Tumor Biology as Predictor of Mortality in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor, with the Milan criteria considered to be the gold standard for patient selection for liver transplantation (LT). MATERIALS AND METHODS: We performed a descriptive observational study, reviewing 20 years of experience of LT in patients with HCC in the Fundacion Valle del Lilí in Cali, Colombia. Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015. RESULTS: Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In the first period patients within the Milan criteria had a recurrence-free survival at 5 years of 66.6%, and in those who exceeded the Milan criteria, recurrence-free survival was 75%. In the second period, patients within the Milan criteria, recurrence-free survival at 5 years was 93.5%, and in those who exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically significant difference was found in either period. For patients with mild and moderate tumor differentiation, the relapse survival rate at 5 years was 69.4% (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90), respectively. All patients with poor tumor differentiation relapsed and died within 3 years. CONCLUSION: Global and recurrence-free survival among patients who met and patients who exceeded the Milan criteria was not significantly different, suggesting an expansion of the Milan criteria to include potential recipients who were previously excluded. Obtaining histologic differentiation and identifying vascular invasion will provide a more worthwhile contribution to LT decision making.

Liver Transplantation in Hepatitis C-Infected Patients: Experience From a South American Transplant Center.

BACKGROUND: Around 2.4% of the world's population is infected with hepatitis C virus (HCV), and it is the most common cause of liver transplantation (LT) in the world. Latin America (LA), with nearly 9% of the world population, has had a continuous increase in the number of LTs per year. Yet, due to the lack of mandatory data collection and a well-developed health-care system, access to transplantation is limited in most LA countries. We report the first LA experience of HCV-infected LT patients. METHODS: We performed a retrospective cohort study by reviewing the medical histories of all HCV-infected LT patients between 1996 and 2016 who acquired HCV before their LT, at the Fundación Valle del Lilí, Cali, Colombia. RESULTS: Between January 1996 and December 2015, a total of 770 LTs were performed, of which 75 had a cirrhotic liver due to HCV infection. With a median follow-up time of 24.4 months (interquartile range [IQR] 4.7-61.2 months), patient survival was 44.9% and 66.9% for the time periods 1996-2006 and 2007-2015, respectively. Hepatocellular carcinoma (HCC) was present in 30.6% of the patients, and overall postoperative complications had an incidence of 80%. CONCLUSIONS: This is the first report of LT in HCV-infected patients in Colombia and in LA. Our results are comparable to those of other transplant centers worldwide with regard to postoperative complications and patient survival. Patients with LT in the 1996-2006 time frame had higher morbidity and mortality. Studies including larger numbers of patients are needed to determine the reason for this finding.

Kidney transplantation for end-stage renal disease in lupus nephritis, a very safe procedure: a single Latin American transplant center experience.

Background Lupus nephritis (LN) is one of the most frequent complications of SLE and occurs in up to 50% of cases depending on the studied population. Of these, approximately 20% progress to end-stage renal disease (ESRD), with the treatment of choice being a kidney transplant. Objective The objective of this study was to describe the clinical outcome of patients transplanted due to LN, compared with patients transplanted for other causes, in a Latin American population from the Fundación Valle del Lili in Cali, Colombia. Methods Observational, retrospective case study with controls matched by age, sex and type of donor in a single center between 1996 and 2014. Results Sixty-five kidney transplants were performed in patients with LN and ESRD. The survival of patients with LN was 98% at 1, 10 and 15 years ( p = .99). For controls by age and sex, survival was also 98% at 15 years post-transplant, and for controls by donor, the survival rate was 100% at 5 years and 98% at 15 years. Graft survival in patients with LN to 1, 5 and 15 years was 92%, 83% and 71%, respectively; for controls by age and sex, it was 90%, 84% and 64%, respectively, and for the controls by donor, it was 89%, 86% and 79%, respectively ( p = .7718). There were no statistically significant differences found in the cumulative incidence of acute graft rejection in the first year, but it was found that acute rejection is a factor that relates to the loss of function of the renal graft ( p = .032). Of the patients transplanted for LN, two (3.1%) experienced a recurrence of the disease. One patient died after a diagnosis of recurrence of LN due to an infection. Conclusions Kidney transplantation is a good option for patients with ESRD due to LN. In this Hispanic population, the survival of patients, graft survival, and cumulative incidence of graft rejection are not different from those of other transplanted patients. In addition, recurrence of LN was rare, showing the benefits of renal transplantation in LN patients with ESRD.

Investigation of lymphocyte depletion and repopulation using alemtuzumab (Campath-1H) in cynomolgus monkeys.

As the target CD52 molecule is expressed on erythrocytes of most nonhuman primate strains, using alemtuzumab in these species would cause massive hemolysis. Six cynomolgus monkeys of Indonesian origin, screened by agglutination assay for absence of CD52 on erythrocytes, were administered alemtuzumab in a cumulative dose to a maximum of 60 mg/kg. In two monkeys, mycophenolate mofetil (MMF) was added as maintenance therapy. Complete depletion of T and B lymphocytes (>99.5%) was achieved with 20 mg/kg alemtuzumab and was more profound than in monkeys treated with antithymocyte globulin (n = 5), as quantified by flow cytometry. Repopulation was suppressed by weekly injections of 10 mg/kg. Without MMF, repopulation of CD20(+)B cells and CD8(+)T cells was complete within 2 and 3 months, respectively, and repopulation of CD4(+)T cells was 67% after 1 year. MMF significantly delayed CD4(+)T-cell repopulation. Among repopulating CD4(+) and CD8(+) T cells, a phenotypic shift was observed from CD45RA(hi)CD62L(hi) naïve cells toward CD45RA(lo)CD62L(lo) effector memory cells. In lymph nodes, the depletion of naïve cells was more profound than of memory cells, which may have initiated a proliferation of memory cells. This model offers opportunities to investigate lymphocyte depletion/repopulation phenomena, as well as the efficacy of alemtuzumab in preclinical transplantation models.

Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs.

I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 +/- 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 +/- 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-beta and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.