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Sample records for rat liver transplantation

  1. Supercooling preservation and transplantation of the rat liver.

    PubMed

    Bruinsma, Bote G; Berendsen, Tim A; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L; Uygun, Korkut

    2015-03-01

    The current standard for liver preservation involves cooling of the organ on ice (0-4 °C). Although it is successful for shorter durations, this method of preservation does not allow long-term storage of the liver. The gradual loss of hepatic viability during preservation puts pressure on organ sharing and allocation, may limit the use of suboptimal grafts and necessitates rushed transplantation to achieve desirable post-transplantation outcomes. In an attempt to improve and prolong liver viability during storage, alternative preservation methods are under investigation. For instance, ex vivo machine perfusion systems aim to sustain and even improve viability by supporting hepatic function at warm temperatures, rather than simply slowing down deterioration by cooling. Here we describe a novel subzero preservation technique that combines ex vivo machine perfusion with cryoprotectants to facilitate long-term supercooled preservation. The technique improves the preservation of rat livers to prolong storage times as much as threefold, which is validated by successful long-term recipient survival after orthotopic transplantation. This protocol describes how to load rat livers with cryoprotectants to prevent both intracellular and extracellular ice formation and to protect against hypothermic injury. Cryoprotectants are loaded ex vivo using subnormothermic machine perfusion (SNMP), after which livers can be cooled to -6 °C without freezing and kept viable for up to 96 h. Cooling to a supercooled state is controlled, followed by 3 h of SNMP recovery and orthotopic liver transplantation.

  2. Supercooling Preservation Of The Rat Liver For Transplantation

    PubMed Central

    Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut

    2015-01-01

    The current standard for liver preservation is limited in duration. Employing a novel subzero preservation technique that includes supercooling and machine perfusion can significantly improve preservation and prolong storage times. By loading rat livers with cryoprotectants to prevent both intra- and extracellular ice formation and protect against hypothermic injury, livers can be cooled to −6 °C without freezing and kept viable for up to 96 hours. Here, we describe the procedures of loading cryoprotectants by means of subnormothermic machine perfusion (SNMP), controlled cooling to a supercooled state, followed by SNMP recovery and orthotopic liver transplantation. PMID:25692985

  3. Consecutive en-bloc liver (30%)-pancreas-duodenum-spleen-stomach transplant in Lewis rats.

    PubMed

    Yoo, C H; Hong, I C; Lee, S; Nam, S; Bai, S; Kim, K; Pivetti, C D; Niewiadomski, S T; Wolf, P; Gittes, R F

    2003-01-01

    It is well-known that 30% of the remaining liver mass, following partial hepatectomy, regenerates to full original mass within 2 weeks in rats. In order to carry the transplanted rat liver to repeated transplantation, a technique of combining 30% of the liver with the pancreaticoduodenum and spleen transplantation is performed in this consecutive organ transplantation study. Our laboratory observed several 37-month-old transplanted rats by carrying through 2-3 generations, and histological disclosure were made. Because the partial liver transplants did not regenerate after the transplantation with other splanchnic organs, this technique is not so difficult though subsequent surgical maneuvers are needed and the liver histology proved entirely normal in every aspect when followed beyond the rat's life span of 24 months.

  4. Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model.

    PubMed

    Zou, Yu-Hong; Liu, Xin; Khlentzos, Alexander M; Asadian, Peyman; Li, Peng; Thorling, Camilla A; Robertson, Thomas A; Fletcher, Linda M; Crawford, Darrell H G; Roberts, Michael S

    2010-01-01

    This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl(4)-treated rats compared to controls (p<0.05). The extraction ratios (E) for all drugs were significantly lower (p<0.05) in fibrotic than in normal livers and the decrease in E was consistent with the decrease in intrinsic clearance and permeability-surface area product. In addition, other than for furosemide, the mean transit times for all drugs were significantly longer (p<0.01) in the fibrotic livers than in normal livers. Pharmacokinetic model and stepwise regression analyses suggest that these differences arise from a reduction in both the transport of drugs across the basolateral membrane and their metabolic clearance and were in a manner similar to those previously found for another group of drugs.

  5. Liver transplant

    MedlinePlus

    ... toxins in the blood Storing sugars, fats, iron, copper, and vitamins The most common reason for a ... cirrhosis or primary sclerosing cholangitis Metabolic disorders of copper or iron ( Wilson's disease and hemochromatosis ) Liver transplant ...

  6. Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats

    PubMed Central

    Liu, Qinlong; Krishnasamy, Yasodha; Rehman, Hasibur; Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi

    2015-01-01

    Background Suppressed mitochondrial biogenesis (MB) contributes to acute kidney injury (AKI) after many insults. AKI occurs frequently after liver transplantation (LT) and increases mortality. This study investigated whether disrupted mitochondrial homeostasis plays a role in AKI after LT. Methods Livers were explanted from Lewis rats and implanted after 18 h cold storage. Kidney and blood were collected 18 h after LT. Results In the kidney, oxidative phosphorylation (OXPHOS) proteins ATP synthase-β and NADH dehydrogenase-3 decreased 44% and 81%, respectively, with marked reduction in associated mRNAs. Renal PGC-1α, the major regulator of MB, decreased 57% with lower mRNA and increased acetylation, indicating inhibited synthesis and suppressed activation. Mitochondrial transcription factor-A, which controls mtDNA replication and transcription, protein and mRNA decreased 66% and 68%, respectively, which was associated with 64% decreases in mtDNA. Mitochondrial fission proteins Drp-1 and Fis-1 and mitochondrial fusion protein mitofusin-1 all decreased markedly. In contrast, PTEN-induced putative kinase 1 and microtubule-associated protein 1A/1B-light chain 3 increased markedly after LT, indicating enhanced mitophagy. Concurrently, 18- and 13-fold increases in neutrophil gelatinase-associated lipocalin and cleaved caspase-3 occurred in renal tissue. Both serum creatinine and blood urea nitrogen increased >2 fold. Mild to moderate histological changes were observed in the kidney, including loss of brush border, vacuolization of tubular cells in the cortex, cast formation and necrosis in some proximal tubular cells. Finally, myeloperoxidase and ED-1 also increased, indicating inflammation. Conclusion Suppression of MB, inhibition of mitochondrial fission/fusion and enhancement of mitophagy occur in the kidneys of recipients of liver grafts after long cold storage, which may contribute to the occurrence of AKI and increased mortality after LT. PMID:26480480

  7. Evaluation of 2-year-old intrasplenic fetal liver tissue transplants in rats.

    PubMed

    Lupp, Amelie; Danz, Manfred; Müller, Dieter

    2003-01-01

    Liver cell transplantation into host organs like the spleen may possibly provide a temporary relief after extensive liver resection or severe liver disease or may enable treatment of an enzyme deficiency. With time, however, dedifferentiation or malignant transformation of the ectopically transplanted cells may be possible. Thus, in the present study syngenic fetal liver tissue suspensions were transplanted into the spleen of adult male rats and evaluated 2 years thereafter in comparison to orthotopic livers for histopathological changes and (as markers for preneoplastic transformation) for cytochrome P450 (P450) and glutathione S-transferase (GST) isoform expression. Because inducibility of P450 and GST isoforms may be changed in preneoplastic foci, prior to sacrifice animals were additionally treated either with beta-naphthoflavone, phenobarbital, dexamethasone, or the respective solvent. In the 2-year-old grafts more than 70% of the spleen mass was occupied by the transplant. The transplanted hepatocytes were arranged in cord-like structures. Also few bile ducts were present. Morphologically, no signs of malignancy were visible. With all rats, transplant recipients as well as controls, however, discrete nodular structures were seen in the livers. Due to age, both livers and transplants displayed only a low P450 2B1 and 3A2 and GST class alpha and mu isoform expression. No immunostaining for P450 1A1 was visible. At both sites, beta-naphthoflavone, phenobarbital, or dexamethasone treatment enhanced P450 1A1, P450 2B1 and 3A2, or P450 3A2 expression, respectively. No immunostaining for GST class pi isoforms was seen in the transplants. The livers of both transplant recipients and control rats, however, displayed GST pi-positive foci, corresponding to the nodular structures seen histomorphologically. Compared to the surrounding tissue, these foci also exhibited a more pronounced staining for GST class alpha and mu isoforms and a stronger inducibility of the P450 1A

  8. Expression of Redox Factor-1 in Early Injury Period After Liver Transplantation in Rat Model

    PubMed Central

    Zhang, Ping; Du, Xiaohong; Sun, Zhipeng; Xu, Lijun

    2009-01-01

    The aims of this study were to observe the relationship between injury of graft and expression of redox factor-1 (Ref-1) in early period (24 h) after liver transplantation in rat model. One hundred and fifty adult male Wister rats were randomly divided into three groups including liver transplant group, sham surgery group and untreated control group. After liver transplantation, animals were sacrificed at different time points, and the changes and significance of the expression of Ref-1 were then explored by immunohistochemistry, serology and histopathology. As compared with sham surgery group and untreated control group, the expression of Ref-1 protein in transplant group was stronger in early period after liver transplantation. With pathology analysis, lots of infiltrating inflammation cells were found around the portal veins. Hepatic tissues were injury. However, the injury in sham surgery and untreated control group were comparatively slight. The serum ALT and AST levels reached the peak at 6-12 h, and decreased significantly after 12 h. These data suggested that the degree of liver injury in earlier period after transplantation peaked at 6 h and then decreased. And Ref-1 protein induced by hepatic ischemic reperfusion injury might play a critical role in repairing the injury. PMID:19728933

  9. Abate Cytochrome C induced apoptosome to protect donor liver against ischemia reperfusion injury on rat liver transplantation model

    PubMed Central

    Zhuang, Zhuonan; Lian, Peilong; Wu, Xiaojuan; Shi, Baoxu; Zhuang, Maoyou; Zhou, Ruiling; Zhao, Rui; Zhao, Zhen; Guo, Sen; Ji, Zhipeng; Xu, Kesen

    2016-01-01

    Objective: Aim of this study is to protect donor liver against ischemia-reperfusion injury by abating Cytochrome C induced apoptosome on rat model. Methods: A total of 25 clean SD inbred male rats were used in this research. The rats in ischemia-reperfusion injury group (I/R group, n=5) were under liver transplantation operation; rats in dichloroacetate diisopropylamine group (DADA group, n=5) were treated DADA before liver transplantation; control group (Ctrl group, n=5); other 10 rats were used to offer donor livers. Results: In DADA therapy group, Cytochrome C expression in donor hepatocellular cytoplasm was detected lower than that in I/R group. And the Cytochrome C induced apoptosome was also decreased in according to the lower expressions of Apaf-1 and Caspase3. Low level of cleaved PARP expression revealed less apoptosis in liver tissue. The morphology of donor liver mitochondria in DADA group was observed to be slightly edema but less than I/R group after operation 12 h. The liver function indexes of ALT and AST in serum were tested, and the results in DADA group showed it is significantly lower than I/R group after operation 12 h. The inflammation indexes of IL-6 and TNF-α expressions in DADA group were significantly lower than that in I/R group after operation 24 h. Conclusion: The dichloroacetate diisopropylamine treatment could protect the hepatocellular mitochondria in case of the spillage of Cytochrome C induced apoptosome, and protect the liver against ischemia-reperfusion injury. Thus, it may be a method to promote the recovery of donor liver function after transplantation. PMID:27186297

  10. Gene silencing of 4-1BB by RNA interference inhibits acute rejection in rats with liver transplantation.

    PubMed

    Shi, Yang; Hu, Shuqun; Song, Qingwei; Yu, Shengcai; Zhou, Xiaojun; Yin, Jun; Qin, Lei; Qian, Haixin

    2013-01-01

    The 4-1BB signal pathway plays a key role in organ transplantation tolerance. In this study, we have investigated the effect of gene silencing of 4-1BB by RNA interference (RNAi) on the acute rejection in rats with liver transplantation. The recombination vector of lentivirus that contains shRNA targeting the 4-1BB gene (LV-sh4-1BB) was constructed. The liver transplantation was performed using the two-cuff technique. Brown-Norway (BN) recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNAi downregulated the 4-1BB gene expression of the splenic lymphocytes in vitro, and the splenic lymphocytes isolated from the rats with liver transplantation. LV-sh4-1BB decreased the plasma levels of liver injury markers including AST, ALT, and BIL and also decreased the level of plasma IL-2 and IFN- γ in recipient rats with liver transplantation. Lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient and alleviated the injury of liver morphology in recipient rats with liver transplantation. In conclusion, our results demonstrate that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation.

  11. Hepatotoxins and liver transplantation decrease pulmonary metastases in rats with hepatoma.

    PubMed

    Freise, C E; Liu, T; Ascher, N L; Roberts, J P

    1996-08-01

    Results following liver transplantation for hepatocellular carcinoma have been dismal, attributed largely to recurrent disease locally or at distance sites. Undetected micrometastases or tumor that embolizes at the time of liver transplant from manipulation of the liver may account for these recurrences. A model and treatment protocol were developed to address this clinical problem. The protocol is modeled on the concept of bone marrow transplantation for leukemia. Hepatotoxins that are lethal to both normal hepatocytes and hepatoma cells are administered followed by liver transplantation to "rescue" the failing liver. The feasibility of this protocol was examined in a rat model. Male Buffalo rats were injected with 1 million Morris hepatoma MH-7777 cells intravenously at Day 0 as a model for micrometastatic disease. Three treatment groups were established. Group 1 received no treatment. Group 2 received 5% dextrose in water (D5W) followed by a syngeneic orthotopic liver transplant (OLTX). Group 3 received the hepatotoxin pyrazofuin (10 mg/kg) followed by OLTX. Animals were followed to Day 35, at which time they were sacrificed and examined for evidence of pulmonary metastases and quantitation of nodules with India ink insufflation. There was a significant decrease in the number with pulmonary nodules as well as the number of animals with pulmonary metastatic disease in the pyrazofurin-treated group compared with groups 1 and 2 (4.8 +/- 4.0 nodules/animal vs 45.2 +/- 11.2 nodules/animal--no treatment and 60.8 +/- 21.4 nodules animal--D5W/OLTX group) These data indicate that this model is reliable for examining metastatic hepatoma and that pyrazofurin is effective in preventing hematogenous micrometastases of hepatoma cells. Other hepatotoxins and the effect of allogeneic transplantation and immunosuppression could be examined in this model.

  12. [Lactate dehydrogenase and Krebs cycle enzyme activity in rat liver during the growth of transplanted and spontaneous tumors].

    PubMed

    Morozkina, T S

    1978-03-01

    Certain distinctions in the mouse and rat liver responses to transplanted and spontaneous tumours have been discovered at the initial periods of their growth. The most pronounced changes (the mosaic distribution of enzymatic activity in the lobe) are observed in the case of spontaneous tumours. Activities the Krebs cycle enzymes, especially of NAD-dependent enzymes are seen inhibited in the tumour-bearing liver at the terminal periods of growth of both spontaneous and transplanted tumours; lactate dehydrogenase activity increases (with the exception of mitochondrial lactate dehydrogenase in the rat liver with transplanted sarcomas). PMID:684845

  13. Liver Transplant

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  14. Heparanase enhances early hepatocyte inclusion in the recipient liver after transplantation in partially hepatectomized rats.

    PubMed

    Tsiperson, Vladislav; Goldshmidt, Orit; Ilan, Neta; Shoshany, Gideon; Vlodavsky, Israel; Veitsman, Ella; Baruch, Yaacov

    2008-03-01

    Hepatocyte transplantation is an emerging approach for the treatment of liver diseases. However, broad clinical application of this method has been limited by restricted source of cells and low efficiency of cell integration within the recipient liver. Heparanase cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, activity that affects cellular invasion associated with cancer metastasis and inflammation. This activity has a multifunctional effect on cell-cell interaction, cell adhesion, and angiogenesis. All these factors are important for successful integration of transplanted hepatocytes. Male donor hepatocytes pretreated with heparanase or untreated were transplanted into recipient female rat spleen following partial hepatectomy. Engraftment efficacy was evaluated by PCR for Y chromosome, histology and PCNA, and heparanase immunohistochemistry. In addition, proliferative activity of hepatocytes in vitro was determined by bromodeoxyuridine immunostaining. The number of heparanase-treated cells detected in the recipient liver was significantly increased three- to fivefold within 24-48 h posttransplantation and twofold at 14 days compared with untreated cells. The transplanted hepatocytes treated with heparanase were clearly seen inside portal vein radicles as cell aggregates up to 72 h posttransplantation. The number of portal radicles filled with heparanase-treated hepatocytes was increased compared to control early after transplantation. Heparanase treatment enhanced hepatocyte and sinusoidal endothelial cell proliferation in the liver, and hepatocyte proliferation within the spleen tissue. Preliminary in vitro studies with isolated hepatocytes treated with heparanase showed increased proliferative activity within 24-48 h of cell culture. These results suggest that preincubation of hepatocytes with heparanase increases the presence of hepatocytes within the recipient liver early following cell transplantation and stimulates

  15. Alloimmune Activation Promotes Anti-Cancer Cytotoxicity after Rat Liver Transplantation

    PubMed Central

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A.; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor. PMID:24651497

  16. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

    PubMed

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  17. Influence of recipient gender on intrasplenic fetal liver tissue transplants in rats: cytochrome P450-mediated monooxygenase functions.

    PubMed

    Lupp, Amelie; Hugenschmidt, Sabine; Rost, Michael; Müller, Dieter

    2004-05-01

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern with consecutive differences in P450-mediated monooxygenase activities, which have been shown to be due to a differential profile of growth hormone (GH) secretion. Parallel to previous investigations on P450 isoforms expression, the aim of the present study was to elucidate the influence of recipient gender on P450-mediated monooxygenase activities in intrasplenic liver tissue transplants in comparison to orthotopic liver. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant-recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the vehicles and sacrificed 24 or 48 h thereafter. P450-dependent monooxygenase activities were assessed by a series of model reactions for different P450 subtypes in liver and spleen 9000 g supernatants. In spleens of male and female control rats only very low monooxygenase activities were detectable, whereas with most model reactions distinct activities were observed in transplant-containing organs. Livers and transplant-containing spleens from male rats displayed higher basal ethoxycoumarin O-deethylase and testosterone 2alpha-, 2beta-, 6beta-, 14alpha-, 15alpha-, 15beta-, 16alpha-, 16beta- and 17-hydroxylase activities than those from females. On the other hand, like the respective livers, spleens from female transplant-recipients demonstrated more pronounced p-nitrophenol- and testosterone 6alpha- and 7alpha-hydroxylase activities than those from male hosts. With nearly all model reactions gender-specific differences in inducibility by BNF, PB or DEX could be demonstrated in livers as well as in transplant-containing spleens. These results further confirm that the P450 system of intrasplenic liver tissue transplants and the respective orthotopic livers is similarly influenced

  18. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I

    PubMed Central

    Zhang, Ludi; Shao, Yanjiao; Li, Lu; Tian, Feng; Cen, Jin; Chen, Xiaotao; Hu, Dan; Zhou, Yan; Xie, Weifen; Zheng, Yunwen; Ji, Yuan; Liu, Mingyao; Li, Dali; Hui, Lijian

    2016-01-01

    Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah−/− rats. The Fah−/− rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure, and renal tubular damage. More importantly, the Fah−/− rats developed remarkable liver fibrosis and cirrhosis, which have not been observed in Fah mutant mice or pigs. Transplantation of wild-type hepatocytes rescued the Fah−/− rats from impending death. Moreover, the highly efficient repopulation of hepatocytes in Fah−/− livers prevented the progression of liver fibrosis to cirrhosis and in turn restored liver architecture. These results indicate that Fah−/− rats may be used as an animal model of HT1 with liver cirrhosis. Furthermore, Fah−/− rats may be used as a tool in studying hepatocyte transplantation and a bioreactor for the expansion of hepatocytes. PMID:27510266

  19. Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a rat model of hereditary tyrosinemia type I.

    PubMed

    Zhang, Ludi; Shao, Yanjiao; Li, Lu; Tian, Feng; Cen, Jin; Chen, Xiaotao; Hu, Dan; Zhou, Yan; Xie, Weifen; Zheng, Yunwen; Ji, Yuan; Liu, Mingyao; Li, Dali; Hui, Lijian

    2016-01-01

    Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah(-/-) rats. The Fah(-/-) rats faithfully represented major phenotypic and biochemical manifestations of human HT1, including hypertyrosinemia, liver failure, and renal tubular damage. More importantly, the Fah(-/-) rats developed remarkable liver fibrosis and cirrhosis, which have not been observed in Fah mutant mice or pigs. Transplantation of wild-type hepatocytes rescued the Fah(-/-) rats from impending death. Moreover, the highly efficient repopulation of hepatocytes in Fah(-/-) livers prevented the progression of liver fibrosis to cirrhosis and in turn restored liver architecture. These results indicate that Fah(-/-) rats may be used as an animal model of HT1 with liver cirrhosis. Furthermore, Fah(-/-) rats may be used as a tool in studying hepatocyte transplantation and a bioreactor for the expansion of hepatocytes. PMID:27510266

  20. Developmental changes in glutathione S-transferase isoforms expression and activity in intrasplenic fetal liver tissue transplants in rats.

    PubMed

    Lupp, Amelie; Anschütz, Tino; Lindström-Seppä, Pirjo; Müller, Dieter

    2003-09-01

    The aim of the present study was to characterise developmental changes in glutathione S-transferase (GST) isoforms expression and in glutathione conjugation capacity in intrasplenic liver tissue transplants. For this purpose, syngenic fetal liver tissue suspensions were transplanted into the spleens of adult male Fischer 344 rats. Three days, 1, 2, 4 weeks, 2, 4, 6 months and 1 year later, transplant-recipients and control animals were sacrificed and class alpha, mu and pi GST isoforms expression and GST activities using the substrates o-dinitrobenzene and 1-chloro-2,4-dinitrobenzene were assessed in livers and spleens. In the hepatocytes of the adult livers no class pi, but a distinct class alpha and mu GST expression was seen. The bile duct epithelia were class pi GST positive. Fetal livers displayed almost no class alpha and mu, but a slight class pi GST expression. The same pattern was seen in 3-day-old intrasplenic liver tissue transplants. Up to 2 weeks after surgery the class alpha and mu GST expression increased in the hepatocytes of the transplants, whereas the immunostaining for class pi GST disappeared. No remarkable changes were seen thereafter. Normal conjugation capacities were observed with the livers of both groups of rats. Control spleens displayed only low GST activities. From 2 months after transplantation on activities were significantly higher in transplant-containing spleens than in respective control organs with a further increase up to one year after grafting. These results show that intrasplenically transplanted fetal liver cells proliferate and differentiate into mature cells displaying a GST expression pattern with respective enzyme activities similar to adult liver.

  1. Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver.

    PubMed Central

    Möller, P. H.; Ivarsson, K.; Stenram, U.; Radnell, M.; Tranberg, K. G.

    1998-01-01

    The aim of this study was to compare interstitial laser thermotherapy with excision of a liver tumour. A dimethylhydrazine-induced adenocarcinoma was transplanted (implanted if not stated otherwise) into the left lateral lobe of the rat liver, and treatment was performed 8 days later. In the main experiment, rats were treated with resection of the tumour-bearing lobe or underwent interstitial laser thermotherapy, which was performed at a steady-state temperature of 46 degrees C for 30 min, 3 mm from the tumour margin. The incidence and extent of intraperitoneal spread was smaller after laser thermotherapy than after resection of the tumour-bearing lobe, with no difference in local control. Metastatic spread after resection of the median liver lobe was similar to that observed after sham procedures for thermotherapy or resection, suggesting that the advantage of thermotherapy was not due to a difference in surgical trauma. Additional studies showed that laser thermotherapy reduced intraperitoneal spread when treatment was suboptimal or in a tumour inoculation model and suggested that immunological mechanisms might be involved. It is concluded that interstitial laser thermotherapy reduces spread of liver tumour compared with resection. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9667664

  2. Microsurgical training curriculum for learning kidney and liver transplantation in the rat.

    PubMed

    Hölzen, Jens Peter; Palmes, Daniel; Langer, Martin; Spiegel, Hans Ullrich

    2005-01-01

    During the education of the next generation of scientists in experimental research, careful instruction in surgical techniques is of major importance. This applies in particular to complicated microsurgical models, which require a structured teaching concept with clearly laid-down working steps and adequate didactic resources. Transplantations in rats are undoubtedly among the most difficult models in experimental surgery. Because completely sutured orthotopic liver transplantation and kidney transplantation have been practiced for many years in our Surgical Research Unit, techniques must be transmitted to future generations. A microsurgical training program has been set up with the aim of being efficient, transparent, and motivating. Simply learning-by-doing in the sense of "laissez-faire" is ineffective and costly. Our training program is based on "three-phase didactics," in which the learning targets are presented in sequence and are clearly defined. This report is intended to give a brief overview of the principal transplantation models and to serve as a guide for teaching these models. PMID:16281279

  3. Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

    PubMed Central

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  4. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  5. Transplanted fibroblast cell sheets promote migration of hepatic progenitor cells in the incised host liver in allogeneic rat model.

    PubMed

    Muraoka, Izumi; Takatsuki, Mitsuhisa; Sakai, Yusuke; Tomonaga, Tetsuo; Soyama, Akihiko; Hidaka, Masaaki; Hishikawa, Yoshitaka; Koji, Takehiko; Utoh, Rie; Ohashi, Kazuo; Okano, Teruo; Kanematsu, Takashi; Eguchi, Susumu

    2015-11-01

    Cell sheet engineering has been noted as a new and valuable approach in the tissue-engineering field. The objective of this study was to explore a procedure to induce hepatic progenitor cells and biliary duct structures in the liver. Sprague-Dawley rat dermal fibroblast (DF) sheets were transplanted into the incised surface of the liver of F344 nude rats. In the control group, an incision was made without transplantation of the DF sheets. Bile duct (BD)-like structures and immature hepatocyte-like cells were observed in the DF sheet transplant sites. These BD-like structures were cytokeratin-8-positive, while the hepatocyte-like cells were both OV-6-positive and α-fetoprotein-positive as well. The proliferation and differentiation of liver progenitor cells were not influenced by hepatectomy. We also transplanted DF sheets transfected with a plasmid encoding the enhanced yellow fluorescent protein target to mitochondria (pEYFP-Mito) by electroporation, and found that the new structures were pEYFP-Mito-negative. We observed new BD-like structures and immature hepatocytes after transplantation of DF sheets onto incised liver surfaces, and clarified that the origin of these BD-like structures and hepatocyte-like cells was the recipient liver. The present study described an aspect of the hepatic differentiation process induced at the site of liver injury.

  6. Liver transplant - series (image)

    MedlinePlus

    Liver failure causes many problems, including malnutrition, problems with blood clotting, bleeding form the gastrointestinal tract, and jaundice. Frequently, patients who undergo liver transplantation are quite ill, and require ...

  7. Hepatitis C: liver transplantation.

    PubMed

    Metts, Julius; Carmichael, Lesley; Kokor, Winfred; Scharffenberg, Robert

    2014-12-01

    Hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma account for approximately 40% of the 6,000 adult liver transplantations performed each year in the United States. Survival rates are 76% to 83% at 2 years and 69% to 72% at 5 years. If eligible for surgery and in the absence of contraindications, any patient with HCV infection who develops decompensated liver disease or hepatocellular carcinoma is a candidate for liver transplantation. Most transplantation programs require that a patient with a history of alcohol or drug abuse be abstinent for at least 6 months and active in a substance abuse rehabilitation program. Prioritization for transplantation is based primarily on a patient's model for end-stage liver disease score, though other factors are considered. Complications after liver transplantation include recurrence of HCV infection, rejection of the transplanted liver, and an increased rate of infection because of immunosuppression. Various drugs are used to prevent infection and organ rejection. Liver transplant recipients also develop diabetes, hypertension, hyperlipidemia, renal dysfunction, osteopenia, and cancers at high rates, likely because of the effects of immunosuppressive drugs, particularly steroids and calcineurin inhibitors. The family physician's role in caring for liver transplant recipients often involves detection and management of these conditions. PMID:25478647

  8. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    PubMed

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

  9. Split liver transplantation.

    PubMed

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  10. Influence of recipient gender on cytochrome P450 isoforms expression in intrasplenic fetal liver tissue transplants in rats.

    PubMed

    Lupp, Amelie; Hugenschmidt, Sabine; Danz, Manfred; Müller, Dieter

    2003-06-30

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern which is regulated by a differential profile of growth hormone (GH) secretion. The aim of the present study was to elucidate whether liver cell transplants at an ectopic site are also subject to this influence. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the solvents and sacrificed 24 or 48 h thereafter. Livers and intrasplenic transplants were evaluated for the expression of the P450 subtypes 1A1, 2B1, 2E1, 3A2 and 4A1 by means of immunohistochemistry. The livers of both male and female rats displayed nearly no P450 1A1, but a distinct P450 2B1, 2E1, 3A2 and 4A1 expression. Whereas no sex differences were seen in the P450 1A1 expression, the immunostaining for P450 2B1, 3A2 and 4A1 was stronger in males and that for P450 2E1 in females. Similarly, in the intrasplenic liver cell transplants almost no P450 1A1, but a noticeable P450 2B1, 2E1, 3A2 and 4A1 expression was observed. Like in the respective livers, the immunostaining for P450 2B1, 3A2 and 4A1 was stronger in the transplants hosted by male than by female rats, whereas the opposite was the case for the P450 2E1 expression. Both in livers and transplants with some sex-specific differences P450 1A1 and 2E1 expression was induced by BNF, that of P450 2B1 by BNF and PB, and that of P450 3A2 by PB and DEX. These results indicate that the P450 system of ectopically transplanted liver cells is influenced by the gender of the recipient organism like that of the orthotopic livers.

  11. Expression and inducibility of cytochrome P450 isoforms in 1-year-old intrasplenic liver cell transplants in rats.

    PubMed

    Lupp, Amelie; Danz, Manfred; Müller, Dieter; Klinger, Wolfgang

    2002-03-01

    Syngenic fetal liver tissue suspensions were transplanted into the spleens of 60- to 90-day-old male Fischer 344 inbred rats. Transplant recipients were compared with age-matched control rats. One year after surgery, the animals were treated orally with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the respective solvents 24 or 48 h before being killed. Expression of cytochrome P450 (P450) isoforms in spleens and orthotopic livers was assessed by immunohistochemistry and P450-dependent monooxygenase functions by the model reactions ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD), pentoxyresorufin O-depentylation (PROD) and ethylmorphine N-demethylation (EMND). Spleens of control animals displayed almost no expression of P450 isoforms and P450-mediated monooxygenase functions. Similar to liver, in the transplanted hepatocytes no P450 1A1 but distinct P450 2B1 and 3A2 expression was observed. Furthermore, the transplant-containing spleens displayed significant EROD, ECOD, PROD and EMND activities. Similar to normal liver, BNF treatment enhanced P450 1A1 and 2B1, PB induced P450 2B1 and 3A2, and DEX induced P450 3A2 expression in the transplanted hepatocytes. Correspondingly, in the transplant-containing spleens EROD, ECOD and PROD activities were significantly enhanced following BNF treatment, EROD, ECOD, PROD and EMND activities after PB administration, and EMND activity by DEX treatment. These results demonstrate that hepatocytes originating from fetal liver tissue suspensions can survive in the spleen at least for 1 year. They have differentiated into adult hepatocytes and even 1 year after transplantation express different P450 isoforms which are inducible by BNF, PB and DEX, corresponding to normal adult liver.

  12. Imaging in liver transplantation

    PubMed Central

    Caruso, Settimo; Miraglia, Roberto; Maruzzelli, Luigi; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2009-01-01

    The aim of this study was to illustrate the role of non-invasive imaging tools such as ultrasonography, multi-detector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation. PMID:19222090

  13. About the Operation: Liver Transplant

    MedlinePlus

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both ...

  14. Diluted Blood Reperfusion as a Model for Transplantation of Ischemic Rat Livers: ALT is a Direct Indicator of Viability

    PubMed Central

    Uygun, Korkut; Tolboom, Herman; Izamis, Maria-Louisa; Uygun, Basak; Sharma, Nripen; Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Hertl, Martin; Berthiaume, François; Yarmush, Martin L.

    2010-01-01

    Donors after Cardiac Death present a significant pool of untapped organs for transplantation, and use of machine perfusion strategies has been an active focus area in experimental transplantation. However, despite two decades of research, a gold standard is yet to emerge for machine perfusion systems and protocols. Whole blood reperfusion has been used as a surrogate for organ transplantation, especially as a model for the short-term response post transplantation, for optimization of perfusion systems. While it is known that there is a strong correlation between liver function in whole-blood reperfusion and survival, the exact nature of these correlations, and to what extent they can be considered as an indicator of viability for transplantation/recipient survival, remain unclear. In this work, we demonstrate that diluted whole-blood reperfusion can be used as a direct model for transplantation of ischemic rat liver grafts. Moreover, it was shown that recipient survival can be predicted based simply on the value of ALT during perfusion, and quantitative criteria of viability was developed for use in this animal model. These results indicate that in the rat model graft survival is highly correlated to hepatocellular damage. PMID:20832525

  15. CD47 Blockade Reduces Ischemia/Reperfusion Injury and Improves Survival in a Rat Liver Transplantation Model

    PubMed Central

    Jia, Jianluo; Manning, Pamela T.; Hiebsch, Ronald R.; Gunasekaran, Muthukumar; Upadhya, Gundumi A.; Frazier, William A.; Mohanakumar, Thalachallour; Lin, Yiing; Chapman, William C.

    2015-01-01

    Orthotopic liver transplantation (OLT) remains the standard treatment option for nonresponsive liver failure. Because ischemia/reperfusion injury (IRI) is an important impediment to the success of OLT, new therapeutic strategies are needed to reduce IRI. We investigated whether blocking the CD47/thrombospondin-1 inhibitory action on nitric oxide signaling with a monoclonal antibody specific to CD47 (CD47mAb400) would reduce IRI in liver grafts. Syngeneic OLT was performed with Lewis rats. Control immunoglobulin G or CD47mAb400 was administered to the donor organ at procurement or to both the organ and the recipient at the time of transplant. Serum transaminases, histological changes of the liver, and animal survival were assessed. Oxidative stress, inflammatory responses, and hepatocellular damage were also quantified. A significant survival benefit was not achieved when CD47mAb400 was administered to the donor alone. However, CD47mAb400 administration to both the donor and the recipient increased animal survival afterward. The CD47mAb400-treated group showed lower serum transaminases, bilirubin, oxidative stress, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining, caspase-3 activity, and proinflammatory cytokine expression of tumor necrosis factor α, interleukin-1β, and interleukin-6. Thus, CD47 blockade with CD47mAb400 administered both to the donor and the recipient reduced liver graft IRI in a rat liver transplantation model. This may translate to decreased liver dysfunction and increased survival of liver transplant recipients. PMID:25482981

  16. Living related liver transplantation.

    PubMed

    Makuuchi, M; Kawarazaki, H; Iwanaka, T; Kamada, N; Takayama, T; Kumon, M

    1992-01-01

    Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.

  17. Liver transplantation: current concepts.

    PubMed Central

    Wall, W J

    1988-01-01

    In this decade liver transplantation has been established as the preferred treatment for children and adults with irreversible end-stage liver disease. Biliary atresia in children and nonalcoholic cirrhosis in adults are the most common indications for the procedure. Transplantation currently plays only a minor role in the treatment of hepatic malignant disease. Blood group compatibility between donor and recipient is preferred, but histocompatibility matching (tissue typing) currently has no significant role in the selection of recipients. Approximately 70% of recipients survive for 1 year, and these patients have an excellent prospect of long-term survival. The emerging evidence indicates that the quality of life and rehabilitation of most liver recipients are good. The current success of liver transplantation can be attributed to critical selection of recipients, modern anesthetic and surgical techniques, improved perioperative care, accurate diagnosis of rejection and superior immunosuppression with cyclosporine. PMID:3289710

  18. Pediatric liver transplantation

    PubMed Central

    Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

    2009-01-01

    In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

  19. Transplantable liver production plan: "Yamaton"--liver project, Japan.

    PubMed

    Hata, Toshiyuki; Uemoto, Shinji; Kobayashi, Eiji

    2013-10-01

    Organ grafts developed in the xenogeneic pig scaffold are expected to resolve most issues of donor safety and ethical concerns about living-donor liver transplantation in Japan. We have been working on so-called "Yamaton" projects to develop transplantable organs using genetically engineered pigs. Our goal is to produce chimeric livers with human parenchyma in such pigs. The Yamaton-Liver project demonstrated the proof of concept by showing that rat-mouse chimeric livers could develop in mice and be successfully transplanted into syngeneic or allogeneic rats. Under conventional immunosuppression, the transplanted livers showed long-term function and protection against rejection. Because chimeric liver grafts have xenogeneic components, additional strategies, such as humanization of pig genes, induction of hematopoietic chimeras in donors, and replacement of pig endothelial cells with human ones, might be required in clinical use. Our projects still need to overcome various hurdles but can bring huge benefits to patients in the future. PMID:23896578

  20. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD.

  1. Liver transplantation in Germany.

    PubMed

    Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

    2016-08-01

    Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. PMID:27082951

  2. THEMES OF LIVER TRANSPLANTATION

    PubMed Central

    Starzl, Thomas E.; Fung, John J.

    2010-01-01

    Liver transplantation was the product of 5 interlocking themes. These began in 1958-59 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g. familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and ALG. With this regimen, the world’s longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979) which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as

  3. Developmental changes of cytochrome P450 dependent monooxygenase functions after transplantation of fetal liver tissue suspension into spleens of adult syngenic rats.

    PubMed

    Lupp, A; Trautmann, A K; Krausse, T; Klinger, W

    1998-06-01

    Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic Fisher 344 inbred rats. Animals were sacrificed at 3 days, 1, 2, 4 weeks, and 2, 4 and 6 months after transplantation and cytochrome P450 (P450) dependent monooxygenase functions in spleen and liver 9000 g supernatants were assessed by measuring three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; mainly 1A), ethoxycoumarin O-deethylation (ECOD; predominantly 1A, 2A, 2B) and ethylmorphine N-demethylation (END; mainly 3A). Values of transplant recipients were compared to those of sham operated and age matched control rats. Spleen weights were significantly higher in transplanted rats, compared to controls or sham operated animals, but there was no influence of the transplants within the spleens on liver weights. With fetal livers at the 21st day of gestation, the day of transplantation, a weak EROD and ECOD, but no END activity was seen. Spleens of controls or sham operated animals displayed nearly no P450 mediated monooxygenase functions. In the explant containing spleens a significant and increasing EROD activity was found from 4 weeks after surgery on and an ECOD activity already 2 weeks after transplantation. END was only slightly enhanced at 6 months after surgery. The livers of all three groups of rats displayed normal EROD, ECOD and END activities. Transplantation of fetal liver tissue suspensions into the spleens did not influence the P450 dependent monooxygenase functions within the livers of the animals. From these results it can be concluded that intrasplenically transplanted liver cells originating from syngenic fetal liver tissue suspensions proliferate and differentiate within the host organs. They display P450 dependent monooxygenase functions with some developmental changes during the observed time period of 6 months.

  4. Liver transplantation in Spain.

    PubMed

    de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel

    2016-09-01

    Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016

  5. Dexmedetomidine Pretreatment Attenuates Kidney Injury and Oxidative Stress during Orthotopic Autologous Liver Transplantation in Rats

    PubMed Central

    Wu, Shan; Jin, Yi; Wang, Yiheng; Cai, Jun

    2016-01-01

    This paper aims to explore whether pretreatment with dexmedetomidine (Dex) has antioxidative and renal protective effects during orthotopic autologous liver transplantation (OALT) and its impact on nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Sprague-Dawley rats were randomized into groups that include sham-operated (group S), model (group M), low dose Dex (group D1), high dose Dex (group D2), atipamezole (a nonspecific α2 receptor blocker) + high dose Dex (group B1), ARC239 (a specific α2B/c receptor blocker) + high dose Dex (group B2), and BRL-44408 (a specific α2A receptor blocker) + high dose Dex (group B3). Then histopathologic examination of the kidneys and measurement of renal function, the renal Nrf2 protein expression, and oxidants and antioxidants were performed 8 hours after OALT. We found that pretreatment with Dex activated Nrf2 in glomerular cells and upregulated antioxidants but reduced oxidants (all P < 0.01, group D2 versus group M). Atipamezole and BRL-44408, but not ARC239, reversed these protective effects. In conclusion, pretreatment with Dex activates Nrf2 through α2A receptor, increases the antioxidant levels, and attenuates renal injury during OALT. PMID:26682005

  6. Obesity and liver transplantation

    PubMed Central

    Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele

    2015-01-01

    The percentage of overweight and obese patients (OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation (LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed. PMID:26421262

  7. Analgesia after liver transplantation

    PubMed Central

    Milan, Zoka

    2015-01-01

    This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intra- and postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience. PMID:26413222

  8. Evaluation of lipid peroxidation activity at intravenous administration of gold nanorods in rats with simulated diabetes and transplanted liver cancer

    NASA Astrophysics Data System (ADS)

    Bucharskaya, Alla B.; Dikht, Natalia I.; Afanasyeva, Galina A.; Terentyuk, Georgy S.; Maslyakova, Galina N.; Zaraeva, Nadezhda V.; Khlebtsov, Nikolai G.; Khlebtsov, Boris N.

    2014-01-01

    In the experiment the white outbred rats with transplanted liver cancer (cholangiocarcinoma line PC-1) and simulated alloxan diabetes were treated by single intravenous injection of gold nanorods. State of lipid peroxidation was evaluated by the following parameters: the malondialdehyde, lipid hydroperoxide, the average weght molecules in the serum of animals by conventional spectrophotometric methods study using a spectrofluorometer RF-5301 PC (Shimadzu, Japan). In both experimental groups of animals the significant increasing of levels of lipid peroxidation products was noted compared with control group. After intravenous administration of nanoparticles in the group of animals with alloxan diabetes the activation of a free radical oxidation was not observed, in group with transplanted liver cancer the increasing of levels of lipid hydroperoxide, malondialdehyde was established.

  9. [Running through the liver transplantation].

    PubMed

    Grecu, F

    2003-01-01

    An overview of the organization, timing and developing of the liver transplantation is difficult to be made in terms of multiple sequences and a great variety of activities during the developing of such activity. A well-trained transplant team must carry out the potential donor, the liver grafts manipulation and the graft receptor, in the condition of a competitive medical system. A summary presentation, showing the essentials of the proceedings in liver transplantation could be assimilated as a guide of multidisciplinary sequences that leads to the completion of the liver grafting. The common feature of all that means the liver transplantation and generally in organ transplantation is the performance and exactingness.

  10. Imaging in pediatric liver transplantation.

    PubMed

    Monti, L; Soglia, G; Tomà, P

    2016-05-01

    Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors. PMID:26909515

  11. Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model.

    PubMed

    Zhang, YeWei; Zhao, HeWei; Bo, Lin; Yang, YinXue; Lu, Xiang; Sun, JingFeng; Wen, JianFei; He, Xia; Yin, GuoWen

    2012-09-01

    Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4(+)CD25(+) regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased significantly to (459.2±76.9) U L(-1), total bilirubin increased to (124.1±33.7) μmol L(-1) (P<0.05) and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly to 1.50%±0.50% (P<0.05) compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

  12. Liver transplantation for malignancies.

    PubMed

    Eghtesad, Bijan; Aucejo, Federico

    2014-09-01

    Liver transplantation (LT) has become an acceptable and effective treatment for selected patients with hepatocellular carcinoma with excellent outcomes. More recently, LT has been tried in different primary and secondary malignancies of the liver. The outcomes of LT for very selected group of patients with hilar cholangiocarcinoma (CCA) have been promising. Excellent results have been reported in LT for patients with unresectable hepatic epithelioid hemangioendothelioma (HEHE). In contrast to excellent results after LT for HEHE, results of LT for angiosarcoma have been disappointing with no long-term survivors. Hepatoblastoma (HB) is the most common primary liver cancer in pediatric age group. Long-term outcomes after LT in patients with unresectable tumor and good response to chemotherapy have been promising. Indication for LT for hepatic metastasis from neuroendocrine tumors (NETs) is mainly for patients with unresectable tumors and for palliation of medically uncontrollable symptoms. Posttransplant survival in those patients with low tumor activity index is excellent, despite recurrence of the tumor. More recent limited outcomes data on LT for unresectable hepatic metastases from colorectal cancer have claimed some survival benefit compared to the previous reports. However, due to the high rate of tumor recurrence in a very short time after LT, especially in the era of organ shortage, this indication has not been favored by the transplant community. PMID:24604263

  13. Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

    PubMed

    Lupp, A; Lau, K; Trautmann, A K; Krausse, T; Klinger, W

    1999-01-01

    In the present study the effects of beta-naphthoflavone (BNF), phenobarbital (PB) and dexamethasone (DEX) on cytochrome P450 (P450) dependent monooxygenase functions were investigated in intrasplenic liver cell explants in comparison to adult liver. Fetal liver tissue suspensions were transplanted into the spleens of 60-90 days old adult male syngenic Fisher 344 inbred rats. 2, 4 or 6 months after surgery, transplant recipients and age matched controls were orally treated with BNF (1x50 mg/kg body weight (b.wt.)), PB (1x50 mg/kg b.wt.), DEX (for 3 days 4 mg/kg b.wt. per day), or the respective solvents (dimethylsulfoxide or 0.9% NaCl). The animals were sacrificed 24 (BNF, DEX) or 48 (PB) hours after the last treatment. P450 mediated monooxygenase functions were measured in spleen and liver 9000 g supernatants by three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; 1A), ethoxycoumarin O-deethylation (ECOD; 1A, 2A, 2B), and ethylmorphine N-demethylation (END; 3A). Spleen weights were significantly higher in transplanted rats, compared to controls, at all three time points after surgery. Induction with PB or DEX, and in some cases also with BNF, lead to a significant increase in liver weights of transplant recipients and control rats independent of the time after transplantation. In contrast, there was no influence on spleen weights due to BNF or PB. At all time points after surgery, with DEX a marked decrease in body weights, weights of adrenal glands and of lymphatic organs like thymus glands and spleens was observed, with the weights of the transplant containing spleens being still higher in comparison to control organs. Spleens of control animals displayed nearly no P450 mediated monooxygenase functions neither without nor with induction. After transplantation, however, significant EROD and ECOD, but hardly any END activities were seen in the host organs at all three time points after surgery. In transplant containing spleens

  14. Interventional Radiology in Liver Transplantation

    SciTech Connect

    Karani, John B. Yu, Dominic F.Q.C.; Kane, Pauline A.

    2005-04-15

    Radiology is a key specialty within a liver transplant program. Interventional techniques not only contribute to graft and recipient survival but also allow appropriate patient selection and ensure that recipients with severe liver decompensation, hepatocellular carcinoma or portal hypertension are transplanted with the best chance of prolonged survival. Equally inappropriate selection for these techniques may adversely affect survival. Liver transplantation is a dynamic field of innovative surgical techniques with a requirement for interventional radiology to parallel these developments. This paper reviews the current practice within a major European center for adult and pediatric transplantation.

  15. Liver transplantation at Mount Sinai.

    PubMed

    Kim-Schluger, L; Florman, S S; Gondolesi, G; Emre, S; Sheiner, P A; Fishbein, T M; Schwartz, M E; Miller, C M

    2000-01-01

    Nearly 2000 liver transplants have been performed over the past 12 years at Mount Sinai, with a recent exponential growth in living donor surgeries. Living-donor liver transplantation has emerged as an important option for our patients with end-stage liver disease. We are only beginning to recognize fully the advantages that 'scheduled' liver transplantation can offer. In this era of severe cadaver organ shortages, living donation offers patients the option of liver replacement in a timely fashion, before life-threatening complications of hepatic failure and/or carcinoma progression prohibit transplantation. The next era of transplantation at Mount Sinai will bring significant increases in the number of transplants performed with living donors, with projections of over 50% of the total transplants each year expected to involve living donations. We are committed to offering this option while recognizing that donor safety remains paramount and cannot be overemphasized. Proper donor and recipient selection, as well as surgical experience are imperative to success with this technically demanding procedure. Recurrent disease after transplantation, particularly with hepatitis C, remains a challenge clinically. Further investigations into the pathogenesis of the rapid progression of recurrent hepatitis C need to be addressed. Living donor transplantation could be an important option for these patients and would allow timely transplantation and the potential for improved survival in patients with hepatocellular carcinoma. PMID:11512318

  16. Liver transplantation for Wilson's disease.

    PubMed

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  17. Non-viral human IL-10 gene expression reduces acute rejection in heterotopic auxiliary liver transplantation in rats.

    PubMed

    Hong, In Chul; Mullen, Patricia M; Precht, Andrew F; Khanna, Ajai; Li, Melissa; Behling, Cynthia; Lopez, Valerie F; Chiou, Henry C; Moss, Ronald B; Hart, Marquis E

    2003-01-01

    We studied nonviral delivery, expression, and the effect of the human interleukin-10 (Hu IL-10) gene on the rat model of heterotopic auxiliary liver transplantation (HALT). Two previous pilot studies showed remarkable expression of the Hu IL-10 gene in donor and recipient rats, and a decreasing effect of acute rejection in certain cases. In this study, we focused on the efficacy of Hu IL-10 gene expression to decrease acute rejection compared with cyclosporine A (CyA) in a HALT model. Three study groups and one control group were designed. Each group consisted of 6 DA donor and 6 Lewis recipient rats, which underwent HALT. In the control group, donors and recipients were not treated at all. In group II, recipients were treated with one dose of CyA. In group III, donors were treated with Hu IL-10 plasmid. In group IV, donors were treated with Hu IL-10 plasmid, and recipients were treated with one dose of CyA. Rejection was established by histopathology: it revealed 100% rejection in control and 33.3% rejection in study groups II, III, and IV. Human IL-10 gene expression prevented acute rejection with the same efficacy as CyA in the HALT model in rats.

  18. Neurologic complications after liver transplantation

    PubMed Central

    Živković, Saša A

    2013-01-01

    Neurologic complications are relatively common after solid organ transplantation and affect 15%-30% of liver transplant recipients. Etiology is often related to immunosuppressant neurotoxicity and opportunistic infections. Most common complications include seizures and encephalopathy, and occurrence of central pontine myelinolysis is relatively specific for liver transplant recipients. Delayed allograft function may precipitate hepatic encephalopathy and neurotoxicity of calcineurin inhibitors typically manifests with tremor, headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or conversion to an alternative medication usually result in clinical improvement. Standard preventive and diagnostic protocols have helped to reduce the prevalence of opportunistic central nervous system (CNS) infections, but viral and fungal CNS infections still affect 1% of liver transplant recipients, and the morbidity and mortality in the affected patients remain fairly high. Critical illness myopathy may also affect up to 7% of liver transplant recipients. Liver insufficiency is also associated with various neurologic disorders which may improve or resolve after successful liver transplantation. Accurate diagnosis and timely intervention are essential to improve outcomes, while advances in clinical management and extended post-transplant survival are increasingly shifting the focus to chronic post-transplant complications which are often encountered in a community hospital and an outpatient setting. PMID:24023979

  19. Size mismatch in liver transplantation.

    PubMed

    Fukazawa, Kyota; Nishida, Seigo

    2016-08-01

    Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. PMID:27474079

  20. Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction.

    PubMed

    Cordoba, Shaun P; Wang, Chuanmin; Williams, Rohan; Li, Jian; Smit, Lynn; Sharland, Alexandra; Allen, Richard; McCaughan, Geoffrey; Bishop, Alex

    2006-04-01

    This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta-analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty-six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT-1, IRF-1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT-PCR. The results were compared to two published high-throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT-1 and IRF-1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT-1, IRF-1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT-1/IRF-1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism.

  1. Nutritional Status and Liver Transplantation

    PubMed Central

    Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

    2012-01-01

    Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as ‘metabolic syndrome’, may play a negative role on the overall survival of liver transplant patients. In this report we

  2. Acute liver failure and liver transplantation.

    PubMed

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

    Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  3. Current Issues in Liver Transplantation

    PubMed Central

    2016-01-01

    The state of liver transplantation continues to evolve. This article focuses on 3 separate yet important issues within this field. First, there is a proposal to change the allocation of donor livers in the United States. The fundamental premise of this proposal is to equalize access to donor livers across the country. To accomplish this goal, the proposal is to increase the geographic area of liver allocation. As might be expected, there is a great deal of controversy surrounding the possibility of a major change in liver allocation and distribution. A second area of interest, and perhaps the most important therapeutic breakthrough in the field of hepatology, is the introduction of direct-acting antiviral agents against hepatitis C virus (HCV) infection. With cure rates up to 100%, an increasing proportion of liver transplant candidates and recipients are being cured of HCV infection with therapies that have minimal side effects. Consequently, the impact of HCV infection on patient and graft survival will likely improve substantially over the next few years. Finally, this article reviews the role of donor-specific antibodies (DSAs) in antibody-mediated rejection. Long recognized as an important factor in graft survival in renal transplantation, DSAs have recently been shown to be a strong predictor of graft and patient survival in liver transplantation. However, the importance of DSAs in liver transplantation is uncertain, in large part due to the absence of proven therapies. PMID:27231452

  4. Biliary Complications After Liver Transplantation.

    PubMed

    Jagannath, Sanjay; Kalloo, Anthony N.

    2002-04-01

    The incidence of biliary complications after liver transplant is estimated to be 8% to 20%. Post-liver transplant biliary complications may lead to acute and chronic liver injury. The early recognition and prompt treatment of such complications improves the long-term survival of the patient and graft. An understanding of the type of biliary reconstruction, the rationale for creating a particular anastomosis, and the technical difficulties in reconstructing the biliary tract are important in assessing and managing complications after liver transplant. Because the clinical presentation of these patients may be subtle, the physician must be aggressive and thoughtful in ordering and interpreting the diagnostic tests. Important points to remember are 1) that noninvasive examinations may fail to detect small obstructions or leaks, 2) a liver biopsy often is performed prior to cholangiography to exclude rejection and ischemia, and 3) the liver biopsy can miss an extrahepatic obstruction by misinterpreting portal inflammation as rejection. Biliary leaks and strictures are the most common biliary complications following liver transplant. Less common complications include ampullary dysfunction and stone/sludge formation. The effective management of biliary complications following a liver transplant depends on understanding the natural history, the prognosis, and the available therapeutic options for each type of complication.

  5. Lipids in liver transplant recipients

    PubMed Central

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-01-01

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  6. Lipids in liver transplant recipients.

    PubMed

    Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H

    2016-03-28

    Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drug-drug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. PMID:27022213

  7. Bone marrow transplantation in the rat. III. Structure of the liver inflammatory lesion in acute graft-versus-host disease

    SciTech Connect

    Leszczynski, D.; Renkonen, R.; Haeyry, P.

    1985-08-01

    The liver is a major parenchymal target organ of acute graft-versus-host disease (aGVHD) after bone marrow transplantation in the rat. The authors have analyzed the nature of cellular infiltrates in the liver using monoclonal antibodies against white cell subsets and investigated the anatomic distribution of the inflammatory cell subsets inside the liver parenchyma. Several types of white cells are present in a normal control liver: In the portal area the T-helper (Th) cells predominate, (surface) immunoglobulin-expressing B cells are present in ample numbers, and most of the phagocytes are Ia-positive. In the central vein area the T-suppressor/killer cells (Tsk) dominate, no B cells are present, and most of the phagocytes are Ia-negative. During aGVHD the number of T cells increases rapidly in the portal area; and after an initial strong increase, the Th/Tsk ratio decreases but remains still above 1. In the central vein area there is also an increase in the number of T cells, compared with that in the syngeneic recipient, but the Th/Tsk ratio rapidly decreases and remains uniformly below 1. During aGVHD the B cells entirely disappear from the portal area, whereas a small but distinct number of mature plasma cells with intracellular immunoglobulin appear in the central vein area. Following irradiation the Ia-positive phagocytic cells entirely disappear from the portal area and decrease distinctly in number in the central vein area. During aGVHD the number of Ia-positive phagocytes increases again in both locations. In the central vein area the positive phagocytes are seen over the background level, and, concomitantly, the Ia-negative phagocytes disappear.

  8. Hepatitis C and liver transplantation

    NASA Astrophysics Data System (ADS)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  9. The history of liver transplantation in Turkey.

    PubMed

    Moray, Gökhan; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    Liver transplantation is the definitive treatment for end-stage liver diseases. The first successful liver transplant was performed in the United States by Thomas Starzl in 1967. The first successful solid organ transplant in Turkey was a living-related kidney transplant performed by Dr. Haberal in 1975. After much effort by Dr. Haberal, the Turkish parliament enacted a law about organ transplantation in 1979. After clinical and experimental studies, the first liver transplant in Turkey was performed by Dr. Haberal in 1988. The first successful partial living-donor liver transplant in children in Turkey was performed by the same team on March 15, 1990. On April 24, 1990, the first living-donor liver transplant was performed on a child in Turkey using a left lateral segment by Dr. Haberal and coworkers. On May 16, 1992, Dr. Haberal performed a simultaneous living-donor liver and kidney transplantation to an adult from the same donor. There currently are 30 liver transplantation centers in Turkey. According to data from the Ministry of Health, there presently are 2065 patients in Turkey who are waiting for a liver transplantation. From January 2002 to June 2013, there were 6091 liver transplants performed in Turkey (4020 living-donor [66% ] and 2071 deceased donor liver transplants [34% ]). From January 2011 to June 2013, there were 2514 patients who had liver transplants in Turkey, and 437 patients (17%) died. The number of liver transplants per year in Turkey reached 1000 transplants in 2012 and more than 1150 transplants in 2013 (15.1/million/y). Therefore, Turkey has one of the highest volumes of liver transplantation per population worldwide, with 90% survival within 1 year after transplantation.

  10. Liver transplantation for hilar cholangiocarcinoma.

    PubMed

    Robles, Ricardo; Sánchez-Bueno, Francisco; Ramírez, Pablo; Brusadin, Roberto; Parrilla, Pascual

    2013-12-28

    The most appropriate treatment for Klatskin tumor (KT) with a curative intention is multimodal therapy based on achieving resection with tumour-free margins (R0 resections) combined with other types of neoadjuvant or adjuvant treatment (the most important factor affecting KT survival is the possibility of R0 resections, achieving 5-year survival rate of 40%-50%). Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%. In irresectable non-disseminated KT patients, using liver transplantation without neoadjuvant treatment, the 5-year survival rate increase to 38%, reaching 50% survival in early stage. In selected cases, with liver transplantation and neoadjuvant treatment (chemotherapy and radiotherapy), the actuarial survival rate is 65% at 5 years and 59% at 10 years. In conclusion, correct staging, neoadjuvant treatment, living donor and priority on the liver transplant waiting list may lead to improved results. PMID:24409049

  11. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    PubMed

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. PMID:27582062

  12. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    PubMed

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model.

  13. Liver transplantation in small babies.

    PubMed

    Vázquez, J; Gámez, M; Santamaría, M L; Murcia, J; Díaz, M C; Camarena, C; Jara, P; Tovar, J A

    1993-08-01

    Pediatric liver transplantation is an effective treatment for end-stage liver disease with 1- and 5-year survivals approaching 90% and 70%, respectively. Survival is influenced by the recipient's age, weight, primary disease, vascular malformations, and nutritional status. Younger patients weighing less than 13 kg are considered to be a high-risk group. The aim of this article is to evaluate the impact of this group of patients on the overall results of our pediatric liver transplant program. From January 1986 through January 1992 we performed 76 liver transplants in 59 pediatric patients. Sixteen received a second graft and a third was required in one. Fourteen patients weighed less than 13 kg (mean, 11 kg; range, 6 to 13 kg). Their mean age was 12 months, with a range of 8 to 36 months. Indications for transplantation were: biliary atresia (9), Byler's disease (1), tyrosinemia (3), and alpha 1-antitrypsin deficiency (1). The incidence of rejection in this group (52%) was not significantly different from that in other patients (61%). Ten episodes of acute rejection required only steroids: in one monoclonal antibodies were added. Five patients had a new graft implanted, four for hepatic artery thrombosis and one for primary liver nonfunction. Nine patients are alive (64%) with the follow-up time ranging from 2 to 56 months (mean, 31). Five patients died of multiorgan failure (3), portal vein thrombosis (1), and primary liver nonfunction (1). Four-year graft and patient survival rates were 47% and 64%, respectively. Small babies are a high-risk group in a pediatric liver transplant program.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Bacterial infection after liver transplantation

    PubMed Central

    Kim, Sang Il

    2014-01-01

    Infectious complications are major causes of morbidity and mortality after liver transplantation, despite recent advances in the transplant field. Bacteria, fungi, viruses and parasites can cause infection before and after transplantation. Among them, bacterial infections are predominant during the first two months post-transplantation and affect patient and graft survival. They might cause surgical site infections, including deep intra-abdominal infections, bacteremia, pneumonia, catheter-related infections and urinary tract infections. The risk factors for bacterial infections differ between the periods after transplant, and between centers. Recently, the emergence of multi-drug resistant bacteria is great concern in liver transplant (LT) patients. The instructive data about effects of infections with extended-spectrum beta lactamase producing bacteria, carbapenem-resistant gram-negative bacteria, and glycopeptide-resistant gram-positive bacteria were reported on a center-by-center basis. To prevent post-transplant bacterial infections, proper strategies need to be established based upon center-specific data and evidence from well-controlled studies. This article reviewed the recent epidemiological data, risk factors for each type of infections and important clinical issues in bacterial infection after LT. PMID:24876741

  15. Infections in liver transplant recipients.

    PubMed

    Romero, Fabian A; Razonable, Raymund R

    2011-04-27

    Liver transplantation is a standard life-saving procedure for the treatment of many end-stage liver diseases. The success of this procedure may be limited by infectious complications. In this article, we review the contemporary state of infectious complications during the post-operative period, with particular emphasis on those that occur most commonly during the first 6 mo after liver transplantation. Bacteria, and less commonly Candida infections, remain the predominant pathogens during the immediate post-operative period, especially during the first month, and infections caused by drug-resistant strains are emerging. Infections caused by cytomegalovirus and Aspergillus sp. present clinically during the "opportunistic" period characterized by intense immunosuppression. As newer potent immunosuppressive therapies with the major aim of reducing allograft rejection are developed, one potential adverse effect is an increase in certain infections. Hence, it is essential for liver transplant centers to have an effective approach to prevention that is based on predicted infection risk, local antimicrobial resistance patterns, and surveillance. A better understanding of the common and most important infectious complications is anticipated to lead to improvements in quality of life and survival of liver transplant recipients.

  16. Split liver transplantation: What's unique?

    PubMed

    Dalal, Aparna R

    2015-09-24

    The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future. PMID:26421261

  17. Infections Following Orthotopic Liver Transplantation

    PubMed Central

    Arnow, Paul M.

    1991-01-01

    The epidemiology of infections associated with orthotopic liver transplantation is summarized herein, and approaches to prophylaxis are outlined. Infection is a major complication following orthotopic liver transplantation, and more than half of transplant recipients develop at least one infection. The risk of infection is highest in the first month after transplantation, and the most common pathogens are bacteria and cytomegalovirus (CMV). Bacterial infections usually occur in the first month, arise in the abdomen, and are caused by aerobes. The peak incidence of CMV infection is late in the first month and early in the second month after transplantationn. CMV syndromes include fever and neutropenia, hepatitis, pneumonitis, gut ulceration, and disseminated infection. Other significant problems are Candida intraabdominal infection, Herpes simplex mucocutaneous infection or hepatitis, adenovirus hepatitis, and Pneumocystis carinii pneumonia. Prophylaxis of infection in liver transplant recipients has not been well-studied. Several different regimens of parenteral, oral absorbable, and/or oral non-absorbable antibiotics active against bacteria and yeast have been used at various centers, but no randomized controlled trials have been conducted. Selective bowel decontamination appears to be a promising approach to the prevention of bacterial and Candida infections, while oral acyclovir may be a relatively convenient and effective agent for CMV prophylaxis. PMID:1650245

  18. Liver transplantation for perihilar cholangiocarcinoma.

    PubMed

    Gores, Gregory J; Darwish Murad, Sarwa; Heimbach, Julie K; Rosen, Charles B

    2013-01-01

    Perihilar cholangiocarcinoma is a complex and devastating disease. Its complexity in part arises from the difficulty of establishing a diagnosis, especially in primary sclerosing cholangitis (PSC) patients. We have found fluorescent in situ hybridization (FISH) of cytologic specimens to be helpful in establishing a diagnosis of cholangiocarcinoma. In particular, FISH polysomy is useful in establishing a diagnosis of this malignancy. Endoscopic ultrasound with fine needle aspirates of regional lymph nodes has high utility in identifying patients who have advanced disease with lymph node metastases. Patients who are resectable by conventional surgical techniques are referred for surgery. However, patients who are not resectable or who have PSC and meet highly selective criteria become eligible for liver transplantation. The protocol employs external beam radiation therapy followed by brachytherapy, and then capecitabine until a staging laparotomy is performed. There is a high dropout rate while patients await liver transplantation of approximately 30% at 12 months, due to tumor progression. Overall, survival rates are approximately 65-70% at 5 years. The disease recurrence rate is 20%. Patients who have masses greater than 3 cm or who do not meet the criteria identified above have worse outcomes. These survival rates are better than those following surgical resection. Vascular complications occur frequently after liver transplantation. Portal venous anastomotic strictures are very common and can be managed by stent placement. In summary, neoadjuvant chemoradiation plus liver transplantation achieves excellent survival for patients with early-stage perihilar cholangiocarcinoma. PMID:23797134

  19. Time course of cyclosporine and ist motabolites in blood, liver and spleen of naive Lewis rats: comparison with preliminary data obtained in transplanted animals.

    PubMed

    Wacher, V J; Liu, T; Roberts, J P; Ascher, N L; Benet, L Z

    1995-05-01

    the time course of intravenously administered cyclosporine (1 mg kg-1) and its metabolite AM1, AM9, and AM1c were examined in the blood, liver, and spleen of naive Lewis rats. Cyclosporine concentration versus time data for all three tissues were qualitatively similar, following a biexponential model C = Ae-gamma 1t + Be-gamma 2t with maximum cyclosporine concentrations reached at 1 h. Whole-blood cyclosporine clearance, terminal half-life, mean residence time, steady state volume of distribution, and hepatic extraction ratio (calculated from blood data) were similar to previously reported results. Cyclosporine in the liver showed the largest area under the concentration-time curve, mean residence time, and disposition and terminal half-lives. Spleen cyclosporine mean residence time and and terminal half-life were not significantly different from blood parameters. Metabolites AM1, AM9, and AM1c showed almost parallel time courses in all three tissues. The hydroxylated derivative AM9 was the major metabolite found in all tissues, with twofold greater levels in the liver compared to the blood and spleen. Slightly less AM1 was found in the liver relative to blood and spleen, where it was present in equal amounts. AM1c levels in the liver were not different from those in the spleen and were greater than observed for blood. The results obtained above were reflected in preliminary studies using liver transplanted rats treated with multiple doses of cyclosporine. Both blood and liver biopsy levels of CyA, AM1, and AM9 post-transplant showed twofold to fourfold decreases from day 3 ( samples taken 4 h post-CyA-dose) and concentrations were not significantly different from similarly sampled naive controls. More importantly, the metabolite/CyA ratios did not vary significantly between liver and blood in the two groups. For naive rats, and liver transplanted animals not undergoing rejection, changes in blood cyclosporine levels seem to predict variations in tissue

  20. Liver transplantation: history, outcomes and perspectives

    PubMed Central

    Meirelles, Roberto Ferreira; Salvalaggio, Paolo; de Rezende, Marcelo Bruno; Evangelista, Andréia Silva; Guardia, Bianca Della; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Pedroso, Pamella Tung; Rocco, Rodrigo Andrey; Meira, Sérgio Paiva

    2015-01-01

    In 1958 Francis Moore described the orthotopic liver transplantation technique in dogs. In 1963, Starzl et al. performed the first liver transplantation. In the first five liver transplantations no patient survived more than 23 days. In 1967, stimulated by Calne who used antilymphocytic serum, Starzl began a successful series of liver transplantation. Until 1977, 200 liver transplantations were performed in the world. In that period, technical problems were overcome. Roy Calne, in 1979, used the first time cyclosporine in two patients who had undergone liver transplantation. In 1989, Starzl et al. reported a series of 1,179 consecutives patients who underwent liver transplantation and reported a survival rate between one and five years of 73% and 64%, respectively. Finally, in 1990, Starzl et al. reported successful use of tacrolimus in patents undergoing liver transplantation and who had rejection despite receiving conventional immunosuppressive treatment. Liver Transplantation Program was initiated at Hospital Israelita Albert Einstein in 1990 and so far over 1,400 transplants have been done. In 2013, 102 deceased donors liver transplantations were performed. The main indications for transplantation were hepatocellular carcinoma (38%), hepatitis C virus (33.3%) and alcohol liver cirrhosis (19.6%). Of these, 36% of patients who underwent transplantation showed biological MELD score > 30. Patient and graft survival in the first year was, 82.4% and 74.8%, respectively. A major challenge in liver transplantation field is the insufficient number of donors compared with the growing demand of transplant candidates. Thus, we emphasize that appropriated donor/receptor selection, allocation and organ preservation topics should contribute to improve the number and outcomes in liver transplantation. PMID:25993082

  1. Liver Transplant: Nutrition

    MedlinePlus

    ... VHA Forms & Publications Quality & Safety Quality of Care Ethics VA/DOD Clinical Practice Guidelines Hospital Quality Data ... decreases the strain on your liver and other organs, and will make your recovery from surgery easier. ...

  2. Liver transplantation for Wilson disease

    PubMed Central

    Catana, Andreea M; Medici, Valentina

    2012-01-01

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  3. Liver transplantation for Wilson disease.

    PubMed

    Catana, Andreea M; Medici, Valentina

    2012-01-27

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  4. Dexmedetomidine Inhibits TLR4/NF-κB Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.

    PubMed

    Yao, Hui; Chi, Xinjin; Jin, Yi; Wang, Yiheng; Huang, Pinjie; Wu, Shan; Xia, Zhengyuan; Cai, Jun

    2015-11-20

    Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-кB(NF-кB) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-κB, tumor necrosis factor-α, and interleukin-1β levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-κB, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using α2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-κB pathway activation. The renoprotective effects are related to α2A-adrenergic receptor subtypes.

  5. Split liver transplantation in adults.

    PubMed

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-09-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  6. Split liver transplantation in adults

    PubMed Central

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

  7. Split liver transplantation in adults

    PubMed Central

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  8. Split liver transplantation in adults.

    PubMed

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-09-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

  9. [Liver transplants from living donors].

    PubMed

    Rogiers, X; Danninger, F; Malagó, M; Knoefel, W T; Gundlach, M; Bassas, A; Burdelski, M; Broelsch, C E

    1996-03-01

    In this article the authors discuss the advantages of Living Related Liver Transplantation (LRLT), criteria for the selection of donors and the standard operation technique. Among a total of 241 liver transplantation (LTx), 42 LRLT were performed at the University of Hamburg between October 1, 1991 and December 19, 1994. The body weight of recipients for LRLT ranged from 4,6 to 39 kg, with 64,2% having less than 10 kg. The volume of the donor left lateral liver lobe ranged from 100 cc to 350 cc. The average one year survival rate among electively operated patients-status 3-4 (UNOS 1995 classification) was 86.7%, two year survival rate 83.3%. The main advantages of LRLT are consired the following: 1. Absence of mortality on the waiting list, 2. Optimal timing of the transplantation (elective procedure, patient in a good condition), 3. Excellent organ (no primary non function), 4. A possible immunologic advantage, 5. Relief of the waiting list for cadaveric organs, 6. Psychological benefit for the family, 7. Cost effectiveness. Potential candidates for living donation with more than one cardiovascular risk factors were excluded. Social and psychological reasons leading to rejection of candidates were as follows: unstable family structure, expected professional or financial difficulties after living donation or withdrawal from consent. LRLT gives parents of a child with TLD a chance to avoid the risk of death on the waiting list or primary non function of the graft. LRLT has therefore established an important place in pediatric liver transplantation. PMID:8768973

  10. [10 years of liver transplantation in Peru].

    PubMed

    Chaman Ortiz, José Carlos; Padilla Machaca, P Martín; Rondon Leyva, Carlos; Carrasco Mascaró, Felix

    2010-01-01

    The article reviews the experience in 10 years of hepatic transplants performed by The Transplant Department of the National Hospital Guillermo Almenara Irigoyen (HNGAI), describing the history, surgical outcomes in adults and children, retransplantation, combined liver-kidney transplants, complications in 72 transplants performed at the time of submission of the article.

  11. Infectious Complications After Liver Transplantation

    PubMed Central

    Hernandez, Maria Del Pilar; Martin, Paul

    2015-01-01

    Orthotopic liver transplantation (OLT) is the standard of care for patients with decompensated cirrhosis and for patients with hepatocellular carcinoma. More than 6000 liver transplants are performed annually in the United States. High patient and graft survival rates have been achieved in great part due to the availability of potent immunosuppressive agents. Systemic immunosuppression has rendered the liver recipient susceptible to de novo infections as well as reactivation of preexisting latent infections. Infections occurring during the first month post-OLT are usually nosocomial, donor-derived, or the result of a perioperative complication. The development of opportunistic infections (OIs) such as Aspergillus and the reactivation of latent infections such as Mycobacterium tuberculosis are more frequent 1 to 6 months posttransplant, when the net state of immunosuppression is the highest. Immunosuppressive therapy is tapered 6 to 12 months post-OLT; therefore, infections occurring during that time period and afterward generally resemble those of the general population. Screening strategies applied to determine the risk of an infection after transplantation and the use of prophylactic antimicrobial therapy have reduced the incidence of OIs after OLT. This article will review the various causes of infection post-OLT and the therapies used to manage complications. PMID:27134589

  12. Exacerbation of pulmonary sarcoidosis after liver transplantation.

    PubMed

    Shibolet, Oren; Kalish, Yossi; Wolf, Dana; Pappo, Orit; Laxer, Uri; Berkman, Neville; Shaham, Dorit; Ashur, Yaffa; Ilan, Yaron

    2002-10-01

    Patients with hepatic sarcoidosis rarely require orthotopic liver transplantation (OLT). Progression of granulomatous activity involving other organs after OLT has rarely been described. We describe a 32-year-old woman who underwent liver transplantation for sarcoidosis-associated end-stage liver disease. She presented 4 years later with shortness of breath, hilar lymphadenopathy, and interstitial lung abnormalities. Liver functions were normal. Open lung biopsy results revealed granulomata compatible with sarcoidosis. The patient made a complete recovery after corticosteroid treatment. To the best of our knowledge, this is a first description of severe exacerbation of pulmonary sarcoidosis in an immunosuppressed patient who underwent liver transplantation for sarcoidosis-associated liver disease.

  13. Effects of different mitogens on intrasplenic liver tissue transplants in comparison to orthotopic liver.

    PubMed

    Lupp, Amelie; Lucas, Norma; Tralls, Manuela; Fuchs, Udo; Danz, Manfred

    2003-06-01

    Ectopic liver cell transplants, when compared to orthotopic liver, can serve as a tool to study topic influences on liver cell differentiation, multiplication, function and responsiveness to xenobiotics. The aim of the present study was to evaluate, if characteristic effects of mitogens are exerted in both liver and intrasplenic liver cell transplants in a similar manner. Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic rats. Four months later, transplant recipients and controls were treated with fluorene (FEN), fluorenone (FON), 2-acetylaminofluorene (AAF), N-nitrosodibenzylamine (NDBA) or the solvent 48 hours before sacrifice. The following parameters were assessed within livers and spleens: mitotic activity of hepatocytes, glycogen content, cytochrome P450 (P450) isoforms expression, P450 mediated monooxygenase functions, tissue content of lipid peroxides (LPO) and of reduced and oxidized glutathione (GSH; GSSG). In both orthotopic livers and intrasplenic transplants FEN, FON or NDBA administration increased the mitotic activity of the hepatocytes. Treatment with the mitogens caused a distinct and characteristic induction of the P450 isoforms expression and of the respective monooxygenase functions in the livers and (with certain differences) also in the transplants. FEN and FON slightly increased, AAF and NDBA reduced liver glycogen content. The latter effect was also seen in the transplants. NDBA administration caused a slight increase in tissue LPO content in livers, but not in spleens. Additionally, AAF or NDBA treatment led to an elevation of liver (but not of spleen) GSH and GSSG concentrations. The results of the present investigation show that characteristic effects of mitogens on orthotopic liver occur with certain differences also in ectopic liver cell transplants.

  14. Transoesophageal echocardiography during liver transplantation

    PubMed Central

    De Pietri, Lesley; Mocchegiani, Federico; Leuzzi, Chiara; Montalti, Roberto; Vivarelli, Marco; Agnoletti, Vanni

    2015-01-01

    Liver transplantation (LT) has become the standard of care for patients with end stage liver disease. The allocation of organs, which prioritizes the sickest patients, has made the management of liver transplant candidates more complex both as regards their comorbidities and their higher risk of perioperative complications. Patients undergoing LT frequently display considerable physiological changes during the procedures as a result of both the disease process and the surgery. Transoesophageal echocardiography (TEE), which visualizes dynamic cardiac function and overall contractility, has become essential for perioperative LT management and can optimize the anaesthetic management of these highly complex patients. Moreover, TEE can provide useful information on volume status and the adequacy of therapeutic interventions and can diagnose early intraoperative complications, such as the embolization of large vessels or development of pulmonary hypertension. In this review, directed at clinicians who manage TEE during LT, we show why the procedure merits a place in challenging anaesthetic environment and how it can provide essential information in the perioperative management of compromised patients undergoing this very complex surgical procedure. PMID:26483865

  15. Diaphragmatic Hernia After Pediatric Liver Transplant.

    PubMed

    Kirnap, Mahir; Akdur, Aydincan; Ozcay, Figen; Soy, Ebru; Coskun, Mehmet; Moray, Gokhan; Haberal, Mehmet

    2015-10-01

    Diaphragmatic hernia is an unusual complication after pediatric liver transplant. Nearly half of bowel obstruction cases, which require surgical intervention in liver transplant patients, are caused by diaphragmatic hernia. The smaller patients are at risk for higher rates of diaphragmatic complication after pediatric liver transplant, but diaphragmatic hernia has not been reported as a unique occurrence. Here, we report 3 cases of diaphragmatic hernia after liver transplant and discuss the possible contributing factors. Diaphragmatic hernia should nevertheless be added to the list of potential complications after liver transplant in the pediatric population. Pediatric transplant physicians and surgeons should be aware of this complication so that it is recognized promptly in both acute and nonacute settings and appropriate action is taken.

  16. Andrological status before and after liver transplantation.

    PubMed

    Madersbacher, S; Grünberger, T; Maier, U

    1994-05-01

    To determine the impact of liver transplantation on andrological status, we compared the endocrine profiles and spermiograms of 2 cohorts of patients before (9) and after (11) transplantation. Before liver transplantation testosterone (1.1 +/- 0.7 ng/ml) and free testosterone (2.0 +/- 1.6 pg/ml) were pathologically decreased in all 9 cases, and luteinizing hormone was lower (1.8 +/- 1.4 mIU/ml) in 5. Only 3 of 9 patients were able to produce ejaculates before liver transplantation, all of which were azoospermic. After a mean interval of 28 +/- 9 months (range 4 to 34 months) following liver transplantation testosterone (5.3 +/- 1.1 ng/ml), free testosterone (15.3 +/- 5.0 pg/ml) and luteinizing hormone (6.2 +/- 3.7 mIU/ml.) were consistently within the normal range, with a highly statistically significant difference (p < 0.025) from pre-liver transplantation values. Semen analyses after liver transplantation revealed normal density, motility and normal forms in 5 patients, 2 suffered from oligoasthenoteratospermia and 4 were unable to produce an ejaculate for semen analyses. These data demonstrate that the hypothalamic-pituitary-testicular hormone axis and gonadal tissue are capable of resuming normal function after liver transplantation in men with chronic liver failure who suffered from massive andrological dysfunction before transplantation.

  17. Indications and Contraindications for Liver Transplantation

    PubMed Central

    Varma, Vibha; Mehta, Naimish; Kumaran, Vinay; Nundy, Samiran

    2011-01-01

    Patients with chronic liver disease and certain patients with acute liver failure require liver transplantation as a life-saving measure. Liver transplantation has undergone major improvements, with better selection of candidates for transplantation and allocation of scarce deceased donor organs (according to more objective criteria). Living donor liver transplantation came into existence to overcome the shortage of donor organs especially in countries where there was virtually no deceased donor programme. Advances in the technical aspects of the procedure, the intraoperative and postoperative care of both recipients and donors, coupled with the introduction of better immunosuppression protocols, have led to graft and patient survivals of over 90% in most high volume centres. Controversial areas like transplantation in alcoholic liver disease without abstinence, acute alcoholic hepatitis, and retransplantation for recurrent hepatitis C virus infection require continuing discussion. PMID:22007310

  18. Liver transplantation in acute liver failure: A challenging scenario

    PubMed Central

    Mendizabal, Manuel; Silva, Marcelo Oscar

    2016-01-01

    Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation. PMID:26819519

  19. Challenges in transplantation for alcoholic liver disease.

    PubMed

    Berlakovich, Gabriela A

    2014-07-01

    Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

  20. Interventional radiology in living donor liver transplant

    PubMed Central

    Cheng, Yu-Fan; Ou, Hsin-You; Yu, Chun-Yen; Tsang, Leo Leung-Chit; Huang, Tung-Liang; Chen, Tai-Yi; Hsu, Hsien-Wen; Concerjero, Allan M; Wang, Chih-Chi; Wang, Shih-Ho; Lin, Tsan-Shiun; Liu, Yueh-Wei; Yong, Chee-Chien; Lin, Yu-Hung; Lin, Chih-Che; Chiu, King-Wah; Jawan, Bruno; Eng, Hock-Liew; Chen, Chao-Long

    2014-01-01

    The shortage of deceased donor liver grafts led to the use of living donor liver transplant (LDLT). Patients who undergo LDLT have a higher risk of complications than those who undergo deceased donor liver transplantation (LT). Interventional radiology has acquired a key role in every LT program by treating the majority of vascular and non-vascular post-transplant complications, improving graft and patient survival and avoiding, in the majority of cases, surgical revision and/or re-transplant. The aim of this paper is to review indications, diagnostic modalities, technical considerations, achievements and potential complications of interventional radiology procedures after LDLT. PMID:24876742

  1. Liver-Regenerative Transplantation: Regrow and Reset

    PubMed Central

    de l’Hortet, A. Collin; Takeishi, K.; Guzman-Lepe, J.; Handa, K.; Matsubara, K.; Fukumitsu, K.; Dorko, K.; Presnell, S. C.; Yagi, H.; Soto-Gutierrez, A.

    2016-01-01

    Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)–derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation. PMID:26699680

  2. [Liver and intestinal transplant in paediatric population].

    PubMed

    de la Rosa, G; Matesanz, R

    2015-12-01

    Our organizational model allows an annual 1,000 liver transplants. Pediatric liver transplantation constitutes 5% of such activity and provides, in children with severe, progressive and irreversible liver disease, a 1 year-survival of 90% and more than 80% after 15 years of follow-up. The main indication is biliary atresia followed by metabolic liver disease and acute liver failure. Around half of the procedures are performed in children under two years and 25-30% in the first year of life. The waiting list remains at around 35 patients, with an average of 100 patients enrolled annually and 60 of them finally transplanted after an average of 136.3 days on the waiting list. The prioritization of the candidates uses the PELD as an objective tool for decision-making. However, the progressive aging of donors, with a profile increasingly different from the requirements of the pediatric patients included in the waiting list, requires strategies such as living donor liver transplantation and the split liver transplantation, to increase the probability of transplant while reducing both time and mortality on the waiting list at the same time. Pediatric intestinal transplantation registers a low indication but involves strict requirements that outline a very uncommon donor in our country which, together with the absence of alternatives that outweigh the impact of these difficulties, penalizes the chances of transplant for these patients. PMID:26611879

  3. The study of indicators of bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous injection of gold nanorods

    NASA Astrophysics Data System (ADS)

    Dikht, Nataliya I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Matveeva, Olga V.; Navolokin, Nikita A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.

    2015-03-01

    In study the evaluation of the influence of gold nanorods on morphological indicators of red bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous administration of gold nanorods was conducted. We used gold nanorods with length 41 ± 8 nm and diameter of 10.2±2 nm, synthesized in the laboratory of nanobiotechnology IBPPM RAS (Saratov). After intravenous administration of gold nanorods the decrease of leukocytes, platelets and lymphocytes was observed in animals of control group in blood. It was marked the decrease of the number of mature cellular elements of the leukocyte germ in bone marrow - stab neutrophils and segmented leukocytes, and the increase of immature elements- metamyelocytes, indicating the activation of leukocyte germ after nanoparticle administration. The decrease of leukocyte amount was noted in blood and the increase of cellular elements of the leukocyte germ was revealed in bone marrow, indicating the activation of leukocyte germ in rats with alloxan diabetes and transplanted tumors. The changes of morphological indicators of blood and bone marrow testify about stimulation of myelocytic sprouts of hemopoiesis in bone marrow as a result of reduction of mature cells in peripheral blood after gold nanoparticle administration.

  4. Immunological aspects of liver cell transplantation

    PubMed Central

    Oldhafer, Felix; Bock, Michael; Falk, Christine S; Vondran, Florian W R

    2016-01-01

    Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation (OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation (LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where long-term graft survival is observed on a regular basis and, hence, the liver has been deemed an immune-privileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells. PMID:27011904

  5. Liver transplantation in the United Kingdom.

    PubMed

    Neuberger, James

    2016-08-01

    Liver transplantation (LT) services in the United Kingdom are provided by 7 designated transplant centers for a population of approximately 64 million. The number of deceased organ donors has grown, and in 2014-2015 it was 1282 (570 donation after circulatory death and 772 donation after brain death). Donor risk is increasing. In 2014-2015, there were 829 LTs from deceased and 38 from living donors. The common causes for transplantation are liver cell cancer, viral hepatitis, and alcohol-related liver disease. Livers are allocated first nationally to super-urgent listed patients and then on a zonal basis. The United Kingdom will be moving toward a national allocation scheme. The median interval between listing and transplantation is 152 days for adults awaiting their first elective transplant. Of the adults listed for the first elective transplant, 68% underwent transplantation at < 1 year; 17% are waiting; and 4% and 11% were removed or died, respectively. The 1- and 5-year adult patient survival rate from listing is 81% and 68%, respectively, and from transplantation is 92% and 80%, respectively. The transplant program is funded through general taxation and is free at the point of care to those who are eligible for National Health Service (NHS) treatment; some have to pay for medication (up to a maximum payment of US $151/year). The competent authority is the Human Tissue Authority which licenses donor characterization, retrieval, and implantation; transplant units are commissioned by NHS England and NHS Scotland. National Health Service Blood and Transplant (NHSBT) promotes organ donation, maintains the organ donor register, obtains consent, and undertakes donor characterization and offering. NHSBT also maintains the national waiting list, develops and applies selection and allocation policies, monitors outcomes, and maintains the UK National Transplant Registry and commissions a national organ retrieval service. Liver Transplantation 22 1129-1135 2016 AASLD.

  6. Liver transplantation at KFSHRC: achievement and challenges.

    PubMed

    Al, Mohammed I; Abaalkhail, Faisal A; Bahili, Hamad Al; Abdo, Almoutaz Hashim; Elsiesy, Hussein A; Al, Mohammed S; El Sheikh, Yasser M; Hegab, Bassem S; Kamel, Yasser M; AlGoufi, Talal T; Hasssan, Hazem H; Burdelski, Martin M; Al, Mohammad A; Abdelfattah, Mohamed R; Attallah, Khaled M; Mahmood, Talat Z; Saleh, Yahya Z; Eldeen, Firas Zahr; Broering, Dieter C

    2014-01-01

    The liver transplantation program at KFSHRC has been active since 2001. More than 450 liver transplants have been performed so far. The program evolved from adult cadaveric transplant to living donor and recently to pediatric and split techniques. The 1-year survival of patients for both pediatric and adult exceeded 90% and the 5-year survival of patients is more than 80%. Associated with this success are challenges that include: organ shortage, quality of organ harvested, inability to meet the growing national need, increased demand of resource to meet the need of the program, and lack of a collaborative national strategy in organ donation and transplantation. PMID:24894777

  7. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  8. Update on liver transplants in Lebanon.

    PubMed

    Faraj, Walid; Haydar, Ali; Nounou, Ghina El; Naaj, Abdallah Abou El; Khoury, Ghattas; Jabbour, Samar; Khalife, Mohamed

    2015-09-01

    Objective-To review all liver transplants performed at the American University of Beirut Medical Center from 1998 to present. Materials and Methods-From 1998 to present, 21 liver transplants (15 into adults and 6 into children) were performed at the American University of Beirut Medical Center. Of the 21 transplants, 5 were living related liver transplants. Results-Patient survival was 76% at 1, 5, and 10 years. Five recipients died at a median of 9 (range, 1-56) days after transplant. Causes of death included 1 case of severe cellular rejection, 1 case of portal and hepatic artery thrombosis, 1 case of intraoperative cardiac arrest, and 2 cases of primary nonfunction. Two biliary complications and 2 major vascular complications also occurred. All 16 survivors are well, with normal findings on liver function tests at a median follow-up time of 93 (range, 10-185) months after transplant. Conclusions-Although our numbers are small, the 10-year survival rate is comparable to reported rates for other series around the world. Deceased organ donations must be encouraged so that we can perform more transplants. As a source of organs, living related liver transplant is important; however, it cannot replace deceased donation.

  9. Changes in nutritional status after liver transplantation.

    PubMed

    Giusto, Michela; Lattanzi, Barbara; Di Gregorio, Vincenza; Giannelli, Valerio; Lucidi, Cristina; Merli, Manuela

    2014-08-21

    Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades, a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass (sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected, dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolic disorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation.

  10. Melatonin Pretreatment Enhances the Homing of Bone Marrow-derived Mesenchymal Stem Cells Following Transplantation in a Rat Model of Liver Fibrosis

    PubMed Central

    Mortezaee, Keywan; Pasbakhsh, Parichehr; Kashani, Iraj Ragerdi; Sabbaghziarani, Fatemeh; Omidi, Ameneh; Zendedel, Adib; Ghasemi, Soudabeh; Dehpour, Ahmad Reza

    2016-01-01

    Background: Bone marrow-derived mesenchymal stem cells (BMMSCs) transplantation has been considered as a promising milestone in liver fibrosis treatment. However, low amounts of homing are a major obstacle. We aimed to investigate the role of melatonin pretreatment in BMMSC homing into experimental liver fibrosis. Methods: BMMSCs were obtained, grown, propagated and preconditioned with 5 µM melatonin and analyzed for multipotency and immunophenotypic features at passage three. The cells were labelled with CM-Dil and infused into the rats received the i.p. injection of carbon tetrachloride (CCl4) for five weeks to induce liver fibrosis. Animals were divided into two groups: One group received BMMSCs, whereas the other group received melatonin-pretreated BMMSCs (MT-BMMSCs). After cell injection at 72 h, animals were sacrificed, and the liver tissues were assessed for further evaluations: fibrosis using Masson’s trichrome and hematoxylin and eosin staining and homing using fluorescent microscopy and flow cytometry. Results: BMMSCs and MT-BMMSCs expressed a high level of CD44 but low levels of CD11b, CD45 and CD34 (for all P≤0.05) and were able to differentiate into adipocytes and Schwann cells. CCl4 induction resulted in extensive collagen deposition, tissue disruption and fatty accumulation with no obvious difference between the two groups. There was a significant increase in homing of MT-BMMSCs in both florescent microscopy (P≤0.001) and flow cytometry (P≤0.01) assays, as compared with non-treated BMMSCs. Conclusion: This study indicates the improved homing potential of BMMSCs in pretreatment with melatonin. Therefore, this strategy may represent an applied approach for improving the stem cell therapy of liver fibrosis. PMID:27130910

  11. Recurrent hepatitis C after liver transplant

    PubMed Central

    deLemos, Andrew S; Schmeltzer, Paul A; Russo, Mark W

    2014-01-01

    End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients. PMID:25152571

  12. Guidelines for surgical procedures after liver transplantation.

    PubMed Central

    Testa, G; Goldstein, R M; Toughanipour, A; Abbasoglu, O; Jeyarajah, R; Levy, M F; Husberg, B S; Gonwa, T A; Klintmalm, G B

    1998-01-01

    OBJECTIVE: The first purpose of this study is to identify the types and incidences of surgical procedures in patients who have previously undergone liver transplantation, with particular focus on the complication rates and the lengths of hospital stay. The second purpose is to present the management guidelines for patients with liver transplants at the preoperative, intraoperative, and postoperative stages of surgical procedure. SUMMARY BACKGROUND DATA: The surgical literature on this issue is scant, and with the growing liver transplant patient population it is not unlikey for any surgery specialist to have to operate on a patient who has undergone liver transplantation. METHODS: A sample of 409 patients with available hospital records, with a minimum of a 2-year follow-up, and with telephone access for interviews was chosen. Type of surgery, time from the liver transplant, hospital stay, immunosuppressive regimen, and complications were recorded. RESULTS: A large proportion of patients (24.2%) underwent some type of surgical procedure 2 to 10 years after liver transplantation. The authors demonstrate that most of the elective procedures can be safely carried out without an increased incidence of complication and without longer hospital stay than the general population. Conversely, emergent procedures are plagued by a greater incidence of complications that not only affect the function of the liver graft but may risk the life of the patient. PMID:9563551

  13. [De novo autoimmune hepatitis after liver transplantation].

    PubMed

    Luo, Bifen; Wei, Lai

    2016-02-01

    Patients who transplanted for non-autoimmune indication may developed de novo autoimmune hepatitis after liver transplantation. It happens about 1.7%-6.6% in liver transplanted population. Most patients with de novo AIH had transplanted for HCV infection, biliary atresia and Cholestatic liver disease. The interval between transplantation and de novo AIH onset is from 3 month to 16 years, mostly more than 1 year. The disease can be seen at any age. More female patients are present in children, while there is no significant difference between male and female in adults. Clinical manifestations of de novo AIH are similar to those of AIH, namely characterized by elevated transaminase with or without bilirubin, as well as elevated serum gammaglobulin (IgG) and positive autoantibodies, while the histological features of an infiltrate rich in plasma cells with interface hepatitis and necro-inflammation and fibrosis. Treatment with corticosteroids and Azathioprine brings good outcomes, but it tends to fluctuate.

  14. Living donor liver transplantation in the USA.

    PubMed

    Kim, Peter T W; Testa, Giuliano

    2016-04-01

    Living donor liver transplant (LDLT) accounts for a small volume of the transplants in the USA. Due to the current liver allocation system based on the model for end-stage liver disease (MELD), LDLT has a unique role in providing life-saving transplantation for patients with low MELD scores and significant complications from portal hypertension, as well as select patients with hepatocellular carcinoma (HCC). Donor safety is paramount and has been a topic of much discussion in the transplant community as well as the general media. The donor risk appears to be low overall, with a favorable long-term quality of life. The latest trend has been a gradual shift from right-lobe grafts to left-lobe grafts to reduce donor risk, provided that the left lobe can provide adequate liver volume for the recipient. PMID:27115007

  15. Nutrition assessment in patients undergoing liver transplant

    PubMed Central

    Bakshi, Neha; Singh, Kalyani

    2014-01-01

    Liver transplantation (LT) is a major surgery performed on patients with end stage liver disease. Nutrition is an integral part of patient care, and protein-energy malnutrition is almost universally present in patients suffering from liver disease undergoing LT. Nutrition assessment of preliver transplant phase helps to make a good nutrition care plan for the patients. Nutrition status has been associated with various factors which are related to the success of liver transplant such as morbidity, mortality, and length of hospital stay. To assess the nutritional status of preliver transplant patients, combinations of nutrition assessment methods should be used like subjective global assessment, Anthropometry mid arm-muscle circumference, Bioelectrical impedance analysis (BIA) and handgrip strength. PMID:25316978

  16. Central nervous system complications after liver transplantation.

    PubMed

    Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

    2015-08-01

    We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology.

  17. Portopulmonary hypertension in liver transplant candidates.

    PubMed

    Bozbas, Serife Savas; Bozbas, Huseyin

    2016-02-14

    Pulmonary vascular disorders including portopulmonary hypertension (PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure (PAP) and liver transplant surgery, survival of patients with PoPHT and advanced liver disease is significantly improved. Because of the prognostic significance of PoPHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild PoPHT can safely undergo liver transplant surgery. In cases of moderate to severe PoPHT, right heart catheterization (RHC) should be performed. In patients with moderate to severe PoPHT on RHC (mean PAP 35-45 mmHg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed. PMID:26877607

  18. Portopulmonary hypertension in liver transplant candidates

    PubMed Central

    Bozbas, Serife Savas; Bozbas, Huseyin

    2016-01-01

    Pulmonary vascular disorders including portopulmonary hypertension (PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure (PAP) and liver transplant surgery, survival of patients with PoPHT and advanced liver disease is significantly improved. Because of the prognostic significance of PoPHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild PoPHT can safely undergo liver transplant surgery. In cases of moderate to severe PoPHT, right heart catheterization (RHC) should be performed. In patients with moderate to severe PoPHT on RHC (mean PAP 35-45 mmHg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed. PMID:26877607

  19. Technical Skills Required in Split Liver Transplantation.

    PubMed

    Liu, Huanqiu; Li, Ruijun; Fu, Jinling; He, Qianyan; Li, Ji

    2016-01-01

    The number of liver grafts obtained from a cadaver can be greatly increased with the application of split liver transplantation. In the last 10 years, pediatric waiting list mortality has been reduced significantly with the use of this form of liver transplantation, which has 2 major forms. In its most commonly used form, the liver can be transplanted into 1 adult and 1 child by splitting it into a right extended and a left lateral graft. For adult and pediatric recipients, the results of this procedure are comparable to those of whole-organ techniques. In another form, 2 hemi-grafts are obtained by splitting the liver, which can be transplanted into a medium-sized adult (the right side) and a large child/small adult (the left side). The adult liver graft pool is expanded through the process of full right/full left splitting; but it is also a critical technique when one considers the knowledge required of the potential anatomic variations and the high technical skill level needed. In this review, we provide some basic insights into the technical and anatomical aspects of these 2 forms of split liver transplantation and present an updated summary of both forms. PMID:27363540

  20. Orthotopic liver transplantation for giant liver haemangioma: A case report.

    PubMed

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-12-24

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  1. [Living donor liver transplantation in adults].

    PubMed

    Neumann, U P; Neuhaus, P; Schmeding, M

    2010-09-01

    The worldwide shortage of adequate donor organs implies that living donor liver transplantation represents a valuable alternative to cadaveric transplantation. In addition to the complex surgical procedure the correct identification of eligible donors and recipients plays a decisive role in living donor liver transplantation. Donor safety must be of ultimate priority and overrules all other aspects involved. In contrast to the slightly receding numbers in Europe and North America, in recent years Asian programs have enjoyed constantly increasing living donor activity. The experience of the past 15 years has clearly demonstrated that technical challenges of both bile duct anastomosis and venous outflow of the graft significantly influence postoperative outcome. While short-term in-hospital morbidity remains increased compared to cadaveric transplantation, long-term survival of both graft and patient are comparable or even better than in deceased donor transplantation. Especially for patients expecting long waiting times under the MELD allocation system, living donor liver transplantation offers an excellent therapeutic alternative. Expanding the so-called "Milan criteria" for HCC patients with the option for living donor liver transplantation is currently being controversially debated.

  2. [Progress of the liver transplantation programme in Hungary].

    PubMed

    Kóbori, László; Görög, Dénes; Fehérvári, Imre; Nemes, Balázs; Fazakas, János; Sárváry, Enikő; Varga, Marina; Gerlei, Zsuzsanna; Doros, Attila; Monostory, Katalin; Perner, Ferenc

    2013-06-01

    The history of organ transplantation in Hungary dates back to 50 years, and the first succesful liver transplantation was performed in the United States in that time as well. The number of patients with end stage liver disease increased worldwide, and over 7000 patients die in each year due to liver disease in Hungary. The most effective treatment of end-stage liver disease is liver transplantation. The indications of liver transplantation represent a wide spectrum including viral, alcoholic or other parenchymal liver cirrhosis, but cholestatic liver disease and acute fulminant cases are also present in the daily routine. In pediatric patients biliary atresia and different forms of metabolic liver disorders represent the main indication for liver transplantation. The results of liver transplantation in Hungary are optimal with over 80% long-term survival. For better survival individual drug therapy and monitoring are introduced in liver transplant candidates.

  3. Living donor liver transplantation in Europe

    PubMed Central

    Capobianco, Ivan; Panaro, Fabrizio; Di Francesco, Fabrizio; Troisi, Roberto; Sainz-Barriga, Mauricio; Muiesan, Paolo; Königsrainer, Alfred; Testa, Giuliano

    2016-01-01

    Living donor liver transplantation (LDLT) sparked significant interest in Europe when the first reports of its success from USA and Asia were made public. Many transplant programs initiated LDLT and some of them especially in Germany and Belgium became a point of reference for many patients and important contributors to the advancement of the field. After the initial enthusiasm, most of the European programs stopped performing LDLT and today the overall European activity is concentrated in a few centers and the number of living donor liver transplants is only a single digit fraction of the overall number of liver transplants performed. In this paper we analyse the present European activities and highlight the European contribution to the advancement of the field of LDLT. PMID:27115011

  4. Non-alcoholic fatty liver disease and liver transplantation.

    PubMed

    Khan, Reenam S; Newsome, Philip N

    2016-08-01

    Cirrhosis secondary to non-alcoholic steatohepatitis (NASH) is a common indication for liver transplant. In comparison to other cirrhotic patients, patients with NASH cirrhosis are more likely to be older and have the metabolic syndrome. Pre-transplant, patients require careful evaluation of cardiovascular risk. As the incidence of non-alcoholic fatty liver disease (NAFLD) is rising, a greater proportion of donor grafts have steatosis greater than 30%, which is associated with poor outcomes. Grafts with steatosis greater than 60% are unsuitable for transplant. Overall, post-transplant survival outcomes for patients with NASH cirrhosis are similar to those with cirrhosis without NASH. However, NASH cirrhosis is associated with a higher 30-day mortality, predominantly from an increase in cardiovascular events and infections. Following liver transplant, there is a significant risk of NASH recurrence, although this seldom results in allograft loss. Furthermore, a significant number of patients who had a liver transplant for other reasons develop NASH de novo. When patients with NASH cirrhosis are considered for transplant, one of the major challenges lies in identifying which patients are too high risk for surgery. This review aims to provide information to aid this decision making process, and to provide guidance on the peri-operative care strategies that can modify risk. PMID:26997540

  5. Reversal of hypersplenism following orthotopic liver transplantation.

    PubMed Central

    Yanaga, K; Tzakis, A G; Shimada, M; Campbell, W E; Marsh, J W; Stieber, A C; Makowka, L; Todo, S; Gordon, R D; Iwatsuki, S

    1989-01-01

    The purpose of this study was to clarify the effect of orthotopic liver transplantation on hypersplenism. In a 1-year period from July 1, 1986 to June 30, 1987, 196 adult patients underwent 233 orthotopic liver transplantations. Of the 58 patients with hypersplenism who were analyzed in this study, hypersplenism was more commonly associated with postnecrotic cirrhosis than other kinds of liver disease (55.3% (47/85) vs. 14.5% (11/76); p less than 0.001). Postoperative platelet counts were statistically higher than preoperative values (p less than 0.05). The latest platelet counts were more than 100,000/mm3 in 53 patients (91.4%). Of the eight patients whose preoperative and postoperative spleen volumes could be compared, all showed the reduction in the spleen size (p less than 0.02). We conclude that orthotopic liver transplantation, which is a radical surgical procedure for portal hypertension, reverses hypersplenism. PMID:2667473

  6. The value of living donor liver transplantation.

    PubMed

    Yang, Xiaoli; Gong, Junhua; Gong, JianPing

    2012-12-31

    Living donor liver transplantation (LDLT) is a very successful procedure that develops liver resources in case of worldwide shortages. As the technology has developed so much in the past 2 decades, LDLT has the same good prognosis as DDLT. However, LDLT still has lots of ethical & technical problems. It causes great psychiatric, physical and psychosocial harm to donors. Also, it has some negative effects on society by providing a platform for organ trade. Therefore, there is much controversy about the social value of LDLT. After review of recent papers, we find much progress can be made in inspiring the public to become organ donors and creating donation model new to improve the consent rate for solid organ donation from deceased donors. That is the key strategy for increasing the liver supply. With this serious shortage of organs, liver donor transplantation still has its advantages, but we should not place all our hopes on LDLT to increase the liver supply. We all need to try our best to increase donor awareness and promote organ donor registration--when cadaver organs could meet the needs for liver transplantation, living donor liver transplants would not be necessary. PMID:23274332

  7. The value of living donor liver transplantation.

    PubMed

    Yang, Xiaoli; Gong, Junhua; Gong, JianPing

    2012-12-31

    Living donor liver transplantation (LDLT) is a very successful procedure that develops liver resources in case of worldwide shortages. As the technology has developed so much in the past 2 decades, LDLT has the same good prognosis as DDLT. However, LDLT still has lots of ethical & technical problems. It causes great psychiatric, physical and psychosocial harm to donors. Also, it has some negative effects on society by providing a platform for organ trade. Therefore, there is much controversy about the social value of LDLT. After review of recent papers, we find much progress can be made in inspiring the public to become organ donors and creating donation model new to improve the consent rate for solid organ donation from deceased donors. That is the key strategy for increasing the liver supply. With this serious shortage of organs, liver donor transplantation still has its advantages, but we should not place all our hopes on LDLT to increase the liver supply. We all need to try our best to increase donor awareness and promote organ donor registration--when cadaver organs could meet the needs for liver transplantation, living donor liver transplants would not be necessary.

  8. ACUTE APENDICITIS IN LIVER TRANSPLANT RECIPIENTS

    PubMed Central

    da FONSECA-NETO, Olival Cirilo Lucena; LIMA, Heloise Caroline de Souza; de MELO, Paulo Sérgio Vieira; LEMOS, Roberto; LEITÃO, Laércio; AMORIM, Américo Gusmão; LACERDA, Cláudio Moura

    2016-01-01

    Background : Appendicitis is a common cause of emergency surgery that in the population undergoing organ transplantation presents a rare incidence due to late diagnosis and treatment. Aim : To report the occurrence of acute appendicitis in a cohort of liver transplant recipients. Methods : Retrospective analysis in a period of 12 years among 925 liver transplants, in witch five cases of acute appendicitis were encountered. Results : Appendicitis occurred between three and 46 months after liver transplantation. The age ranged between 15 and 58 years. There were three men and two women. The clinical presentations varied, but not discordant from those found in non-transplanted patients. Pain was a symptom found in all patients, in two cases well located in the right iliac fossa (40%). Two patients had symptoms characteristic of peritoneal irritation (40%) and one patient had abdominal distention (20%). All patients were submitted to laparotomies. In 20% there were no complications. In 80% was performed appendectomy complicated by suppuration (40%) or perforation (40%). Superficial infection of the surgical site occurred in two patients, requiring clinical management. The hospital stay ranged from 48 h to 45 days. Conclusion : Acute appendicitis after liver transplantation is a rare event being associated with a high rate of drilling, due to delays in diagnosis and therapy, and an increase in hospital stay. PMID:27120736

  9. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

    PubMed Central

    Telles-Correia, Diogo; Mega, Inês

    2015-01-01

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  10. Liver transplantation: Current status and challenges

    PubMed Central

    Jadlowiec, Caroline C; Taner, Timucin

    2016-01-01

    Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155

  11. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  12. [Nutritional support in liver transplantation].

    PubMed

    Planas, M; Farriol, M; Schwartz, S; López, J; Pérez, A; Padró, J B

    1991-01-01

    Given the malnutrition present in patients suffering from advanced hepatic illness, as well as the implications of this in the post-hepatic transplant period, a study was made of various biochemical parameters (prealbumin, retinol-bound protein, zinc, magnesium, cholesterol and amino acid pattern) as indicators of the nutritional condition of a series of 15 patients who underwent hepatic transplants and required total parenteral nutrition (TPN) during the first 10 post-transplant days. Before the transplants were carried out, all the patients studied showed a decrease in all evaluated parameters. Ten days after the transplant, and having been fed parenterally during this time, the different parameters corrected themselves, with the exception of cholesterol. TPN, administered with enrichment of branched amino acids by 35%, practically normalized the plasma amino acid pattern. PMID:1764532

  13. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    PubMed Central

    Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  14. Liver transplantation for alcoholic liver disease: selection and outcome.

    PubMed

    Maldonado, J R; Keeffe, E B

    1997-08-01

    There is clear consensus that patients with alcoholic cirrhosis should be considerated for liver transplantation, barring complicating medical or psychosocial problems. Short-term and long-term survival rates are comparable to patients receiving transplants for other conditions, and the relapse rate to alcohol use averages 15%, with troublesome drinking seen uncommonly. To date, no nationally accepted selection criteria have been established and proved effective in predicting long-term sobriety and compliance. To maximize the outcome of liver transplantation in patients with alcoholic liver disease, an approach to the selection of candidates is outlined herewith. 1. Minimum pretransplant sobriety period of 6 months. 2. Assessment of overall psychosocial support and stress. 3. Assessment of comorbid psychiatric conditions that may impair ability to comply with the transplant protocol during and after transplantation. 4. Assessment of past and present compliance with medical treatment. 5. Acceptance of problem with alcohol and willingness to sign an alcohol contract. 6. Willingness to participate in alcohol rehabilitation treatment program. 7. Willingness to participate in liver support groups to improve understanding of the condition and obtain social support. 8. Willingness to undergo random toxicology screening to assess compliance with sobriety. PMID:15562571

  15. Early postoperative complications following liver transplantation.

    PubMed

    Mueller, Andrea R; Platz, Klaus-Peter; Kremer, Bernd

    2004-10-01

    Liver transplantation is a highly successful treatment for patients with end-stage liver disease and acute liver failure. However, serious postoperative complications can significantly compromise patient survival. Complications can be technical, medical, or immunological in nature. The risk of developing early postoperative complications is associated with the patient's preoperative condition, the quality of the donor liver, the quality of the donor and recipient procedure, initial graft function, and perioperative anaesthesiological and intensive care management. The patient's preoperative condition can include gastrointestinal bleeding, acute renal failure, a requirement for cathecholamines or mechanical ventilation, and prolonged encephalopathy for the most detrimental risk factors for developing early postoperative complications. The necessity for prolonged mechanical ventilation or the requirement for reintubation after transplantation can significantly increase the risk of developing pneumonia, sepsis, and multiple organ dysfunction. A decrease in infectious and other complications can be achieved by early postoperative enteral nutition, including the application of probiotics. PMID:15494284

  16. Liver transplantation in acute-on-chronic liver failure: lessons learnt from acute liver failure setting.

    PubMed

    Reddy, Mettu Srinivas; Rajalingam, Rajesh; Rela, Mohamed

    2015-10-01

    Acute-on-chronic liver failure is a clinical entity with high risk of mortality. These patients can have severe liver dysfunction complicated with multiple organ failure. Liver transplantation is the definitive treatment for these patients. Literature regarding management of acute liver failure with special emphasis on liver transplantation was reviewed. Lessons learnt from the management of patients with acute liver failure which could be extrapolated to the management of patients with acute-on-chronic liver failure are discussed. Significant improvement in outcomes of acute liver failure has been reported across the world. Several aspects in transplantation for acute liver failure were found to be relevant to the management of acute-on-chronic liver failure. These include defining criteria to identify patients needing early liver transplantation, prioritizing patients with acute liver failure on the waiting list, defining when to abandon transplantation in acute liver failure, emphasis on graft quality and the need for a multi-disciplinary approach to manage multiple organ dysfunction. Useful lessons can be learnt from the progress made in the management of acute liver failure and these can be extrapolated to the management of patients with acute-on-chronic liver failure. PMID:25788191

  17. Dental health in liver transplant patients.

    PubMed

    Díaz-Ortiz, María Luisa; Micó-Llorens, José María; Gargallo-Albiol, Jordi; Baliellas-Comellas, Carmen; Berini-Aytés, Leonardo; Gay-Escoda, Cosme

    2005-01-01

    Since the first liver transplantation in Spain was carried out in 1984, advances in surgical technique and immunosuppressive drugs have facilitated an increase in the number of transplants performed. The present study evaluates buccodental health in liver transplant patients. A cross-sectional descriptive study was made of a sample of patients subjected to liver transplantation in Príncipes de España Hospital (Bellvitge University Health Care Complex, L'Hospitalet de Llobregat, Barcelona--Spain). Information was collected relating to demographic characteristics, general clinical history, buccodental history and intraoral exploratory findings. A total of 53 individuals were evaluated (28 males and 25 females, with a mean age of 57.6 years). The mean time elapsed from transplantation was 3 years and 9 months. The most frequent indication for liver transplantation was liver cirrhosis due to hepatitis C virus (HCV) infection (49.1% of the global series). The most widely used immunosuppressors were cyclosporine and tacrolimus. The CAOD index of the series was 11.2. In relation to periodontal disease, 22% of the dentate patients showed gingival overgrowth, while half of those with teeth had gingival recessions, and 34% presented some type of dental mobility. The examination of the oral mucosa showed fissured tongue to be the most common disorder (39.6%), followed by saburral tongue (28.3%) and xerostomia (18.9%). Buccodental pathology in these patients is related to the use of immunosuppressor medication and other factors such as a lack of preventive measures. The findings of the present study point to the need for preventive treatments in this population group.

  18. Supercooling enables long-term transplantation survival following 4 days of liver preservation.

    PubMed

    Berendsen, Tim A; Bruinsma, Bote G; Puts, Catheleyne F; Saeidi, Nima; Usta, O Berk; Uygun, Basak E; Izamis, Maria-Louisa; Toner, Mehmet; Yarmush, Martin L; Uygun, Korkut

    2014-07-01

    The realization of long-term human organ preservation will have groundbreaking effects on the current practice of transplantation. Herein we present a new technique based on subzero nonfreezing preservation and extracorporeal machine perfusion that allows transplantation of rat livers preserved for up to four days, thereby tripling the viable preservation duration.

  19. Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats.

    PubMed

    Arkadopoulos, N; Lilja, H; Suh, K S; Demetriou, A A; Rozga, J

    1998-11-01

    To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic. Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta1 (TGF-beta1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic. Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group 1 anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01). Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta1 levels when compared with sham-transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta1 levels in rats rendered anhepatic. PMID:9794923

  20. Ethical issues in split versus whole liver transplantation.

    PubMed

    Vulchev, Anntim; Roberts, John P; Stock, Peter G

    2004-11-01

    Technologic advances in split liver transplantation have resulted in an ethical dilemma. Although splitting a liver maximizes the number of patients receiving an organ transplant, it may increase the morbidity and mortality for the individual patient receiving the split liver. This essay explores the ethical issues involved in the allocation of split livers, and proposes general policy guidelines for the allocation of split versus whole liver transplants. PMID:15476469

  1. Liver transplantation at the University of Chicago.

    PubMed

    Millis, J M; Alonso, E M; Piper, J B; Bruce, D S; Newell, K A; Woodle, E S; Baker, A L; Whitington, P F; Thistlethwaite, J R

    1995-01-01

    Over the past 5 years, we have employed several strategies to increase the donor pool for both the pediatric and adult populations. The innovative expansion of the donor pool with the use living-related donors for children and cadaveric, high-risk donors for adults has increased our ability to serve our recipients and transplant them at an earlier stage in the disease process, thereby improving survival. As Hepatitis C is now the leading indication for liver transplantation in the adult population, the investigation of the natural history of Hepatitis C prior to and after transplantation provides a major challenge and is currently a focus of both laboratory and clinical efforts. For those recipients of Hepatitis C-positive-donor livers, determining the role of recipient and donor genotypes in the progression of recurrent hepatitis should help define the proper utilization of these organs. For patients on CsA-based immunosuppression regimens who experience steroid-resistant rejection, tacrolimus has proved to be extremely effective in reversing the rejection episodes and maintaining normal graft function. The long-term results of this therapy appear to be superior to OKT3 therapy. The recipients of living-related liver transplantation continue to have a survival advantage in comparison to recipients of cadaveric grafts. The donor operation can be routinely performed with minimal risk. Because of the superior results achieved and minimal donor risks, we feel that providing the option of living-donor transplantation is ethically justified, and medically necessary. Despite the encouraging results from living-donor transplantation, unexpected complications including portal vein complications and hepatic artery thrombosis have forced technical modifications of the original technique which may have implications to pediatric liver transplantation in general. As the volume of pediatric liver transplants and the number of immmunosuppressive regimens have increased over the

  2. Living-donor liver transplantation: current perspective.

    PubMed

    Lobritto, Steven; Kato, Tomoaki; Emond, Jean

    2012-11-01

    The disparity between the number of available deceased liver donors and the number of patients awaiting transplantation continues to be an ongoing issue predisposing to death on the liver transplant waiting list. Deceased donor shortage strategies including the use of extended donor-criteria deceased donor grafts, split liver transplants, and organs harvested after cardiac death have fallen short of organ demand. Efforts to raise donor awareness are ongoing, but the course has been arduous to date. Living donor transplantation is a means to access an unlimited donor organ supply and offers potential advantages to deceased donation. Donor safety remains paramount demanding improvements and innovations in both the donor and recipient operations to ensure superior outcomes. The specialty operation is best preformed at centers with specific expertise and shuttling of select patients to these centers supported by third party payers is critical. Training future surgeons at centers with this specific experience can help disseminate this technology to improve local availability. Ongoing research in immunosuppression minimization, withdrawal and tolerance induction may make living donation a desired first-line operation rather than a necessary albeit less-desirable option. This chapter summarizes the progress of living liver donation and its potential applications. PMID:23397534

  3. Metabolic complications in liver transplant recipients

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-01-01

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS. PMID:27605877

  4. Metabolic complications in liver transplant recipients

    PubMed Central

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-01-01

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS.

  5. Metabolic complications in liver transplant recipients.

    PubMed

    Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel

    2016-07-28

    The metabolic syndrome (MS), which includes obesity, dyslipidaemia, hypertension and hyperglycaemia according to the most widely accepted definitions now used, is one of the most common post-transplant complications, with a prevalence of 44%-58%. The MS, together with the immunosuppression, is considered the main risk factor for the development of cardiovascular disease (CVD) in transplant recipients, which in turn accounts for 19%-42% of all deaths unrelated to the graft. The presence of MS represents a relative risk for the development of CVD and death of 1.78. On the other hand, non-alcoholic fatty liver disease (NAFLD), considered as the manifestation of the MS in the liver, is now the second leading reason for liver transplantation in the United States after hepatitis C and alcohol. NAFLD has a high rate of recurrence in the liver graft and a direct relation with the worsening of other metabolic disorders, such as insulin resistance or diabetes mellitus. Consequently, it is vitally important to identify and treat as soon as possible such modifiable factors as hypertension, overweight, hyperlipidaemia or diabetes in transplanted patients to thus minimise the impact on patient survival. Additionally, steroid-free regimens are favoured, with minimal immunosuppression to limit the possible effects on the development of the MS. PMID:27605877

  6. Living donor liver transplantation in Egypt

    PubMed Central

    Marwan, Ibrahim

    2016-01-01

    In Egypt there is no doubt that chronic liver diseases are a major health concern. Hepatitis C virus (HCV) prevalence among the 15−59 years age group is estimated to be 14.7%. The high prevalence of chronic liver diseases has led to increasing numbers of Egyptian patients suffering from end stage liver disease (ESLD), necessitating liver transplantation (LT). We reviewed the evolution of LT in Egypt and the current status. A single center was chosen as an example to review the survival and mortality rates. To date, deceased donor liver transplantation (DDLT) has not been implemented in any program though Egyptian Parliament approved the law in 2010. Living donor liver transplantation (LDLT) seemed to be the only logical choice to save many patients who are in desperate need for LT. By that time, there was increase in number of centers doing LDLT (13 centers) and increase in number of LDLT cases [2,400] with improvement of the results. Donor mortality rate is 1.66 per 1,000 donors; this comprised four donors in the Egyptian series. The exact recipient survival is not accurately known however, and the one-year, three-year and five-year survival were 73.17%, 70.83% and 64.16% respectively in the International Medical Center (IMC) in a series of 145 adult to adult living donor liver transplantation (AALDLT) cases. There was no donor mortality in this series. LDLT are now routinely and successfully performed in Egypt with reasonable donor and recipient outcomes. Organ shortage remains the biggest hurdle facing the increasing need for LT. Although LDLT had reasonable outcomes, it carries considerable risks to healthy donors. For example, it lacks cadaveric back up, and is not feasible for all patients. The initial success in LDLT should drive efforts to increase the people awareness about deceased organ donation in Egypt. PMID:27115003

  7. Liver transplantation: fifty years of experience.

    PubMed

    Song, Alice Tung Wan; Avelino-Silva, Vivian Iida; Pecora, Rafael Antonio Arruda; Pugliese, Vincenzo; D'Albuquerque, Luiz Augusto Carneiro; Abdala, Edson

    2014-05-14

    Since 1963, when the first human liver transplantation (LT) was performed by Thomas Starzl, the world has witnessed 50 years of development in surgical techniques, immunosuppression, organ allocation, donor selection, and the indications and contraindications for LT. This has led to the mainstream, well-established procedure that has saved innumerable lives worldwide. Today, there are hundreds of liver transplant centres in over 80 countries. This review aims to describe the main aspects of LT regarding the progressive changes that have occurred over the years. We herein review historical aspects since the first experimental studies and the first attempts at human transplantation. We also provide an overview of immunosuppressive agents and their potential side effects, the evolution of the indications and contraindications of LT, the evolution of survival according to different time periods, and the evolution of methods of organ allocation. PMID:24833866

  8. Care of the liver transplant patient

    PubMed Central

    Bhat, Mamatha; Al-Busafi, Said A; Deschênes, Marc; Ghali, Peter

    2014-01-01

    OBJECTIVE: To provide an approach to the care of liver transplant (LT) patients, a growing patient population with unique needs. METHODS: A literature search of PubMed for guidelines and review articles using the keywords “liver transplantation”, “long term complications” and “medical management” was conducted, resulting in 77 articles. RESULTS: As a result of being on immunosuppression, LT recipients are at increased risk of infections and must be screened regularly for metabolic complications and malignancies. DISCUSSION: Although immunosuppression is key to maintaining allograft health after transplantation, it comes with its own set of medical issues to follow. Physicians following LT recipients must be aware of the greater risk for hypertension, diabetes, dyslipidemia, renal failure, metabolic bone disease and malignancies in these patients, all of whom require regular monitoring and screening. Vaccination, quality of life, sexual function and pregnancy must be specifically addressed in transplant patients. PMID:24729996

  9. Orthotopic liver transplantation in liver-based metabolic disorders.

    PubMed

    Mowat, A P

    1992-01-01

    The efficacy of orthotopic liver transplantation (OLT) in the management of more common liver-based metabolic disorders associated with severe liver damage, alpha-1-antitrypsin deficiency (PIZZ), Wilson disease and tyrosinaemia has been demonstrated and indications defined. An early mortality in excess of 15% and finite resources limit its use. Phenotypic heterogeneity make the precise indication in other disorders less certain. In disorders in which endstage liver disease is less frequent such as cystic fibrosis, haemochromatosis and galacosaemia it has been a very effective therapy. It has been used with encouraging results in disorders in which the liver is structurally normal such as Crigler-Najjar type I, primary hyperoxaluria type I and primary hypercholesterolaemia. In these it should be performed before there is permanent damage to brain, kidneys or heart. OLT in the short term prevents hyperammonaemic coma in urea cycle defects and may prevent extrahepatic disease in glycogen storage disease type IV. Its limitation in reversing all metabolic effects in these and other disorders is discussed. It is ineffective in protoporphyria or Niemann Pick disease type II (Sea Blue Histiocyte syndrome) in which the transplanted liver acquires the lesions of the initial disorder and extrahepatic features progress. Early referral provides optimum circumstances to assess the benefits of OLT as compared with those of other forms of management and to achieve transplantation at the ideal time. The place of OLT in management will require constant review as metabolic disorders are better defined, new forms of therapy evolve and as techniques of liver transplantation and modes of immunosuppression improve.

  10. The Liver Transplant Program at Tianjin First Center Hospital.

    PubMed

    Shen, Zhongyang

    2011-01-01

    The liver transplant program at the transplant center of Tianjin First Center Hospital opened in 1994 and has become a leading center for academic research and development in clinical liver transplantation during the past 18 years. As of Nov 30, 2011, we had performed 4,103 liver transplantations in patients ranging from 6 months to 79 years old. Since 1998, the program has ranked first in mainland China in the annual number of liver transplants performed, the cumulative total liver transplants and the number of long-surviving patients. We've accomplished a number of "firsts" among the Chinese liver transplant centers, including: the first split liver transplantation, the first pediatric liver transplant, the first living donor simultaneous liver-kidney transplant, the first dual-graft liver transplant using a domino right lobe and a living donor left lobe, the first laparoscopic assisted live donor right hepatectomy including the middle hepatic vein and we have assembled the first liver transplant chain comprising multiple donors and recipients. We have performed the largest number of living related and split liver transplantations in mainland China. The combined prophylactic protocol of "Lamivudine and HBIG" to prevent HBV recurrence post transplantation was first used by our center in China and now is utilized by most of the domestic transplant centers. We have begun using livers from donors after cardiac death (DCD) during the past 2 years, with careful donor selection and recipient management. All the approaches and techniques we've developed are aimed at the utilization of all types of available grafts. However, increasing the rate of transplantation with excellent graft and recipient survival are still the challenges facing us.

  11. The Liver Transplant Program at Tianjin First Center Hospital.

    PubMed

    Shen, Zhongyang

    2011-01-01

    The liver transplant program at the transplant center of Tianjin First Center Hospital opened in 1994 and has become a leading center for academic research and development in clinical liver transplantation during the past 18 years. As of Nov 30, 2011, we had performed 4,103 liver transplantations in patients ranging from 6 months to 79 years old. Since 1998, the program has ranked first in mainland China in the annual number of liver transplants performed, the cumulative total liver transplants and the number of long-surviving patients. We've accomplished a number of "firsts" among the Chinese liver transplant centers, including: the first split liver transplantation, the first pediatric liver transplant, the first living donor simultaneous liver-kidney transplant, the first dual-graft liver transplant using a domino right lobe and a living donor left lobe, the first laparoscopic assisted live donor right hepatectomy including the middle hepatic vein and we have assembled the first liver transplant chain comprising multiple donors and recipients. We have performed the largest number of living related and split liver transplantations in mainland China. The combined prophylactic protocol of "Lamivudine and HBIG" to prevent HBV recurrence post transplantation was first used by our center in China and now is utilized by most of the domestic transplant centers. We have begun using livers from donors after cardiac death (DCD) during the past 2 years, with careful donor selection and recipient management. All the approaches and techniques we've developed are aimed at the utilization of all types of available grafts. However, increasing the rate of transplantation with excellent graft and recipient survival are still the challenges facing us. PMID:22755414

  12. Recent advance in living donor liver transplantation.

    PubMed

    Hashikura, Yasuhiko; Kawasaki, Seiji; Miyagawa, Shinichi; Terada, Masaru; Ikegami, Toshihiko; Nakazawa, Yuichi; Urata, Koichi; Chisuwa, Hisanao; Ogino, Shiro; Makuuchi, Masatoshi

    2002-02-01

    Living donor liver transplantation (LDLT)has been performed in more than 2000 cases around the world. This procedure is considered to have certain advantages over cadaveric liver transplantation, because detailed preoperative evaluation of the donor liver is possible and superior graft quality is available. The indication has recently been widened to include adult patients. The results of LDLT have been reported to be very good. In this article,several considerations on LDLT,including living donor selection and application to adult patients, are discussed. Between June 1990 and March 2001, 143 patients underwent LDLT at Shinshu University Hospital. During this period, 160 patients were determined to be candidates for liver transplantation in our institution, and 185 candidates were evaluated as potential donors for these patients. Thirty-eight of 185 donor candidates were excluded for reasons including liver dysfunction and withdrawal of consent. The recipients included 60 adults, 50 (83%) of whom are currently alive. Taking into account the worldwide shortage of cadaveric organ donation,the importance of LDLT will probably never diminish. This procedure should be established on the basis of profound consideration of donor safety as well as accumulated expertise of hepatobiliary surgery. PMID:11865355

  13. MedlinePlus: Liver Transplantation

    MedlinePlus

    ... and Research Clinical Trials Journal Articles Resources Reference Desk Find an Expert For You Children Patient Handouts Summary Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove ...

  14. Liver Transplantation after Exertional Heatstroke-Induced Acute Liver Failure

    PubMed Central

    Virk, Hafeez Ul Hasan

    2016-01-01

    Exertional heatstroke (EHS) is a life-threatening disease characterized clinically by central nervous system dysfunction and severe hyperthermia. It frequently occurs among athletes, soldiers, and laborers. While cardiopulmonary symptoms are common in patients undergoing EHS, irreversible acute liver failure is a rarely described phenomenon. When managing cases of EHS complicated by acute liver failure, it is crucial to act promptly with aggressive total body cooling in order to prevent progression of the clinical syndrome. However, an urgent liver transplantation can be a therapeutic strategy when patients fail to improve with supportive measures. PMID:27738568

  15. The antibody crossmatch in liver transplantation

    PubMed Central

    Gordon, Robert D.; Fung, John J.; Markus, Bernd; Fox, Ira; Iwatsuki, Shunzaburo; Esquivel, Carlos O.; Tzakis, Andreas; Todo, Satoru; Starzl, Thomas E.

    2011-01-01

    Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection. PMID:3532391

  16. Hepatocyte transplantation in the Long Evans Cinnamon rat model of Wilson's disease.

    PubMed

    Park, Seon Mee; Vo, Kim; Lallier, Michel; Cloutier, Alexis-Simon; Brochu, Pierre; Alvarez, Fernando; Martin, Steven R

    2006-01-01

    Wilson's disease (WD), caused by a mutation in the P-type copper transporting ATPase (Atp7b) gene, results in excessive accumulation of copper in the liver. Long Evans Cinnamon rats (LEC) bear a mutation in the atp7b gene and share clinical characteristics of human WD. To explore hepatocyte transplantation (HT) as therapy for metabolic liver diseases, 8-week-old LEC rats (n = 12) were transplanted by intrasplenic injection of hepatocytes from donor Long Evans (LE) rats. Immunosuppression was maintained with intraperitoneal tacrolimus. The success of HT was monitored at 24 weeks of life. Serum aminotransferases and bilirubin peaked at 14-21 weeks in both HT rats and nontransplanted controls, but at 24 weeks, survival was 97% in LEC-HT versus 63% in controls. All transplanted rats showed restored biliary copper excretion and reduced liver iron concentration associated with increased ceruloplasmin oxidase activity. Liver tissue expressed atp7b mRNA (11.9 +/- 13.6%) indicative of engraftment of normal cells in 7 of 12 HT rats, associated with a reduced liver copper concentration compared to untreated LEC rats. Periportal islets of normal appearing hepatocytes, recognized by atp7b antibody, were observed in transplanted livers while lobular host cells showed persistent pleomorphic changes and inflammatory infiltrates. In conclusion, transplantation of normal hepatocytes prevented fulminant hepatitis, reduces chronic inflammation, and improved 6-month survival in LEC rats. Engraftment of transplanted cells, which express atp7b mRNA, repopulated the recipient liver with normal functional capacity.

  17. The International Liver Transplant Society Guideline on Living Liver Donation.

    PubMed

    Miller, Charles M; Durand, Francois; Heimbach, Julie K; Kim-Schluger, Leona; Lee, Sung-Gyu; Lerut, Jan; Lo, Chung-Mau; Quintini, Cristiano; Pomfret, Elizabeth Anne

    2016-06-01

    The following guideline represents the position of the International Liver Transplantation Society (ILTS) on key preoperative, operative, and postoperative aspects surrounding living liver donation. These recommendations were developed from experts in the field from around the world. The authors conducted an analysis of the National Library of Medicine indexed literature on "living donor liver transplantation" [Medline search] using Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). ILTS members, and many more nonmembers, were invited to comment. Recommendations have been based on information available at the time of final submission (March 2016). The lack of randomized controlled trials in this field to date is acknowledged and is reflected in the grading of evidence. Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care.

  18. Muscle Mass Predicts Outcomes Following Liver Transplantation

    PubMed Central

    DiMartini, Andrea; Cruz, Ruy J.; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Kim, Kevin H.; Fontes, Paulo

    2015-01-01

    Background and aims For patients with end-stage liver disease commonly used indices of nutritional status (i.e. body weight and BMI) are often inflated due to fluid overload (i.e. ascites, peripheral edema) resulting in an underdiagnosis of malnutrition. As muscle is the largest protein reservoir in the body, an estimate of muscle mass may be a more reliable and valid estimate of nutritional status. Methods Therefore, we used pre-transplant computerized tomography data of 338 liver transplant (LTX) candidates to identify muscle and fat mass based on a specific abdominal transverse section commonly used in body composition analyses and investigated the contribution of this measure to specific post-LTX outcomes. Results We found the majority, 68%, of our patients could be defined as cachetic. For men muscle mass predicted many important post-transplant outcomes including intensive care unit (ICU) and total length of stay and days of intubation. Muscle mass was a significant predictor of survival and also predicted disposition to home vs another facility. For women muscle mass predicted lengths of ICU and total stay and days of intubation but the effect was modest. Muscle mass did not predict survival or disposition for women. Conclusions As pre-transplant muscle mass was associated with many important post-operative outcomes we discuss these findings in the context of possible pre-transplant interventions to either improve or sustain muscle mass before surgery. PMID:23960026

  19. Arterial hypertension in liver transplant recipients.

    PubMed

    Hryniewiecka, E; Zegarska, J; Paczek, L

    2011-10-01

    Hypertension is an important cardiovascular risk factor that influences patient survival. This study sought to evaluate hypertension incidence and circadian rhythms of blood pressure (BP) among liver transplant recipients during the first posttransplant month. We also compared hypertension incidence according to clinical and automated blood pressure monitoring methods. BP was determined by clinical blood pressure monitoring (CBPM) methods and by automated blood pressure monitoring (ABPM) using the SpaceLabs device. We also assessed blood biochemistry, particularly kidney function parameters and immunosuppressive drug blood trough levels, among 32 white subjects (10 women and 22 men) of average age 47.58±14.19 years. The leading cause for transplantation was liver insufficiency due to viral hepatitis B and/or C infection (43.75%). The majority (93.75%) of patients was prescribed immunosuppressive treatment with tacrolimus. Although we observed hypertension in 28 patients (87.5%) by ABPM measurements and in 25 (78.12%) using CBPM method, the difference did not reach statistical significance. However, BP control was inadequate in 28 patients (87.5%) by ABPM assessment versus 3 (9.38%) according to CBPM readings (P=.025). The BP circadian rhythm was altered in 30 patients (93.75%) including 15 with higher nighttime BP readings. There was no correlation between tacrolimus blood levels and BP values or with kidney function as assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We concluded that prevalence of arterial hypertension among liver transplant recipients within 1 month after transplantation is high. The majority of the patients show disturbed circadian rhythms in the early period after liver transplantation with loss or even reversal of the normal nocturnal decrease in BP. Owing to the fact that ABPM enables more adequate daily assessment of BP values, it is an optimal method to adjust antihypertensive therapy to optimal levels

  20. Split liver transplantation: King's College Hospital experience.

    PubMed Central

    Rela, M; Vougas, V; Muiesan, P; Vilca-Melendez, H; Smyrniotis, V; Gibbs, P; Karani, J; Williams, R; Heaton, N

    1998-01-01

    BACKGROUND: The purpose of split liver transplantation is to increase the source of pediatric grafts without compromising the adult donor pool. Early results have been discouraging because of technical complications and selection of poor risk patients. METHODS: The results of a single center experience of 41 split liver transplantations were analyzed. Patient and graft survival and complications related to the technique were analyzed. RESULTS: Patient and graft survival for the whole group was 90% and 88% respectively at a median follow up of 12 months (range 6-70 months). Patient and graft survival for the right lobe graft was 95% and the left lateral segment 86% and 82% respectively. Four patients died, of which two of the patients were first two splits following technical complications. Two others died, one from cerebral lymphoma and the other of multiorgan failure secondary to sepsis. One patient has been retransplanted for chronic biliary sepsis. CONCLUSION: Split liver transplantation has now become an acceptable treatment option for both adult and pediatric recipients with end stage liver disease. Right lobe recipients are not disadvantaged by the procedure. Good results can be achieved with better patient selection and by the use of good quality organs. PMID:9488528

  1. Current developments in pediatric liver transplantation

    PubMed Central

    Hackl, Christina; Schlitt, Hans J; Melter, Michael; Knoppke, Birgit; Loss, Martin

    2015-01-01

    In 1953, the pioneer of human orthotopic liver transplantation (LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT (pLT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, pLT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and post-operative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of pLT, with a focus on alternatives to full-size deceased-donor organ transplantation. PMID:26085910

  2. Current developments in pediatric liver transplantation.

    PubMed

    Hackl, Christina; Schlitt, Hans J; Melter, Michael; Knoppke, Birgit; Loss, Martin

    2015-06-18

    In 1953, the pioneer of human orthotopic liver transplantation (LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT (pLT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, pLT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and post-operative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of pLT, with a focus on alternatives to full-size deceased-donor organ transplantation. PMID:26085910

  3. The hepatic artery in liver transplantation.

    PubMed

    Merion, R M; Burtch, G D; Ham, J M; Turcotte, J G; Campbell, D A

    1989-09-01

    Hepatic artery complications after liver transplantation are uncommon, but represent an important cause of morbidity and mortality. In addition, these complications tax an already limited supply of donor organs because of the frequent need for retransplantation in this group of patients. In this study, we examined the incidence of hepatic arterial anomalies in donors and recipients of orthotopic liver transplants, focusing on the techniques that are available for hepatic arterial reconstruction and on the occurrence of hepatic arterial complications. A total of 77 liver transplants were carried out in 68 patients. Standard recipient anatomy was present in 60 of 68 patients (88%). Anomalous vessels were identified in eight patients (12%), including six cases of replaced right hepatic artery (9%) and two cases of replaced left hepatic artery (3%). Donor liver arterial anatomy was standard in 62 cases (80%). Anomalous arterial supply was identified in 15 of 77 donor livers (20%), including replaced left hepatic artery in nine (12%) and replaced right hepatic artery in six (8%). A variety of methods were used to manage the anomalous vessels. There was one hepatic artery pseudoaneurysm, three cases of hepatic artery thrombosis (4%), and one patient developed a dissection of the native celiac axis. In primary transplants, utilization of the recipient's proper hepatic artery was associated with a significantly higher risk of hepatic artery thrombosis (P less than 0.04) when compared with the common hepatic artery or the branch patch technique. Use of a Carrel patch on the donor artery was associated with a significantly reduced incidence of hepatic artery thrombosis (P less than 0.0003). For retransplantation, it is recommended that a more proximal recipient anastomotic site be chosen. An innovative method is described that provides increased length of the donor arterial supply without the use of an arterial graft. PMID:2675403

  4. Caroli's disease and orthotopic liver transplantation.

    PubMed

    Habib, Shahid; Shakil, Obaid; Couto, Osvaldo F; Demetris, Anthony J; Fung, John J; Marcos, Amadeo; Chopra, Kapil

    2006-03-01

    Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver

  5. Perioperative monitoring in liver transplant patients.

    PubMed

    Singh, Shweta; Nasa, Vaibhav; Tandon, Manish

    2012-09-01

    Liver transplant (LT) is a major surgical undertaking involving major fluid shifts, hemodynamic instability and metabolic derangements in a patient with preexisting liver failure and multisystemic derangements. Monitoring and organ support initiated in the preoperative phase is continued intraoperatively and into the postoperative phase to ensure an optimal outcome. As cardiovascular events are the leading cause of non-graft related death among LT recipients, major emphasis is placed on cardiovascular monitoring. The other essential monitoring are the continuous assessment of coagulapathy, extent of metabolic derangements, dyselectrolytemis and intracranial pressure monitoring in patients with fulminant hepatic failure. The type and extent of monitoring differs with need according to preexisting child status of the patient and the extent of systemic derangements. It also varies among transplant centers and is mainly determined by individual or institutional practices.

  6. Perioperative monitoring in liver transplant patients.

    PubMed

    Singh, Shweta; Nasa, Vaibhav; Tandon, Manish

    2012-09-01

    Liver transplant (LT) is a major surgical undertaking involving major fluid shifts, hemodynamic instability and metabolic derangements in a patient with preexisting liver failure and multisystemic derangements. Monitoring and organ support initiated in the preoperative phase is continued intraoperatively and into the postoperative phase to ensure an optimal outcome. As cardiovascular events are the leading cause of non-graft related death among LT recipients, major emphasis is placed on cardiovascular monitoring. The other essential monitoring are the continuous assessment of coagulapathy, extent of metabolic derangements, dyselectrolytemis and intracranial pressure monitoring in patients with fulminant hepatic failure. The type and extent of monitoring differs with need according to preexisting child status of the patient and the extent of systemic derangements. It also varies among transplant centers and is mainly determined by individual or institutional practices. PMID:25755443

  7. One thousand liver transplants. The lessons learned.

    PubMed Central

    Busuttil, R W; Shaked, A; Millis, J M; Jurim, O; Colquhoun, S D; Shackleton, C R; Nuesse, B J; Csete, M; Goldstein, L I; McDiarmid, S V

    1994-01-01

    OBJECTIVE: To evaluate the first 1000 liver transplants performed at UCLA Medical Center to determine factors responsible for improved results. SUMMARY BACKGROUND DATA: Liver transplant has evolved impressively since the first case was performed in 1963. The 1980s have highlighted this progress with the development of better organ preservation, standardization of operative procedure, improved immunosuppressive agents, and better understanding of patient selection. METHODS: The first 100 consecutive liver transplants (group 1) performed from February 1984 through October 1986 were compared with the last 200 (group 2) performed between September 1991 and June 1992. An analysis was made of donor use; changes in patient candidacy; patient care variables; morbidity and mortality; survival data; and hospital resource use. RESULTS: In group 1, 31% of donors were refused because of medical unsuitability compared with 4% in group 2 (p < 0.0001). In group 1, alcoholic patients comprised 1% of liver transplant candidates compared with 20% group 2 (p < 0.0001). High-risk patients (United Network for Organ Sharing criteria 4) only comprised 11% of patients in group 1 compared with 37% in group 2 (p < 0.0001). Operative time (7.6 hours compared with 5.4 hours), packed cell replacement (17 units compared with 9.5 units), intensive care unit stay (10 days compared with 5 days), and hospital stay (50 days compared with 31 days) were all significantly improved (p < 0.05). In group 1, the 1-year survival rate was 73% and improved to 88% in group 2 (p < 0.0001). CONCLUSIONS: Despite unfavorable donor characteristics (obesity, cause of death, age, hypotension), most organs function well and should not be refused based on history alone. The older and high-risk patient (renal failure, ventilator dependence, portal vein pathology, and so on) is routinely transplanted with good success. Despite liberalization of both donor and recipient criteria, patient survival after liver transplant is

  8. Hepatocyte transplantation for inherited metabolic diseases of the liver.

    PubMed

    Jorns, C; Ellis, E C; Nowak, G; Fischler, B; Nemeth, A; Strom, S C; Ericzon, B G

    2012-09-01

    Inherited metabolic diseases of the liver are characterized by deficiency of a hepatic enzyme or protein often resulting in life-threatening disease. The remaining liver function is usually normal. For most patients, treatment consists of supportive therapy, and the only curative option is liver transplantation. Hepatocyte transplantation is a promising therapy for patients with inherited metabolic liver diseases, which offers a less invasive and fully reversible approach. Procedure-related complications are rare. Here, we review the experience of hepatocyte transplantation for metabolic liver diseases and discuss the major obstacles that need to be overcome to establish hepatocyte transplantation as a reliable treatment option in the clinic.

  9. Transfusion and coagulation management in liver transplantation

    PubMed Central

    Clevenger, Ben; Mallett, Susan V

    2014-01-01

    There is wide variation in the management of coagulation and blood transfusion practice in liver transplantation. The use of blood products intraoperatively is declining and transfusion free transplantations take place ever more frequently. Allogenic blood products have been shown to increase morbidity and mortality. Primary haemostasis, coagulation and fibrinolysis are altered by liver disease. This, combined with intraoperative disturbances of coagulation, increases the risk of bleeding. Meanwhile, the rebalancing of coagulation homeostasis can put patients at risk of hypercoagulability and thrombosis. The application of the principles of patient blood management to transplantation can reduce the risk of transfusion. This includes: preoperative recognition and treatment of anaemia, reduction of perioperative blood loss and the use of restrictive haemoglobin based transfusion triggers. The use of point of care coagulation monitoring using whole blood viscoelastic testing provides a picture of the complete coagulation process by which to guide and direct coagulation management. Pharmacological methods to reduce blood loss include the use of anti-fibrinolytic drugs to reduce fibrinolysis, and rarely, the use of recombinant factor VIIa. Factor concentrates are increasingly used; fibrinogen concentrates to improve clot strength and stability, and prothrombin complex concentrates to improve thrombin generation. Non-pharmacological methods to reduce blood loss include surgical utilisation of the piggyback technique and maintenance of a low central venous pressure. The use of intraoperative cell salvage and normovolaemic haemodilution reduces allogenic blood transfusion. Further research into methods of decreasing blood loss and alternatives to blood transfusion remains necessary to continue to improve outcomes after transplantation. PMID:24876736

  10. Predictors and impacts of hospital readmissions following liver transplantation.

    PubMed

    Yataco, Maria; Cowell, Alissa; David, Waseem; Keaveny, Andrew P; Taner, C Burcin; Patel, Tushar

    2016-01-01

    While liver transplantation is the definitive therapy for end stage liver disease, it remains a major procedure, with many potential complications. Hospital readmissions after the initial hospitalization for liver transplantation can be associated with adverse outcomes, increased cost, and resource utilization. Our aim was to define the incidence and reasons for hospital readmission after liver transplant and the impact of readmissions on patient outcomes. We retrospectively analyzed 30- and 90-day readmission rates and indications in patients who underwent liver transplant at a large-volume transplant center over a 3-year period. Four hundred seventy-nine adult patients underwent their first liver transplant during the study period. The 30-day readmission rate was 29.6%. Recipient and donor age, etiology of liver disease, biological Model for End-Stage Liver Disease score, and cold ischemia time were similar between patients who were readmitted within 30 days and those who were not readmitted. Readmissions occurred in 25% of patients who were hospitalized prior to liver transplant compared to 30% who were admitted for liver transplant. The most common indications for readmission were infection, severe abdominal pain, and biliary complications. Early discharge from hospital (fewer than 7 days after liver transplant), was not associated with readmission; however, a prolonged hospital stay after liver transplant was associated with an increased risk of readmission (p = 0.04). In conclusion, patients who undergo liver transplant have a high rate of readmission. In our cohort, readmissions were unrelated to pre-existing recipient or donor factors, but were associated with a longer hospital stay after liver transplant. PMID:27049489

  11. Predictors and impacts of hospital readmissions following liver transplantation.

    PubMed

    Yataco, Maria; Cowell, Alissa; David, Waseem; Keaveny, Andrew P; Taner, C Burcin; Patel, Tushar

    2016-01-01

    While liver transplantation is the definitive therapy for end stage liver disease, it remains a major procedure, with many potential complications. Hospital readmissions after the initial hospitalization for liver transplantation can be associated with adverse outcomes, increased cost, and resource utilization. Our aim was to define the incidence and reasons for hospital readmission after liver transplant and the impact of readmissions on patient outcomes. We retrospectively analyzed 30- and 90-day readmission rates and indications in patients who underwent liver transplant at a large-volume transplant center over a 3-year period. Four hundred seventy-nine adult patients underwent their first liver transplant during the study period. The 30-day readmission rate was 29.6%. Recipient and donor age, etiology of liver disease, biological Model for End-Stage Liver Disease score, and cold ischemia time were similar between patients who were readmitted within 30 days and those who were not readmitted. Readmissions occurred in 25% of patients who were hospitalized prior to liver transplant compared to 30% who were admitted for liver transplant. The most common indications for readmission were infection, severe abdominal pain, and biliary complications. Early discharge from hospital (fewer than 7 days after liver transplant), was not associated with readmission; however, a prolonged hospital stay after liver transplant was associated with an increased risk of readmission (p = 0.04). In conclusion, patients who undergo liver transplant have a high rate of readmission. In our cohort, readmissions were unrelated to pre-existing recipient or donor factors, but were associated with a longer hospital stay after liver transplant.

  12. Loss of liver transplant surgeons into alternate career paths.

    PubMed

    Thomas, Michael; Angele, Martin; Stangl, Manfred; Rentsch, Markus; Pratschke, Sebastian; Andrassy, Joachim; Jauch, Karl-Walter; Guba, Markus

    2014-11-01

    In Germany, long-term commitment of surgeons to transplantation is rare. Most surgeons leave transplant surgery after a short stint and follow careers in other surgical fields. This rapid turnover of liver transplant surgeons may result in poor resource utilization and potentially compromise patient safety. In this report, we have analyzed the caseload and the careers of 25 surgeons in liver transplantation over a period of 22 years. The median time in liver transplantation was short. Of all surgeons who engaged in liver transplantation, the median time was 3.5 years. Surgeons who completed their training remained in the field for 7 years. Surgeons who prematurely stopped their training remained for 2 years. Individual total caseloads of transplant surgeons were relatively low. The median number of procedures was 40 for all surgeons, 153 for currently active surgeons, 51 for surgeons who completed training, 27 for surgeons currently in training, and a median of four liver transplantations for surgeons who prematurely stopped liver transplantation. The vast majority (75%) of surgeons prematurely quit liver transplantation to follow alternate surgical careers. Structural changes in academic transplant surgery have to be made to facilitate long-term commitments of interested surgeons and to avoid "futile" transplant careers. PMID:24975042

  13. Quality of life after liver transplantation.

    PubMed

    Braun, F; Teren, K; Wilms, P; Günther, R; Allmann, J; Broering, D C; Küchler, T

    2009-01-01

    Quality of life (QoL) is an outcome criterion of increasing importance after orthotopic liver transplantation (OLT). The background of this development is the dramatic improvement in patient survival rates over the past two decades combined with the question of the quality of this survival. Among 339 OLT performed in Kiel since 1987, 123 recipients (70 males, 53 females) of mean age 56.7 +/- 13.1 years who underwent transplantation between August 1992 and June 2007 were subjected to European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 plus a liver transplant specific module to analyze QoL. In addition, we included 40 patients listed for OLT in the univariate and multivariate analyses performed using SPSS13.0. A cohort of healthy individuals served as the control group. QoL (global health) among liver recipients was reduced compared with the control group and improved compared with patients on the waiting list. Comparison of the underlying liver diseases showed a comparable QoL between postalcoholic cirrhosis and cholestatic liver diseases. Retransplantation was accompanied by a significant loss of QoL. Cyclosporine-treated recipients displayed a better QoL compared with those treated with tacrolimus. After establishing a system of continuous, systematic QoL assessment, we combined these results with survival outcomes. Further research must focus on advanced statistical methodology that combines these 2 major outcome parameters (QoL and survival). Furthermore, the influence of medical parameters, such of co-morbidity or immunosuppression, needs to be further established with reference to QoL.

  14. Role of NK, NKT cells and macrophages in liver transplantation

    PubMed Central

    Fahrner, René; Dondorf, Felix; Ardelt, Michael; Settmacher, Utz; Rauchfuss, Falk

    2016-01-01

    Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer (NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review. PMID:27468206

  15. De novo autoimmune hepatitis after liver transplantation.

    PubMed

    Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

    2007-10-01

    The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

  16. Overview of the Indications and Contraindications for Liver Transplantation

    PubMed Central

    Farkas, Stefan; Hackl, Christina; Schlitt, Hans Jürgen

    2014-01-01

    Liver transplantation is the only definitive treatment option for patients with irrevocable acute or chronic liver failure. In the last four decades, liver transplantation has developed from an experimental approach with a very high mortality to an almost routine procedure with good short- and long-term survival rates. Here, we present an up-to-date overview of the indications and contraindications for liver transplantation. It is shown how the evaluation of a candidate and finally listing for transplantation has to be performed in a multidisciplinary setting. Meticulous listing, timing, and organ allocation are the crucial factors to achieve an optimal outcome for the individual patient on the one hand, and reasonably using the limited deceased donor pool on the other hand. Living-donor liver transplantation is demanding but necessarily increasing. Because patients after liver transplantation need lifelong aftercare, it is important for primary care clinicians to understand the basic medical problems and risks. PMID:24789874

  17. [Orthotopic liver transplantation: surgery research center's experience].

    PubMed

    Got'e, S V; Eramishantsev, A K; Tsirul'nikova, O M; Skipenko, O G; Filin, A V; Lokshin, L S; Kozhevnikov, V A; Eremenko, A A; Zhidkov, I L

    1997-01-01

    From 1990 to 1996, 178 patients with severe diffuse and advanced focal liver diseases with grave prognosis were observed for indications to orthotopic liver transplantation (OLT). According to the revealed indications and contraindications, 95 patients were enrolled for the procedure. Eighteen patients underwent 19 OLTs, including 1 urgent retransplantation and 3 living related graftings. Surgical techniques were conventional; with these, intraoperative mortality and biliary complications could be avoided. Long-term survival (6 to 68 months) was achieved in 8 recipients, including in those after liver retransplantation. Double or triple suppressive regimens were used. These included corticosteroids, cyclosporin A, azathioprine, antithymocytic globulin. The life quality of recipients promoted restoration of their working capacities. Two recipients gave birth to healthy babies.

  18. Liver transplantation in Turkey: historical review and future perspectives.

    PubMed

    Akbulut, Sami; Yilmaz, Sezai

    2015-07-01

    Since the first successful liver transplantation by Starzl et al. in 1967, liver transplantation has become the standard therapy for many liver diseases, mainly chronic liver disease. Most liver transplantations performed in Europe and North America utilize deceased donors while a considerable portion of organ requirements is supplied by living donors in Asian countries including Turkey. The actual history of solid organ transplantation in Turkey began with the pioneering work of Dr. Haberal in collaboration with Thomaz E. Starzl in 1974 in Colorado University at Denver. The first successful solid organ transplantation in Turkey was accomplished by Haberal in 1975 with a living donor renal transplantation. Subsequently, legislations no 2238 and 2594 dated 1979 and 1982, respectively, were passed, paving the way for cadaveric tissue/organ utilization and preservation in Turkey. The first deceased donor liver transplantation and the first living donor liver transplantation were performed in 1988 and 1990, respectively. There are currently 45 liver transplantation centers in Turkey. Of these, 25 are state universities, 8 are private (foundation) universities, 9 are private hospitals, and 3 are training and research hospitals belonging to the Ministry of Health. A total of 7152 liver transplantations were performed in Turkey between January 2002 and May 2014. Of these, 4848 (67.8%) used living donors and 2304 (32.2%) used deceased donors. These figures indicate that, despite widespread organ donation campaigns and media-sponsored propaganda, desired targets have not been met yet in providing deceased organ donation. Despite unsatisfactory levels attained in supplying deceased donors, both the number of annual liver transplantations and improvements in overall survival rates of organ transplanted patients continues to increase. Actually, the one-year patient survival rate after liver transplantation in 2013 was 80.5%. This rate is getting better with each passing year

  19. Differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation.

    PubMed

    Jiang, Shui-Ming; Zhang, Qi-Shun; Zhou, Guang-Wen; Huang, Shi-Feng; Lu, Hai-Ming; Peng, Cheng-Hong

    2010-11-01

    The aim of this study was to investigate the differences in portal hemodynamics between whole liver transplantation and living donor liver transplantation (LDLT). Twenty patients who underwent LDLT (the L group) and 42 patients who underwent whole liver transplantation (the W group) were enrolled, and colored Doppler ultrasonography was performed preoperatively and on postoperative days (PODs) 1, 3, 5, 7, 30, and 90. The changes in the portal blood flow velocity (PBV) and portal blood flow volume (PBF) were monitored. The graft and spleen sizes were measured with angiographic computed tomography, and upper endoscopy was used to measure esophageal varices on PODs 14, 30, and 90. Although the portal venous pressure (PVP) decreased after graft implantation, it was higher in the L group with a smaller graft size ratio (25.7 ± 5.1 cm H₂O for the L group and 18.5 ± 4.6 cm H₂O for the W group, P < 0.05). PBF and PBV increased in both the W and L groups on POD 1 after transplantation; however, the PBF and PBV peaks were significantly higher in the W group. The postoperative PVP and graft volume were greatly related to PBF on POD 1. Grafts in the L group regenerated rapidly after the operation, and the volume increased from 704 ± 115 to 1524 ± 281 mL as early as 1 month after transplantation. A rapid improvement in splenomegaly was observed in both groups. An improvement in esophageal varices was observed in the W group on POD 14 after transplantation, whereas no change was observed in the L group. The portal venous flow in patients with portal hypertension showed a high perfusion state after LDLT, but in contrast to whole liver transplantation, the PVP elevation after LDLT postponed the closing time of the collateral circulation and affected the recovery from splenomegaly.

  20. Bioengineered transplantable porcine livers with re-endothelialized vasculature.

    PubMed

    Ko, In Kap; Peng, Li; Peloso, Andrea; Smith, Charesa J; Dhal, Abritee; Deegan, Daniel B; Zimmerman, Cindy; Clouse, Cara; Zhao, Weixin; Shupe, Thomas D; Soker, Shay; Yoo, James J; Atala, Anthony

    2015-02-01

    Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure.

  1. Bioengineered transplantable porcine livers with re-endothelialized vasculature.

    PubMed

    Ko, In Kap; Peng, Li; Peloso, Andrea; Smith, Charesa J; Dhal, Abritee; Deegan, Daniel B; Zimmerman, Cindy; Clouse, Cara; Zhao, Weixin; Shupe, Thomas D; Soker, Shay; Yoo, James J; Atala, Anthony

    2015-02-01

    Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure. PMID:25433603

  2. Post-liver Transplant Biliary Complications.

    PubMed

    Atwal, Tegpal; Pastrana, Mariel; Sandhu, Bimaljit

    2012-03-01

    Biliary tract complications remain a common source of morbidity and mortality in liver transplant (LT) recipients with an estimated incidence of 5-30% after orthotopic LT and a mortality rate of up to 10%. Biliary complications after LT may be related to various factors including hepatic artery thrombosis or stenosis, ischemia reperfusion injury, immunologic injury, infections, donor pool, and technical issues which include imperfect anastomosis and T-tube-related complications. Management of the detected biliary complications includes nonsurgical and surgical methods. A majority of these post transplant biliary complications can be treated with endoscopic retrograde cholangiography. If unsuccessful, a percutaneous intervention or surgery may be required. In this article, we review the incidence, clinical presentation, and management of the main types of biliary complications.

  3. Liver transplantation for malignancy: Current treatment strategies and future perspectives

    PubMed Central

    Hackl, Christina; Schlitt, Hans J; Kirchner, Gabriele I; Knoppke, Birgit; Loss, Martin

    2014-01-01

    In 1967, Starzl et al performed the first successful liver transplantation for a patient diagnosed with hepatoblastoma. In the following, liver transplantation was considered ideal for complete tumor resection and potential cure from primary hepatic malignancies. Several reports of liver transplantation for primary and metastatic liver cancer however showed disappointing results and the strategy was soon dismissed. In 1996, Mazzaferro et al introduced the Milan criteria, offering liver transplantation to patients diagnosed with limited hepatocellular carcinoma. Since then, liver transplantation for malignant disease is an ongoing subject of preclinical and clinical research. In this context, several aspects must be considered: (1) Given the shortage of deceased-donor organs, long-term overall and disease free survival should be comparable with results obtained in patients transplanted for non-malignant disease; (2) In this regard, living-donor liver transplantation may in selected patients help to solve the ethical dilemma of optimal individual patient treatment vs organ allocation justice; and (3) Ongoing research focusing on perioperative therapy and anti-proliferative immunosuppressive regimens may further reduce tumor recurrence in patients transplanted for malignant disease and thus improve overall survival. The present review gives an overview of current indications and future perspectives of liver transplantation for malignant disease. PMID:24833863

  4. Biliary complications after liver transplantation: a review.

    PubMed

    Verdonk, Robert C; Buis, Carlijn I; Porte, Robert J; Haagsma, Elizabeth B

    2006-01-01

    After liver transplantation, the prevalence of complications related to the biliary system is 6-35%. In recent years, the diagnosis and treatment of biliary problems has changed markedly. The two standard methods of biliary reconstruction in liver transplant recipients are the duct-to-duct choledochocholedochostomy and the Roux-en-Y-hepaticojejunostomy. Biliary leakage occurs in approximately 5-7% of transplant cases. Leakage from the site of anastomosis, the T-tube exit site and donor or recipient remnant cystic duct is well described. Symptomatic bile leakage should be treated by stenting of the duct by endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTCD). Biliary strictures can occur at the site of the anastomosis (anastomotic stricture; AS) or at other locations in the biliary tree (non-anastomotic strictures; NAS). AS occur in 5-10% of cases and are due to fibrotic healing. Treatment by ERCP or PTCD with dilatation and progressive stenting is successful in the majority of cases. NAS can occur in the context of a hepatic artery thrombosis, or with an open hepatic artery (ischaemic type biliary lesions or ITBL). The incidence is 5-10%. NAS has been associated with various types of injury, e.g. macrovascular, microvascular, immunological and cytotoxic injury by bile salts. Treatment can be attempted with multiple sessions of dilatation and stenting of stenotic areas by ERCP or PTCD. In cases of localized diseased and good graft function, biliary reconstructive surgery is useful. However, a significant number of patients will need a re-transplant. When biliary strictures or ischaemia of the graft are present, stones, casts and sludge can develop. PMID:16782628

  5. Liver regeneration after living donor transplant

    PubMed Central

    Olthoff, Kim M.; Emond, Jean C.; Shearon, Tempie H.; Everson, Greg; Baker, Talia B.; Fisher, Robert A.; Freise, Chris E.; Gillespie, Brenda W.; Everhart, James E.

    2014-01-01

    Background & Aims Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Methods 350 donors and 353 recipients in A2ALL (Adult to Adult Living Donor Liver Transplantation Cohort Study) transplanted between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV, SLV), the model for end-stage liver disease (MELD) score (in recipients), remnant and graft size, remnant to donor and graft to recipient weight ratio (RDWR, GRWR), remnant/TLV, and graft/SLV. Results Among donors, 3-month absolute growth was 676±251g (mean± SD) and percent reconstitution was 80%±13%. Among recipients, GRWR was 1.3%±0.4% (8<0.8%). Graft weight was 60%±13% of SLV. Three-month absolute growth was 549±267g and percent reconstitution was 93%±18%. Predictors of greater 3-month liver volume included larger patient size (donors, recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth, but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (p=0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR=4.50, p=0.001), but not by GRWR or graft fraction (p>0.90 for each). Conclusions Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, confirming previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3 month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction impacts post

  6. Preoperative risk factor analysis in orthotopic liver transplant-ation with pretransplant artificial liver support therapy

    PubMed Central

    Yuan, Jin-Zhong; Ye, Qi-Fa; Zhao, Ling-Ling; Ming, Ying-Zi; Sun, Hong; Zhu, Shai-Hong; Huang, Zu-Fa; Wang, Min-Min

    2006-01-01

    AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was: 28 kept alive and 6 patients died. CONCLUSION: Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly. PMID:16937506

  7. Biliary complications in right lobe living donor liver transplantation.

    PubMed

    Chok, Kenneth S H; Lo, Chung Mau

    2016-07-01

    Living donor liver transplantation is an alternative to deceased donor liver transplantation in the face of insufficient deceased donor liver grafts. Unfortunately, the incidence of biliary complication after living donor liver transplantation is significantly higher than that after deceased donor liver transplantation using grafts from non-cardiac-death donations. The two most common biliary complications after living donor liver transplantation are bile leakage and biliary anastomotic stricture. Early treatment with endoscopic and interventional radiological approaches can achieve satisfactory outcomes. If treatment with these approaches fails, the salvage measure for prompt rectification will be surgical revision, which is now seldom performed. This paper also discusses risk factors in donor biliary anatomy that can affect recipients. PMID:26932842

  8. Liver transplantation for chronic liver disease: advances and controversies in an era of organ shortages

    PubMed Central

    Prince, M; Hudson, M

    2002-01-01

    Since liver transplantation was first performed in 1968 by Starzl et al, advances in case selection, liver surgery, anaesthetics, and immunotherapy have significantly increased the indications for and success of this operation. Liver transplantation is now a standard therapy for many end stage liver disorders as well as acute liver failure. However, while demand for cadaveric organ grafts has increased, in recent years the supply of organs has fallen. This review addresses current controversies resulting from this mismatch. In particular, methods for increasing graft availability and difficulties arising from transplantation in the context of alcohol related cirrhosis, primary liver tumours, and hepatitis C are reviewed. Together these three indications accounted for 42% of liver transplants performed for chronic liver disease in the UK in 2000. Ethical frameworks for making decisions on patients' suitability for liver transplantation have been developed in both the USA and the UK and these are also reviewed. PMID:11884694

  9. [FEATURES LIVER TRANSPLANTATION IN PORTAL VEIN THROMBOSIS].

    PubMed

    Abbasov, P A

    2015-07-01

    In 2012 - 2013 years in 265 patients for liver transplantation was performed, including in 224 (84.5%)--from a living donor, in 41 (15.5%)--from the dead body. Using a Foley catheter to stop bleeding, and the imposition of vascular sutures during endovenectomy in portal vein thrombosis (PVT) and its possible damage under all conditions. In particular, PVT IV degree (Grade IV) in order to restore blood flow in the graft using the left gastric and renal vein is an alternative, if they are cryopreserved vein may be suitably used.

  10. Mozart's Requiem–Liver Transplantation in 1988

    PubMed Central

    1990-01-01

    Liver transplantation is one of the most spectacular of surgical achievements. It is a demanding and expensive procedure, requiring great surgical skill and a great depth of supporting services. Precisely because it is a procedure at the leading edge of medicine, more and more units in developed countries are pressing to be allowed to carry it out. But there are many moral and ethical problems, some of which can be usefully examined using a “Mozart model” as proposed by Starzl. PMID:2282327

  11. Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease

    PubMed Central

    Hajifathalian, Kaveh; Humberson, Annette; Hanouneh, Mohamad A; Barnes, David S; Arora, Zubin; Zein, Nizar N; Eghtesad, Bijan; Kelly, Dympna; Hanouneh, Ibrahim A

    2016-01-01

    AIM To evaluate risk of recidivism on a case-by-case basis. METHODS From our center’s liver transplant program, we selected patients with alcoholic liver disease who were listed for transplant based on Ohio Solid Organ Transplantation Consortium (OSOTC) exception criteria. They were considered to have either a low or medium risk of recidivism, and had at least one or three or more months of abstinence, respectively. They were matched based on gender, age, and Model for End-Stage Liver Disease (MELD) score to controls with alcohol-induced cirrhosis from Organ Procurement and Transplant Network data. RESULTS Thirty six patients with alcoholic liver disease were approved for listing based on OSOTC exception criteria and were matched to 72 controls. Nineteen patients (53%) with a median [Inter-quartile range (IQR)] MELD score of 24 (13) received transplant and were followed for a median of 3.4 years. They were matched to 38 controls with a median (IQR) MELD score of 25 (9). At one and five years, cumulative survival rates (± standard error) were 90% ± 7% and 92% ± 5% and 73% ± 12% and 77% ± 8% in patients and controls, respectively (Log-rank test, P = 0.837). Four (21%) patients resumed drinking by last follow-up visit. CONCLUSION Compared to traditional criteria for assessment of risk of recidivism, a careful selection process with more flexibility to evaluate eligibility on a case-by-case basis can lead to similar survival rates after transplantation. PMID:27721920

  12. Liver transplantation in adults: Choosing the appropriate timing

    PubMed Central

    Siciliano, Maria; Parlati, Lucia; Maldarelli, Federica; Rossi, Massimo; Ginanni Corradini, Stefano

    2012-01-01

    Liver transplantation is indicated in patients with acute liver failure, decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs. Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution. Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history. However, because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other, patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical, surgical and psychological contraindications. Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity. Thus, the appropriate timing of transplantation depends on recipient disease severity and, although this is still a matter of debate, also on donor quality. These two variables are known to determine the “transplant benefit” (i.e., when the expected patient survival is better with, than without, transplantation) and should guide donor allocation. PMID:22966483

  13. Preconditioning of the liver for efficient repopulation by primary hepatocyte transplants.

    PubMed

    Krause, Petra; Rave-Frank, Margret; Christiansen, Hans; Koenig, Sarah

    2014-01-01

    The therapeutic potential of liver cell transplantation has been demonstrated in multiple clinical studies to correct hereditary metabolic or chronic liver diseases. However, there are several outstanding issues, which need to be investigated: most notably donor cell engraftment and the subsequent selective expansion of transplanted cells. This protocol describes the preconditioning of the liver in a dipeptidyl peptidase-IV (DPPIV(-))-deficient rat model of efficient repopulation utilizing a selective external beam irradiation technique combined with regional transient portal ischemia (RTPI). Irradiation of the host liver impairs endogenous cell division, and the subsequent RTPI constitutes a strongly proliferative stimulus. Transplanted cells benefit from this stimulus, whereas endogenous cells have no ability to respond, due to a reduction in the mitotic capacity of the host liver. As described here, an effective preparative regime for liver repopulation is external beam liver irradiation in the form of a single dose of 25 Gy applied to the whole organ followed (4 days later) by RTPI of the right liver lobes lasting 90 min. After 1 h of reperfusion, the donor hepatocytes may be transplanted directly into the spleen as implantation site for further redistribution into the portal system and liver. This preparative regime certainly has the potential to be implemented in the clinic, since neither toxins nor highly potent carcinogens are used.

  14. Present and Future of Regenerative Medicine: Liver Transplantation.

    PubMed

    Caralt, M

    2015-10-01

    In recent years, the creation of new organs using bioengineering has been proposed as a possible solution to the shortage of organs for transplantation. After decellularization of livers, the remaining extracellular matrix can be used as scaffolds that can be reseeded with different kinds of cells. Mature hepatocytes and fetal liver cells have been used, showing viability, functionality, and differentiation into mature cells. After perfusion in a bioreactor, the seeded scaffold or liver organoid may be transplanted. However, viability of these transplanted scaffolds is poor owing to the formation of thrombosis. We analyzed the recent advances in decellularizing and recellularizing and the results after transplantation reported in the literature.

  15. Biomarkers for detection of alcohol consumption in liver transplantation

    PubMed Central

    Staufer, Katharina; Yegles, Michel

    2016-01-01

    Alcoholic liver disease is an established, yet controversial, indication for liver transplantation. Although an abstinence period of up to 6 mo prior to transplantation is mandatory, alcohol relapse after transplantation is a common event. In case of recurrence of heavy drinking, graft survival is significantly impaired. Guidelines on detection and surveillance of alcohol consumption in this patient cohort are lacking. This review summarizes the challenge of patient selection as well as the current knowledge on established and novel alcohol biomarkers with special focus on liver transplant candidates and recipients. PMID:27076757

  16. Reducing transfusion requirements in liver transplantation.

    PubMed

    Donohue, Ciara I; Mallett, Susan V

    2015-12-24

    Liver transplantation (LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusion-free transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical "piggyback" techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management (PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT. PMID:26722645

  17. Reducing transfusion requirements in liver transplantation

    PubMed Central

    Donohue, Ciara I; Mallett, Susan V

    2015-01-01

    Liver transplantation (LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusion-free transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical “piggyback” techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management (PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT. PMID:26722645

  18. Recurrence of hepatitis C after liver transplantation

    PubMed Central

    Vinaixa, Carmen; Rubín, Angel; Aguilera, Victoria; Berenguer, Marina

    2013-01-01

    Recurrence of hepatitis C virus (HCV) infection following liver transplantation is a major source of morbidity and mortality. The natural history of hepatitis C in the transplant setting is shortened. Overall, one third of HCV-infected recipients have developed allograft cirrhosis due to HCV recurrence by the 5th-7th year post-transplantation. The most significant variables which determine disease progression are the use of organs from old donors, the use of an inadequate immunosuppression (too low, inducing treatment rejection episodes, too potent or too rapidly changing), and the presence of comorbid conditions that also impact the quality of the graft (biliary complications, metabolic syndrome). The only factor consistently shown to modify the natural history of recurrent disease is antiviral therapy. A sustained viral response, achieved by one third of those treated with dual therapy, is associated with improved histology, reduced liver-related complications and increased survival. Variables associated with enhanced viral response with dual therapy include an adequate genetic background (IL28B C/C of both donor and recipient), good treatment adherence (full doses of ribavirin, treatment duration), lack of graft cirrhosis at baseline, and viral genotype non-1. Data with triple therapy are encouraging. Response rates of about 60% at end-of-therapy have been described. Drug-drug interactions with calcineurin inhibitors are present but easily manageable with strict trough levels monitoring. Side effects are frequent and severe, particularly anemia, infections and acute renal insufficiency. In the future new oral antivirals will likely prevent viral reinfection. In this review, we will cover the most significant but also controversial aspects regarding recurrent HCV infection, including the natural history, retransplantation, antiviral therapy, and outcome in HIV-HCV patients. PMID:24714603

  19. Liver transplantation in children: part 2--long-term issues.

    PubMed

    Taylor, Rachel M; Franck, Linda S; Gibson, Faith; Dhawan, Anil

    2005-12-01

    This two-part review provides a comprehensive summary of clinical and research literature on paediatric liver transplantation. Part 2 focuses on the long-term physical consequences and psychological impact of transplantation and critically examines neurobehavioural, sexual development, psychosocial function and overall impact on children's quality of life. This review highlights the implications for clinical practice in specialist and local services and suggests areas where research is required to improve the lives of children after liver transplantation.

  20. Renal function in pediatric liver transplant patients.

    PubMed

    McDiarmid, S V

    1996-01-01

    Actuarial five-year patient survivals after pediatric orthotopic liver transplantation (OLT) of 75 to 80% are now commonplace. However, renal dysfunction after pediatric OLT remains a serious complication and maybe broadly divided into four categories. The first is pre-existing renal disease in association with liver disease. This includes tyrosinemia with Fanconi syndrome, congenital cystic disease of the liver with associated polycystic disease of the kidney, Alagille's syndrome and primary hyperoxaluria. Second is hepatorenal syndrome. Resolution is dependent on successful OLT, although short-term dialysis may be required. Children with renal failure prior to transplantation have a significantly increased mortality. Third is peri- and early post-transplant renal impairment. The four major influences on early renal function after OLT are: (i) pretransplant renal function; (ii) early liver graft function; (iii) induction therapy with cyclosporine and tacrolimus; (iv) use of other nephrotoxic drugs. Fourth is long-term nephrotoxicity of cyclosporine and tacrolimus (FK-506). Both of these essential immunosuppressives carry the risk of long-term irreversible toxicity. In one study children, treated with cyclosporine, surviving > one year after OLT, 73% had a true GFR < 77 ml/min/1.73 m2. Children treated for > or = 24 months had a significantly lower GFR than those treated from 12 to 24 months. Half the children with a GFR < or = 50 ml/min/1.73 m2 had hypertension. Another study showed that 46% of pediatric OLT patients had a > or = 20% decrease in GFR over two to four years. FK-506 nephrotoxicity is comparable to that of cyclosporine. In a randomized control trial comparing FK-506 and cyclosporine, there was a 52% decrease in GFR over the first year in the FK-506 group, which was not significantly different to that of the cyclosporine group. In 60% of patients converted from cyclosporine to FK-506 one study showed a 50% or more drop in GFR. Both FK-506 and

  1. Acute renal failure in liver transplant patients: Indian study.

    PubMed

    Naik, Pradeep; Premsagar, B; Mallikarjuna, M

    2015-01-01

    The acute renal failure is the frequent medical complication observed in liver transplant patients. The objective of this study was to determine the cause of acute renal failure in post liver transplant patients. A total of 70 patients who underwent (cadaveric 52, live 18) liver transplantation were categorized based on clinical presentation into two groups, namely hepatorenal failure (HRF, n = 29), and Hepatic failure (HF, n = 41). All the patients after the liver transplant had received tacrolimus, mycophenolate and steroids. We analyzed the modification of diet in renal disease, (MDRD) serum urea, creatinine and albumin before and after 5th and 30th day of liver transplant and data was categorized into survivors and non-survivors group. In HRF survivor group, serum creatinine, and urea levels were high and, albumin, MDRD were low in pre- transplant and reached to normal levels on 30th day of post transplant, and 79.3 % of patients in this group showed resumption of normal kidney function. On the contrary in HRF nonsurvivor group, we did not observed any significant difference and 20.7 % of patients showed irreversible changes after the liver transplant. In HF survivor group, 82.9 % of liver failure patients did not show any deviation in serum creatinine, urea, albumin and MDRD, whereas in HF non survivor group, 17.1 % of liver failure patients who had HCV positive before the transplant developed acute renal failure. The levels of creatinine, urea, albumin and MDRD were normal before the transplant and on day 30th, the levels of albumin and MDRD were significantly low whereas serum urea, creatinine levels were high. In conclusion, based on these observations, an diagnosis and treatment of Acute renal failure is important among the liver transplantation cases in the early postoperative period.

  2. Improvement of Liver Cell Therapy in Rats by Dietary Stearic Acid

    PubMed Central

    Goradel, Nasser Hashemi; Eghbal, Mohammad Ali; Darabi, Masoud; Roshangar, Leila; Asadi, Maryam; Zarghami, Nosratollah; Nouri, Mohammad

    2016-01-01

    Background: Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen (APAP)-induced liver damage. Methods: Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y (SRY) primers. Results: The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver injury were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats. Conclusion: Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury. PMID:27090202

  3. Utilization of split liver grafts in orthotopic liver transplantation.

    PubMed

    Moreno-González, E; Gómez, S R; García, G I; Loinaz, S C; González-Pinto, I; Riaño, D; Ibáñez, J; Pérez-Cerdá, F; Bercedo, J; Dávila, P

    1993-02-01

    Among a total of 220 liver transplants, reduced-size liver was used in 21 cases due to discrepancies in size between recipient and donors in 19 patients. In the case of two adult patients suffering from fulminant hepatic failure and in a critical condition, only one donor organ became available, so that the graft was divided to give the two recipients an equal opportunity. The two patients with fulminant hepatic failure were admitted to the ICU requiring mechanical respiration almost at the same time. Hepatitis serologies were HBcAb+, HBsAb+, and VCA+ in one and negative in the second. They had different blood groups (A.Rh+, O.Rh-), and the only donor available was located in Milan, Italy. The graft perfused with UW. was divided into two (right side, segments IV, V, VI, VII, and VIII, and left side, segments I, II and III). The recipients were transplanted 50 and 48 hours after admission. The cold ischemia time was 7.10 and 16.50 hours. The first patient, who received the right lobe, was extubated at 48 hours and discharged on the 40th postransplant day. The second patient remained unconscious with progressive deterioration; an EEG on the 4th day revealed absence of higher cortical function.

  4. Infectious complications in living related liver transplantation.

    PubMed

    Uemoto, S; Tanaka, K; Fujita, S; Sano, K; Shirahase, I; Kato, H; Yamamoto, E; Inomata, Y; Ozawa, K

    1994-04-01

    During the last 31 months, 50 children between 3 months and 15 years of age have undergone living related liver transplantation (LRLT) for end-stage liver diseases (39 biliary atresia, 2 Budd-Chiari syndrome, 2 progressive intrahepatic cholestasis, 3 liver cirrhosis, 1 Wilson disease, 1 protoporphyria, 1 tyrosinemia, and 1 fulminant hepatitis). Combined FK-506 and low-dose steroids were routinely used for immunosuppression. There were seven deaths, two of which were related to infection (Candida pneumonia and Epstein-Barr virus [EBV]-associated lymphoproliferative syndrome [LPS]). Five patients had a bacterial infection, all of which were associated with surgical complications. Three patients had Candida infection, all of which were malnourished, had biliary atresia, and had been managed with prolonged antibiotics against obstinate ascending cholangitis. There were 14 symptomatic viral infections (1 herpes simplex virus, 1 herpes zoster virus, 5 cytomegalovirus [CMV], 6 EBV, and 1 EBV-associated LPS). Three of the five CMV infections appeared in patients whose graft was ABO-incompatible, who were managed with prophylactic OKT-3. Most of the viral infections (except 1 EBV-associated LPS) were minor and were treated successfully. The low incidence and successful treatment of CMV infection are related to the high compatibility and low incidence of allograft rejection in LRLT. Bacterial and fungal infections can be decreased by greater refinement of surgical technique and more aggressive preoperative management. Treatment of EBV infection is still an unsolved problem.

  5. Predictors of employment after liver transplantation.

    PubMed

    Sahota, Amandeep; Zaghla, Hassan; Adkins, Rodney; Ramji, Alnoor; Lewis, Susan; Moser, Jennifer; Sher, Linda S; Fong, Tse-Ling

    2006-01-01

    Employment after orthotopic liver transplantation (OLT) indicates recipients' physical/psychosocial adjustment. Our aim was to determine clinical, socioeconomic and health-related quality of life parameters influencing employment after OLT. Questionnaire on demographics, medical conditions, alcohol and drug use before/after OLT, and a validated 12-Item Short Form Health Survey (SF-12) were mailed to 126 adult OLT patients. Stepwise logistic regression was conducted to identify best predictors of post-OLT employment. Among non-retirees, 49% were employed after OLT. The predictors of employment were: employment status, income, disability status before OLT and Model of End Stage Liver Disease score. These variables had prediction rate of 82%. Individuals working during the five yr prior to OLT were likely to return to work (p<0.0001), particularly those who held a job for >6 months prior to OLT (p<0.0001), income>$80 000 before OLT compared with <$30 000 (p=0.036). Patients receiving Social Security Insurance (SSI) payment for >or=6 months prior to OLT, were less likely to work (p=0.0005). Severity/duration of liver dysfunction prior to OLT did not correlate with employment. Sense of physical health was poorer in those employed after OLT than in unemployed (p=0.0003). Socioeconomic factors were the most important predictors of post-OLT employment. PMID:16842527

  6. Declining Liver Graft Quality Threatens the Future of Liver Transplantation in the United States

    PubMed Central

    Orman, Eric S.; Mayorga, Maria E.; Wheeler, Stephanie B.; Townsley, Rachel M.; Toro-Diaz, Hector H.; Hayashi, Paul H.; Barritt, Sidney A.

    2015-01-01

    National liver transplant volume has declined since 2006, in part due to worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next two decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating liver transplant volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer liver transplants. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. Institution of “opt-out” organ donation policies to increase the donor pool would still result in 1380-1866 fewer transplants. Ex-vivo perfusion techniques that increase the use of marginal donor livers may stabilize liver transplant volume. Otherwise, the number of liver transplants in the US will decrease substantially over the next 15 years. Conclusions The transplant community will need to accept inferior grafts and potentially worse post-transplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of liver transplants at the current level. PMID:25939487

  7. Cell transplantation after oxidative hepatic preconditioning with radiation and ischemia-reperfusion leads to extensive liver repopulation

    NASA Astrophysics Data System (ADS)

    Malhi, Harmeet; Gorla, Giridhar R.; Irani, Adil N.; Annamaneni, Pallavi; Gupta, Sanjeev

    2002-10-01

    The inability of transplanted cells to proliferate in the normal liver hampers cell therapy. We considered that oxidative hepatic DNA damage would impair the survival of native cells and promote proliferation in transplanted cells. Dipeptidyl peptidase-deficient F344 rats were preconditioned with whole liver radiation and warm ischemia-reperfusion followed by intrasplenic transplantation of syngeneic F344 rat hepatocytes. The preconditioning was well tolerated, although serum aminotransferase levels rose transiently and hepatic injury was observed histologically, along with decreased catalase activity and 8-hydroxy adducts of guanine, indicating oxidative DNA damage. Transplanted cells did not proliferate in the liver over 3 months in control animals and animals preconditioned with ischemia-reperfusion alone. Animals treated with radiation alone showed some transplanted cell proliferation. In contrast, the liver of animals preconditioned with radiation plus ischemia-reperfusion was replaced virtually completely over 3 months. Transplanted cells integrated in the liver parenchyma and liver architecture were preserved normally. These findings offer a paradigm for repopulating the liver with transplanted cells. Progressive loss of cells experiencing oxidative DNA damage after radiation and ischemia-reperfusion injury could be of significance for epithelial renewal in additional organs.

  8. Posttransplant Sarcopenia: An Underrecognized Early Consequence of Liver Transplantation

    PubMed Central

    Dasarathy, Srinivasan

    2014-01-01

    Liver transplantation is believed to reverse the clinical and metabolic abnormalities of cirrhosis. Reduced skeletal muscle mass or sarcopenia contributes to increased mortality and adverse consequences of cirrhosis. Failure of reversal of sarcopenia of cirrhosis after liver transplantation is not well recognized. Six temporally, geographically, and methodologically distinct follow-up studies in 304 cirrhotics reported conflicting data on changes in indirect measures of skeletal muscle mass after transplantation. Distinct measures of body composition but not skeletal muscle mass were used and did not focus on the clinical consequences of sarcopenia after transplantation. A number of studies reported an initial rapid postoperative loss of lean mass followed by incomplete recovery with a maximum follow-up of 2 years. Posttransplant sarcopenia may be responsible for metabolic syndrome and impaired quality of life after liver transplantation. Potential reasons for failure to reverse sarcopenia after liver transplantation include use of immunosuppressive agents [mammalian target of rapamycin (mTOR) and calcineurin inhibitors] that impair skeletal muscle growth and protein accretion. Repeated hospitalizations, posttransplant infections, and renal failure also contribute to posttransplant sarcopenia. Finally, recovery from muscle deconditioning is limited by lack of systematic nutritional and physical-activity-based interventions to improve muscle mass. Despite the compelling data on sarcopenia before liver transplantation, the impact of posttransplant sarcopenia on clinical outcomes is not known. There is a compelling need for studies to examine the mechanisms and consequences of sarcopenia post liver transplantation to permit development of therapies to prevent and reverse this disorder. PMID:23912247

  9. The morphological changes in transplanted tumors in rats at plasmonic photothermal therapy

    NASA Astrophysics Data System (ADS)

    Bucharskaya, Alla B.; Maslyakova, Galina N.; Navolokin, Nikita A.; Dikht, Nataliya I.; Terentyuk, Georgy S.; Bashkatov, Alexey N.; Genina, Elina A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

    2016-04-01

    The aim of work was to study the morphological changes in transplanted liver tumors of rats after plasmonic photothermal therapy (PPTT). The gold nanorods functionalized with thiolated polyethylene glycol were injected intravenously to rats with transplanted liver cancer PC-1. A day after injection the tumors were irradiated by the infrared 808-nm diode laser. The withdrawal of the animals from the experiment and sampling of tumor tissue for morphological study were performed 24 hours after the laser exposure. The standard histological and immunohistochemical staining with antibodies to proliferation marker Ki-67 and apoptosis marker BAX were used for morphological study of transplanted tumors. The plasmonic photothermal therapy had pronounced damaging effect in rats with transplanted liver tumors expressed in degenerative and necrotic changes in the tumor cells. The decrease of proliferation marker Ki-67 and increase of expression of apoptosis marker BAX were observed in tumor cells after PPTT.

  10. Current status of auxiliary partial orthotopic liver transplantation for acute liver failure.

    PubMed

    Rela, Mohamed; Kaliamoorthy, Ilankumaran; Reddy, Mettu Srinivas

    2016-09-01

    Auxiliary partial orthotopic liver transplantation (APOLT) is a technique of liver transplantation (LT) where a partial liver graft is implanted in an orthotopic position after leaving behind a part of the native liver. APOLT was previously considered technically challenging with results inferior to orthotopic liver transplantation. Results of this procedure have continued to improve with improving surgical techniques and a better understanding of the natural history of acute liver failure (ALF) and liver regeneration. The procedure is being increasingly accepted as a valid treatment option for ALF-especially in children. This article reviews the historical background to this operation, advances in the technique, and its current place in the management of ALF. Liver Transplantation 22 1265-1274 2016 AASLD. PMID:27357489

  11. Posttransplant lymphoproliferative disorders following liver transplantation: Where are we now?

    PubMed Central

    Dierickx, Daan; Cardinaels, Nina

    2015-01-01

    Liver transplantation has emerged as a life-saving treatment for several patients with acute liver failure, end stage liver disease and primary hepatic malignancies. However, long term immunosuppressive therapy aiming to reduce the risk of transplant rejection increases the incidence of several complications including malignancies. This is illustrated by the observation of a high ratio between observed and expected cases of lymphoproliferative disorders following liver transplantation. Despite a huge heterogeneity in morphological appearance of these disorders ranging from reactive-like lesions to real lymphomas, they are collectively termed posttransplant lymphoproliferative disorders. In this review we will provide an overview of this rare but challenging disorder as a complication of liver transplantation. PMID:26494960

  12. Pediatric liver transplantation in metabolic disease: clinical decision making.

    PubMed

    Shneider, Benjamin L

    2002-02-01

    Proper utilization of liver transplantation in the management of pediatric metabolic diseases requires a comprehensive understanding of both metabolic disease and the risk and benefits of transplantation. This brief review focuses on issues that pertain to the treatment of tyrosinemia type I, bile acid biosynthesis disorders, primary hyperoxaluria, Crigler-Najjar Type I, and mitochondrial diseases. These entities are used as prototypes to illustrate many of the principles that are applied in a more general sense to the management of metabolic diseases. The natural history of these disorders are considered in the context of the risks of liver transplantation. Indications, contraindications, and both current and future alternatives to transplantation, are considered.

  13. Brain death and marginal grafts in liver transplantation

    PubMed Central

    Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C

    2015-01-01

    It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation. PMID:26043077

  14. From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant.

    PubMed

    Reddy, Sheela S; Civan, Jesse M

    2016-05-01

    This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending. PMID:27095638

  15. Liver transplantation for advanced hepatocellular carcinoma

    PubMed Central

    Lee, Hae Won; Suh, Kyung-Suk

    2016-01-01

    There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future. PMID:27729631

  16. Ischemia time and liver transplantation, today.

    PubMed

    Maggi, U; Fornoni, G; Centonze, L; Melada, E; Conte, G; Rossi, G

    2014-09-01

    The aim of our study was to retrospectively evaluate the impact of ischemia time and other clinical factors on the development of liver allograft primary nonfunction (PNF). We enrolled 531 consecutive liver transplantations from 1998 to 2013, identifying 10 PNF (1.9%). PNF was found to be statistically related to 4 different variables: donor age>60 years (P=.01), female donor gender (P=.01), total ischemia time>10 hours (P=.03) and infusion of more than 30 fresh frozen plasma units during surgery (P=.02). The study focused on the clinical impact of total ischemia time. We grouped total ischemia time into 4 groups (Group 1: ≤7.5 hours; Group 2: between 7.5 and 10 hours; Group 3: between 10 and 12 hours; Group 4: >12 hours) and 2 groups (assigning a cut-off value of 10 hours): both these grouping systems significantly influenced the development of PNF and 1-year graft survival, with limited impact on long-term survival. We split total ischemia time in a "technical time," "hepatectomy time," and "warm ischemia time." Only the first 2 components were found to be statistically related to PNF development with P=.02 and P=.003, respectively. Further studies should focus on these aspects of PNF. PMID:25242773

  17. Underutilization of palliative care services in the liver transplant population

    PubMed Central

    Kathpalia, Priya; Smith, Alexander; Lai, Jennifer C

    2016-01-01

    AIM To evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant. METHODS Evaluated were end-stage liver disease patients who were removed from the liver transplant wait-list or died prior to transplant at a single transplant center over a 2-year period. Those who were removed due to noncompliance or ultimately transplanted elsewhere were excluded from this study. Patient characteristics associated with palliative care consultation were assessed using logistic regression analysis. RESULTS Six hundred and eighty-three patients were listed for liver transplant in 2013-2014 with 107 (16%) dying (n = 62) or removed for clinical decompensation prior to liver transplant (n = 45): Median age was 58 years, and the majority were male (66%), Caucasian (53%), had Child C cirrhosis (61%) or hepatocellular carcinoma (52%). The palliative care team was consulted in only 18 of the 107 patients (17%) who died or were removed, 89% of which occurred as inpatients. Half of these consultations occurred within 72 h of death. In univariable analysis, patients of younger age, white race, and higher end-stage liver disease scores at time of listing and delisting were more likely to receive palliative care services. Only younger age [Odds ratio (OR) = 0.92; P = 0.02] and Caucasian race (OR = 4.90; P = 0.02) were still associated with integration of palliative care services through multivariable analysis. CONCLUSION Palliative care services are grossly underutilized in older, non-white patients with cirrhosis on the liver transplant wait-list. We encourage early integration of these services into clinical decision-making in the transplant population, with further studies aimed at understanding barriers to consultation. PMID:27683638

  18. Underutilization of palliative care services in the liver transplant population

    PubMed Central

    Kathpalia, Priya; Smith, Alexander; Lai, Jennifer C

    2016-01-01

    AIM To evaluate use of palliative care services in patients with end-stage liver disease who do not have access to liver transplant. METHODS Evaluated were end-stage liver disease patients who were removed from the liver transplant wait-list or died prior to transplant at a single transplant center over a 2-year period. Those who were removed due to noncompliance or ultimately transplanted elsewhere were excluded from this study. Patient characteristics associated with palliative care consultation were assessed using logistic regression analysis. RESULTS Six hundred and eighty-three patients were listed for liver transplant in 2013-2014 with 107 (16%) dying (n = 62) or removed for clinical decompensation prior to liver transplant (n = 45): Median age was 58 years, and the majority were male (66%), Caucasian (53%), had Child C cirrhosis (61%) or hepatocellular carcinoma (52%). The palliative care team was consulted in only 18 of the 107 patients (17%) who died or were removed, 89% of which occurred as inpatients. Half of these consultations occurred within 72 h of death. In univariable analysis, patients of younger age, white race, and higher end-stage liver disease scores at time of listing and delisting were more likely to receive palliative care services. Only younger age [Odds ratio (OR) = 0.92; P = 0.02] and Caucasian race (OR = 4.90; P = 0.02) were still associated with integration of palliative care services through multivariable analysis. CONCLUSION Palliative care services are grossly underutilized in older, non-white patients with cirrhosis on the liver transplant wait-list. We encourage early integration of these services into clinical decision-making in the transplant population, with further studies aimed at understanding barriers to consultation.

  19. Living Related Liver Transplantation in an Infant with Neonatal Hemochromatosis

    PubMed Central

    Choi, Shin Jie; Choi, Jong Sub; Chun, Peter; Yoo, Jung Kyung; Moon, Jin Soo; Kim, Woo Sun; Kang, Gyeong Hoon; Yi, Nam-Joon

    2016-01-01

    Neonatal hemochromatosis (NH) is a severe neonatal liver injury that is confirmed by extra-hepatic iron accumulation. Although a recent study described treating NH with exchange transfusions and intravenous immunoglobulin, liver transplantation should be considered for patients with severe liver failure that does not respond to other medical treatment. Herein, we report the case of a two-month-old female infant who presented with persistent ascites and hyperbilirubinemia. Her laboratory findings demonstrated severe coagulopathy, high indirect and direct bilirubin levels, and high ferritin levels. Abdominal magnetic resonance imaging presented low signal intensity in the liver on T2-weighted images, suggesting iron deposition. The infant was diagnosed with NH as a result of the clinical findings and after congenital infection and metabolic diseases were excluded. The infant was successfully treated with a living-donor liver transplantation. Living related liver transplantation should be considered as a treatment option for NH in infants. PMID:27437193

  20. Living Related Liver Transplantation in an Infant with Neonatal Hemochromatosis.

    PubMed

    Choi, Shin Jie; Choi, Jong Sub; Chun, Peter; Yoo, Jung Kyung; Moon, Jin Soo; Ko, Jae Sung; Kim, Woo Sun; Kang, Gyeong Hoon; Yi, Nam-Joon

    2016-06-01

    Neonatal hemochromatosis (NH) is a severe neonatal liver injury that is confirmed by extra-hepatic iron accumulation. Although a recent study described treating NH with exchange transfusions and intravenous immunoglobulin, liver transplantation should be considered for patients with severe liver failure that does not respond to other medical treatment. Herein, we report the case of a two-month-old female infant who presented with persistent ascites and hyperbilirubinemia. Her laboratory findings demonstrated severe coagulopathy, high indirect and direct bilirubin levels, and high ferritin levels. Abdominal magnetic resonance imaging presented low signal intensity in the liver on T2-weighted images, suggesting iron deposition. The infant was diagnosed with NH as a result of the clinical findings and after congenital infection and metabolic diseases were excluded. The infant was successfully treated with a living-donor liver transplantation. Living related liver transplantation should be considered as a treatment option for NH in infants. PMID:27437193

  1. Isolating Lysosomes from Rat Liver.

    PubMed

    Pryor, Paul R

    2016-04-01

    This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays.

  2. Fatigue and related factors after liver transplantation

    PubMed Central

    Hong, Kwangpyo; Kim, Hyeyoung; Lee, Jeong-Moo; Lee, Kwang-Woong; Yi, Nam-Joon; Lee, Hae Won; Choi, YoungRok; Suh, Suk-Won; Hong, Suk Kyun; Yoon, Kyung Chul; Kim, Hyo-Sin

    2015-01-01

    Backgrounds/Aims Fatigue is common in chronic hepatitis and end-stage liver disease. However, little is known about fatigue after liver transplantation (LT). We therefore evaluated the prevalence, severity, and related factors of fatigue after LT. Methods We retrospectively reviewed adult recipients who responded to our survey at outpatient clinics between April and May 2013. Fatigue and its severity were assessed using a questionnaire with the Fatigue Severity Scale (FSS). We defined fatigue as FSS of 4.0 or more and severe fatigue as FSS of 5.1 or more. The related factors including hepatocellular carcinoma and complications were analyzed. Results A total of 93 patients were included in this study. The mean age was 54.9 (19-76) years and two-thirds were men (67.7%). Living donor LT was 77.4%. Hepatitis B related liver disease was the main underlying disease (77.4%), with hepatocellular carcinoma accompanied in 33.3%. The mean follow-up period was 66.8±43.2 (2-171) months. The mean FFS was 2.83±1.48 (1.0-6.7) overall and 5.10±0.82 (4.0-6.7) in the fatigue group. Of the 93 adult patients, fatigue was presented in 20 patients (21.5%). Among these, 9 patients (45.0%) showed severe fatigue. Even though post-LT complications tended to be greater in the fatigue group (50.0% vs. 30.1% in the non-fatigue group, p=0.098), there were no significant related factors of fatigue after LT, including hepatocellular carcinoma and major complication. Conclusions Fatigue is present in a considerable portion of recipients after LT, and almost half of them have severe fatigue. Further efforts are needed to decrease fatigue in LT recipients. PMID:26693233

  3. An update on liver transplantation: A critical review.

    PubMed

    Neuberger, James

    2016-01-01

    Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems.

  4. [The Application of Machine Perfusion on Clinical Liver Transplantation].

    PubMed

    Ren, Fenggang; Zhu, Haoyang; Yan, Xiaopeng; Liu, Chang; Zhang, Xiaogang; Lv, Yi

    2015-11-01

    Liver transplantation is the only way to treat end-stage liver disease. In order to overcome the shortage of donor, marginal donors have been used widely, which bring about a series of problems. Machine perfusion can stimulate the circulation in vivo and is beneficial for the protection of liver. It could also improve the graft function and reduce postoperative complications, which makes it a hot spot in recent years. The aim of this study is to summarize the current status and prospects of application of machine perfusion on clinical liver transplantation.

  5. Hepatic haemangioendothelioma in adults: excellent outcome following liver transplantation.

    PubMed

    Lerut, Jan P; Orlando, Giuseppe; Sempoux, Christine; Ciccarelli, Olga; Van Beers, Bernard E; Danse, Etienne; Horsmans, Yves; Rahier, Jacques; Roggen, Francine

    2004-05-01

    Hepatic epithelioid haemangioendotheliomas (HEHEs) are rare, low-grade vascular tumours. Five adults with HEHEs and one adult with a vascular tumour showing combined features of haemangioma and haemangioendothelioma underwent liver transplantation. Two HEHE patients had extrahepatic metastases at the time of transplantation. Median survival time following diagnosis was 10.7 years (range 40 months to 195 months). One patient needed resection of a HEHE in the breast 13 years post-transplantation. All six patients are surviving free from disease 22 to 166 months after transplantation (median 77 months). One HEHE-patient who had been treated for 8 years for vertebral and cerebral localisations is free of disease without immunosuppression 56 months after transplantation. We can conclude that liver transplantation is a valuable treatment for hepatic haemangioendothelioma, even in cases of extrahepatic localisation of the disease. PMID:15114438

  6. Perioperative thrombotic complications in liver transplantation

    PubMed Central

    Feltracco, Paolo; Barbieri, Stefania; Cillo, Umberto; Zanus, Giacomo; Senzolo, Marco; Ori, Carlo

    2015-01-01

    Although the perioperative bleeding complications and the major side effects of blood transfusion have always been the primary concern in liver transplantation (OLT), the possible cohesion of an underestimated intrinsic hypercoagulative state during and after the transplant procedure may pose a major threat to both patient and graft survival. Thromboembolism during OLT is characterized not only by a complex aetiology, but also by unpredictable onset and evolution of the disease. The initiation of a procoagulant process may be triggered by various factors, such as inflammation, venous stasis, ischemia-reperfusion injury, vascular clamping, anatomical and technical abnormalities, genetic factors, deficiency of profibrinolytic activity, and platelet activation. The involvement of the arterial system, intracardiac thrombosis, pulmonary emboli, portal vein thrombosis, and deep vein thrombosis, are among the most serious thrombotic events in the perioperative period. The rapid detection of occlusive vascular events is of paramount importance as it heavily influences the prognosis, particularly when these events occur intraoperatively or early after OLT. Regardless of the lack of studies and guidelines on anticoagulant prophylaxis in this setting, many institutions recommend such an approach especially in the subset of patients at high risk. However, the decision of when, how and in what doses to use the various chemical anticoagulants is still a difficult task, since there is no common consensus, even for high-risk cases. The risk of postoperative thromboembolism causing severe hemodynamic events, or even loss of graft function, must be weighed and compared with the risk of an important bleeding. In this article we briefly review the risk factors and the possible predictors of major thrombotic complications occurring in the perioperative period, as well as their incidence and clinical features. Moreover, the indications to pharmacological prophylaxis and the current

  7. Primary amyloidosis with spontaneous splenic rupture, cholestasis, and liver failure treated with emergency liver transplantation.

    PubMed

    Sandberg-Gertzén, H; Ericzon, B G; Blomberg, B

    1998-11-01

    A 61-yr-old man with cholestatic jaundice soon after presentation had an emergency operation because of spontaneous rupture of the spleen. This was found to be caused by primary systemic amyloidosis. After the splenectomy, the patient deteriorated with liver failure and was successfully treated with liver transplantation. Osteopenic fractures of the thoracic columna developed after transplantation. Except for this, the patient is well 18 months after transplantation.

  8. Current concepts on cytomegalovirus infection after liver transplantation

    PubMed Central

    Lee, Sang-Oh; Razonable, Raymund R

    2010-01-01

    Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, valganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. In this article, the authors review the

  9. Physical activity and metabolic syndrome in liver transplant recipients.

    PubMed

    Kallwitz, Eric R; Loy, Veronica; Mettu, Praveen; Von Roenn, Natasha; Berkes, Jamie; Cotler, Scott J

    2013-10-01

    There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross-sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3-299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389-6.092] and older age (OR = 1.036, 95% CI = 1.001-1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536-0.887), older age (OR = 1.056, 95% CI = 1.014-1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300-13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver

  10. Liver transplantation in the management of unresectable hepatoblastoma in children.

    PubMed

    Meyers, Rebecka L; Tiao, Greg M; Dunn, Stephen P; Langham, Max R

    2012-01-01

    Complete surgical resection is essential to long-term survival in children with hepatoblastoma. We present the guidelines from the Children's Oncology Group (COG), liver tumor study group of the Societe Internationale Oncologie Pediatrique (SIOPEL), and German Pediatric Oncology Group (GPOH) for early referral of children with potentially unresectable hepatoblastoma to a specialty center with expertise in extreme resection and liver transplantation. Patients who will become candidates for liver transplantation should receive chemotherapy following the same protocols as for children undergoing a partial hepatectomy. The Pediatric Liver Unresectable Tumor Observatory (PLUTO) is an international prospective database established to collect data and make future recommendations on controversial issues regarding the use of transplant in hepatoblastoma including: 1) What is the optimal treatment of multifocal tumors. 2) What is the role of extreme resection vs. liver transplant in patients with major venous involvement. 3) What is the role of transplant in patients who present with lung metastasis. 3) Should patients with tumor relapse be offered a rescue transplant. 4) What is the role of pre- and post- transplant chemotherapy. PMID:22201955

  11. Strategies to reduce hepatitis C virus recurrence after liver transplantation

    PubMed Central

    Ciria, Ruben; Pleguezuelo, María; Khorsandi, Shirin Elizabeth; Davila, Diego; Suddle, Abid; Vilca-Melendez, Hector; Rufian, Sebastian; de la Mata, Manuel; Briceño, Javier; Cillero, Pedro López; Heaton, Nigel

    2013-01-01

    Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients. PMID:23717735

  12. Three-dimensional print of a liver for preoperative planning in living donor liver transplantation.

    PubMed

    Zein, Nizar N; Hanouneh, Ibrahim A; Bishop, Paul D; Samaan, Maggie; Eghtesad, Bijan; Quintini, Cristiano; Miller, Charles; Yerian, Lisa; Klatte, Ryan

    2013-12-01

    The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers.

  13. Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

    PubMed

    Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

    2016-07-01

    Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. PMID:27405894

  14. Cardiac Failure after Liver Transplantation Requiring a Biventricular Assist Device

    PubMed Central

    Soe, Eiei; D'Alessandro, David; Shin, Julia; Jakobleff, William; Schwartz, Daniel; Kinkhabwala, Milan; Gaglio, Paul J.

    2014-01-01

    Increased hepatic iron load in extrahepatic organs of cirrhotic patients with and without hereditary hemochromatosis portends a poorer long term prognosis after liver transplant. Hepatic as well as nonhepatic iron overload is associated with increased infectious and postoperative complications, including cardiac dysfunction. In this case report, we describe a cirrhotic patient with alpha 1 antitrypsin deficiency and nonhereditary hemochromatosis (non-HFE) that developed cardiogenic shock requiring mechanical circulatory support for twenty days after liver transplant. Upon further investigation, she was found to have significant iron deposition in both the liver and heart biopsies. Her heart regained complete and sustained recovery following ten days of mechanical biventricular support. This case highlights the importance of preoperatively recognizing extrahepatic iron deposition in patients referred for liver transplantation irrespective of etiology of liver disease as this may prevent postoperative complications. PMID:25431733

  15. Current status and perspectives in split liver transplantation.

    PubMed

    Lauterio, Andrea; Di Sandro, Stefano; Concone, Giacomo; De Carlis, Riccardo; Giacomoni, Alessandro; De Carlis, Luciano

    2015-10-21

    Growing experience with the liver splitting technique and favorable results equivalent to those of whole liver transplant have led to wider application of split liver transplantation (SLT) for adult and pediatric recipients in the last decade. Conversely, SLT for two adult recipients remains a challenging surgical procedure and outcomes have yet to improve. Differences in organ shortages together with religious and ethical issues related to cadaveric organ donation have had an impact on the worldwide distribution of SLT. Despite technical refinements and a better understanding of the complex liver anatomy, SLT remains a technically and logistically demanding surgical procedure. This article reviews the surgical and clinical advances in this field of liver transplantation focusing on the role of SLT and the issues that may lead a further expansion of this complex surgical procedure. PMID:26494957

  16. Decreased collagen types I and IV, laminin, CK-19 and α-SMA expression after bone marrow cell transplantation in rats with liver fibrosis.

    PubMed

    Carvalho, S N; Lira, D C; Oliveira, G P; Thole, A A; Stumbo, A C; Caetano, C E; Marques, R G; Carvalho, L

    2010-11-01

    Bone marrow cells have frequently been tested in animal models of liver fibrosis to assess their role in hepatic regeneration. The mononuclear fraction of bone marrow cells is of particular interest, as many studies show that these cells may be beneficial to treat hepatic fibrosis. In this study, we used the bile duct ligation model to induce hepatic fibrosis in an irreversible manner, and rats were treated with bone marrow mononuclear (BMMN) cells after fibrosis was established. Analysis of collagen types I and IV, laminin and α-SMA showed a decreased expression of these proteins in fibrotic livers after 7 days of BMMN cell injection. Moreover, cytokeratin-19 analysis showed a reduction in bile ducts in the BMMN cell-treated group. These results were accompanied by ameliorated levels of hepatic enzymes GPT (Glutamic-pyruvic transaminase), GOT (glutamic-oxaloacetic transaminase) and alkaline phosphatase (AP). Therefore, we showed that BMMN cells decrease hepatic fibrosis by significantly reducing myofibroblast numbers and through reduction of the collagen and laminin-rich extracellular matrix of fibrotic septa and hepatic sinusoids.

  17. Treatment Experience of Severe Abdominal Infection after Orthotopic Liver Transplantation

    PubMed Central

    Wang, Y-G; Wu, J-S; Jiang, B; Wang, J-H; Liu, C-P; Peng, C; Tian, B-Z

    2015-01-01

    ABSTRACT This study aims to investigate the causes and treatment experience of severe abdominal infection after orthotopic liver transplantation. Clinical data were retrospectively analysed in perioperative severe abdominal infection of 186 orthotopic liver transplantation cases from March 2004 to November 2011. Among the 186 patients, 16 cases had severe abdominal infection: five cases had bile duct anastomotic leakage-inducing massive hydrops and infection under liver interstice, 10 cases had extensive bleeding of surgical wound leading to massive haematocele and infection around the liver, and one case had postoperative lower oesophageal fistula leakage causing massive hydrops and infection under the left diaphragm. After definite diagnosis, 12 cases underwent surgery within three days, with no death. Among the four cases that underwent surgery three days after diagnosis, one case died of multiple-organ failure five days after abdominal cavity exploration, which was performed 21 days after liver transplantation. Severe abdominal infections after liver transplantation were the most common causes of death in perioperative liver transplantation. Comprehensive treatment with efficacious antibiotics, multiple-organ support, controlled surgical removal of the lesion, and adequate drainage establishment was the key to the entire treatment. PMID:26426173

  18. Frailty predicts waitlist mortality in liver transplant candidates.

    PubMed

    Lai, J C; Feng, S; Terrault, N A; Lizaola, B; Hayssen, H; Covinsky, K

    2014-08-01

    We aimed to determine whether frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, predicts mortality in liver transplant candidates. Consecutive adult outpatients listed for liver transplant with laboratory Model for End-Stage Liver Disease (MELD) ≥ 12 at a single center (97% recruitment rate) underwent four frailty assessments: Fried Frailty, Short Physical Performance Battery (SPPB), Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales. Competing risks models associated frailty with waitlist mortality (death/delisting for being too sick for liver transplant). Two hundred ninety-four listed liver transplant patients with MELD ≥ 12, median age 60 years and MELD 15 were followed for 12 months. By Fried Frailty score ≥3, 17% were frail; 11/51 (22%) of the frail versus 25/243 (10%) of the not frail died/were delisted (p = 0.03). Each 1-unit increase in the Fried Frailty score was associated with a 45% (95% confidence interval, 4-202) increased risk of waitlist mortality adjusted for MELD. Similarly, the adjusted risk of waitlist mortality associated with each 1-unit decrease (i.e. increasing frailty) in the Short Physical Performance Battery (hazard ratio 1.19, 95% confidence interval 1.07-1.32). Frailty is prevalent in liver transplant candidates. It strongly predicts waitlist mortality, even after adjustment for liver disease severity demonstrating the applicability and importance of the frailty construct in this population.

  19. Liver transplantation in glycogen storage disease type I

    PubMed Central

    2014-01-01

    Glycogen storage disease type I (GSDI), an inborn error of carbohydrate metabolism, is caused by defects in the glucose-6-transporter/glucose-6-phosphatase complex, which is essential in glucose homeostasis. Two types exist, GSDIa and GSDIb, each caused by different defects in the complex. GSDIa is characterized by fasting intolerance and subsequent metabolic derangements. In addition to these clinical manifestations, patients with GSDIb suffer from neutropenia with neutrophil dysfunction and inflammatory bowel disease. With the feasibility of novel cell-based therapies, including hepatocyte transplantations and liver stem cell transplantations, it is essential to consider long term outcomes of liver replacement therapy. We reviewed all GSDI patients with liver transplantation identified in literature and through personal communication with treating physicians. Our review shows that all 80 GSDI patients showed improved metabolic control and normal fasting tolerance after liver transplantation. Although some complications might be caused by disease progression, most complications seemed related to the liver transplantation procedure and subsequent immune suppression. These results highlight the potential of other therapeutic strategies, like cell-based therapies for liver replacement, which are expected to normalize liver function with a lower risk of complications of the procedure and immune suppression. PMID:24716823

  20. Recipient-derived hepatocytes in liver transplants: a rare event in sex-mismatched transplants.

    PubMed

    Fogt, Franz; Beyser, Kurt H; Poremba, Christopher; Zimmerman, Robert L; Khettry, Urmila; Ruschoff, Josef

    2002-07-01

    Bone marrow-derived stem cells have been shown to engraft and populate native tissues during repair and in transplanted animal tissues. Very few studies have been performed in humans to evaluate the possibility of stem cell engraftment in transplanted tissues. In human renal transplants, recipient cells have been demonstrated within vascular and interstitial structures. In a previous study of patients with hepatic transplants, hepatocytes with XY chromosome patterns have been detected in sex-mismatched female to male transplanted livers in a small number of cases. Because of the possibility of Y chromosome microchimerism of females with male offspring, we analyzed the presence of X and Y chromosomes in liver biopsies of 13 patients with sex-mismatched liver transplants (8 female to male, 5 male to female) and long transplant to biopsy intervals (1.2 to 12 years; mean, 4.5 years). We were able to detect recipient-specific sex chromosomal patterns in inflammatory cells by fluorescent in situ hybridization/immunohistochemistry combination within the liver parenchyma but not within hepatocytes. In conclusion, recipient engraftment of stem cells may be an early feature in liver transplant but may be an infrequent persistent feature in long-term grafts.

  1. Societal reintegration following cadaveric orthotopic liver transplantation

    PubMed Central

    Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah

    2016-01-01

    Background Studies on patients’ societal reintegration following orthotopic liver transplantation (OLT) are scarce. Methods Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re-integration following OLT and potential barriers they might have encountered. Results Among 157 eligible patients 110 (70%) participated. Mean participants’ age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. Conclusions Although patients’ satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients’ economical status and societal ability to recoup resources committed for OLT. PMID:27275465

  2. Cell sources, liver support systems and liver tissue engineering: alternatives to liver transplantation.

    PubMed

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-05-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  3. Cell Sources, Liver Support Systems and Liver Tissue Engineering: Alternatives to Liver Transplantation

    PubMed Central

    Lee, Soo Young; Kim, Han Joon; Choi, Dongho

    2015-01-01

    The liver is the largest organ in the body; it has a complex architecture, wide range of functions and unique regenerative capacity. The growing incidence of liver diseases worldwide requires increased numbers of liver transplant and leads to an ongoing shortage of donor livers. To meet the huge demand, various alternative approaches are being investigated including, hepatic cell transplantation, artificial devices and bioprinting of the organ itself. Adult hepatocytes are the preferred cell sources, but they have limited availability, are difficult to isolate, propagate poor and undergo rapid functional deterioration in vitro. There have been efforts to overcome these drawbacks; by improving culture condition for hepatocytes, providing adequate extracellular matrix, co-culturing with extra-parenchymal cells and identifying other cell sources. Differentiation of human stem cells to hepatocytes has become a major interest in the field of stem cell research and has progressed greatly. At the same time, use of decellularized organ matrices and 3 D printing are emerging cutting-edge technologies for tissue engineering, opening up new paths for liver regenerative medicine. This review provides a compact summary of the issues, and the locations of liver support systems and tissue engineering, with an emphasis on reproducible and useful sources of hepatocytes including various candidates formed by differentiation from stem cells. PMID:26019753

  4. Information needs of family caregivers regarding liver transplant candidates.

    PubMed

    Sá, Amanda Silva; Ziviani, Luciana Costa; Castro-E-Silva, Orlando; Galvão, Cristina Maria; Mendes, Karina Dal Sasso

    2016-03-01

    Objective To assess the information needs of family caregivers of candidates on the waiting list for a liver transplant. Methods It is a cross-sectional study conducted in a transplant center in São Paulo State in the period between April and October of 2012. For the assessment of information needed, an instrument submitted to face and content value was used. The caregivers put 10 subjects in order according to their importance and the amount of interest they had in learning about each, prior to the transplant their family member would be subjected to. Sociodemographic characteristics were also recorded. For data analysis, descriptive statistics were used. Results 42 families participated in the study. The information need about liver disease complications, complications after transplantation and care needed after surgery had higher averages. Conclusions Knowing the information needs of caregivers is important to plan teaching-learning strategies aimed at improving assistance to patients and families in transplant programs.

  5. Portopulmonary Hypertension and Liver Transplant: Recent Review of the Literature.

    PubMed

    Cosarderelioglu, Caglar; Cosar, Arif M; Gurakar, Merve; Pustavoitau, Aliaksei; Russell, Stuart D; Dagher, Nabil N; Gurakar, Ahmet

    2016-04-01

    Portopulmonary hypertension is one of the main pulmonary conditions affecting patients with liver disease and/or portal hypertension. Other conditions include hepatopulmonary syndrome and hepatic hydrothorax. Portopulmonary hypertension is caused by pulmonary vasoconstriction and increased pulmonary vascular resistance. It develops as a result of portal hypertension with or without liver disease and is associated with a higher morbidity and mortality. However, portopulmonary hypertension is usually asymptomatic; the most common symptoms are dyspnea, fatigue, and peripheral edema. All liver transplant candidates should be screened for potential portopulmonary hypertension because its coexistence can affect survival rates after transplant. All patients with cirrhosis who present with dyspnea should also be screened. Transthoracic echocardiography is a noninvasive, useful method for screening, but right heart-sided catheterization remains the criterion standard for diagnosis. Portopulmonary hypertension carries a poor prognosis without liver transplant, and its severe form is considered to be a contraindication for liver transplant. Treating patients with pulmonary arterial hypertension-specific therapies before liver transplant for moderate and severe portopulmonary hypertension appears to be beneficial. PMID:27015528

  6. The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation

    PubMed Central

    Qi, Xiang; Ng, Kevin Tak-Pan; Shao, Yan; Li, Chang Xian; Geng, Wei; Ling, Chang Chun; Ma, Yuen Yuen; Liu, Xiao Bing; Liu, Hui; Liu, Jiang; Yeung, Wai Ho; Lo, Chung Mau; Man, Kwan

    2016-01-01

    Background and Aims: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth. GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study. Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation. Methods: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established. To investigate the clinical relevance of GPx3, 105 HCC patients who underwent liver transplantation were recruited. The suppressive role of GPx3 in HCC cells was studied using wound healing, Matrigel invasion assay and lung metastasis model. The real-time intravital imaging system was applied to directly visualize the tumor cells invasion in a living animal. The underlying mechanism was further explored. Results: GPx3 was identified as a down-regulated protein in small-for-size liver graft and significantly associated with invasive phenotype of tumor growth in a rat model. Plasma GPx3 was significantly lower in small-for-size graft group post-transplantation (day1: 33 vs 1147; day3: 3209 vs 4459; day7: 303 vs 2506; mU/mL, P<0.05) in rat model. Clinically, the plasma GPx3 was significantly lower in the recipients with HCC recurrence post-transplantation (day1: 4.16 vs 8.99 µg/mL, P<0.001; day7: 3.86 vs 9.99 µg/mL, P<0.001). Furthermore, lower plasma GPx3 was identified as an independent predictor (HR=4.528, P=0.046) for poor overall survival post-transplantation. Over-expression of GPx3 significantly suppressed migration, invasiveness and metastasis of HCC cells. Real-time intravital imaging showed that GPx3 significantly suppressed HCC invasiveness in a live animal. GPx3 suppressed the tumor invasiveness through inhibition of JNK-cJun-MMP2 pathway. Conclusion: GPx3 may possess prognostic and therapeutic

  7. When Your Child Needs a Liver Transplant

    MedlinePlus

    ... Your Child for Surgery Hepatitis Hereditary Hemochromatosis Digestive System Blood Test: Hepatic (Liver) Function Panel What Happens in the Operating Room? Hepatitis Your Liver Your Digestive System Anesthesia - ...

  8. Evaluation of liver transplant candidates: A pulmonary perspective

    PubMed Central

    Bozbas, Serife Savas; Eyuboglu, Fusun

    2011-01-01

    Chronic liver disease is one of the leading causes of mortality and morbidity in the worldwide adult population. Liver transplant is the gold standard therapy for end-stage liver disease and many patients are on the waiting list for a transplant. A variety of pulmonary disorders are encountered in cirrhotic patients. Pleura, lung parenchyma, and pulmonary vasculature may be affected in these patients. Hypoxemia is relatively common and can be asymptomatic. Hepatopulmonary syndrome should be investigated in hypoxic cirrhotic patients. Gas exchange abnormalities are common and are generally correlated with the severity of liver disease. Both obstructive and restrictive types of airway disease can be present. Abnormal diffusion capacity is the most frequently observed pulmonary function disorder in patients with cirrhosis. Hepatic hydrothorax is another finding which is usually seen in conjunction with, but occasionally without ascites. Portopulmonary hypertension is a complication of long standing liver dysfunction and when severe, is accepted as a containdication to liver transplant. Since respiratory disorders are common and have significant impact on postoperative outcome in patients undergoing liver transplant, a careful preoperative pulmonary assessment is important. PMID:21760840

  9. Liver transplantation in the Nordic countries – An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982–2013

    PubMed Central

    Fosby, Bjarte; Melum, Espen; Bjøro, Kristian; Bennet, William; Rasmussen, Allan; Andersen, Ina Marie; Castedal, Maria; Olausson, Michael; Wibeck, Christina; Gotlieb, Mette; Gjertsen, Henrik; Toivonen, Leena; Foss, Stein; Makisalo, Heikki; Nordin, Arno; Sanengen, Truls; Bergquist, Annika; Larsson, Marie E.; Soderdahl, Gunnar; Nowak, Greg; Boberg, Kirsten Muri; Isoniemi, Helena; Keiding, Susanne; Foss, Aksel; Line, Pål-Dag; Friman, Styrbjörn; Schrumpf, Erik; Ericzon, Bo-Göran; Höckerstedt, Krister; Karlsen, Tom H.

    2015-01-01

    Abstract Aim and background. The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013. Materials and methods. The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report. Results. Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004–2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively. Conclusion. The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR). PMID:25959101

  10. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    PubMed Central

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis. PMID:27049380

  11. Adherence to immunosuppressive therapy following liver transplantation: an integrative review

    PubMed Central

    Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

    2016-01-01

    ABSTRACT Objective: to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. Method: integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. Results: were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. Conclusion: there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. PMID:27579933

  12. Role of liver transplantation in human immunodeficiency virus positive patients

    PubMed Central

    Joshi, Deepak; Agarwal, Kosh

    2015-01-01

    End-stage liver disease (ESLD) is a leading cause of morbidity and mortality amongst human immunodeficiency virus (HIV)-positive individuals. Chronic hepatitis B and hepatitis C virus (HCV) infection, drug-induced hepatotoxicity related to combined anti-retro-viral therapy, alcohol related liver disease and non-alcohol related fatty liver disease appear to be the leading causes. It is therefore, anticipated that more HIV-positive patients with ESLD will present as potential transplant candidates. HIV infection is no longer a contraindication to liver transplantation. Key transplantation outcomes such as rejection and infection rates as well as medium term graft and patient survival match those seen in the non-HIV infected patients in the absence of co-existing HCV infection. HIV disease does not seem to be negatively impacted by transplantation. However, HIV-HCV co-infection transplant outcomes remain suboptimal due to recurrence. In this article, we review the key challenges faced by this patient cohort in the pre- and post-transplant period. PMID:26604639

  13. Monogenic diseases that can be cured by liver transplantation.

    PubMed

    Fagiuoli, Stefano; Daina, Erica; D'Antiga, Lorenzo; Colledan, Michele; Remuzzi, Giuseppe

    2013-09-01

    While the prevalence of most diseases caused by single-gene mutations is low and defines them as rare conditions, all together, monogenic diseases account for approximately 10 in every 1000 births according to the World Health Organisation. Orthotopic liver transplantation (LT) could offer a therapeutic option in monogenic diseases in two ways: by substituting for an injured liver or by supplying a tissue that can replace a mutant protein. In this respect, LT may be regarded as the correction of a disease at the level of the dysfunctional protein. Monogenic diseases that involve the liver represent a heterogeneous group of disorders. In conditions associated with predominant liver parenchymal damage (i.e., genetic cholestatic disorders, Wilson's disease, hereditary hemochromatosis, tyrosinemia, α1 antitrypsin deficiency), hepatic complications are the major source of morbidity and LT not only replaces a dysfunctional liver but also corrects the genetic defect and effectively cures the disease. A second group includes liver-based genetic disorders characterised by an architecturally near-normal liver (urea cycle disorders, Crigler-Najjar syndrome, familial amyloid polyneuropathy, primary hyperoxaluria type 1, atypical haemolytic uremic syndrome-1). In these defects, extrahepatic complications are the main source of morbidity and mortality while liver function is relatively preserved. Combined transplantation of other organs may be required, and other surgical techniques, such as domino and auxiliary liver transplantation, have been attempted. In a third group of monogenic diseases, the underlying genetic defect is expressed at a systemic level and liver involvement is just one of the clinical manifestations. In these conditions, LT might only be partially curative since the abnormal phenotype is maintained by extrahepatic synthesis of the toxic metabolites (i.e., methylmalonic acidemia, propionic acidemia). This review focuses on principles of diagnosis, management

  14. Outcomes of liver transplantation in patients with hepatorenal syndrome

    PubMed Central

    Modi, Rohan M; Patel, Nishi; Metwally, Sherif N; Mumtaz, Khalid

    2016-01-01

    Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community. PMID:27648152

  15. Outcomes of liver transplantation in patients with hepatorenal syndrome.

    PubMed

    Modi, Rohan M; Patel, Nishi; Metwally, Sherif N; Mumtaz, Khalid

    2016-08-28

    Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m(2) may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community. PMID:27648152

  16. Outcomes of liver transplantation in patients with hepatorenal syndrome

    PubMed Central

    Modi, Rohan M; Patel, Nishi; Metwally, Sherif N; Mumtaz, Khalid

    2016-01-01

    Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.

  17. Bone marrow-derived progenitor cells in de novo liver regeneration in liver transplant.

    PubMed

    Lee, Sung-Gyu; Moon, Sung-Hwan; Kim, Hee-Je; Lee, Ji Yoon; Park, Soon-Jung; Chung, Hyung-Min; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Hojong; Kwon, Tae-Won; Cho, Yong-Pil

    2015-09-01

    The study was designed (1) to examine the hypothesis that circulating progenitor cells play a role in the process of de novo regeneration in human liver transplants and that these cells arise from a cell population originating in, or associated with, the bone marrow and (2) to investigate whether the transplanted liver volume has an effect on the circulating recipient-derived progenitor cells that generate hepatocytes during this process. Clinical data and liver tissue characteristics were analyzed in male individuals who underwent sex-mismatched adult-to-adult living donor liver transplantation using dual left lobe grafts. Dual left lobe grafts were examined at the time of transplantation and 19 to 27 days after transplantation. All recipients showed recovery of normal liver function and a significant increase in the volume of the engrafted left lobes after transplantation. Double staining for a Y-chromosome probe and the CD31 antigen showed the presence of hybrid vessels composed of recipient-derived cells and donor cells within the transplanted liver tissues. Furthermore, CD34-expressing cells were observed commingling with Y-chromosome+ cells. The ratio of recipient-derived vessels and the number of Y+ CD34+ cells tended to be higher when smaller graft volumes underwent transplantation. These findings suggest that the recruitment of circulating bone marrow-derived progenitor cells could contribute to vessel formation and de novo regeneration in human liver transplants. Moreover, graft volume may be an important determinant for the active mobilization of circulating recipient-derived progenitor cells and their contribution to liver regeneration.

  18. Liver Transplantation in Antituberculosis Drugs-Induced Fulminant Hepatic Failure

    PubMed Central

    Li, Xiaoyan; Liu, Yujie; Zhang, Erhong; He, Qiong; Tang, Yong-Bo

    2015-01-01

    Abstract The antituberculosis drugs isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) usually expose patients to the risk of fulminant hepatic failure (FHF). This report presents a case of liver transplantation in antituberculosis drugs-induced FHF and reviews the relevant literature. A 39-year-old woman with pelvic and salpinx tuberculosis experienced complex pelvic exenteration. After the operation, she was administrated INH, RMP, PZA, and EMB to prevent tuberculosis. Two months later, examination revealed severe FHF and the antituberculosis therapy regimen was changed to ciprofloxacin and streptomycin. Subsequently, urgent orthotopic liver transplantation was performed. Posttransplantation, her serum transaminases improved gradually, but her total bilirubin level and direct bilirubin level continued to worsen, which may have been related to the rejection. However, irreversible damage from antituberulosis drugs was note excluded. Two liver biopsies and histological examinations were performed. One year after transplantation, she died as a consequence of ischemic cholangitis and pulmonary infection. A literature review revealed 9 other published cases of antituberculosis drugs-associated FHF with liver transplantation. This report suggests that, in most cases of antituberculosis drugs-induced FHF, discontinuation of toxic drugs and orthotopic liver transplantation are always sufficient treatment. PMID:26656321

  19. Venous outflow obstruction and portopulmonary hypertension after orthotopic liver transplantation

    PubMed Central

    Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo

    2013-01-01

    Patient: Female, 54 Final Diagnosis: Suprahepatic inferior vena cava anastomosis stricture Symptoms: Ascites • fatigue • lower limb edema • hepatomegaly Medication: — Clinical Procedure: — Specialty: Transplantology • Critical Care Medicine Objective: Unusual clinical course Background: Suprahepatic inferior vena cava anastomosis stricture is an unusual vascular complication after orthotopic liver transplantation with the “piggyback” technique. Clinical manifestations are dependent upon the severity of the stenosis. Portopulmonary hypertension after orthotopic liver transplantation is a complication that carries high mortality due to cardiopulmonary dysfunction. The pathogenesis of pulmonary vascular disorders after orthotopic liver transplantation remains uncertain. Case Report: We report a case of acute right heart pressure overload after surgical correction of the suprahepatic inferior vena cava anastomotic stricture in a 54-year-old woman who had preexisting pulmonary arterial hypertension associated with portal hypertension after orthotopic liver transplantation. Twenty months posttransplantation, she developed fatigue and progressive ascites. On admission, the patient had hepatomegaly, ascites, and lower limb edema. Symptoms in the patient developed gradually over time. Conclusions: Recurrent portal hypertension by vascular complications is a cause of pulmonary arterial hypertension after orthotopic liver transplantation. Clinical manifestations of suprahepatic inferior vena cava anastomotic stenosis are dependent upon their severity. Sildenafil is an effective drug for treatment of pulmonary arterial hyper-tension after portal hypertension by vascular complications. PMID:24046802

  20. [Diagnosis of rejection in a transplanted liver].

    PubMed

    Sticová, Eva; Honsová, Eva

    2015-01-01

    Despite advances in immunosupressive therapy rejection remains the most common complication of liver transplantation in both the early and the late post-transplant period. Unlike other solid organs, liver graft rejection has some specific characteristics likely attributable to the unique immunobiologic properties and the remarkable regenerative capabilities of liver parenchyma. Acute cellular rejection is the most frequent type of the rejection episode in the liver allograft, whereas chronic (ductopenic) rejection and humoral rejection are uncommon. Since the clinical findings are not entirely characteristic, histopathological evaluation of liver biopsy remains the gold standard in the diagnosis of rejection. However, the close cooperation between the pathologist and the clinician is essential for the correct interpretation of morphologic changes.

  1. [The system of hemostasis in experimental liver transplantation].

    PubMed

    Zhidkov, I L; Michailov, I E; Broun, N K; Smirnova, L A; Buianov, V V; Eramishantsev, A K

    1997-01-01

    The status of haemostatic factors in 28 pigs after orthotopic liver transplantation was evaluated. The major changes took place in fibrinolytic system during the "non-liver" stage: rapid increase of fibrinolytic activity, plasmin activity, plasmin activator activity. From the moment of blood supply restoration to a transplanted liver the tendency to normalisation of fibrinolysis was detected. The deficiency of plasma haemostatic factors and platelets has increased during all the follow-up period and should be corrected in time. The following principles of corrective therapy are formulated: inhibition of fibrinolysis, correction of antithrombin-3 and blood clotting factors. Correction of haemostasis should be done in "pre-non-liver" period and later in "non-liver" reperfusion periods.

  2. Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation

    PubMed Central

    Abdoh, Qusay A.; Abaalkhail, Faisal A.; Al Sebayel, Mohammed; Al-Hussaini, Hussa F.; Helmy, Hazem; Almansour, Mohamad; Elsiesy, Hussien A.

    2016-01-01

    HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation. PMID:27446853

  3. Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation.

    PubMed

    Abdoh, Qusay A; Alnajjar, Asma M; Abaalkhail, Faisal A; Al Sebayel, Mohammed; Al-Hussaini, Hussa F; Al-Hamoudi, Waleed K; Helmy, Hazem; Almansour, Mohamad; Elsiesy, Hussien A

    2016-01-01

    HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation. PMID:27446853

  4. [Treatment of alcoholic liver diseases. Abstinence, nutritional support, drug therapy, liver transplantation].

    PubMed

    Pár, A

    2000-04-16

    The review summarizes clinically established treatment forms of alcoholic liver disease in four main chapters: abstinence, nutritional supportation, drug therapy and liver transplantation are discussed. Drug therapy is described according to the three types of alcoholic hepatopathies (fatty liver, hepatitis and cirrhosis). Early diagnosis and treatment depending on the severity and stage of alcoholic liver disease are of importance for the attempts to retard progression and improve prognosis. PMID:10817009

  5. The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut?

    PubMed

    Ling, Qi; Xu, Xiao; Wang, Baohong; Li, Lanjuan; Zheng, Shusen

    2016-04-01

    New-onset diabetes is a frequent complication after solid organ transplantation. Although a number of common factors are associated with the disease, including recipient age, body mass index, hepatitis C infection, and use of immunosuppressive drugs, new-onset diabetes after liver transplantation (NODALT) has the following unique aspects and thus needs to be considered its own entity. First, a liver graft becomes the patient's primary metabolic regulator after liver transplantation, but this would not be the case for kidney or other grafts. The metabolic states, as well as the genetics of the graft, play crucial roles in the development of NODALT. Second, dysfunction of the islets of Langerhans is common in cirrhotic patients and would be exacerbated by immunosuppressive agents, particularly calcineurin inhibitors. On the other hand, minimized immunosuppressive protocols have been widely advocated in liver transplantation because of liver tolerance (immune privilege). Third and last, through the "gut-liver axis," graft function is closely linked to gut microbiota, which is now considered an important metabolic organ and known to independently influence the host's metabolic homeostasis. Liver transplant recipients present with specific gut microbiota that may be prone to trigger metabolic disorders. In this review, we proposed 3 possible sites for the origin of NODALT, which are liver, islets, and gut, to help elucidate the underlying mechanism of NODALT.

  6. The Role of Liver Transplantation in the Management of Paediatric Liver Tumours

    PubMed Central

    Stringer, Mark D

    2007-01-01

    In recent years, considerable progress has been made in the treatment of children with hepatoblastoma largely due to effective pre-operative chemotherapy. Total hepatectomy and liver transplantation has emerged as an effective treatment for the small proportion of children with unresectable hepatoblastoma limited to the liver. A 5-year survival of 70% can be achieved in such cases. In contrast, the results of liver transplantation in children with hepatocellular cancer remain poor because these tumours are usually advanced with evidence of major vascular invasion and/or extrahepatic spread at the time of presentation. An exception is those children in whom the hepatocellular carcinoma is detected during surveillance of chronic liver disease – they typically have smaller tumours and frequently have a good prognosis after liver transplantation. The role of liver transplantation in children with other primary hepatic malignancies remains uncertain because experience is very limited. Liver transplantation is rarely needed in the management of children with benign liver tumours but, if other treatments have failed, it can be a life-saving intervention. PMID:17316514

  7. ANESTHETIC MANAGEMENT DURING COMBINED LIVER AND KIDNEY TRANSPLANTATION.

    PubMed

    El Kouny, Amr; Harbi, Mohammed; Ismail, Hesham; Abouras, Chadi; Basha, Abdulatif; Abojeesh, Ibrahim; Naeim, Annas; Kashkoush, Sami; Khalid, Abdullah; Ohali, Wael; Dimitriou, Vassilios

    2016-06-01

    Combined liver and kidney transplantation is a highly demanding and challenging procedure for anesthesiologists due to the lengthy and complicated nature of the procedure, the critical patient condition and the need to balance the intravascular volume to maintain the venous outflow of the hepatic allograft and also the diuresis of the renal allograft. Intravascular volume management and coagulation control, seem to be the most important issues during combined liver and kidney transplantation. There is sparsity of data in the literature concerning the anesthetic and fluid management in CLKT. We present and discuss the anesthetic management in a case series in three patients, who underwent combined liver and kidney transplantation in our institution during the last two years. PMID:27487641

  8. Liver transplantation in Latin America: the state-of-the-art and future trends.

    PubMed

    Salvalaggio, Paolo R; Caicedo, Juan C; de Albuquerque, Luiz Carneiro; Contreras, Alan; Garcia, Valter D; Felga, Guilherme E; Maurette, Rafael J; Medina-Pestana, José O; Niño-Murcia, Alejandro; Pacheco-Moreira, Lucio F; Rocca, Juan; Rodriguez-Davalos, Manuel; Ruf, Andres; Rusca, Luis A Caicedo; Vilatoba, Mario

    2014-08-15

    We reviewed the current status of liver transplantation in Latin America. We used data from the Latin American and Caribbean Transplant Society and national organizations and societies, as well as information obtained from local transplant leaders. Latin America has a population of 589 million (8.5% of world population) and more than 2,500 liver transplantations are performed yearly (17% of world activity), resulting in 4.4 liver transplants per million people (pmp) per year. The number of liver transplantations grows at 6% per year in the region, particularly in Brazil. The top liver transplant rates were found in Argentina (10.4 pmp), Brazil (8.4 pmp), and Uruguay (5.5 pmp). The state of liver transplantation in some countries rivals those in developed countries. Model for End-Stage Liver Disease-based allocation, split, domino, and living-donor adult and pediatric transplantations are now routinely performed with outcomes comparable to those in advanced economies. In contrast, liver transplantation is not performed in 35% of Latin American countries and lags adequate resources in many others. The lack of adequate financial coverage, education, and organization is still the main limiting factor in the development of liver transplantation in Latin America. The liver transplant community in the region should push health care leaders and authorities to comply with the Madrid and Istambul resolutions on organ donation and transplantation. It must pursue fiercely the development of registries to advance the science and quality control of liver transplant activities in Latin America.

  9. Pyruvate carboxylase deficiency--insights from liver transplantation.

    PubMed

    Nyhan, William L; Khanna, Ajai; Barshop, Bruce A; Naviaux, Robert K; Precht, Andrew F; Lavine, Joel E; Hart, Marquis A; Hainline, Bryan E; Wappner, Rebecca S; Nichols, Sharon; Haas, Richard H

    2002-01-01

    Pyruvate carboxylase deficiency, complex form, presents in early infancy with lethal metabolic acidosis, resulting from ketoacidosis and lactic acidemia. Renal tubular acidosis, hyperammonemia, and citrullinemia complete the picture. In an infant with this disease, large amounts of glucose ameliorated the ketoacidosis, but worsened the lactic acidosis. Orthotopic hepatic transplantation completely reversed the ketoacidosis and the renal tubular abnormality and ameliorated the lactic acidemia. Concentrations of glutamine in cerebrospinal fluid were low and did not improve with liver transplantation.

  10. Atypical Presentation of Cytomegalovirus Infection in a Liver Transplant Patient

    PubMed Central

    Bansal, Naresh; Arora, Anil; Kumaran, Vinay; Mehta, Naimish; Varma, Vibha; Sharma, Praveen; Tyagi, Pankaj; Sachdeva, Munish; Kumar, Ashish

    2012-01-01

    Cytomegalovirus (CMV) is the most common viral infection in solid organ transplant recipients. Symptomatic infection usually presents with fever, pneumonia, colitis, or cytopenia. We describe a case of symptomatic CMV infection in a liver transplant recipient presenting with atypical symptoms of only persistent nausea and vomiting, in the absence of classical symptoms and signs; thus, highlighting the importance of high index of suspicion of CMV in immunocompromised patients, keeping in mind the high morbidity and mortality associated with this disease. PMID:25755388

  11. Massive haemorrhage in liver transplantation: Consequences, prediction and management.

    PubMed

    Cleland, Stuart; Corredor, Carlos; Ye, Jia Jia; Srinivas, Coimbatore; McCluskey, Stuart A

    2016-06-24

    From its inception the success of liver transplantation has been associated with massive blood loss. Massive transfusion is classically defined as > 10 units of red blood cells within 24 h, but describing transfusion rates over a shorter period of time may reduce the potential for survival bias. Both massive haemorrhage and transfusion are associated with increased risk of mortality and morbidity (need for dialysis/surgical site infection) following liver transplantation although causality is difficult to prove due to the observational design of most trials. The blood loss associated with liver transplantation is multifactorial. Portal hypertension secondary to cirrhosis results in extensive collateral circulation, which can bleed during hepatectomy particular if portal pressures are increased. Avoiding volume loading and maintenance of a low central venous pressure together with the use of vasopressors have been shown to reduce blood loss and transfusion during liver transplantation, but may increase the risk of renal impairment post-operatively. Coagulation defects may be present pre-transplant, but haemostasis is often re-balanced due to a deficit in both pro- and anti-coagulation factors. Further derangement of haemostasis may develop in the anhepatic and neohepatic phases due to absent hepatic metabolic function, hyperfibrinolysis and platelet sequestration in the donor liver. Point-of-care tests of coagulation such as the viscoelastic tests rotation thromboelastometry/thromboelastometry allow and more accurate and rapid assessment of these derangements in coagulation and guide the use of factor replacement and antifibrinolytics. Transfusion protocols guided by these tests have been shown to reduce transfusion rates compared with conventional coagulation tests, but have not shown improvements in mortality or morbidity. Pre-operative factors associated with massive transfusion include previous surgery, re-do transplantation, the aetiology and severity of liver

  12. Massive haemorrhage in liver transplantation: Consequences, prediction and management

    PubMed Central

    Cleland, Stuart; Corredor, Carlos; Ye, Jia Jia; Srinivas, Coimbatore; McCluskey, Stuart A

    2016-01-01

    From its inception the success of liver transplantation has been associated with massive blood loss. Massive transfusion is classically defined as > 10 units of red blood cells within 24 h, but describing transfusion rates over a shorter period of time may reduce the potential for survival bias. Both massive haemorrhage and transfusion are associated with increased risk of mortality and morbidity (need for dialysis/surgical site infection) following liver transplantation although causality is difficult to prove due to the observational design of most trials. The blood loss associated with liver transplantation is multifactorial. Portal hypertension secondary to cirrhosis results in extensive collateral circulation, which can bleed during hepatectomy particular if portal pressures are increased. Avoiding volume loading and maintenance of a low central venous pressure together with the use of vasopressors have been shown to reduce blood loss and transfusion during liver transplantation, but may increase the risk of renal impairment post-operatively. Coagulation defects may be present pre-transplant, but haemostasis is often re-balanced due to a deficit in both pro- and anti-coagulation factors. Further derangement of haemostasis may develop in the anhepatic and neohepatic phases due to absent hepatic metabolic function, hyperfibrinolysis and platelet sequestration in the donor liver. Point-of-care tests of coagulation such as the viscoelastic tests rotation thromboelastometry/thromboelastometry allow and more accurate and rapid assessment of these derangements in coagulation and guide the use of factor replacement and antifibrinolytics. Transfusion protocols guided by these tests have been shown to reduce transfusion rates compared with conventional coagulation tests, but have not shown improvements in mortality or morbidity. Pre-operative factors associated with massive transfusion include previous surgery, re-do transplantation, the aetiology and severity of liver

  13. Rapid height growth after liver transplantation in adulthood.

    PubMed

    Szili, Balázs; Görög, Dénes; Gerlei, Zsuzsanna; Győri, Gabriella; Lakatos, Péter; Takács, István

    2016-08-01

    Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia, hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The exact mechanism of short stature in this disease is unclear, the most feasible possibility is that it is caused by impairment of growth-hormone and insulin-like growth factor I axis. Here we report the case of a patient who showed typical symptoms of glycogen storage disease Ib since his infancy, his height being under 1 percentile since then. Later-developed hypothyroidism and hypogonadism have also contributed to his short stature. Hypothyroidism was treated but sexual steroid substitution was not started because of an increased risk of hepatic adenomas. Because he developed hepatic adenoma at the age of 23, he had to undergo orthotopic liver transplantation. At the time of the transplantation his height was 128cm. The transplantation was followed by rapid height growth; our patient's height reached 160.3cm 62months after transplantation. We observed that while his IGF-I level increased, his GH level remained unchanged. During the post-transplantation period we ensured adequate calcium and vitamin D supplementation, leaving hormonal substitution unchanged. According to our knowledge, this is the first report of a rapid height growth as big as 32cm, of an individual over the age of 20, not related to endocrine treatment but liver transplantation. PMID:27041087

  14. Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

    PubMed

    Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

    2010-06-27

    The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

  15. Challenging hepatitis C-infected liver transplant patients

    PubMed Central

    Oliver, Madeleine; Ortiz, Christopher Chiodo; Ortiz, Jorge

    2016-01-01

    Caring for liver transplant patients suffering from chronic hepatitis C virus (HCV) infection is a challenging task for transplant surgeons and primary physicians alike. HCV is the leading cause of liver transplantation in the USA and comes with a myriad of complications that increase morbidity and mortality. This review focuses on patient follow-up, spanning from before the liver transplant occurs to the patient’s long-term health. Pretransplant, both donor and recipient variables, must be carefully chosen to ensure optimal surgical success. Risk factors must be identified and HCV viral load must be reduced to a minimum. In addition to standard transplant complications, HCV patients suffer from additional problems, such as fibrosing cholestatic hepatitis and widespread viremia. Physicians must focus on the balance of immunosuppressive and antiviral medications, while considering possible side effects from these potent drugs. Over the years following surgery, physicians must identify any signs of failing liver health, as HCV-positive patients have an increased risk for cirrhosis and certain life-threatening malignancies. PMID:26889091

  16. Fontan-associated liver disease: Implications for heart transplantation.

    PubMed

    Greenway, Steven C; Crossland, David S; Hudson, Mark; Martin, Steven R; Myers, Robert P; Prieur, Tim; Hasan, Asif; Kirk, Richard

    2016-01-01

    Chronic liver diseases are associated with multiple complications, including cirrhosis, portal hypertension, ascites, synthetic dysfunction and hepatocellular carcinoma, and these processes are increasingly recognized in post-Fontan patients. Fontan-associated liver disease (FALD) can be defined as abnormalities in liver structure and function that result from the Fontan circulation and are not related to another disease process. FALD arises due to chronic congestion of the liver created by the elevated venous pressure and low cardiac output of the Fontan circulation, which may be superimposed on previous liver injury. Pathology studies have generally shown that FALD worsens as time post-Fontan increases, but the prevalence of FALD is not well defined because the majority of Fontan patients, even those with significant hepatic fibrosis, appear to be asymptomatic and biochemical or functional hepatic abnormalities are usually subtle or absent. Alternate non-invasive investigations, derived from the study of other chronic liver diseases, have been tested in small series of pediatric and adult Fontan patients, but they have been confounded by congestion and do not correlate well with liver biopsy findings. Liver disease can complicate Fontan circulatory failure and may even be significant enough to be considered a contraindication to heart transplantation or require combined heart-liver transplantation. The search for the optimal management strategy continues in the setting of increasing numbers of Fontan patients surviving to adulthood and being referred for heart transplantation. Thus, in this review we attempt to define the scope and significance of FALD and address transplant-related assessment and management of this challenging disorder. PMID:26586487

  17. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  18. Clinical application of modern ultrasound techniques after liver transplantation.

    PubMed

    Teegen, Eva Maria; Denecke, Timm; Eisele, Robert; Lojewski, Christian; Neuhaus, Peter; Chopra, Sascha Santosh

    2016-10-01

    Liver transplantation has been established as a first-line therapy for a number of indications. Conventional ultrasound and contrast-enhanced ultrasound (CEUS) are methods of choice during the postoperative period as a safe and fast tool to detect potential complications and to enable early intervention if necessary. CEUS increases diagnostic quality and is an appropriate procedure for the examination of vessels and possibly bile ducts. This article presents the state of the art of ultrasound application during the early period after liver transplantation. It addresses common vascular complications and describes the identification of postoperative abnormal findings using ultrasound and CEUS.

  19. Kidney and liver transplantation in children with fibrocystic liver-kidney disease: data from the US Scientific Registry of Transplant Recipients: 1990-2010.

    PubMed

    Wen, Jessica W; Furth, Susan L; Ruebner, Rebecca L

    2014-11-01

    The natural history and survival of children with fibrocystic liver-kidney disease undergoing solid organ transplantation have infrequently been described. We report outcomes in a cohort of US children with fibrocystic liver-kidney disease receiving solid organ transplants over 20 yr. Retrospective cohort study of pediatric transplant recipients with diagnoses of fibrocystic liver-kidney disease from 1/1990 to 3/2010, using data from the SRTR. Subjects were categorized by the first transplanted organ: LT, KT, or SLK. Primary outcomes were death, re-transplant, transplant of the alternate organ, or initiation of dialysis. Seven hundred and sixteen subjects were transplanted in this period. Median age at first transplant was 9.7 yr. Of the LT, 14 (19%) required a second liver transplant at median of 0.2 yr, and five (7%) required kidney transplant or dialysis at a median of 9.0 yr. Of the KT, 188 (31%) required a second kidney transplant or dialysis at a median of 5.9 yr. Twenty-nine (5%) subsequently received liver transplant at a median of 6.0 yr. Among patients in this registry, far more children underwent kidney than liver transplants. The risk of subsequently needing transplantation of an alternate organ was low.

  20. Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment

    PubMed Central

    Hartmann, Matthias; Szalai, Cynthia; Saner, Fuat H

    2016-01-01

    Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation system: While it is important to recognize that procoagulant factors are reduced in liver cirrhosis, it is also evident that synthesis of anticoagulant factors and fibrinolytic proteins produced in the liver is also diminished. Similarly, the decreased platelet count may be counterbalanced by increased platelet aggregability caused by highly active von Willebrand multimeres. The coagulation system is therefor stated to be rebalanced. While under normal “unstressed” conditions diffuse bleeding is rarely observed, however both diffuse bleeding or thrombus formation may occur when compensation mechanisms are exhausted. While most patients presenting for liver transplantation have severe cirrhosis, liver function and thus production of pro- and anticoagulant factors can be preserved especially in cholestatic liver disease. During liver transplantation, profound changes in the hemostasis system can occur. Surgical bleeding can lead to diffuse bleeding as coagulation factors and platelets are already reduced. Ischemia and tissue trauma can lead to alterations of hemostasis comparable to trauma induced coagulopathy. A further common disturbance often starting with the reperfusion of the transplanted organ is hyperfibrinolysis which can eventually precipitate complete consumption of fibrinogen and an endogenous heparinization by glycocalyx shedding. Moreover, thrombotic events in liver transplantations are not uncommon and contribute to increased mortality. Besides conventional

  1. Dynamics of defective hepatitis C virus clones in reinfected liver grafts in liver transplant recipients: ultradeep sequencing analysis.

    PubMed

    Ohtsuru, Shigeru; Ueda, Yoshihide; Marusawa, Hiroyuki; Inuzuka, Tadashi; Nishijima, Norihiro; Nasu, Akihiro; Shimizu, Kazuharu; Koike, Kaoru; Uemoto, Shinji; Chiba, Tsutomu

    2013-11-01

    Hepatitis C virus (HCV) reinfects liver allografts in transplant recipients by replicating immediately after transplantation, causing a rapid increase in blood serum HCV RNA levels. We evaluated dynamic changes in the viral genetic complexity after HCV reinfection of the graft liver; we also identified the characteristics of replicating HCV clones using a massively parallel ultradeep sequencing technique to determine the full-genome HCV sequences in the liver and serum specimens of five transplant recipients with genotype 1b HCV infection before and after liver transplantation. The recipients showed extremely high genetic heterogeneity before transplantation, and the HCV population makeup was not significantly different between the liver and blood serum specimens of the individuals. Viral quasispecies complexity in serum was significantly lower after liver transplantation than before it, suggesting that certain HCV clones selectively proliferated after transplantation. Defective HCV clones lacking the structural region of the HCV genome did not increase in number, and full-genome HCV clones selectively increased in number immediately after liver transplantation. A re-increase in the same defective clone existing before transplantation was detected 22 months after transplantation in one patient. Ultradeep sequencing technology revealed that the genetic heterogeneity of HCV was reduced after liver transplantation. Dynamic changes in defective HCV clones after liver transplantation indicate that these clones have important roles in the HCV life cycle. PMID:23985907

  2. MR tracking of SPIO-labeled mesenchymal stem cells in rats with liver fibrosis could not monitor the cells accurately.

    PubMed

    Zhou, Bin; Li, Dan; Qian, Jiesheng; Li, Zhengran; Pang, Pengfei; Shan, Hong

    2015-01-01

    Our previous study showed that in vivo magnetic resonance (MR) imaging is effective in tracking superparamagnetic iron oxide (SPIO)-labeled bone marrow mesenchymal stem cells (BMSCs) in rats with liver fibrosis. SPIO-labeling-induced signal reduction on MR images was completely reversed within 15 days after transplantation. It is still unclear whether the signal changes in MR imaging could reflect the number of transplanted cells in the liver. In the present study, BMSCs of male rats were doubly labeled with enhanced green fluorescent protein (EGFP) and SPIO and injected intravascularly into female rats with liver fibrosis. At different time points after injection, MR imaging was performed. The distribution of SPIO particles and EGFP-positive cells was determined by Prussian blue staining and EGFP immunohistochemistry, respectively. The distribution of transplanted BMSCs in various organs was assessed by detection of the SRY gene using real-time quantitative PCR. At 15 days post transplantation, the numbers of transplanted cells were significantly decreased in the lung, kidney, spleen and muscle, but not liver and heart, in comparison with those at 7 days after transplantation. EGFP staining-positive cells were observed in the liver intralobular parenchyma, while Prussian blue staining was negative at 42 days after transplantation. Taken together, SPIO particles and EGFP-labeled BMSCs show a different tissue distribution pattern in rats with liver fibrosis after a long-term period of monitoring. SPIO-based MR imaging may not be suitable for long-term tracking of transplanted BMSCs in vivo. PMID:26153152

  3. MR tracking of SPIO-labeled mesenchymal stem cells in rats with liver fibrosis could not monitor the cells accurately.

    PubMed

    Zhou, Bin; Li, Dan; Qian, Jiesheng; Li, Zhengran; Pang, Pengfei; Shan, Hong

    2015-01-01

    Our previous study showed that in vivo magnetic resonance (MR) imaging is effective in tracking superparamagnetic iron oxide (SPIO)-labeled bone marrow mesenchymal stem cells (BMSCs) in rats with liver fibrosis. SPIO-labeling-induced signal reduction on MR images was completely reversed within 15 days after transplantation. It is still unclear whether the signal changes in MR imaging could reflect the number of transplanted cells in the liver. In the present study, BMSCs of male rats were doubly labeled with enhanced green fluorescent protein (EGFP) and SPIO and injected intravascularly into female rats with liver fibrosis. At different time points after injection, MR imaging was performed. The distribution of SPIO particles and EGFP-positive cells was determined by Prussian blue staining and EGFP immunohistochemistry, respectively. The distribution of transplanted BMSCs in various organs was assessed by detection of the SRY gene using real-time quantitative PCR. At 15 days post transplantation, the numbers of transplanted cells were significantly decreased in the lung, kidney, spleen and muscle, but not liver and heart, in comparison with those at 7 days after transplantation. EGFP staining-positive cells were observed in the liver intralobular parenchyma, while Prussian blue staining was negative at 42 days after transplantation. Taken together, SPIO particles and EGFP-labeled BMSCs show a different tissue distribution pattern in rats with liver fibrosis after a long-term period of monitoring. SPIO-based MR imaging may not be suitable for long-term tracking of transplanted BMSCs in vivo.

  4. Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

    PubMed

    Okumura, Shinya; Teratani, Takumi; Fujimoto, Yasuhiro; Zhao, Xiangdong; Tsuruyama, Tatsuaki; Masano, Yuki; Kasahara, Naoya; Iida, Taku; Yagi, Shintaro; Uemura, Tadahiro; Kaido, Toshimi; Uemoto, Shinji

    2016-09-01

    Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD. PMID:27102080

  5. Bridge therapy to liver transplantation in fulminant hepatic failure.

    PubMed

    Merritt, W T

    2001-12-01

    The management of patients with fulminant hepatic failure is a major clinical endeavor. Early intensive care at an institution able to perform liver transplantation is essential. It is recognized that therapy focused solely on attempts at preventing/reversing increased intracranial pressure, and the treatment of other failing organs as they occur falls well short of ideal. This review covers the non-biological and biological techniques utilized in efforts to support liver function. The goal is to foster recovery, or to buy enough time for successful liver transplantation. Prospective, controlled trials are beginning to acknowledge subgroups of fulminant hepatic failure and properly randomize therapy. Our understanding of the essential elements of liver support is improving, but no single device has yet proved indispensable.

  6. Physician predictions of graft survival following liver transplantation

    PubMed Central

    Feurer, Irene D.; Austin, Mary T.; Porayko, Michael K.; Wright, J. Kelly; Lorenzi, Nancy M.; Pinson, C. Wright; Aronsky, Dominik

    2007-01-01

    Introduction. Due to the scarcity of cadaveric livers, clinical judgment must be used to avoid futile transplants. However, the accuracy of human judgment for predicting outcomes following liver transplantation is unknown. The study aim was to assess expert clinicians’ ability to predict graft survival and to compare their performance to published survival models. Materials and methods. Pre-transplant case summaries were prepared based on 16 actual, randomly selected liver transplants. Clinicians specializing in the care of liver transplant patients were invited to assess the likelihood of 90-day graft survival for each case using (1) a 4-point Likert scale ranging from poor to excellent, and (2) a visual analog scale denoting the probability of survival. Four published models were also used to predict survival for the 16 cases. Results. Completed instruments were received from 50 clinicians. Prognostic estimates on the two scales were highly correlated (median r=0.88). Individual clinicians’ predictive ability was 0.61±0.13, by area under the receiver operating characteristic curve. The performance of published models was MELD 0.59, Desai 0.66, Ghobrial 0.61, and Thuluvath 0.45. For three cases, clinicians consistently overestimated the probability of survival (87±10%, 89±9%, 86±9%); these patients had early graft failures caused by postoperative complications. Discussion. Clinicians varied in their ability to predict survival for a set of pre-transplant scenarios, but performed similarly to published models. When clinicians overestimated the chance of transplant success, either sepsis or hepatic artery thrombosis was involved; such events may be hard to predict before surgery. PMID:18345303

  7. Orthotropic liver transplantation for intractable neurological manifestations of Wilson's disease.

    PubMed

    Sutariya, Vaibhav K; Tank, Anad H; Modi, Pranjal R

    2015-01-01

    Wilson's disease (WD) is an inherited autosomal recessive disorder characterized by copper accumulation and toxicity, affecting mainly the liver and brain. Orthotopic liver transplantation (OLT) is the definitive therapy for patients with WD. Acute fulminant hepatic failure and decompensated cirrhosis are well-established indications for OLT. Patients with severe neurologic impairment can also be benefited by OLT. Here, we present a patient who underwent OLT for isolated neurological WD.

  8. Periodontal Management of a Patient Undergoing Liver Transplantation.

    PubMed

    Clozza, Emanuele; Segelnick, Stuart L; Sigal, Samuel H; Rovner, Deborah N; Weinberg, Mea A

    2016-01-01

    This case report describes the periodontal management of a patient with end-stage liver disease undergoing liver transplantation. In the first part of this article, all medical and dental findings are reported to elaborate adequate diagnoses. A patient-specific treatment plan was structured given the challenging periodontal and systemic scenarios. The second part describes the periodontal therapy delivered in close interaction with the referring physicians. Last, the article reviews current principles and protocols in managing these patients. PMID:26901304

  9. Evaluation of 100 patients for living donor liver transplantation.

    PubMed

    Trotter, J F; Wachs, M; Trouillot, T; Steinberg, T; Bak, T; Everson, G T; Kam, I

    2000-05-01

    The initial success of living donor liver transplantation (LDLT) in the United States has resulted in a growing interest in this procedure. The impact of LDLT on liver transplantation will depend in part on the proportion of patients considered medically suitable for LDLT and the identification of suitable donors. We report the outcome of our evaluation of the first 100 potential transplant recipients for LDLT at the University of Colorado Health Sciences Center (Denver, CO). All patients considered for LDLT had first been approved for conventional liver transplantation by the Liver Transplant Selection Committee and met the listing criteria of United Network for Organ Sharing status 1, 2A, or 2B. Once listed, those patients deemed suitable for LDLT were given the option to consider LDLT and approach potential donors. Donors were evaluated with a preliminary screening questionnaire, followed by formal evaluation. Of the 100 potential transplant recipients evaluated, 51 were initially rejected based on recipient characteristics that included imminent cadaveric transplantation (8 patients), refusal of evaluation (4 patients), lack of financial approval (6 patients), and medical, psychosocial, or surgical problems (33 patients). Of the remaining 49 patients, considered ideal candidates for LDLT, 24 patients were unable to identify a suitable donor for evaluation. Twenty-six donors were evaluated for the remaining 25 potential transplant recipients. Eleven donors were rejected: 9 donors for medical reasons and 2 donors who refused donation after being medically approved. The remaining 15 donor-recipient pairs underwent LDLT. Using our criteria for the selection of recipients and donors for LDLT gave the following results: (1) 51 of 100 potential transplant recipients (51%) were rejected for recipient issues, (2) only 15 of the remaining 49 potential transplant recipients (30%) were able to identify an acceptable donor, and (3) 15 of 100 potential living donor

  10. Using old liver grafts for liver transplantation: where are the limits?

    PubMed

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-08-21

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

  11. Using old liver grafts for liver transplantation: Where are the limits?

    PubMed Central

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-01-01

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573

  12. Using old liver grafts for liver transplantation: where are the limits?

    PubMed

    Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2014-08-21

    The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573

  13. Transplant arteriosclerosis in a rat aortic model.

    PubMed Central

    Isik, F. F.; McDonald, T. O.; Ferguson, M.; Yamanaka, E.; Gordon, D.

    1992-01-01

    Transplant arteriosclerosis (TA) has emerged as an obstacle to the long-term survival of transplanted organs, especially cardiac transplants. The animal models that have been used to study TA have not been fully characterized with regard to features such as the time course of cell proliferation and the sequence of cell types arriving in the developing intimal lesion. We present a model of TA based on a transplanted segment of abdominal aorta that helps address these questions. Two strains of rats (PVG x DA) underwent orthotopic aortic transplantation without immunosuppression and were killed at 14, 20, 40, and 60 days after transplantation. The within-strain control group displayed minimal evidence of cellular rejection with minimal to absent intimal lesions. In contrast, the allograft group showed a linearly increasing intimal lesion, up through 60 days after transplantation. The mechanism of intimal thickening was by an increase in cell number at the earlier time points with the later deposition of extracellular matrix. The early intimal lesion consisted mostly of mononuclear inflammatory cells (45%) with gradually increasing presence of smooth muscle cells (SMC) in the intima between 20 and 60 days. Conversely, the media showed gradual infiltration by macrophage-type cells with virtual loss of all SMC from the media by 40 days. The proliferative index showed a peak of 6% and 8% at 20 days in both the intima and media, respectively, and was preceded by the presence of macrophages. In fact, most of the proliferating cells at the earlier time points were either monocytes/macrophages, or were immediately adjacent to monocyte-/macrophage-rich regions. This straight artery segment model of transplant arteriosclerosis provides an easily quantifiable system in which the effects of different interventions (e.g., immunosuppressive regimens) can be tested. Images Figure 2 Figure 3 Figure 6 Figure 7 Figure 8 Figure 9 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure

  14. MARS therapy, the bridging to liver retransplantation – Three cases from the Hungarian liver transplant program

    PubMed Central

    Fazakas, János; Zádori, Gergely; Görög, Dénes; Kóbori, László; Dabasi, Eszter; Mándli, Tamás; Piros, László; Smudla, Anikó; Szabó, Tamás; Toronyi, Éva; Tóth, Szabolcs; Tőzsér, Gellért; Végső, Gyula; Doros, Attila; Nemes, Balázs

    2013-01-01

    Besides orthotopic liver transplantation (OLT) there is no long-term and effective replacement therapy for severe liver failure. Artificial extracorporeal liver supply devices are able to reduce blood toxin levels, but do not replace any synthetic function of the liver. Molecular adsorbent recirculating system (MARS) is one of the methods that can be used to treat fulminant acute liver failure (ALF) or acute on chronic liver failure (AoCLF). The primary non-function (PNF) of the newly transplanted liver manifests in the clinical settings exactly like acute liver failure. MARS treatment can reduce the severity of complications by eliminating blood toxins, so that it can help hepatic encephalopathy (HE), hepatorenal syndrome (HRS), and the high rate mortality of cerebral herniation. This might serve as a bridging therapy before orthotopic liver retransplantation (reOLT). Three patients after a first liver transplantation became candidate for urgent MARS treatment as a bridging solution prior to reOLT in our center. Authors report these three cases, fo-cusing on indications, MARS sessions, clinical courses, and final outcomes. PMID:24265893

  15. The Chinese Herb Jianpijiedu Contributes to the Regulation of OATP1B2 and ABCC2 in a Rat Model of Orthotopic Transplantation Liver Cancer Pretreated with Food Restriction and Diarrhea

    PubMed Central

    Sun, Baoguo; Chen, Yan; Xiang, Ting; Zhang, Lei; Chen, Zexiong; Zhang, Shijun; Zhou, Houming; Chen, Shuqing

    2015-01-01

    Traditional Chinese Medicine Jianpijiedu decoction (JPJD) could improve the general status of liver cancer patients in clinics, especially the symptoms of decreased food intake and diarrhea. In this study, our results showed that the survival rate of the liver cancer with food restriction and diarrhea (FRD-LC) rats was lower than the liver cancer (LC) rats, and the tumor volume of the FRD-LC rats was higher than the LC rats. It was also shown that the high dose of JPJD significantly improved the survival rate, weight, and organ weight when compared with FRD-LC-induced rats. Moreover, JPJD administration upregulated the mRNA and protein levels of ABCC2 and downregulated the mRNA and protein levels of OATP1B2 in liver tissues. However, opposite results were observed in the cancer tissues. In conclusion, the study indicated that the Chinese Medicine JPJD could contribute to the rats with liver cancer which were pretreated with food restriction and diarrhea by regulating the expression of ABCC2 and OATP1B2 in liver tissues and cancer tissues. PMID:26665149

  16. Longitudinal assessment of mortality risk among candidates for liver transplantation.

    PubMed

    Merion, Robert M; Wolfe, Robert A; Dykstra, Dawn M; Leichtman, Alan B; Gillespie, Brenda; Held, Philip J

    2003-01-01

    Liver allocation policy recently was modified to use the Model for End-Stage Liver Disease (MELD) for patients with chronic liver disease to stratify potential recipients according to risk for waitlist death. In this study, a retrospective cohort of 760 adult patients with chronic liver disease placed on the liver transplant waitlist between January 1995 and March 2001 and followed up for up to 74 months was studied to assess the ability of the MELD to predict mortality among waitlisted candidates and evaluate the prognostic importance of changes in MELD score over time. Serial MELD scores predicted waitlist mortality significantly better than baseline MELD scores or medical urgency status. Each unit of the 40-point MELD score was associated with a 22% increased risk for waitlist death (P <.001), whereas medical urgency status was not a significant independent predictor. For any given MELD score, the magnitude and direction of change in MELD score during the previous 30 days (DeltaMELD) was a significant independent mortality predictor. Patients with MELD score increases greater than 5 points over 30 days had a threefold greater waitlist mortality risk than those for whom MELD scores increased more gradually (P <.0001). We conclude that mortality risk on the liver transplant waitlist is predicted more accurately by serial MELD score determinations than by medical urgency status or single MELD measurements. DeltaMELD score over time reflects progression of liver disease and conveys important additional prognostic information that should be considered in the further evolution of national liver allocation policy.

  17. A Metabolomic Approach (1H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers

    PubMed Central

    Vivot, Kevin; Benahmed, Malika A.; Seyfritz, Elodie; Bietiger, William; Elbayed, Karim; Ruhland, Elisa; Langlois, Allan; Maillard, Elisa; Pinget, Michel; Jeandidier, Nathalie; Gies, Jean-Pierre; Namer, Izzie-Jacques; Sigrist, Séverine; Reix, Nathalie

    2016-01-01

    Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. 1H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation. Inflammatory markers (Interleukin-6, α2-macroglobulin) are not suitable to follow islet reactions as they are not islet specific. To study islet specific inflammatory events, immunohistochemistry was performed on sections of islet transplanted livers for thrombin (indicator of the instant blood-mediated inflammatory reaction (IBMIR)) and granulocytes and macrophages. We observed a specific correlation between IBMIR and granulocyte and macrophage infiltration after 12 h. In parallel, we identified a metabolic response associated with transplantation: after 12 h, glucose, alanine, aspartate, glutamate and glutathione were significantly increased. An increase of glucose is a marker of tissue degradation, and could be explained by immune cell infiltration. Alanine, aspartate and glutamate are inter-connected in a common metabolic pathway known to be activated during hypoxia. An increase of glutathione revealed the presence of antioxidant protection. In this study, IBMIR visualization combined with 1H HRMAS NMR facilitated the characterization of cellular and molecular pathways recruited following islet transplantation. PMID:27766032

  18. Hepatitis C virus–HIV-coinfected patients and liver transplantation

    PubMed Central

    Kardashian, Ani A.; Price, Jennifer C.

    2016-01-01

    Purpose of review To review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients. Recent findings The prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug–drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required. Summary Liver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population. PMID:25944240

  19. Assessing and treating alcohol relapse risk in liver transplantation candidates.

    PubMed

    Dom, G; Wojnar, M; Crunelle, C L; Thon, N; Bobes, J; Preuss, U W; Addolorato, G; Seitz, H K; Wurst, F M

    2015-03-01

    In Europe between 30 and 50% of all liver transplantations (LTX) are done within the context of chronic end-stage alcoholic liver disease (ALD). However, post-operatively 20-25% of these patients lapse or relapse into heavy alcohol use. Thus, assessment of alcohol relapse risk before enlisting and therapeutic follow-up during and after LTX is of utmost importance. However, as yet there are enormous differences between European countries and between transplant centers, with regard to the assessment methods and criteria and the implementation of therapeutic follow-up. Only the so-called '6-month abstinence' rule is widely used. However, there are not much scientific data validating its use in predicting relapse. Thus, there is a clear need of a more homogeneous approach, which was the focus of a symposium of the European Federation of Addiction Societies during the 14th conference of the European Society for Biomedical Research on Alcoholism, 2013 (ESBRA), entitled 'Liver transplantation: A European perspective'. In a follow-up on this symposium, the authors aim to sum up the evidence of psychiatric assessment criteria and psychiatric treatment interventions relevant in the context of patient selection and patient follow-up within ALD transplantation procedures. Based upon these findings, we propose elements of a procedure that can serve as a first step toward a model of good practice regarding addiction-specialist input within the pre- and post-transplantation period.

  20. Management of ABO-incompatible living-donor liver transplantation: past and present trends.

    PubMed

    Raut, Vikram; Uemoto, Shinji

    2011-03-01

    Based on the concept that the liver is a "privileged organ," which resists acute rejection, Thomas Starzl introduced liver transplantation across the ABO blood group. However, with improved survival after liver transplantation came reports of an increased incidence of acute rejection, biliary and vascular complications, and decreased survival after ABO-incompatible liver transplantation. As a result, ABO-incompatible liver transplantations are performed only in emergencies when ABO-compatible grafts are unavailable. In living-donor liver transplantation (LDLT), donors are restricted to family members; therefore, breaking ABO blood group barriers becomes inevitable. This inevitable situation has forced liver transplant surgeons to exploit many innovative techniques to overcome the challenges of ABO-incompatible liver transplantation. This review looks at the history and current practices of ABO-incompatible LDLT to provide insight so that the protocol can be improved further.

  1. Liver transplantation for hepatic epithelioid hemangioendothelioma: The Canadian multicentre experience

    PubMed Central

    Nudo, Carmine G; Yoshida, Eric M; Bain, Vincent G; Marleau, Denis; Wong, Phil; Marotta, Paul J; Renner, Eberhard; Watt, Kymberly D; Deschênes, Marc

    2008-01-01

    INTRODUCTION: Hepatic epithelioid hemangioendothelioma (HEHE) is a rare entity. At the present time, there is no standardized effective therapy. Liver transplantation (LT) has emerged as a treatment for this rare tumour. OBJECTIVE: To evaluate the outcome of liver transplantation for HEHE at eight centres across Canada. METHODS: The charts of patients who were transplanted for HEHE at eight centres across Canada were reviewed. RESULTS: A total of 11 individuals (eight women and three men) received a LT for HEHE. All LTs were performed between 1991 and 2005. The mean (± SD) age at LT was 38.7±13 years. One patient had one large liver lesion (17 cm × 14 cm × 13 cm), one had three lesions, one had four lesions and eight had extensive (five or more) liver lesions. One patient had spleen involvement and two had involved lymph nodes at the time of transplantation. The mean duration of follow-up was 78±63 months (median 81 months). Four patients (36.4%) developed recurrence of HEHE with a mean time to recurrence of 25±25 months (median 15.6 months) following LT. The calculated survival rate following LT for HEHE was 82% at five years. CONCLUSIONS: The results of LT for HEHE are encouraging, with a recurrence rate of 36.4% and a five-year survival rate of 82%. Further studies are needed to help identify patients who would benefit most from LT for this rare tumour. PMID:18925305

  2. What I Need to Know about Liver Transplantation

    MedlinePlus

    ... rejected. [ Top ] What other problems can damage my new liver? Recurrence of the disease that caused the need for a transplant can ... of all medical advances. Clinical trials look at new ways to prevent, detect, or treat disease. Researchers also use clinical trials to look at ...

  3. SPLIT TOLERANCE INDUCED BY ORTHOTOPIC LIVER TRANSPLANTATION IN MICE1

    PubMed Central

    Dahmen, Uta; Qian, Shiguang; Rao, Abdul S.; Demetris, Anthony J.; Fu, Fumin; Sun, Hong; Gao, Lan; Fung, John J.; Starzl, Thomas E.

    2011-01-01

    Spontaneous orthotopic liver allograft acceptance associated with microchimerism in mice induces tolerance to subsequent skin or heart transplants from the donor but not third-party animals. Despite in vivo hyporesponsiveness, in vitro MLC and CTL assays showed continuing antidonor reactivity. Cells isolated from recipients’ spleens and grafted livers, when tested in MLC and CTL assays, were antidonor reactive out to 3 months to the same degree as splenocytes obtained from either naive or presensitized (with skin or heart) mice. Nevertheless, passive transfer of splenocytes or liver lymphocytes from liver tolerant mice, but not naive or sensitized donor strain mice, were able to prolong skin graft survival significantly in naive irradiated recipients. By using a strain combination in which the donor but not the recipient expressed the stimulatory endogenous super-Ag (Mlsf), it was possible to determine whether super-Ag-reactive T cells bearing Vβ5 and Vβ11 were deleted or anergic. Phenotypic analysis of cells isolated from recipients’ spleens and grafted livers (up to 90 days after transplant), when compared with naive animals, showed no significant difference in Vβ5 and Vβ11 TCR expression. Additionally, when these isolated spleen cells were tested for antibody-mediated stimulation, both anti-Vβ5 and Vβ11 TCR mAb led to marked proliferation of cells obtained from naive and liver-transplanted recipients, but as expected, proliferation was very low in cells from naive donors. These results suggest that liver transplantation induces donor-specific tolerance in vivo, which may not be reflected in in vitro proliferative and cytotoxicity assays (split tolerance). Furthermore, this tolerance does not seem to be induced by clonal deletion or anergy of minor-lymphocyte-stimulating-antigen-reactive T cells in the recipients. PMID:8036695

  4. New insights into the coagulopathy of liver disease and liver transplantation

    PubMed Central

    Senzolo, M; Burra, P; Cholongitas, E; Burroughs, AK

    2006-01-01

    The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery. PMID:17203512

  5. Living donor liver transplantation in Brazil—current state

    PubMed Central

    Andraus, Wellington; D’Alburquerque, Luiz A. C.

    2016-01-01

    Currently in Brazil, living donor liver transplantation (LDLT) represents 8.5% of liver transplantation (LT), being the majority pediatric one. Up to now, according to Brazilian Organ Transplantation Association (ABTO) annual report, 2,086 procedures have been done nationwide, most of them in southeast and south regions. Based on national centers reports, biliary complication is the most common recipient postoperative complication (14.5–20.6%), followed by hepatic artery thrombosis (3.1–10.7%) and portal vein thrombosis (2.3–9.1%). Patient and graft overall 5-y survival correspond to 76% and 74%, respectively. Regarding the donor, morbidity rate ranges from 12.4% to 28.3%, with a national mortality rate of 0.14%. In conclusion, Brazilian LDLT programs enhance international experience that this is a feasible and safe procedure, as well as an excellent alternative strategy to overcome organs shortage. PMID:27115012

  6. Probiotic use in preventing postoperative infection in liver transplant patients

    PubMed Central

    Chen, Jim; Wu, Jinshan; Chalson, Helen; Merigan, Lynn; Mitchell, Andrew

    2013-01-01

    Background Although liver transplantation has been widely practised, post-operative bacterial infection is still a frequent complication which contributed to an increased risk of fatality. There were studies on preoperative use of probiotics for liver transplant patients and acquired reduction in postoperative sepsis and wound infection, but the relevant clinical experience with pre- and probiotics is still limited. Objectives This study is to assess fibre and probiotic use aimed at preventing bacterial sepsis and wound complications in patients undergoing liver transplantation. Study methods There were a total of sixty-seven adult patients scheduled for liver transplantation were included in a public teaching hospital. From January to December 2011, 34 continuous patients following liver transplantation were put on fibre + probiotics. In retrospectively, from January to December 2010, 33 continuous patients were collected as a control group and they were only received fibre post operation. The incidence of bacterial infections was compared in patients receiving either fibre and lactobacillus or fibre only. Statistical analysis was performed using SPSS 15. The t test, fisher’s and chi- square test was used to compare discrete variables. Results In summary, in the analysis of 67 liver transplant recipients, 8.8% group A patients developed infections compared to 30.3% group B patients. The difference between groups A and B was statistically significant in both cases. In addition, the duration of antibiotic therapy was significantly shorter in the lactobacillus-group. Wound infection was the most frequent infections and enterococci the most frequently isolated bacteria. Fibre and lactobacilli were well tolerated in most cases. The operating time, amount of intra- and post-operatively transfused units of blood, fresh frozen plasma and albumin did not differ significantly between the groups. Conclusions Combined fibre and probiotics could lower the incidence of

  7. Differential migration of passenger leukocytes and rapid deletion of naive alloreactive CD8 T cells after mouse liver transplantation.

    PubMed

    Tay, Szun S; Lu, Bo; Sierro, Fred; Benseler, Volker; McGuffog, Claire M; Bishop, G Alex; Cowan, Peter J; McCaughan, Geoffrey W; Dwyer, Karen M; Bowen, David G; Bertolino, Patrick

    2013-11-01

    Donor passenger leukocytes (PLs) from transplanted livers migrate to recipient lymphoid tissues, where they are thought to induce the deletion of donor-specific T cells and tolerance. Difficulties in tracking alloreactive T cells and PLs in rats and in performing this complex surgery in mice have limited progress in identifying the contribution of PL subsets and sites and the kinetics of T cell deletion. Here we developed a mouse liver transplant model in which PLs, recipient cells, and a reporter population of transgenic CD8 T cells specific for the graft could be easily distinguished and quantified in allografts and recipient organs by flow cytometry. All PL subsets circulated rapidly via the blood as soon as 1.5 hours after transplantation. By 24 hours, PLs were distributed differently in the lymph nodes and spleen, whereas donor natural killer and natural killer T cells remained in the liver and blood. Reporter T cells were activated in both liver and lymphoid tissues, but their numbers dramatically decreased within the first 48 hours. These results provide the first unequivocal demonstration of the differential recirculation of liver PL subsets after transplantation, and show that alloreactive CD8 T cells are deleted more rapidly than initially reported. This model will be useful for dissecting early events leading to the spontaneous acceptance of liver transplants.

  8. Getting a New Liver: Facts about Liver Transplants

    MedlinePlus

    ... liver does several things: • It helps digest your food. • It clears wastes from your blood. • It makes proteins that help your blood to clot. • It stores the sugars (glycogen) that are used for ... liver also controls the way your body uses food and the way it works with your immune ...

  9. An Empirically Informed Analysis of the Ethical Issues Surrounding Split Liver Transplantation in the United Kingdom.

    PubMed

    Moorlock, Greg; Neuberger, James; Bramhall, Simon; Draper, Heather

    2016-07-01

    Surgical advances have allowed for the development of split liver transplantation, providing two recipients with the opportunity to potentially benefit from one donated liver by splitting the liver into two usable parts. Although current data suggest that the splitting of livers provides overall benefit to the liver-recipient population, relatively low numbers of livers are actually split in the United Kingdom. This article addresses the question of whether ethical concerns are posing an unnecessary barrier to further increasing the number of life-saving transplantations. Recognizing that an important aspect of exploring these concerns is gaining insight into how transplant staff and patients regard splitting livers, the article presents the findings of a qualitative study examining the views of senior transplant staff and liver transplant patients in the UK and uses these to inform a commentary on the ethical issues relating to split liver transplantation. PMID:27348828

  10. Age and equity in liver transplantation: An organ allocation model.

    PubMed

    Cucchetti, Alessandro; Ross, Lainie Friedman; Thistlethwaite, J Richard; Vitale, Alessandro; Ravaioli, Matteo; Cescon, Matteo; Ercolani, Giorgio; Burra, Patrizia; Cillo, Umberto; Pinna, Antonio Daniele

    2015-10-01

    A moral liver allocation policy must be fair. We considered a 2-step, 2-principle allocation system called "age mapping." Its first principle, equal opportunity, ensures that candidates of all ages have an equal chance of getting an organ. Its second principle, prudential lifespan equity, allocates younger donor grafts to younger candidates and older donors to older candidates in order to increase the likelihood that all recipients achieve a "full lifespan." Data from 2476 candidates and 1371 consecutive adult liver transplantations (from 1999 to 2012) were used to determine whether age mapping can reduce the gap in years of life lost (YLL) between younger and older recipients. A parametric Weibull prognostic model was developed to estimate total life expectancy after transplantation using survival of the general population matched by sex and age as a reference. Life expectancy from birth was calculated by adding age at transplant and total life expectancy after transplantation. In multivariate analysis, recipient age, hepatitis C virus status, Model for End-Stage Liver Disease score at transplant of >30, and donor age were significantly related to prognosis after surgery (P < 0.05). The mean (and standard deviation) number of years of life from birth, calculated from the current allocation model, for various age groups were: recipients 18-47 years (n = 340) = 65.2 (3.3); 48-55 years (n = 387) = 72.7 (2.1); 56-61 years (n = 372) = 74.7 (1.7) and for recipients >61 years (n = 272) = 77.4 (1.4). The total number of YLL equaled 523 years. Redistributing liver grafts, using an age mapping algorithm, reduces the lifespan gap between younger and older candidates by 33% (from 12.3% to 8.3%) and achieves a 14% overall reduction of YLL (73 years) compared to baseline liver distribution. In conclusion, deliberately incorporating age into an allocation algorithm promotes fairness and increases efficiency.

  11. Neoplastic disease after liver transplantation: Focus on de novo neoplasms

    PubMed Central

    Burra, Patrizia; Rodriguez-Castro, Kryssia I

    2015-01-01

    De novo neoplasms account for almost 30% of deaths 10 years after liver transplantation and are the most common cause of mortality in patients surviving at least 1 year after transplant. The risk of malignancy is two to four times higher in transplant recipients than in an age- and sex-matched population, and cancer is expected to surpass cardiovascular complications as the primary cause of death in transplanted patients within the next 2 decades. Since exposure to immunosuppression is associated with an increased frequency of developing neoplasm, long-term immunosuppression should be therefore minimized. Promising results in the prevention of hepatocellular carcinoma (HCC) recurrence have been reported with the use of mTOR inhibitors including everolimus and sirolimus and the ongoing open-label prospective randomized controlled SILVER. Study will provide more information on whether sirolimus-containing vs mTOR-inhibitor-free immunosuppression is more efficacious in reducing HCC recurrence. PMID:26269665

  12. Liver transplantation for hepatic and neurological Wilson's disease.

    PubMed

    Geissler, I; Heinemann, K; Rohm, S; Hauss, J; Lamesch, P

    2003-06-01

    Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

  13. Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post-transplant year.

    PubMed

    Grąt, Michał; Lewandowski, Zbigniew; Grąt, Karolina; Wronka, Karolina Maria; Krasnodębski, Maciej; Barski, Krzysztof; Zborowska, Hanna; Patkowski, Waldemar; Zieniewicz, Krzysztof; Krawczyk, Marek

    2014-10-01

    Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long-term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post-transplant year (p = 0.655) but worse during the five subsequent years among the five-yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post-transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post-transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non-ALD recipients up to the fifth post-transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre-transplant diagnosis of ALD yields negative effects on post-transplant outcomes beyond the fifth post-transplant year, not attributable to recidivism.

  14. Human Liver Transplantation As A Model To Study HCV Pathogenesis

    PubMed Central

    Hughes, Michael G.; Rosen, Hugo R.

    2010-01-01

    Hepatitis C is a leading etiology of liver cancer and cause for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (~50%) fail to respond to antiviral treatment, thus remaining at risk for disease progression. While chimpanzees have been used to study HCV biology and treatments, their cost is quite high and their use is strictly regulated; indeed, the NIH no longer supports the breeding of chimpanzees for study. The development of HCV therapies has been hindered by the relative paucity of small animal models to study HCV pathogenesis. This review presents the strengths of the human liver transplant, highlighting the advances derived from this model, including insights into viral kinetics and quasispecies, viral receptor binding and entry, innate and adaptive immunity. Moreover, consideration is made of current and emerging antiviral therapeutic approaches based on translational research results. PMID:19877210

  15. Delayed Gastric Emptying after Living Donor Hepatectomy for Liver Transplantation

    PubMed Central

    Griesemer, Adam D.; Parsons, Ronald F.; Graham, Jay A.; Emond, Jean C.; Samstein, Benjamin

    2014-01-01

    Delayed gastric emptying is a significant postoperative complication of living donor hepatectomy for liver transplantation and may require endoscopic or surgical intervention in severe cases. Although the mechanism of posthepatectomy delayed gastric emptying remains unknown, vagal nerve injury during intraoperative dissection and adhesion formation postoperatively between the stomach and cut liver surface are possible explanations. Here, we present the first reported case of delayed gastric emptying following fully laparoscopic hepatectomy for living donor liver transplantation. Additionally, we also present a case in which symptoms developed after open right hepatectomy, but for which dissection for left hepatectomy was first performed. Through our experience and these two specific cases, we favor a neurovascular etiology for delayed gastric emptying after hepatectomy. PMID:25610698

  16. Perfusion machines for liver transplantation: technology and multifunctionality.

    PubMed

    Rubbini, Michele

    2014-06-01

    The reliability of machine perfusion (alternative to static cold storage) for the preservation of liver for transplantation has been well investigated in experimental models, by taking into account the temperature, oxygenation, flow, pressure, and settings of the machine or proposed circuit. Machine perfusion is considered by many researchers as a valid method for preserving organs. While circuits or machines for preservation have been described, no agreement has been reached concerning how these devices should be developed. The machines proposed to date are considered here to identify the technical and functional features necessary for a machine to have multifunctionality and adaptability to cater all the needs of preservation, according to the type and features of the liver to be transplanted, including marginal livers. The need to establish a uniform method for the use of this machine is also emphasized, to achieve a clinical protocol for its use.

  17. Glucose tolerance normalization following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic ZDF rats.

    PubMed

    Rogers, Sharon A; Chen, Feng; Talcott, Mike; Liapis, Helen; Hammerman, Marc R

    2006-11-01

    Pancreas or pancreatic islet transplantation in humans is limited by organ availability, and success of the latter is negatively impacted upon by tissue loss post-transplantation and limited potential for expansion of beta cells. A way to overcome the supply and expansion problems is to xenotransplant embryonic tissue. Previously, we have shown that beta cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin-diabetic (type 1) Lewis rats engraft without the need for host immune-suppression and normalize glucose tolerance. Here we show long-term engraftment of pig beta cells within liver, pancreas and mesenteric lymph nodes post-transplantation of E28 pig pancreatic primordia into diabetic ZDF rats, a model for type 2 diabetes. Porcine insulin is present in circulation after an oral glucose load. Glucose tolerance is normalized in transplanted ZDF hosts and insulin sensitivity restored in formerly diabetic ZDF males. Release of porcine insulin in vitro from tissue originating in transplanted rats occurs within 1 min of glucose stimulation characteristic of first-phase secretion from beta cells. Of potential importance for application of this transplantation technology to treatment of type 2 diabetes in humans and confirmatory of our previous findings in Lewis rats, no host immunosuppression is required for engraftment of E28 pig pancreatic primordia. PMID:17138051

  18. Aspartate carbamoyltransferase from rat liver

    PubMed Central

    Bresnick, E.; Mossé, Helena

    1966-01-01

    1. Aspartate-carbamoyltransferase activity was concentrated from rat-liver preparations. Only l-aspartate, β-benzyl-l-aspartate and β-erythro-hydroxy-dl-aspartate were carbamoylated enzymically. The Km for l-aspartate and carbamoyl phosphate have been determined by three methods: colorimetric procedure, radioactive assay with [14C]aspartate and an assay with [14C]carbamoyl phosphate. 2. The Km for aspartate has been determined as a function of the pH; the pK of the functional group at the active site of the enzyme, pKe, was at pH9·0. Enzymic activity was diminished in the presence of N-ethylmaleimide, p-hydroxymercuribenzoate and the heavy metals Ag+, Hg2+, or Zn2+. The inhibitions could be prevented by mercaptoethanol. These findings suggested the association of a thiol group with the enzymic activity. 3. Enzymic activity was also decreased by sodium lauryl sulphate, urea and dioxan. Competitive inhibition (with l-aspartate) was manifested by maleate, succinate, oxaloacetate, β-erythro-hydroxy-dl-aspartate and β-benzyl-l-aspartate. The Ki for most of these inhibitions has been determined. 4. The properties of the liver enzyme are compared with those of Escherichia coli aspartate carbamoyltransferase and the implications of the findings are discussed. PMID:5339547

  19. Directly acting drugs prostacyclin or nitroglycerine and endothelin receptor blocker bosentan improve cell engraftment in rat liver

    PubMed Central

    Bahde, Ralf; Kapoor, Sorabh; Bandi, Sriram; Bhargava, Kuldeep K.; Palestro, Christopher J.; Gupta, Sanjeev

    2012-01-01

    To optimize strategies for liver-directed cell therapy prevention of initial transplanted cell losses is particularly important for subsequent liver repopulation. After cell transplantation in hepatic sinusoids, perturbations in hepatic microcirculation along with changes in various liver cell types are among the earliest changes. Therefore, for advancing further concepts in cell engraftment, we studied vascular and related events in the liver after transplanting syngeneic hepatocytes into dipeptidyl peptidase IV-deficient rats. We treated rats with vascular drugs to define whether deleterious cell transplantation-induced events could be controlled followed by improvements in transplanted cell engraftment and proliferation. We found cell transplantation altered liver gene expression related to vessel tone, inflammation, cell adhesion, thrombosis, or tissue damage/remodeling. This was due to hepatic ischemia, endothelial injury and activation of neutrophils, Kupffer cells and hepatic stellate cells. Treatment of rats before cell transplantation with angiotensin converting enzyme blocker, lisinopril, or angiotensin II receptor blocker, losartan, did not improve cell engraftment. By contrast, direct-acting nitroglycerine or prostacyclin improved cell engraftment and also kinetics of liver repopulation. These drugs lowered hepatic ischemia and inflammation. Whereas pretreatment of rats with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hepatic ischemia or inflammation, without improving liver repopulation. However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro and produced superior cell engraftment and proliferation in vivo. We concluded that cell transplantation-induced changes in hepatic microcirculation contributed to transplanted cell clearances from liver. Vascular drugs, such as nitroglycerine, prostacyclin and bosentan, offer opportunities for improving cell therapy results

  20. Liver transplantation for acute liver failure accompanied by severe acute pancreatitis.

    PubMed

    Kirino, Izumi; Fujimoto, Yasuhiro; Hata, Koichiro; Uemoto, Shinji

    2016-01-01

    The role of liver transplantation (LT) in acute liver failure (ALF) complicated by severe acute pancreatitis is still unclear. We here report a case of deceased-donor LT for idiopathic ALF accompanied by severe acute pancreatitis. A 58-year-old man with no history of liver disease presented with idiopathic ALF and acute pancreatitis. After careful consideration, he received a liver from a deceased donor. Following surgery, the patient's liver function rapidly reverted to normal level and the acute pancreatitis simultaneously subsided. The patient later developed a pancreatic pseudocyst, which was treated successfully with combination interventional radiology. LT can be considered for ALF associated with severe acute pancreatitis if there is no clinical evidence of an absolute contraindication for organ transplantation, such as systemic or local infection. Moreover, we recommend a close follow-up by ultrasonography to allow early detection and treatment of pancreatic pseudocysts following surgery. PMID:27600056

  1. Living donor liver transplantation in Taiwan-challenges beyond surgery.

    PubMed

    Pillai, Vinod G; Chen, Chao-Long

    2016-04-01

    Taiwan has a high prevalence of hepatitis B and C viral infections, and consequently a high burden of chronic liver diseases. Liver transplantation (LT) began in Taiwan in 1984, and living donor liver transplantation (LDLT) in 1994. Education and collaboration between physicians on a national and international scale were important factors in the development of transplantation in East Asia. Technical innovations in donor hepatectomy, vascular and biliary reconstruction, and interventional radiology, perioperative management of transplant patients and development of associated specialties have enabled achievement of excellent results after both adult and pediatric LDLT. The establishment of rigorous protocols to withstand strict medico-legal scrutiny, combined with technical excellence has contributed to excellent surgical outcomes. The socioeconomic development of Taiwan and the first nationwide hepatitis B vaccination program in the world have also contributed to the decrease in disease burden and improvement of quality of healthcare. This article examines the factors enabling the development of LT in Taiwan, the innovations that have contributed to excellent outcomes, and indicates the future prospects of LDLT in Taiwan. PMID:27115009

  2. Living donor liver transplantation in Taiwan—challenges beyond surgery

    PubMed Central

    Pillai, Vinod G.

    2016-01-01

    Taiwan has a high prevalence of hepatitis B and C viral infections, and consequently a high burden of chronic liver diseases. Liver transplantation (LT) began in Taiwan in 1984, and living donor liver transplantation (LDLT) in 1994. Education and collaboration between physicians on a national and international scale were important factors in the development of transplantation in East Asia. Technical innovations in donor hepatectomy, vascular and biliary reconstruction, and interventional radiology, perioperative management of transplant patients and development of associated specialties have enabled achievement of excellent results after both adult and pediatric LDLT. The establishment of rigorous protocols to withstand strict medico-legal scrutiny, combined with technical excellence has contributed to excellent surgical outcomes. The socioeconomic development of Taiwan and the first nationwide hepatitis B vaccination program in the world have also contributed to the decrease in disease burden and improvement of quality of healthcare. This article examines the factors enabling the development of LT in Taiwan, the innovations that have contributed to excellent outcomes, and indicates the future prospects of LDLT in Taiwan. PMID:27115009

  3. Liver graft regeneration in right lobe adult living donor liver transplantation.

    PubMed

    Cheng, Y-F; Huang, T-L; Chen, T-Y; Tsang, L L-C; Ou, H-Y; Yu, C-Y; Concejero, A; Wang, C-C; Wang, S-H; Lin, T-S; Liu, Y-W; Yang, C-H; Yong, C-C; Chiu, K-W; Jawan, B; Eng, H-L; Chen, C-L

    2009-06-01

    Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 +/- 12.6% (range, 58-151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

  4. Comprehensive risk assessment for early neurologic complications after liver transplantation

    PubMed Central

    Wu, Si-Yuan; Chen, Teng-Wei; Feng, An-Chieh; Fan, Hsiu-Lung; Hsieh, Chung-Bao; Chung, Kuo-Piao

    2016-01-01

    AIM: To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon. METHODS: In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis. RESULTS: In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients’ age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m2, Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174. CONCLUSION: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation. PMID:27350733

  5. Use of IGL-1 preservation solution in liver transplantation.

    PubMed

    Wiederkehr, J C; Igreja, M R; Nogara, M S; Goncalves, N; Montemezzo, G P; Wiederkehr, H A; Wassen, M P; Nobrega, H A; Zenatti, K B; Mori, L Y; Tudisco, M S

    2014-01-01

    University of Wisconsin (UW) solution has been known as the standard solution for liver graft preservation. Alternative preservation solutions have been used in liver transplantation, such as histidine-tryptophan-ketoglutarate (HTK) and Celsior solution. Institut Georges Lopez-1 (IGL-1) is a new preservation solution with lower potassium and lower viscosity than UW solution that has recently been used in liver transplant. Data from 178 patients who received transplants from August 2008 to June 2013 at Hospital Santa Isabel, Blumenau, Brazil, were analyzed. All patients received grafts from brain death donors. In November 2011 we started to use IGL-1 as an alternate preservation solution. Therefore, 53 patients using IGL-1 preserved grafts were compared to 125 using HTK solution. The donor age in the HTK group ranged from 11-77 years, with a mean of 43.4 ± 4.8. In the IGL-1 group donor age ranged from 9-62 years, with a mean of 35.8 ± 4.5. Cold ischemia time in the HTK group ranged from 85-1145 minutes, mean 443.5 ± 183.5 minutes. In the IGL-1 group, cold ischemia time ranged from 85-670 minutes, mean 329.3 ± 134.8 minutes. The overall operative mortality rate was 14% (25 patients); in the HTK group, 14.4% (18 patients); and in the IGL-1 group, 13.4% (7 patients). One graft in the HTK group presented with primary non-function (PNF), 0.7%; there were none in the IGL-1 group. In our study, IGL-1 has been shown to be safe to use as a preservation solution for liver transplantation. Early post-transplant graft function was comparable to that observed with HTK solution, although a tendency for lower alanine aminotransferase levels was noticed. IGL-1 has been shown to be safe, cost efficient, and an effective preservation solution.

  6. Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

    PubMed Central

    Olthof, Pim B; Reiniers, Megan J; Dirkes, Marcel C; van Gulik, Thomas M; Heger, Michal; van Golen, Rowan F

    2015-01-01

    Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided. PMID:26552060

  7. KidsETransplant: a platform for liver-transplanted children.

    PubMed

    McLin, Valérie; Spahni, Stéphane; Boggini, Thomas; Guardia, Alberto; Wildhaber, Barbara E; Geissbuhler, Antoine

    2013-01-01

    Since 1989, all pediatric liver transplants in Switzerland are centralized at the University Hospitals of Geneva (HUG). Approximately 125 children have received transplants since then, and their survival rate is greater than 90% - one of the highest in Europe. Maximizing the chances of success requires that patients understand and comply with follow-up treatment. The KidsETransplant project aims at helping the child - and his family - to better understand his health situation, to have access to shared resources and to be able to better communicate with healthcare professionals and other patients. PMID:23921000

  8. Hepatitis viruses and liver transplantation: evolving trends in antiviral management.

    PubMed

    Verna, Elizabeth C

    2014-08-01

    Viral hepatitis is both a leading indication for liver transplant (LT) and an important cause of posttransplant graft loss and mortality. Treatment and prevention of hepatitis B virus in LT recipients, with the observed corresponding improvement in post-LT outcomes, is among the great success stories in transplantation. By comparison, treatment of hepatitis C virus with safe and effective regimens is only just becoming a reality. Chronic hepatitis E virus infection in LT recipients represents a newly described phenomenon that can also lead to graft loss; early diagnosis and treatment may be key in the management of these patients. PMID:25017077

  9. Prognostic and diagnostic value of procalcitonin in the post-transplant setting after liver transplantation

    PubMed Central

    Stirkat, Falk; Croner, Roland S.; Vassos, Nikolaos; Raptis, Dimitrios; Yedibela, Süleyman; Hohenberger, Werner; Müller, Volker

    2016-01-01

    Introduction The aim of the study was to assess the diagnostic accuracy of procalcitonin (PCT) as a marker for complications and as a prognostic factor for mortality after liver transplantation. Material and methods Liver transplant patients between January 2007 and April 2011 were prospectively included in the study. Procalcitonin serum concentration was recorded before, 6 h after reperfusion and then daily. Postoperative clinical course was prospectively analyzed from admission to discharge. Main surgical data such as operating procedure, type of reperfusion, operating and ischemic times, high urgency (HU) status and MELD score at the time of transplantation were also recorded. Results Sixteen patients with initial PCT > 5 ng/ml suffered ≥ 1 complication (p = 0.03). However, there was no association between the level of the 1st peak PCT and the further postoperative course or the occurrence of complications. Patients in whom a 2nd PCT peak occurred had a significantly higher risk for a complicated course, for a complicated sepsis course and for mortality (p < 0.0001). Warm ischemic time over 58 min, operating time over 389 min and HU status were significant independent factors for a complicated postoperative course (p < 0.001, p < 0.001 and p = 0.03 respectively). Conclusions Based on our results, we believe that PCT course and the occurrence of a 2nd peak seem to possess important diagnostic and prognostic power in the post-transplant setting after liver transplantation. PMID:27186183

  10. The interaction among donor characteristics, severity of liver disease and the cost of liver transplantation

    PubMed Central

    Salvalaggio, Paolo R.; Dzebisashvili, Nino; MacLeod, Kara E.; Lentine, Krista L.; Gheorghian, Adrian; Schnitzler, Mark A.; Hohmann, Samuel; Segev, Dorry L.; Gentry, Sommer E.; Axelrod, David A.

    2010-01-01

    Introduction Accurate assessment of the impact of donor quality on liver transplant (LT) costs has been limited by the lack of a large, multicenter study of detailed clinical and economic data. Methods A novel, retrospective database linking information from the University HealthSystem Consortium and the OPTN registry was analyzed using multivariate regression to determine the relationship between donor quality (assessed through the Donor Risk Index (DRI)), recipient illness severity, and total inpatient costs (transplant and all readmissions) for 1 year following LT. Results Cost data were available for 9,059 LT recipients. Increasing MELD score, higher DRI, simultaneous liver kidney transplant, female gender and prior liver transplant were associated with increasing cost of LT (P<0.05). MELD and DRI interact to synergistically increase the cost of LT (P<0.05). Donors in the highest DRI quartile added close to $12,000 to the cost of transplantation and nearly $22,000 to post-transplant costs in comparison to the lowest risk donors. Among the individual components of the DRI, donation after cardiac death (increased $20,769 vs. brain dead donors) had the greatest impact on transplant costs. Overall one year costs were increased in older donors, minority donors, nationally shared organs, and those with cold ischemic times 7–13 hours (p<0.05 for all) Conclusion Donor quality, as measured by the DRI, is an independent predictor of LT costs in the perioperative and post-operative periods. Centers in highly competitive regions who transplant higher MELD patients with high DRI livers may be particularly affected by the synergistic impact of these factors. PMID:21384505

  11. Medicaid enrollment after liver transplantation: Effects of medicaid expansion.

    PubMed

    Tumin, Dmitry; Hayes, Don; Washburn, W Kenneth; Tobias, Joseph D; Black, Sylvester M

    2016-08-01

    Liver transplantation (LT) recipients in the United States have low rates of paid employment, making some eligible for Medicaid public health insurance after transplant. We test whether recent expansions of Medicaid eligibility increased Medicaid enrollment and insurance coverage in this population. Patients of ages 18-59 years receiving first-time LTs in 2009-2013 were identified in the United Network for Organ Sharing registry and stratified according to insurance at transplantation (private versus Medicaid/Medicare). Posttransplant insurance status was assessed through June 2015. Difference-in-difference multivariate competing-risks models stratified on state of residence estimated effects of Medicaid expansion on Medicaid enrollment or use of uninsured care after LT. Of 12,837 patients meeting inclusion criteria, 6554 (51%) lived in a state that expanded Medicaid eligibility. Medicaid participation after LT was more common in Medicaid-expansion states (25%) compared to nonexpansion states (19%; P < 0.001). Multivariate analysis of 7279 patients with private insurance at transplantation demonstrated that after the effective date of Medicaid expansion (January 1, 2014), the hazard of posttransplant Medicaid enrollment increased in states participating in Medicaid expansion (hazard ratio [HR] = 1.5; 95% confidence interval [CI] = 1.1-2.0; P = 0.01), but not in states opting out of Medicaid expansion (HR = 0.8; 95% CI = 0.5-1.3; P = 0.37), controlling for individual characteristics and time-invariant state-level factors. No effects of Medicaid expansion on the use of posttransplant uninsured care were found, regardless of private or government insurance status at transplantation. Medicaid expansion increased posttransplant Medicaid enrollment among patients who had private insurance at transplantation, but it did not improve overall access to health insurance among LT recipients. Liver Transplantation 22 1075-1084 2016 AASLD.

  12. Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection

    PubMed Central

    Ackermann, Hanns; Bechstein, Wolf O.; Grünwald, Frank

    2016-01-01

    Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n = 13) or hepatic resection (n = 26) were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (p = 0.011). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS's time-activity-curve (p = 0.001). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX. PMID:27563464

  13. Accuracy of Hepatobiliary Scintigraphy after Liver Transplantation and Liver Resection.

    PubMed

    Eckenschwiller, Manuel; Ackermann, Hanns; Bechstein, Wolf O; Grünwald, Frank

    2016-01-01

    Background and Aims. Biliary complications are the most frequent complications after common liver surgeries. In this study, accuracy of hepatobiliary scintigraphy (HBS) and impact of hyperbilirubinemia were evaluated. Methods. Between November 2007 and February 2016, 131 patients underwent hepatobiliary scintigraphy after having liver surgery. 39 patients with 42 scans after LTX (n = 13) or hepatic resection (n = 26) were evaluated in the study; 27 were male, with mean age 60 years. The subjects underwent hepatobiliary scintigraphy with Tc-99m labeled Mebrofenin. The results were compared to ERCP as gold standard performed within one month after HBS. We calculated sensitivity, specificity, PPV, and NPV. We compared LTX patients to patients with other liver surgeries. Furthermore the influence of hyperbilirubinemia on HBS scans was evaluated. Results. HBS always provided the correct diagnosis in cases of bile leak in the liver-resected group (14/14). Overall diagnostic accuracy was 76% (19/25) in this group and 54% (7/13) in the LTX group. False negative (FN) diagnoses occurred more often among LTX patients (p = 0.011). Hyperbilirubinemia (>5 mg/dL) significantly influenced the excretion function of the liver, prolonging HBS's time-activity-curve (p = 0.001). Conclusions. Hepatobiliary scintigraphy is a reliable tool to detect biliary complications, but reduced accuracy must be considered after LTX. PMID:27563464

  14. Transplantation of rat hepatic stem-like (HSL) cells with collagen matrices.

    PubMed

    Ueno, Yasuharu; Nagai, Hirokazu; Watanabe, Go; Ishikawa, Kiyoshi; Yoshikawa, Kiwamu; Koizumi, Yukio; Kameda, Takashi; Sugiyama, Toshihiro

    2005-12-01

    Organ restitution using somatic stem cells is of great clinical interest. Recent advances in the field of tissue engineering have demonstrated that the use of collagen matrices as scaffolds facilitates tissue reconstruction. Here, we examine the efficacy of transplantation of HSL cells, a previously established liver epithelial cell line with a potential for differentiation, using collagen scaffolds. To this end, HSL cells were transplanted into Nagase's analbuminemic rat with spongy or gelatinous type I collagen matrices. Consequently, immunohistochemical analyses and genomic PCR experiments revealed engraftment of the transplanted cells. Furthermore, the levels of serum albumin in recipient rats were found to increase up to 2.5-fold relative to controls after transplantation. These findings suggest that HSL cells are able to differentiate into functional hepatocytes in vivo, and that biodegradable collagen matrices enhance this phenomenon by providing an appropriate microenvironment for hepatocytic repopulation.

  15. Summary of the British Transplantation Society UK Guidelines for Living Donor Liver Transplantation.

    PubMed

    Manas, Derek; Burnapp, Lisa; Andrews, Peter Antony

    2016-06-01

    The British Transplantation Society Guidelines for Living Donor Liver Transplantation was published in July 2015 and is the first national guideline in the field of living donor liver transplantation. The guideline aims to review the evidence relating to the evaluation process of both recipient and donor candidates; address the moral and ethical issues surrounding the procedure; outline the technical aspects of the procedure, including the middle hepatic vein controversy and the "small for size syndrome"; review donor and recipient outcomes and complications including donor mortality; and examine evidence relating to the advantages and disadvantages of living donor liver transplantation. In line with previous guidelines published by the BTS, the guideline has used the Grading of Recommendations Assessment, Development and Evaluation system to rate the strength of evidence and recommendations. This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for the delivery of living liver donation in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at http://www.bts.org.uk/BTS/Guidelines_Standards/Current/BTS/Guidelines_Standards/Current_Guidelines.aspx?hkey=e285ca32-5920-4613-ac08-fa9fd90915b5. PMID:26950721

  16. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children

    PubMed Central

    Mehl, Ashley; Bohorquez, Humberto; Serrano, Maria-Stella; Galliano, Gretchen; Reichman, Trevor W

    2016-01-01

    Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described. PMID:27358773

  17. Liver transplantation and the management of progressive familial intrahepatic cholestasis in children.

    PubMed

    Mehl, Ashley; Bohorquez, Humberto; Serrano, Maria-Stella; Galliano, Gretchen; Reichman, Trevor W

    2016-06-24

    Progressive familial intrahepatic cholestasis (PFIC) is a constellation of inherited disorders that result in the impairment of bile flow through the liver that predominantly affects children. The accumulation of bile results in progressive liver damage, and if left untreated leads to end stage liver disease and death. Patients often present with worsening jaundice and pruritis within the first few years of life. Many of these patients will progress to end stage liver disease and require liver transplantation. The role and timing of liver transplantation still remains debated especially in the management of PFIC1. In those patients who are appropriately selected, liver transplantation offers an excellent survival benefit. Appropriate timing and selection of patients for liver transplantation will be discussed, and the short and long term management of patients post liver transplantation will also be described. PMID:27358773

  18. Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts.

    PubMed

    Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

    2015-01-01

    During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that's constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

  19. [Reperfusion injury in the isolated rat liver after hypothermic preservation].

    PubMed

    Kopecký, M; Balás, P; Semecký, V; Tilser, I; Rouchalová, E

    2002-03-01

    Histological changes which appear as a result of reperfusion injury of cold-preserved rat liver were studied at intervals of 0 hr, 3 hr, 24 hr and 48 hr of cold storage. The isolated livers were stored in a UW solution (University of Wisconsin), which is used in human liver transplantations. Computer image analysis of light microscopic sections (methyl green-pyronin stained) was used for the study and quantification of injured cells. The method of TUNEL was performed to prove possible apoptosis of sinusoidal endothelial cells and heptocytes. Bile production during reperfusion and ALT, AST, LDH and ACP were measured in the reperfusion medium at the end of the 90 min reperfusion. It has been confirmed that prolongation of the cold storage of liver results in extensive changes in the liver structure and increased injury of liver cells. Sinusoidal endothelial cells were damaged more and earlier than hepatocytes. It has been shown that methyl green-pyronin stained sections are advantageous for the study of these morphological changes, allowing the strongest view of these changes. The appearance of TUNEL positive cells and an increase in the levels of biochemical parameters, e.g. AST or ALT, indicate earlier cell injury. The methodology described in this article can be used for the study of reperfusion injury of the liver and for the study of this phenomenon in other experiments. PMID:11928282

  20. Liver transplantation at the Ochsner Clinic: programmatic expansion and outcomes improvement.

    PubMed

    Carmody, Ian C; Reichman, Trevor W; Bohorquez, Humberto; Cohen, Ari J; Bruce, David S; Therapondos, George; Girgrah, Nigel; Joshi, Shobha; Loss, George E

    2012-01-01

    Liver transplantation has become the best and most durable treatment for both acute and chronic liver disease. Over 1400 liver transplants have been performed at the Ochsner Clinic since the first successful transplant in 1987. Since its inception, the program has gone through several changes and advancements and has become one of the largest liver transplant programs in the United States. We have helped evolve steroid sparing immunosuppression and the use of extended criteria, donor organs. Establishment of criteria for the selection of recipients for re-transplantation has resulted in better than expected short and long-term results. Our center has faced the challenge of Hurricane Katrina and overcome it. We have improved steadily in both outcomes and transplants performed. The Ochnser Clinic Liver Transplant program will continue to improve access and outcomes for all patients with liver disease.

  1. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival

    PubMed Central

    Fahrner, René; Dondorf, Felix; Ardelt, Michael; Dittmar, Yves; Settmacher, Utz; Rauchfuß, Falk

    2015-01-01

    Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation. PMID:26576092

  2. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.

  3. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  4. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  5. Anesthesia in orthotopic liver transplantation. Report of 8 cases.

    PubMed

    Shiao, J; Haosheng, B; Zicheng, M; Chongrong, G

    1981-09-01

    The anesthetic management of orthotopic liver transplantation has become a new problem with special requirements. From the anesthetist's point of view the operation is divided into four phases: the first is the phase of removal of the diseased liver, characterized by heavy bleeding; the second is the anhepatic phase, dominated by a sudden reduction of blood return to the heart due to cross-clamping of inferior vena cava; the third is the phase of partial re-establishment of circulation of the donated liver, marked by a progressive drop in body temperature and great changes in acid-base equilibrium and electrolytes, especially potassium, and disturbances of blood coagulation potassium, and disturbances of blood coagulation; the fourth is the phase of release of the clamps from the inferior vena cava, which causes a rise in the central venous and systolic pressures, and may also aggravate the metabolic acidosis. Eight cases of orthotopic liver transplantation for late-stage unresectable hepatocarcinoma have been operated upon under combined neurolept anesthesia in recent 3 years. The age of the patients is between 29-50 years. We think that neurolept analgesia with the combined use of gamma-OH, diazepam, ketamine and gallamine is one of the safest methods of anesthesia, which has a minimal toxicity to the liver, a smooth induction and rapid recovery of consciousness, and puts little burden on the circulation. The postoperative survival of first seven patients was between 6-264 days. There were no postanesthetic complications in our series. The authors conclude that the proper choice of anesthesia, careful monitoring and judicious management of the patients during the various phases of operation, the maintenance of good condition of the donated liver and skillful surgical technique are the basic requirements for successful transplantation. PMID:7025697

  6. Informational needs of liver transplant recipients during a two-year post transplant period

    PubMed Central

    Ko, Dami; Lee, Insook; Muehrer, Rebecca J

    2016-01-01

    Objectives To describe the informational needs of liver transplant (LTx) recipients, examine potential differences in informational needs by socio-demographic and clinical variables, and examine informational needs at various time points post-transplant. Methods This study used a descriptive, cross-sectional design. Informational needs were assessed by the INQ-liver, a new questionnaire developed to include LTx recipients’ perspective. In order to examine information needs at different post-transplant time points, participants were classified into four groups (0–1, 2–4, 5–9, and 10–24 months post-transplant). Results Participants (159) who were married, single, had higher levels of education, or higher monthly incomes had significantly greater informational needs. Informational needs related to disease and physical and emotional management remained high after transplant. Four subscales (medication, wound management, diet, and daily and social activities) indicated patients experience different informational needs across time. Participants who were 2–4 months post-transplant had higher informational needs related to wound management and daily and social activities. The highest informational needs related to medication and diet were reported by participants who were 5–9 months post-transplant. Discussion The findings indicated that informational needs vary among LTx recipients who are at different time points post-transplant. Marital status, education, and monthly income can influence informational needs. Conclusion Healthcare providers should tailor information given to LTx recipients to their needs at different time points. Longitudinal studies are needed to confirm the changing patterns of informational needs. PMID:26289361

  7. Quality of life after liver transplantation: State of the art

    PubMed Central

    Onghena, Louis; Develtere, Wouter; Poppe, Carine; Geerts, Anja; Troisi, Roberto; Vanlander, Aude; Berrevoet, Frederik; Rogiers, Xavier; Van Vlierberghe, Hans; Verhelst, Xavier

    2016-01-01

    Quality of life (QoL) after deceased donor liver transplantation is increasingly recognized as a major outcome parameter. We reviewed recent publications in this rapidly evolving field in order to summarize recent achievements in the field and to define opportunities and perspectives for research and improvement of patient care. QoL does improve after liver transplantation according to a typical pattern. During the first year, there is a significant improvement in QoL. After one year, the improvement does stabilise and tends to decline slightly. In addition to the physical condition, different psychological parameters (such as depression, anxiety, sexual function) and sociodemographic elements (professional state, sex, marital state) seem to impact QoL. Opportunities for further research are the use of dedicated questionnaires and identification of influencing factors for QoL. PMID:27366301

  8. Anaesthetic considerations for liver transplantation in propionic acidemia

    PubMed Central

    Rajakumar, Akila; Kaliamoorthy, Ilankumaran; Reddy, Mettu Srinivas; Rela, Mohamed

    2016-01-01

    Propionic acidemia (PA) is an autosomal recessive disorder of metabolism due to deficiency of the enzyme propionyl-CoA carboxylase (PCC) that converts propionyl-CoA to methylmalonyl-CoA with the help of the cofactor biotin inside the mitochondria. The resultant accumulation of propionyl-CoA causes severe hyperammonaemia and life-threatening metabolic acidosis. Based on the positive outcomes, liver transplantation is now recommended for individuals with recurrent episodes of hyperammonaemia or acidosis that is not adequately controlled with appropriate medical therapies. We report anaesthetic management of two children with PA for liver transplantation at our institution. It is essential for the anaesthesiologist, caring for these individuals to be familiar with the manifestations of the disease, the triggers for decompensation and management of an acute episode. PMID:26962256

  9. An unusual surgical site infection in a liver transplant recipient

    PubMed Central

    Gandhi, Vidhyachandra; Nagral, Aabha; Nagral, Sanjay; Das, Suryasnata; Rodrigues, Camilla

    2010-01-01

    Mycobacterium abscessus is a rare cause of human infection and is difficult to diagnose unless it is suspected. A 45-year-old woman underwent deceased donor liver transplantation following which she developed non-healing surgical site infection, which did not resolve with routine antibiotics for 2 months. The scraping of the wound revealed M abscessus infection. Definitive identification of this species of mycobacterium was possible by its growth characteristics on culture and reverse line blot hybridisation assay. She was treated with clarithromycin and cotrimaxazole as per sensitivity and showed complete recovery from the infection within 6 weeks of starting the drugs, which were continued for 6 months. We believe that this is the first documented case of surgical site infection by M abscessus in a liver transplant recipient. PMID:22778369

  10. Management of immunosuppressant agents following liver transplantation: Less is more

    PubMed Central

    Ascha, Mustafa S; Ascha, Mona L; Hanouneh, Ibrahim A

    2016-01-01

    Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient. PMID:26839639

  11. Treatment of Hepatitis C Virus Infection in Liver Transplant Recipients

    PubMed Central

    Suraweera, Duminda; Sundaram, Vinay

    2016-01-01

    Chronic hepatitis C virus (HCV) infection is the leading cause of liver transplantation in adults. Although the recurrence of HCV infection after liver transplantation is nearly universal, the recent advances in direct-acting antiviral (DAA) agents have revolutionized the management of HCV infection in the posttransplant setting. A number of these agents have been evaluated in recent clinical trials and have shown high sustained virologic response rates, shorter durations of treatment, and decreased adverse events when compared with the previous treatment of pegylated interferon and ribavirin. This article will review the current literature on the efficacy, tolerability, and potential drug interactions of various DAA agents in patients with recurrent HCV infection posttransplant. PMID:27330501

  12. Melatonin role preventing steatohepatitis and improving liver transplantation results.

    PubMed

    Esteban-Zubero, Eduardo; García-Gil, Francisco Agustín; López-Pingarrón, Laura; Alatorre-Jiménez, Moisés Alejandro; Ramírez, José Manuel; Tan, Dun-Xian; García, José Joaquín; Reiter, Russel J

    2016-08-01

    Liver steatosis is a prevalent process that is induced due to alcoholic or non-alcoholic intake. During the course of these diseases, the generation of reactive oxygen species, followed by molecular damage to lipids, protein and DMA occurs generating organ cell death. Transplantation is the last-resort treatment for the end stage of both acute and chronic hepatic diseases, but its success depends on ability to control ischemia-reperfusion injury, preservation fluids used, and graft quality. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other because of its efficacy in organs; melatonin has been investigated to improve the outcome of organ transplantation by reducing ischemia-reperfusion injury and due to its synergic effect with organ preservation fluids. Moreover, this indolamine also prevent liver steatosis. That is important because this disease may evolve leading to an organ transplantation. This review summarizes the observations related to melatonin beneficial actions in organ transplantation and ischemic-reperfusion models. PMID:27022943

  13. Cytomegalovirus infection following liver transplantation: review of the literature.

    PubMed

    Kanj, S S; Sharara, A I; Clavien, P A; Hamilton, J D

    1996-03-01

    Cytomegalovirus (CMV) remains a major cause of problems following solid organ transplantation, accounting for a significant increase in morbidity and affiliated costs. Infection with CMV following orthotopic liver transplantation (OLT) is commonly seen as a result of marked cell-mediated immunosuppression and is an independent risk factor for opportunistic and fungal infections. The role of CMV infection in acute cellular or chronic rejection remains unclear. Recent advances in diagnostic modalities, particularly the use of the antigenemia assay and the polymerase chain reaction, have provided ways to quantitate viral load during infection or disease, as well as providing a useful marker of response to therapy. Ganciclovir remains the best antiviral agent for the treatment of CMV disease, but the use of combination therapy with other antivirals or CMV immunoglobulin may improve outcome for patients with severe disease. The ideal prophylactic therapy for patients undergoing OLT remains to be identified, as tested regimens have shown variable efficacy when analyzed with regard to defined risk groups. The use of risk group-specific prophylaxis may prove to be most successful, however, in terms of efficacy and cost savings. Future advances in basic CMV virology and transplant immunology will be essential in defining rational approaches to control and prevention of CMV infection and disease following liver transplantation. PMID:8852975

  14. Passive transient transfer of peanut allergy by liver transplantation.

    PubMed

    Dewachter, P; Vézinet, C; Nicaise-Roland, P; Chollet-Martin, S; Eyraud, D; Creusvaux, H; Vaillant, J C; Mouton-Faivre, C

    2011-07-01

    We report a case of transient symptomatic transferred IgE-mediated peanut allergy after elective blood-group compatible liver transplantation. We show that the allergy was transient and therefore passive, authorizing further uneventful peanut consumption. Skin tests with commercial peanut extract and native peanut were performed in the recipient. Circulating specific IgE against peanut and recombinant peanut allergens (rArah1, rArah2, rArah3) was measured in stored serum samples collected from the recipient between 6 months before and 8 months after liver transplantation. Specific IgE levels in the donor were measured at the time of multiorgan donation. In the recipient, diagnosis of IgE-mediated peanut anaphylaxis was based on the clinical history and detection of specific IgE against peanut and recombinant major peanut allergens (rArah1, rArah2 and rArah3). Skin tests were negative and specific IgE undetectable 6 months after the clinical reaction. Oral peanut challenge was negative excluding persistent peanut allergy. This case confirms that IgE-mediated peanut allergy can be transferred by liver transplantation and shows that it may be transient and therefore passively acquired.

  15. Passive transfer of nut allergy after liver transplantation.

    PubMed

    Phan, Tri Giang; Strasser, Simone I; Koorey, David; McCaughan, Geoff W; Rimmer, Janet; Dunckley, Heather; Goddard, Louise; Adelstein, Stephen

    2003-01-27

    An anaphylactic reaction to cashew nut developed in a nonatopic 60-year-old man 25 days after receiving a liver allograft from a 15-year-old atopic boy who died of anaphylaxis after peanut ingestion. The liver recipient had no history of nut allergy. Posttransplantation skin prick test results were positive for peanut, cashew nut, and sesame seed, and the donor had allergen-specific IgE antibodies to the same 3 allergens. Contact tracing of the recipients of other solid organs from the same donor disclosed no other development of allergic symptoms after ingestion of peanut or cashew nut. Results of molecular HLA typing did not detect any donor-origin leukocytes in the recipient after transplantation, which excluded peripheral microchimerism. The patient inadvertently ingested peanut-contaminated food and suffered a second anaphylactic reaction 32 weeks after the transplantation. This case illustrates that transfer of IgE-mediated hypersensitivity can occur after liver transplantation and have potentially serious consequences. We therefore recommend that organ donors undergo screening for allergies, and that recipients be advised regarding allergen avoidance.

  16. Orthotopic liver transplant for multifocal lymphangioendotheliomatosis with thrombocytopenia.

    PubMed

    Yang, Christine H; Zhou, Shengmei; Alexopoulos, Sophoclis; Wang, Larry; Baron, Howard I; Genyk, Yuri; Kerkar, Nanda

    2016-05-01

    An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach-Merritt-like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d-dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan to manage her GI lesions with APC post-transplant. Post-transplant, her liver function and coagulopathy normalized, and GI tract lesions disappeared upon screening with capsule endoscopy. The patient is doing well, without recurrence of either GI lesions or thrombocytopenia, at 18 months after transplantation. PMID:26917412

  17. Liver transplantation: an appraisal of the present situation.

    PubMed

    Otto, Gerd

    2013-01-01

    Liver transplantation (LT) is an established approach to treatment of end-stage liver diseases, metabolic diseases and early hepatocellular carcinoma, and the results of this procedure have improved considerably. MELD allocation and the great number of transplant centers had a negative influence on outcome in Germany. Typical surgical issues following transplantation are vascular thrombosis and the development of biliary lesions. Nonanastomotic strictures impact graft survival and cause considerable posttransplant morbidity. Nonsurgical issues in LT are hepatitis C reinfection, selection of appropriate patients with hepatocellular carcinoma and individualized immunosuppression. In hepatitis C the new antiviral drugs (protease and polymerase inhibitors) are promising tools to prevent reinfection. Nephrotoxicity caused by calcineurin inhibitors - which remain the mainstay of immunosuppression - can only partially be avoided. So far, alternative forms of treatment using mycophenolic acid and mTOR inhibitors cannot totally replace calcineurin inhibitors. In view of graft scarcity, we need to think about a benefit-based model of liver allocation which focuses on the optimal use of this resource. Deciding on this form of organ allocation requires an ethical consensus: not the most urgent patient is the first candidate to receive a graft, but rather the patient who is supposed to have the greatest benefit. PMID:23797139

  18. Role of cardiovascular intervention as a bridge to liver transplantation.

    PubMed

    Raval, Zankhana; Harinstein, Matthew E; Flaherty, James D

    2014-08-21

    End stage liver disease (ESLD) is associated with many specific derangements in cardiovascular physiology, which influence perioperative outcomes and may profoundly influence diagnostic and management strategies in the preoperative period. This review focuses on evidence-based diagnosis and management of coronary, hemodynamic and pulmonary vascular disease in this population with an emphasis on specific strategies that may provide a bridge to transplantation. Specifically, we address the underlying prevalence of cardiovascular disease states in the ESLD population, and relevant diagnostic criteria thereof. We highlight traditional and non-traditional predictors of cardiovascular outcomes following liver transplant, as well as data to guide risk-factor based diagnostic strategies. We go on to discuss the alterations in cardiovascular physiology which influence positive- and negative-predictive values of standard noninvasive testing modalities in the ESLD population, and review the data regarding the safety and efficacy of invasive testing in the face of ESLD and its co-morbidities. Finally, based upon the totality of available data, we outline an evidence-based approach for the management of ischemia, heart failure and pulmonary vascular disease in this population. It is our hope that such evidence-driven strategies can be employed to more safely bridge appropriate candidates to liver transplant, and to improve their cardiovascular health and outcomes in the peri-operative period. PMID:25152569

  19. Passive transient transfer of peanut allergy by liver transplantation.

    PubMed

    Dewachter, P; Vézinet, C; Nicaise-Roland, P; Chollet-Martin, S; Eyraud, D; Creusvaux, H; Vaillant, J C; Mouton-Faivre, C

    2011-07-01

    We report a case of transient symptomatic transferred IgE-mediated peanut allergy after elective blood-group compatible liver transplantation. We show that the allergy was transient and therefore passive, authorizing further uneventful peanut consumption. Skin tests with commercial peanut extract and native peanut were performed in the recipient. Circulating specific IgE against peanut and recombinant peanut allergens (rArah1, rArah2, rArah3) was measured in stored serum samples collected from the recipient between 6 months before and 8 months after liver transplantation. Specific IgE levels in the donor were measured at the time of multiorgan donation. In the recipient, diagnosis of IgE-mediated peanut anaphylaxis was based on the clinical history and detection of specific IgE against peanut and recombinant major peanut allergens (rArah1, rArah2 and rArah3). Skin tests were negative and specific IgE undetectable 6 months after the clinical reaction. Oral peanut challenge was negative excluding persistent peanut allergy. This case confirms that IgE-mediated peanut allergy can be transferred by liver transplantation and shows that it may be transient and therefore passively acquired. PMID:21668638

  20. Liver transplantation in Latin America: the state-of-the-art and future trends.

    PubMed

    Salvalaggio, Paolo R; Caicedo, Juan C; de Albuquerque, Luiz Carneiro; Contreras, Alan; Garcia, Valter D; Felga, Guilherme E; Maurette, Rafael J; Medina-Pestana, José O; Niño-Murcia, Alejandro; Pacheco-Moreira, Lucio F; Rocca, Juan; Rodriguez-Davalos, Manuel; Ruf, Andres; Rusca, Luis A Caicedo; Vilatoba, Mario

    2014-08-15

    We reviewed the current status of liver transplantation in Latin America. We used data from the Latin American and Caribbean Transplant Society and national organizations and societies, as well as information obtained from local transplant leaders. Latin America has a population of 589 million (8.5% of world population) and more than 2,500 liver transplantations are performed yearly (17% of world activity), resulting in 4.4 liver transplants per million people (pmp) per year. The number of liver transplantations grows at 6% per year in the region, particularly in Brazil. The top liver transplant rates were found in Argentina (10.4 pmp), Brazil (8.4 pmp), and Uruguay (5.5 pmp). The state of liver transplantation in some countries rivals those in developed countries. Model for End-Stage Liver Disease-based allocation, split, domino, and living-donor adult and pediatric transplantations are now routinely performed with outcomes comparable to those in advanced economies. In contrast, liver transplantation is not performed in 35% of Latin American countries and lags adequate resources in many others. The lack of adequate financial coverage, education, and organization is still the main limiting factor in the development of liver transplantation in Latin America. The liver transplant community in the region should push health care leaders and authorities to comply with the Madrid and Istambul resolutions on organ donation and transplantation. It must pursue fiercely the development of registries to advance the science and quality control of liver transplant activities in Latin America. PMID:25093292

  1. Successful staged kidney and liver transplantation for glycogen storage disease type Ib: A case report.

    PubMed

    Martin, A P; Bartels, M; Schreiber, S; Buehrdel, P; Hauss, J; Fangmann, J

    2006-12-01

    Glycogen storage disease type Ib is a rare metabolic disease caused by a defect of the G6P transporter. Patients suffer from hypoglycemic episodes; growth and developmental delay; osteoporosis; neutropenia; and tendency to infections, ovarian cysts, and liver adenomas. Terminal kidney disease is a rare complication. Liver transplantation has been performed to prevent malignant transformation of hepatic adenomas. We present the case of a female patient with glycogenosis type Ib who had severe hypoglycemic episodes and recurrent infections since early childhood. She became dialysis dependent at the age of 24 years. Kidney transplantation was performed at age 30, and liver transplantation 2 years later. The main indication for liver transplantation were the persistent, therapy-refractory hypoglycemic episodes. The transplanted kidney function is stable. The liver transplantation resulted in the disappearance of hypoglycemic episodes, with the patient leading a normal life and eating a normal diet. The neutropenia did not recover, but there were no more significant infectious episodes after liver transplantation. This is, to the best of our knowledge, the first communication of a dual kidney and liver transplant performed in a patient with glycogenosis type Ib. It confirmed the beneficial effect of liver transplantation on the quality of life of patients with severe hypoglycemia. The transplantation should be attempted earlier in the course of the disease to reduce complications and allow catch-up growth. Hepatocyte transplantation may be considered; however, long-term results seem to be rather poor in the few documented cases. PMID:17175348

  2. Usefulness of liver stiffness measurement during acute cellular rejection in liver transplantation.

    PubMed

    Crespo, Gonzalo; Castro-Narro, Graciela; García-Juárez, Ignacio; Benítez, Carlos; Ruiz, Pablo; Sastre, Lydia; Colmenero, Jordi; Miquel, Rosa; Sánchez-Fueyo, Alberto; Forns, Xavier; Navasa, Miquel

    2016-03-01

    Liver stiffness measurement (LSM) is a useful method to estimate liver fibrosis and portal hypertension. The inflammatory process that takes place in post-liver transplant acute cellular rejection (ACR) may also increase liver stiffness. We aimed to explore the association between liver stiffness and the severity of ACR, as well as to assess the relationship between liver stiffness and response to rejection treatment in a prospective study that included 27 liver recipients with biopsy-proven ACR, 30 stable recipients with normal liver tests, and 30 hepatitis C virus (HCV)-infected LT recipients with histologically diagnosed HCV recurrence. Patients with rejection were stratified into 2 groups (mild and moderate/severe) according to the severity of rejection evaluated with the Banff score. Routine biomarkers and LSM with FibroScan were performed at the time of liver biopsy (baseline) and at 7, 30, and 90 days in patients with rejection and at baseline in control patients. Median baseline liver stiffness was 5.9 kPa in the mild rejection group, 11 kPa in the moderate/severe group (P = 0.001), 4.2 kPa in stable recipients (P = 0.02 versus mild rejection), and 13.6 kPa in patients with recurrent HCV (P = 0.17 versus moderate/severe rejection). The area under the receiver operator characteristic curve of LSM to discriminate mild versus moderate/severe ACR was 0.924, and a LSM value of 8.5 kPa yielded a positive predictive value of 100% to diagnose moderate/severe rejection. Liver stiffness improved in 7%, 21%, and 64% of patients with moderate/severe rejection at 7, 30, and 90 days. In conclusion, according to the results of this exploratory study, LSM is associated with the severity of ACR in liver transplantation and thus may be of help in its assessment. PMID:26609794

  3. Effect of living donor liver transplantation on outcome of children with inherited liver disease and hepatocellular carcinoma.

    PubMed

    Ozçay, Figen; Canan, Oğuz; Bilezikçi, Banu; Torgay, Adnan; Karakayali, Hamdi; Haberal, Mehmet

    2006-01-01

    We described six children with heritable liver disease and hepatocellular carcinoma treated with living-related liver transplantation. Underlying liver diseases were type-1 tyrosinemia (three patients), progressive familial intrahepatic cholestasis type II (two patients), and Wilson's disease (one patient). Two of the tumors were found incidentally during liver transplantation. Number of nodules was 12, 15, 3, 2, and 1 (in two patients). Three patients were treated with chemotherapy before the procedure. Chemotherapy was not given to any patient after liver transplantation. The mean follow-up was 17.7 +/- 6 months (range: 7-24). All patients are tumor recurrence free. Both graft and patient survival rates are 100% at a median of 18.5 months follow-up. Physicians in charge of treating children with heritable liver disease should screen them periodically for the development of hepatocellular carcinoma. Liver transplantation may offer these children better survival rates.

  4. Current techniques for AB0-incompatible living donor liver transplantation.

    PubMed

    Rummler, Silke; Bauschke, Astrid; Bärthel, Erik; Jütte, Heike; Maier, Katrin; Ziehm, Patrice; Malessa, Christina; Settmacher, Utz

    2016-09-24

    For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients' graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0i LDLT is a feasible option today and almost free of severe complications. PMID:27683633

  5. Current techniques for AB0-incompatible living donor liver transplantation

    PubMed Central

    Rummler, Silke; Bauschke, Astrid; Bärthel, Erik; Jütte, Heike; Maier, Katrin; Ziehm, Patrice; Malessa, Christina; Settmacher, Utz

    2016-01-01

    For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients’ graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0i LDLT is a feasible option today and almost free of severe complications. PMID:27683633

  6. Current techniques for AB0-incompatible living donor liver transplantation

    PubMed Central

    Rummler, Silke; Bauschke, Astrid; Bärthel, Erik; Jütte, Heike; Maier, Katrin; Ziehm, Patrice; Malessa, Christina; Settmacher, Utz

    2016-01-01

    For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients’ graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0i LDLT is a feasible option today and almost free of severe complications.

  7. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    PubMed

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  8. Early post-transplant neopterin associated with one year survival and bacteremia in liver transplant recipients.

    PubMed

    Oweira, Hani; Lahdou, Imad; Daniel, Volker; Hofer, Stefan; Mieth, Markus; Schmidt, Jan; Schemmer, Peter; Opelz, Gerhard; Mehrabi, Arianeb; Sadeghi, Mahmoud

    2016-01-01

    Bacterial infections are the most common complications, and the major cause of mortality after liver transplantation (Tx). Neopterin, a marker of immune activation, is produced in monocyte/macrophages in response to inflammation. The aim of our study was to investigate whether early post-operation serum levels of neopterin were associated with post-transplant bacteremia and mortality in liver transplant recipients. We studied 162 of 262 liver Tx patients between January 2008 and February 2011 of whom pre- and early post-Tx sera samples were available. Pre- and early post-operative risk factors of infection and mortality were evaluated in 45 bacteremic patients and 117 non-bacteremic patients. During one-year follow-up, 28 of 262 patients died because of graft failure, septicemia and other diseases. Post-Tx serum neopterin on day 10 (p<0.001) were significantly higher in bacteriemic patients than in patients without bacteremia. Logistic regression analyses showed that day 10 post-Tx neopterin serum level ⩾40 nmol/l has a predictive value (OR=6.86: p<0.001) for bacteremia and mortality (OR=3.47: p=0.021). Our results suggest that early post-Tx neopterin serum levels are very sensitive predictive markers of one-year post-Tx bacteremia and mortality in liver Tx recipients.

  9. From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting liver transplantation.

    PubMed

    Umbro, I; Tinti, F; Fiacco, F; Zavatto, A; Di Natale, V; Ginanni Corradini, S; Rossi, M; Poli, L; Berloco, P B; Mitterhofer, A P

    2013-09-01

    Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of evaluation for orthotopic liver transplantation (OLT). The numerous causes of renal dysfunction in ESLD patients sometimes relate to the extent of liver damage or sometimes more closely to organic nephropathy. The aim of this study was to evaluate renal function through a specific nephrologic form applied in our outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April 2008 to January 2012. All patients were evaluated at listing and every 3 months until OLT. The most interesting result was the stable values of serum creatinine from listing to transplantation. We think that dedicated liver transplant nephrologic evaluation is important in the follow-up of ESLD patients awaiting OLT, because the presence of renal dysfunction may represent an important criterion for specific therapeutic interventions to minimize pre-OLT renal injuries that limit the effect of impaired renal function on patient outcomes.

  10. Antioxidant Effects of Bone Marrow Mesenchymal Stem Cell against Carbon Tetrachloride-Induced Oxidative Damage in Rat Livers

    PubMed Central

    Ayatollahi, M.; Hesami, Z.; Jamshidzadeh, A.; Gramizadeh, B.

    2014-01-01

    Background: Liver fibrosis results from excessive accumulation of extracellular matrix, which affects liver function over time and leads to its failure. In the past, liver transplant was thought to be the only treatment for end-stage liver disease, but due to the shortage of proper donors other medical treatments have been taken into consideration. Objective: To evaluate the therapeutic effects of bone marrow derived mesenchymal stem cells (BM-MSC) in CCl4 damaged rats. Methods: Liver damage in adult male Wistar rats was induced with carbon tetrachloride (CCl4). The rats were divided into normal control group, receiving CCl4, and those receiving CCl4 + marrow derived-MSC. Human BM-MSC was isolated, cultured, and characterized. The rats were injected with xenograft MSCs into the hepatic lobes of the liver. In the eighth week, blood samples were taken from all groups. Histological examination and biochemical analyses were used to compare the morphological and functional liver regeneration among different groups. Measurement of lipid peroxidation and glutathione transferase activity was also performed. Results: Histopathology and biochemical analyses indicated that local injection of human BM-MSCs was effective in treating liver failure in the rat model. Furthermore, oxidative stress was attenuated by increased level of GSH content after MSC transplantation. Conclusion: Evidence of this animal model approach showed that bone marrow-derived MSCs promote an antioxidant response and support the potential of using MSCs transplantation as an effective treatment modality for liver disease. PMID:25426285

  11. Beyond the Pediatric end-stage liver disease system: solutions for infants with biliary atresia requiring liver transplant.

    PubMed

    Tessier, Mary Elizabeth M; Harpavat, Sanjiv; Shepherd, Ross W; Hiremath, Girish S; Brandt, Mary L; Fisher, Amy; Goss, John A

    2014-08-28

    Biliary atresia (BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches: (1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and (2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant. PMID:25170195

  12. Changing Pattern of Donor Selection Criteria in Deceased Donor Liver Transplant: A Review of Literature

    PubMed Central

    Routh, Dronacharya; Naidu, Sudeep; Sharma, Sanjay; Ranjan, Priya; Godara, Rajesh

    2013-01-01

    During the last couple of decades, with standardization and progress in surgical techniques, immunosuppression and post liver transplantation patient care, the outcome of liver transplantation has been optimized. However, the principal limitation of transplantation remains access to an allograft. The number of patients who could derive benefit from liver transplantation markedly exceeds the number of available deceased donors. The large gap between the growing list of patients waiting for liver transplantation and the scarcity of donor organs has fueled efforts to maximize existing donor pool and identify new avenues. This article reviews the changing pattern of donor for liver transplantation using grafts from extended criteria donors (elderly donors, steatotic donors, donors with malignancies, donors with viral hepatitis), donation after cardiac death, use of partial grafts (split liver grafts) and other suboptimal donors (hypernatremia, infections, hypotension and inotropic support). PMID:25755521

  13. Amelioration of Hyperbilirubinemia in Gunn Rats after Transplantation of Human Induced Pluripotent Stem Cell-Derived Hepatocytes

    PubMed Central

    Chen, Yong; Li, Yanfeng; Wang, Xia; Zhang, Wei; Sauer, Vanessa; Chang, Chan-Jung; Han, Bing; Tchaikovskaya, Tatyana; Avsar, Yesim; Tafaleng, Edgar; Madhusudana Girija, Sanal; Tar, Krisztina; Polgar, Zsuzsanna; Strom, Stephen; Bouhassira, Eric E.; Guha, Chandan; Fox, Ira J.; Roy-Chowdhury, Jayanta; Roy-Chowdhury, Namita

    2015-01-01

    Summary Hepatocyte transplantation has the potential to cure inherited liver diseases, but its application is impeded by a scarcity of donor livers. Therefore, we explored whether transplantation of hepatocyte-like cells (iHeps) differentiated from human induced pluripotent stem cells (iPSCs) could ameliorate inherited liver diseases. iPSCs reprogrammed from human skin fibroblasts were differentiated to iHeps, which were transplanted into livers of uridinediphosphoglucuronate glucuronosyltransferase-1 (UGT1A1)-deficient Gunn rats, a model of Crigler-Najjar syndrome 1 (CN1), where elevated unconjugated bilirubin causes brain injury and death. To promote iHep proliferation, 30% of the recipient liver was X-irradiated before transplantation, and hepatocyte growth factor was expressed. After transplantation, UGT1A1+ iHep clusters constituted 2.5%–7.5% of the preconditioned liver lobe. A decline of serum bilirubin by 30%–60% and biliary excretion of bilirubin glucuronides indicated that transplanted iHeps expressed UGT1A1 activity, a postnatal function of hepatocytes. Therefore, iHeps warrant further exploration as a renewable source of hepatocytes for treating inherited liver diseases. PMID:26074313

  14. PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

    PubMed Central

    Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

    2014-01-01

    Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

  15. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation.

    PubMed

    Yderstraede, K B; Starklint, H; Steinbruchel, D; Jørgensen, T W; Gotfredsen, C F

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding. PMID:8401812

  16. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation.

    PubMed

    Yderstraede, K B; Starklint, H; Steinbruchel, D; Jørgensen, T W; Gotfredsen, C F

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding.

  17. Clostridium difficile Infection in Hospitalized Liver Transplant Patients: A Nationwide Analysis

    PubMed Central

    Ali, Muhammad; Ananthakrishnan, Ashwin N.; Ahmad, Shahryar; Kumar, Nilay; Kumar, Gagan; Saeian, Kia

    2012-01-01

    Introduction Incidence of Clostridium difficile infection (CDI) is increasing among hospitalized patients. Liver transplant patients are at higher risk for acquiring CDI. Small, single-center studies, but no nation-wide analyses, have assessed this association. Methods We used the Healthcare Cost and Utilization Project- Nationwide Inpatient Sample (HCUP-NIS) from years 2004–2008 for this retrospective cross sectional study. Patients with any discharge diagnosis of liver transplant comprised the study population and were identified using ICD-9-CM codes. Those with a discharge diagnosis of CDI were considered cases. Our primary outcomes were prevalence of CDI and effect of CDI on inpatient mortality. Our secondary outcomes included length of stay and hospitalization charges. Regression analysis was used to derive odds ratios adjusted for potential confounders. Results There were 193,714 discharges with a diagnosis of liver transplant from 2004–2008. Prevalence of CDI was 2.7% in liver transplant population compared to 0.9% in non liver transplant population (p <0.001). Most of the liver transplant patients were in the 50–64 age group. Liver transplant patients were at higher odds of developing CDI (OR 2.88, 95% CI 2.68–3.10). Increasing age, increasing comorbidity, IBD and NG tube placement were also independent risk factors for CDI. CDI in liver transplant was associated with a higher mortality, 5.5% as compared to 2.3% in liver transplant only population (adjusted OR 1.7, 95% CI 1.3–2.2). Conclusions Liver transplant patients have a higher prevalence of CDI as compared to non liver transplant patients (2.7% vs. 0.9%).CDI was an independent risk factor for mortality in liver transplant population. PMID:22505356

  18. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

    PubMed Central

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  19. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.

    PubMed

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-08-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  20. Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation

    PubMed Central

    Remiszewski, Piotr; Szczerba, Ewa; Kalinowski, Piotr; Gierej, Beata; Dudek, Krzysztof; Grodzicki, Mariusz; Kotulski, Marcin; Paluszkiewicz, Rafał; Patkowski, Waldemar; Zieniewicz, Krzysztof; Krawczyk, Marek

    2014-01-01

    AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE). METHODS: Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ2 test. A P-value < 0.05 indicated statistical significance. RESULTS: No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ2 test = 1.784, df = 2, P = 0.409). CONCLUSION: Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients. PMID:25170219

  1. Definition and classification of negative outcomes in solid organ transplantation. Application in liver transplantation.

    PubMed Central

    Clavien, P A; Camargo, C A; Croxford, R; Langer, B; Levy, G A; Greig, P D

    1994-01-01

    OBJECTIVE: This study defined negative outcomes of solid organ transplantation, proposed a new classification of complications by severity, and applied the classification to evaluate the results of orthotopic liver transplantation (OLT). SUMMARY AND BACKGROUND DATA: The lack of uniform reporting of negative outcomes has made reports of transplantation procedures difficult to interpret and compare. In fact, only mortality is well reported; morbidity rates and severity of complications have been poorly described. METHODS: Based on previous definition and classification of complications for general surgery, a new classification for transplantation in four grades is proposed. Results including risk factors of the first 215 OLTs performed at the University of Toronto have been evaluated using the classification. RESULTS: All but two patients (99%) had at least one complication of any kind, 92% of patients surviving more than 3 months had grade 1 (minor) complications, 74% had grade 2 (life-threatening) complications, and 30% had grade 3 (residual disability or cancer) complications. Twenty-nine per cent of patients had grade 4 complications (retransplantation or death). The most common grade 1 complications were steroid responsive rejection (69% of patients) and infection that did not require antibiotics or invasive procedures (23%). Grade 2 complications primarily were infection requiring antibiotics or invasive procedures (64%), postoperative bleeding requiring > 3 units of packed red cells (35%), primary dysfunction (26%), and biliary disease treated with antibiotics or requiring invasive procedures (18%). The most frequent grade 3 complication was renal failure, which is defined as a permanent rise in serum creatinine levels > or = twice the pretransplantation values (11%). Grade 4 complications (retransplantation or death) mainly were infection (14%) and primary dysfunction (11%). Comparison between the first and last 50 OLTs of the series indicates a significant

  2. Liver transplantation for Wilson's disease in pediatric patients: decision making and timing.

    PubMed

    Narumi, S; Umehara, M; Toyoki, Y; Ishido, K; Kudo, D; Kimura, N; Kobayashi, T; Sugai, M; Hakamada, K

    2012-03-01

    Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilson's disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilson's disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention.

  3. Cardiovascular risk assessment of the liver transplant candidate.

    PubMed

    Raval, Zankhana; Harinstein, Matthew E; Skaro, Anton I; Erdogan, Ata; DeWolf, Andre M; Shah, Sanjiv J; Fix, Oren K; Kay, Nina; Abecassis, Michael I; Gheorghiade, Mihai; Flaherty, James D

    2011-07-12

    Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.

  4. Liver transplantation for cholangiocarcinoma: Current status and new insights

    PubMed Central

    Sapisochín, Gonzalo; Fernández de Sevilla, Elena; Echeverri, Juan; Charco, Ramón

    2015-01-01

    Cholangiocarcinoma is a malignant tumor of the biliary system that can be classified into intrahepatic (iCCA), perihiliar (phCCA) and distal. Initial experiences with orthotopic liver transplantation (OLT) for patients with iCCA and phCCA had very poor results and this treatment strategy was abandoned. In the last decade, thanks to a strict selection process and a neoadjuvant chemoradiation protocol, the results of OLT for patients with non-resectable phCCA have been shown to be excellent and this strategy has been extended worldwide in selected transplant centers. Intrahepatic cholangiocarcinoma is a growing disease in most countries and can be diagnosed both in cirrhotic and in non-cirrhotic livers. Even though OLT is contraindicated in most centers, recent investigations analyzing patients that were transplanted with a misdiagnosis of HCC and were found to have an iCCA have shown encouraging results. There is some information suggesting that patients with early stages of the disease could benefit from OLT. In this review we analyze the current state-of-the-art of OLT for cholangiocarcinoma as well as the new insights and future perspectives. PMID:26464755

  5. Predictive roles of intraoperative blood glucose for post-transplant outcomes in liver transplantation.

    PubMed

    Park, Chul Soo

    2015-06-14

    Diabetogenic traits in patients undergoing liver transplantation (LT) are exacerbated intraoperatively by exogenous causes, such as surgical stress, steroids, blood transfusions, and catecholamines, which lead to intraoperative hyperglycemia. In contrast to the strict glucose control performed in the intensive care unit, no systematic protocol has been developed for glucose management during LT. Intraoperative blood glucose concentrations typically exceed 200 mg/dL in LT, and extreme hyperglycemia (> 300 mg/dL) is common during the neohepatic phase. Only a few retrospective studies have examined the relationship between intraoperative hyperglycemia and post-transplant complications, with reports of infectious complications or mortality. However, no prospective studies have been conducted regarding the influence of intraoperative hyperglycemia in LT on post-transplant outcome. In addition to absolute blood glucose values, the temporal patterns in blood glucose levels during LT may serve as prognostic features. Persistent neohepatic hyperglycemia (without a decline) throughout LT is a useful indicator of early graft dysfunction. Moreover, intraoperative variability in glucose levels may predict the need for reoperation for hemorrhage after LT. Thus, there is an urgent need for guidelines for glucose control in these patients, as well as prospective studies on the impact of glucose control on various post-transplant complications. This report highlights some of the recent studies related to perioperative blood glucose management focused on LT and liver disease. PMID:26078559

  6. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients

    PubMed Central

    Obed, Aiman; Stern, Steffen; Jarrad, Anwar; Lorf, Thomas

    2015-01-01

    Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed. PMID:25892898

  7. The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

    PubMed

    Zhang, Qi-Kun; Wang, Meng-Long

    2015-10-01

    Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.

  8. Problem of living liver donation in the absence of deceased liver transplantation program: Mansoura experience.

    PubMed

    Wahab, Mohamed Abdel; Hamed, Hosam; Salah, Tarek; Elsarraf, Waleed; Elshobary, Mohamed; Sultan, Ahmed Mohamed; Shehta, Ahmed; Fathy, Omar; Ezzat, Helmy; Yassen, Amr; Elmorshedi, Mohamed; Elsaadany, Mohamed; Shiha, Usama

    2014-10-01

    We report our experience with potential donors for living donor liver transplantation (LDLT), which is the first report from an area where there is no legalized deceased donation program. This is a single center retrospective analysis of potential living donors (n = 1004) between May 2004 and December 2012. This report focuses on the analysis of causes, duration, cost, and various implications of donor exclusion (n = 792). Most of the transplant candidates (82.3%) had an experience with more than one excluded donor (median = 3). Some recipients travelled abroad for a deceased donor transplant (n = 12) and some died before finding a suitable donor (n = 14). The evaluation of an excluded donor is a time-consuming process (median = 3 d, range 1 d to 47 d). It is also a costly process with a median cost of approximately 70 USD (range 35 USD to 885 USD). From these results, living donor exclusion has negative implications on the patients and transplant program with ethical dilemmas and an economic impact. Many strategies are adopted by other centers to expand the donor pool; however, they are not all applicable in our locality. We conclude that an active legalized deceased donor transplantation program is necessary to overcome the shortage of available liver grafts in Egypt. PMID:25309092

  9. Nutrition therapy: Integral part of liver transplant care.

    PubMed

    Anastácio, Lucilene Rezende; Davisson Correia, Maria Isabel Toulson

    2016-01-28

    Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality. PMID:26819518

  10. Nutrition therapy: Integral part of liver transplant care.

    PubMed

    Anastácio, Lucilene Rezende; Davisson Correia, Maria Isabel Toulson

    2016-01-28

    Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality.

  11. Nutrition therapy: Integral part of liver transplant care

    PubMed Central

    Anastácio, Lucilene Rezende; Davisson Correia, Maria Isabel Toulson

    2016-01-01

    Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality. PMID:26819518

  12. Interferon-gamma inducible protein 10 (IP10) induced cisplatin resistance of HCC after liver transplantation through ER stress signaling pathway

    PubMed Central

    Geng, Wei; Lo, Chung-Mau; Ng, Kevin T.P.; Ling, Chang-Chun; Qi, Xiang; Li, Chang-Xian; Zhai, Yuan; Liu, Xiao-Bing; Ma, Yuen-Yuen; Man, Kwan

    2015-01-01

    Tumor recurrence remains an obstacle after liver surgery, especially in living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC). The acute-phase liver graft injury might potentially induce poor response to chemotherapy in recurrent HCC after liver transplantation. We here intended to explore the mechanism and to identify a therapeutic target to overcome such chemoresistance. The associations among graft injury, overexpression of IP10 and multidrug resistant genes were investigated in a rat liver transplantation model, and further validated in clinical cohort. The role of IP10 on HCC cell proliferation and tumor growth under chemotherapy was studied both in vitro and in vivo. The underlying mechanism was revealed by detecting the activation of endoplasmic reticulum (ER) stress signaling pathways. Moreover, the effect of IP10 neutralizing antibody sensitizing cisplatin treatment was further explored. In rat liver transplantation model, significant up-regulation of IP10 associated with multidrug resistant genes was found in small-for-size liver graft. Clinically, high expression of circulating IP10 was significant correlated with tumor recurrence in HCC patients underwent LDLT. Overexpression of IP10 promoted HCC cell proliferation and tumor growth under cisplatin treatment by activation of ATF6/Grp78 signaling. IP10 neutralizing antibody sensitized cisplatin treatment in nude mice. The overexpression of IP10, which induced by liver graft injury, may lead to cisplatin resistance via ATF6/Grp78 ER stress signaling pathway. IP10 neutralizing antibody could be a potential adjuvant therapy to sensitize cisplatin treatment. PMID:26336986

  13. Relative Quantification of Several Plasma Proteins during Liver Transplantation Surgery

    PubMed Central

    Parviainen, Ville; Joenväärä, Sakari; Tukiainen, Eija; Ilmakunnas, Minna; Isoniemi, Helena; Renkonen, Risto

    2011-01-01

    Plasma proteome is widely used in studying changes occurring in human body during disease or other disturbances. Immunological methods are commonly used in such studies. In recent years, mass spectrometry has gained popularity in high-throughput analysis of plasma proteins. In this study, we tested whether mass spectrometry and iTRAQ-based protein quantification might be used in proteomic analysis of human plasma during liver transplantation surgery to characterize changes in protein abundances occurring during early graft reperfusion. We sampled blood from systemic circulation as well as blood entering and exiting the liver. After immunodepletion of six high-abundant plasma proteins, trypsin digestion, iTRAQ labeling, and cation-exchange fractionation, the peptides were analyzed by reverse phase nano-LC-MS/MS. In total, 72 proteins were identified of which 31 could be quantified in all patient specimens collected. Of these 31 proteins, ten, mostly medium-to-high abundance plasma proteins with a concentration range of 50–2000 mg/L, displayed relative abundance change of more than 10%. The changes in protein abundance observed in this study allow further research on the role of several proteins in ischemia-reperfusion injury during liver transplantation and possibly in other surgery. PMID:22187521

  14. Relative quantification of several plasma proteins during liver transplantation surgery.

    PubMed

    Parviainen, Ville; Joenväärä, Sakari; Tukiainen, Eija; Ilmakunnas, Minna; Isoniemi, Helena; Renkonen, Risto

    2011-01-01

    Plasma proteome is widely used in studying changes occurring in human body during disease or other disturbances. Immunological methods are commonly used in such studies. In recent years, mass spectrometry has gained popularity in high-throughput analysis of plasma proteins. In this study, we tested whether mass spectrometry and iTRAQ-based protein quantification might be used in proteomic analysis of human plasma during liver transplantation surgery to characterize changes in protein abundances occurring during early graft reperfusion. We sampled blood from systemic circulation as well as blood entering and exiting the liver. After immunodepletion of six high-abundant plasma proteins, trypsin digestion, iTRAQ labeling, and cation-exchange fractionation, the peptides were analyzed by reverse phase nano-LC-MS/MS. In total, 72 proteins were identified of which 31 could be quantified in all patient specimens collected. Of these 31 proteins, ten, mostly medium-to-high abundance plasma proteins with a concentration range of 50-2000 mg/L, displayed relative abundance change of more than 10%. The changes in protein abundance observed in this study allow further research on the role of several proteins in ischemia-reperfusion injury during liver transplantation and possibly in other surgery.

  15. Indication of liver transplantation for hepatocellular carcinoma in Japan.

    PubMed

    Tanikawa, K

    1992-01-01

    Approximately 20,000 patients die of hepatocellular carcinoma (HCC) annually in Japan and most of them are hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers. Recently, small HCC, less than 3 cm in diameter, have frequently been found by ultrasonography in the follow-up of patients with chronic liver diseases. Such cases are mainly treated by either surgical resection or percutaneous ethanol injection therapy (PEIT) with a satisfactory 5 year survival rate of 50%. In addition, the survival rate of advanced cases has gradually improved thanks to transcatheter arterial chemo-embolization combined with PEIT, radiation, hyperthermia, or immune therapy. On the other hand, our autopsy study has indicated a high frequency of extrahepatic metastasis in advanced cases. From these results, liver transplantation for HCC does not seem to be the treatment of first choice, at present, in Japan. In the future, the means to control the underlying infection of HBV or HCV as well as making an accurate imaging diagnosis for the detection of extrahepatic metastasis will become inevitably more important for successful liver transplantation in HCC.

  16. Challenges to liver transplantation and strategies to improve outcomes.

    PubMed

    Dutkowski, Philipp; Linecker, Michael; DeOliveira, Michelle L; Müllhaupt, Beat; Clavien, Pierre-Alain

    2015-02-01

    Liver transplantation (LT) is a highly successful treatment for many patients with nonmalignant and malignant liver diseases. However, there is a worldwide shortage of available organs; many patients deteriorate or die while on waiting lists. We review the important clinical challenges to LT and the best use of the scarce organs. We focus on changes in indications for LT and discuss scoring systems to best match donors with recipients and optimize outcomes, particularly for the sickest patients. We also cover controversial guidelines for the use of LT in patients with hepatocellular carcinoma and cholangiocarcinoma. Strategies to increase the number of functional donor organs involve techniques to perfuse the organs before implantation. Partial LT (living donor and split liver transplantation) techniques might help to overcome organ shortages, and we discuss small-for-size syndrome. Many new developments could increase the success of this procedure, which is already one of the major achievements in medicine during the second part of the 20th century. PMID:25224524

  17. Measuring Coping Behavior in Liver Transplant Candidates: A Psychometric Analysis of the Brief COPE.

    PubMed

    Amoyal, Nicole; Fernandez, Anne C; Ng, Reuben; Fehon, Dwain C

    2016-09-01

    Liver transplant candidates must cope with significant physiological and psychological challenges. The Brief COPE is a frequently used measure of coping behavior; however, knowledge of the scale's factor structure and construct validity is limited with regard to liver transplant candidates. This study assessed the validity of the Brief COPE in 120 liver transplant candidates using exploratory factor analysis. Results revealed a 6-factor solution, only 2 of which were consistent with the original scale assignments. Construct validity of the 6 Brief COPE scales yielded in this study was demonstrated. The results indicate that the Brief COPE is valid, reliable, and can be meaningfully interpreted in liver transplant patients. Future research should confirm this factor structure and examine its predictive validity prior to widespread use among liver transplant patients. Suggestions are presented for enhancing the care of transplant candidates by promoting the use of adaptive coping mechanisms to manage distress.

  18. Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by TNF-α and PGE2 and is crucial for liver transplant tolerance.

    PubMed

    You, Yu; Zhang, Jiqin; Gong, Jianping; Chen, Yupei; Li, Yue; Yang, Kang; Liu, Zuojin

    2015-07-01

    The role of mesenchymal stromal cells (MSCs) in the modulation of liver transplant tolerance has attracted significant interest. However, the interaction between MSCs and Kupffer cells (KCs) has received little attention, and the effect of this interaction on liver transplant tolerance remains unclear. KCs were cultured in the presence and absence of MSCs. After 24 h, cells were treated with lipopolysaccharide (LPS), after which the production of cytokines and the expression of surface antigens were measured for cell function identification. Moreover, the effects of the KCs and the prostaglandin E2 (PGE2) levels produced by the MSCs were determined using an experimental rat liver transplantation model. Blood and liver samples were collected at three time points after transplantation for further analysis. After LPS treatment, when compared with the KC single cultures, the expression of pro-inflammatory cytokines (IL-1β, IL-6, MHC-II, CD40, CD80, and CD86) in the coculture system was down-regulated, whereas the expression of anti-inflammatory cytokines (TGF-β, IL-4, PGE2, and IL-10) was markedly increased. These data indicate that MSCs can reprogram the phenotype of KCs. However, KCs treated with miR/TNF-α (tumor necrosis factor) plasmid prior to coculture to inhibit the production of TNF-α resulted in an inhibition of the reprogramming effect of MSCs. Moreover, overexpression of PGE2 in MSCs increased the effect of MSCs on KC reprogramming. After rat liver transplantation, allograft recipients that received MSCs showed better allograft tolerance when compared with rats in which KC function was inhibited. Furthermore, rats treated with MSCs overexpressing PGE2 demonstrated the best liver tolerance of all of the groups tested. MSCs reprogram the phenotype of KCs through TNF-α and PGE2, and this process is crucial for the immunomodulatory function of MSCs in liver transplantation. PMID:25982496

  19. Mesenchymal stromal cell-dependent reprogramming of Kupffer cells is mediated by TNF-α and PGE2 and is crucial for liver transplant tolerance.

    PubMed

    You, Yu; Zhang, Jiqin; Gong, Jianping; Chen, Yupei; Li, Yue; Yang, Kang; Liu, Zuojin

    2015-07-01

    The role of mesenchymal stromal cells (MSCs) in the modulation of liver transplant tolerance has attracted significant interest. However, the interaction between MSCs and Kupffer cells (KCs) has received little attention, and the effect of this interaction on liver transplant tolerance remains unclear. KCs were cultured in the presence and absence of MSCs. After 24 h, cells were treated with lipopolysaccharide (LPS), after which the production of cytokines and the expression of surface antigens were measured for cell function identification. Moreover, the effects of the KCs and the prostaglandin E2 (PGE2) levels produced by the MSCs were determined using an experimental rat liver transplantation model. Blood and liver samples were collected at three time points after transplantation for further analysis. After LPS treatment, when compared with the KC single cultures, the expression of pro-inflammatory cytokines (IL-1β, IL-6, MHC-II, CD40, CD80, and CD86) in the coculture system was down-regulated, whereas the expression of anti-inflammatory cytokines (TGF-β, IL-4, PGE2, and IL-10) was markedly increased. These data indicate that MSCs can reprogram the phenotype of KCs. However, KCs treated with miR/TNF-α (tumor necrosis factor) plasmid prior to coculture to inhibit the production of TNF-α resulted in an inhibition of the reprogramming effect of MSCs. Moreover, overexpression of PGE2 in MSCs increased the effect of MSCs on KC reprogramming. After rat liver transplantation, allograft recipients that received MSCs showed better allograft tolerance when compared with rats in which KC function was inhibited. Furthermore, rats treated with MSCs overexpressing PGE2 demonstrated the best liver tolerance of all of the groups tested. MSCs reprogram the phenotype of KCs through TNF-α and PGE2, and this process is crucial for the immunomodulatory function of MSCs in liver transplantation.

  20. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan

    PubMed Central

    Lee, Kwai-Fong; Tsai, Yi-Ting; Lin, Chih-Yuan; Hsieh, Chung-Bao; Wu, Sheng-Tang; Ke, Hung-Yen; Lin, Yi-Chang; Lin, Feng-Yen; Lee, Wei-Hwa; Tsai, Chien-Sung

    2016-01-01

    Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex. PMID:27196400

  1. Chemoembolization followed by orthotopic liver transplant for epithelioid hemangioendothelioma.

    PubMed

    St Peter, Shawn D; Moss, Adyr A; Huettl, Eric A; Leslie, Kevin O; Mulligan, David C

    2003-12-01

    Hepatic epithelioid hemangioendothelioma (HEHE) is a rare liver tumor with an indolent course relative to other hepatic malignancies. Over the past two decades, primary treatment for these lesions has been defined as resection for localized disease, or transplantation for diffuse and multifocal tumors. No published report to date has described effective pre- or post-operative adjuvant treatment for this disease. In this report, we present the first case of HEHE effectively managed with chemoembolization followed by transplantation, documenting objective tumor response to embolization. Furthermore, diagnosis for this lesion can easily be mistaken, directing management in erroneous directions. This case illustrates diagnostic pitfalls affiliated with the work-up of this tumor. PMID:14756273

  2. Metabolic and cardiovascular complications in the liver transplant recipient

    PubMed Central

    Luca, Laura De; Westbrook, Rachel; Tsochatzis, Emmanuel A.

    2015-01-01

    Metabolic syndrome (MS) is an established risk factor for atherosclerosis and cardiovascular disease that affects 20-30% of the adult population in the western world, correlating with increased incidence of cardiovascular disease. Survival following liver transplantation (LT) has been steadily improving over the last 2 decades, with graft loss becoming a relatively rare cause of morbidity and mortality post LT. The improvement in short-term survival following LT has resulted in an increased incidence of metabolic and cardiovascular complications, which affect the mid- and long term survival. Patients following LT typically gain weight and might develop diabetes, hypertension and dyslipidemia as a consequence of their immunosuppressive therapy and their lifestyle. In this paper we review the prevalence of metabolic and cardiovascular complications following LT, their impact on post-transplant morbidity and mortality and their optimal management. PMID:25830307

  3. New-onset diabetes mellitus after pediatric liver transplantation.

    PubMed

    Regelmann, Molly O; Goldis, Marina; Arnon, Ronen

    2015-08-01

    In the first five yr after liver transplant, approximately one in 10 pediatric recipients will develop NODAT. Factors associated with higher risk for NODAT have been difficult to identify due to lack of uniformity in reporting and data collection. Limited studies have reported higher risk in those who are at an older age at transplant, those with high-risk ethnic backgrounds, and in those with particular underlying conditions, such as CF and primary sclerosing cholangitis. Immunosuppressive medications, including tacrolimus, cyclosporine A, GC, and sirolimus, have been implicated as contributing to NODAT, to varying degrees. Identifying those at highest risk, appropriately screening, and diagnosing NODAT is critical to initiating timely treatment and avoiding potential complications. In the pediatric population, treatment is limited primarily to insulin, with some consideration for metformin. Children with NODAT should be monitored carefully for complications of DM, including microalbuminuria, hypertension, hyperlipidemia, and retinopathy.

  4. Liver transplantation as a cure for acute intermittent porphyria.

    PubMed

    Soonawalla, Zahir F; Orug, Taner; Badminton, Michael N; Elder, George H; Rhodes, Jonathan M; Bramhall, Simon R; Elias, Elwyn

    2004-02-28

    Acute intermittent porphyria occasionally causes frequent and crippling acute neurovisceral attacks associated with increased hepatic production of porphyrin precursors, resulting in long-term damage, poor quality of life, and shortened life expectancy. There has been no cure for this condition, but replacement of deficient hepatic enzymes might restore excretion of porphyrin precursors to normal and prevent acute attacks. We aimed to treat severe acute intermittent porphyria in a 19-year-old woman by liver transplantation. After the transplant, concentrations of haem precursors in the patient's urine returned to normal, and 1.5 years later her quality of life was good. Our report suggests some hope of cure for selected patients with severe forms of this disease. PMID:15001330

  5. Liver uptake of biguanides in rats.

    PubMed

    Sogame, Yoshihisa; Kitamura, Atsushi; Yabuki, Masashi; Komuro, Setsuko

    2011-09-01

    Metformin is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus. The liver is the primary target, metformin being taken up into human and rat hepatocytes via an active transport mechanism. The present study was designed to compare hepatic uptake of two biguanides, metformin and phenformin, in vitro and in vivo. In in vitro experiments, performed using rat cryopreserved hepatocytes, phenformin exhibited a much higher affinity and transport than metformin, with marked differences in kinetics. The K(m) values for metformin and phenformin were 404 and 5.17μM, respectively, with CLint (V(max)/K(m)) values 1.58μl/min per 10(6) cells and 34.7μl/min per 10(6) cells. In in vivo experiments, when (14)C-metformin and (14)C-phenformin were given orally to male rats at a dose of 50mg/kg, the liver concentrations of radioactivity at 0.5 hour after dosing were 21.5μg eq./g with metformin but 147.1μg eq./g for phenformin, ratios of liver to plasma concentrations being 4.2 and 61.3, respectively. In conclusion, the results suggest that uptake of biguanides by rat hepatocytes is in line with the liver distribution found in vivo, phenformin being more efficiently taken up by liver than metformin after oral administration.

  6. Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis.

    PubMed

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34(+) cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34(+) cells were injected via the spleen. After 7 days, CD34(+) cells were effectively expanded in a serum-free culture medium. Expanded CD34(+) cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34(+) cells increased compared with nonexpanded CD34(+) cells. Expanded CD34(+) cell transplantation reduced liver fibrosis, with a decrease of αSMA(+) cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34(+) cells over non-expanded CD34(+) cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34(+) cells and aggravated liver fibrosis. These findings suggest that expanded CD34(+) cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  7. Ex vivo expansion of circulating CD34+ cells enhances the regenerative effect on rat liver cirrhosis

    PubMed Central

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34+ cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34+ cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34+ cells were injected via the spleen. After 7 days, CD34+ cells were effectively expanded in a serum-free culture medium. Expanded CD34+ cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34+ cells increased compared with nonexpanded CD34+ cells. Expanded CD34+ cell transplantation reduced liver fibrosis, with a decrease of αSMA+ cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34+ cells over non-expanded CD34+ cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34+ cells and aggravated liver fibrosis. These findings suggest that expanded CD34+ cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  8. Validation of cardiovascular risk scores in a liver transplant population.

    PubMed

    Guckelberger, Olaf; Mutzke, Florian; Glanemann, Matthias; Neumann, Ulf P; Jonas, Sven; Neuhaus, Ruth; Neuhaus, Peter; Langrehr, Jan M

    2006-03-01

    Increased prevalence of cardiovascular risk factors has been acknowledged in liver transplant recipients, and an increased incidence of cardiovascular events has been suspected. Individual risk determination, however, has not yet been established. Outpatient charts of 438 primary liver transplants have been reviewed, and suspected cardiovascular risk factors were correlated with cardiovascular events observed during a follow-up period of 10 yr. Receiver operation characteristics curve (ROC) analysis was performed to validate established cardiovascular risk scores. For calibration, the Hosmer-Lemeshow test was performed. A total of 303 of 438 patients were available for risk factor analysis at 6 months and demonstrated complete follow-up data (175 male, 128 female). A total of 40 of those 303 patients experienced fatal or nonfatal cardiovascular events (13.2%). In univariate analysis, age (P < 0.001), gender (P = 0.002), body mass index (P = 0.018), cholesterol (P = 0.044), creatinine (P = 0.006), diabetes mellitus (P = 0.017), glucose (0.006), and systolic blood pressure (P = 0.043), but not cyclosporine A (P = 0.743), tacrolimus (P = 0.870), or steroid medication (P = 0.991), were significantly associated with cardiovascular events. Multivariate analysis, however, identified only age, gender, and cholesterol as independent predictors. In ROC analysis, corresponding areas under the curve for Systematic Coronary Risk Evaluation Project (SCORE), Prospective Cardiovascular Münster Study (PROCAM), and Framingham risk scores (FRSs) were calculated with 0.800, 0.778, and 0.707, respectively. Calibration demonstrated an improved goodness of fit for PROCAM compared to SCORE risk calculations. In conclusion, SCORE and PROCAM proved to be valuable in discriminating our liver transplant recipients for their individual risk of cardiovascular events. Furthermore, calibrated PROCAM risk estimates are required to calculate the number of patients needed to treat in the setup of

  9. Clonal Origin of Hepatocellular Carcinoma and Recurrence After Liver Transplantation.

    PubMed

    Wang, Zhenglu; Gong, Weihua; Shou, Dawei; Zhang, Luzhou; Gu, Xiangqian; Wang, Yuliang; Teng, Dahong; Zheng, Hong

    2016-01-01

    BACKGROUND This study aimed to determine whether patterns of tumor clonal origin in pluri-nodular hepatocellular carcinoma (PNHC) could serve as an indicator of tumor recurrence following liver transplantation. MATERIAL AND METHODS Tumor tissue samples from 60 PNHC patients who underwent liver transplantation were examined. The diagnosis of patients conformed to the University of California San Francisco (UCSF) standards for pluri-nodular hepatocellular carcinoma. We performed loss of heterozygosity tests at multiple microsatellite sites to determine the clonal origins of the tumors. Clinical information, pathological data, preoperative serum alpha-feto protein (AFP) and postoperative follow-ups were obtained and correlations between the clonal origin of the tumor, tumor-free survival, pathological characteristics, and AFP levels in serum were studied. RESULTS A total of 165 tumor nodules were collected. Tumor clonal origins were identified as intrahepatic metastasis (IM; 41.67%), multicentric occurrence (MO; 55%) or unidentified (3.33%). Three-year tumor-free survival for the IM group was 48% compared to 75.76% in the MO group (p<0.05), while the occurrence of microscopic tumor thrombus was 100% and 3.03% (p<0.05) for these groups, respectively. The degree of tumor differentiation was 80% for the IM group and 18.18% for the MO group (p<0.05), while the mean AFP concentration for these groups was 226.80 μg/L (2.78-3000 μg/L) and 24.59 μg/L (1.16-531. 30 μg/L; p<0.05), respectively. CONCLUSIONS Clonal origin patterns can serve as important indicators to predict the recurrence of PNHC following liver transplantation. Taken together with pathological characteristics and preoperative serum AFP levels, the risk of recurrence can be established in advance. PMID:27487734

  10. Postperfusion Syndrome in Cadaveric Liver Transplantations: A Retrospective Study

    PubMed Central

    Aydınlı, Bahar; Karadeniz, Ümit; Demir, Aslı; Güçlü, Çiğdem Yıldırım; Kazancı, Dilek; Koçulu, Rabia; Haytural, Candan; Özgök, Ayşegül; Bostancı, Erdal Birol; Zorlu, Ali

    2016-01-01

    Objective To evaluate the factors that affects the postperfusion syndrome in cadaveric liver transplantations and the effect of the postperfusion syndrome on discharge from the hospital. Methods Patients who underwent cadaveric liver transplantations between 2007 and 2013 were scanned retrospectively. Intraoperative anaesthesia records, intensive care unit follow-up forms and discharge reports were examined from patient files. Overall, 43 patients having complete data were included in the study. The postperfusion syndrome is defined as asystoli or a decrease in mean arterial pressure of more than 30%, which occurred in the first 5 min of reperfusion and continued for 1 min. Patients were divided into two groups: those who had the postperfusion syndrome and those who did not. Results The number of patients who had the postperfusion syndrome was 25 of 43 (58.1%). The MELD score of patients without the postperfusion syndrome was calculated as 16.9±3.2 and that of patients with the postperfusion syndrome was 19.7±3.6. A statistically significant relationship was detected between the postperfusion syndrome occurrence and a high MELD score (p=0.013). The diastolic blood pressure just before reperfusion was statistically lower in the group with the postperfusion syndrome than in the other group (p=0.023, 50±8 vs. 58±11). According to the logistic regression analysis, the MELD score and the decrease in diastolic blood pressure before reperfusion were defined as independent predictive factors. Conclusion According to the study, the ratio for having the postperfusion syndrome was found to be 58.1%. The independent predictor factors affecting the postperfusion syndrome were detected as the MELD score and the decrease in diastolic blood pressure before reperfusion. The postperfusion syndrome during orthotropic liver transplantation is an important issue for anaesthesiologists. The awareness of the related factors with the postperfusion syndrome may help in the development

  11. Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. The Acute Liver Failure Study Group.

    PubMed

    Fontana, R J; McCashland, T M; Benner, K G; Appelman, H D; Gunartanam, N T; Wisecarver, J L; Rabkin, J M; Lee, W M

    1999-11-01

    Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

  12. Anaphylaxis on reperfusion during liver transplantation with coagulopathy.

    PubMed

    Woehlck, Harvey J; Johnson, Christopher P; Roza, Allan M; Gottschall, Jerome L; Brumwell, Melanie; Cronin, David C

    2012-09-01

    We present a case in which anaphylaxis on hepatic reperfusion during liver transplantation presented only with hypotension and coagulopathy. There were no cutaneous manifestations or clinical features distinguishing anaphylaxis from postreperfusion syndrome. The recipient regularly consumed seafood, and the organ donor died of anaphylaxis to shellfish. The trigger for anaphylaxis was postulated to be passive transfer of immunoglobulin to the recipient. Anesthesiologists should be notified of donor factors to anticipate anaphylaxis. In this report, we discuss coagulopathy of anaphylaxis and contrast it with disseminated intravascular coagulation.

  13. Methods in renal research: kidney transplantation in the rat.

    PubMed

    Tillou, Xavier; Howden, Brian O; Kanellis, John; Nikolic-Paterson, David J; Ma, Frank Y

    2016-06-01

    Kidney transplantation in small animals has been crucial in the development of anti-rejection therapies. While there is no substitute for a skilled microsurgeon, there are many aspects of the transplant procedure that can be modified to optimize the reproducibility and utility of the technique. This article provides a detailed description, including video recording, of orthotopic kidney transplantation in the rat. The key variables in the technique are also discussed. PMID:26648592

  14. Intraoperative intracardiac thrombosis in a liver transplant patient

    PubMed Central

    Sibulesky, Lena; Peiris, Prith; Taner, C Burcin; Kramer, David J; Canabal, Juan M; Nguyen, Justin H

    2010-01-01

    A 66-year-old female with cryptogenic cirrhosis complicated by ascites, hepatic encephalopathy, variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique. Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow. The liver graft was recirculated without any hemodynamic instability. Subsequently, the patient became hypotensive progressing to asystole. She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle. The patient was noted to be coagulopathic at the time. She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus. PMID:21160996

  15. Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats.

    PubMed

    von Heesen, Maximilian; Dold, Stefan; Müller, Simon; Scheuer, Claudia; Kollmar, Otto; Schilling, Martin K; Menger, Michael D; Moussavian, Mohammed R

    2015-06-01

    Major hepatectomy or small-for-size liver transplantation may result in postoperative liver failure. So far, no treatment is available to improve liver regeneration. Herein, we studied whether cilostazol, a selective phosphodiesterase III inhibitor, is capable of improving liver regeneration after major hepatectomy. Sprague-Dawley rats (n = 74) were treated with cilostazol (5 mg/kg daily) or a glucose solution and underwent either 70% liver resection or a sham operation. Before and after surgery, hepatic arterial and portal venous blood flow and hepatic microvascular perfusion were analyzed. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, western blotting, and bile excretion analysis. Cilostazol significantly increased hepatic blood flow and microcirculation before and after hepatectomy in comparison with sham-operated controls. This was associated with an elevation of hepatic vascular endothelial growth factor expression, an increase of hepatocellular proliferation, and an acceleration of liver regeneration. Furthermore, cilostazol protected the tissue of the remnant liver as indicated by an attenuation of hepatocellular disintegration. In conclusion, cilostazol increases hepatic blood perfusion, microcirculation, and liver regeneration after a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce the rate of liver failure after both extended hepatectomy and small-for-size liver transplantation.

  16. Access to adult liver transplantation in Canada: a survey and ethical analysis.

    PubMed Central

    Mullen, M A; Kohut, N; Sam, M; Blendis, L; Singer, P A

    1996-01-01

    OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and

  17. Integration of Palliative Care in End-Stage Liver Disease and Liver Transplantation

    PubMed Central

    Curry, Michael; Buss, Mary; Chittenden, Eva

    2014-01-01

    Abstract Background: Patients with end-stage liver disease (ESLD) have a life-limiting illness that causes multiple distressing symptoms and negatively affects quality of life (QOL). This population traditionally has not had much attention within the palliative care community. Discussion: This article provides an evidence-based review of palliative care issues that patients with ESLD and those awaiting liver transplant face, including approaches to prognosis, symptom management, advance care planning, and end-of-life care. Conclusion: Tremendous opportunity exists to integrate palliative medicine into the care of these patients. PMID:25390468

  18. P08.10SINGLE BRAIN METASTASIS 9 YEARS AFTER ORTHOTOPIC LIVER TRANSPLANT WITH HISTOLOGICAL NEGATIVE EXPIANTED LIVER: CASE REPORT

    PubMed Central

    Fornaro, R.; Agnoletti, A.; Specchia, F.M. Calamo; Garbossa, D.; Lanotte, M.; Ducati, A.

    2014-01-01

    We describe the case of a 67 years old man, that underwent orthotopic liver transplant (OLT) in 2004 for cirrhosis. Native liver hystological examination was negative for focal hepatocarcinoma (HCC) areas. In 2008, during regular follow up, pulmonary lesions were found and diagnosed as hepatocarcinoma metastasis.In 2013, patient accused vertigo and dizziness: neuroimaging showed a cerebellar lesion. Hystological diagnosis was HCC metastases. The peculiarity is the onset of lung metastasis after transplant, with negative analysis on native liver, and brain metastasis after stable disease. This case is also relevant due to long survival related to the unavailability of many oncologic therapies in transplanted patients.

  19. Right lobe split liver transplantation versus whole liver transplantation in adult recipients: A systematic review and meta-analysis.

    PubMed

    Wan, Ping; Li, Qigen; Zhang, Jianjun; Xia, Qiang

    2015-07-01

    Split liver transplantation (SLT) has proven to be an effective technique to reduce the mortality of children on the waiting list, but whether creating 2 split grafts from 1 standard-criteria whole liver would compromise outcomes of adult recipients remains uncertain. We conducted this meta-analysis to compare outcomes of right lobe SLT and whole liver transplantation (WLT) in adult patients. PubMed, Embase, and the Cochrane Library were searched for relevant articles published before December 2014. Outcomes assessed were patient survival (PS), graft survival (GS), and major surgical complications after transplantation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to synthesize the results. Seventeen studies with a total of 48,457 patients met the full inclusion criteria. PS and GS rates were all found to be equivalent between SLT and WLT recipients. However, SLT was associated with higher rates of overall biliary complications (OR = 1.66; 95% CI = 1.29-2.15; P < 0.001), bile leaks (OR = 4.30; 95% CI = 2.97-6.23; P < 0.001), overall vascular complications (OR = 1.81; 95% CI = 1.29-2.53; P < 0.001), hepatic artery thromboses (OR = 1.71; 95% CI = 1.17-2.50; P = 0.005), and outflow tract obstructions (OR = 4.17; 95% CI = 1.75-9.94; P = 0.001). No significant difference was observed in incidences of biliary stricture, portal vein complications, postoperative bleeding requiring surgical treatments, primary nonfunction, and retransplantations. In subgroup analyses, biliary and vascular complications only increased after ex vivo SLT rather than in situ SLT, and SLT recipients had more retransplantations if they matched with WLT recipients in terms of urgent status. In conclusion, adult right lobe SLT was associated with increased biliary and vascular complications compared with WLT, but it did not show significant inferiority in PSs and GSs. PMID:25832308

  20. SlimQuick™-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

    PubMed Central

    Whitsett, Maureen; Rossi, Simona

    2014-01-01

    Green tea extract is a popular ingredient in herbal weight loss supplements. There have been reports of hepatotoxicity associated with the use of dietary supplements, some of these cases lead to fatal outcomes. To our knowledge, we report the first case of fulminant hepatic failure requiring orthotopic liver transplantation caused by SlimQuick™ (Wellnx Life Sciences, Wilmington, DE), a widely available weight loss supplement containing green tea extract. PMID:26157882

  1. Methaqualone metabolism by rat liver microsomes.

    PubMed

    Manowitz, P; Shull, C M

    1976-01-01

    A rat hepatic microsomal system has been established which metabolizes methaqualone. The microsomes are obtained from livers of rats treated with phenobarbital. The methaqualone is dissolved in polyethylene glycol-200 prior to addition to the incubation mixture. A comparison is made between the metabolites obtained in this in vitro system and metabolites obtained from urines of phenobarbital treated rats injected with methaqualone. The same two and sometimes three metabolites, as determined by thin layer and gas liquid chromatography, were found in both the complete microsomal incubation system and the urines.

  2. Lessons Learned From a Case of Gastric Cancer After Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Yang, Kun; Zhu, Hong; Chen, Chong-Cheng; Wen, Tian-Fu; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Guo, Dong-Jiao; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Abstract Nowadays, de novo malignancies have become an important cause of death after transplantation. According to the accumulation of cases with liver transplantation, the incidence of de novo gastric cancer is anticipated to increase among liver transplant recipients in the near future, especially in some East Asian countries where both liver diseases requiring liver transplantation and gastric cancer are major burdens. Unfortunately, there is limited information regarding the relationship between de novo gastric cancer and liver transplantation. Herein, we report a case of stage IIIc gastric cancer after liver transplantation for hepatocellular carcinoma, who was successfully treated by radical distal gastrectomy with D2 lymphadenectomy but died 15 months later due to tumor progression. Furthermore, we extract some lessons to learn from the case and review the literatures. The incidence of de novo gastric cancer following liver transplantations is increasing and higher than the general population. Doctors should be vigilant in early detection and control the risk factors causing de novo gastric cancer after liver transplantation. Curative gastrectomy with D2 lymphadenectomy is still the mainstay of treatment for such patients. Preoperative assessments, strict postoperative monitoring, and managements are mandatory. Limited chemotherapy could be given to the patients with high risk of recurrence. Close surveillance, early detection, and treatment of posttransplant cancers are extremely important and essential to improve the survival. PMID:26886605

  3. Childhood Abuse, Nonadherence, and Medical Outcome in Pediatric Liver Transplant Recipients

    ERIC Educational Resources Information Center

    Shemesh, Eyal; Annunziato, Rachel A.; Yehuda, Rachel; Shneider, Benjamin L.; Newcorn, Jeffrey H.; Hutson, Carolyn; Cohen, Judith A.; Briere, John; Gorman, Jack M.; Emre, Sukru

    2007-01-01

    Objective: The study assessed the relationship between a history of child abuse, nonadherence to medications, and medical outcome in children who had a liver transplant. Method: Abuse history for children and adolescents ages 8 to 21 who underwent a liver transplantation at Mount Sinai Medical Center in New York was obtained in interviews in 2002.…

  4. Orthotopic liver transplantation for hepatitis C infection: the best Christmas present?

    PubMed

    Johnston, S D; McNulty, O; Mayne, E; Callender, M E

    1998-11-01

    We report the case of a 60-year-old man with mild Christmas disease, Factor IX 10% of normal, who developed chronic hepatitis C infection after receiving coagulation factor concentrates. Subsequently he developed encephalopathy and liver failure and was referred for liver transplantation. Following transplantation, Factor IX levels rapidly normalised and have remained so, representing a phenotypic cure of his Christmas disease.

  5. Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

    PubMed Central

    ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

    2015-01-01

    Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

  6. Resolution of severe graft steatosis following dual-graft living donor liver transplantation.

    PubMed

    Moon, DeokBog; Lee, SungGyu; Hwang, Shin; Kim, KiHun; Ahn, ChulSoo; Park, KwangMin; Ha, TaeYong; Song, GiWon

    2006-07-01

    Although severely steatotic liver grafts are not suitable for transplantation, they have been used when other, more optimal donors were not available, especially for living donor liver transplantation (LDLT) using two liver grafts. Here we present two cases of dual-graft LDLT in which the recipients showed rapid and complete clearing of fat from livers with previously severe steatosis. In the first case, two left lateral segment grafts were used, one of which was 70% steatotic. Preoperative and posttransplant two-week liver-to-spleen computed tomography-value (L/S) ratios were 0.48 and 1.25, respectively. A liver biopsy taken two weeks after transplantation showed that the fatty changes had almost disappeared. The second case used one left lobe and one left lateral segment graft, the latter of which was 80% steatotic. Preoperative and two-week L/S ratio were 0.58 and 1.34, respectively, and a liver biopsy taken two weeks after transplantation showed less than 3% steatosis. The two donors of the severely steatotic liver grafts recovered uneventfully. These findings show that the fat content of the liver grafts was rapidly removed after transplantation. This observation is helpful in understanding the recovery sequences following transplantation of steatotic liver grafts, as well as expanding the acceptability of steatotic liver grafts.

  7. Parvovirus B19 in anemic liver transplant recipients.

    PubMed Central

    Ndimbie, O K; Frezza, E; Jordan, J A; Koch, W; van Thiel, D H

    1996-01-01

    Five hundred thirty-three liver transplant recipients were seen for follow-up care over a 6-month period. Of these, 23 (4.3%) had a hemoglobin level of < or = 9 g/dl, with 19 being eligible for inclusion in this study. The median hemoglobin level was 8.7 g/dl. Two patients had iron-deficiency anemia. All of the patients were on therapeutic drugs which can suppress erythropoiesis or shorten the lifespan of mature erythrocytes. Six patients (31.6%) were viremic for human parvovirus B19 but none was B19 immunoglobulin M seropositive. Two patients were immunoglobulin M seropositive for cytomegalovirus. The patients with circulating B19 DNA were not easily distinguished from those without the virus by their laboratory results. The absence of reticulocyte counts for these patients contributed to this inability to differentiate B19 from other causes of anemia, particularly drug myelotoxicity. The high likelihood of making a specific diagnosis with the increasing availability of PCR should spur the search for this virus in the liver transplant population. PMID:8914771

  8. Percutaneous Management of Biliary Strictures After Pediatric Liver Transplantation

    SciTech Connect

    Miraglia, Roberto Maruzzelli, Luigi; Caruso, Settimo; Riva, Silvia; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2008-09-15

    We analyze our experience with the management of biliary strictures (BSs) in 27 pediatric patients who underwent liver transplantation with the diagnosis of BS. Mean recipient age was 38 months (range, 2.5-182 months). In all patients percutaneous transhepatic cholangiography, biliary catheter placement, and bilioplasty were performed. In 20 patients the stenoses were judged resolved by percutaneous balloon dilatation and the catheters removed. Mean number of balloon dilatations performed was 4.1 (range, 3-6). No major complications occurred. All 20 patients are symptom-free with respect to BS at a mean follow-up of 13 months (range, 2-46 months). In 15 of 20 patients (75%) one course of percutaneous stenting and bilioplasty was performed, with no evidence of recurrence of BS at a mean follow-up of 15 months (range, 2-46 months). In 4 of 20 patients (20%) two courses of percutaneous stenting and bilioplasty were performed; the mean time to recurrence was 9.8 months (range, 2.4-24 months). There was no evidence of recurrence of BS at a mean follow-up of 12 months (range, 2-16 months). In 1 of 20 patients (5%) three courses of percutaneous stenting and bilioplasty were performed; there was no evidence of recurrence of BS at a mean follow-up of 10 months. In conclusion, BS is a major problem following pediatric liver transplantation. Radiological percutaneous treatment is safe and effective, avoiding, in most cases, surgical revision of the anastomosis.

  9. Liver Transplantation Utilizing Mixed Biologic and Synthetic Arterial Conduits

    PubMed Central

    Grezzana-Filho, Tomaz J. M.; Chedid, Aljamir D.; Hendges, Luiz Pedro P.; Leipnitz, Ian; Alvares-da-Silva, Mario R.; Backes, Ariane N.; Reis, Matheus J.; Kruel, Cleber Dario P.; Kruel, Cleber R. P.

    2016-01-01

    Arterial conduits are necessary in nearly 5% of all liver transplants and are usually constructed utilizing segments of donor iliac artery. However, available segments of donor iliac artery may not be lengthy enough or may not possess enough quality to enable its inclusion in the conduit. Although there are few reports of arterial conduits constructed solely utilizing prosthetic material, no previous reports of conduits composed of a segment of donor iliac artery and prosthetic material (mixed biologic and synthetic arterial conduits) were found in the medial literature to date. Two cases reporting successful outcomes after creation of mixed biologic and prosthetic arterial conduits are outlined in this report. Reason for creation of conduits was complete intimal dissection of the recipient's hepatic artery in both cases. In both cases, available segments of donor iliac artery were not lengthy enough to bridge infrarenal aorta to porta hepatis. Both patients have patent conduits and normally functioning liver allografts, respectively, at 4 and 31 months after transplant. Mixed biologic and synthetic arterial conduits constitute a viable technical option and may offer potential advantages over fully prosthetic arterial conduits.

  10. Operative start times and complications after liver transplantation.

    PubMed

    Lonze, B E; Parsikia, A; Feyssa, E L; Khanmoradi, K; Araya, V R; Zaki, R F; Segev, D L; Ortiz, J A

    2010-08-01

    The recent national focus on patient safety has led to a re-examination of the risks and benefits of nighttime surgery. In liver transplantation, the hypothetical risks of nighttime operation must be weighed against either the well-established risks of prolonging cold ischemia or the potential risks of strategies to manipulate operative start times. A retrospective review was conducted of 578 liver transplants performed at a single institution between 1995 and 2008 to determine whether the incidence of postoperative complications correlated with operative start times. We hypothesized that no correlation would be observed between complication rates and operative start times. No consistent trends in relative risk of postoperative wound, vascular, biliary, or other complications were observed when eight 3-h time strata were compared. When two 12-h time strata (night, 3 p.m.-3 a.m., and day, 3 a.m.-3 p.m.) were compared, complications were not significantly different, but nighttime operations were longer in duration, and were associated a twofold greater risk of early death compared to daytime operations (adjusted OR 2.9, 95% CI 1.16-7.00, p = 0.023), though long-term survival did not differ significantly between the subgroups. This observation warrants further evaluation and underscores the need to explore and identify institution-specific practices that ensure safe operations regardless of time of day.

  11. Tolerance in liver transplantation: Biomarkers and clinical relevance

    PubMed Central

    Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Parrilla, Pascual; Martínez-Alarcón, Laura; Ramírez, Pablo; Pons, José Antonio

    2016-01-01

    Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as “operational tolerance”. However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio. PMID:27678350

  12. Tolerance in liver transplantation: Biomarkers and clinical relevance.

    PubMed

    Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Parrilla, Pascual; Martínez-Alarcón, Laura; Ramírez, Pablo; Pons, José Antonio

    2016-09-14

    Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as "operational tolerance". However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio. PMID:27678350

  13. Tolerance in liver transplantation: Biomarkers and clinical relevance

    PubMed Central

    Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Parrilla, Pascual; Martínez-Alarcón, Laura; Ramírez, Pablo; Pons, José Antonio

    2016-01-01

    Transplantation is the optimal treatment for end-stage organ failure, and modern immunosuppression has allowed important progress in short-term outcomes. However, immunosuppression poorly influences chronic rejection and elicits chronic toxicity in current clinical practice. Thus, a major goal in transplantation is to understand and induce tolerance. It is well established that human regulatory T cells expressing the transcription factor FoxP3 play important roles in the maintenance of immunological self-tolerance and immune homeostasis. The major regulatory T cell subsets and mechanisms of expansion that are critical for induction and long-term maintenance of graft tolerance and survival are being actively investigated. Likewise, other immune cells, such as dendritic cells, monocyte/macrophages or natural killer cells, have been described as part of the process known as “operational tolerance”. However, translation of these results towards clinical practice needs solid tools to identify accurately and reliably patients who are going to be tolerant. In this way, a plethora of genetic and cellular biomarkers is raising and being validated worldwide in large multi-center clinical trials. Few of the studies performed so far have provided a detailed analysis of the impact of immunosuppression withdrawal on pre-existing complications derived from the long-term administration of immunosuppressive drugs and the side effects associated with them. The future of liver transplantation is aimed to develop new therapies which increase the actual low tolerant vs non-tolerant recipients ratio.

  14. Longterm results of liver transplantation from donation after circulatory death.

    PubMed

    Blok, Joris J; Detry, Olivier; Putter, Hein; Rogiers, Xavier; Porte, Robert J; van Hoek, Bart; Pirenne, Jacques; Metselaar, Herold J; Lerut, Jan P; Ysebaert, Dirk K; Lucidi, Valerio; Troisi, Roberto I; Samuel, Undine; den Dulk, A Claire; Ringers, Jan; Braat, Andries E

    2016-08-01

    Donation after circulatory death (DCD) liver transplantation (LT) may imply a risk for decreased graft survival, caused by posttransplantation complications such as primary nonfunction or ischemic-type biliary lesions. However, similar survival rates for DCD and donation after brain death (DBD) LT have been reported. The objective of this study is to determine the longterm outcome of DCD LT in the Eurotransplant region corrected for the Eurotransplant donor risk index (ET-DRI). Transplants performed in Belgium and the Netherlands (January 1, 2003 to December 31, 2007) in adult recipients were included. Graft failure was defined as either the date of recipient death or retransplantation whichever occurred first (death-uncensored graft survival). Mean follow-up was 7.2 years. In total, 126 DCD and 1264 DBD LTs were performed. Kaplan-Meier survival analyses showed different graft survival for DBD and DCD at 1 year (77.7% versus 74.8%, respectively; P = 0.71), 5 years (65.6% versus 54.4%, respectively; P = 0.02), and 10 years (47.3% versus 44.2%, respectively; P = 0.55; log-rank P = 0.038). Although there was an overall significant difference, the survival curves almost reach each other after 10 years, which is most likely caused by other risk factors being less in DCD livers. Patient survival was not significantly different (P = 0.59). Multivariate Cox regression analysis showed a hazard ratio of 1.7 (P < 0.001) for DCD (corrected for ET-DRI and recipient factors). First warm ischemia time (WIT), which is the time from the end of circulation until aortic cold perfusion, over 25 minutes was associated with a lower graft survival in univariate analysis of all DCD transplants (P = 0.002). In conclusion, DCD LT has an increased risk for diminished graft survival compared to DBD. There was no significant difference in patient survival. DCD allografts with a first WIT > 25 minutes have an increased risk for a decrease in graft survival. Liver Transplantation 22 1107

  15. Extensive exchange of rat liver microsomal phospholipids.

    PubMed

    Zilversmit, D B; Hughes, M E

    1977-08-15

    Liver microsomal fractions were prepared from rats injected with a single dose of choline [14C]methylchloride or with single or multiple doses of 32Pi. Exchangeability of microsomal phospholipids was determined by incubation with an excess of mitochondria and phospholipid exchange proteins derived from beef heart, beef liver or rat liver. Labeled phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were found to act as a single pool and were 85--95% exchangeable in 1--2h. High latencies of mannose-6-phosphate phosphohydrolase activities and impermeability of microsomes to EDTA proved that phospholipid exchange proteins did not have access to the intracisternal space. If microsomal membranes are largely composed of phospholipid bilayers, the experiments suggest that one or more of the phospholipid classes in microsomal membranes undergo rapid translocation between the inner and outer portions of the bilayer.

  16. Extensive exchange of rat liver microsomal phospholipids.

    PubMed

    Zilversmit, D B; Hughes, M E

    1977-08-15

    Liver microsomal fractions were prepared from rats injected with a single dose of choline [14C]methylchloride or with single or multiple doses of 32Pi. Exchangeability of microsomal phospholipids was determined by incubation with an excess of mitochondria and phospholipid exchange proteins derived from beef heart, beef liver or rat liver. Labeled phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were found to act as a single pool and were 85--95% exchangeable in 1--2h. High latencies of mannose-6-phosphate phosphohydrolase activities and impermeability of microsomes to EDTA proved that phospholipid exchange proteins did not have access to the intracisternal space. If microsomal membranes are largely composed of phospholipid bilayers, the experiments suggest that one or more of the phospholipid classes in microsomal membranes undergo rapid translocation between the inner and outer portions of the bilayer. PMID:889827

  17. Gastric Metastasis of Hepatocellular Carcinoma With Gastrointestinal Bleeding After Liver Transplant: A Case Report.

    PubMed

    Li, L; Zhang, W H; Meng, F P; Ma, X M; Shen, L J; Jin, B; Li, H W; Han, J; Zhou, G D; Liu, S H

    2015-10-01

    Gastrointestinal (GI) metastasis of hepatocellular carcinoma is very rare. This is the first report of post-transplantation gastric metastasis. A 43-year-old man with a history of hepatitis B-related hepatocellular carcinoma (HCC) in the right anterior segment of the liver received an orthotopic liver transplant. Three months after the transplantation, pulmonary metastasis was found by chest computed tomography, and he received 1 course of gamma knife treatment. He complained of melena with anemia 17 months post liver transplantation. Abdominal CT scan showed new occupying lesions in the liver and a mass in the stomach and around the spleen with embolus in the splenic vein. Endoscopy revealed a large irregular cauliflower-like mass in fundus with ulceration and bleeding on the surface. He received symptomatic treatment, but died of cancer-related bleeding 4 months later. GI bleeding may due to gastric metastasis after liver transplantation. PMID:26518968

  18. Gastric Metastasis of Hepatocellular Carcinoma With Gastrointestinal Bleeding After Liver Transplant: A Case Report.

    PubMed

    Li, L; Zhang, W H; Meng, F P; Ma, X M; Shen, L J; Jin, B; Li, H W; Han, J; Zhou, G D; Liu, S H

    2015-10-01

    Gastrointestinal (GI) metastasis of hepatocellular carcinoma is very rare. This is the first report of post-transplantation gastric metastasis. A 43-year-old man with a history of hepatitis B-related hepatocellular carcinoma (HCC) in the right anterior segment of the liver received an orthotopic liver transplant. Three months after the transplantation, pulmonary metastasis was found by chest computed tomography, and he received 1 course of gamma knife treatment. He complained of melena with anemia 17 months post liver transplantation. Abdominal CT scan showed new occupying lesions in the liver and a mass in the stomach and around the spleen with embolus in the splenic vein. Endoscopy revealed a large irregular cauliflower-like mass in fundus with ulceration and bleeding on the surface. He received symptomatic treatment, but died of cancer-related bleeding 4 months later. GI bleeding may due to gastric metastasis after liver transplantation.

  19. Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts

    PubMed Central

    Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

    2015-01-01

    During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that’s constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

  20. Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.

    PubMed Central

    Linton, M F; Gish, R; Hubl, S T; Bütler, E; Esquivel, C; Bry, W I; Boyles, J K; Wardell, M R; Young, S G

    1991-01-01

    Apolipoprotein (apo) E and the two B apolipoproteins, apoB48 and apoB100, are important proteins in human lipoprotein metabolism. Commonly occurring polymorphisms in the genes for apoE and apoB result in amino acid substitutions that produce readily detectable phenotypic differences in these proteins. We studied changes in apoE and apoB phenotypes before and after liver transplantation to gain new insights into apolipoprotein physiology. In all 29 patients that we studied, the postoperative serum apoE phenotype of the recipient, as assessed by isoelectric focusing, converted virtually completely to that of the donor, providing evidence that greater than 90% of the apoE in the plasma is synthesized by the liver. In contrast, the cerebrospinal fluid apoE phenotype did not change to the donor's phenotype after liver transplantation, indicating that most of the apoE in CSF cannot be derived from the plasma pool and therefore must be synthesized locally. The apoB100 phenotype (assessed with immunoassays using monoclonal antibody MB19, an antibody that detects a two-allele polymorphism in apoB) invariably converted to the phenotype of the donor. In four normolipidemic patients, we determined the MB19 phenotype of both the apoB100 and apoB48 in the "chylomicron fraction" isolated from plasma 3 h after a fat-rich meal. Interestingly, the apoB100 in the chylomicron fraction invariably had the phenotype of the donor, indicating that the vast majority of the large, triglyceride-rich apoB100-containing lipoproteins that appear in the plasma after a fat-rich meal are actually VLDL of hepatic origin. The MB19 phenotype of the apoB48 in the plasma chylomicron fraction did not change after liver transplantation, indicating that almost all of the apoB48 in plasma chylomicrons is derived from the intestine. These results were consistent with our immunocytochemical studies on intestinal biopsy specimens of organ donors; using apoB-specific monoclonal antibodies, we found evidence for

  1. Cirrhotic cardiomyopathy in the pre- and post-liver transplantation phase.

    PubMed

    Zardi, Enrico Maria; Zardi, Domenico Maria; Chin, Diana; Sonnino, Chiara; Dobrina, Aldo; Abbate, Antonio

    2016-02-01

    Patients with advanced liver cirrhosis may develop a clinical syndrome characterized by a blunted contractile responsiveness to stress and/or altered diastolic relaxation, called "cirrhotic cardiomyopathy." This syndrome, which is initially asymptomatic, is often misdiagnosed due to the presence of symptoms that characterize other disorders present in patients with advanced liver cirrhosis, such as exercise intolerance, fatigue, and dyspnea. Stress and other conditions such as liver transplantation and transjugular intrahepatic portosystemic shunt (TIPS) may unmask this syndrome. Liver transplantation in this group of patients results in a clinical improvement and can be a cure for the cardiomyopathy. However, post-transplant prognosis depends on the identification of cirrhotics with cardiomyopathy in the pre-transplant phase; an early diagnosis of cirrhotic cardiomyopathy in the pre-transplant phase may avoid an acute onset or worsening of cardiac failure after liver transplantation. Since a preserved left ventricular ejection fraction may mask the presence of cirrhotic cardiomyopathy, the use of newer noninvasive diagnostic techniques (i.e. tissue Doppler, myocardial strain) is necessary to identify cirrhotics with this syndrome, in the pre-transplant phase. A pre-transplant treatment of heart failure in cirrhotics with cardiomyopathy improves the quality of life in this phase and reduces the complications during and immediately after liver transplantation. Since specific therapies for cirrhotic cardiomyopathy are lacking, due to the absence of a clear understanding of the pathophysiology of the cardiomyopathy, further research in this field is required. PMID:26074443

  2. Heterozygote to homozygote related living donor liver transplantation in maple syrup urine disease: a case report.

    PubMed

    Patel, N; Loveland, J; Zuckerman, M; Moshesh, P; Britz, R; Botha, J

    2015-05-01

    Liver transplantation is an accepted treatment modality in the management of MSUD. To our knowledge, ours is only the second successful case to date of a patient with MSUD receiving an allograft from an RLD who is a heterozygous carrier for the disease. In view of the worldwide shortage of available organs for transplantation, heterozygote to homozygote transplantation in the setting of MSUD may provide a viable alternative for those awaiting transplantation. We report on the case of a two-yr-old infant with MSUD, who received a left lateral segment (segments II and III) liver transplant from his mother, a heterozygote carrier of one of the three abnormal genes implicated in MSUD. Post-operative BCAA levels normalized in our patient and remained so on an unrestricted protein diet and during times of physiological stress. To date, this is only the second case of a successful RLD liver transplant in a child with MSUD. Preliminary results indicate that RLD liver transplants are at least equivalent to deceased donor liver transplants in the treatment of MSUD, although longer term follow-up is required. Heterozygote to homozygote RLD transplant in patients with MSUD presents a new pool of potential liver donors. PMID:25677046

  3. Transplantation of tectal tissue in rats. IV. Maturation of transplants and development of host retinal projection.

    PubMed

    Harvey, A R; Lund, R D

    1984-01-01

    We have examined the time course of maturation of embryonic tectal tissue transplanted to the midbrain region of newborn rats and studied the development of the host retinal projection to the grafts. Transplants were examined 2-19 days after transplantation. The morphology of developing transplants was studied using Holmes silver and neutral red stained material. Tectal transplants attained their mature morphology about 17 days after transplantation. The time course of tectal transplant maturation appeared to be similar to that of normal superior colliculus in situ. The development of the host retinal projection into the transplants was examined by injecting the host eyes with horseradish peroxidase (HRP) at various times after transplantation. Retinal fibers anterogradely labeled with HRP were first seen growing into the transplants 3-4 days after transplantation. Ingrowing fibers were always located close to the surface of the transplants. The rate of growth of optic axons into the grafts was estimated to be about 250 to 300 micron per day. Patch-like arborizations of retinal afferents were formed soon after innervation and the mature pattern of optic innervation was established by about two weeks. There was no evidence for an initial transitory phase in which the axons invaded the whole transplant. The development of the host retinal projection preceded morphological maturation of the transplants. The mode of ingrowth of retinal axons into tectal grafts was in many respects similar to the way optic fibers grow into the superior colliculus during normal in situ development. The transplant technique thus provides an opportunity to manipulate and analyze the factors which guide optic fiber growth in intact brains. PMID:6697254

  4. Effects of liver transplantation on endocrine function: a systematic review.

    PubMed

    Gariani, Karim; Toso, Christian; Philippe, Jacques; Orci, Lorenzo A

    2016-10-01

    Patients with chronic liver disease (CLD) often experience secondary endocrine dysfunction. Therefore, because the liver plays a major role in endocrine function, liver transplantation (LT) may also be beneficial for the restoration of hormonal regulation. This systematic review collects and interprets the available literature on the effect of LT on endocrine and sexual function in adult patients. A systematic review was conducted by searching Pubmed (including Medline) and EMBASE for studies published from database inception until November 2015. We collected all relevant studies that discussed changes in hormonal and sexual function after LT. Studies were included if they assessed the effect of LT on sexual function or one of the following components of the hormone/endocrine axis: the hypothalamus-pituitary-gonadal axis, growth hormone (GH), insulin-like growth factor-1 (IGF-1) or thyroid function. The results are reported according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Twenty-one studies with a total of 1274 patients were included. The results collected from the included studies suggested that LT improves the hormonal perturbation associated with CLD by restoring physiological levels of circulating GH, IGF-1, testosterone, estradiol, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Thyroid function was not affected by LT, and sexual function was partially improved after LT. This systematic review suggests that LT is associated with an improvement in endocrine and sexual function in patients with CLD. This information should encourage clinicians who treat CLD patients to identify endocrine disturbances in this population, inform their patients of the effects of LT and assess post-transplantation improvements. PMID:27163168

  5. Human neonatal hepatocyte transplantation induces long-term rescue of unconjugated hyperbilirubinemia in the Gunn rat.

    PubMed

    Tolosa, Laia; López, Silvia; Pareja, Eugenia; Donato, María Teresa; Myara, Anne; Nguyen, Tuan Huy; Castell, José Vicente; Gómez-Lechón, María José

    2015-06-01

    Crigler-Najjar type 1 disease is a rare inherited metabolic disease characterized by high levels of unconjugated bilirubin due to the complete absence of hepatic uridine diphosphoglucuronate-glucuronosyltransferase activity. Hepatocyte transplantation (HT) has been proposed as an alternative treatment for Crigler-Najjar syndrome, but it is still limited by the quality and the low engraftment and repopulation ability of the cells used. Because of their attachment capability and expression of adhesion molecules as well as the higher proportion of hepatic progenitor cells, neonatal hepatocytes may have an advantage over adult cells. Adult or neonatal hepatocytes were transplanted into Gunn rats, a model for Crigler-Najjar disease. Engraftment and repopulation were studied and compared by immunofluorescence (IF). Additionally, the serum bilirubin levels, the presence of bilirubin conjugates in rat serum, and the expression of uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) in rat liver samples were also analyzed. Here we show that neonatal HT results in long-term correction in Gunn rats. In comparison with adult cells, neonatal cells showed better engraftment and repopulation capability 3 days and 6 months after transplantation, respectively. Bilirubinemia decreased in the transplanted animals during the whole experimental follow-up (6 months). Bilirubin conjugates were also present in the serum of the transplanted animals. Western blots and IF confirmed the presence and expression of UGT1A1 in the liver. This work is the first to demonstrate the advantage of using neonatal hepatocytes for the treatment of Crigler-Najjar in vivo. PMID:25821167

  6. Comparison of therapeutic characteristics of islet cell transplantation simultaneous with pancreatic mesenchymal stem cell transplantation in rats with Type 1 diabetes mellitus.