Skip directly to content

PubMed Liver Transplant

Subscribe to PubMed Liver Transplant feed PubMed Liver Transplant
NCBI: db=pubmed; Term=liver transplant
Updated: 44 min ago

Mitochondrial DNA Damage can Promote Atherosclerosis Independently of Reactive Oxygen Species through Effects on Smooth Muscle Cells and Monocytes, and Correlates with Higher Risk Plaques in Humans.

Fri, 07/12/2013 - 10:55

Mitochondrial DNA Damage can Promote Atherosclerosis Independently of Reactive Oxygen Species through Effects on Smooth Muscle Cells and Monocytes, and Correlates with Higher Risk Plaques in Humans.

Circulation. 2013 Jul 10;

Authors: Yu E, Calvert PA, Mercer JR, Harrison J, Baker L, Figg NL, Kumar S, Wang JJ, Hurst LA, Obaid DR, Logan A, West NE, Clarke MC, Vidal-Puig A, Murphy MP, Bennett MR

Abstract
BACKGROUND: Mitochondrial DNA (mtDNA) damage occurs in both circulating cells and the vessel wall in human atherosclerosis. However it is unclear whether mtDNA damage directly promotes atherogenesis or is a consequence of tissue damage, which cell types are involved, and whether its effects are only mediated through reactive oxygen species (ROS).
METHODS AND RESULTS: MtDNA damage occurred early in the vessel wall in Apolipoprotein E null (ApoE(-/-)) mice, before significant atherosclerosis developed. MtDNA defects were also identified in circulating monocytes and liver, and associated with mitochondrial dysfunction. To determine whether mtDNA damage directly promotes atherosclerosis, we studied ApoE(-/-) mice deficient for mitochondrial polymerase-γ proofreading activity (polG(-/-)/ApoE(-/-)). polG(-/-)/ApoE(-/-) mice showed extensive mtDNA damage and defects in oxidative phosphorylation, but no increase in ROS. polG(-/-)/ApoE(-/-) mice showed increased atherosclerosis, associated with impaired proliferation and apoptosis of vascular smooth muscle cells, and hyperlipidemia. Transplantation with polG(-/-)/ApoE(-/-) bone marrow increased features of plaque vulnerability, and polG(-/-)/ApoE(-/-) monocytes showed increased apoptosis and inflammatory cytokine release. To examine mtDNA damage in human atherosclerosis, we assessed mtDNA adducts in plaques, and in leukocytes from patients who had undergone virtual histology intravascular ultrasound characterization of coronary plaques. Human atherosclerotic plaques showed increased mtDNA damage compared with normal vessels; in contrast, leukocyte mtDNA damage was associated with higher-risk plaques but not plaque burden.
CONCLUSIONS: We show that mtDNA damage in vessel wall and circulating cells is widespread, causative and indicates higher risk in atherosclerosis. Protection against mtDNA damage and improvement of mitochondrial function are potential areas for new therapeutics.

PMID: 23841983 [PubMed - as supplied by publisher]

ASKP1240, a Fully Human Anti-CD40 Monoclonal Antibody, Prolongs Pancreatic Islet Allograft Survival in Nonhuman Primates.

Fri, 07/12/2013 - 10:55

ASKP1240, a Fully Human Anti-CD40 Monoclonal Antibody, Prolongs Pancreatic Islet Allograft Survival in Nonhuman Primates.

Am J Transplant. 2013 Jul 10;

Authors: Watanabe M, Yamashita K, Suzuki T, Kamachi H, Kuraya D, Koshizuka Y, Ogura M, Yoshida T, Aoyagi T, Fukumori D, Shimamura T, Okimura K, Maeta K, Miura T, Sakai F, Todo S

Abstract
A strategy for inhibiting CD40 has been considered as an alternative approach for immunosuppression because of undesirable effects of anti-CD154 monoclonal antibodies (mAbs). Previously, we demonstrated that ASKP1240, which is a fully human anti-CD40 mAb, significantly prolonged kidney and liver allograft survival in cynomolgus monkeys without causing thromboembolic complications. Herein, we evaluated the effect of ASKP1240 on pancreatic islet transplantation (PITx) in cynomolgus monkeys. Diabetes was induced by total pancreatectomy, and islet allografts were transplanted into the liver. Following PITx (8201-12 438 IEQ/kg), blood glucose levels normalized promptly in all animals. Control islet allografts were rejected within 9 days (n = 3), whereas ASKP1240 (10 mg/kg) given on postoperative days 0, 4, 7, 11 and 14 (induction treatment, n = 5) significantly prolonged graft survival time (GST) to >15, >23, 210, 250 and >608 days, respectively. When ASKP1240 (5 mg/kg) was administered weekly thereafter up to post-PITx 6 months (maintenance treatment, n = 4), GST was markedly prolonged to >96, >115, 523 and >607 days. During the ASKP1240 treatment period, both anti-donor cellular responses and development of anti-donor antibodies were abolished, and no serious adverse events were noted. ASKP1240 appears to be a promising candidate for immunosuppression in clinical PITx.

PMID: 23841873 [PubMed - as supplied by publisher]

The role of platelets in chronic liver disease and acute liver injury.

Fri, 07/12/2013 - 10:55

The role of platelets in chronic liver disease and acute liver injury.

Hepatol Res. 2013 Jul 11;

Authors: Nowatari T, Murata S, Fukunaga K, Ohkohchi N

Abstract
Platelets contain not only hemostatic factors but also many growth factors that play important roles in wound healing and tissue repair, and has been already used for the promotion of tissue regeneration in the clinical setting, such as dental implantation and plastic surgery. Thrombocytopenia, which is frequently found in patients with chronic liver disease and cirrhosis, is due to various causes such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism. However, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in chronic liver disease are poorly understood. In acute liver injury, it is reported that platelets are recruited to the liver and contributes to liver damage by promoting the induction of chemotactic factors and the accumulation of leukocytes in the liver, whereas platelets or mediators released by platelets can have a protective effect against liver injury. In this review, we highlight the recent accumulated knowledge concerning the role of platelets in chronic liver disease and acute liver injury.

PMID: 23841688 [PubMed - as supplied by publisher]

B cells assist allograft rejection in the deficiency of protein kinase c-theta.

Fri, 07/12/2013 - 10:55

B cells assist allograft rejection in the deficiency of protein kinase c-theta.

Transpl Int. 2013 Jun 15;

Authors: Yan W, Xu R, Ma LL, Han W, Geevarghese SK, Williams PE, Sciammas R, Chong AS, Yin DP

Abstract
We have previously shown that mice deficient in protein kinase C theta (PKCθ) have the ability to reject cardiac allografts, but are susceptible to tolerance induction. Here we tested role of B cells in assisting alloimmune responses in the absence of PKCθ. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKCθ knockout (PKCθ(-/-) ), PKCθ and B cell double-knockout (PBDK, H-2b) mice and wild-type (WT) C57BL/6 (H-2b) mice. PBDK mice spontaneously accepted the allografts with the inhibition of NF-κB activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKCθ(-/-) , but not in WT mice. Co-transfer of PKCθ(-/-) T plus PKCθ(-/-) B cells or primed sera triggered allograft rejection in Rag1(-/-) mice, and only major histocompatibility complex class II-enriched B cells, but not class I-enriched B cells, were able to promote rejection. This, together with the inability of PKCθ(-/-) and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKCθ(-/-) T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKCθ(-/-) T cells to mediate acute allograft rejection.

PMID: 23841454 [PubMed - as supplied by publisher]

Local Therapies for Unresectable Primary Hepatocellular Carcinoma

Fri, 07/12/2013 - 10:55

Local Therapies for Unresectable Primary Hepatocellular Carcinoma

Book. 2013 05

Authors: Belinson S, Yang Y, Chopra R, Shankaran V, Samson D, Aronson N

Abstract
OBJECTIVES: To characterize the comparative effectiveness and harms of various local hepatic therapies for patients with unresectable primary hepatocellular carcinoma (HCC) who are not candidates for surgical resection or liver transplantation. Local hepatic therapies include those related to ablation, embolization, and radiotherapy.
DATA SOURCES: We searched MEDLINE(®) and Embase(®) from January 2000 to July 2012. We also searched for gray literature in databases with regulatory information, clinical trial registries, abstracts and conference papers, as well as information from manufacturers.
REVIEW METHODS: We sought studies reporting two final health outcomes—overall survival and quality of life—and various adverse events related to the different interventions. Data were dually abstracted by a team of four reviewers. A third reviewer resolved conflicts when necessary. We assessed the quality of individual studies and graded the strength of the body of evidence according to prespecified methods.
RESULTS: We identified 1,707 articles through the literature search, excluded 1,665 at various stages of screening, and included 42 articles. To these we added 6 hand-searched articles for a total of 48 articles included in this review. Our searches of gray literature sources did not yield any additional published studies. The included literature was comprised of 6 randomized controlled trials (RCTs), 4 nonrandomized comparative studies, 35 case series, and 3 case reports. One RCT was rated as good, three were rated as fair, and two were rated as poor quality. We included 13 local hepatic therapies in this review; however, there was sufficient comparative evidence (three RCTs) to assess only one direct comparison: radiofrequency ablation (RFA) versus percutaneous ethanol injection (PEI)/percutaneous acetic acid injection (PAI). Three-year survival when treated with RFA was superior to that for PEI/PAI for unresectable HCC, with a moderate grade of evidence. Time to progression (TTP) and local recurrence were better for RFA than PEI/PAI, but length of stay (LOS) was longer after RFA than PEI/PAI. Strength of evidence for all other comparisons was rated insufficient. There was a low level of evidence to support longer overall survival following RFA than PEI/PAI for the subgroup of patients with larger lesion size.
CONCLUSIONS: Of the 13 interventions included in this report, only 1 comparison had sufficient evidence to receive a rating above insufficient. There was moderate strength of evidence demonstrating better overall survival at 3 years, a low level of evidence supporting improved overall survival for patients with larger lesion sizes, and low strength of evidence for improved TTP and local control for RFA than PEI/PAI for the treatment of unresectable HCC. A low level of evidence also supports a longer LOS following RFA than PEI/PAI. For all other outcomes and comparisons, there is insufficient evidence to permit conclusions on the comparative effectiveness of local hepatic therapies for unresectable HCC. Additional RCTs are necessary for all comparisons. Focusing on comparisons with RFA may allow for the greatest integration of new data with the current body of evidence.


PMID: 23844445

Curcumin Attenuates Acute Graft-versus-Host Disease Severity via In Vivo Regulations on Th1, Th17 and Regulatory T Cells.

Thu, 07/11/2013 - 11:05

Curcumin Attenuates Acute Graft-versus-Host Disease Severity via In Vivo Regulations on Th1, Th17 and Regulatory T Cells.

PLoS One. 2013;8(6):e67171

Authors: Park MJ, Moon SJ, Lee SH, Yang EJ, Min JK, Cho SG, Yang CW, Park SH, Kim HY, Cho ML

Abstract
BACKGROUND: In this study we examined the in vivo and in vitro effects and mechanisms of action of curcumin on the development of acute graft-versus-host disease (GVHD) using a murine model.
METHODOLOGY/PRINCIPAL FINDINGS: Mixed lymphocyte reactions were used to determine the in vitro effects of curcumin. Treatment with curcumin attenuated alloreactive T cell proliferation and inhibited the production of interferon (IFN)-γ and interleukin (IL)-17. In a murine acute GVHD model, transplantation of curcumin-treated allogeneic splenocytes into irradiated recipient mice significantly reduced the clinical severity scores of acute GVHD manifested in the liver, skin, colon and lung as compared with animals receiving vehicle-treated splenocytes. c-Fos and c-Jun expression levels in the skin and intestine, which are major target organs, were analyzed using immunohistochemical staining. Expression of both proteins was reduced in epithelial tissues of skin and intestine from curcumin-treated GVHD animals. The IFN-γ-expressing CD4(+) splenocytes and IFN-γ-expressing lymph node cells were dramatically decreased in curcumin-treated mice. In contrast, CD4(+)Foxp3(+) splenocytes were increased in the curcumin-treated acute GVHD animals. Flow cytometric analysis revealed that animals transplanted with curcumin-treated allogeneic splenocytes showed increased populations of CD4(+) regulatory T cells (Tregs) as well as CD8(+) Treg cells, compared to animals administered vehicle-treated splenocytes. Curcumin-treated acute GVHD animals could have a change in B cell subpopulations.
CONCLUSION/SIGNIFICANCE: In the present study, we investigated the efficacy and mechanism of action of curcumin treatment against acute GVHD. The acute GVHD mice administered with curcumin-treated splenocytes showed significantly reduced severity of acute GVHD. Curcumin exerted in vivo preventive effects on acute GVHD by reciprocal regulation of T helper 1 (Th1) and Treg (both CD4(+) and CD8(+) Treg) cell lineages as well as B cell homeostasis.

PMID: 23840617 [PubMed - in process]

Epstein-Barr virus negative primary hepatic leiomyoma: Case report and literature review.

Thu, 07/11/2013 - 11:05

Epstein-Barr virus negative primary hepatic leiomyoma: Case report and literature review.

World J Gastroenterol. 2013 Jul 7;19(25):4094-8

Authors: Luo XZ, Ming CS, Chen XP, Gong NQ

Abstract
Primary hepatic leiomyoma is a neoplasm of mesenchymal origin and occurs only rarely. Secondary to benign smooth muscle proliferation, it is usually found in adult women and is associated with Epstein-Barr virus (EBV) infection. Here, we report the 29(th) case of primary hepatic leiomyoma with its unique features related to diagnosis, treatment and developmental biology. A 48-year-old man, with an immunocompromised status, complained of pain in the upper quadrant of the abdomen. Serological analysis indicated no presence of hepatitis virus, no human immunodeficiency virus, and no EBV infection. The levels of α-fetoprotein and carcinoembryonic antigen were normal. A mass was detected in segment III of the hepatic lobe by ultrasonography and an abdominal computed tomography scan. Endoscopy had negative findings. Exploratory laparotomy found no existing extrahepatic tumor and left lateral lobectomy was performed. Pathological examination showed the mass to be a typical leiomyoma. The cells were positive for α-smooth muscle actin and desmin, and negative for the makers of gastrointestinal stromal tumor (GIST), including CD117, CD34 and DOG1 (discovered on GIST1). In situ hybridization revealed negative status for EBV-encoded small RNA. After left lateral lobectomy, the patient was not given chemotherapy or radiotherapy. During a 2-year follow-up, no sign of local recurrence or distant metastasis was observed. In conclusion, we report a rare case of primary hepatic leiomyoma in a male patient without EBV infection. Hepatic resection was curative. This case presents data to expand our knowledge concerning the complex and heterogeneous nature of primary liver leiomyoma, indicating that EBV infection is important but neither necessary nor sufficient for the development of primary liver leiomyoma.

PMID: 23840159 [PubMed - in process]

Unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis.

Thu, 07/11/2013 - 11:05

Unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis.

World J Gastroenterol. 2013 Jul 7;19(25):4015-22

Authors: Yilmaz M, Akbulut S, Kutluturk K, Sahin N, Arabaci E, Ara C, Yilmaz S

Abstract
AIM: To investigate the prevalence and implications of unusual histopathological findings in appendectomy specimens from patients with suspected acute appendicitis.
METHODS: The demographic and histopathological data of 1621 patients (≥ 16 years-old) who underwent appendectomy to treat an initial diagnosis of acute appendicitis between January 1999 and November 2011 were retrospectively assessed. Microscopic findings were used to classify the patients under six categories: appendix vermiformis, phlegmonous appendicitis, gangrenous appendicitis, perforated appendicitis, supurative appendicitis, and unusual histopathologic findings. The demographic and clinicopathologic characteristics of patients with unusual histopathologic findings were evaluated in detail, and re-analysis of archived resected appendix specimens was carried out.
RESULTS: A total of 912 males and 709 females, from 16 to 94 years old, were included in the study and comprised 789 cases of suppurative appendicitis, 370 cases of appendix vermiformis, 243 cases of perforated gangrenous appendicitis, 53 cases of flegmaneous appendicitis, 32 cases of gangrenous appendicitis, and 134 (8.3%) cases of unusual histopathological findings. The unusual histopathological findings included fibrous obliteration (n = 62), enterobius vermicularis (n = 31), eosinophilic infiltration (n = 10), mucinous cystadenoma (n = 8), carcinoid tumor (n = 6), granulomatous inflammation (n = 5), adenocarcinoma (n = 4; one of them mucinous), and mucocele (n = 3), adenomatous polyp (n = 1), taenia sup (n = 1), ascaris lumbricoides (n = 1), appendiceal diverticula (n = 1), and B cell non-hodgkin lymphoma (n = 1). None of the 11 patients with subsequent diagnosis of tumor were suspected of cancer prior to the appendectomy.
CONCLUSION: Even when the macroscopic appearance of appendectomy specimens is normal, histopathological assessment will allow early diagnosis of many unusual diseases.

PMID: 23840147 [PubMed - in process]

It's more than just size: Obesity and transplantation.

Thu, 07/11/2013 - 11:05

It's more than just size: Obesity and transplantation.

Liver Transpl. 2013 Jul 9;

Authors: Orloff MS, Dokus MK

PMID: 23840031 [PubMed - as supplied by publisher]

Serum interleukin-22 level is a negative prognostic indicator in patients with HBV-related hepatocellular carcinoma.

Thu, 07/11/2013 - 11:05

Serum interleukin-22 level is a negative prognostic indicator in patients with HBV-related hepatocellular carcinoma.

Hepatology. 2013 Jul 10;

Authors: Jiang R, Zhang C, Xia Y, Qian X, Wang X, Sun B

PMID: 23839975 [PubMed - as supplied by publisher]

Protease Inhibitors for Hepatitis C: Economic Implications.

Thu, 07/11/2013 - 11:05

Protease Inhibitors for Hepatitis C: Economic Implications.

Pharmacoeconomics. 2013 Jul 10;

Authors: Turner SJ, Brown J, Paladino JA

Abstract
Chronic hepatitis C virus (HCV) infection, a blood-borne virus, is the leading cause of chronic liver disease and liver transplantation worldwide. Chronic HCV infection is usually asymptomatic in the early stages of the disease, making an estimation of the total population affected difficult to elicit. The gold standard treatment option to date has been a combination of pegylated interferon and ribavirin. Recent developments have led to the introduction of two protease inhibitors for use in chronic HCV-boceprevir and telaprevir. Phase III studies have shown both agents have the potential to significantly increase the probability of attaining a sustained virologic response (the primary outcome of interest in chronic HCV) in genotype 1 infections. However, the added cost of these agents also presents the need for decision makers to determine their place on drug formularies. The protease inhibitors are to be administered as triple therapy with the existing gold standard. However, significant variation exists as to the proposed duration of triple therapy, use of lead-in pegylated interferon and ribavirin and subsequent pegylated interferon therapy after finishing the course of triple therapy. Treatment algorithms also exist for the use of stopping rules in the case of early non-responders.The aim of this review is to highlight the current understanding of the economic impact protease inhibitors may have on health care systems and considerations required in the treatment of HCV. Economic and health-related quality of life issues are addressed from multiple viewpoints. The major aspects of the economic evaluations, to date, that included triple therapy as an alternative in the treatment of chronic HCV are brought to light. Future economic evaluations in alternative settings would be useful. The review also emphasizes the challenges for future research. This includes the potential for new therapies to no longer require inclusion of pegylated interferon and/or ribavirin, as well as the use of protease inhibitors in non-genotype 1 patients or those with significant co-morbidities such as HIV/AIDS.

PMID: 23839698 [PubMed - as supplied by publisher]

Mucosal Addressin Cell Adhesion Molecule (MAdCAM-1) Expression Is Upregulated in the Cirrhotic Liver and Immunolocalises to the Peribiliary Plexus and Lymphoid Aggregates.

Thu, 07/11/2013 - 11:05

Mucosal Addressin Cell Adhesion Molecule (MAdCAM-1) Expression Is Upregulated in the Cirrhotic Liver and Immunolocalises to the Peribiliary Plexus and Lymphoid Aggregates.

Dig Dis Sci. 2013 Jul 10;

Authors: Ala A, Brown D, Khan K, Standish R, Odin JA, Fiel MI, Schiano TD, Hillan KJ, Rahman SA, Hodgson HJ, Dhillon AP

Abstract
BACKGROUND: Enhanced cell expression of MAdCAM-1 is critical in tissue recruitment of lymphocytes in response to stimuli expressing the α4β7 integrin. MAdCAM-1 is well characterized in gut mucosa with emerging evidence of hepatic expression.
AIMS: (i) Compare quantitative/semi-quantitatively MAdCAM-1 expression in relation to early and advanced liver diseases (ii) Define the fine structure of vascular plexuses/lymphatics in the portal tract on which MAdCAM-1 is expressed.
METHODS: Using alkaline phosphatase anti-alkaline phosphatase methodology on paraffin embedded tissue sections (n = 28) from cirrhotic individuals who underwent orthotopic liver transplant, we evaluated MAdCAM-1 expression and compared with pre-cirrhotic, fulminant hepatitis B, and non-cirrhotic portal hypertension tissue sections. The positive controls included normal colon tissue with negative controls without primary antibody and isotype-matched purified IgG. We developed a real time PCR to quantify levels of MAdCAM-1 mRNA in our samples.
RESULTS: MAdCAM-1 was expressed in 27/28 of the cirrhotic sections, localized primarily to septal areas within (i) endothelium of the peribiliary vascular plexus (PBP) (ii) lymphoid aggregates, with absence from normal, non-cirrhotic portal hypertension and pre-cirrhotic livers. There was significant upregulation of MAdCAM-1 mRNA in cirrhosis (p < 0.011), consistent with immunohistochemical analysis.
CONCLUSIONS: MAdCAM-1 is up-regulated in cirrhosis with expression on PBP and lymphoid aggregates. MAdCAM-1 is likely to contribute to the localization and recruitment of α4β7 lymphocytes during the pathogenesis of cirrhosis. MAdCAM-1 could be a useful marker of advanced liver disease. Further studies with respect to the expression of MAdCAM-1 in the presence of reversible and non-reversible stages of liver disease may be of merit.

PMID: 23839340 [PubMed - as supplied by publisher]

Recent advances in the treatment of homozygous familial hypercholesterolaemia.

Thu, 07/11/2013 - 11:05

Recent advances in the treatment of homozygous familial hypercholesterolaemia.

Curr Opin Lipidol. 2013 Aug;24(4):288-94

Authors: Marais AD, Blom DJ

Abstract
PURPOSE OF REVIEW: To review publications in the English literature over the past 18 months relating to the management of homozygous familial hypercholesterolaemia.
RECENT FINDINGS: Experience with plasmapheresis has been summarized, guidelines are being introduced to enhance patient care and registries are under consideration to improve analysis of management in this rare but serious disorder. Liver transplantation has been reviewed for its biochemical efficacy, but still does not ensure freedom from vascular complications. For patients without access to plasmapheresis, there is now evidence that high-dose statins do improve the prognosis, but combination therapy with additional agents should still be considered for better outcome. Promising new agents that inhibit LDL production by limiting apolipoprotein B100 synthesis by means of antisense oligonucleotides (mipomersen) or by inhibition of microsomal triacylglycerol transfer protein (lomitapide) have made significant additional LDL reduction possible but are associated with hepatic fat accumulation and long-term safety data is still required. Several other lipid modulating agents and gene therapy are still being explored.
SUMMARY: The management of homozygous familial hypercholesterolaemia by pharmacological means is improving with agents that limit lipoprotein production but plasmapheresis, generally in combination with additional pharmacological treatment, remains the proven option. Liver transplantation is now less likely to be undertaken owing to improved pharmacological options and prognosis.

PMID: 23839331 [PubMed - in process]

Development and validation of a nomogram based on clinical factors and standard laboratory tests for prediction of clinically significant liver fibrosis in chronic hepatitis C virus infection.

Thu, 07/11/2013 - 11:05

Development and validation of a nomogram based on clinical factors and standard laboratory tests for prediction of clinically significant liver fibrosis in chronic hepatitis C virus infection.

Eur J Gastroenterol Hepatol. 2013 Jul 3;

Authors: Sagrini E, Ardoino I, Marano G, Gianstefani A, Orlandini A, Sebastiani G, Donati G, Cucchetti A, Pelosi G, Ferrari C, Alberti A, Biganzoli E, Piscaglia F, Bolondi L

Abstract
OBJECTIVES: Staging liver fibrosis in chronic viral hepatitis C (HCV) patients is essential for prompting surveillance and treatment. The aim of this study was to develop a nomogram, on the basis of simple clinical and laboratory variables, to predict three clinically significant stages of fibrosis (nil-mild, moderate, advanced/cirrhosis), using histology as reference, and to compare its performance with that of FibroTest, a widely used noninvasive fibrosis score.
MATERIALS AND METHODS: Nomograms are graphical representations of a mathematical formula, used as predictive tools. The study retrospectively recruited 406 HCV patients undergoing liver biopsy. Nomogram was developed in a training set of 252 patients and tested in a validation set of 154 patients. Histology was staged according to the Metavir system. Fibrosis stages were subgrouped as follows: advanced fibrosis/cirrhosis (F3/F4, 24%), nil-mild (F0/F1, 36%), and moderate (F2, 40%). Age at biopsy, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, and prothrombin activity formed the basis for the so-called Fibro-Nomogram, which, in one graphical representation, estimates probability for different stages of fibrosis.
RESULTS: Areas under the receiver-operating characteristic curves for advanced fibrosis/cirrhosis were similar for training (0.86) and validation sets (0.87). For nil-mild fibrosis, area under the receiver-operating characteristics were 0.81 and 0.79. Compared with FibroTest, Fibro-Nomogram performed slightly better at predicting severe fibrosis (F3/F4) with positive likelihood ratio (LR+) 5.07 (95% confidence interval 3.08-8.37) versus LR+ 3.82 (95% confidence interval 2.56-5.71) for FibroTest. For nil-mild fibrosis, the two tests showed limited but comparable performances.
CONCLUSION: In HCV patients, Fibro-Nomogram, an inexpensive and readily available predictive tool, could enable clinicians to interpret patients' profile, concurrently stratifying patients into three clinically relevant probability categories with good overall performance.

PMID: 23839163 [PubMed - as supplied by publisher]

Targeting the microbiota in the management of gastrointestinal and liver disease.

Thu, 07/11/2013 - 11:05

Targeting the microbiota in the management of gastrointestinal and liver disease.

Rev Gastroenterol Peru. 2013 APRIL-JUNE;33(2):139-144

Authors: Quigley EM, Monsour HP

Abstract
Thanks to rapid advances in technology the details of the human microbiome and its functions in health and disease are being progressively revealed. Though many reports have linked various disease states with an altered microbiome and while some associations between the microbiome and disease states are well established, many of these studies are largely descriptive and the changes reported in the microbiome have yet to be shown to be causative. A number of strategies are available to modify the microbiota; some such as the use of antibiotics for specific indications, are well established, others such as the use of probiotics and prebiotics in a variety of disease states are supported by more limited data. Fecal transplantation has emerged as an exciting, albeit rather drastic, intervention for intestinal and, perhaps, other disorders. Other approaches, such as the isolation, purification and formulation of small molecules with specific biological actions, derived from the microbiota look very promising.Key words: Gastrointestinal diseases; Intestinal diseases; Liver diseases (source: MeSH NLM).

PMID: 23838941 [PubMed - as supplied by publisher]

Effect of Donor Right Hepatectomy on Splenic Volume and Platelet Count for Living Donor Liver Transplantation.

Thu, 07/11/2013 - 11:05

Effect of Donor Right Hepatectomy on Splenic Volume and Platelet Count for Living Donor Liver Transplantation.

J Gastrointest Surg. 2013 Jul 10;

Authors: Kim SJ, Na GH, Choi HJ, You Y, Kim DG

Abstract
BACKGROUND: Donor hepatectomy for living donor liver transplantation accompanies physio-morphological changes of the liver and spleen. Therefore, the long-term consequences of these organs should be characterized to ensure donor's safety.
METHODS: A total of 382 right liver harvests for liver transplantation were performed from October 2000 to February 2011. Clinical parameters across donor operations were compared, and the associations were investigated.
RESULTS: The remaining liver grew continually, reaching 81.5 ± 11.2 % of the entire liver until 6 months after donation. The spleen grew to 143.1 ± 28.8 % of the pre-donation value within 1 week after surgery, and thereafter, its size decreased gradually to 130.6 ± 25.1 % at 6 months. At 6 months post-donation, 48.1 % (114/237) of donors showed an increase of ≥30 % in splenic volume, and 15.9 % (50/315) of donors exhibited a decrease of ≥30 % in platelet count. However, patients with splenic enlargement and/or decrease in platelet count at 6 months post-donation were not different in liver function, liver regeneration, or overall complications.
CONCLUSIONS: Although splenic enlargement and/or decrease in platelet count can persist for more than 6 months after donation in patient population after donor right hepatectomy, such a change did not impact donor's safety.

PMID: 23838887 [PubMed - as supplied by publisher]

Clinical relevance of human leukocyte antigen antibodies in liver, heart, lung and intestine transplantation.

Thu, 07/11/2013 - 11:05

Clinical relevance of human leukocyte antigen antibodies in liver, heart, lung and intestine transplantation.

Curr Opin Organ Transplant. 2013 Aug;18(4):463-9

Authors: Campbell P

Abstract
PURPOSE OF REVIEW: Solid phase assays identify human leukocyte antigen (HLA) antibodies with a great sensitivity. Whether to accept or decline an organ if the virtual crossmatch is positive, when to monitor and whether to treat de-novo donor-specific antibody (DSA) posttransplant remain challenging issues for the transplant clinician.
RECENT FINDINGS: Technologies that can differentiate which antibodies pose the greatest risk for antibody-mediated rejection (AMR) are evolving. Complement fixing luminex assays have been used to predict high-risk antibodies, but using these assays alone will miss some preformed antibodies. How these technologies fit into the laboratory's testing algorithm will likely need to be individualized. Posttransplant de-novo DSAs are associated with inferior outcomes. In hearts, similar to renal transplantation, acute rejection is a risk factor for developing de-novo DSA. Further data are needed to determine whether other risk factors are similar to those reported for renal transplants. Antibodies to self-antigens are increasingly recognized posttransplant and how the alloimmune response contributes to altered autoregulation is a current research focus.
SUMMARY: Identification of DSA enables the clinician to make informed decisions regarding whether or not to accept an organ and if augmented immunosuppression is indicated. Monitoring for DSA posttransplant identifies recipients at a greater risk for AMR and can guide management. However, the best approach to dealing with de-novo DSA remains unclear.

PMID: 23838652 [PubMed - in process]

Biomarkers of tolerance.

Thu, 07/11/2013 - 11:05

Biomarkers of tolerance.

Curr Opin Organ Transplant. 2013 Aug;18(4):416-20

Authors: Gökmen R, Hernandez-Fuentes MP

Abstract
PURPOSE OF REVIEW: As the induction and maintenance of donor-specific tolerance is a central aim in solid organ transplantation, it is essential that clinicians are able to identify and monitor tolerance accurately and reliably. This review highlights recent advances in defining sets of biomarkers in noninvasive samples that may guide minimization and withdrawal of immunosuppression in tolerant recipients.
RECENT FINDINGS: Recent studies in liver and kidney transplant recipients have identified distinct biomarker profiles that are associated with operational tolerance. Although there is some heterogeneity in the findings of these studies, these have suggested novel cellular mechanisms for the development of tolerance.
SUMMARY: Multiple platforms such as microarray gene expression analysis, flow cytometry, and immune cell functional assays have been used to discover and validate composite sets of biomarkers, which identify recipients with operational tolerance both in liver and kidney transplantation. These studies suggest that distinct cellular and molecular mechanisms lead to the development of tolerance in different transplanted organs. These putative biomarker profiles now need to be validated prospectively in trials of immunosuppression withdrawal and in novel approaches to induce transplant tolerance.

PMID: 23838646 [PubMed - in process]

Addressing Geographic Disparities in Liver Transplantation Through Redistricting.

Thu, 07/11/2013 - 11:05

Addressing Geographic Disparities in Liver Transplantation Through Redistricting.

Am J Transplant. 2013 Jul 9;

Authors: Gentry SE, Massie AB, Cheek SW, Lentine KL, Chow EH, Wickliffe CE, Dzebashvili N, Salvalaggio PR, Schnitzler MA, Axelrod DA, Segev DL

Abstract
Severe geographic disparities exist in liver transplantation; for patients with comparable disease severity, 90-day transplant rates range from 18% to 86% and death rates range from 14% to 82% across donation service areas (DSAs). Broader sharing has been proposed to resolve geographic inequity; however, we hypothesized that the efficacy of broader sharing depends on the geographic partitions used. To determine the potential impact of redistricting on geographic disparity in disease severity at transplantation, we combined existing DSAs into novel regions using mathematical redistricting optimization. Optimized maps and current maps were evaluated using the Liver Simulated Allocation Model. Primary analysis was based on 6700 deceased donors, 28 063 liver transplant candidates, and 242 727 Model of End-Stage Liver Disease (MELD) changes in 2010. Fully regional sharing within the current regional map would paradoxically worsen geographic disparity (variance in MELD at transplantation increases from 11.2 to 13.5, p = 0.021), although it would decrease waitlist deaths (from 1368 to 1329, p = 0.002). In contrast, regional sharing within an optimized map would significantly reduce geographic disparity (to 7.0, p = 0.002) while achieving a larger decrease in waitlist deaths (to 1307, p = 0.002). Redistricting optimization, but not broader sharing alone, would reduce geographic disparity in allocation of livers for transplant across the United States.

PMID: 23837931 [PubMed - as supplied by publisher]

Non-invasive assessment of liver fibrosis using magnetic resonance elastography in liver transplant recipients with hepatitis C.

Thu, 07/11/2013 - 11:05

Non-invasive assessment of liver fibrosis using magnetic resonance elastography in liver transplant recipients with hepatitis C.

Clin Transplant. 2013 Jul 10;

Authors: Crespo S, Bridges M, Nakhleh R, McPhail A, Pungpapong S, Keaveny AP

Abstract
BACKGROUND: Liver biopsy has been the reference standard when evaluating fibrosis due to recurrent hepatitis after liver transplantation. Magnetic resonance elastography estimates liver stiffness, correlating to fibrosis.
AIM: To investigate the utility of elastography in staging liver fibrosis in transplant recipients with hepatitis C.
METHODS: Fifty-four patients, ≥12 months post-transplant, underwent elastography within three months of biopsy. Discriminatory capability for METAVIR fibrosis stages F0-2 vs. F3-4 and receiver operating characteristic curve (ROC) analysis were determined.
RESULTS: On biopsy, 27 patients had METAVIR fibrosis score 0-1; 12 had a 3 or 4. There was significant correlation between histologic fibrosis and shear stiffness (R² = 0.588, p < 0.0001). Using a cutoff value of 3.5 kPa, elastography was 91% sensitive and 72% specific in differentiating fibrosis scores of ≥3 from 0 to 1. The AUC of elastography in predicting a fibrosis score of ≥3 was 0.92. Multivariate analysis revealed no correlation between the grade of histologic inflammation and liver stiffness measured by magnetic resonance elastography (R² = 0.265, p = 0.47).
CONCLUSION: Magnetic resonance elastography is an accurate non-invasive technique for excluding stage ≥3 graft in recipients with hepatitis C.

PMID: 23837611 [PubMed - as supplied by publisher]

Pages