Use of Grafts From Anti-HBc–Positive Donors in Liver Transplantation: A 5-Year,Single-Center Experience

Introduction

Liver transplantation (OLT) is the treatment of choice for advanced hepatic disease. The growing gap between waiting list patients and the number of donations has led to acceptance of less than optimal donors. The aim of this study was to evaluate the 5-year experience with anti hepatitis B core antigen (HBc)–positive liver donors.

Patients and Methods

All recipients of anti-HBc–positive grafts from January 2005 to December 2010 were evaluated annually after OLT for liver disease etiology, Model for End-Stage Liver Disease (MELD) score, and the presence of hepatocellular carcinoma (HCC) liver biopsy histology and serology for hepatitis B virus (HBsAg, anti-HBs, HBV-DNA), hepatitis C virus, and hepatitis D virus as well as antiviral prophylaxis to prevent de novo HBV.

Results

Among the 249 OLT performed from January 2005 to December 2010, (9.3%) cases used grafts from anti-HBc–positive donors. Etiologics of liver disease among the recipients were HBV (n = 13; 32.5%), HCV (n = 13; 32.5%) or other causes (n = 14; 35%). In 20 of the 40 patients (50%), HCC was found in the explanted organ. Of 40 recipients of anti-HBc–positive grafts 11 died, and 7 (17.5%) required retransplantation. Various regimens were employed as post-transplantation antiviral prophylaxis: (l) Immune globulin (25.8%); (2) Oral antiviral drugs (9.7%); and (3) combined prophylaxis (51.6%) or no treatment (12.9%). No difference was observed in patient or graft survival in relation to the etiology of liver disease, the MELD score, or the presence of HCC at the time of OLT, except graft survival was significantly reduced among recipient who underwent transplantation for non-HBV or non-HCV liver diseases compared with those engrafted due to viral hepatitis (P = .0062). No difference was observed in histologic features (grading and staging) compared with the antiviral prophylactic therapy; the 2 patients (5%) who developed de novo HBV had not received prophylaxis after OLT.

Conclusions

Matching anti-HBc–positive grafts to recipients without HBV infection before OLT, may be especially safe.     

Liver Transplantation in Children With Congenital Cardiac Defects: A Case Report and a Short Literature Review

Advances in surgical techniques and follow-up of patients with complex congenital heart disease who were corrected in childhood increasingly survive to adolescence or adulthood. Increasingly anesthesiologists encounter these cases for major noncardiac surgery, including orthotopic liver transplantation (OLT) wherein there is an augmented risk of significant perioperative hemodynamic instability. We performed a successful OLT in a 12-year-old boy with end-stage cryptogenetic liver fibrosis and hepatopulmonary syndrome who was born with a double outflow right ventricle, pulmonary atresia, and pulmonary artery hypoplasia corrected at the age of 1 month. By the time he was considered for OLT his altered pulmonary valve apparatus resulted in severe pulmonary regurgitation, dilated right atrium and ventricle, and elevated right heart pressures. After a temporarily successful angioplasty he was at first placed on the waiting list, then removed, and finally relisted following implantation of a prosthetic pulmonary valve that resulted in significant reduction of right heart pressures.     

Chronic heat stress up-regulates leptin and adiponectin secretion and expression and improves leptin, adiponectin and insulin sensitivity in mice

Heat stress (HS) induces adaptive responses that are responsible for alterations of carbohydrate and lipid metabolism. This study aimed to evaluate the effects of chronic heat treatment on the expression and secretion of leptin and adiponectin, important regulators of energy homeostasis, food intake and insulin action. C57BL/6 mice were subdivided into three groups (24 mice each). The first group was kept under control conditions (C: 22±2?°C). The second group was exposed to HS (35±1?°C). The third group was kept under control conditions and was food restricted (FR). The HS group had higher rectal temperature than the C and FR groups and lower food intake than the C group. Hspa1 (Hspa1a) gene expression in adipose tissue, muscle and liver was higher under HS than FR and C. Heat treatment resulted in decreased blood glucose and non-esterified fatty acids; increased leptin, adiponectin and insulin secretion; and greater glucose disposal. Leptin, adiponectin, leptin and adiponectin receptors, insulin receptor substrate-1 and glucose transporter mRNAs were up-regulated in HS mice. This study provides evidence that HS improves leptin and adiponectin signalling in adipose tissue, muscle and liver. Heat stress was responsible for improving insulin sensitivity and glucose uptake in peripheral tissues, probably mediated by adipokines. Changes in the adipokine levels and sensitivity to them may be considered as an adaptive response to heat.     

Variants in KITLG predispose to testicular germ cell cancer independently from spermatogenic function

Epidemiological data suggest an association and a common pathogenetic link between male infertility and testicular germ cell tumor (TGCT) development. Genome-wide studies identified that TGCT susceptibility is associated with KITLG (c-KIT ligand), which regulates the formation of primordial germ cells, from which TGCT is believed to arise and spermatogenesis develops. In this study, we analyzed the link between KITLG, TGCT, and spermatogenic disruption by performing an association study between the KITLG markers rs995030 and rs4471514 and 426 TGCT cases and 614 controls with normal and abnormal sperm count. We found that TGCT risk was increased more than twofold per copy of the major G allele and A allele in KITLG rs995030 and rs4471514 (odds ratio (OR)=2.38, 95% confidence interval (95% CI)=1.81-3.12; OR=2.43, 95% CI=1.86-3.17 respectively), and homozygotes for the risk allele had a sevenfold increased risk of TGCT. KITLG markers were strongly associated with seminoma subtype (per allele risk increased more than threefold, homozygote risk increased by 13- to 16-fold) and weakly with nonseminoma. KITLG markers were not associated with sperm production, as no difference was observed in men with normozoospermia and azoo-oligozoospermia, both in controls and in TGCT cases. In conclusion, this study provides evidence that KITLG variants are involved in TGCT development and they represent an independent and strong specific risk factor for TGCT independently from spermatogenic function. A shared genetic cause and a common pathogenetic link between TGCT development and impairment of spermatogenesis are not evident from this study.     

Lumbar spine MRI in upright position for diagnosing acute and chronic low back pain: statistical analysis of morphological changes

Background

Patients with low back pain frequently demonstrate recumbent magnetic resonance imaging (MRI) alterations not always related to homogeneous clinical symptoms. The purpose of this study was to evaluate and quantify the statistical significance of variations of some anatomical parameters of the lumbosacral spine and reveal occult disc pathologies from recumbent to upright position in patients with acute and chronic low back pain.

Materials and methods

Fifty-seven patients complaining of low back pain (27 women, 30 men) underwent dynamic lumbosacral MRI with a 0.25-T tilting system (G-scan Esaote). We settled five parameters for which variations have been evaluated: lumbosacral angle, lordosis angle, L3–L4 intersomatic disc height, L3–L4 interspinous processes distance, and widest anteroposterior dural sac diameter. Images were obtained in both recumbent and upright positions.

Results

Statistically significant differences [one-way analysis of variance (ANOVA), p = 0.0043] were found between each pair of values of parameters sampled in recumbent and upright positions. In 70 % of patients, on visual qualitative analysis only, an increment of disc protrusions and/or spondylolisthesis was found in the upright position; in three cases, in the upright position only, an interarticular pseudocyst was found.

Conclusions

Dynamic MRI with an open-configuration, low-field tilting MRI system is a feasible and promising tool to study degenerative pathology of the spine. Moreover, in cases of low back pain with negative MRI in the recumbent position or in patients with pain in the upright position only, tilting MRI permits visualization of occult spine and disc pathologies in patients with acute or chronic low back pain.     

Vitamin D deficiency in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness.