic vein-cava stenoses). Sex distribution was similar between portal vein and hepatic vein to cava, as was the mean patient age. Portal vein stenoses occurred in 32 LRD, 3 RSS, and 3 FS, while hepatic vein-cava stenoses occurred in 2 LRD, 8 RSS, and 2 FS. In the 38 portal vein stenoses, 9 had prior perioperative portal vein and/or 5 hepatic artery thrombectomies. Portal vein stenoses were identified after bleeding (17/38), ascites (6/38), increased liver function tests (6/38), splenomegaly (5/38), or screening ultrasound (4/38). Portal vein stenosis was associated most often with cryopreserved vein for portal conduits. Excluding conduits, the incidence of late portal vein complications was reduced to 1%. Lesions became symptomatic at a mean of 50.8 Ϯ 184.2 months posttransplant. All patients underwent venous angioplasty with a 66% (25/38) success rate, while 7 of 25 required further angioplasty and stenting. In the 13 unsuccessful angioplasties, 8 required surgical shunts for complete portal vein thrombosis. Recurrence occurred in 9 patients: all were amenable to stenting. Nine patients (24%) eventually died of sepsis (4) and surgical deaths at shunt or retransplant (5). Hepatic vein-cava stenoses occurred after a mean of 37.2 Ϯ 35.2 months, presenting with ascites (n ϭ 10), increased liver function tests (n ϭ 2), and splenomegaly (n ϭ 2). All patients were diagnosed by venogram and managed by balloon dilatation alone (n ϭ 6) or stented (n ϭ 4), with an 80% (10/12) success, with two late recurrences amenable to repeat angioplasty or stenting. Long-term survival was 80% at 1 year. ConclusionsThe use of segmental grafts without venous conduits is not associated with a significant rate of long-term venous complication. When late venous complications do occur, venous angiop...

Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.

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tients in the half-life of A77 1726, the known risk of toxic effects on the liver, and the requirement for doses that exceed recommendations for rheumatoid arthritis, this therapy should be monitored by fre-quent analysis of blood levels of the active metabolite and liver enzymes.

While regional heterogeneity in islet distribution has been well studied in rodents, less is known about human pancreatic histology. To fill gaps in our understanding, regional differences in the adult human pancreas were quantitatively analyzed including the pathogenesis of type 2 diabetes (T2D). Cadaveric pancreas specimens were collected from the head, body and tail regions of each donor, including subjects with no history of diabetes or pancreatic diseases (n = 23) as well as patients with T2D (n = 12). The study further included individuals from whom islets were isolated (n = 7) to study islet yield and function in a clinical setting of islet transplantation. The whole pancreatic sections were examined using an innovative large-scale image capture and unbiased detailed quantitative analyses of the characteristics of islets from each individual (architecture, size, shape and distribution). Islet distribution/density is similar between the head and body regions, but is >2-fold higher in the tail region. In contrast to rodents, islet cellular composition and architecture were similar throughout the pancreas and there was no difference in glucose-stimulated insulin secretion in islets isolated from different regions of the pancreas. Further studies revealed preferential loss of large islets in the head region in patients with T2D. The present study has demonstrated distinct characteristics of the human pancreas, which should provide a baseline for the future studies integrating existing research in the field and helping to advance bi-directional research between humans and preclinical models.