Óscar Caso Maestro

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.

Liver Transplantation from Donor after Cardiac Death (DCD) Maastricht type IIA, our Experience after 10 years

Introduction Ten years after the beginning of the donation after cardic death (DCD) programme in the University Hospital 12 de Octubre, we study the evolution of the results of said programme over time. Objectives To compare the results of liver transplantation (LT) using grafts obtained from donors after cardiac death (DCD type Maastricht IIA) performed during the first period (A) of the programme (January 2006 to December 2010) versus those performed during a later period defined from January 2011 to December 2016 (B). Materials and Methods Retrospective analysis of the DCD liver transplantation series in the University Hospital 12 de Octubre. Results 75 LT from DCD type IIA have been reviewed, 44 performed during period A and 31 during period B. Mean recipient ages were 59+8 y 58+6 (NS) respectively, with a similar number of male patients (79,5% vs. 71% NS). There were no statistically significant differences found regarding other recipient characteristics such as MELD score, hepatocellular carcinoma or HCV infection. Mean donor age was 38+9 years in group A and 46+7 in group B (p 0.000). When reviewing ischemia times (IT), cold IT was shorter in group B (A 7:00 vs. B 6:05; p 0.046) as was warm IT (A 1:08 vs. B 0:58, p 0.025). However NECMO time was significantly shorter during the first period (3:16 vs. 3:37 min, p 0.027). Recipient survival during period A at 1, 3 and 5 years was 77.3%, 61.4% and 59.1% while during period B it was 87.1%, 83.7% and 83.7% (p 0.039). Graft survival after period A was significantly lower as well (63.6%, 50% and 47.7% vs. 83.9%, 80.5% and 80.5% in group B; p 0.008). The incidence of ischemic cholangiopathy was higher in group A (43.2% vs. 13.3%; p 0.006), as well as the retransplantation rate (A 18.2% vs. B 3.2%; p 0.05). There were non-statistically significant differences found regarding the incidence of primary graft non-function (A 11.4% vs. 3.3% in group B; p 0.214). Conclusions The study shows a significant improvement in the results of DCD liver transplantation through time, possibly related to graft ischemia time optimization.

Long Term Outcome of Patients with Portal Thrombosis Previous to Liver Transplantation

Introduction Portal vein thrombosis is a late consequence of advanced cirrhosis. Its development has been associated with worse long term patient and graft survival, as well as a higher risk of vascular complications after liver transplantation. Material and Methods We reviewed all patients over 18 years old who underwent liver transplantation (LT) at University Hospital “12 de Octubre” between January 2002 and January 2017. Pediatric recipients and cases of retransplantation were excluded. Patients were divided according to the presence of preoperative portal thrombosis (PT, 126 patients) or no PT (N-PT, 724 patients). Results Mean recipient age was 55.5±9 in PT vs 53.7±11 in N-PT (p 0.085), with a similar number of male patients in both groups (76.2% en PT vs 72.8% in N-PT; p 0.431). There was a 59,2% rate of HCV infection in the PT group (52.4% in N-PT; p 0.157), and 22.2% of patients in the same group had a diagnosis of hepatocellular carcinoma (vs 29,9% in N-PT group; p 0.080). Mean preoperative MELD score was 14.7 en TP vs 15.6 in N-PT (p 0.067). There were no significant differences found regarding preoperative BMI, haemoglobin, MELD-Na score and Child-Pugh score.16.7 % of patients in the PT group received a subobtimal graft for LT, vs 21.7% in the N-PT group (p 0.204). In relation to blood products transfusion, an average of 12.3 units of RBC was administered in the the PT group and 9.2 in the N-PT (p 0.084), with an average of 14.6 and 12.8 FFP units respectively (p 0.093) and no differences found when reviewing platelets and fibrinogen. Mean ICU stay was 9.2 days in PT vs 6.7 in N-PT (p 0.075), while mean ward stay was 17.7 days in PT vs 19.4 in N-PT (p 0.429). Portal thrombosis recurrence rate was 4% in patients with a previous diagnosis of PT, significantly higher than in those without said previous history (1.1% in N-PT; p 0.015). However, the rate of arterial thrombosis was 4.8% in the PT group vs 3.8% in the N-PT group with no statistical significance (p 0.890). Retransplantation rate was 4% in PT and 6.2% in N-PT (p 0.326). Actuarial survival at 1, 3 and 5 years was 86.5%, 79.1% and 76.2% respectively in the PT group, vs 84.5%, 78.3% y 74.3% in the N-PT group (p=0.489). Conclusion Pretransplant portal thrombosis is a diagnosis that has not been associated with a decreased survival after LT in our series; but seems to determine an increase in transfusion requirements and a higher risk of postoperative vascular complications.

Liver Transplantation as Curative Treatment in Severe Pulmonary Hypertension due to Hepatic Vascular Malformations in Rendu-Osler-Weber Disease

Introduction Hereditary haemorragic telangiectasia (HHT) is an autosomal dominant disease characterised by development of arterio-venous malformations (AVM) more common in mucosa, brain, lung, liver and gastrointestinal tract. Pulmonary hypertension (PH) is defined as mean pulmonary arterial pressure (mPAP) > 25 mmHg. Liver transplatation is still controversial in this patients. MaterialsMethods Woman, 38 years old, with personal history of eclampsia, HELLP síndrome and HHT type 2 (Rendu-Osler-Weber) with exon 9 in the ALK1 gen mutation that presents as systemic manifestations self-limited epistaxis and liver AVM with mainly arterio-systemic intrahepatic shunt which lead to high output cardiac arrest and moderate to severe PH with a NYHA II functional class. Lung and brain AVM were not observed in radiologic tests and bubble test was positive due to extracardiac shunt (>6 heart-beats). Results Due to the high risk related to liver transplantation (LT) in this patient, transarterial embolization of liver vascular malformations was performed first, with a 24% reducción in cardiac output (table 1) and development of several complications as intranodal reentry tachycardia and ischemic hepatitis. Because of partial improvement treatment with bevacizumab was iniciated, despite this, the patient suffered recurrent episodes of cardiac arrest and liver function deterioration (MELD 25). In July 2016, orthotopic LT was performed with a cold ischemia time of 355 min and a warm ischemia time of 40 min, during which he bled profusely requiring massive blood transfusion. After LT, a 53.2% reduction in the cardiac output was observed in a right catheterism, because extracardiac shunt was eliminated. Furthermore, a pulmonary vascular resistance (PVR) reduction, wich means an absence of vascular branch remodelation, and a normalization in mPAP was shown; which demonstrate the resolution of HP after LT (table 2). Table. No title available. Table. No title available. Conclusion - LT might be a curative treatment in patients with haemorrhagic vascular diseases if severe HP and cardiac arrest are due to liver AVM - Liver AVM embolization in moderate-severe HP with elevated cardiac output has mild results - Diagnosis of Lung AVM causing HP, by angio-TC or angiography, is essential because might contraindicated isolated LT.

Can Biliary Papillomatosis Recur after Liver Transplantation in the Absence of Infiltrative Carcinoma

Introduction Biliary papillomatosis (BP) is a rare entity characterized by the presence of multiple papillary tumours in the intrahepatic and/or extrahepatic biliary tree. Chappet was the first who described in 1894 this condition and less than 100 cases have been described in the literature since then. To our knowledge, only 8 cases of BP treated with LT have been described in the literature in the since the year 2000. Vibert et al 6 argued in 2010 that in the absence of infiltrative carcinoma and positive lymph nodes, LT is the best choice of treatment and that LT might even be considered in highly selected patients with superficial foci of malignancy without positive lymph nodes. Material and Methods We report the case of a 43-year-old male who was admitted to our hospital with cholangitis. Complementary studies revealed a wide dilatation of the biliary tree and a tumour over the papilla. He underwent cephalic pancreaticoduodenectomy and the histological study showed the presence of BP affecting the margins of biliary and pancreatic resections. Total pancreatectomy was carried out to exclude carcinoma foci in the pancreas and finally LT was performed. No carcinoma foci or lymph node infiltration were identified in the histological study. After 24 months the patient developed a large hepatic recurrence and died a few weeks after the diagnosis. Discussion BP is considered a premalignant disease with a high risk of malignant transformation. Surgical treatment must be aggressive to achieve resection of all affected areas. Since 2000, only 8 cases of diffuse BP treated with LT have been described in the literature. All of them had both intra- and extrahepatic biliary tract involvement and in 3 cases the main pancreatic duct was affected too. Of the 8 cases described, only 4 histological studies showed invasive carcinoma in the explant liver after transplantation, in 1 of them with lymph node involvement. Two of them had recurrence at 16 months and at 6 years respectively, and the remaining 2 were alive without recurrence at 18 and 22 months, respectively. The present case is the first to describe recurrence of the disease after LT in the absence of invasive carcinoma and positive lymph nodes, confirming the recurrent nature of the disease despite a radical curative treatment. Prognosis in cases of recurrence is bad regardless of the presence of foci of invasive carcinoma in the surgical specimen, since all published cases with recurrence after LT died in a short period of time. Probably, immunosuppression makes the recurrence of the disease more aggressive and with a worse prognosis. Conclusion BP is a premalignant disease that can recur after liver transplantation even in the absence of infiltrative carcinoma foci.

Liver Transplantation Outcomes after Acute Liver Failure: Still Some Questions to be Asked

Introduction Before de use of liver transplantation (LT) in acute liver failure (ALF), mortality of these patients was up to 85%. Today, it is around 20-25%. Despite the good results, ALF has a worse short-term survival compared to other indications. The aim of this study is to evaluate our results in LT after ALF and identify prognostic factors in order to better select patients that will benefit from a LT and save grafts in those cases of unavoidable decease. Materials and Methods We underwent a longitudinal and retrospective study of all patients over 15 years old receiving a LT due to an acute liver failure, from January 2006 to December 2016, in our department. Multiple parameters were evaluated. Patient and graft survival were as well studied. Finally, we compared the characteristics of patients surviving more than 30 days to those deceasing the first month. Results During this period we found 31 patients who received a LT to treat an ALF. The mean recipient age was 39 years and 17 (55%) patients were female. We found 8 (25.8%) smokers, 5 (16.1%) patients with hypertension and 8 (25.8%) patients with previous surgical history. The main cause of ALF was drugs (11 patients-35.5%-) followed by virus (6 patients-19.4%-). Hyperacute course was found in 14 (45%) patients. At the moment of the transplantation, 28 (90%) patients had encephalopathy. Orotracheal intubation was required in 19 (61%) patients, vasoactive drugs in 9 (30%) patients and MARS therapy in 19 (61%) patients. Mean MELD score was 27. One of the LT was performed with a partial graft. Median transfusion requirements were in 7 RBC, 10 FFP and 1 PP. Mean cold and warm ischemia time were 426 and 60 minutes, respectively. No cases of primary non-function were present. We identified vascular complications in 1 (3%) patient, biliary complications in 2 (6.5%), infections in 10 (32%) and acute renal failure in 14 (45%). Seven (22.6%) patients developed a rejection. In 2 (6.5%) patients re-transplantation was necessary. Patient and graft survival at 5 years were 75% and 72%, respectively. After the descriptive analysis, we found 21 patients alive after 30 days and 10 patients who died during the first month. We performed a comparative analysis between both groups and we found that previous worse medical status and patients needing intubation or MARS had a poorer outcome. Transfusion requirements were higher in patients surviving less than 30 days, but complication rates were similar between both groups. Figure. No caption available. Figure. No caption available. Figure. No caption available. Figure. No caption available. Conclusion LT is the treatment of choice in ALF not responding to intensive medical treatment. Intubation, MARS therapy, vasoactive drugs and high transfusion requirements were associated with higher mortality rates within 30 days. A longer sample is needed in order to better identify prognostic factors of LT failure after ALF.

Risk Factors and Consequences of Ischemic Cholangiopathy in Liver Transplantation from DCD Maastricht IIA

Introduction Although donors after cardiac death (DCD) Maastricht type IIA have been established as an acceptable source of grafts in the current setting of organ shortage, biliary complications, especially ischemic cholangiopathy (IC), remain a considerable difficulty in the management of these patients, with a significant impact in long term results and quality of life. Objectives To study the incidence and impact of ischemic cholangiopathy among DCD IIA liver transplant recipients, and identify risk factors related to this complication. Materials and Methods Retrospective analysis of the DCD Maastricht type IIA liver transplantation series in University Hospital 12 de Octubre, registered from January 2006 to December 2016. Results 75 LT from DCD type IIA were performed during the study period, with 23 cases of IC diagnosed (30.7%). Comparing patients who suffered this complication (IC) with those who did not (no-IC), there were no significant differences found in recipient age (no-IC 58.4+7.7, IC 59.5+7.7 years), MELD score (no-IC 13.9+4.8 vs IC 15.6+4.8), donor age, HCV infection or hepatocellular carcinoma prevalence. Mean MELD-Na was 19+7 in those patients who developed IC, and 15.9+5.8 in those who did not, although the difference was not significant. Ischemia times and ECMO flow rates were similar in both groups. Retransplantation rate was higher in the no-IC group (11.5% vs. 13%, NS). No differences were achieved comparing liver function tests. Median time from transplantation to development of ischemic cholangiopathy was 5.8 months (range 1.2-70.3). Multivariate analysis shows an increased risk of IC in those grafts with AST levels over four times the upper limit of the normal range in the last blood sample obtained during NECMO (OR, 5.93; 95% CI, 1.001-35.208; p 0.05). No other statistically relevant risk factors were identified in this analysis. Differences found when comparing actuarial survival at 1, 3 and 5 years in recipients who did not develop IC (76.5%, 70.3% and 70.3%) with those who did (91.3%, 69.6% and 65.2%) were not statistically significant (p 0.915). Similar results were obtained when studying graft survival (no IC 70.6%, 64.3%, 64.3% vs. IC 78.3%, 60.9%, 56.5%; p 0.958). Conclusions AST levels 4 times above the usual laboratory range have been identified as a significant risk factor in the developement of ischemic cholangiopathy, suggesting that grafts with this characteristic should be discarded to minimize said complication.

Liver-kidney simultaneous transplantation in adult patients with primary hyperoxaluria. Experience at Hospital Universitario 12 de Octubre

Primary hyperoxaluria (PH) is a metabolic liver disease with an autosomal recessive inheritance that results in oxalate overproduction that cannot be metabolized by the liver. Urinary excretion of oxalate results in lithiasis and nephrocalcinosis leading to a progressive loss of renal function that often requires renal replacement therapy despite medical treatment. Type 1 PH is the most common form and is due to a deficiency in the alanine-glycolate aminotransferase enzyme found in hepatic peroxisomes. Therefore, a liver-kidney simultaneous transplant (LKST) is the definitive treatment for end-stage renal disease (ESRD) patients. However, some studies suggest that the morbidity and mortality rates are greater when this procedure is performed instead of only a kidney transplant (IKT). Herein, we report five patients with PH and a mean glomerular filtration rate of 20.2 ± 1.3 ml/min/1.73 m2 who received a LKST between 1999 and 2015 at the Hospital Universitario 12 de Octubre. Recurrence and liver or kidney graft loss was not observed during the postoperative period and only one case of late acute rejection without graft loss was diagnosed. The recipient survival rate was 100% with a median follow up of 84 months. As LKST is a curative and safe procedure with a low mortality and high survival rate, it must be considered as the treatment of choice in adults with HP and ESRD.