Skip directly to content

PubMed Liver Transplant

Subscribe to PubMed Liver Transplant feed PubMed Liver Transplant
NCBI: db=pubmed; Term=liver transplant
Updated: 58 min 41 sec ago

Hepatic stimulator substance resists hepatic ischemia-reperfusion injury by regulating Drp1 translocation and activation.

58 min 41 sec ago
Related Articles

Hepatic stimulator substance resists hepatic ischemia-reperfusion injury by regulating Drp1 translocation and activation.

Hepatology. 2017 Jun 23;:

Authors: Zhang C, Huang J, An W

Abstract
Ischemia-reperfusion injury (IRI), induced by abnormal mitochondrial fission related apoptosis, is a major concern in liver transplantation settings. Our previous studies have demonstrated that hepatic stimulator substance (HSS) is an anti-apoptotic effector and could protect liver from IRI. However, the underlying mechanism remains unclear. In the present study, we report that in vitro and in vivo HSS could regulate mitochondrial fission and hepatocyte apoptosis during liver IRI by orchestrating the translocation and activation of dynamin-related protein 1 (Drp1). Using a mouse model of IR-induced liver injury, we found that HSS haploinsufficient (HSS(+/-) ) mice displayed exacerbated liver damage based on their increased serum aminotransferase levels, cell structural destruction, and apoptosis levels compared to the wild type (HSS(+/+) ) littermates. Disruption of HSS markedly increased cyclin-dependent kinase 1 (CDK1) and Bax expression, accompanied with elevated p-Drp1 and release of cytochrome c. In parallel in vitro studies, we found that HSS could inhibit the expression of CDK1 and that HSS inhibits hepatocytes apoptosis through its suppression of CDK1/cyclin B -mediated phosphorylation at Ser-616 of Drp1, thereby decreasing Drp1 accumulation in mitochondria and Drp1-mediated activation of the mitochondrial fission program. On the contrary, knockdown of HSS increased of CDK1 as well as Drp1 phosphorylation and aggravated hepatocellular apoptosis. Mechanistic investigation showed that HSS was able to reduce the stability and translation of CDK1 mRNA by modulating the expression of several miRNAs, including miR-410-3p, miR-490-3p and miR-582-5p. Our data reveal a novel mechanism for HSS in regulating the mitochondrial fission machinery and further suggest that modulation of HSS may provide a therapeutic approach for combating liver damage. This article is protected by copyright. All rights reserved.

PMID: 28646508 [PubMed - as supplied by publisher]

Liver involvement in kidney disease and vice versa.

58 min 41 sec ago
Related Articles

Liver involvement in kidney disease and vice versa.

Pediatr Nephrol. 2017 Jun 23;:

Authors: Van Hoeve K, Mekahli D, Morava E, Levtchenko E, Witters P

Abstract
The liver and kidneys are often similarly affected by a single disease. This is the case in metabolic, immunological, toxic, and infectious diseases, and in the different congenital malformation syndromes. Also, an enzymatic defect in an otherwise healthy liver or the consequences of advanced liver disease by itself can cause kidney disease as a secondary phenomenon. In this review, we describe numerous pathogenic mechanisms leading to dysfunction or malformations of the liver and kidneys in children. We encourage multidisciplinary management for optimal care. A combined liver-kidney transplantation is sometimes needed.

PMID: 28646278 [PubMed - as supplied by publisher]

Over Expression of Long Non-Coding RNA PANDA Promotes Hepatocellular Carcinoma by Inhibiting Senescence Associated Inflammatory Factor IL8.

58 min 41 sec ago
Related Articles

Over Expression of Long Non-Coding RNA PANDA Promotes Hepatocellular Carcinoma by Inhibiting Senescence Associated Inflammatory Factor IL8.

Sci Rep. 2017 Jun 23;7(1):4186

Authors: Peng C, Hu W, Weng X, Tong R, Cheng S, Ding C, Xiao H, Lv Z, Xie H, Zhou L, Wu J, Zheng S

Abstract
It has been reported that long non-coding RNA PANDA was disregulated in varieties types of tumor, but its expression level and biological role in hepatocellular carcinoma (HCC) remains contradictory. We detected PANDA expression in two independent cohorts (48 HCC patients following liver transplantation and 84 HCC patients following liver resection), and found that PANDA was down-regulated in HCC. Thereafter we explored its function in cancer biology by inversing its low expression. Surprisingly, overexpression of PANDA promoted HCC proliferation and carcinogenesis in vitro and in vivo. Mechanistically, PANDA repressed transcriptional activity of senescence associated inflammatory factor IL8, which leaded to inhibition of cellular senescence. Therefore, our research help to better understand the complex role of PANDA in HCC, and suggest more thoughtful strategies should be applied before it can be treated as a potential therapeutic target.

PMID: 28646235 [PubMed - in process]

Gastrointestinal stromal tumors (GIST) presenting in the liver: Diagnostic, prognostic and therapeutic issues.

58 min 41 sec ago
Related Articles

Gastrointestinal stromal tumors (GIST) presenting in the liver: Diagnostic, prognostic and therapeutic issues.

Clin Res Hepatol Gastroenterol. 2017 Jun 20;:

Authors: Joyon N, Dumortier J, Aline-Fardin A, Caramella C, Valette PJ, Blay JY, Scoazec JY, Dartigues P

Abstract
CONTEXT: Extra-gastrointestinal stromal tumors (E-GIST) presenting in the liver are exceedingly rare and raise difficult diagnostic and therapeutic challenges.
METHODS: We report on two cases of liver E-GIST with different clinical presentations. We describe their clinical and imaging features, their histopathological and molecular characteristics, their treatment and their course.
RESULTS: The first case was that of a 56-year-old male presenting with a 10-cm liver mass; the initial diagnosis, made in 1986 from a biopsy sample, was leiomyosarcoma; liver transplantation was performed in 1987; no extra-hepatic tumor was found; the course was uneventful until 1999, when tumor recurrence was diagnosed along the initial biopsy route; after reevaluation of available material, the definitive pathological diagnosis was GIST; imatinib treatment resulted in major response; the patient died of end-stage kidney disease 22 years after the initial diagnosis and 9 years after tumor recurrence. The second case is that of a 59-year-old female presenting with a 23-cm abdominal mass connected to the liver; on biopsy, the tumor was diagnosed as epithelioid GIST with exon 11 KIT mutation; imatinib treatment resulted in stable disease.
CONCLUSIONS: The diagnosis of E-GIST must be for any sarcoma presenting in the liver and confirmed by immunohistochemical and molecular techniques. Treatment might require aggressive strategies, which can be successful despite apparently adverse histoprognostic factors.

PMID: 28645742 [PubMed - as supplied by publisher]

alfapump System vs. Large Volume Paracentesis for Refractory Ascites: A Multicenter Randomized Controlled Study.

58 min 41 sec ago
Related Articles

alfapump System vs. Large Volume Paracentesis for Refractory Ascites: A Multicenter Randomized Controlled Study.

J Hepatol. 2017 Jun 20;:

Authors: Bureau C, Adebayo D, de Rieu MC, Elkrief L, Valla D, Peck-Radosavljevic M, McCune A, Vargas V, Simon-Talero M, Cordoba J, Angeli P, Rosi S, MacDonald S, Malago M, Stepanova M, Younossi ZM, Trepte C, Watson R, Borisenko O, Sun S, Inhaber N, Jalan R

Abstract
BACKGROUND AND AIMS: Patients with refractory ascites (RA) require repeated large volume paracenteses (LVP), which involves frequent hospital visits and is associated with poor quality-of-life. This study assessed safety and efficacy of an automated, low-flow pump (alfapump [AP]) compared with LVP [SoC].
METHODS: Randomized, controlled trial, in 7 centers, with 6M patient observation. Primary outcome was time to first LVP. Secondary outcomes included paracentesis requirement, safety, health-related quality-of-life (HRQoL), and survival. Nutrition and hemodynamics were assessed in a sub-study at 3M.
RESULTS: 60 patients randomized and 58 were analyzed (27-AP, 31-SoC, mean age 61.9y, mean MELD 11.7). Eighteen patients were included in the sub-study. Compared with SoC, median time to first LVP was not reached after 6 months in the AP group, meaning a significant reduction in LVP requirement for the AP patients (AP, median not reached; SoC, 15.0 days (95%CI 13.0, 22.0); HR: 0.13, p<0.001), and Chronic Liver Disease Questionnaire (HRQoL) score (p<0.05 between treatment arms). Improvements in nutritional parameters were observed for hand-grip strength (p=0.044) and body mass index (p<0.001) in the sub-study. Compared with SoC, more AP patients reported adverse events (AEs; 96.3% vs. 77.4%, p=0.057) and serious AEs (85.2 vs. 45.2%, p=0.002). AEs consisted predominantly of acute kidney injury in the immediate post-operative period, and re-intervention for pump related issues, and were treatable in most cases. Survival was similar in AP and SoC.
CONCLUSIONS: The AP system is effective in reducing need for paracentesis and improving HRQoL in cirrhotic patients with RA. Although the frequency of SAEs (and by inference hospitalizations) were significantly higher in the AP group, they were generally limited and did not impact survival. www.clinicaltrials.gov#NCT01528410 LAY SUMMARY: The alfapump moves abdominal fluid into the bladder from where it is then removed by urination. Compared with standard treatment, the alfapump reduces the need for large volume paracentesis (manual fluid removal by needle) in patients with medically untreatable ascites. This can improve life quality for these patients.

PMID: 28645737 [PubMed - as supplied by publisher]

Liver transplantation in the most severely ill cirrhotic patients: a multicenter study in acute-on-chronic liver failure grade 3.

58 min 41 sec ago
Related Articles

Liver transplantation in the most severely ill cirrhotic patients: a multicenter study in acute-on-chronic liver failure grade 3.

J Hepatol. 2017 Jun 20;:

Authors: Artru F, Louvet A, Ruiz I, Levesque E, Labreuche J, Ursic-Bedoya J, Lassailly G, Dharancy S, Boleslawski E, Lebuffe G, Kipnis E, Ichai P, Coilly A, De Martin E, Antonini TM, Vibert E, Jaber S, Herrerro A, Samuel D, Duhamel A, Pageaux GP, Mathurin P, Saliba F

Abstract
BACKGROUND & AIMS: Liver transplantation (LT) for the most severely ill patients with cirrhosis with dysfunction of several organs (accurately assessed by the acute-on-chronic liver failure (ACLF) classification) remains controversial. We aimed to report the results of LT in patients with ACL3 and to compare these patients to non-transplanted patients with cirrhosis and multiple organ dysfunction and to patients transplanted with lower ACLF grade. -Methods: All patients with ACLF3 transplanted in 3 liver ICU were retrospectively included. Each patient with ACLF3 was matched a) to non-transplanted patients hospitalized in the ICU with multiple organ dysfunction, b) to control patients transplanted with each of the lower ACLF grades (3 groups).
RESULTS: 73 patients were included. These severely ill patients (at LT, MELD at 40, CLIF-C ACLF at 63.5) were transplanted following management to stabilize their condition a median of 9 days after admission (progression of mean organ failure from 4.03 to 3.67, p=0.009). One-year survival of transplanted patients with ACLF3 was higher than that of non-transplanted controls: 83.9 vs. 7.9%, p<0.0001. This high survival rate was not different from that of matched control patients with no ACLF (90%), ACLF1 (82.3%) or ACLF2 (86.2%). However, a higher rate of complications was observed (100 vs. 51.2 vs. 76.5 vs. 74.3%, respectively), with the longer hospital stay. The notion of a "transplantation window" is discussed.
CONCLUSIONS: LT strongly influences survival in patients with cirrhosis and ACLF3 with a 1-year survival comparable to that of patients with a lower grade of ACLF. A rapid decision-making process is needed because of the short "transplantation window" suggesting that patients with ACLF3 should be rapidly referred to a specific liver intensive care unit.
LAY SUMMARY: Liver transplantation improves survival of patients with very severe cirrhosis. These patients must be carefully monitored and managed in a specialized unit. The decision to transplant a patient must be quick to avoid a high risk of mortality.

PMID: 28645736 [PubMed - as supplied by publisher]

Post-transplant cholangiopathy: Classification, pathogenesis, and preventive strategies.

58 min 41 sec ago
Related Articles

Post-transplant cholangiopathy: Classification, pathogenesis, and preventive strategies.

Biochim Biophys Acta. 2017 Jun 20;:

Authors: de Vries Y, von Meijenfeldt FA, Porte RJ

Abstract
Biliary complications are the most frequent cause of morbidity, re-transplantation, and even mortality after liver transplantation. In general, biliary leakage and anastomotic and non-anastomotic biliary strictures (NAS) can be recognized. There is no consensus on the exact definition of NAS and different names and criteria have been used in literature. We propose to use the term post-transplant cholangiopathy for the spectrum of abnormalities of large donor bile ducts, that includes NAS, but also intraductal casts and intrahepatic biloma formation, in the presence of a patent hepatic artery. Combinations of these manifestations of cholangiopathy are not infrequently found in the same liver and ischemia-reperfusion injury is generally considered the common underlying mechanism. Other factors that contribute to post-transplant cholangiopathy are biliary injury due to bile salt toxicity and immune-mediated injury. This review provides an overview of the various types of post-transplant cholangiopathy, the presumed pathogenesis, clinical implications, and preventive strategies.

PMID: 28645651 [PubMed - as supplied by publisher]

BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells.

58 min 41 sec ago
Related Articles

BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells.

Cancer Lett. 2017 Jun 20;:

Authors: Liu Q, Chen K, Liu Z, Huang Y, Zhao R, Wei L, Yu X, He J, Liu J, Qi J, Qin Y, Li B

Abstract
Accumulating evidence has revealed the importance of cancer stem cells (CSCs) in chemoresistance and recurrence. BORIS, a testes-specific CTCF paralog, has been shown to be associated with stemness traits of embryonic cancer cells and epithelial CSCs. We previously reported that BORIS is correlated with the expression of the CSC marker CD90 in hepatocellular carcinoma (HCC). These results encourage us to wonder whether BORIS exerts functions on CSC-like traits of human liver cancer cells. Here, we report that BORIS was enriched in HCC tissues. Exogenous overexpression of BORIS promoted CSC-like properties, including self-renewal, chemoresistance, migration and invasion in Huh7 and HCCLM3 cells. Conversely, BORIS knockdown suppressed CSC-like properties in SMMC-7721 and HepG2 cells and inhibited tumorigenicity in SMMC-7721 cells. Moreover, BORIS alteration did not affect the DNA methylation status of the minimal promoter and exon 1 region of OCT4. However, BORIS overexpression enhanced the amount of BORIS bound on the OCT4 promoter and increased H3K4me2, while reducing H3K27me3; BORIS depletion decreased BORIS and H3K4me2 on the OCT4 promoter, while increasing H3K27me3. These results revealed that BORIS is associated with the CSC-like traits of human liver cancer cells through the epigenetic regulation of OCT4.

PMID: 28645561 [PubMed - as supplied by publisher]

Establishment of an orthotopic patient-derived xenograft mouse model using uveal melanoma hepatic metastasis.

58 min 41 sec ago
Related Articles

Establishment of an orthotopic patient-derived xenograft mouse model using uveal melanoma hepatic metastasis.

J Transl Med. 2017 Jun 23;15(1):145

Authors: Kageyama K, Ohara M, Saito K, Ozaki S, Terai M, Mastrangelo MJ, Fortina P, Aplin AE, Sato T

Abstract
BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment. To overcome these limitations, we developed a new method to directly transplant biopsy specimens to the liver of immunocompromised mice.
RESULTS: By using two metastatic uveal melanoma cell lines, we demonstrated that the liver provides a more suitable microenvironment for tumor growth compared to subcutaneous sites and that surgical orthotopic implantation (SOI) of tumor pieces allows the creation of a liver tumor in immunocompromised mice. Subsequently, 10 of 12 hepatic metastasis specimens from patients were successfully xenografted into the immunocompromised mice (83.3% success rate) using SOI, including 8 of 10 needle biopsy specimens (80%). Additionally, four cryopreserved PDX tumors were re-implanted to new mice and re-establishment of PDX tumors was confirmed in all four mice. The serially passaged xenograft tumors as well as the re-implanted tumors after cryopreservation were similar to the original patient tumors in histologic, genomic, and proteomic expression profiles. CT imaging was effective for detecting and monitoring PDX tumors in the liver of living mice. The expression of Ki67 in original patient tumors was a predictive factor for implanted tumor growth and the success of serial passages in PDX mice.
CONCLUSIONS: Surgical orthotopic implantation of hepatic metastasis from uveal melanoma is highly successful in the establishment of orthotopic PDX models, enhancing their practical utility for research applications. By using CT scan, tumor growth can be monitored, which is beneficial to evaluate treatment effects in interventional studies.

PMID: 28645290 [PubMed - in process]

Prognostic analysis of radical resection for intrahepatic cholangiocarcinoma: a retrospective cohort study.

Sat, 06/24/2017 - 12:45
Related Articles

Prognostic analysis of radical resection for intrahepatic cholangiocarcinoma: a retrospective cohort study.

Oncotarget. 2017 Jun 13;:

Authors: Ni Q, Shen W, Zhang M, Yang C, Cai W, Wu M, Yang J

Abstract
The aim of this study was to investigate the relationship between the clinicopathological characteristics of intrahepatic cholangiocarcinoma (ICC) and both disease-free survival (DFS) and overall survival (OS) in intrahepatic cholangiocarcinoma (ICC) patients who underwent radical resection (R0). We retrospectively analyzed the clinicopathological characteristics of 319 patients who underwent radical resection of ICC between October 1999 and December 2003. The independent adverse prognostic factors that affected DFS after radical resection of ICC were as follows: maximum tumor diameter (HR = 1.330, P = 0.014), complicated bile duct stone (HR = 1.923, P = 0.013), macroscopic tumor thrombus (HR = 1.826, P = 0.009), and lymph node metastasis (Pathology N1) (HR = 2.330, P = 0.005) were independent adverse prognostic factors that affected the DFS after radical resection of ICC. The postoperative median DFS was 6 months. The independent adverse prognostic factors that affected OS after radical resection of ICC were as follows: maximum tumor diameter (HR = 1.326, P = 0.014), complicated bile duct stone (HR = 2.349, P = 0.001), and lymph node metastasis (Pathology N1) (HR = 2.420, P = 0.003). The postoperative median survival time was 22 months, the 3-year survival rate was 33.9%, and the 5-year survival rate was 23.2%. Macroscopic tumor thrombus (OR = 2.991, P = 0.004) was an independent risk factor for death within 1 year after radical resection.

PMID: 28645113 [PubMed - as supplied by publisher]

Across state lines: Fulminant Babesia microti infection in a liver transplant recipient.

Sat, 06/24/2017 - 12:45
Related Articles

Across state lines: Fulminant Babesia microti infection in a liver transplant recipient.

Transpl Infect Dis. 2017 Jun 23;:

Authors: Meissner EG, McGillicuddy JW, Squires J, Skipper D, Self S, Wray D, Moritz ED, Stramer SL, Nadig S

Abstract
The potential for transmission of Babesia microti by blood transfusion is well recognized. Physicians may be unaware that products used for transfusion may be collected from geographically diverse regions. We describe a liver transplant recipient in South Carolina who likely acquired B. microti infection from a unit of blood collected in Minnesota. This article is protected by copyright. All rights reserved.

PMID: 28644910 [PubMed - as supplied by publisher]

Clinical Characteristics and Outcome of Liver Transplantation for Alagille Syndrome in Children.

Sat, 06/24/2017 - 12:45
Related Articles

Clinical Characteristics and Outcome of Liver Transplantation for Alagille Syndrome in Children.

J Dig Dis. 2017 Jun 23;:

Authors: Zhou T, Zhang J, Luo Y, Liu Y, Zhuang S, Xue F, Han L, Xia Q

Abstract
AIM: The aim of this study was to analyze clinical characteristics and outcome of liver transplantation for Alagille syndrome in children.
METHOD: By retrospectively reviewing the medical records of 9 Alagille syndrome patients(AGS) with liver transplantation(LT) in Renji Hospital between 2006 and 2015,After operative,the height and weight Z score were compared with preoperative.
RESULT: There were 9 patients included in the study; cholestasis and peculiar faces were seen in all of the patients (100%), heart defect in 8 patients (88.9%), while 6 of them indicated stenosis of pulmonary atria. Complex heart defect(atrial septal defect, pulmonary stenosis and tricuspid insufficiency) existed in 1 patient. Butterfly vertebrae were seen in 4 patients(44.4%) and posterior embryotoxon in 2 patients (22.2%). Liver biopsy after transplantation indicated paucity of interlobular bile in 6 patients(66.7%), intrahepatic cholestasis in 2 patients(22.2%) and biliary proliferation in 1 patient(11.1%). 7 Alagille syndrome patients are still alive with a median follow-up time of 18 month (range: 5 mo. to 31 mo.). 2 patients died due to pulmonary arterial rupture and sepsis. Liver function, serum bilirubin and cholesterol level returned to normal after LT and mass of xanthoma began to decrease. Our results indicate that All 7 survivors showed catch-up growth during follow-up. Mean height Z score improved from -3.7 to -0.8 two years after LT and weight Z score from -3.3 to 0.45.
CONCLUSION: Liver transplantation is an effective treatment for Alagille syndrome with end-stage liver disease, which is better for the patients' growth.

PMID: 28644566 [PubMed - as supplied by publisher]

Hemostatic efficiency of modern topical sealants: Comparative evaluation after liver resection and splenic laceration in a swine model.

Sat, 06/24/2017 - 12:45
Related Articles

Hemostatic efficiency of modern topical sealants: Comparative evaluation after liver resection and splenic laceration in a swine model.

J Biomed Mater Res B Appl Biomater. 2017 Jun 23;:

Authors: Fonouni H, Kashfi A, Majlesara A, Stahlheber O, Konstantinidis L, Gharabaghi N, Kraus TW, Mehrabi A, Oweira H

Abstract
Parenchymal transection during hepatobiliary surgery can disrupt small vasculature or bile ducts, which could be managed difficultly. Sealants are helpful tools to achieve better hemostasis. The aim of this study is to analyze the hemostatic efficiency of four modern sealants in a porcine model. In this study, 40 landrace pigs were assigned equally to the control (without sealant) and four sealant groups. Standardized liver resection and splenic lesions were performed and left without using sealant (control) or treated with one of the following sealants: TachoSil(®) , Tissucol Duo(®) , Coseal(®) , and FloSeal(®) . We measured relative and absolute bleeding times (seconds) as well as total blood loss (g) in a maximum observation time of 300 s. Sealants could show a significantly improved hemostasis comparing to the control group. However, hemostasis was heterogeneous among the sealant groups (liver resection: 60%-100%, spleen injury: 70%-100%). The mean blood loss decreased significantly using sealants comparing to control group (liver resection: 6-120 fold, spleen injury: 2.5-36 fold). The hemostatic time in groups that achieved complete hemostasis was different in each sealant group (liver resection: 30-166 s, spleen injury: 60-180 s). We conclude that the hemostatic efficacy of modern sealants is impressive but heterogeneous in liver resection or splenic lesion. To maximize the effectiveness of these tools, the indication of each sealant should be carefully considered in individual settings by the surgeons. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017.

PMID: 28644516 [PubMed - as supplied by publisher]

Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma.

Sat, 06/24/2017 - 12:45
Related Articles

Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma.

Pediatr Blood Cancer. 2017 Jun 23;:

Authors: Friend BD, Venick RS, McDiarmid SV, Zhou X, Naini B, Wang H, Farmer DG, Busuttil RW, Federman N

Abstract
Although checkpoint inhibitor therapies have demonstrated significant efficacy in many malignancies, they have not been well studied in patients with a history of solid organ transplant. We describe two patients with recurrent, refractory, and progressive advanced fibrolamellar hepatocellular carcinoma (HCC) following orthotopic liver transplantation who received programmed cell death protein 1 (PD-1) inhibitor, nivolumab, on a patient access, off-label basis. Both rapidly developed irreversible acute liver rejection shortly after starting therapy, and ultimately died. While checkpoint inhibitors clearly have tremendous potential as a targeted therapy, they should be avoided or used with extreme caution in the context of an organ transplant.

PMID: 28643391 [PubMed - as supplied by publisher]

Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population.

Sat, 06/24/2017 - 12:45
Related Articles

Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population.

Apoptosis. 2017 Jun 22;:

Authors: Liu F, Li F, Luo L, Yang H, Wei Y, Wang W, Yan L, Wen T, Yang J, Li B

Abstract
Cell death pathway plays an important role in apoptosis, and corruption of this signaling pathway has been shown to participate in carcinogenesis. We aimed at determining whether genetic variants in CASP8, CASP10 and CFLAR influence the development and clinical outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A hospital-based case-control study, including 600 HCC cases and 600 HBsAg positive controls without HCC, was conducted to assess the relationship between 11 tagging SNPs in CASP8, CASP10 and CFLAR and HBV-related HCC risk and prognosis in a Chinese Han population. Among the 11 polymorphisms, only CASP8 rs3834129 (-652 6N ins/del) modified HCC risk. Compared with CASP8 -652 insins genotype, the deldel (adjusted OR 0.717, 95% CI 0.553-0.930) and insdel (adjusted OR 0.731, 95% CI 0.554-0.964) genotypes had a significantly decreased HCC risk. Furthermore, this polymorphism was significantly associated with decreased portal vein tumor thrombosis (adjusted OR 0.554; P = 0.044) and reduced postoperative recurrence (adjusted OR 0.356; P < 0.001) of resected HCC. In addition, the multivariate analysis showed that the -652 6N ins/del polymorphism was significantly associated with improved overall survival and recurrence-free survival of resected HCC patients. The expression levels of CASP8 in HCC tumor tissues were significantly lower than those in paracancerous liver tissues, although no significant association between -652 6N ins/del genotypes and the expression levels of CASP8 were observed in these tissues. These results suggest that the CASP8 -652 6N ins/del polymorphism may play a protective role in the development, progression, and survival of HBV-related HCC among the Chinese Han population.

PMID: 28643196 [PubMed - as supplied by publisher]

Interleukin-6 in Allogeneic Stem Cell Transplantation: Its Possible Importance for Immunoregulation and As a Therapeutic Target.

Sat, 06/24/2017 - 12:45
Related Articles

Interleukin-6 in Allogeneic Stem Cell Transplantation: Its Possible Importance for Immunoregulation and As a Therapeutic Target.

Front Immunol. 2017;8:667

Authors: Tvedt THA, Ersvaer E, Tveita AA, Bruserud Ø

Abstract
Allogeneic stem cell transplantation is associated with a high risk of treatment-related mortality mainly caused by infections and graft-versus-host disease (GVHD). GVHD is characterized by severe immune dysregulation and impaired regeneration of different tissues, i.e., epithelial barriers and the liver. The balance between pro- and anti-inflammatory cytokine influences the risk of GVHD. Interleukin-6 (IL-6) is a cytokine that previously has been associated with pro-inflammatory effects. However, more recent evidence from various autoimmune diseases (e.g., inflammatory bowel disease, rheumatoid arthritis) has shown that the IL-6 activity is more complex with important effects also on tissue homeostasis, regeneration, and metabolism. This review summarizes the current understanding of how pro-inflammatory IL-6 effects exerted during the peritransplant period shapes T-cell polarization with enhancement of Th17 differentiation and suppression of regulatory T cells, and in addition we also review and discuss the results from trials exploring non-selective IL-6 inhibition in prophylaxis and treatment of GVHD. Emerging evidence suggests that the molecular strategy for targeting of IL-6-initiated intracellular signaling is important for the effect on GVHD. It will therefore be important to further characterize the role of IL-6 in the pathogenesis of GVHD to clarify whether combined IL-6 inhibition of both trans- (i.e., binding of the soluble IL-6/IL-6 receptor complex to cell surface gp130) and cis-signaling (i.e., IL-6 ligation of the IL-6 receptor/gp130 complex) or selective inhibition of trans-signaling should be tried in the prophylaxis and/or treatment of GVHD in allotransplant patients.

PMID: 28642760 [PubMed - in process]

Risk of Hepatocellular Cancer in HCV Patients Treated with Direct Acting Antiviral Agents.

Sat, 06/24/2017 - 12:45
Related Articles

Risk of Hepatocellular Cancer in HCV Patients Treated with Direct Acting Antiviral Agents.

Gastroenterology. 2017 Jun 19;:

Authors: Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, El-Serag HB

Abstract
BACKGROUND AND AIMS: The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct acting antivirals (DAA) is unclear. Our aim was to examine the risk and determinants of HCC in patients cured with DAA.
METHODS: We conducted a retrospective cohort study of HCV patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between 1/1/2015 and 12/31/2015. We calculated the annual incidence rates for HCC by SVR. We used Cox regression models to compare the risk of HCC in patients with vs. those without SVR and to identify factors associated with incident HCC among patients with SVR. We reviewed a sample of HCC patients for tumor size and stage at diagnosis.
RESULTS: Among 22,500 patients treated with DAA (19,518 with SVR; 2,982 without SVR), the mean (SD) age was 61.6 (6.1) year, and 39.0% had cirrhosis. There were 271 new cases of HCC, including 183 in patients with SVR. Compared to patients without SVR, those with SVR had a significantly reduced risk of HCC (0.90 vs. 3.45 HCC/100 PY; adjusted hazard ratio [HR], 0.28, 95% CI=0.22-0.36). Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82 vs. 0.34/100 PY in patients without cirrhosis; adjusted HR, 4.73. 95% CI, 3.34-6.68). Most (>44.8%) HCC were classified as stage I. Maximum size of the largest lesion was ≤5 cm in over 75% of cases.
CONCLUSIONS: Among patients treated with DAA, SVR was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute HCC risk remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance.

PMID: 28642197 [PubMed - as supplied by publisher]

Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases.

Sat, 06/24/2017 - 12:45
Related Articles

Laparoscopic versus robotic surgery for hepatocellular carcinoma: the first 46 consecutive cases.

J Surg Res. 2017 May 08;:

Authors: Magistri P, Tarantino G, Guidetti C, Assirati G, Olivieri T, Ballarin R, Coratti A, Di Benedetto F

Abstract
BACKGROUND: Hepatocellular carcinoma has a growing incidence worldwide, and represents a leading cause of death in patients with cirrhosis. Nowadays, minimally invasive approaches are spreading in every field of surgery and in liver surgery as well.
MATERIALS AND METHODS: We retrospectively reviewed demographics, clinical, and pathologic characteristics and short-term outcomes of patients who had undergone minimally invasive resections for hepatocellular carcinoma at our institution between June 2012 and May 2016.
RESULTS: No significant differences in demographics and comorbidities were found between patients in the laparoscopic (n = 24) and robotic (n = 22) groups, except for the rates of cirrhotic patients (91.7% and 68.2%, respectively, P = 0.046). Perioperative data analysis showed that the operative time (mean, 211 and 318 min, respectively, P < 0.001) was the only parameter in favor of laparoscopy. Conversely, robotic-assisted resections were related to less Clavien I-II postoperative complications (22 cases versus 13 cases; P = 0.03). As regards resection margins, the two groups were similar with no statistically significant differences in rates of disease-free resection margins.
CONCLUSIONS: A modern hepatobiliary center should offer both open and minimally invasive approaches to liver disease to provide the best care for each patient, according to the individual comorbidities, risk factors, and personal quality of life expectations. Our results show that the robotic approach is a reliable tool for accurate oncologic surgery, comparable to the laparoscopic approach. Robotic surgery also allows the surgeon to safely approach liver segments that are difficult to resect in laparoscopy, namely segments I-VII-VIII.

PMID: 28641762 [PubMed - as supplied by publisher]

The Development of Stem Cell-Based Treatment for Liver Failure.

Sat, 06/24/2017 - 12:45
Related Articles

The Development of Stem Cell-Based Treatment for Liver Failure.

Curr Stem Cell Res Ther. 2017 Jun 15;:

Authors: Zhu T, Li Y, Guo Y, Zhu C

Abstract
Liver failure is a devastating clinical syndrome with a persistently mortality rate despite advanced care. According to the pathological histology, hepatic failure was divided into four categories: acute liver failure (ALF), subacute liver failure (SALF), acute - on - chronic liver failure (ACLF) and chronic liver failure (CLF). Orthotopic liver transplantation protected patients from hepatic failure. Yet, limitations including postoperative complications, high costs, and shortages of donor organs defect its application. The development of stem cell therapy complements the deficiencies of liver transplantation. Due to its proliferation and differentiation, stem cells had been applied into pre-clinical researches to promote the convalescence of hepatocellular function. With the emerging of the co-cultured system, and genetic engineering, function of stem cells has been further enhanced. In this review, we highlight current findings and present the future prospects in the area of stem cell-based treatment for acute liver failure.

PMID: 28641515 [PubMed - as supplied by publisher]

[Acute Liver Failure, Acute-On-Chronic Liver Failure, Hepatorenal Syndrome, Hepatopulmonary Syndrome and Portopulmonary Hypertension, Artificial Liver Support on the ICU].

Sat, 06/24/2017 - 12:45
Related Articles

[Acute Liver Failure, Acute-On-Chronic Liver Failure, Hepatorenal Syndrome, Hepatopulmonary Syndrome and Portopulmonary Hypertension, Artificial Liver Support on the ICU].

Zentralbl Chir. 2017 Jun;142(3):275-286

Authors: Lodes U, Jacob D, Meyer F

Abstract
Background Acute hepatic dysfunction in the form of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) is a disease with a high risk of mortality and requires interdisciplinary intensive care. Aim This article explains the nomenclature, pathophysiology, prognosis and possible treatment options of ALF and ACLF, including the possibilities of extracorporeal liver support therapy at the point of liver transplantation (LTx). Method Narrative review with a selective literature review and representative case studies. Results/Corner Points ALF and ACLF may have several causes and are associated with high mortality. The causes of ALF must be accurately diagnosed because targeted treatment options are available. Both ALF and ACLF may require a liver transplantation for the patient's survival. For ALF and ACLF there are different criteria for decision-making on liver transplantation and graft allocation. For extracorporeal liver support therapy, two methods have been established (MARS [molecuar adsorbent recirculating system] and FPSA [fractionated plasma separation and adsorption] Prometheus(®)). Both approaches may have the potential to increase the probability of survival of patients with ALF or ACLF. In some cases they can be used for bridging to liver transplantation, in individual cases also for primary poison elimination, e.g. after Amatoxin ingestion. Both methods are not suitable for long-term therapy. Conclusion Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are serious diseases with a high risk of mortality. Affected patients should receive immediate interdisciplinary intensive care in a (tertiary) centre with the aim to clarify the cause of the disease as well as possible treatment options with respect to available extracorporeal liver support therapy and liver transplantation.

PMID: 28641354 [PubMed - in process]

Pages