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Background Nonalcoholic steatohepatitis (NASH), a clinically aggressive variant of nonalcoholic fatty liver disease (NAFLD), is becoming an increasingly common indication for liver transplantation (LT); however, relatively little is known regarding its clinical course post-LT. The aim of the current study is to describe disease recurrence and clinical course after LT. Methods All surviving patients transplanted for NASH at the authors' institution had transient elastography (TE) to evaluate hepatic steatosis and fibrosis. The charts of deceased patients were reviewed for liver biopsy to evaluate for disease recurrence. Finally, causes of mortality in these patients were evaluated. Results Of the 103 patients who met criteria, 56 had TE, whereas 34 had a liver biopsy. Steatosis was detected in 49 (87.5%) of the patients who had a TE and were defined to have recurrent NAFLD. Most patients had liver stiffness measurements consistent with no fibrosis (42.9%) or F1-F2 fibrosis (30.4%). Advanced fibrosis was noted in 26.8%, whereas 5.4% had cirrhosis but were clinically compensated. In patients with liver biopsy, 88.2% had recurrent NAFLD, whereas 41.2% had recurrent NASH. Bridging fibrosis was noted in 20.6% of patients but no patients had cirrhosis. Within the cohort, 32 patients died with the leading cause of mortality cancer (25%), infectious complications (25%), and cardiovascular disease (21.9%). Only 9% of deaths were attributable to graft cirrhosis. Conclusions Recurrent NAFLD is common post-LT occurring in nearly 88% of all patients, whereas nearly a quarter of patients were noted to have advanced fibrosis.

BACKGROUND Hepatocellular carcinoma is a major cause of death among patients with cirrhosis. A standardized approach of multimodality therapy with intent-to-treat by transplantation for all patients with hepatocellular carcinoma was instituted at our transplant center in 1997. Data were prospectively collected to evaluate the impact of multimodality therapy on posttransplant patient survival, tumor recurrence, and patient survival without transplantation. METHODS All patients with hepatocellular carcinoma were eligible for multimodality therapy. Multimodality therapy consisted of hepatic resection, radiofrequency ablation, transarterial chemoembolization, transarterial chemoinfusion, yttrium-90 microsphere radioembolization, and sorafenib. RESULTS Approximately 715 patients underwent multimodality therapy; 231 patients were included in the intent-to-treat with transplantation arm, and 484 patients were treated with multimodality therapy or palliative therapy because of contraindications for transplantation. A 60.2% transplantation rate was achieved in the intent-to-treat with transplantation arm. Posttransplant survivals at 1 and 5 years were 97.1% and 72.5%, respectively. Tumor recurrence rates at 1, 3, and 5 years were 2.4%, 6.2%, and 11.6%, respectively. Patients with contraindications to transplant had increased 1- and 5-year survival from diagnosis with multimodality therapy compared with those not treated (73.1% and 46.5% versus 15.5% and 4.4%, P

BACKGROUND: Single pediatric kidney transplantation (SKT) in adult recipients has traditionally been considered a high risk because of concerns of technical complications leading to poor graft outcomes. The primary goal of this single-center, retrospective analysis was to compare outcomes after SKT to standard-criteria deceased-donor kidney transplantation (SCDKT). METHODS: We compared outcomes in adult recipients after SKT (n=31; mean donor weight, 27 kg); SCDKT (n=283); pediatric en bloc (n=21), living-donor (n=275), and extended criteria-donor (n=100) kidney transplantations. RESULTS: The death-censored 5-year graft survival after SKT was significantly superior to SCDKT (81.4% vs. 74.5%, P=0.02). The serum creatinine level at 5 years after transplantation was significantly lower in SKT compared with that in SCDKT (1.2 vs. 1.6 mg/dL, P

Background En bloc kidneys from pediatric donors have been considered suboptimal for transplantation to adult recipients and their outcomes have rarely been compared with living donor kidney transplantation (LDKT). Traditionally, there has been hesitancy in transplanting en bloc kidneys from donors weighing less than 10 kg due to high risk of technical complications. Methods Retrospective chart reviews were performed to compare outcomes after pediatric en bloc (n=20, mean donor weight 11.4 kg), standard criteria deceased (n=249), and living donor (n=215) kidney transplantation in adult recipients at our center. The outcomes after en bloc transplantation from young donors weighing less than or equal to 10 kg were compared with those from 11 to 15 kg donors. Results The 5-year graft survival after en bloc, standard deceased, and LDKT were 92%, 70%, and 88%, respectively (P=ns). There were no vascular complications, and urine leak was seen in 1 of 20 en bloc transplants. The 1-year serum creatinine of 1.1±0.2 mg/dL in recipients from less than or equal to 10 kg donors was comparable with 0.9±0.5 mg/dL in 11 to 15 kg group (P=ns). Conclusions Excellent long-term outcome after pediatric en bloc kidney transplantation from donors weighing less than or equal to 15 kg are comparable with those after LDKT. By using meticulous surgical technique and judicious recipient selection criteria, technical graft losses can be minimized when using en bloc pediatric kidneys from donors weighing less than or equal to 10 kg. Use of pediatric en bloc kidneys should be encouraged continuously to address the problem of organ shortage.

Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P

Background. It has been previously demonstrated that addition of anti-LFA-1 to a combination of CTLA4Ig and anti-CD40L induces the permanent acceptance of dopaminergic fetal pig xenografts when transplanted into the brain of wild-type mice. The purpose of this study was to test whether this costimulation blockade also can induce acceptance of adult pig islets transplanted to C5713L/6 mice with streptozotocin-induced diabetes. Methods. Recipients were treated with CTLA4Ig/anti-CD40L +/- anti-LFA-1 or isotype control antibodies during the first week after transplantation. Half of the costimulation blockade-treated recipients had their grafts removed after 8 weeks. The other half was observed up to 5 months. Results. Recipients treated with CTLA4Ig/anti-CD40L/anti-LFA-1 had significantly lower blood glucose and gained more weight than CTLA4Ig/anti-CD40L-treated recipients. CTLA4Ig/anti-CD40L-treated recipients exhibited unstable blood glucose. IPGTT of these recipients revealed a slow recovery to normal blood glucose levels at week 4. In comparison, CTLA4Ig/anti-CD40L/anti-LFA-1 treated recipients exhibited a significantly superior glucose clearance. CTLA4Ig/anti-CD40L +/- anti-LFA-1 treated recipients did not produce anti-pig IgG, whereas control antibody-treated mice did. CD4+ T cells from costimulation blockade-treated recipients proliferated less than CD4+ T cells from control antibody-treated mice when co-cultured with syngeneic antigen presenting cells loaded with pig islet antigens. Conclusions. CTLA4Ig/anti-CD40L/anti-LFA-1-treated recipients had superior islet function compared with CTLA4Ig/anti-CD40L-treated recipients. However, both costimulation blockade regimens led to islet graft acceptance up to 5 months after a 1-week treatment. (Less)