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.

Lung adenocarcinoma during pregnancy: clinical case and literature review.

Lung cancer during pregnancy is a very rare disease with less than 70 cases published to date. Information about specific lung cancer as adenocarcinoma is even more limited. Genetic techniques can detect oncogene mutations which seem to be more frequent among cases of lung cancer in pregnant women and could determine both the treatment and prognosis. We present a recent case seen at our hospital and a literature review.

Intraoperative Portal Vein Flow > 123 mL/min Per 100 g Predicts a Better Survival of Patients After Liver Transplantation.

OBJECTIVE: To assess the importance of intraoperative portal vein flow measurement during liver transplantation in relation to postoperative complications and graft and patient survival. MATERIALS AND METHODS: Retrospective review including 291 patients who had all the information and covering a period of 10 years (2007-2017). Using a receiver operating characteristic curve, a cut-off point that would have the greatest impact on the probability of being alive at 5 years was established. In relation to this value, 2 groups were formed (low and high flow) and demographic variables, intraoperative variables, postoperative complications, and graft and patient survival were compared. RESULTS: A portal flow of 123 mL/min per100 g of liver tissue was established (area under the curve = 0.58), obtaining a low-flow (n = 129) and a high-flow group (n = 162). The 2 groups were similar in their preoperative characteristics, except for a higher proportion of preoperative ascites, a higher Model for End-Stage Liver Disease score and a lower weight of donors in the high-flow group. The arterial and portal flows were significantly higher in the high-flow group. In the postoperative period, the high-flow group presented a higher rate of ascites. The 5-year survival rate of patients was significantly higher in the high-flow group (76% vs 84%, P = .03). CONCLUSIONS: Patients undergoing liver transplantation with an intraoperative portal vein flow measurement >123 mL/min per 100 g present a greater 5-year survival rate.

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.

Detection of p53 Mutations in Circulating DNA of Transplanted Hepatocellular Carcinoma Patients as a Biomarker of Tumor Recurrence.

p53 is the most commonly mutated gene in malignant human cancers. To detect p53 mutations in circulating DNA (cirDNA) of transplanted hepatocellular carcinoma (HCC) patients could be an interesting approach to know of any tumor recurrence. In this study, our objective was to determine the utility of this method in the diagnosis and the prognosis of HCC tumor recurrence.Twenty four liver transplanted HCC patients were included in the study together with a group of healthy controls. Detection of the specific p53 mutation in cirDNA was performed by high-resolution melting PCR (HRM-PCR) and COLD-PCR immediately before the transplantation. Serum anti-p53 was also determined using a p53-autoantibody ELISA kit.The results of the HRM-PCR and COLD-PCR showed two well-differentiated groups of transplanted patients after normalization by healthy controls. These data allow us to distinguish between patients with p53 mutated cirDNA and those with wild type cirDNA. Moreover, we have found that most of p53 mutated patients also presented elevated anti-p53 antibodies. The present results indicate that it is possible to detect mutated p53 genes with the cirDNA and that this could be used as a biomarker of tumor recurrence during the clinical evolution of the transplanted patients.

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.

Shipping impact on liver graft: results of liver transplantation program in Andalusia.

Liver transplantation for the treatment of patients with advanced liver disease is organized according to a waiting list taking into account different criteria. The agreed distribution model in Andalusia assumes that sometimes an organ is extracted in a different province to that where the implantation is to be performed (shipping), which, therefore, increases the graft ischemic time. The aim of the present study was to determine whether transportation of the organ and being harvested by a team other than the implantation team have a negative effect on final patient survival.

Study of liver transplant rejection in alcoholism-induced cirrhosis.

Rejection is the most usual cause of primary dysfunction of hepatic allograft transplants. Acute rejection (AR) often occurs in the early post-transplantation weeks, with an incidence of 12%-19%. Chronic rejection (CR) is less usual (2.5%-17%) and irreversible. Our aim was to determine the incidence of AR and CR in patients who underwent transplantaton due to alcoholism-induced cirrhosis and the survival of these groups. We undertook a retrospective study of the 93 patients who received a liver transplant due to hepatic cirrhosis between 2005 and 2012. AR occurred in 23.7% of cases, and CR in 11.8%. The median time from implantation to the appearance of AR was 34.5 days, and for CR it was 334 days. The survival of the patients with AR and CR showed no significant differences as compared with the control group (P = .77). From our clinical appraisal, symptoms of previous AR may lead to CR, although the relationship was not significant.

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.

Results of liver transplants from donors aged 70 plus: analysis of Andalusian transplant register.

The progressive increase in the number of liver transplantation candidates has brought with it a consequent increase in waiting list mortality, making it necessary to revise donor selection criteria and to analyze the factors that optimize outcomes. This retrospective observational study of 1802 liver transplantations performed in Andalusia between 2000 and 2010 analyzes the outcomes from donors aged 70 years or older (n = 211) in terms of survival rates of the graft and the recipient, the type of transplant, donor age, and DMELD (Donor-Model for End-Stage Liver Disease) score. The most frequent reasons for transplantation were alcoholic cirrhosis (45.5%), hepatitis C cirrhosis (20.4%), and liver cancer (11.8%). The overall survival rate at 5 years was 67%; with a significant decrease in survival rates for recipients with a DMELD greater than 1400 (44%). In the 70-year-old-plus donor group, the overall patient and graft survival rates were 57% and 52%, respectively. The re-transplantation rate increased proportionately with donor age: 5.9% between 70 and 74 years, 9.5% from 75 to 79 years, and 17.6% from 80 to 84 years. In the alcoholic cirrhosis recipient sub-group, the overall survival rate at 5 years was 69% (P < .05) compared to 34% in hepatitis C patients (P < .05). The widening of the donor age selection criteria is therefore a safe option, provided that a DMELD score less than 1400 is obtained. Although re-transplantation rates increase progressively with donor age, they remain less than 10%. It is necessary to carefully screen recipients of older organs, taking into account that the best results are obtained for patients who have alcoholic cirrhosis, are hepatitis C negative, and have a DMELD score that is less than 1,400.

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.

Impact of the model for end-stage liver disease score on mortality after liver transplantation.

OBJECTIVE: The objective of this study was to analyze survival, and mortality, rates as well as its causes during the month following liver transplantation with respect to the model for end-stage liver disease (MELD) model. MATERIAL AND METHODS: We reviewed the mortality at 24 and 48 hours as well as 1 and 4 weeks of 380 transplanted patients over the past 7 years with regard to the MELD score. RESULTS: The mean patient age was 55 years. Among subjects with MELD score ≤ 15 (n = 142; 37.36%), there were 34 deaths (23.94%), including 7 (4.92%) who died during the first month. The mean cause of death during this period was hemorrhage (n = 3; 8.8%). Among those with MELD scores between 16 and 18 (n = 76; 20%), the mortality rate increased to 23.68% (n = 18), including 3 who died during the first month (3.94%) with 1 case due to hemorrhage. Among the cohort with MELD scores between 19 and 21 (n = 78; 20.52%), 25 (32.05%) died, including 9 during the first month (11.53%). The most frequent cause of death was septic shock (n = 5; 20%). The mortality rate among patients with a MELD score between 22 and 24 was 22% (n = 11), of which 8% (n = 4) died in the month. The mean cause of death during this period was multiple organ dysfunction (n = 2; 18.1%). The patient group with a MELD score >24 had a 32.3% mortality rate (n = 11); 4 patients died during the first month following transplantation (11.76%). The most frequent cause of death was hemorrhage (n = 2; 18.1%). CONCLUSIONS: Survival during the first month did not seem to be related to the MELD score at the time of transplantation, nor did we observe a direct correlation between the MELD score and the overall risk of mortality.

Liver transplantation due to fulminant hepatic failure.

OBJECTIVES: To analyze the epidemiology, causes, complications, and mortality of liver transplants following fulminant hepatic failure over the last 16 years. MATERIALS AND METHODS: We completed a descriptive analysis of 21 patients with fulminant hepatic failure and a liver transplant. In almost half of the cases, the origin of liver failure was unknown. RESULTS: The mean age was 36 years; the study group was 47.61% female (n = 10) and 52.39% male (n = 11). The most common early complication was transplant rejection, which occurred in 33.3% of all patients (n = 7) and was confirmed by liver biopsy; the most frequent long-term complication was autoimmune hepatitis. Two retransplantations were necessary. The total mortality rate was 38.1% (n = 8) with late mortality in three patients (14.3%). CONCLUSIONS: Orthotopic liver transplantation as a treatment for fulminant hepatitis has a higher mortality rate than orthotopic liver transplantation due to other causes. It does, however, enable the survival of 62% of the patients who otherwise would have died due to liver failure. The etiology of most of the cases was unknown. We should point out the high incidence rates for transplant rejection and late autoimmune hepatitis, in addition to the possibility of hemorrhagic colonic diseases that may be associated with the condition causing liver failure. Multidisciplinary control over the patient is useful for deciding at which time a liver transplant would become the only treatment option.

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.