Liver Cirrhosis From Chronic Hypervitaminosis A Resulting in Liver Transplantation: A Case Report.

Herein we report a case of liver dysfunction caused by consumption of vitamin A supplements leading to liver transplantation. The patient was a 48-year-old male with a medical history of congenital ichthyosiform erythroderma in treatment with vitamin A until 12 years of age, at which point he discontinued the supplements because he had developed ascites. Liver cirrhosis was diagnosed as secondary to hypervitaminosis A on the basis of histologic examination of liver biopsy and the absence of other potential causes of chronic liver disease. Despite interruption of administration of vitamin A, the patient continued to deteriorate over the years, with development of portal hypertension signs. His medical conditions were aggravated with the development of hepatic insufficiency manifested by refractory ascites, renal insufficiency, and severe encephalopathy and he underwent orthotopic liver transplantation, followed by disappearance of all signs of portal hypertension. This case highlights the need to take a careful history of consumption of vitamin A when evaluating a patient with liver failure.

Analysis of the First 1000 Liver Transplants in Virgen del Rocío Hospital.

The goal of this work has been to analyze the first 1000 liver transplantations (LTs) performed in the Virgen del Rocío Hospital of Seville and to evaluate the changes in that time. We included 916 patients who had 1000 LTs. We distinguish 2 stages in the follow-up: the first stage, between 1990 and 2002, and the second, from 2003 to 2013 (Model for End-stage Liver Disease [MELD] stage). We analyzed recipient features, LT indications, donation criteria, surgical technique, complications, and survival both for patients and grafts. The median age of recipients was 53.50 ± 46.49 years old, with a noticeable increase after 2000. There were 3 times as many men as women. The most frequent indications for LT were hepatocellular disease (48.8%), followed by hepatocarcinoma (17.8%), retransplantation (8.1%), and cholestatic diseases (3.6%). Donors of Andalusian centers accounted for 88.2% of LTs, and 8.3% of LTs presented some arterial or venous complication. Biliary complications occurred in 15.6%. Patient survival at 1, 5, and 10 years was 77%, 63.5%, and 51.3%, respectively. In conclusion, some of the factors that negatively influenced survival of the patient were stage of the LT, hepatitis C virus-positive recipient, emergency cases, hepatocarcinoma, high consumption of blood products, and second transplantations.

Survival Outcomes in Liver Transplantation With Elderly Donors: Analysis of Andalusian Transplant Register.

Recently, there has been a large discrepancy between the number of patients on the waiting list for a liver transplant and the availability of deceased donors, with an increase in annual wait list mortality rates. Elderly donor livers are thought to be marginal grafts; however, in recent years, their utilization has constantly increased. The aim of this study is to evaluate the utilization of elderly donors in Andalusia and post-transplant outcomes. This retrospective observational study of 2408 liver transplants, performed in Andalusia between 2000 and 2014, analyzes the outcomes from donors aged 70 plus (n = 423) in terms of survival rates of the graft and the recipient, the type of transplant, donor age, and D-MELD score (product of donor age and preoperative Model for End-stage Liver Disease score). The most frequent indications for transplant were alcoholic cirrhosis (49.2%), hepatitis C cirrhosis (13%), and hepatocellular carcinoma (12.5%). The overall survival at 5 years was 64%, with a significant fall in survival for recipients with a D-MELD greater than 1500 (57%; P = .045). In the 70-year-old-plus donor group, the overall patient survival was 58.4%. The retransplant rate increased proportionately with donor age. In the alcoholic cirrhosis recipient subgroup, the overall survival at 5 years was 67.6% (P < .05) compared with 33.5% in patients with hepatitis C. Use of elderly donors is a safe strategy to reduce the scarcity of donors, provided that a D-MELD score below 1500 is obtained. Retransplant rates increase progressively with donor age. It is necessary to carefully screen recipients of older organs, taking into account that the best results are obtained for alcoholic cirrhosis, negative viral load hepatitis C, and a D-MELD score below 1500.

Recurrent Hepatocellular Carcinoma After Liver Transplantation: Analysis of Risk Factors.

BACKGROUND: Survival after orthotopic liver transplantation (LT) for hepatocellular carcinoma (HCC) is influenced by tumor recurrence. This study examines the survival of patients who underwent LT for HCC and developed recurrence of tumor after transplantation. METHODS: A retrospective analysis was performed of the 200 patients who underwent LT secondary to HCC from 1990 to 2014. We excluded 19 patients from the study owing to early postoperative deaths in the 1st month. We divided our sample into 2 groups according to the presence of recurrence. We performed a univariate analysis to identify variables that are significantly associated with the risk of recurrence. Afterward we use multivariate analysis regression analysis to find independent significance. RESULTS: Univariate analysis shows significant relationship between high Edmondson-Steiner grades (G3-G4) and the development of tumor recurrence. Tumor size, vascular invasion, and capsular invasion were found to be independent risk factors of tumor recurrence in the multivariate analysis. CONCLUSIONS: Tumor recurrence defines survival of patients who underwent LT for HCC. In this study we discuss which histologic factor are associated with higher risk of tumor recurrence, and therefore a negative the impact on patient's survival.

Outcomes of Liver Transplantation During Adulthood After Kasai Portoenterostomy Due to Biliary Atresia.

Biliary atresia (BA) is a neonatal progressive cholangiopathy of unknown etiology and one of the most common reasons for liver transplantation (LT) in children. Kasai portoenterostomy (KP) improves survival of the native liver, although LT remains the only ultimate treatment. In some cases KP makes it possible to defer the ultimate LT until adulthood. We report our experience regarding 5 cases of BA treated with LT during adulthood. KP was performed in all patients at an average age of 176 days (range, 60-280), which allowed an average survival of the native liver of 19.01 years (range, 14.06-22.32). Five-year survival rate was 100%. Ten-year survival rate did not reach 100% because of a death 9.55 years after LT due to chronic graft rejection, in a patient who was already prepared for a new LT. Our results corroborate that KP remains the first-line treatment of BA. Early performance of the KP provides children with the best chance of survival, allowing the delay of the LT to adulthood. LT during adulthood in these patients achieves good post-LT survival rate; we have not found any data regarding this group of patients in the literature.

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.

Impact of the learning curve on the outcome of domino liver transplantation.

Domino liver transplantation (DLT) is a strategy used to increase the number of available grafts. In this procedure, the transplant recipient is a living donor of her own liver. It is mandatory that the graft should be fully functional and the genetic defect should recur with sufficient latency period in the new recipient. Corino-Andrade disease, or familial amyloidotic polyneuropathy (FAP), satisfies these conditions. We retrospectively reviewed our prospective database of DLT. From July 2004 to April 2013, we performed 12 DLTs. We assessed age, sex, real Model for End-Stage Liver Disease (MELD) score, waiting list time, cold and warm ischemia times, intraoperative transfusion requirements, hospital stay, early peritransplantation morbidity (post-reperfusion syndrome, intraoperative cardiac arrest, post-transplantation thrombotic events, and biliary morbidity), acute cellular rejection, retransplantation, mortality, patient and graft survivals. With the intention to study the effect of the learning curve in the global survival results (including both donors and recipients of livers with FAP), we divided our series into 2 periods: the early period (from 2004 to 2008) and the present period (from 2009 to 2013). The crude mortality was 40% vs 0% (P = .042) in the early and present periods, respectively. The cumulative patient survival was also significantly in favor of the present period (P = .049). The graft loss prevalence was 60% vs 7.1% (P = .019) in the early and present periods, respectively. The cumulative graft survival was also significantly in favor of the present period (P = .030; Fig 2). In conclusion, we consider DLT to be a complex procedure, whose initial results are conditioned by the learning curve.

Fifteen years of follow-up of a liver transplant recipient with glycogen storage disease type Ia (Von Gierke disease).

Von Gierke's disease or glycogen storage disease type Ia (GSD-Ia) is an infrequent metabolic disease caused by an atypical accumulation of glycogen. The principal cause of this pathology is deficiency of the glucose-6-phosphatase enzyme. Herein we have reported a case of a young man with a history of Von Gierke's disease (GSD-Ia) since childhood who developed hepatocellular adenomatosis brought to light by ultrasounds and TACs. The patient began to develop early chronic renal failure, necessitating simultaneous liver and kidney transplantation. Years later continuous reviews at the nephrology and hepatobiliopancreatic surgery services show he has a good quality of life and a normal hepatorenal profile.

Modigraf administration through jejunostomy in liver transplant recipient: case report.

We report our experience with a 61-year-old patient with alcoholic and hepatitis C cirrhosis who underwent liver transplantation. On the 3rd postoperative day he presented a mediastinitis secondary to esophageal perforation produced by a Linton tube. An esophagectomy with jejunostomy was performed. Tacrolimus granules for oral suspension (Modigraf) were administered through the jejunostomy. This case report highlights the use of Modigraf and the absence of secondary effects. We observed biochemical parameters during the jejunostomy period. We discuss the administration strategy applied and whether tacrolimus granules for oral suspension by jejunostomy affect the bioavailability and its side effects.

Intraoperative hepatic artery blood flow predicts early hepatic artery thrombosis after liver transplantation.

Hepatic artery complications after orthotopic liver transplantation are associated with a high rate of graft loss and mortality (23% to 35%) because they can lead to liver ischemia. The reported incidence of hepatic artery thrombosis (HAT) after adult liver transplantation is 2.5% to 6.8%. Typically, these patients are treated with urgent surgical revascularization or emergent liver retransplantation. Since January 2007, we have recorded the postanastomotic hepatic artery flow after revascularization. The aim of this study was to assess the relationship between hepatic blood flow on revascularization and early HAT. Retrospectively, we reviewed perioperative variables from 110 consecutive liver transplantation performed at the Virgen del Rocío University Hospital (Seville, Spain) between January 2007 and October 2010. We evaluated the following preoperative (donor and recipient) and intraoperative variables: donor and recipient age, cytomegalovirus serology, ABO-compatibility, anatomical variations of the donor hepatic artery, number of arterial anastomoses, portal and hepatic artery flow before closure, cold ischemia time, and blood transfusion. These variables were included in a univariate analysis. Of the 110 patients included in the study, 85 (77.7%) were male. The median age was 52 years. ABO blood groups were identical between donor and recipient in all the patients. The prevalence of early HAT was 6.36% (7 of 110). Crude mortality with/without HAT was 22% versus 2% (P = .001), respectively. Crude graft loss rate with/without HAT was 27% versus 4% (P = .003), respectively. Early HAT was shown to be primarily associated with intraoperative hepatic artery blood flow (93.3 mL/min recipients with HAT versus 187.7 mL/min recipients without HAT, P < .0001). No retransplantation showed early HAT. In our experience, intraoperative hepatic artery blood flow predicts early HAT after liver transplantation.

Spontaneous clearance of HCV in HIV-hepatitis C virus coinfected liver transplant patients: prospective study.

BACKGROUND: Hepatitis C virus (HCV) clearance is an independent predictive factor for long-term survival in HIV-HCV liver transplantation patients. After 46 months of antiviral therapy it is achieved in up to 80% of cases. Little is known, however, about spontaneous viral clearance. We performed prospective study of HIV-HCV coinfected liver transplant patients. METHODS: Between January 1, 2001, and December 31, 2011, we analyzed the parameters from among HIV-HCV coinfected liver transplant patients of donor and recipient ages, transplant cause, Model for End-Stage Liver Disease (MELD) score, donor and recipient serology, transplant date, viral load before and after transplantation, immunosuppressive therapy, HCV recurrence, HCV viral clearance (spontaneous and duration), retransplant cause, and viral load before and after retransplant, as well as survival. RESULTS: The seven transplanted HIV-HCV coinfected patients had most commonly HCV-related hepatocarcinoma (n = 5, 71.42%). Three subjects (42.85%) developed HCV recurrences. Two patients (28.57%) were retransplanted, both due to HCV recurrence with one of them developing a spontaneous clearance of HCV (14.28%). This patient showed a preoperative HIV viral load < 50 copies IU/mL, CD4+ count 486/µL, HCV-RNA 2564 IU copies/mL, Anti-HBc+, and MELD 30. The donor was an 81-year-old female who was Anti-HBc+. Immunosuppressive therapy consisted of cyclosporine, mycophenolate, and prednisone. One month after transplantation, the patient developed an acute cellular rejection episode with progression of liver disease secondary to the HCV recurrence (56.5 × 105 copies IU/mL). He started antiviral treatment (α-interferon and ribavirin), but due to side effects and interactions with the antiretrovirals, they were stopped after four doses. The viral load decreased spontaneously and progressively until it became negative at 146 days after transplantation; he was retransplanted and HCV-RNA has continued to be negative after 772 days. CONCLUSION: Spontaneous clearance of HCV among HIV-HCV coinfected liver transplant patients is possible. Despite no treatment, one patient still has no detectable HCV viral load after retransplantation.

Use of fully covered self-expandable stent in biliary complications after liver transplantation: a case series.

AIMS: To present our case series of fully covered self-expandable metallic stents (FCSESs) placed to treat biliary stenosis after liver transplantation and leakage after failure of plastic stenting. MATERIALS AND METHODS: We retrospectively reviewed the courses of patients who had undergone liver transplantation with a biliary complication that was treated by an FCSES installed by endoscopic retrograde cholangiopancreatography. We evaluated the following variables: gender, age, indication for transplantation, time between transplant and diagnosis of the complication, number of plastic stents placed before the FCSES, and procedure-related complications. RESULTS: From April 2008 to March 2010, 11 patients who had undergone a duct-to-duct anastomosis suffered posttransplant biliary stenosis or leakage with failure of endoscopic treatment using a plastic biliary stent: Namely, eight cases of stenosis and three of biliary leaks. Three patients underwent a papillotomy to place the FCSES, with no significant morbidity. No severe complications were observed after the endoscopic treatments; two patients developed mild pancreatitis; two, hyperamylasemia; and one, mild biliary sepsis. We removed the FCSES after a mean of 280 (range=173-310) days. Five patients lost the FCSES spontaneously. One patient underwent a choledocojejunostomy and two are waiting biliary surgery. CONCLUSION: We avoided cholangiojejunostomy in 6/9 cases (not including the two deaths). Papillotomy did not engender a greater morbidity. The spontaneous loss of the stent is a problem that need to be resolved.

Variability of the extrahepatic arterial anatomy in 500 hepatic grafts.

PURPOSE: To review the extrahepatic arterial anatomy in 500 consecutive liver grafts. MATERIALS AND METHODS: From April 1990 to January 2005 we performed 500 liver transplantations. We received 108 deceased donor liver grafts (21.4%) from other centers. Donor arterial anatomy was recorded as described in the surgical notes of both the donor harvest and the recipient procedures. We used the modified Michels classification scheme proposed by Busuttil. We assessed incidences of mortality, retransplantation, postreperfusion syndrome, intraoperative arrest, hemorrhagic complications, and primary malfunction, comparing with chi-squared tests. RESULTS: There were 376 type I (75.2%), 51 type II (10.2%), 32 type III (6.4%), 18 type IV (3.6%), 3 type V (0.6%), 2 type VI (0.4%) and 18 others (3.6%). No significant associations were found between arterial vascular anomalies of the graft and the studied variables. CONCLUSION: In our experience, extrahepatic arterial anomalies of the donor graft did not influence the short-term outcomes of liver transplantation.

Outcomes of liver transplantation in candidates with portal vein thrombosis.

OBJECTIVE: The objective of the present study was to analyze the incidence of portal vein thrombosis (PVT), comparing morbidity and mortality rates among those affected with and those free of this complication. In the PVT group, we also analyzed mortality related to partial (PPVT) and total (TPVT) thrombosis. METHODS: We undertook a retrospective study of orthotopic liver transplantations from deceased donors in 617 recipients from January 1991 until October 2008. Recipients were classified according to whether they had PVT. In all cases, we considered age, sex, Model for End-stage Liver Disease score, Child-Pugh score, indication for transplantation, type of thrombosis, surgical technique blood product transfusion, and survival rate. RESULTS: There were 48 patients with PVT (7.78%) among 670 transplantations in 617 recipients in our institution. Concerning the type of thrombosis, 28 (58.3%) were partial and 20 (41.7%) total with complete occlusion of the portal vein lumen. CONCLUSION: PVT in liver transplant candidates is a rare event (7.8%) that entails greater difficulty in the procedure, expressed as a longer operative time, greater consumption of blood products, and complex surgical techniques. The prognosis for these patients depends on the type of thrombosis: patients with TPVT showed a higher mortality, whereas those with PPVT had survival rates comparable to those of candidates with a permeable portal vein.

Outcomes of domino liver transplantation: a single institution's experience.

AIMS: Domino liver transplantation (DLT) is a strategy to increase the donor pool. Explanted liver from patients with familial amyloidotic polyneuropathy (FAP) are often used as domino grafts, because the liver is normal apart from the production of the mutated transthyretin variant. We present the outcomes for both donors and recipients of DLT. MATERIALS AND METHODS: Retrospective analysis of initial DLT for 16 consecutive adult patients performed between July 2004 and July 2009. All cases of FAP donor to grafts were removed preserving the cava vein with reconstruction of the hepatic veins, except the first and seventh cases, where in we removed the retrohepatic vena cava with the liver without venovenous bypass. The postoperative follow-up period for surviving DLT recipients at the end of September 2009 was 2-62 months (mean, 26). RESULTS: Two patients out of 8 FAP donors died due to pulmonary thromboembolism on the 31st postransplant day, or sepsis at 35 days namely, an overall survival of 75%. One patient out of 8 recipients died namely, an early portal thrombosis on the 22nd postransplant day) with a crude survival of 87.5% in the recipient group (P = no significant [NS]). Four grafts from 8 FAP donors were lost-2 deaths and 2 retransplants due to thrombotic events on the first and second postransplant day-with a crude survival of 50%. Two of 8 recipients lost their grafts: 1 death and 1 retransplantation for an acute Budd-Chiari syndrome on the first postransplant day with a crude survival of 75% in the recipient group (P = not significant [NS]). CONCLUSION: We believe that the FAP liver graft is an excellent option for selected patients. Special care must be taken with thrombotic events.

Switching from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients with gastrointestinal complications.

OBJECTIVE: Our aim was to safely and effectively reduce adverse gastrointestinal (GI) events resulting from the use of mycophenolate mofetil (MMF) in liver transplant patients by switching to enteric-coated mycophenolate sodium (EC-MPS). PATIENTS AND METHODS: We studied 19 patients on maintenance therapy presenting with GI intolerance to MMF whose therapy was switched to EC-MPS. The variables recorded were: calcineurin inhibitor (CNI) dose levels, MMF/EC-MPS dose levels, lipid profile, hematology, renal and hepatic function markers, and rejection episodes. These variables were recorded at the visit prior to the day of conversion, on the day of conversion, and 1, 3, 6, and 9 months thereafter. RESULTS: Of the 19 patients, 16 were men (mean age, 56.6 +/- 15.9 years) and 3 were women (58.3 +/- 12.1 years). While 31.6% were on MMF monotherapy, 52.6% were on combined therapy with tacrolimus and 15.8% with cyclosporine. On the day of conversion, 21% were not on MMF, 36.8% were on 1000 mg/d, 26.3% were on 1500 mg/d, 5.3% were on 750 mg/d, and 10.6% were on 500 mg/d. The starting daily doses of EC-MPS were: 360 mg (26.3%), 720 mg (31.6%), 540 mg (26.3%), 1080 mg (10.5%), and 1440 mg (5.3%). GI complications were significantly reduced from the first month postconversion (P < .01), as 57.2% of patients did not display any symptoms; however, at 9 months, this incidence rose by 12% relative to month 1 (P < .05). There were no changes in the other variables and there were no reported rejection episodes. Treatment was suspended in 2 patients due to dyspnea and nervousness. CONCLUSION: In liver transplant patients with GI complications from chronic MMF use, the use of EC-MPS was safe and efficacious, as it significantly reduced their incidence.

Causes and predisposing factors of de novo tumors in our series of liver transplant recipients.

INTRODUCTION: Liver transplant recipients suffer a high risk of developing cancer, mainly as a consequence of immunosuppressant treatment, although a variety of other factors are involved. Our purposes were to evaluate the frequency of de novo tumours and to determine predisposing factors. MATERIAL AND METHODS: We analyzed all of the transplantations performed during 1990, with a total of almost 700 cases. We analyzed the frequency of de novo tumors, their location, time since transplantation, survival, and recurrence rates and factors that may influence their appearance. RESULTS: The series included 64 cases in 50 patients with a frequency of 7%. Skin tumors were the most frequent (39.06%), followed by those in the otolaryngologic (ear, nose, and throat) region (15.62%) and the lung (14.06%). The average time to progression between the transplantation and diagnosis was less than 4 years (47.74 months). The recurrence rate was 16%. The factors with the greatest influence on their appearance were age and gender of the recipient, alcohol consumption, and Child-Pugh score. Plasma transfusion was statistically, although not clinically, significant. DISCUSSION: Our frequency of de novo tumors was consistent with that described in the literature. Despite some factors that influence their appearance, the main predisposing factor was immunosuppression and its duration.