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.

Clinical relevance and prevalence of polymorphisms in CYP3A5 and MDR1 genes that encode tacrolimus biotransformation enzymes in liver transplant recipients.

OBJECTIVES: To study the prevalence and clinical significance of polymorphisms in the CYP3A5 and MDR1 genes in liver transplant patients and their donors; to determine the relative importance of genes from the donor and the recipient; to assess the relationship of polymorphisms with the variability of concentration/dose of tacrolimus for optimization and individualization regimens. MATERIALS AND METHODS: This prospective study included 53 liver transplant recipients who received tacrolimus de novo. CYP3A5 and MDR1 gene polymorphisms were identified in the donors and recipients using polymerase chain reaction. We collected indicator variables of graft function and the patient for 3 months after the transplantation: days 0, 1, 3, 7, 14, 30, 60, and 90. RESULTS: The frequencies of CYP3A5 polymorphisms were: 90.6% (G/G), 9.4% (G/A) and 0% (A/C) in donors and 88.7% (G/G), 11.3% (G/A), and 0% (A/A) in recipients. For the MDR1 gene, they were: 26.4% (C/C), 50.9% (C/T), and 22.6% (T/T) in donors and 17.0% (C/C), 71.7% (C/T), and 11.3% (T/T) in recipients. In the early days after transplant, G/A recipients from G/A donors did not reach the minimum drug levels. Between days 30 and 60, G/G recipients from G/A donors required higher tacrolimus doses. G/G recipients (CYP3A5) from C/T donors (MDR1) had a lower frequency of renal dysfunction, the same rejection rate, and a higher rate of diabetes than the other groups. CONCLUSIONS: For CYP3A5, the presence of the A allele appeared to be related to greater requirements for tacrolimus in the early days after transplantation. Pharmacogenetics combined with pharmacodynamics may be a useful tool to adjust the concentration of tacrolimus depending on the absorption by the individual patient.

Influence of donor age on survival in liver transplantation due to hepatitis C virus.

Cirrhosis secondary to hepatitis C virus (HCV) is one of the most frequent indications for liver transplantation. During recent years, the age of donors has increased, which has led to a worse prognosis for persons undergoing transplantations because of this virus. In this study, we analyzed the 93 transplantations performed during a 6-year period (2000-2005) due to HCV, dividing them into 2 groups according to donor age: <60 years (group A) and >/=60 years (group B). We examined graft and recipient survivals with a mean follow-up of 34 months. Recipient survival among group A was 61% compared with 57% among Group B, the difference being greater if we excluded the initial months after transplantation, since this eliminated the complications inherent to the intervention. Graft survival, according to the Knodell histological activity index, was summarized as: 55.7% histological recurrence, 16.7% fibrosis, and 21% cirrhosis among group A versus 65.6%, 25%, and 18.7%, respectively, among group B. In conclusion, there was improved survival and disease progression was slower among group A compared with group B, suggesting that donor age was an important factor; patient and graft survivals fell progressively with increased donor age.

Efficacy and safety of mycophenolate mofetil monotherapy in liver transplant patients with renal failure induced by calcineurin inhibitors.

OBJECTIVE: To assess the efficacy and safety of mycophenolate mofetil (MMF) monotherapy in liver transplant recipients with renal failure secondary to the use of calcineurin inhibitors (CNIs). MATERIALS AND METHODS: Thirty-one patients on MMF monotherapy with creatinine levels >1.3 mg/dL, previously immunosuppressed with CNIs and MMF, were analyzed. Conversion was started in patients with no acute or chronic rejection episodes and stable liver chemistry. CNI doses were reduced by 25% every 2 to 3 months, or to 50% if the dose was lower than 1 mg/d of tacrolimus or 50 mg/d of cyclosporine. Different variables were recorded from the time that conversion to monotherapy was decided, on the discontinuation day of the calcineurin inhibitor, and during the follow-up. RESULTS: Mean times from transplant to conversion ranged from 14 to 186 months. The minimum follow-up time in monotherapy was 12 months. Renal function improved at 6 months in 70% of cases and at 12 months in 69.6%. Patients with no renal function improvement maintained stable creatinine values. There were no rejection episodes, graft losses, or deaths. No leukopenia occurred, and triglyceride and uric acid values improved. CONCLUSIONS: MMF monotherapy is a safe alternative in patients with posttransplant renal failure secondary to the use of CNIs. Renal function improvement was achieved in almost 70% of patients at 12 months, and creatinine values were maintained in all other patients. The risk of rejection due to the slow tapering of CNIs is minimum.

[Atypical peritoneal tuberculosis. Use of laparoscopy in the diagnosis]. / Presentación atípica de tuberculosis peritoneal. Caso clínico diagnosticado por laparoscopia.

The presence of peritoneal tuberculosis has to be clinically suspected in all patients with abdominal pain of unknown etiology, particularly when it is accompanied by fever, ascites, and abdominal distension. Access to the abdominal cavity using routine laparoscopy provides essential information on the diagnosis, from both macroscopic images and biopsy sampling, which will later provide a pathological and microbiological confirmation. This helps discriminate between potential differential diagnoses that may include similar symptoms. Other laboratory tests have to be considered as diagnostic aids, as well as for the indication of laparoscopy, including ADA, and Gallium-67 or Ca-125 scans.

Scoring guide when deciding to accept an organ for a liver transplant.

UNLABELLED: Our objective was establish a scoring system that allows a donor to be evaluated quickly and easily using a set of variables that are evaluated prior to the donation and another set that are evaluated during surgery. MATERIALS AND METHODS: Prior to the donation we analyzed age, medication requirements, natremia, hepatic biochemistry, gas levels, days in ICU, history of hypertension, and weight. A value of 40% was allocated to this group of factors. During the transplant we assessed the characteristics of the organ-shine, consistency, surface, edge, color, presence of steatosis, and atheromatosis. A value of 60% was allocated to this set. We established a scale of 1 to 10, only accepting organs scoring 5 or more points. Those grafts that received a score between 5 and 7.5 points were called suboptimal and those with over 7.5 points, optimal. We prospectively analyzed 133 donors whose organs were implanted. RESULTS: The survival rate at 1 year was 85%, and the rejection rate was 12%. The incidence of primary graft dysfunction was 8.2% (n = 11) and that of primary graft nonfunction 2.2% (n = 3). The incidence of primary graft dysfunction was greater within the group with fewer points (suboptimal). There were no differences between the optimal and suboptimal groups in terms of primary malfunction, survival, or rejection rate. CONCLUSIONS: The score provided a guide to decide whether to accept viable organs for implantation, given that the point system was obtained quickly and easily. When greater than 5, it correlated with low rates of primary nonfunction (<3%) and of primary graft dysfunction (<15%), with acceptable survival at 1 year (>80%) and acute rejections rate (<15%).

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.

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.

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.

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.

Intestinal obstruction by eosinophilic jejunitis.

Eosinophilic enteritis is an uncommon disease that rarely develops as a surgical emergency. Although it may be associated with infestation by Ancylostoma caninum, its etiology is unknown and often related to a personal or family history of atopy. A transmural involvement may cause intestinal obstruction--more frequently in the jejunum--or even acute abdomen, which may or may not be accompanied by intestinal perforation. The latter two conditions tend to be more commonly associated with ileum disease, causing pain in the lower right quadrant of the abdomen. Patient history, eosinophil count--which may be paradoxically reduced when the disease appears in this way--, ultrasonography, and/or CT lead to the suspicion of this condition before a surgical procedure is considered. A definitive diagnosis, however, must be reached by means of an anatomopathological study. Macroscopically, intestinal loops exhibit a thickened appearance with an elastic consistency. Laparoscopic intestinal biopsy may play a major role in the diagnosis of disease.