Carlos Jiménez-Romero

Using old liver grafts for liver transplantation: where are the limits?

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

Infectious Complications Following Small Bowel Transplantation.

Microbiological spectrum and outcome of infectious complications following small bowel transplantation (SBT) have not been thoroughly characterized. We performed a retrospective analysis of all patients undergoing SBT from 2004 to 2013 in Spain. Sixty‐nine patients underwent a total of 87 SBT procedures (65 pediatric, 22 adult). The median follow‐up was 867 days. Overall, 81 transplant patients (93.1%) developed 263 episodes of infection (incidence rate: 2.81 episodes per 1000 transplant‐days), with no significant differences between adult and pediatric populations. Most infections were bacterial (47.5%). Despite universal prophylaxis, 22 transplant patients (25.3%) developed cytomegalovirus disease, mainly in the form of enteritis. Specifically, 54 episodes of opportunistic infection (OI) occurred in 35 transplant patients. Infection was the major cause of mortality (17 of 24 deaths). Multivariate analysis identified retransplantation (hazard ratio [HR]: 2.21; 95% confidence interval [CI]: 1.02–4.80; p = 0.046) and posttransplant renal replacement therapy (RRT; HR: 4.19; 95% CI: 1.40–12.60; p = 0.011) as risk factors for OI. RRT was also a risk factor for invasive fungal disease (IFD; HR: 24.90; 95% CI: 5.35–115.91; p < 0.001). In conclusion, infection is the most frequent complication and the leading cause of death following SBT. Posttransplant RRT and retransplantation identify those recipients at high risk for developing OI and IFD.

Conversion from bladder to enteric drainage for complications after pancreas transplantation.

OBJECTIVE Bladder drainage (BD) of exocrine secretions is associated with urological and pancreatitis complications. Herein we have analyzed our experience with conversion from BD to enteric drainage (ED). PATIENTS AND METHODS From March 1995 to September 2008, 118 patients underwent pancreas transplantation. There were 68 men and 50 women of a overall mean age at transplantation of 37.8 years. There were 66 patients with bladder drainage (BD) and 52 with enteric drainage (ED). RESULTS Eight of 66 BD pancreas recipients (12.1%) underwent ED conversion. The mean time from pancreas transplantation to ED conversion was 29.3 +/- 30.6 months (range, 1-91 months). The major indications for conversion were recurrent reflux pancreatitis and chronic urinary tract infections in 7 patients; metabolic acidosis in 8; urethritis with severe perineoscrotal swelling in 1; and duodenocystostomy leak in 1. A comparative analysis of converted ED and not converted BD showed only a significantly prolonged period in the intensive care unit for patients who needed ED conversion (89 vs 47 hours; P < .01). Only 1 patient showed a duodenoenteric leak and peritonitis after conversion that required removal of the pancreas graft. The remaining 7 patients did not develop any postoperative complications and are currently well, showing normal pancreas graft function at a mean follow-up of 51.7 months after ED conversion. Patient and graft survivals were 100% and 87.5%, respectively. After ED conversion all urological complications disappeared; patients discontinued the use of oral bicarbonate. CONCLUSION ED conversion in pancreas transplant recipients with urological and reflux pancreatitis complications was a safe, effective procedure.

Incidence, risk factors and outcome of de novo tumors in liver transplant recipients focusing on alcoholic cirrhosis

Orthotopic liver transplantation (OLT) is an established life-saving procedure for alcoholic cirrhotic (AC) patients, but the incidence of de novo tumors ranges between 2.6% and 15.7% and is significantly increased in comparison with patients who undergo OLT for other etiologies. Tobacco, a known carcinogen, has been reported to be between 52% and 83.3% in AC patients before OLT. Other risk factors that contribute to the development of malignancies are dose-dependent immunosuppression, advanced age, viral infections, sun exposure, and premalignant lesions (inflammatory bowel disease, Barretts esophagus). A significantly more frequent incidence of upper aerodigestive (UAD) tract, lung, skin, and kidney-bladder tumors has been found in OLT recipients for AC in comparison with other etiologies. Liver transplant recipients who develop de novo non-skin tumors have a decreased long-term survival rate compared with controls. This significantly lower survival rate is more evident in AC recipients who develop UAD tract or lung tumors after OLT mainly because the diagnosis is usually performed at an advanced stage. All transplant candidates, especially AC patients, should be encouraged to cease smoking and alcohol consumption in the pre- and post-OLT periods, use skin protection, avoid sun exposure and over-immunosuppression, and have a yearly otopharyngolaryngeal exploration and chest computed tomography scan in order to prevent or reduce the incidence of de novo malignancies. Although still under investigation, substitution of calcineurin inhibitors for sirolimus or everolimus may reduce the incidence of de novo tumors after OLT.

Estudio cooperativo del Grupo Español de Trasplante de Páncreas (GETP): complicaciones quirúrgicas

UNLABELLED Technical failure in pancreas transplant has been the main cause of the loss of grafts. In the last few years, the number of complications has reduced, and therefore the proportion of this problem. OBJECTIVES The Spanish Pancreas Transplant Group wanted to analyze the current situation with regard to surgical complications and their severity. MATERIAL AND METHODS A retrospective and multicenter study was performed. 10 centers participated, with a total of 410 pancreas transplant recipients between January and December 2013. RESULTS A total of 316 transplants were simultaneous with kidney, 66 after kidney, pancreas-only 10, 7 multivisceral and 11 retrasplants. Surgical complication rates were 39% (n=161). A total of 7% vascular thrombosis, 13% bleeding, 6% the graft pancreatitis, 12% surgical infections and others to a lesser extent. Relaparotomy rate was 25%. The severity of complications were of type IIIb (13%), type II (12%) and type IVa (8.5%). Graft loss was 8%. Early mortality was 0.5%. The percentage of operations for late complications was 17%. CONCLUSIONS The number of surgical complications after transplantation is not negligible, affecting one in 3 patients. They are severe in one out of 5 and, in one of every 10 patients graft loss occurs. Therefore, there is still a significant percentage of surgical complications in this type of activity, as shown in our country.

Octogenarian liver grafts: Is their use for transplant currently justified?

AIM To analyse the impact of octogenarian donors in liver transplantation. METHODS We present a retrospective single-center study, performed between November 1996 and March 2015, that comprises a sample of 153 liver transplants. Recipients were divided into two groups according to liver donor age: recipients of donors ≤ 65 years (group A; n = 102), and recipients of donors ≥ 80 years (group B; n = 51). A comparative analysis between the groups was performed. Quantitative variables were expressed as mean values and SD, and qualitative variables as percentages. Differences in properties between qualitative variables were assessed by χ2 test. Comparison of quantitative variables was made by t-test. Graft and patient survivals were estimated using the Kaplan-Meier method. RESULTS One, 3 and 5-year overall patient survival was 87.3%, 84% and 75.2%, respectively, in recipients of younger grafts vs 88.2%, 84.1% and 66.4%, respectively, in recipients of octogenarian grafts (P = 0.748). One, 3 and 5-year overall graft survival was 84.3%, 83.1% and 74.2%, respectively, in recipients of younger grafts vs 84.3%, 79.4% and 64.2%, respectively, in recipients of octogenarian grafts (P = 0.524). After excluding the patients with hepatitis C virus cirrhosis (16 in group A and 10 in group B), the 1, 3 and 5-year patient (P = 0.657) and graft (P = 0.419) survivals were practically the same in both groups. Multivariate Cox regression analysis demonstrated that overall patient survival was adversely affected by cerebrovascular donor death, hepatocarcinoma, and recipient preoperative bilirubin, and overall graft survival was adversely influenced by cerebrovascular donor death, and recipient preoperative bilirubin. CONCLUSION The standard criteria for utilization of octogenarian liver grafts are: normal gross appearance and consistency, normal or almost normal liver tests, hemodynamic stability with use of < 10 μg/kg per minute of vasopressors before procurement, intensive care unit stay < 3 d, CIT < 9 h, absence of atherosclerosis in the hepatic and gastroduodenal arteries, and no relevant histological alterations in the pre-transplant biopsy, such as fibrosis, hepatitis, cholestasis or macrosteatosis > 30%.

Histologic Evaluation of Post-implantation Immediate C4d Deposition in 13 Intestinal Grafts: Correlation With Cell-based Crossmatching, Cold Ischemia Time, and Preservation Injury

C4d deposits are predictive of humoral rejection in kidney and heart transplantation. The aim of this study was to identify C4d deposit patterns in intestinal mucosa of the grafts on biopsy specimens obtained immediately after implantation and to detect if it could be a valuable tool to predict humoral or acute rejection. A second objective was to search for a statistically significant relationship between positive C4d deposition and other collected variables. Thirteen immediately post-transplantation mucosal graft biopsy specimens, formalin fixed, underwent immunohistochemical stain for C4d deposits. Diffuse intense staining of capillary endothelium was considered positive and absent, focal or weak stains as negative. Preservation injury grade and cold ischemia times were registered for each case. Donor-specific preformed antibodies were detected by complement dependent cytotoxicity serologic technique (crossmatching). Another 19 endoscopic follow-up biopsy specimens from days 2 to 6 were also evaluated. Statistical studies were made using the index of correlation ρ (Spearmans test). Diffuse intense C4d deposits were observed in 2 grafts, focal and weak in 5, and completely negative in 6. The mean cold ischemia time was 327 ± 101 minutes. Two cases showed diffuse positive deposits, 1 had a positive crossmatch and the cold ischemia time was 360 minutes whereas the other had not preformed antibodies and its cold ischemia time was 475 minutes. Humoral or acute rejection was not observed in follow-up mucosal biopsy specimens. There was no statistically significant relationship between the C4d deposition, cold ischemia time, crossmatching results, and preservation injury degree. In conclusion, C4d deposition was not a helpful tool for diagnosis of humoral rejection and prediction of acute rejection during the early post-transplantation period.

Complement C3F allotype synthesized by liver recipient modifies transplantation outcome independently from donor hepatic C3

Complement component 3 (C3) presents both slow (C3S) and fast (C3F) variants, which can be locally produced and activated by immune system cells. We studied C3 recipient variants in 483 liver transplant patients by RT‐PCR‐HRM to determine their effect on graft outcome during the first year post‐transplantation. Allograft survival was significantly decreased in C3FF recipients (C3SS 95% vs C3FS 91% vs C3FF 83%; P=.01) or C3F allele carriers (C3F absence 95% vs C3F presence 90%, P=.02). C3FF genotype or presence of C3F allele independently increased risk for allograft loss (OR: 2.38, P=.005 and OR: 2.66, P=.02, respectively). C3FF genotype was more frequent among patients whose first infection was of viral etiology (C3SS 13% vs C3FS 18% vs C3FF 32%; P=.04) and independently increased risk for post‐transplant viral infections (OR: 3.60, P=.008). On the other hand, C3FF and C3F protected from rejection events (OR: 0.54, P=.03 and OR: 0.63, P=.047, respectively). Differences were not observed in hepatitis C virus recurrence or patient survival. In conclusion, we show that, independently from C3 variants produced by donor liver, C3F variant from recipient diminishes allograft survival, increases susceptibility to viral infections, and protects from rejection after transplantation. C3 genotyping of liver recipients may be useful to stratify risk.

Long-term Outcomes Using Uncontrolled Donors after Circulatory Death (uDCD) for Liver Transplantation. A 10-Year Single Center Experience

Introduction The good results obtained along the years with liver transplantation (LT) have led to an increasing number of candidates on the waiting list, while the number of liver grafts is not enough to attend all patients who need an OLT. That is because many LT teams have proposed to expand the number of available grafts using livers from donors after circulatory death (DCD). The aim of this study is to analyse the use of liver grafts from type 2 uDCD donors for LT, comparing post-OLT complications and recipient outcome at 10-year follow-up with a group of patients who received liver grafts from donors after brain death (DBD). To our knowledge this series represents the largest experience using this kind of donors. Materials and Methods Between January 2006 and December 2016 we performed 783 LT in adult recipients. Seventy-five LT were performed using grafts from uDCD (Maastricht type 2), and 265 LT using livers from DBD donors. We compared the results using uDCD donors vs. DBD donors in adult recipients. Results The mean age of recipients of uDCD donors was 58.8±8 years vs. 54.7±10 (p=0.000) in DBD donors. Comparing both groups of recipients, there were no statistically significant differences in relation with gender, body mass index, Child-Pugh, MELD score, LT indication, and pre-LT laboratory tests. Mean age of uDCD donors was 41.7±10 years vs. 47.8±15 of DBD donors (p=0.001), with a higher frequency use of vasopressors in uDCD group (100%) vs. 48.3% in DBD (p=0.001), and higher significantly levels of AST prior to donation. No differences were found with respect to the presence of esteatosis, preservation injury, and cold ischemia time. Mean warm ischemia time was significantly lower in recipients of uDCD donors: 62±14 min in uDCD vs 70 ±36 in DBD (p=0.010). The units of transfused hemoderivates (packed red blood cells, fresh frozen plasma, platelets and fibrinogen) was significantly higher in recipients of uDCD than in recipients of DBD donors. Primary non-function of liver graft was significantly higher in uDCD group: 8.1% vs 2.1% in DBD group (p=0.031). Retransplant rate was also higher in recipients of uDCD donors: 12% vs. 4.6% in DBD (0.028). Moreover, ischemic cholangiopathy was significantly more frequent in uDCD: 31.1% vs. 5.6% in recipients of DBD liver donors (p=0.000). Patient survival at 1, 3 and 5-year was in recipients of uDCD donors was 81.3%, 70.2% and 68.6%, respectively, while in recipients of DBD donors was 89%, 83.7% and 78.8% (p=0.070). Graft survival at 1, 3 and 5-year in uDCD group was 72%, 62.2% and 60.7%, vs 87.1%, 81.9% and 76.5%, in DBD (p=0.003). Conclusion Even with the associated higher risk of primary non-function of liver graft and higher risk of ischemic cholangiopathy, liver grafts from uDCD donors type 2 constitute a safe source of grafts for LT.

Outcome of patients with hemodialysis or peritoneal dialysis undergoing simultaneous pancreas-kidney transplantation. Comparative study

Controversy remains with regard to the higher risk of intra‐abdominal infections and lower patient and graft survival when peritoneal dialysis (PD) rather than hemodialysis (HD) is used in simultaneous pancreas‐kidney transplantation (SPKT).