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Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell.

Wed, 12/19/2012 - 11:51
Related Articles

Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell.

Biochem Biophys Res Commun. 2012 Aug 24;425(2):468-72

Authors: Xu N, Shen C, Luo Y, Xia L, Xue F, Xia Q, Zhang J

Abstract
Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of patients with advanced liver cancer. However, acquisition of cisplatin resistance is common in patients with hepatocellular carcinoma (HCC), and the underlying mechanism of such resistance is not fully understood. In the study, we found that miR-130a levels were significantly increased in HCC patients treated with cisplatin-based chemotherapy. miR-130a levels were also higher in cisplatin-resistant Huh7 cells than in Huh7 cells. Overexpression of miR-130a contributed to cisplatin resistance in Huh7 cell, whereas knockdown of miR-130a overcame cisplatin resistance in cisplatin-resistant Huh7 cell. We further demonstrated that upregulated miR-130a directly inhibited expression of tumor suppressor gene RUNX3, which resulted in activation of Wnt/β-catenin signaling and increased drug resistance. These data suggest that miR-130a/RUNX3/Wnt signaling represents a novel pathway regulating chemoresistance, thus offering a new target for chemotherapy of HCC.

PMID: 22846564 [PubMed - indexed for MEDLINE]

Mast cell leukemia.

Tue, 12/18/2012 - 11:14

Mast cell leukemia.

Blood. 2012 Dec 14;

Authors: Georgin-Lavialle S, Lhermitte L, Dubreuil P, Chandesris MO, Hermine O, Damaj G

Abstract
Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis accounting for less than 1% of all mastocytosis. It may appear de novo or secondary to previous mastocytosis and shares more clinicopathological aspects with systemic mastocytosis than with acute myeloid leukemia. Symptoms of mast cell activation, involvement of the liver, spleen, peritoneum, bones and marrow are frequent. Diagnosis is based on the presence of ≥ 20% atypical mast cells in the marrow or ≥ 10% in the blood; however, an aleukemic variant is frequently encountered in which the number of circulating MCs is < 10%. The common phenotypic features of pathologic mast cells encountered in most forms of mastocytosis are unreliable in MCL. Unexpectedly, non KIT D816V mutations are frequent and therefore, complete gene sequencing is necessary. Therapy usually fails and the median survival time is less than 6 months. The role of combination therapies and bone marrow transplantation needs further investigation.

PMID: 23243287 [PubMed - as supplied by publisher]

Donor-Transmitted Malignancy in a Liver Transplant Recipient: A Case Report and Review of Literature.

Tue, 12/18/2012 - 11:14

Donor-Transmitted Malignancy in a Liver Transplant Recipient: A Case Report and Review of Literature.

Dig Dis Sci. 2012 Dec 16;

Authors: Kim B, Woreta T, Chen PH, Limketkai B, Singer A, Dagher N, Cameron A, Lin MT, Kamel I, Gurakar A

Abstract
Donor-transmitted malignancy is a rare complication of organ transplantation. This case illustrates a donor-transmitted adenocarcinoma in a patient 11 months after an orthotopic liver transplant for cryptogenic cirrhosis and hepatocellular carcinoma (HCC). Diagnosis of donor-transmitted malignancy may be challenging and can be confused with HCC recurrence. A timely diagnosis is crucial as a delay may limit treatment options. Biopsy of newly found liver lesions and the use of karyotypic and microsatellite analysis may be essential for diagnosis. Protocols should be in place to help recognize and limit the incidence of donor-transmitted malignancy.

PMID: 23242807 [PubMed - as supplied by publisher]

To TOE or not to TOE? That is the question in patients with portal hypertension and varices.

Tue, 12/18/2012 - 11:14

To TOE or not to TOE? That is the question in patients with portal hypertension and varices.

Gut. 2012 Dec 15;

Authors: Leung C, Yeoh SW, Lim LY, Boyapati R, Testro AG, Vaughan R, Marion K, Burrell LM, Angus PW

PMID: 23242210 [PubMed - as supplied by publisher]

Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation.

Tue, 12/18/2012 - 11:14

Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation.

Eur J Gastroenterol Hepatol. 2012 Dec 13;

Authors: Raevens S, De Pauw M, Reyntjens K, Geerts A, Verhelst X, Berrevoet F, Rogiers X, Troisi RI, Van Vlierberghe H, Colle I

Abstract
Portopulmonary hypertension (POPH) is a part of group 1 pulmonary hypertension (pulmonary hypertension associated with portal hypertension). Liver transplantation (LTx) may be curative, but is usually restricted to patients with mild-to-moderate POPH. The presence of severe POPH may be a contraindication to transplantation because of the elevated risk of peritransplantation and post-transplantation morbidity and mortality. This report describes a series of seven patients with onset of moderate (two patients) or severe (five patients) POPH before LTx, of whom six were treated with oral vasodilator therapy for POPH. Although previous studies recommend aggressive parenteral prostacyclin therapy (epoprostenol), we describe the opportunity to treat cases of severe POPH with an oral phosphodiesterase type 5 inhibitor (sildenafil) and/or an endothelin receptor antagonist (bosentan/ambrisentan) as a bridge to successful LTx in selected patients.

PMID: 23242127 [PubMed - as supplied by publisher]

[Biliary cast syndrome in non-liver surgery patients].

Tue, 12/18/2012 - 11:14

[Biliary cast syndrome in non-liver surgery patients].

Korean J Gastroenterol. 2012 Dec 25;60(6):382-5

Authors: Ha SI, Choi JS, Kim YH, Jun HS, Jo YG, Lee WH, Park SG, Lee SH

Abstract
Biliary cast describes the presence of casts within the biliary tree. It is resultant sequel of cholangitis and hepatocyte damage secondary to bile stasis and bile duct injury. Biliary cast syndrome was first reported in patient undergone liver transplantation. The pathogenesis of biliary cast is not clearly identified, but proposed etiologic factors include post-transplant bile duct damage, ischemia, biliary infection, or post-operative biliary drainage tube. Although biliary casts are uncommon, most of biliary cast syndrome are reported in the liver transplant or hepatic surgery patients. A few reports have been published about non-transplant or non-liver surgery biliary cast. We report two cases of biliary cast syndrome in non-liver surgery patients. (Korean J Gastroenterol 2012;60:382-385).

PMID: 23242023 [PubMed - in process]

Biological variation and prognosis usefulness of new biomarkers in liver transplantation.

Tue, 12/18/2012 - 11:14

Biological variation and prognosis usefulness of new biomarkers in liver transplantation.

Clin Chem Lab Med. 2012 Dec 8;:1-9

Authors: Miguel D, Prieto B, Alvarez FV

Abstract
Abstract Background: An observational retrospective study has been conducted, including 52 patients (37 male and 15 female), ranging from 22 to 65 years old, who underwent an orthotopic liver transplantation (OLT) at the Hospital Universitario Central de Asturias (HUCA) between 2007 and 2010. Methods: The main objective was to evaluate the post-OLT critical complication prognosis usefulness of the precursors of three new biomarkers: mid-regional proadrenomedullin (MR-proADM), carboxy-terminal-proendothelin-1 (CT-ProET-1) and mid-regional proatrial natriuretic peptide (MR-ProANP). As all of them are blood pressure mediators, stress-associated physiological phenomena are expected to affect their expression and secretion, mainly those related to blood circulation. Therefore, as a second goal, the biological variability of the biomarkers has been studied in a set of OLT patients without complications during the first postoperative week. The knowledge of the reference change value of the new biomarkers will be interesting for their correct interpretation in future investigations. The prognostic value of the new biomarkers was also compared to that of procalcitonin (PCT). Results: It has been shown that the basal concentration of the biomarkers is higher in patients that undergo OLT than in the normal population, correlating with the severity of the pathology. The intra-individual biological variation of these biomarkers is similar to other biochemical parameters, the reference change value for OLT patients being 90% for CT-proET-1, 112% for MR-proADM and 127% for MR-proANP. Conclusions: Multivariate analysis showed that MR-proADM was the best biomarker for the prognosis of severe complications.

PMID: 23241604 [PubMed - as supplied by publisher]

The economic burden of advanced liver disease among patients with Hepatitis C Virus: a large state Medicaid perspective.

Tue, 12/18/2012 - 11:14

The economic burden of advanced liver disease among patients with Hepatitis C Virus: a large state Medicaid perspective.

BMC Health Serv Res. 2012 Dec 15;12(1):459

Authors: Menzin J, White LA, Nichols C, Deniz B

Abstract
ABSTRACT: BACKGROUND: Chronic hepatitis C virus (HCV) may progress to advanced liver disease (ALD), including decompensated cirrhosis and/or hepatocellular carcinoma (HCC). ALD can lead to significant clinical and economic consequences, including liver transplantation. This study evaluated the health care costs associated with ALD among HCV infected patients in a Medicaid population. METHODS: Using Florida Medicaid claims data, cases were patients with at least 1 diagnosis of HCV or prescription therapy for HCV (ribavirin plus interferon, peginterferon, or interferon alfacon-1) prior to an incident ALD-related diagnosis ("index event") between 1999 and 2007. ALD-related conditions included decompensated cirrhosis, HCC, or liver transplant. A cohort of HCV patients without ALD (comparison group subjects) were matched 1-to-1 based on age, sex, and race. Baseline and follow-up were the 12 months prior to and following index, respectively; with both periods allowing for a maximum one month gap in eligibility. For both case and comparison patient cohorts, per-patient-per-eligible month (PPPM) costs were calculated as total Medicaid paid amount for each patient over their observed number of eligible months in follow-up, divided by the patient's total number of eligible months. A generalized linear model (GLM) was constructed controlling for age, race, Charlson score, alcoholic cirrhosis, and hepatitis B to explore all-cause PPPM costs between study groups. The final study group included 1,193 cases and matched comparison patients (mean age: 49 years; 45% female; 54% white, 23% black, 23% other). RESULTS: The majority of ALD-related diagnoses were for decompensated cirrhosis (92%), followed by HCC (6%) and liver transplant (2%). Cases had greater comorbidity (mean Charlson score: 3.1 vs. 2.3, P < 0.001). All-cause inpatient use up to 1-year following incident ALD diagnosis was significantly greater among cases with ALD (74% vs. 27%, P < 0.001). In the GLM, cases had 2.39 times greater total adjusted mean all-cause PPPM costs compared to the comparison group ($4,956 vs. $1,735 respectively; P < 0.001). Among cases, mean total unadjusted ALD-related costs were $1,356 PPPM, which were largely driven by inpatient costs ($1,272). CONCLUSIONS: Our results suggest that among patients diagnosed with HCV, the incremental costs of developing ALD are substantial, with inpatient stays as the main driver of these increased costs.

PMID: 23241078 [PubMed - as supplied by publisher]

Genetic polymorphisms in innate immunity receptors do not predict the risk of bacterial and fungal infections and acute rejection after liver transplantation.

Tue, 12/18/2012 - 11:14

Genetic polymorphisms in innate immunity receptors do not predict the risk of bacterial and fungal infections and acute rejection after liver transplantation.

Transpl Infect Dis. 2012 Dec 13;

Authors: de Mare-Bredemeijer EL, Mancham S, Utomo WK, de Canck I, van Thielen M, de Meester E, Rossau R, van der Laan LJ, Hansen BE, Tilanus HW, Kazemier G, Janssen HL, Metselaar HJ, Kwekkeboom J

Abstract
INTRODUCTION: We studied the influence of a broad range of genetic variants in recipient and donor innate immunity receptors on bacterial and fungal infections and acute rejection after liver transplantation (LT). METHODS: Seventy-six polymorphisms in TLR 1-10, NOD2, LBP, CD14, MD2, SIGIRR, Ficolins 1, -2, and -3, MASP 1, -2, and -3, and the complement receptor C1qR1 were determined in 188 LT recipients and 135 of their donors. Associations with clinically significant infections and acute rejection were analyzed for 50 polymorphisms. Significant associations were validated in an independent cohort of 181 recipients and 167 donors. RESULTS: Three recipient polymorphisms and 3 donor polymorphisms were associated with infections in the identification cohort, but none of these associations were confirmed in the validation cohort. Three donor polymorphisms were associated with acute rejection in the identification cohort, but not in the validation cohort. CONCLUSION: In contrast to their effect in the general population, 50 common genetic variations in innate immunity receptors do not influence susceptibility to bacterial/fungal infections after LT. In addition, no reproducible associations with acute rejection after LT were observed. Likely, transplant-related factors play a superior role as risk factors for bacterial/fungal infections and acute rejection after LT.

PMID: 23240652 [PubMed - as supplied by publisher]

Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients.

Tue, 12/18/2012 - 11:14

Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients.

Transpl Infect Dis. 2012 Dec 13;

Authors: Lee SO, Brown RA, Razonable RR

Abstract
BACKGROUND: Toll-like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double-stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein-receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation. METHODS: The clinical characteristics of 611 liver recipients (HCV-infected: n = 153, non-HCV-infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes. RESULTS: TLR3 L412F is common, and it was significantly more prevalent among the HCV-infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13-2.65, P = 0.01). In an analysis that compared HCV-infected patients with wild-type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007-1.06, P = 0.02). CONCLUSION: TLR3 L412F is significantly common in HCV-infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.

PMID: 23240626 [PubMed - as supplied by publisher]

Vitreous surgery impact in glaucoma development in liver transplanted familial amyloidosis ATTR V30M Portuguese patients.

Tue, 12/18/2012 - 11:14
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Vitreous surgery impact in glaucoma development in liver transplanted familial amyloidosis ATTR V30M Portuguese patients.

Amyloid. 2012 Sep;19(3):146-51

Authors: Beirão NM, Matos ME, Meneres MJ, Beirão IM, Costa PP, Torres PA

Abstract
PURPOSE: Familial amyloidosis with polyneuropathy (FAP) sometimes courses with vitreous amyloid. The aim of this study was to evaluate the incidence of glaucoma after vitrectomy in FAP patients.
METHODS: A total of 79 eyes of 42 liver transplanted FAP patients and 16 eyes of 16 non-FAP patients with rhegmatogenous retina detachment were collected. The patients were divided in to three groups: Group I - FAP patients with vitreous opacities submitted to vitrectomy, Group II - FAP patients without vitreous opacities and not submitted to vitrectomy and, Group III - non-FAP patients with rhegmatogenous retinal detachment submitted to vitrectomy. The Group I was subdivided into: Ia - "complete" vitrectomy; Ib - "incomplete" vitrectomy. The onset of glaucoma was considered when the intraocular pressure level was higher than 21 mmHg, with concomitant visual field abnormalities and optic nerve cupping.
RESULTS: Post vitrectomy glaucoma was more frequent in Group I (56.1%) than in Group III (12.5%) and in Group II (10.5%). We observed a higher incidence of glaucoma in the Ia than in the Ib subgroup (86.4 vs. 21.1%) and earlier appearance in subgroup Ia (7.9 ± 3.6 vs. 39.5 ± 6.6 months).
CONCLUSION: Vitrectomy induced the development of glaucoma in FAP patients.

PMID: 22856884 [PubMed - indexed for MEDLINE]

Spatial visual contrast sensitivity in liver transplanted Portuguese familial amyloidotic polyneuropathy (ATTR V30M) patients.

Tue, 12/18/2012 - 11:14
Related Articles

Spatial visual contrast sensitivity in liver transplanted Portuguese familial amyloidotic polyneuropathy (ATTR V30M) patients.

Amyloid. 2012 Sep;19(3):152-5

Authors: Beirão M, Matos E, Reis R, Beirão I, Costa PP, Torres P

Abstract
Liver transplanted patients with familial amyloidosis (FAP) patients develop earlier presbyopia due to the deposition of amyloid on the anterior capsule of the lens. Despite normal visual acuity of 20/20 Snellen chart, some patients reported complaints of impaired vision. The aim of this study is to investigate the visual spatial contrast sensitivity in these patients. This is a retrospective, nonrandomized study. Spatial contrast sensitivity was performed in both eyes of 25 FAP patients with best correct visual acuity of 20/20 Snellen chart. In each patient, one eye had visible opacification of anterior capsule of the lens. FAP patients had poorer visual contrast sensitivity than normal even in absence of visible opacification of the anterior capsule of the lens. Comparing eyes with visible opacification of anterior capsule of the lens with eyes without visible opacification of the anterior capsule of the lens, a worse visual sensitivity was observed at all frequencies tested. This occurred with similar lacrimal function in both groups. The eyes of FAP patients have decreased spatial contrast sensitivity which is worse in presence of visible opacification of the anterior capsule of the lens. This could explain the visual complaints in presence of normal visual acuity by Snellen chart.

PMID: 22856676 [PubMed - indexed for MEDLINE]

Neuroendocrine tumours of the ampulla of Vater: clinico-pathological features, surgical approach and assessment of prognosis.

Tue, 12/18/2012 - 11:14
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Neuroendocrine tumours of the ampulla of Vater: clinico-pathological features, surgical approach and assessment of prognosis.

Langenbecks Arch Surg. 2012 Aug;397(6):933-43

Authors: Dumitrascu T, Dima S, Herlea V, Tomulescu V, Ionescu M, Popescu I

Abstract
BACKGROUND/AIMS: Neuroendocrine tumours occur very rarely in the ampulla of Vater and their clinical behaviour is unknown. The aim of this study is to assess the clinico-pathological features, surgical approach and prognosis of these patients.
METHODS: Six patients with neuroendocrine tumours of the ampulla of Vater treated with curative intent surgery at a single centre were retrospectively analysed. A univariate analysis of potential prognostic factors was also performed (data provided from the present study and literature review).
RESULTS: Pancreaticoduodenectomy was curative in all the patients. Overall and disease-free survival rates were significantly better for G1/G2 tumours (p = 0.006 and p = 0.004, respectively). Although frequent, lymph node metastases did not influenced both overall (p = 0.760) and disease-free survival rates (p = 0.745). No significant differences of survival were observed in patients with ENETS stage I/II disease, as compared to ENETS stage III disease (p = 0.169 and p = 0.137, respectively). No differences were observed according to UICC staging system (p = 0.073 and p = 0.177, respectively). Tumours that are less than 2 cm or limited to the ampulla appear to have a better prognosis.
CONCLUSION: The WHO 2010 classification appear to accurately predict patient prognosis, while the ENETS or UICC staging systems have a limited value (especially in regard to lymph node metastases). Radical surgery (i.e. pancreaticoduodenectomy with lymphadenectomy) should be the standard approach in most patients with NET of the ampulla of Vater because this procedure removes all the potential tumour-bearing tissue.

PMID: 22476195 [PubMed - indexed for MEDLINE]

Preneoplastic conditions underlying bile duct cancer.

Tue, 12/18/2012 - 11:14
Related Articles

Preneoplastic conditions underlying bile duct cancer.

Langenbecks Arch Surg. 2012 Aug;397(6):861-7

Authors: Sibulesky L, Nguyen J, Patel T

Abstract
BACKGROUND: Malignancies arising from the biliary tract can arise from the epithelial lining of the biliary tract and surrounding tissues. Conditions that predispose to malignancy as well as preneoplastic changes in biliary tract epithelia have been identified. In this overview, we discuss preneoplastic conditions of the biliary tract and emphasize their clinical relevance.
RESULTS: Chronic biliary tract inflammation predisposes to cancer in the biliary tract. Biliary tract carcinogenesis involves a multistep process as a consequence of chronic biliary epithelial injury or inflammation. Reminiscent of other gastrointestinal epithelial malignancies such as gastric, colon, and pancreatic cancer, biliary tract cancers may evolve via multistep progression from epithelial hyperplasia and dysplasia to malignant transformation. The potential role of initiating cells is also becoming recognized.
CONCLUSIONS: In spite of improved risk factor recognition, and advances in diagnostic tools, the early diagnosis of pre-malignant or malignant biliary tract conditions is extremely challenging, and there is a paucity of evidence on which to base their management. As a result, the role of pre-emptive surgery remains largely undefined.

PMID: 22391777 [PubMed - indexed for MEDLINE]

Adult to adult living related liver transplantation: Where do we currently stand?

Mon, 12/17/2012 - 10:05

Adult to adult living related liver transplantation: Where do we currently stand?

World J Gastroenterol. 2012 Dec 14;18(46):6729-36

Authors: Carlisle EM, Testa G

Abstract
Adult to adult living donor liver transplantation (AALDLT) was first preformed in the United States in 1997. The procedure was rapidly integrated into clinical practice, but in 2002, possibly due to the first widely publicized donor death, the number of living liver donors plummeted. The number of donors has since reached a steady plateau far below its initial peak. In this review we evaluate the current climate of AALDLT. Specifically, we focus on several issues key to the success of AALDLT: determining the optimal indications for AALDLT, balancing graft size and donor safety, assuring adequate outflow, minimizing biliary complications, and maintaining ethical practices. We conclude by offering suggestions for the future of AALDLT in United States transplantation centers.

PMID: 23239910 [PubMed - in process]

Liver transplantation after stage II palliation for hypoplastic left heart syndrome.

Mon, 12/17/2012 - 10:05

Liver transplantation after stage II palliation for hypoplastic left heart syndrome.

Liver Transpl. 2012 Dec 13;

Authors: Feier FH, Neto JS, Porta G, Fonseca EA, Vincenzi R, Cândido HL, Benavides M, Ketzer B, Pugliese R, Miura IK, Baggio V, Guimarães T, Porta A, Foronda G, Donizete E, da Silva JP, Faria L, Kondo M, Chapchap P

Abstract
The association of biliary atresia with congenital heart diseases has been extensively described, and there are a number of reports on the outcomes of this group of patients submitted to liver transplantation. Intraoperative management and the timing to proceed with liver transplant in a patient with end-stage liver disease is a matter of debate, especially with complex heart diseases. This report describes the outcome after liver transplantation of a pediatric recipient with biliary atresia and hypoplastic left heart syndrome. The patient was submitted to a Norwood-Sano and Glenn procedures for heart palliation before the liver transplantation. The patient was cyanotic, severely malnourished, and with complications secondary to the chronic liver failure. At transplant the child was 16 months old and weighted 5175g. Despite the critical clinical scenario and the long hospitalization period, there were no cardiac, vascular or biliary complications after the liver transplant. At the age of 48 months the patient awaits the final cardiac repair. The presence of complex cardiac malformations may not be a contraindication for liver transplantation. An experienced surgical team and a multidisciplinary approach are the key for a successful outcome. © 2012 American Association for the Study of Liver Diseases.

PMID: 23239564 [PubMed - as supplied by publisher]

Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy.

Mon, 12/17/2012 - 10:05

Functional elements associated with hepatic regeneration in living donors after right hepatic lobectomy.

Liver Transpl. 2012 Dec 13;

Authors: Everson GT, Hoefs JC, Niemann CU, Olthoff KM, Dupuis R, Lauriski S, Herman A, Milne N, Gillespie BW, Goodrich NP, Everhart JE

Abstract
We quantified rates of hepatic regeneration and functional recovery for 6 months after right hepatic lobectomy in living donors for liver transplantation. Twelve donors were studied at baseline; eight retested at (mean±SD) 11±3 days(T1), 10 at 91±9 days(T2), and 10 at 185±17 days(T3) after donation. Liver and spleen volumes were measured by computed tomography (CT) and single photon emission computed tomography (SPECT). Hepatic metabolism was assessed from caffeine and erythromycin, and hepatic blood flow from cholates,galactose, and perfused hepatic mass (PHM, by SPECT). Regeneration rates (mL liver per kg body weight per day) were 0.60±0.22 from baseline to T1, 0.05±0.02 from T1 to T2,0.01±0.01 from T2 to T3 by CT, 0.54±0.20, 0.04±0.01 and 0.01±0.02 by SPECT. At T3, liver volume was 84±7% of baseline by CT and 92±13% by SPECT. Changes in hepatic metabolism did not achieve statistical significance. At T1, unadjusted clearance ratios relative to baseline were 0.75±0.07 for intravenous cholate (p=0.0001), 0.88±0.15 for galactose (p=0.0681), 0.84±0.08 (p=0.002) for PHM, and 0.83±0.19 (p=0.056) for estimated hepatic blood flow. These ratios approached 1.00 by T3. At T1, ratios adjusted per L liver were 20%-50% greater than baseline and trended toward baseline by T3. Several findings were consistent with alteration of the portal circulation: increased cholate shunt, increased spleen volume, decreased platelet count, and decreased clearance of orally-administered cholate. During the first 2 weeks after donation, hepatic regeneration is rapid and accounts for nearly two-thirds of total regeneration. Increases in hepatic blood flow and uptake of cholate characterize the early phase of regeneration. Right lobe donation alters the portal circulation of living donors, but long-term clinical consequences, if any, are unknown. © 2012 American Association for the Study of Liver Diseases.

PMID: 23239552 [PubMed - as supplied by publisher]

Meeting report of the international liver transplantation society's 18th annual international congress: Hilton San Francisco Hotel, San Francisco, CA, May 16-19, 2012.

Mon, 12/17/2012 - 10:05

Meeting report of the international liver transplantation society's 18th annual international congress: Hilton San Francisco Hotel, San Francisco, CA, May 16-19, 2012.

Liver Transpl. 2012 Dec 12;

Authors: Levitsky J, Oniscu GC

Abstract
From May 16-19, 2012, the International Liver Transplantation Society held its annual congress in San Francisco, CA. More than 1300 registrants attended the meeting, which included a premeeting conference entitled Balancing Risk in Liver Transplantation, focused topic sessions, and a variety of oral and poster presentations. This report is not all-inclusive and focuses on specific research abstracts on key topics in liver transplantation. As always, the new data herein are presented in the context of the published literature to further enhance knowledge in the field. Liver Transpl, 2012. © 2012 AASLD.

PMID: 23239473 [PubMed - as supplied by publisher]

Infection with hepatitis E virus in kidney transplant recipients in southeastern France.

Mon, 12/17/2012 - 10:05

Infection with hepatitis E virus in kidney transplant recipients in southeastern France.

J Med Virol. 2012 Dec 12;

Authors: Moal V, Legris T, Burtey S, Morange S, Purgus R, Dussol B, Garcia S, Motte A, Gérolami R, Berland Y, Colson P

Abstract
Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in Europe, particularly in southern France, and HEV is a new causative agent of chronic hepatitis and cirrhosis in immunocompromised patients. However, the data regarding HEV infection after kidney transplantation are still scarce with respect to the clinical issues that have been raised, and no study has specifically focused on kidney transplant recipients. This study described the clinical features and outcomes of HEV infections in a cohort of kidney transplant recipients living in southeastern France. The epidemiological, clinical, and virological characteristics of HEV infections diagnosed by PCR over a 53-month period were retrospectively analyzed in a cohort of 1,350 kidney transplant recipients monitored at the Marseille University Hospital. Sixteen HEV infections were diagnosed, all of which were autochthonous and involved genotype 3 viruses (HEV-3). Chronic infections occurred in 80% of these patients and resolved in half of the cases after a median time of 39 months. The rate of HEV clearance was 54% after a decrease in the dose of immunosuppressants. One patient developed liver cirrhosis 14 months after infection and experienced acute rejection after a decrease in the dose of immunosuppressants. Autochthonous HEV-3 infections in kidney transplant recipients progress to chronicity in most cases and might be complicated by early liver cirrhosis. Chronic HEV infection can resolve following the reduction of immunosuppressive therapy, but ribavirin may be required if reduction of the immunosuppressant dose is not associated with HEV clearance or is inappropriate for the patient management. J. Med. Virol. © 2012 Wiley Periodicals, Inc.

PMID: 23239466 [PubMed - as supplied by publisher]

Serum metabolic variables associated with impaired glucose tolerance induced by high-fat-high-cholesterol diet in Macaca mulatta.

Mon, 12/17/2012 - 10:05

Serum metabolic variables associated with impaired glucose tolerance induced by high-fat-high-cholesterol diet in Macaca mulatta.

Exp Biol Med (Maywood). 2012 Nov 1;237(11):1310-21

Authors: Li X, Chen Y, Liu J, Yang G, Zhao J, Liao G, Shi M, Yuan Y, He S, Lu Y, Cheng J

Abstract
Dyslipidemia caused by 'Western-diet pattern' is a strong risk factor for the onset of diabetes. This study aimed to disclose the relationship between the serum metabolite changes induced by habitual intake of high-fat and high-cholesterol (HFHC) diet and the development of impaired glucose tolerance (IGT) and insulin resistance through animal models of Macaca mulatta. Sixteen M. mulatta (six months old) were fed a control diet or a HFHC diet for 18 months. The diet effect on serum metabolic profiles was investigated by longitudinal research. Islet function was assessed by intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp test. Metabonomics were determined by (1)H proton nuclear magnetic resonance spectroscopy. Prolonged diet-dependent hyperlipidemia facilitated visceral fat accumulation in liver and skeletal muscle and disorder of glucose homeostasis in juvenile monkeys. Glucose disappearance rate (K(Glu)) and insulin response to the glucose challenge effects in HFHC monkeys were significantly lower than in control monkeys. Otherwise, serum trimethylamine-N-oxide (TMAO), lactate and leucine/isoleucine were significantly higher in HFHC monkeys. Sphingomyelin and choline were the most positively correlated with K(Glu) (R(2) = 0.778), as well as negative correlation (R(2) = 0.64) with total cholesterol. The HFHC diet induced visceral fat, abnormal lipid metabolism and IGT prior to weight gain and body fat content increase in juvenile monkeys. We suggest that increased serum metabolites, such as TMAO, lactate, branched-chain amino acids and decreased sphingomyelin and choline, may serve as possible predictors for the evaluation of IGT and insulin resistance risks in the prediabetic state.

PMID: 23239442 [PubMed - in process]

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