Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...
Lausada, Natalia R; Gondolesi, G E; Ortiz, E; Dreizzen, E; Raimondi, J C
The orthotopic rat liver transplant model is a widely used technique in transplantation research. It has many advantages over other animal transplant models because of its availability and low cost. However, it must be emphasized that success with the rat model requires thorough training. The aim of this paper is to describe the microsurgical technique involved in 60 rat liver transplants and to discuss the complications and their treatments. Forty-nine liver transplants were performed at the Experimental Laboratory of the University Hospital, Ontario, Canada (ELUH) and 11 were performed at the Laboratorio de Trasplante de Organos de la Facultad de Ciencias Médicas de La Plata, Buenos Aires. Argentina (LTO). Among the transplants performed at the ELUH, the observed complications were haemorrhage (n = 4), pneumothorax (n = 1), anastomotic failure (n = 15), bile leak (n = 3), and bile duct necrosis (n = 9). The remaining 17 rats at the ELUH were healthy at day 7 after surgery. Animal survival immediately postop, at 24 hours postop and at 7 days postop was achieved with the 9th, 20th and 21st transplants respectively. At the LTO, 3 rats died as a result of anaesthetic complications. Seven-day animal survival was achieved with the 11th transplant. We beleive that the description of the orthotopic rat liver transplantation technique, as well as the discussion regarding complications and their management, can be useful for researchers interested in performing liver transplantation in rats.
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Bruinsma, Bote G; Berendsen, Tim A; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L; Uygun, Korkut
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.
Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut
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
Zhuang, Jianbin; Wang, Yijun; Du, Zhi; Wang, Sumei
Liver-specific protein F is commonly used in liver transplantation studies for its allograft immunogenicity. The objective of this study was to investigate immune tolerance induced by protein F in liver transplantation in rats. Healthy inbred male Wistar and Sprague-Dawley (SD) rats were used in this study. The transplant recipient rats were randomly divided into three groups. The SD rats transplanted with liver tissues from SD rats or Wistar rats were defined as intragraft control group (Group A) or acute reaction group (Group B), respectively. The SD rats that received thymic administration of 4 mg protein F 1 week prior to transplantation with livers from Wistar rats were defined as protein F interference group (Group C). Kamada's two-cuff technique was utilized in the liver transplantation surgeries. The postoperative general condition, transplantation survival time, pathological examination, and serum IFN-γ level (quantified by ELISA) were recorded and compared to evaluate the immune response and outcomes in the recipient rats after liver transplantation. Group A rats exhibited good postoperative condition and prolonged survival (median survival time was 92 days). In contrast, Group B rats lost body weight rapidly after liver transplantation, and died starting at day 12 (median survival time was 15 days). Compared to Group B, Group C rats showed significantly longer survival (medium survival time was 71 days). Our findings indicate that protein F is an important transplantation antigen with allograft immunogenicity, which could successfully induce immune tolerance in liver transplantation.
Praet, Marleen; De Hemptinne, Bernard
In the rat model of heterotopic auxiliary liver transplantation (HALTx), the opinion varies on whether and how the recipient's native liver should be handicapped. To avoid atrophy of the transplanted organ, in this study, two different handicaps were evaluated and their effects on post-operative animal survival and liver biology are described. With a sole portacaval shunt (group 1) all rats survived longer than 3 months. An additional handicap of the liver with either a 68% partial hepatectomy (68% PH) (group 2), or both a 68% PH and a common bile duct ligation (CBDL) (group 3) led to a 100% mortality within 2 days after surgery. When an auxiliary liver was transplanted to the rats handicapped with a 68% PH (group 4), serum Bilirubin and ALAT values were significantly lower than those handicapped with both a 68% PH and a CBDL (group 5). Autopsy and histology of the long-term survivors revealed the atrophy of the engrafted livers and the regeneration of the native livers in group 4, whereas it showed the opposite in group 5. Thus the various manipulations of the native liver do influence differently the post-transplant animal survival, serum liver biochemistry and the outcome of the engrafted liver in this rat model of HALTx. PMID:10468113
Hata, Toshiyuki; Uemoto, Shinji; Kobayashi, Eiji
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
Zhu, Xinhua; Qiu, Yudong; Shi, Mingke; Ding, Yitao
The effect of matrine on cold ischemia and reperfusion injury of sinusoidal endothelial cells (SEC) was investigated in rats using an orthotopic liver transplantation (OLT) model. Syngeneic Sprague-Dawley (SD) rats were randomly assigned to 4 groups of 32 rats: untreated group (controls), low-dose treated group, high-dose treated group, and sham operation group (normals). After 5 hr of preservation in Ringer's solution, orthotopic implantation of the donor liver was performed. At 1, 2, 4, and 24 hr after reperfusion, 6 rats from each group were killed to collect blood and to excise the median hepatic lobe; the other 8 rats were observed to assess the 1-wk survival rate post-transplantation. All transplant recipients in the untreated group (controls) died within 48 hr, mostly between 10 to 20 hr. Matrine treatment increased the 1-wk survival rate to 75% in both treated groups. Plasma levels of hyaluronic acid (HA) at 1, 2, and 4 hr post-implantation were decreased significantly by matrine treatment. The immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) in rat liver decreased significantly in both treated groups, and the pathological changes of SEC were ameliorated. Matrine markedly inhibited the activation of Kupffer cells and their release of tumor necrosis factor (TNF). Hepatic malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were improved by matrine administration. In conclusion, matrine can protect SEC from cold ischemia and reperfusion injury after rat orthotopic liver transplantation.
Lupp, Amelie; Danz, Manfred; Müller, Dieter
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
Mosbah, I B; Zaouali, M A; Martel, C; Bjaoui, M; Abdennebi, H B; Hotter, G; Brenner, C; Roselló-Catafau, J
Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality. PMID:22402603
Sumimoto, R; Shinomiya, T
We examined the appearance of donor (DA) type class I antigen in the serum of rats that had received isogeneic (DA----DA) or allogeneic (DA----PVG, DA----BN, DA----LEW) liver transplants with or without cyclosporin A treatment, using two-site enzyme immunoassay. We also tested the serum titre of class I antigen in the normal DA rats with either 70% hepatectomy or cyclosporin A treatment, in order to clarify the relationship between the fluctuation in the serum titre of class I antigen in the recipient and the outcome of the transplanted liver graft. The suppression of liver graft rejection by cyclosporin A treatment significantly lowered the serum level of donor liver-derived class I antigen as compared with that of the recipient without cyclosporin A for a certain period. However, there was almost no correlation between the intensity of rejection of the liver graft and the serum level type class I among these allogeneic rejection and non-rejection liver transplantation combinations. The amount of donor-type class I antigen in the recipient's serum is dependent on whether the grafted liver is severely damaged following partial hepatectomy, whether the liver has associated biliary complications or ischaemic damage, or whether the liver has had absolute residual parenchymal cell volume or function following liver rejection. Our results suggest that the appearance of donor type class I antigen following liver transplantation is dependent on many factors, and therefore the titre of serum class 1 antigen may not always be a decisive indicator of liver graft rejection. PMID:2070555
Zhuang, Zhuonan; Lian, Peilong; Wu, Xiaojuan; Shi, Baoxu; Zhuang, Maoyou; Zhou, Ruiling; Zhao, Rui; Zhao, Zhen; Guo, Sen; Ji, Zhipeng; Xu, Kesen
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
Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan
The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.
Schmeding, Maximilian; Hunold, Gerhard; Ariyakhagorn, Veravoorn; Rademacher, Sebastian; Boas-Knoop, Sabine; Lippert, Steffen; Neuhaus, Peter; Neumann, Ulf P
Human recombinant Erythropoietin (rHuEpo) has recently been shown to be a potent protector of ischemia- reperfusion injury in warm-liver ischemia. Significant enhancement of hepatic regeneration and survival after large volume partial hepatic resection has also been demonstrated. It was the aim of this study to evaluate the capacities of rHuEpo in the setting of rat liver transplantation. One-hundred-and-twenty Wistar rats were used: 60 recipients received liver transplantation following donor organ treatment (60 donors) with either 1000 IU rHuEpo or saline injection (controls) into portal veins (cold ischemia 18 h, University of Wisconsin (UW) solution). Recipients were allocated to two groups, which either received 1000 IU rHuEpo at reperfusion or an equal amount of saline (control). Animals were sacrificed at defined time-points (2, 4.5, 24, 48 h and 7 days postoperatively) for analysis of liver enzymes, histology [hematoxylin-eosin (HE) staining, periodic acid Schiff staining (PAS)], immunostaining [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Hypoxyprobe] and real-time polymerase chain reaction (RT-PCR) of cytokine mRNA (IL-1, IL-6). Lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) values were significantly reduced among the epo-treated animals 24 and 48 h after liver transplantation (LT). The TUNEL and Hypoxyprobe analyses as well as necrotic index evaluation displayed significant reduction of apoptosis and necrosis in rHuEpo-treated graft livers. Erythropoietin reduces ischemia-reperfusion injury after orthotopic liver transplantation in rats.
Maeda, Hiromichi; Shigoka, Masatoshi; Wang, Yongchun; Fu, Yingxin; Wesson, Russell N.; Lin, Qing; Montgomery, Robert A.; Enzan, Hideaki; Sun, Zhaoli
Background and Aim Green fluorescent protein (GFP) is a widely used molecular tag to trace transplanted cells in rodent liver injury models. The differing results from various previously reported studies using GFP could be attributed to the immunogenicity of GFP. Methods Hepatocytes were obtained from GFP-expressing transgenic (Tg) Lewis rats and were transplanted into the livers of wild-type Lewis rats after they had undergone a partial hepatectomy. The proliferation of endogenous hepatocytes in recipient rats was inhibited by pretreatment with retrorsine to enhance the proliferation of the transplanted hepatocytes. Transplantation of wild-type hepatocytes into GFP-Tg rat liver was also performed for comparison. Results All biopsy specimens taken seven days after transplantation showed engraftment of transplanted hepatocytes, with the numbers of transplanted hepatocytes increasing until day 14. GFP-positive hepatocytes in wild-type rat livers were decreased by day 28 and could not be detected on day 42, whereas the number of wild-type hepatocytes steadily increased in GFP-Tg rat liver. Histological examination showed degenerative change of GFP-positive hepatocytes and the accumulation of infiltrating cells on day 28. PCR analysis for the GFP transgene suggested that transplanted hepatocytes were eliminated rather than being retained along with the loss of GFP expression. Both modification of the immunological response using tacrolimus and bone marrow transplantation prolonged the survival of GFP-positive hepatocytes. In contrast, host immunization with GFP-positive hepatocytes led to complete loss of GFP-positive hepatocytes by day 14. Conclusion GFP-positive hepatocytes isolated from GFP-Tg Lewis rats did not survive long term in the livers of retrorsine-pretreated wild-type Lewis rats. The mechanism underlying this phenomenon most likely involves an immunological reaction against GFP. The influence of GFP immunogenicity on cell transplantation models should be
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Ma, Zheng-Wei; Liu, Li-Dong; Li, Kun; Zhang, Yu-Jun; Dong, Jia-Hong
Nutritional supports are required for liver transplant patients. However, no systematical assessment has been made of the optimal composition of energy yielding substrates in these patients. This study is to evaluate whether mixed energy system consisting of carbohydrate and lipid emulsions is more advantageous over single energy source of glucose for nutritional support in liver transplant recipients and whether structured lipid emulsion (STG) is superior to medium-chain triglyceride/long-chain triglycerides (MCT/LCT) and long-chain triglycerides (LCT) using a total parenteral nutrition model. Liver transplant rats were randomly divided to four groups according to the energy source, i.e. glucose (GLU), MCT/LCT, STG and LCT groups. Sham operated rats served as control. Hepatic function and lipid profile were determined to investigate the roles of lipid emulsion in hepatic function and lipid metabolism. Morphological changes of liver were observed, and nitrogen balance was determined. The results showed that infusion of lipid emulsion was well tolerated. The 1-week survival rate in the lipid emulsion groups was significantly higher than in the GLU group (100% versus 50%, P<0.05); compared with the GLU group, hepatic function recovered quickly and returned to normal level, and morphological alterations were less severer in the lipid emulsion groups, especially in the STG group; the lipid emulsions groups had normal serum TG and TC levels, especially STG and MCT/LCT groups; the lipid emulsions groups achieved a positive nitrogen balance on day 7 compared with the GLU group, and the STG group had the highest nitrogen balance. In conclusion, lipid emulsion is beneficial in improving hepatic function and the recipients' survival and does not influence the lipid metabolism. Mixed energy system consisting of carbohydrate and lipid is more advantageous over single energy source of glucose after liver transplantation, and STG is superior to MCT/LCT and LCT.
... this page: //medlineplus.gov/ency/presentations/100090.htm Liver transplant - series—Normal anatomy To use the sharing ... to slide 5 out of 5 Overview The liver is in the right upper abdomen. The liver ...
Sun, Lihua; Fan, Xiaotang; Zhang, Lijuan; Shi, Guixiu; Aili, Maimaiti; Lu, Xiaobo; Jiang, Tao; Zhang, Yuexin
In the present study, we assessed the efficiency of four BMSC transplantation methods as a therapy for liver failure. A rat model (80 Sprague-Dawley rats) of D-galactosamine (D-gal)/lipopolysaccharide (LPS)-induced acute liver failure (ALF) was established and the rats were divided into 5 groups: a hepatic artery injection group, a portal vein injection group, a vena caudalis injection group, an intraperitoneal injection group and a control group (16 per group). Following transplantation, the liver tissue and blood samples were collected on days 1, 3 and 7, we detected the EdU (5-ethynyl-2'-deoxyuridine)-labeled cells homing to the liver tissue and assessed the proliferating cell nuclear antigen (PCNA) and cysteine-containing aspartate-specific protease (caspase)-3 expression in the liver tissue and detected the levels of stromal cell-derived factor 1 (SDF-1) and hepatocyte growth factor (HGF) in the liver tissues. Compared with the control group, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and damage to the liver tissue in the hepatic artery group, the portal vein group and the vena caudalis group improved in vivo. The expression of PCNA and HGF in the liver was higher and caspase-3 expression was lower in the hepatic artery injection group, the portal vein injection group and the vena caudalis injection group than that in the intraperitoneal injection and control groups. The EdU-labeled BMSCs were only observed homing to the liver tissue in these three groups. However, no significant differences were observed between these three groups. Liver function in the rats with ALF was improved following BMSC transplantation via 3 endovascular implantation methods (through the hepatic artery, portal vein and vena caudalis). These 3 methods were effective in transplanting BMSCs for the treatment of ALF. However, the selection of blood vessel in the implantation pathway does not affect the transplantation outcome. Transplantation via
Faris, R A; Hixson, D C
Although proliferation of oval cells is often observed during the early stages of chemical hepatocarcinogenesis, the role of these putative hepatic stem cells during the neoplastic process is unknown. In earlier studies our laboratory showed that feeding a choline-deficient (CD) diet containing 0.05% 2-acetylaminofluorene (CD-AAF) to rats produced three subpopulations of oval cells that antigenically resemble biliary duct cells, fetal liver cells, and transitional cells. In the present investigation we have employed a semiallogeneic transplantation protocol in order to study the fate of these nonparenchymal epithelial cells (NPEC) beyond the 4-week endpoint imposed by the lethality of CD-AAF diet. An enriched NPEC suspension containing gamma-glutamyl-transpeptidase (GGT)-positive oval cells (greater than 75%) was isolated from ACI rats maintained on CD-AAF diet for 3 weeks. The donor cells were transplanted via the portal vein into livers of male F1 progeny (LExACI) that had been fed a CD diet for 7 days prior to receiving a partial hepatectomy and the cell suspension. Host rats were then fed either a CD or choline-supplemented (CS) diet for 12 weeks and killed. Colonies of donor-derived cells identified in frozen sections by their lack of reactivity with ACI anti-LE alloantiserum in indirect immunofluorescence (IF) assays were only observed in rats continuously fed the CD diet. Histochemical analysis indicated that the donor-derived colonies expressed GGT, a preneoplastic marker for liver cancer. IF assays using MAbs previously shown to be capable of distinguishing between oval cells and mature hepatocytes indicated that the donor-derived colonies consisted of a mixture of cells with phenotypes resembling those of mature and immature hepatocytes rather than those of oval or ductal cells. Although the cellular origin of the GGT+ donor-derived colonies has not been unequivocally resolved, our results demonstrate that the livers of rats fed a CD-AAF diet contain a
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
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
Chen, Xiao-Wu; Zhu, Da-Jian; Ju, Yong-Le; Zhou, Shu-Feng
Summary Background There are only few reports about the use of bone marrow stromal stem cells (BMSCs) for the treatment of traumatic liver injury. This study aimed to study the therapeutic effect of fluorescence-labeled BMSCs administered to rats subject to traumatic liver injury. Material/Methods Male SD rats with a 70% resection of the liver were injected with feridex-labeled BMSCs which could be induced to functional hepatocytes in vitro. Liver function was assayed and the liver scanned by 1.5-T MRI at 12 hrs and on days 1, 3, 5, 7, and 14 post-operation. The pathological changes of liver sections were monitored. Results The serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, and total bilirubin in the transplantation group were significantly lower than the control group. The MRI showed rats of the transplantation group had an oval low signal area at 12 hr after operation; the low signal range gradually expanded and the signal intensity gradually decreased over 14 days after operation. The low signal range in the control group disappeared 12 hr after the operation. After Prussian blue staining, rats of the transplantation group contained blue granules with no significant hypertrophy or edema in hepatocytes, while the control group showed no blue granules with significant hypertrophy and edema. Conclusions The BMSCs transplanted into the injured rat liver gradually migrate to the surrounding liver tissue and partially repair the liver surgical injury in rats. BMSCs may represent an effective therapeutic approach for acute liver injury. PMID:23018343
Alexander, J A; Demetrius, A J; Gavaler, J S; Makowka, L; Starzl, T E; Van Thiel, D H
Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.
Ishii, Eiichi; Shimizu, Akira; Takahashi, Mikiko; Terasaki, Mika; Kunugi, Shinobu; Nagasaka, Shinya; Terasaki, Yasuhiro; Ohashi, Ryuji; Masuda, Yukinari; Fukuda, Yuh
Orthotopic liver transplantation (OLT) in rats is technically feasible and useful for the assessment of clinical liver transplantation and analysis of inflammatory liver diseases. OLT in rats was pioneered by Lee et al. in 1973 using hand-suture techniques of all vessels. This model has not been widely used due to the long operative time and technical demand. The cuff method was introduced by Kamada in 1979, and today, the Kamada technique is the one most commonly used worldwide. However, this technique does not include hepatic artery reconstruction, although this procedure is routinely performed in clinical transplantation. Nevertheless, several techniques for hepatic artery reconstruction in rat OLT have been reported recently, and our group also developed a simple splint technique from recipient right renal artery to donor celiac axis bearing the hepatic artery. In the present article, we describe the Kamada technique, as a standard surgical method for rat OLT. In addition, we also describe our splint technique for hepatic artery reconstruction. Then, we compare the features of Kamada technique and our splint technique for hepatic artery reconstruction and all other surgical techniques currently in use for rat OLT. The widespread use of the rat OLT model should help to provide full assessment of transplant immunology and the mechanism and treatment of inflammatory liver diseases.
MÃ¶ller, P. H.; Ivarsson, K.; Stenram, U.; Radnell, M.; Tranberg, K. G.
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
Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria
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
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
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.
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Wong, W. W.; Bain, V. G.
OBJECTIVE: To review recent developments in liver transplantation with particular emphasis on issues relevant to patient care before and after transplantation. QUALITY OF EVIDENCE: Preference was given to recent studies with well-designed cohort methods and large numbers of study subjects. Data on natural history are summarized from large databases in Canada and the United States. Due to the nature of the subjects involved, most treatment studies are open studies or consecutive series rather than randomized controlled trials. MAIN MESSAGE: Substantial advances in liver transplantation have established it as an effective treatment for most end-stage liver diseases, with 1-year survival rates higher than 85% in many centres. Early referral by family physicians and careful patient selection by transplant centres remain crucial to continued success. Managing these patients requires special care from family physicians because of post-transplantation immunosuppression, increased risk of opportunistic infection, and transplantation-associated medical problems. Other unresolved issues include recurrence of disease (hepatitis B and C, and malignancy) and an ongoing shortage of organs. CONCLUSIONS: Liver transplantation is an effective form of therapy for end-stage liver disease, improving both patients' likelihood of survival and their quality of life. Because medical care of liver transplant patients is so complex, coordinated efforts between primary care physicians and transplant teams are crucial. PMID:10349068
Chen, Zhong; Chang, Renan; Guan, Weijun; Cai, Hongyu; Tang, Fei; Zhu, Wencai; Chen, Jiahui
In this study, free porcine hepatocytes suspension (Group A), porcine hepatocytes embedded in collagen gel (Group B), porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel (Group C), and PLA-O-CMC nanoparticles alone (Group D) were transplanted into peritoneal cavity of ALF rats, respectively. The result showed that plasma HGF levels were elevated post-transplantation with a peak at 12 hr. The rats in Group C showed highest plasma HGF levels at 2, 6, 12, 24 and 36 hr post-transplantation and lowest HGF level at 48 hr. Plasma VEGF levels were elevated at 48 hr post-transplantation with a peak at 72 hr. The rats in Group C showed highest plasma HGF levels at 48, 72, and 96 hr post-transplantation. The liver functions in Group C were recovered most rapidly. Compared with Group B, Group C had significant high liver Kiel 67 antigen labeling index (Ki-67 LI) at day 1 post-HTx (P < .05). Ki-67 LI in groups B and C was higher than that in groups A and D at days 5 and 7 post-HTx. In conclusion, intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can promote significantly liver regeneration in ALF rats. PMID:21603218
... 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 ...
... 2002 December 2006 March 2012 Getting A New Liver Facts About Liver Transplants American Society of Transplantation 1120 Route 73, ... views of the Society. _________________________________________________________________ 1 Getting a New Liver Facts About Liver Transplants A liver transplant is ...
Yang, Z-L; Cheng, K; Sun, H G; Zou, W W; Wu, M M
In this study, early expressions of peripheral blood Th1 and Th2 cells were documented following rat liver transplantation and related to immune status. Rats were divided into 3 groups: group A (control): syngeneic transplantation (Brown Norway (BN) → BN); group B: allogeneic transplantation + cyclosporine A (CsA); group C: allogeneic transplantation (Lewis → BN). Flow cytometry was used to analyze peripheral blood CD4(+)CD45RC percentage on days 1, 3, 5, 7, and 14 following transplantation, and were compared to graft rejection pathological grades and receptor survival times. The average survival of groups A and B exceeded 100 days, which was significantly longer than that of group C (3.56 ± 34.3 days). With the exception of the first day, rejection grades were significantly higher in groups C and B compared to group A, and group C rejection grades were significantly higher than those of group B. Three days after transplantation, the CD4(+)CD45RC(+) to CD4(+)CD45RC(-) ratio of group C was significantly higher than that of groups A and B. In group B, the CD4(+)CD45RC(+) to CD4(+)CD45RC(-) ratio was negatively correlated to the rejection grade (r = -0.565, P < 0.01), whereas this relationship was positive in group C (r = 0.745, P < 0.01). In conclusion, peripheral blood Th1 was highly expressed during rejection in rat liver grafts. Peripheral blood Th2 tended to increase early under rejection inhibition with CsA, and its high expression level may correlate with long-term acceptance or tolerance of transplanted livers.
Uygun, Korkut; Tolboom, Herman; Izamis, Maria-Louisa; Uygun, Basak; Sharma, Nripen; Yagi, Hiroshi; Soto-Gutierrez, Alejandro; Hertl, Martin; Berthiaume, François; Yarmush, Martin L.
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
Starzl, Thomas E.; Fung, John J.
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
Ho, Cheng-Maw; Chen, Ya-Hui; Chien, Chin-Sung; Ho, Yi-Tian; Ho, Shu-Li; Hu, Rey-Heng; Chen, Hui-Ling; Lee, Po-Huang
The impact of the rate of intraportal hepatocyte transplantation on early engraftment and repopulation is unclear. The aim of this study was to address this and to improve the engraftment and repopulation efficiencies of hepatocyte transplantation for the treatment of a rat model of acute liver failure in a clinically useful way without preconditioning. Acute hepatic injury was induced into Sprague-Dawley rats with D-galactosamine. Hepatocytes were infused intraportally over a period of 30, 70, or 100 seconds to study early engraftment (2 days) and repopulation (7 days). Three groups had significant differences in hepatocyte engraftment (P = 0.018) and repopulation efficiencies (P = 0.037), and an infusion over a period of 70 seconds produced superior outcomes. After the 70-second infusion, the transplanted cells immediately transmigrated the sinusoidal endothelial layer and rarely accumulated in the portal venules, with liver function improving significantly. The mean first peak pressures, without significant differences, were 14.8 ± 6.5, 17.7 ± 3.7, and 13.6 ± 3.0 mm Hg in the 30-, 70-, and 100-second groups, respectively. Differential hepatocyte transfusion rates contributed to accelerated early engraftment and repopulation in rats with acute liver injury. These proof-of-concept findings are of clinical significance because they are easy to translate into practice.
Ayloo, Subhashini; Armstrong, John; Hurton, Scott; Molinari, Michele
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
Kern, Hans; Bald, Christian; Brill, Thomas; Fend, Falko; von Weihern, Claus Hann; Kriner, Monika; Hüser, Norbert; Thorban, Stefan; Stangl, Manfred; Matevossian, Edouard
Dysfunction of the graft after liver transplantation caused by ischaemia-/reperfusion (I/R) injury is a serious clinical problem. The aim of this study was to evaluate the influence of different kinds of reperfusion on I/R injury in a rat model. Arterialized orthoptic rat liver treatment was performed on male LEWIS-(RT(1))-rats. Three groups (n = 7) were formed. Group I: antegrade reperfusion with a 6-min delayed reperfusion via the hepatic artery. Group II: Antegrade reperfusion, simultaneously, via the portal vein and the hepatic artery. Group III: Retrograde reperfusion via the vena cava. Serum parameters were determined one, 24 and 48 h after operation. Furthermore, after 48 h, the liver was taken for histological assessment. After 48 h, rats of group III showed significantly lower aspartate amino transferase and alanine amino transferase serum levels compared with group I and group II rats. Forty-eight hours after transplantation, glutamate dehydrogenase serum level was significantly lower in group III than in group II. In histology, group III livers showed significantly less necrotic spots than group I and group II livers. Maximum size of the necrotic spots was significantly lower in group III than in group I. Also, significantly more necrotic spots were seen in the 'Rappaport's zone' 1 and 2 of group I than in group III. Our data suggested that the expression of I/R-injury correlates with the type of reperfusion. Furthermore, under standard conditions, this study was able to demonstrate that in a rat model, the retrograde reperfusion leads to a lower expression of I/R-injury than the antegrade reperfusion.
Dirsch, Olaf; Chi, Haidong; Ji, Yuan; Gu, Yan Li; Broelsch, Christoph E; Dahmen, Uta
AIM: Recently it has been reported that granulocyte colony stimulating factor (G-CSF) can induce hypercoagulability in healthy bone marrow donors. It is conceivable that the induction of a prothrombotic state in a recipient of an organ graft with already impaired perfusion might cause further deterioration in the transplanted organ. This study evaluated whether G-CSF treatment worsens liver perfusion following liver transplantation in the rat model. METHODS: A non-arterialized rat liver transplantation model was employed to evaluate the effect of G-CSF treatment on the liver in a syngeneic and allogeneic strain combination. Study outcomes included survival time and liver damage as investigated by liver enzymes and liver histology. Observation times were 1 d, 1 wk and 12 wk. RESULTS: Rats treated with G-CSF had increased incidence and severity of biliary damage following liver transplantation. In these animals, hepatocellular necrosis was accentuated in the centrilobular region. These lesions are indicative of impaired perfusion in G-CSF treated animals. CONCLUSION: G-CSF should be used with caution in recipients of liver transplantation, as treatment might enhance preexisting, undetected perfusion problems and ultimately lead to ischemia induced biliary complications. PMID:16937499
Carrion, Andres F; Aye, Lydia; Martin, Paul
Improved outcomes in liver transplant recipients reflect advances in surgical technique, post-operative care, immunosuppression as well as better selection of potential candidates. The pre-transplant evaluation is a multidisciplinary process intended to recognize and treat important comorbid conditions that may impair outcomes during the peri- and post-transplant periods. Important psychosocial issues should also be ascertained and tackled early during the pre-transplant evaluation with an overarching intention to improve the success of liver transplantation.
Shi, Yanjun; Rehman, Hasibur; Wright, Gary L; Zhong, Zhi
This study investigated the roles of inducible nitric oxide synthase (iNOS) in the failure of rat liver grafts from cardiac death donors (GCDD). Livers were explanted after 30-minute aorta clamping and implanted after 4-hour storage in University of Wisconsin solution. The iNOS expression increased slightly in grafts from non-cardiac death donors (GNCDD) but markedly in GCDD. Serum nitrite and nitrate and hepatic 3-nitrotyrosine adducts, indicators of NO and peroxynitrite production, respectively, were substantially higher after transplantation of GCDD than GNCDD. Production of reactive nitrogen species (RNS) was largely blocked by 1400W (N-[1-naphthyl]ethylenediamine dihydrochloride; 5 μM), a specific iNOS inhibitor. Alanine aminotransferase release, bilirubin, necrosis, and apoptosis were 6.4-fold, 6.5-fold, 2.3-fold, and 2.7-fold higher, respectively, after transplantation of GCDD than GNCDD. The inhibitor 1400W effectively blocked these alterations and also increased survival of GCDD to 80% from 33%. Increased RNS production and failure of GCDD were associated with activation of c-Jun-N-terminal kinase (JNK), an effect that was blocked by inhibition of iNOS. Inhibition of JNK also improved the outcome after transplantation of GCDD. Together, the data indicate that iNOS increases substantially in GCDD, leading to RNS overproduction, JNK activation, and more severe graft injury. Inhibitors of iNOS are suggested as effective therapies to improve the outcome after transplantation of GCDD.
Goarin, A-C; Homer, L
Management during their sexual life of patients with a liver transplantation is a more or less common situation depending centers. Based on literature review, a focus on management of recipient women was conducted, from contraception to pregnancy, describing the complications related to the status of transplant recipient, but also those that may be related to immunosuppressive agents. If fertility and access to contraception are only slightly modified by graft, complications related to graft or immunosuppressive drugs can affect the pregnancy. On the maternal side, hypertension and preeclampsia are more common, as well as renal dysfunction, iatrogenic diabetes and bacterial or viral infections, acute rejection and graft loss do not appear to be influenced by pregnancy. The fetus is also exposed to risks such as induced prematurity and IUGR. Pregnancy in recipients of hepatic grafts therefore requires joint follow-up by transplant specialist and perinatologist, which leads in most cases to successful outcome for mother and child.
Nakano, Toshiaki; Goto, Shigeru; Lai, Chia-Yun; Hsu, Li-Wen; Tseng, Hui-Peng; Chen, Kuang-Den; Chiu, King-Wah; Wang, Chih-Chi; Cheng, Yu-Fan; Chen, Chao-Long
Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.
Joseph, Brigid; Kapoor, Sorabh; Schilsky, Michael L; Gupta, Sanjeev
Insights into disease-specific mechanisms for liver repopulation are needed for cell therapy. To understand the efficacy of pro-oxidant hepatic perturbations in Wilson disease, we studied Long-Evans Cinnamon (LEC) rats with copper toxicosis under several conditions. Hepatocytes from healthy Long-Evans Agouti (LEA) rats were transplanted intrasplenically into the liver. A cure was defined as lowering of copper to below 250 microg/g liver, presence of ATPase, Cu++ transporting, beta polypeptide (atp7b) messenger RNA (mRNA) in the liver and improvement in liver histology. Treatment of animals with the hydrophobic bile salt, cholic acid, or liver radiation before cell transplantation produced cure rates of 14% and 33%, respectively; whereas liver radiation plus partial hepatectomy followed by cell transplantation proved more effective, with cure in 55%, P < 0.01; and liver radiation plus cholic acid followed by cell transplantation was most effective, with cure in 75%, P < 0.001. As a group, cell therapy cures in rats preconditioned with liver radiation plus cholic acid resulted in less hepatic copper, indicating greater extent of liver repopulation. We observed increased hepatic catalase and superoxide dismutase activities in LEC rats, suggesting chronic oxidative stress. After liver radiation or cholic acid, hepatic lipid peroxidation levels increased, indicating further oxidative injury, although we did not observe overt additional cytotoxicity. This contrasted with healthy animals in which liver radiation and cholic acid produced hepatic steatosis and loss of injured hepatocytes. We concluded that pro-oxidant perturbations were uniquely effective for cell therapy in Wilson disease because of the nature of preexisting hepatic damage.
Celli, S.; Valdivia, L.A.; Kelly, R.H.; Demetris, A.J.; Fung, J.J.; Rao, A.S.; Pan, F.; Tsugita, M.; Starzl, T.E.
Long-term survival after hamster-to-rat liver xenotransplantation has provided the opportunity to study the posttransplantation source of major serum proteins and the functional consequences of several different receptor-ligand interactions, where one or the other is a xenogeneic protein. We report here that serum albumin, α-1-antitrypsin, complement component 3, and other acute phase reactants switch from recipient to donor origin during the first week after transplantation while serum immunoglobulins remain largely that of recipient. Despite the disparate source of complement (hamster) and immunoglobulins (rat), these two proteins were able to cooperate effectively to produce lysis of sheep red blood cells. Moreover, rat IgA was successfully processed by hamster hepatocytes and biliary epithelial cells, being present in the bile of successful liver xenograft recipients within one day after transplantation. The ability of these liver xenograft recipients to survive long-term in conventional and viral-free animal facilities without grossly obvious morbidity or unusual susceptibility to stress, suggests that xenogeneic proteins are able to successfully interact with several different physiologic systems in the hamster-to-rat combination. PMID:21318076
Karani, John B. Yu, Dominic F.Q.C.; Kane, Pauline A.
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.
Pedersen, Mark; Seetharam, Anil
Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581
Carrion, Andres F; Bhamidimarri, Kalyan Ram
Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.
Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha
Objective: The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Materials and Methods: Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. Results: In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months–17 years). The 4 most common reasons for liver transplantation were: Wilson’s disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. Conclusion: The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature. PMID:28149148
Adachi, K; Fujino, M; Kitazawa, Y; Funeshima-Fuji, N; Takahara, S; Kimura, H; Li, X-K
Modulation of donor organs by transfection of a gene encoding immmunosuppresive molecules has been recognized as a less toxic approach to prevent allograft rejection. Fas-ligand (FasL) plays a critical role in activation-induced cell death of activated cytotoxic lymphocytes. This may provide a potential for induction of "immune privileged sites" to escape the host immune surveillance system. Cytokine response modifier A (CrmA), a gene product of cowpox virus, blocks caspase as well as perforin/granzyme-mediated apoptotic pathways. Therefore, it may suppress intragraft apoptosis. The aim of the present study was to investigate whether transfection of FasL or CrmA genes prolonged the survival of rat liver allografts. Using the high responder rat combination of DA (RT-1(a)) donor to LEW (RT-1(1)) recipient, we performed orthotopic liver transplantation with subsequent delivery of adenoviral vectors containing FasL, CrmA, or LacZ, at a dose of 1 x 10(9) pfu via a recipient tail vein using a Cre-mediated gene expression system. Recipient survival was assessed as well as immunohistochemical examination of the grafts for anti-CD2, TUNEL, and H&E staining. Statistical analysis was performed with the Mann-Whitney U test. The therapeutic groups showed significantly prolonged recipient survival compared with the LacZ-treated control group. Histologic analysis revealed reduced hepatocyte apoptosis in the CrmA-treated group and increased apoptosis of infiltrating mononuclear cells in the FasL-treated group. These data suggested that FasL and CrmA may be potent genes to prolong rat liver allograft survival.
Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero
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 review
Hüsing, Anna; Kabar, Iyad; Schmidt, Hartmut H
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
Brown, Robert S.
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.
Leszczynski, D.; Renkonen, R.; Haeyry, P.
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.
... 2-Year-Old When Your Child Needs a Liver Transplant KidsHealth > For Parents > When Your Child Needs ... regular checkups to monitor liver function. Causes of Liver Failure The liver — a soft, triangular-shaped organ — ...
Moray, Gökhan; Arslan, Gülnaz; Haberal, Mehmet
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.
Kim, Sang Il
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.
Kim, Sang Il
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
Romero, Fabian A; Razonable, Raymund R
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. PMID:21603030
The constant updating in the field of liver transplant led to the holding of the III Consensus Meeting of the Spanish Liver Transplant Association. Three current topics of great clinical interest were debated during this meeting; transplant in patients with liver cirrhosis due to hepatitis C, live donor liver transplant and the evaluation of the quality of liver grafts. A subject of great interest to Liver Transplant Units was also discussed: the assessment of their quality.
Herrero, J Ignacio
The constant updating in the field of liver transplant led to the holding of the III Consensus Meeting of the Spanish Liver Transplant Association. Three current topics of great clinical interest were debated during this meeting; transplant in patients with liver cirrhosis due to hepatitis C, live donor liver transplant and the evaluation of the quality of liver grafts. A subject of great interest to Liver Transplant Units was also discussed: the assessment of their quality.
... instructions before and after surgery. • Have a compatible blood type. • Have an emotional tie with the recipient. • Not ... test is to find out if the donor's blood type matches the recipient’s blood type. Next, the transplant ...
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
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
... poultry, eggs, fish, tofu, and soy protein. Low Sodium -- Symptoms of advanced liver disease include excess fluid ... in the legs (edema). A high level of sodium, or salt, intake increases the amount of water ...
Jiménez-Castro, Mónica B; Negrete-Sánchez, Elsa; Casillas-Ramírez, Araní; Gulfo, Jose; Álvarez-Mercado, Ana I; Cornide-Petronio, María Eugenia; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen
In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.
Haga, Junko; Enosawa, Shin; Kobayashi, Eiji
Advances in stem cell research suggest that cell therapy is a potential alternative to liver transplantation. The use of individualized and minimally invasive cell therapy is desirable to avoid rejection and reduce patient burden. While allo-hepatocyte transplantation has been performed for metabolic hepatic disease, auto-bone marrow transplantation (BMT) has shifted toward mesenchymal stem cells (MSCs) transplantation for liver cirrhosis. In this article, an overview of cell transplantation research for liver disease is provided through our recent rat studies. We have developed various kinds of rat imaging models and have evaluated the effect of cell therapy for liver disease. Bone marrow cells (BMCs) of the Alb-DsRed2 rat were transplanted via the portal vein (PV) in acute and chronic liver damage models. The number of Alb-DsRed2+ albumin-producing cells increased, and the size of the cells increased in the chronic liver damage model as well as in the acute liver damage model. Luciferase transgenic (luc-Tg) rat hepatocytes were transplanted into the hepatectomized LEW rat via the PV. Luminescence intensity lasted for 2 months in the hepatectomized rat. BMCs obtained from green fluorescent protein (GFP) Tg rats were transplanted repeatedly via the PV using an implanted catheter with a port. Repeated BMT via the PV reduced the liver fibrosis. Adipocyte-derived MSCs from the luc-Tg rat were transplanted into the hepatectomized rat model via the PV after ischemic reperfusion. MSCs inhibited hepatocyte apoptosis and promoted liver regeneration. Transplanting the optimal number of cells by an effective and safe way is important for clinical application. Bioimaging rats are a powerful tool for cell transplantation research because it makes observation of the in vivo kinetics of transplanted cells possible. Cell transplantation research using bioimaging rats contributes greatly to evaluating effective methods of cell therapy. PMID:28174669
Meyers, Rebecka L.; Tiao, Greg M.; Feusner, James H.
Hepatoblastoma is the most common pediatric liver tumor and is usually diagnosed before five years of age. Treatment consists of a combination of chemotherapy and surgery, with the goal being attainment of complete local control by surgical resection and eradication of any extrahepatic disease. Neoadjuvant chemotherapy is utilized and is often beneficial in rendering tumors resectable; however, prolonged chemotherapy administration attempting to render tumors resectable by conventional resection should be avoided. For patients whose tumors are too extensive to be conventionally resected, liver transplantation can be curative and remains the treatment of choice for eligible patients otherwise incurable by conventional resection. PMID:28138611
Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M
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
Chaman Ortiz, José Carlos; Padilla Machaca, P Martín; Rondon Leyva, Carlos; Carrasco Mascaró, Felix
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.
Hernandez, Maria Del Pilar; Martin, Paul
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
Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A; Thomson, Angus W
The surgically demanding mouse orthotopic liver transplant model was first described in 1991. It has proved to be a powerful research tool for the investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction, and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, because the mouse genome is well characterized and there is much greater availability of both genetically modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice have provided valuable mechanistic insights into the immunobiology and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in the regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/immune-mediated events in the hepatic environment and systemically. In conclusion, orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology, and allograft tolerance that may result in therapeutic innovation in the liver and in the treatment of other diseases.
Kirnap, Mahir; Akdur, Aydincan; Ozcay, Figen; Soy, Ebru; Coskun, Mehmet; Moray, Gokhan; Haberal, Mehmet
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.
Bottino, R; Fernandez, L A; Ricordi, C; Lehmann, R; Tsan, M F; Oliver, R; Inverardi, L
Early impairment of islet function and graft loss limit the success of allogeneic islet transplantation. Nonspecific inflammatory events occurring at the transplant site immediately after grafting, involving the production of cytokines and free radicals and sinusoidal endothelial cell (SEC) activation, may contribute to islet cell damage. To evaluate whether Kupffer cell inactivation would result in prolonged allograft survival in a model system of intrahepatic islet transplantation in rats, we systemically administered either gadolinium chloride (GdCl3) or dichloromethylene diphosphonate (Cl2MDP) to assess the effects of macrophage inactivation on rejection and on the release of proinflammatory molecules, as well as to assess the functional profile of SEC. The results obtained were compared with those observed in untreated, sham-injected animals and in rats receiving intraportal infusions of microbeads. Transient macrophage inhibition, particularly in hepatic Kupffer cells, is associated with significant prolongation of graft survival after intraportal islet allotransplantation (ITx) in rats: 7.2 days in the control group versus 11.9 days in the GdCl3 group (P < 0.01) and 15.6 days in the Cl2MDP group (P < 0.0006), respectively. Although systemic release of inflammatory mediators was observed only when islet transplantations were performed and it could be inhibited by macrophage-targeting treatments, perturbation of the functional profile of endothelial cells was also observed when microembolization was induced by the use of microbeads and could not be prevented by macrophage inhibition. These experiments provide evidence to support the concept that macrophages play a key role in early inflammatory events known to adversely affect islet engraftment and suggest that manipulation of nonspecific immune activation by inhibition of macrophage function may facilitate hepatic engraftment of islet allografts. The mechanisms mediating this effect are likely to include
Todo, Satoru; Hall, Roberta; Tzakis, Andreas; Starzl, Thomas E.
Two patients with situs inversus and biliary atresia were treated with hepatic transplantation, one with an auxiliary liver and the other with an orthotopic graft which was placed using a piggy-back technique. Both transplants functioned well initially. The auxiliary liver was rejected after 1 ½ months, and the patient died after an attempt at retransplantation many months later. The recipient of the orthotopic liver has perfect liver function 10 months postoperatively. PMID:10147625
Mendizabal, Manuel; Silva, Marcelo Oscar
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
Berlakovich, Gabriela A
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
Parajuli, Sandesh; Foley, David; Djamali, Arjang; Mandelbrot, Didier
Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant.
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
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.
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.
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
Lv, Hu; Han, Cui-hong; Sun, Xue-jun; Liu, Wen-wu
In recent years, hyperbaric oxygen (HBO) has been used in the treatment of a lot of diseases such as decompression sickness, arterial gas embolism, carbon dioxide poisoning, soft tissue infection, refractory osteomyelitis, and problematic wound, but little is known about its application in liver transplantation. Although several studies have been conducted to investigate the protective effects of HBO on liver transplantation and liver preservation, there are still some controversies on this issue, especially its immunomodulatory effect. In this short review, we briefly summarize the findings supporting the application of HBO during liver transplantation (including donors and recipients). PMID:28217293
Thurman, R G; Gao, W; Connor, H D; Adachi, Y; Stachlewitz, R F; Zhong, Z; Knecht, K T; Bradford, B U; Mason, R P; Lemasters, J J
Kupffer cells have been implicated in mechanisms of pathophysiology following liver transplantation. Recently, postoperative injury in ethanol-induced fatty liver has been evaluated because fatty livers often fail following transplantation. The low-flow, reflow liver perfusion model was used to study the role of Kupffer cells (KC) in reperfusion injury to fatty livers from rats fed a diet containing ethanol for 4-5 weeks. Treatment with GdCl3, which selectively destroys KC, decreased cell death significantly. Thus, destruction of KC minimized hepatic reperfusion injury, most likely by inhibiting free radical formation and improving microcirculation. Since it was demonstrated recently that destruction of KC prevented the hypermetabolic state observed with acute alcohol exposure, their involvement in events leading to alcohol-induced liver disease was investigated. In rats exposed to ethanol continuously via intragastric feeding for up to 4 weeks, GdCl3 treatment prevented elevation of aspartate aminotransferase (AST) and dramatically reduced the average hepatic pathological score. These results indicate that KC participate in the early phases of alcohol-induced liver injury. Endotoxaemia occurs in alcoholics and activates KC; therefore, we evaluated the effect of minimizing bacterial endotoxin by intestinal sterilization with the antibiotics polymyxin B and neomycin. Antibiotics diminished plasma endotoxin levels significantly and prevented ethanol-induced increases in AST values. These results indicate that endotoxin is involved in the mechanism of ethanol-induced liver injury. A six-line radical spectrum was detected with electron paramagnetic resonance spectroscopy in bile from alcohol-treated rats which was blocked by GdCl3. The free radical adducts had hyperfine coupling constants characteristic of lipid-derived free radical products. In conclusion, these studies demonstrate that KC are involved in reperfusion injury to ethanol-induced fatty livers and hepatic
Birnbaum, David Jérémie; Grégoire, Emilie; Hardwigsen, Jean; Le Treut, Yves Patrice
Hepatic gas gangrene is an uncommon situation mainly due to bacterial infection by Clostridium perfringens. It remains a life-threatening condition associated with a high mortality rate. Quick diagnosis and aggressive therapy including liver transplantation should be proposed to improve the outcome. This report describes a rare case of hepatic gas gangrene on native liver, secondary to iatrogenic hepatic artery thrombosis and instrumental biliary tree infection, which was successfully treated by liver transplantation.
As surgical and graft preservation techniques have improved and immunosuppressive drugs have advanced, liver transplantation (LT) is now considered the gold standard for treating patients with end-stage liver disease worldwide. However, despite the improved survival following LT, severe hemodynamic disturbances during LT remain a serious issue for the anesthesiologist. The greatest hemodynamic disturbance is postreperfusion syndrome (PRS), which occurs at reperfusion of the donated liver after unclamping of the portal vein. PRS is characterized by marked decreases in mean arterial pressure and systemic vascular resistance, and moderate increases in pulmonary arterial pressure and central venous pressure. The underlying pathophysiological mechanisms of PRS are complex. Moreover, risk factors associated with PRS are not fully understood. Rapid and appropriate treatment with vasopressors, volume replacement, or venesection must be provided depending on the cause of the hemodynamic disturbance when hemodynamic instability becomes profound after reperfusion. The negative effects of PRS on postoperative early morbidity and mortality are clear, but the effect of PRS on postoperative long-term mortality remains a matter of debate. PMID:26634075
Oldhafer, Felix; Bock, Michael; Falk, Christine S; Vondran, Florian W R
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
Petrowsky, Henrik; Busuttil, Ronald W
The growing discrepancy between the need and the availability of donor livers has resulted in evolving surgical approaches in liver transplantation during the last two decades to expand the donor pool. One approach is to transplant partial grafts, obtained either from a living donor or splitting a cadaveric donor liver. For both surgical methods, it is important to obtain a minimal viable graft volume to prevent small-for-size syndrome and graft failure. This minimal volume, expressed as graft-to-whole body ratio, must be between 0.8 and 1%. Living donor liver transplantation (LDLT) became the primary transplant option in many Asian countries and is increasingly performed as an adjunct transplant option in countries with low donation rates. Split liver transplantation (SLT) is a surgical method that creates two allografts from one deceased donor. The most widely used splitting technique is the division of the liver into a left lateral sectoral graft (segments 2 and 3) for a pediatric patient and a right trisegmental graft (segments 1 and 4 to 8) for an adult patient. Both LDLT and SLT are also important and established methods for the treatment of pediatric patients. Another evolving surgical approach is auxiliary liver transplantation, which describes the transplanting a whole or partial graft with preservation of the partial native liver. This bridging technique is applied in patients with fulminate liver failure and should allow the regeneration of the injured liver with the potential to discontinue immunosuppression. Other methods such as xenotransplantation, as well as hepatocyte and stem cell transplantation, are promising approaches that are still in experimental phases.
He, Ning; Jia, Jun-Jun; Li, Jian-Hui; Zhou, Yan-Fei; Lin, Bing-Yi; Peng, Yi-Fan; Chen, Jun-Jie; Chen, Tian-Chi; Tong, Rong-Liang; Jiang, Li; Xie, Hai-Yang; Zhou, Lin; Zheng, Shu-Sen
AIM To investigate the underlying mechanisms of the protective role of remote ischemic perconditioning (RIPerC) in rat liver transplantation. METHODS Sprague-Dawley rats were subjected to sham, orthotopic liver transplantation (OLT), ischemic postconditioning (IPostC) or RIPerC. After 3 h reperfusion, blood samples were taken for measurement of alanine aminotransferase, aspartate aminotransferase, creatinine (Cr) and creatinine kinase-myocardial band (CK-MB). The liver lobes were harvested for the following measurements: reactive oxygen species (ROS), H2O2, mitochondrial membrane potential (ΔΨm) and total nitric oxide (NO). These measurements were determined using an ROS/H2O2, JC1 and Total NOx Assay Kit, respectively. Endothelial NO synthase (eNOS) was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting, and peroxynitrite was semi-quantified by western blotting of 3-nitrotyrosine. RESULTS Compared with the OLT group, the grafts subjected to RIPerC showed significantly improved liver and remote organ functions (P < 0.05). ROS (P < 0.001) including H2O2 (P < 0.05) were largely elevated in the OLT group as compared with the sham group, and RIPerC (P < 0.05) reversed this trend. The collapse of ΔΨm induced by OLT ischemia/reperfusion (I/R) injury was significantly attenuated in the RIPerC group (P < 0.001). A marked increase of NO content and phosphoserine eNOS, both in protein and mRNA levels, was observed in liver graft of the RIPerC group as compared with the OLT group (P < 0.05). I/R-induced 3-nitrotyrosine content was significantly reduced in the RIPerC group as compared with the OLT group (P < 0.05). There were no significant differences between the RIPerC and IPostC groups for all the results except Cr. The Cr level was lower in the RIPerC group than in the IPostC group (P < 0.01). CONCLUSION Liver graft protection by RIPerC is similar to or better than that of IPostC, and involves inhibition of oxidative stress and up
Dikht, Nataliya I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Matveeva, Olga V.; Navolokin, Nikita A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.
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.
Lang, H; Oldhafer, K J; Weimann, A; Schlitt, H J; Scheumann, G F; Flemming, P; Ringe, B; Pichlmayr, R
OBJECTIVE: This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA: Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS: In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS: Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS: In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective. Images Figure 1. Figure 3. PMID:9114792
Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S
Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395
Faraj, Walid; Haydar, Ali; Nounou, Ghina El; Naaj, Abdallah Abou El; Khoury, Ghattas; Jabbour, Samar; Khalife, Mohamed
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.
Ferrarese, Alberto; Zanetto, Alberto; Gambato, Martina; Bortoluzzi, Ilaria; Nadal, Elena; Germani, Giacomo; Senzolo, Marco; Burra, Patrizia; Russo, Francesco Paolo
Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release. PMID:26819523
Abradelo, Manuel; Fondevila, Constantino
The disbalance between the number of candidates to liver transplant and the number of liver grafts leads to waiting list mortality. Two potential ways of increasing the number of liver grafts are split liver transplantation and the transplantation of grafts from non-heart beating donors. Both of them were discussed in a consensus meeting of the Spanish Society of Liver Transplantation in October 2012. This paper outlines the conclusions of that meeting.
Testa, G; Goldstein, R M; Toughanipour, A; Abbasoglu, O; Jeyarajah, R; Levy, M F; Husberg, B S; Gonwa, T A; Klintmalm, G B
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
deLemos, Andrew S; Schmeltzer, Paul A; Russo, Mark W
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
Pérez-San-Gregorio, M A; Martin-Rodríguez, A; Asián-Chavez, E; Gallego-Corpa, A; Pérez-Bernal, J
We analyzed the influence of two variables (place of hospitalization of the patients and the mental health of relatives) on symptoms of anxiety and depression in liver transplant patients. The subject groups were made up of 48 liver transplant recipients (mean age 51.15; SD = 8.57) and their close relatives. The tests applied were a psychosocial questionnaire, and the two tests: "The Hospital Anxiety and Depression Scale" and "The Leeds Scales for the Self-Assessment of Anxiety and Depression." The liver transplant recipients showed more symptoms of depression when they were in the intensive care unit (ICU) and more symptoms of anxiety in the post-ICU phase when their close relatives were more depressed in that phase. The place of hospitalization of the patients and the mental health of relatives influenced the symptoms of anxiety and depression in liver transplant recipients.
Bakshi, Neha; Singh, Kalyani
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
Mortezaee, Keywan; Pasbakhsh, Parichehr; Kashani, Iraj Ragerdi; Sabbaghziarani, Fatemeh; Omidi, Ameneh; Zendedel, Adib; Ghasemi, Soudabeh; Dehpour, Ahmad Reza
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
Geramizadeh, B.; Malek-Hosseini, S. A.
A successful liver transplantation team consists of several specialists to work closely together. The histopathologist (anatomical pathologist) is one of the key players in this multidisciplinary team. This role starts with the pre-transplantation evaluation of the recipient’s liver by diagnosis or confirming the underlying liver disease and continues with the evaluation of the explanted recipient’s liver for any further information about the underlying liver disease including malignancies such as hepatocellular carcinoma, cholangiocarcinoma, or any other incidental findings. The evaluation of the new donor liver begins with determining the suitability of the donor liver for transplantation during or before the operation and continues throughout the entire post-transplantation period by evaluating not only the allograft diseases but also evaluating other tissues for infections, malignancies, etc. It is worthy to note that in many of the above-mentioned situations, histopathology is the gold-standard diagnostic test. In this review, we present on various tasks of a histopathologist according to the current literature and our own experience in the largest liver transplantation center in Iran. PMID:28299022
Tang, H; Boulton, R; Gunson, B; Hubscher, S; Neuberger, J
Background—Uncertainty exists about the extent and consequences of a return to alcohol consumption after liver transplantation for alcoholic liver disease (ALD). Aims—To determine the prevalence and consequences of alcohol consumption in patients transplanted for ALD. Methods—A retrospective case controlled study of all patients transplanted for ALD at the Queen Elizabeth Hospital, Birmingham, between 1987 and 1996. Results—Seventy patients with ALD were transplanted, of which 59 survived more than three months; 56 were interviewed. Twenty eight had consumed some alcohol after transplantation; for the nine "heavy drinkers" (HD), the median time to resumption of alcohol intake was six months and for the 19 "moderate drinkers" (MD) it was eight months. There was no significant difference in episodes of acute rejection or compliance with medication between those who were abstinent, MD, or HD. Histological evidence of liver injury was common in ALD patients who had returned to drink. Mild fatty change was found in 1/11 biopsy specimens from abstinent patients but moderate to severe fatty change and ballooned hepatocytes were seen in 3/5 MD and 2/5 HD specimens. Two HD patients had early fibrosis. One HD patient has died of alcohol related complications. Conclusions—Moderate to heavy alcohol consumption occurs in patients transplanted for ALD. Patient recall of abstinence advice is unreliable, and patients return to alcohol mainly within the first year after liver transplantation. Return to alcohol consumption after liver transplantation is associated with rapid development of histological liver injury including fibrosis. Keywords: alcohol consumption; liver transplantation PMID:9771419
Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu
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.
Mnatsakanova, Diana; Živković, Saša A
Liver transplantation has been used in treatment of transthyretin amyloidosis, and some patients undergo domino liver transplantation (DLT) with explanted liver being transplanted to another patient with liver failure as the liver is otherwise usually functionally normal. Until end of 2015, there were 1154 DLT performed worldwide. DLT for transthyretin amyloidosis is associated with the risk of developing de novo systemic amyloidosis and amyloid neuropathy, and the risk may be greater with some non-Val30Met mutations. De novo amyloid neuropathy has been described in up to 23% of transplant recipients. Neuropathy may be preceded by asymptomatic amyloid deposition in various tissues and symptoms of neuropathy started after a median of 7 years following DLT (5.7 ± 3.2 years; range 2 mo to 10 years). Typical initial symptoms include neuropathic pain and sensory loss, while dysautonomia usually starts later. Progression of neuropathy may necessitate liver re-transplantation, and subsequent improvement of neuropathy has been reported in some patients. Explant allograft recipients need close monitoring for signs of systemic amyloidosis, neuropathy and dysautonomia as progressive symptoms may require re-transplantation. PMID:28217248
Sakcak, Ibrahim; Olmez, Aydemir; Ozgor, Dincer; Eris, Cengiz; Kayaalp, Cuneyt; Yılmaz, Sezai
A liver from a donor with brain death due to a ruptured cerebral aneurysm was transplanted. The liver had multiple bilobar simple cysts; the largest was less than 3 cm in diameter. The noncystic liver volume was greater than 50%, and the liver had neither fibrosis nor venous congestion. The donor surgery was performed in accordance with the standard protocol without rupture of the cysts. The recipient was a 40-year-old man with cirrhosis associated with hepatitis B. The recipient operation was done by using the piggyback method with no complications. Excessive drainage of chylous ascites (10 000 mL/d) started in the first days after surgery and continued, gradually decreasing until the end of the second month. The patient was discharged with no complications at the end of the third month. No growth in the cysts was observed on follow-up computed tomography scans. Excluding this particular case, a total of 7 other patients have received a polycystic liver transplant. In all 7 cases, the fact that the donor had polycystic liver disease was not known but was encountered by coincidence during procurement. The case reported here is the first case where the polycystic liver disease was diagnosed before procurement and the transplant was still carried out. It appears that, if the donor liver has enough healthy noncystic volume, polycystic livers can be transplanted.
Liu, Huanqiu; Li, Ruijun; Fu, Jinling; He, Qianyan; Li, Ji
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.
Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael
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.
Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael
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
Davis, Gary L
Chronic hepatitis C virus (HCV) is a worldwide health problem. Approximately 4 million people in the United States are chronically infected with HCV. The incidence of infection peaked between 2 and 3 decades ago, and we are now beginning to see an increase in the complications of cirrhosis from HCV. This trend is expected to continue for another 2 to 3 decades. Survival is poor once complications of cirrhosis, such as liver failure or hepatocellular carcinoma, ensue, and liver transplantation is often the only option. Complications of chronic HCV are the most common indication for liver transplantation, accounting for more than 40% of transplants performed in the United States and Europe. HCV recurs in all patients and rapid development of hepatic fibrosis is very common. Several strategies have been proposed to reduce the risk of graft loss from recurrent HCV infection after transplantation, as the progression of the resulting liver disease is rapid. Although antiviral treatment is successful in some patients, it is extremely difficult to administer and requires dose reductions in the majority of cases. Retransplantation in the current era of the Model for End-Stage Liver Disease (MELD) system for prioritizing listing for transplant is associated with very low survival rates at a high cost. Furthermore, the system raises difficult ethical issues of utilization of limited resources and fairness to other transplant candidates.
Hammad, Ahmed; Kaido, Toshimi; Uemoto, Shinji
Protein-energy malnutrition is frequently seen in patients with end-stage liver disease who undergo liver transplantation. This causes a deterioration of the patients' clinical condition and affects their post-transplantation survival. Accurate assessment of the nutritional status and adequate intervention are prerequisites for perioperative nutritional treatment. However, the metabolic abnormalities induced by liver failure make the traditional assessment of the nutritional status difficult. The methods that were recently developed for accurately assessing the nutritional status by body bioelectrical impedance may be implemented in pre-transplant management. Because preoperative malnutrition and the loss of skeletal muscle mass, called sarcopenia, have a significant negative impact on the post-transplantation outcome, it is essential to provide adequate nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the necessary caloric intake. We herein discuss both bioelectrical impedance and the latest findings in the current perioperative nutritional interventions in liver transplant patients regarding synbiotics, micronutrients, branched-chain amino acid supplementation, the use of immune system modulating formulas, the fluid balance and the offering of nocturnal meals.
Zajko, Albert B.; Bron, Klaus M.; Starzl, Thomas E.; Van Thiel, David H.; Gartner, J. Carlton; Iwatsuki, Shunzaburo; Shaw, Byers W.; Zitelli, Basil J.; Malatack, J. Jeffrey; Urbach, Andrew H.
Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transplantation, and 53 examinations in 44 patients after transplantation. Transplantation feasibility was influenced by patency of the portal vein and inferior vena cava. Selective arterial portography, wedged hepatic venography, and transhepatic portography were used to assess the portal vein if sonography or computed tomography was inconclusive. Major indications for angiography after transplantation included early liver failure, sepsis, unexplained elevation of liver enzyme levels, and delayed bile leakage, all of which may be due to hepatic artery thrombosis. Other indications included gastrointestinal tract bleeding, hemobilia, and evaluation of portal vein patency in patients with chronic rejection who were being considered for retransplantation. Normal radiographic features of hepatic artery and portal vein reconstruction are demonstrated. Complications diagnosed using results of angiography included hepatic artery or portal vein stenoses and thromboses and pancreaticoduodenal aneurysms. Intrahepatic arterial narrowing, attenuation, slow flow, and poor filling were seen in five patients with rejection PMID:3901102
Capobianco, Ivan; Panaro, Fabrizio; Di Francesco, Fabrizio; Troisi, Roberto; Sainz-Barriga, Mauricio; Muiesan, Paolo; Königsrainer, Alfred; Testa, Giuliano
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
Hanchnale, Pavan; Jain, Mayank; Vargese, Joy; V, Jayanthi; Rela, Mohamed
Nocardiosis is usually a disseminated disease seen in immunocompromised individuals. We herein present a rare case of isolated Nocardia liver abscess post liver transplantation. The patient responded well to treatment and is on long-term antibiotics for Nocardia infection. This article is protected by copyright. All rights reserved.
Hartmann, Christina; Schuchmann, Marcus; Zimmermann, Tim
Posttransplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Many posttransplant lymphomas develop from the uncontrolled proliferation of Epstein-Barr virus (EBV)-infected B-cells, whereas EBV-negative PTLDs were increasingly recognized within the past decade. Major risk factors for the development of PTLDs after liver transplantation are immunosuppressive therapy and the type of underlying disease: viral hepatitis, autoimmune liver disease, or alcoholic liver cirrhosis contribute to an increased risk for PTLD. Therapeutic regimens include reduction of immunosuppression, the anti-CD20 antibody rituximab, and chemotherapy, as well as new approaches using interferon-α and anti-interleukin-6 antibodies. Despite the different therapeutic regimens, mortality from PTLD remains high. Therefore, it is of major importance to identify patients at risk at an early stage of the disease. In this review, risk factors for PTLD development after liver transplantation, clinical presentation, diagnosis, and therapy are discussed.
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
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
Lane, Maria; Boczonadi, Veronika; Bachtari, Sahar; Gomez-Duran, Aurora; Langer, Thorsten; Griffiths, Alexandra; Kleinle, Stephanie; Dineiger, Christine; Abicht, Angela; Holinski-Feder, Elke; Schara, Ulrike; Gerner, Patrick; Horvath, Rita
Liver failure is a heterogeneous condition which may be fatal and the primary cause is frequently unknown. We investigated mitochondrial oxidative phosphorylation in patients undergoing liver transplantation. We studied 45 patients who had liver transplantation due to a variety of clinical presentations. Blue native polyacrylamide gel electrophoresis with immunodetection of respiratory chain complexes I-V, biochemical activity of respiratory chain complexes II and IV and quantification of mitochondrial DNA (mtDNA) copy number were investigated in liver tissue collected from the explanted liver during transplantation. Abnormal mitochondrial function was frequently present in this cohort: ten of 40 patients (25 %) had a defect of one or more respiratory chain enzyme complexes on blue native gels, 20 patients (44 %) had low activity of complex II and/or IV and ten (22 %) had a reduced mtDNA copy number. Combined respiratory chain deficiency and reduced numbers of mitochondria were detected in all three patients with acute liver failure. Low complex IV activity in biliary atresia and complex II defects in cirrhosis were common findings. All six patients diagnosed with liver tumours showed variable alterations in mitochondrial function, probably due to the heterogeneity of the presenting tumour. In conclusion, mitochondrial dysfunction is common in severe liver failure in non-mitochondrial conditions. Therefore, in contrast to the common practice detection of respiratory chain abnormalities in liver should not restrict the inclusion of patients for liver transplantation. Furthermore, improving mitochondrial function may be targeted as part of a complex therapy approach in different forms of liver diseases.
Schilsky, Michael L; Moini, Maryam
With the growing number of patients in need of liver transplantation, there is a need for adopting new and modifying existing allocation policies that prioritize patients for liver transplantation. Policy should ensure fair allocation that is reproducible and strongly predictive of best pre and post transplant outcomes while taking into account the natural history of the potential recipients liver disease and its complications. There is wide acceptance for allocation policies based on urgency in which the sickest patients on the waiting list with the highest risk of mortality receive priority. Model for end-stage liver disease and Child-Turcotte-Pugh scoring system, the two most universally applicable systems are used in urgency-based prioritization. However, other factors must be considered to achieve optimal allocation. Factors affecting pre-transplant patient survival and the quality of the donor organ also affect outcome. The optimal system should have allocation prioritization that accounts for both urgency and transplant outcome. We reviewed past and current liver allocation systems with the aim of generating further discussion about improvement of current policies.
Schilsky, Michael L; Moini, Maryam
With the growing number of patients in need of liver transplantation, there is a need for adopting new and modifying existing allocation policies that prioritize patients for liver transplantation. Policy should ensure fair allocation that is reproducible and strongly predictive of best pre and post transplant outcomes while taking into account the natural history of the potential recipients liver disease and its complications. There is wide acceptance for allocation policies based on urgency in which the sickest patients on the waiting list with the highest risk of mortality receive priority. Model for end-stage liver disease and Child-Turcotte-Pugh scoring system, the two most universally applicable systems are used in urgency-based prioritization. However, other factors must be considered to achieve optimal allocation. Factors affecting pre-transplant patient survival and the quality of the donor organ also affect outcome. The optimal system should have allocation prioritization that accounts for both urgency and transplant outcome. We reviewed past and current liver allocation systems with the aim of generating further discussion about improvement of current policies. PMID:26973389
Telles-Correia, Diogo; Mega, Inês
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
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
Jadlowiec, Caroline C; Taner, Timucin
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
Fishman, Joel E; Rabkin, John M
Renal transplantation accounts for more than half of all solid organ transplants performed in the U.S., and the liver is the second most commonly transplanted solid organ. Although abdominal imaging procedures are commonplace in these patients, there has been relatively little attention paid to thoracic imaging applications. Preoperative imaging is crucial to aid in the exclusion of infectious or malignant disease. In the perioperative time period, thoracic imaging focuses both on standard intensive care unit care, including monitoring devices and their complications, and on the early infections that can occur. Postoperative management is divided into three time periods, and the principles governing the occurrence of infections and malignancies are reviewed. Anatomic and pathologic aspects unique to kidney and liver transplantation patients are also discussed.
Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José
Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program.
Lima, Thais Carneiro; Bezerra, Regis Otaviano Franca; Siqueira, Luiz Tenório de Brito; Menezes, Marcos Roberto de; Leite, Claudia da Costa; Porta, Gilda; Cerri, Giovanni Guido
Paracoccidioidomycosis is a granulomatous systemic mycosis that is endemic in Latin America; it is an extremely rare infection following solid organ transplantation. In this study, we describe the first report of disseminated paracoccidioidomycosis in a 3-year-old girl who underwent liver transplantation 2 years previously. The radiologic diagnosis and patient follow-up are described. In addition, we review the clinical evolution and treatment regimens for this infection.
Vodkin, Irine; Kuo, Alexander
Mortality rates on the liver transplant waiting list are increasing. The shortage of organs has resulted in higher utilization of extended criteria donors (ECDs), with centers pushing the limits of what is acceptable for transplantation. Donor quality is more appropriately represented as a continuum of risk, and careful selection and matching of ECD grafts with recipients may lead to excellent outcomes. Although there is no precise definition for what constitutes an ECD liver, this review focuses on frequently cited characteristics, including donor age, steatosis, donation after cardiac death, and donors with increased risk of disease transmission.
Demetriou, A A; Whiting, J; Levenson, S M; Chowdhury, N R; Schechner, R; Michalski, S; Feldman, D; Chowdhury, J R
A technique has been developed by the authors that allows hepatocyte attachment on collagen-coated microcarriers resulting in prolonged hepatocyte viability and function both in vivo and in vitro. Rat hepatocytes were obtained by portal vein collagenase perfusion. Intraperitoneally transplanted microcarrier-attached normal hepatocytes into congeneic Gunn rats were functioning 3-4 weeks later, as shown by the presence and persistence of conjugated bilirubin in recipient bile, sustained decrease in serum bilirubin, uptake of Tc99m-DESIDA, and morphologic criteria. Intraperitoneal transplantation of normal microcarrier-attached hepatocytes into genetically albumin deficient rats (NAR) resulted in marked increase in plasma albumin levels (6 days without and 21 days with Cyclosporin A immunosuppression). Microcarrier-attached hepatocytes transplanted after 2 weeks of storage at -80 C into congeneic Gunn rats were viable and functional as assessed by criteria outlined above. An extracorporeal liver perfusion system was developed using the microcarrier-attached hepatocytes that was capable of synthesizing and conjugating bilirubin and synthesizing liver-specific proteins. Images FIGS. 5A and B. FIG. 7. FIG. 8. FIG. 9. FIG. 12. PMID:3530153
Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin
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.
Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin
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
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
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.
Johnson, Scott R; Karp, Seth J; Curry, Michael P; Barugel, Martin; Rodrigue, James R; Mandelbrot, Didier A; Rogers, Christin P; Hanto, Douglas W
Recent changes in Center for Medicare & Medicaid Services (CMS) condition for participation, using benchmark volume/outcomes requirements for certification, have been implemented. Consequently, the ability of a transplant center to assess its risk tolerance is important in successful management. An analysis of SRTR data was performed to determine donor/recipient risk factors for graft loss or patient death in the first year. Each transplant performed was then assigned a prospective relative risk (RR) of failure. Using a Monte-Carlo simulation, transplants were selected at random that met the centers' acceptable risk tolerance. Transplant center volume was fixed and its risk tolerance was adjusted to determine the impact on outcomes. The model was run 1000 times on centers with varying volume. The modeling demonstrates that centers with smaller annual volumes must use a more risk taking strategy than larger volume centers to avoid being flagged for CMS volume requirements. The modeling also demonstrates optimal risk taking strategies for centers based upon volume to minimize the probability of being flagged for not meeting volume or outcomes benchmarks. Small volume centers must perform higher risk transplants to meet current CMS requirements and are at risk for adverse action secondary to chance alone.
Nagral, Sanjay; Nanavati, Aditya; Nagral, Aabha
As the liver transplant journey in India reaches substantial numbers and suggests quality technical expertise, it is time to dispassionately look at the big picture, identify problems, and consider corrective measures for the future. Several features characterize the current scenario. Although the proportion of deceased donor liver transplants is increasing, besides major regional imbalances, the activity is heavily loaded in favor of the private sector and live donor transplants. The high costs of the procedure, the poor participation of public hospitals, the lack of a national registry, and outcomes reporting are issues of concern. Organ sharing protocols currently based on chronology or institutional rotation need to move to a more justiciable severity-based system. Several measures can expand the deceased donor pool. The safety of the living donor continues to need close scrutiny and focus. Multiple medical challenges unique to the Indian situation are also being thrown up. Although many of the deficits demand state intervention and policy changes the transplant community needs to take notice and highlight them. The future of liver transplantation in India should move toward a more accountable, equitable, and accessible form. We owe this to our citizens who have shown tremendous faith in us by volunteering to be living donors as well as consenting for deceased donation.
Nagral, Sanjay; Nanavati, Aditya; Nagral, Aabha
As the liver transplant journey in India reaches substantial numbers and suggests quality technical expertise, it is time to dispassionately look at the big picture, identify problems, and consider corrective measures for the future. Several features characterize the current scenario. Although the proportion of deceased donor liver transplants is increasing, besides major regional imbalances, the activity is heavily loaded in favor of the private sector and live donor transplants. The high costs of the procedure, the poor participation of public hospitals, the lack of a national registry, and outcomes reporting are issues of concern. Organ sharing protocols currently based on chronology or institutional rotation need to move to a more justiciable severity-based system. Several measures can expand the deceased donor pool. The safety of the living donor continues to need close scrutiny and focus. Multiple medical challenges unique to the Indian situation are also being thrown up. Although many of the deficits demand state intervention and policy changes the transplant community needs to take notice and highlight them. The future of liver transplantation in India should move toward a more accountable, equitable, and accessible form. We owe this to our citizens who have shown tremendous faith in us by volunteering to be living donors as well as consenting for deceased donation. PMID:26900275
Jiménez-Pérez, Miguel; González-Grande, Rocío; Omonte Guzmán, Edith; Amo Trillo, Víctor; Rodrigo López, Juan Miguel
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
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
Amer, Khaled E; Marwan, Ibrahim
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.
Song, Alice Tung Wan; Avelino-Silva, Vivian Iida; Pecora, Rafael Antonio Arruda; Pugliese, Vincenzo; D’Albuquerque, Luiz Augusto Carneiro; Abdala, Edson
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
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.
Arkadopoulos, N; Lilja, H; Suh, K S; Demetriou, A A; Rozga, J
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.
Lerut, J. P.; Gordon, R. D.; Tzakis, A. G.; Stieber, A. C.; Iwatsuki, S.; Starzl, T. E.
Summary Hepatic artery thrombosis (HAT) is a dreadful complication of orthotopic liver transplantation (OLT). This complication occurred in 27 grafts (68% = 27/393 grafts) in 25 patients (9% = 25/313 patients). HAT was responsible for a high mortality (64% = 16/25 patients) despite a high retransplantation rate (70% = 19/27 grafts). HAT should be suspected in case of fulminant liver failure, delayed bile leak or unexplained fever of sepsis of unknown etiology occurring after liver transplantation. Pulsed doppler examination and arteriogram are the decisive diagnostic procedures. Patients presenting HAT can only be rescued by early diagnosis and retransplantation. Aneurysms of the hepatic arterial supply must also be treated urgently, either by conventional vascular repair if possible or by retransplantation, because or the high incidence of fatal rupture (3/4 patients = 75%). PMID:3049463
Gopal, Palepu B.; Kapoor, Dharmesh; Raya, Ravichandra; Subrahmanyam, M.; Juneja, Deven; Sukanya, B.
Over the last decade, liver transplantation has become an operational reality in our part of the world. As a result, clinicians working in an intensive care unit are more likely to be exposed to these patients in the immediate postoperative period, and thus, it is important that they have a working knowledge of the common complications, when they are likely to occur, and how to deal with them. The main focus of this review is to address the variety of critical care issues in liver transplant recipients and to impress upon the need to provide favorable circumstances for the new liver to start functioning and maintain the function of other organs to aid in this process. PMID:20040807
Carrion, Andres F; Czul, Frank; Arosemena, Leopoldo R; Selvaggi, Gennaro; Garcia, Monica T; Tekin, Akin; Tzakis, Andreas G; Martin, Paul; Ghanta, Ravi K
Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.
Fukumitsu, K; Yagi, H; Soto-Gutierrez, A
About 27,000 deaths are registered annually in the United States due to liver disease. At this time, the only definitive treatment of hepatic failure is orthotopic transplantation. However, there is a critical shortage of organs with the total waiting list for all organs currently at 100,000 requests. The number is increasing by 5% every year. Given that only organs in pristine condition are transplantable and that the hidden demand for organs as an anti-aging solution will be many times the current figures, orthotopic transplantation will always remain a limited pool. The increasing donor organ shortage requires consideration of alternative emerging technologies. Regenerative medicine may offer novel strategies to treat patients with end-stage organ failure. The ultimate aim of cell transplantation, tissue engineering, and stem cells is to regenerate tissues and organs. With the development of whole organ decellularization methods, the equation of organ shortage may dramatically change in the near future. Decellularized organs provide the ideal transplantable scaffold with all the necessary microstructure and extracellular cues for cell attachment, differentiation, vascularization, and function. New techniques to re-engineer organs may have major implications for the fields of drug discovery, regeneration biology, and ultimately organ transplantation. In this review we have provided an overview of complementary approaches to study and enhance the success of organ repopulation strategies creating new grafts/organs for transplantation.
Washburn, W K; Bradley, J; Cosimi, A B; Freeman, R B; Hull, D; Jenkins, R L; Lewis, W D; Lorber, M I; Schweizer, R T; Vacanti, J P; Rohrer, R J
Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly
DiMartini, Andrea; Cruz, Ruy J.; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Kim, Kevin H.; Fontes, Paulo
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
Roland, Michelle E; Stock, Peter G
Although human immunodeficiency virus (HIV)-infected patients are living longer and dying less often from complications related to acquired immunodeficiency syndrome (AIDS), they are experiencing significant morbidity and mortality related to end-stage liver disease. Advances in the management of HIV disease have made it difficult to continue denying transplantation to this population based upon futility arguments alone. Patient and graft survival rates in HIV-infected study subjects appear similar to those in large transplant databases. There are no reports suggesting significant HIV disease progression. There are substantial interactions between immunosuppressants and antiretroviral drugs that require careful monitoring and dose adjustment. The evaluation and management of HIV-infected transplant candidates and recipients require excellent communication among a multidisciplinary team and the primary HIV care provider. It is critical that HIV clinicians and hepatologists are aware that liver transplantation is an option for HIV-infected patients at many transplant centers as delays in referral result in unnecessary mortality during the pretransplantation evaluation process.
Lee, David D; Croome, Kristopher P; Perry, Dana K; Burns, Justin M; Nguyen, Justin H; Keaveny, Andrew P; Taner, C Burcin
Over the sixteen year history of liver transplantation (LT) at Mayo Clinic in Jacksonville, Florida (MCF), we have maintained a practice devoted to excellence in pre- and post-LT management for patients suffering from end stage liver disease. With an emphasis on quality, MCF has made several adjustments with the goal of better utilizing marginal grafts for both successful post-transplant outcomes and minimizing waitlist mortality. This systematic approach is most exemplified in our experience with donation after cardiac death (DCD) liver allografts. Understanding the events during procurement has been critical to reducing the complications associated with donor warm ischemia time that are unique to DCD allografts. Better matching of donors to recipients has helped identify patients who are safe to receive more marginal grafts with successful patient and graft survival. Recognizing the spectrum of degree of sickness in patients undergoing LT, we implemented a multidisciplinary approach that allows for the avoidance of the intensive care unit after LT. In these ways, MCF continues to distinguish itself as an innovator in the field of transplantation for the benefit of continued better care for our patients suffering from end stage liver disease.
Kantola, T; Ilmakunnas, M; Koivusalo, A-M; Isoniemi, H
Acute liver failure is a life-threatening condition in the absence of liver transplantation option. The aetiology of liver failure is the most important factor determining the probability of native liver recovery and prognosis of the patient. Extracorporeal liver assist devices like MARS (Molecular Adsorbent Recirculating System) may buy time for native liver recovery or serve as bridging therapy to liver transplantation, with reduced risk of cerebral complications. MARS treatment may alleviate hepatic encephalopathy even in patients with a completely necrotic liver. Taking this into account, better prognostic markers than hepatic encephalopathy should be used to assess the need for liver transplantation in acute liver failure.
Dunn, S P; Haynes, J H; Nicolette, L A; Falkenstein, K; Pierson, A; Billmire, D F; Vinocur, C D; Weintraub, W
The division of a single hepatic allograft to create two reduced-size grafts has been reported with decreased graft survival (50%) resulting in decreased enthusiasm for this approach. The authors reviewed their experience with 12 recipients of this procedure to evaluate the outcome of the children electively undergoing transplant with the "leftover liver." A retrospective review of six pairs of children receiving part of one hepatic allograft included donor anatomy, recipient operation, and allograft and patient outcomes. Recipient pairs were selected according to blood type compatibility, medical priority, and size restrictions of the larger right lobe and the smaller left lateral segment. Patient and graft survival were compared with elective and urgent patients undergoing whole or reduced-size transplants. Six donors weighed 71.8 +/- 17.4 kg and were 22.6 +/- 11.0 years of age. Recipients of the right lobe were 11.8 +/- 4.2 years of age and weighed 41.9 +/- 14 kg. Recipients of the left lateral segment were 1.81 +/- 1.1 years of age and weighed 9.85 +/- 1.82 kg. Six patients were initially offered the donor allograft because of their hospitalization, critical illness or waiting time. Six additional patients electively underwent transplantation with the leftover liver. Donor organs were screened for normal arterial anatomy. Division of the allograft was performed on the back table in the falciform groove. Generally the left lateral segment graft received the major portion of the hepatic artery and the right lobe the major portion of the portal vein. Five of six (83%) elective patients, two receiving the right lobe and three receiving the left lateral segment had prompt recovery and left the hospital without surgical complication. One recipient of a right lobe transplant died from primary allograft nonfunction. These results are not different from the outcomes of all elective patients who underwent transplantation with whole or reduced-sized transplants in the
Patients with hepatic failure and liver-based metabolic disorders require management which is both costly and complex. Hepatocyte transplantation has been very encouraging as an alternative to organ transplantation for liver disease treatment, and studies in rodents, show that transplants involving isolated liver cells can reverse hepatic failure, and correct various metabolic deficiencies of the liver. This 2016 review is based on a literature search using PubMed including original articles, reviews, cases and clinical guidelines. The search terms were “hepatocyte transplantation”, “liver transplantation”, “liver cell failure”, “metabolic liver disorders”, “orthotropic liver transplantation”, “hepatocytes” and “stem cell transplantation”. The goal of this review is to summarize the significance of hepatocyte transplantation, the sources of hepatocytes and the barriers of hepatocyte transplantation using a detailed review of literature. Our review shows that treatment of patients with liver disease by hepatocyte transplantation has expanded exponentially, especially for patients suffering from liver-based metabolic disorders. Once hepatocyte transplantation has been shown to effectively replace organ transplantation for a portion of patients with life-threatening liver metabolic diseases and those with liver failure it will make cell therapy effective and available for a broad population of patients with liver disorders. PMID:27957309
Singh, Shweta; Nasa, Vaibhav; Tandon, Manish
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
DiMartini, Andrea; Dew, Mary Amanda; Day, Nancy; Fitzgerald, Mary Grace; Jones, Bobby L.; deVera, Michael; Fontes, Paulo
Any use of alcohol in the years following liver transplantation (LTX) approaches 50% of patients transplanted for alcoholic liver disease (ALD). We collected detailed prospective data on alcohol consumption following LTX for ALD to investigate ongoing patterns of use. Using trajectory modeling we identified four distinct alcohol use trajectories. One group had minimal use over time. Two other groups developed early onset moderate to heavy consumption and one group developed late onset moderate use. These trajectories demonstrate that alcohol use varies based on timing of onset, quantity, and duration. Using discriminant function analysis, we examine characteristics of recipient’s pre-LTX alcohol histories and early post-LTX psychological stressors to identify the profile of those at risk for these specific trajectories. We discuss the relevance of these findings to clinical care and preliminarily to outcomes. PMID:20726963
Jara, Paloma; Hierro, Loreto
Liver transplantation allows long-term survival (10 years or more) in 75% of children receiving transplants before 2000. The risk of mortality after the first year is 4-10% in the next 10-20 years. Chronic rejection affects 6%. The need for late retransplantation is 3-5%. However, the follow-up of these patients involves the management of diverse problems in the graft (immunological, biliary, vascular) and others related to the use of immunosuppressants (renal dysfunction, lymphoproliferative syndrome). The transition from pediatric to adult care generates special needs. Adolescence and young adulthood are associated with a lack of compliance. Adult specialists should be aware of the special features of the original diagnosis and the surgical techniques used in childhood transplantation. Final quality of life is good overall but is lower than that in healthy young persons.
Caicedo, Luis Armando; Buitrago, Diego; Thomas, Laura S.; Villegas, Jorge I.; Duque, Mauricio; Serrano, Oscar; Arrunategui, Ana M.; Restrepo, Juan Guillermo; Echeverri, Gabriel Jaime
Liver transplantation is an option that improves quality of life and prolongs life expectancy in patients with different types of liver disease. Liver transplantation is controversial for colorectal metastases and is not recommended in clinical practice guidelines. In this case report, we present, to our knowledge, the first liver transplantation for colorectal metastases conducted in Colombia, with a successful follow-up of more than 2 years. Patients with these characteristics who underwent liver transplantation experience reduced mortality and exponentially improved quality of life. PMID:28203128
Clevenger, Ben; Mallett, Susan V
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.
Clevenger, Ben; Mallett, Susan V
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
Strovski, Evgeny; Liu, Dave; Scudamore, Charles; Ho, Stephen; Yoshida, Eric; Klass, Darren
Hepatic vein stenosis is a rare but serious complication following liver transplantation. Multiple modalities can be utilized to image the hepatic vasculature. Magnetic resonance venography (MRV) provides certain advantages over ultrasound, computed tomography angiography and digital subtraction venography. MRV utilizes the same imaging principles of magnetic resonance angiography in order to image the venous system. Blood pool contrast agents, specifically gadofosveset trisodium, allow for steady state imaging up to 1 h following injection, with improved visualisation of vital venous structures by utilising delayed steady state imaging. Additionally, the inherent physics properties of magnetic resonance imaging also provide excellent soft tissue detail and thus help define the extent of complications that often plague the post-liver transplant patient. This case report describes the use of gadofosveset trisodium in a patient with hepatic venous stenosis following liver transplantation. Initial venography failed to outline the stenoses and thus MRV using a blood pool contrast agent was utilised in order to delineate the anatomy and plan a therapeutic endovascular procedure.
Gaglio, Paul J; Gaglio, Paul J
Cirrhosis caused by alcohol-associated liver disease is a common indication for liver transplantation worldwide. Patients with alcohol-associated liver disease who undergo liver transplantation face multiple challenging comorbid medical issues that enhance the potential for perioperative and postoperative complications. Awareness of these issues and appropriate therapeutic intervention may minimize the negative effect of these complications on posttransplantation survival. This article reviews important posttransplantation problems in patients transplanted for alcohol-associated liver disease.
Fahrner, René; Dondorf, Felix; Ardelt, Michael; Settmacher, Utz; Rauchfuss, Falk
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
Ben Ari, Ziv
In the recent decade the subject of general hepatology has undergone significant upgrading. Several breakthrough discoveries have lead to substantial improvement in the antiviral treatment of viral hepatitis, the therapy of hepatocellular carcinoma and the development of noninvasive diagnosis of the severity of liver disease. Nonalcoholic fatty liver disease (NAFLD] is now established as one of the most common causes of chronic liver disease in the Western world. NAFLD can progress to cirrhosis and its associated complications. This issue of "Harefuah" is dedicated to the current knowledge and challenges in liver disease and transplantation and to novel discoveries in this field. Two new important guidelines of the Israeli Association for the Study of the Liver are published in this issue, the first deals with the management of ascites and its complications and the second relates to the innovative antiviral treatment of chronic hepatitis C virus infection. An extensive review on this latter subject is also included, summarizing the major breakthroughs in this field: the development of the new direct acting antiviraL agents and the role of IL28B polymorphism in the response to treatment. One article argues the concept of the high hepatitis B virus (HBV) vertical transmission in an Arab cohort in Israel, while another paper provides data on a significantly improved response rate to antiviral therapy in HIV-HCV co-infected patients. Increased serum level of lipoprotein-associated phospholipase A2 level, an independent predictor of coronary heart disease, was detected in patients with nonalcohoLic fatty liver disease [NAFLD] in another article. The issue also provides encouraging data showing that following two decades of liver transplantation in Israel, the survival rate has improved. Several additional articles in the issue shed further light on recent discoveries in the field of hepatology.
Shan, Yuhua; Huang, Lifeng; Xia, Qiang
Hepatocellular carcinoma is the most common liver malignancy. Salvage liver transplantation (SLT) is viewed as a feasible cure for recurrence of HCC after resectomy, but the effect is under dispute. A retrospective study examined data at Renji Hospital for 239 transplants from January 2006 to December 2015, including 211 who received primary liver transplantation (PLT) and 28 who underwent SLT. A multivariable cox regression model was employed to pick out relative factors to overall survival (OS) and recurrence free survival (RFS). Propensity score matching (PSM) was used to balance the bias. Both OS and RFS were worse in SLT group than in PLT group, especially for those patients within Milan criteria. Our study demonstrates that SLT bears higher risk of recurrence and death than PLT, indicating that SLT should be given a more careful thought at performance. PMID:28294176
Ng, Kelvin K; Lo, Chung Mau
With the technical advances and improvements in perioperative management and immunosuppressants, liver transplantation is the standard treatment for patients with end-stage liver diseases. In Asia, a shortage of deceased donor liver grafts is the universal problem to be faced with in all transplant centres. Many surgical innovations are then driven to counteract this problem. This review focuses on 3 issues that denote the development of liver transplantation in Asian countries. These include living donor liver transplantation (LDLT), split liver transplantation (SLT) and liver transplantation for hepatocellular carcinoma (HCC). Minimal graft weight, types of liver graft to donate and the inclusion of the middle hepatic vein with the graft are the main issues to be established in LDLT. The rapid growth and wide dissemination of LDLT has certainly alleviated the supply-and-demand problem of liver grafts in Asia. SLT is another attractive approach. Technical expertise, donor selection and graft allocation are the main determinants for its success. Liver transplantation plays a key role in the management of HCC in Asia. LDLT would be the main strategy in this aspect. The issue of extending the selection criteria for HCC patients for LDLT is still controversial. On the whole, future developments to increase the donor pool for the expanding recipient need in Asia would involve transplantation from non-heart beating donor and ABO incompatible transplantation.
Pruvot, François-René; Boleslawski, Emmanuel
Organ shortage remains a major problem in liver transplantation for which the number of patients on the waiting list is superior to the number of liver grafts harvested each year. In 2007, 1061 liver transplantations have covered 78.7% of the needs for 1348 new candidates. Improvement of the results (5 year-survival 74.9% and 63% at 10 years) do not influence the number of major indications (hepatocellular carcinoma, hepatitis C virus, alcohol), despite a slight decrease in the rate of activity of 1 to 2% per year. Introduction of the national score for each patient to be registered on the waiting list, the use of split grafts or grafts from marginal criteria donors may enlarge the donor pool. Liver grafts from cardiac deceased donors or from living donors are less frequent and are controversial from a technical and psychological point of view. The most efficient solution in order to overcome organ shortage is the increase in the pool of brain dead donors by accompanying people acceptance of organ donation and the use of parts of human body after death. Such education of the population could be made by the valorisation of organ donation, through public campaigns suggesting reflexion rather than coercition.
Gedik, Ender; Çelik, Muhammet Reha; Otan, Emrah; Dişli, Olcay Murat; Erdil, Nevzat; Bayındır, Yaşar; Kutlu, Ramazan; Yılmaz, Sezai
Various types of extracorporeal membrane oxygenation methods have been used in liver transplant operations. The main indications are portopulmonary or hepatopulmonary syndromes and other cardiorespiratory failure syndromes that are refractory to conventional therapy. There is little literature available about extracorporeal membrane oxygenation, especially after liver transplant. We describe our experience with 2 patients who had living-related liver transplant. A 69-year-old woman had refractory aspergillosis pneumonia and underwent pumpless extracorporeal lung assist therapy 4 weeks after liver transplant. An 8-month-old boy with biliary atresia underwent urgent liver transplant; he received venoarterial extracorporeal membrane oxygenation therapy on postoperative day 1. Despite our unsuccessful experience with 2 patients, extracorporeal membrane oxygenation and pumpless extracorporeal lung assist therapy for liver transplant patients may improve prognosis in selected cases.
Farkas, Stefan; Hackl, Christina; Schlitt, Hans Jürgen
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
Akbulut, Sami; Yilmaz, Sezai
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
Washburn, W K; Lewis, W D; Jenkins, R L
Since January 1994, we have used percutaneous placement of both the subclavian and femoral cannulae to establish access for venovenous bypass during orthotopic liver transplantation. Percutaneous subclavian and femoral cannulae were used in 36 patients of which 5 had portal decompression by placement of a cannula in inferior mesenteric vein percutaneously through the abdominal wall. Intraoperative placement of the subclavian cannula is facilitated by placing a subclavian central venous line before the abdominal incision. One patient underwent exploration for femoral vein bleeding early in our experience. Another patient sustained hypotension as a result of a kinked subclavian cannula. In 4 patients, early in this experience, we had difficulty placing the subclavian cannula and resorted to axillary vein cut-down. There were no episodes of deep venous thrombosis detected by routine postoperative duplex ultrasonography. Minimum and maximum flow rates were significantly better (P < .01), with percutaneously placed cannulae in comparison to a control group of patients who underwent transplantation in whom we used the standard venous cut-down approach with a #7 Gott shunt (2.14 and 3.17 L/min v 1.65 and 2.41 L/min, respectively). Percutaneous placement of cannulae for venovenous bypass during liver transplantation is quick, safe, and effective. We would advocate this technique as an alternative approach for patients in whom bypass is deemed necessary.
Feltracco, Paolo; Carollo, Cristiana; Barbieri, Stefania; Pettenuzzo, Tommaso; Ori, Carlo
The poor clinical conditions associated with end-stage cirrhosis, pre-existing pulmonary abnormalities, and high comorbidity rates in patients with high Model for End-Stage Liver Disease scores are all well-recognized factors that increase the risk of pulmonary complications after orthotopic liver transplantation (OLT) surgery. Many intraoperative and postoperative events, such as fluid overload, massive transfusion of blood products, hemodynamic instability, unexpected coagulation abnormalities, renal dysfunction, and serious adverse effects of reperfusion syndrome, are other factors that predispose an individual to postoperative respiratory disorders. Despite advances in surgical techniques and anesthesiological management, the lung may still suffer throughout the perioperative period from various types of injury and ventilatory impairment, with different clinical outcomes. Pulmonary complications after OLT can be classified as infectious or non-infectious. Pleural effusion, atelectasis, pulmonary edema, respiratory distress syndrome, and pneumonia may contribute considerably to early morbidity and mortality in liver transplant patients. It is of paramount importance to accurately identify lung disorders because infectious pulmonary complications warrant speedy and aggressive treatment to prevent diffuse lung injury and the risk of evolution into multisystem organ failure. This review discusses the most common perioperative factors that predispose an individual to postoperative pulmonary complications and these complications' early clinical manifestations after OLT and influence on patient outcome.
Singal, Ashwani K.; Parker, Charles; Bowden, Christine; Thapar, Manish; Liu, Lawrence; McGuire, Brendan M.
Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Liver transplantation (LT) may be needed for recurrent and/or life-threatening acute attack in acute intermittent porphyria or acute liver failure or end-stage chronic liver disease in erythropoietic protoporphyria. LT in acute intermittent porphyria is curative. Erythropoietic protoporphyria patients needing LT should be considered for bone marrow transplantation to achieve cure. Conclusion This article provides an overview of porphyria with diagnostic approaches and management strategies for specific porphyrias and recommendations for LT with indications, pretransplant evaluation, and posttransplant management. PMID:24700519
Cucchetti, Alessandro; Vitale, Alessandro; Cescon, Matteo; Gambato, Martina; Maroni, Lorenzo; Ravaioli, Matteo; Ercolani, Giorgio; Burra, Patrizia; Cillo, Umberto; Pinna, Antonio D
Liver transplantation (LT) represents the only chance of long-term survival for patients with end-stage liver disease. When the mortality rate for transplant patients returns to the same level as that for the general population, they can be considered statistically cured. However, cure models in the setting of LT have never been applied. Data from 1371 adult patients undergoing LT for the first time between January 1999 and December 2012 at 2 Italian centers were reviewed in order to establish probabilities of being cured by LT. A parametric Weibull model was applied to compare the mortality rate after LT to the rate expected for the general population (matched by sex and age). The observed 3-, 5-, and 10-year overall survival rates after LT were 77.8%, 73.3%, and 65.6%, respectively, and they did not differ between the 2 centers (P = 0.37). The cure fraction for the entire study population was 63.4% (95% confidence interval = 52.6%-72.0%), and the time to cure was 10 years with a 90% confidence level. The best cure fraction was observed for younger recipients without hepatitis C virus (HCV) who had favorable donor-recipient matches, that is, low Donor Model for End-Stage Liver Disease (D-MELD) scores (90.1%); conversely, the lowest probability was observed for elderly HCV recipients with high D-MELD scores (34.6%). The time to cure was 6.22 years for non-HCV patients and 14.78 years for HCV patients. The median survival time for uncured patients was 2.29 years. Among uncured recipients, the longest survival time was observed for younger patients (7.31 years). In conclusion, we provide here a new clinical measure for LT suggesting that survival after transplantation can approximate that of the general population and provide a statistical cure.
NACIF, Lucas Souto; ANDRAUS, Wellington; MARTINO, Rodrigo Bronze; SANTOS, Vinicius Rocha; PINHEIRO, Rafael Soares; HADDAD, Luciana BP; D'ALBUQUERQUE, Luiz Carneiro
Background Liver transplantation is performed at large transplant centers worldwide as a therapeutic intervention for patients with end-stage liver diseases. Aim To analyze the outcomes and incidence of liver transplantation performed at the University of São Paulo and to compare those with the State of São Paulo before and after adoption of the Model for End-Stage Liver Disease (MELD) score. Method Evaluation of the number of liver transplantations before and after adoption of the MELD score. Mean values and standard deviations were used to analyze normally distributed variables. The incidence results were compared with those of the State of São Paulo. Results There was a high prevalence of male patients, with a predominance of middle-aged. The main indication for liver transplantation was hepatitis C cirrhosis. The mean and median survival rates and overall survival over ten and five years were similar between the groups (p>0.05). The MELD score increased over the course of the study period for patients who underwent liver transplantation (p>0.05). There were an increased number of liver transplants after adoption of the MELD score at this institution and in the State of São Paulo (p<0.001). Conclusion The adoption of the MELD score led to increase the number of liver transplants performed in São Paulo. PMID:25184772
Prince, M; Hudson, M
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
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
Kirchner, K; Malessa, Ch; Herzberg, N; Krumnow, S; Habrecht, O; Scheuerlein, H; Bauschke, A; Settmacher, U
A reproducible and transparent quality of clinical treatments plays an important role in the performance of a hospital. In liver transplantation (LT), this is particularly important for patient safety, resource planning, documentation, and quality management. Thus, the clinical pathway for LT was documented in an electronic format within our research project PIGE. Data from clinical information systems were linked to this pathway, which allows for process monitoring (the assessment of the current state for every patient in the LT process) and a retrospective analysis of all treatments in addition to all data pertaining to the treatment, for example, cost, time, number of personnel, etc.
Hajifathalian, Kaveh; Humberson, Annette; Hanouneh, Mohamad A; Barnes, David S; Arora, Zubin; Zein, Nizar N; Eghtesad, Bijan; Kelly, Dympna; Hanouneh, Ibrahim A
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
Ye, Carrie; Saincher, Meghana; Tandon, Puneeta; Meeberg, Glenda; Williams, Randy; Burak, Kelly W; Bain, Vincent G
BACKGROUND: Ischemic cardiac events can cause significant morbidity and mortality postliver transplantation; however, no validated protocols to screen patients before transplantation exist. OBJECTIVES: To report the introduction of a noninvasive cardiac screening protocol used at the Liver Unit, University of Calgary (Calgary, Alberta); to determine whether the protocol decreases use of coronary angiograms; and to compare cardiac outcomes using the new protocol with an appropriately matched historical control group. METHODS: A new cardiac screening protocol was introduced into the program in 2005, which uses perfusion scintigraphy to screen high-risk cardiac patients, reserving coronary angiograms for abnormal results. Transplanted patients screened using this protocol were compared with matched historical controls. Electronic charts were reviewed for cardiac outcomes intra- and postliver transplantation. RESULTS: A total of 396 patients were screened between April 2005 and February 2009. Eighty-two were transplanted by February 2009 and included in the study. Eighty-one patients were successfully matched according to age, sex, cardiac history and presence of diabetes. Twelve of 82 (14.6%) and 11 of 81 (13.6%) in the study and control groups, respectively, underwent coronary angiograms (P=0.85). Coronary artery disease was found in six of 12 (50.0%) study patients and three of 11 (27.3%) control patients who underwent coronary angiography (P=0.27). The mean (± SD) length of the follow-up period was 1.87±0.91 years and 4.45±1.89 years in the study and control groups, respectively. One of 81 in the control group and zero of 82 in the study group experienced an acute coronary syndrome event postoperatively. CONCLUSIONS: Coronary events are infrequent in liver transplant recipients. The described protocol is an effective method of coronary artery disease screening before liver transplant but does not reduce the number of cardiac investigations performed. PMID
Staufer, Katharina; Yegles, Michel
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
Carmody, Ian C.; Romano, John; Bohorquez, Humberto; Bugeaud, Emily; Bruce, David S.; Cohen, Ari J.; Seal, John; Reichman, Trevor W.; Loss, George E.
Background: Biliary complications remain a significant problem following liver transplantation. Several surgical options can be used to deal with a significant size mismatch between the donor and recipient bile ducts during the biliary anastomosis. We compared biliary transposition to recipient biliary ductoplasty in cadaveric liver transplant. Methods: A total of 33 reconstructions were performed from January 1, 2005 to December 31, 2013. In the biliary transposition group (n=23), 5 reconstructions were performed using an internal stent (5 or 8 French pediatric feeding tube), and 18 were performed without. Of the 10 biliary ductoplasties, 2 were performed with a stent. All patients were managed with standard immunosuppression and ursodiol. Follow-up ranged from 2 months to 5 years. Results: No patients in the biliary transposition group required reoperation; 1 patient had an internal stent removed for recurrent unexplained leukocytosis, and 2 patients required endoscopic retrograde cholangiography and stent placement for evidence of stricture. Three anastomotic leaks occurred in the biliary ductoplasty group, and 2 patients in the biliary ductoplasty group required reoperation for biliary complications. Conclusion: Our results indicate that biliary reconstruction can be performed with either biliary transposition or biliary ductoplasty. These techniques are particularly useful when a significant mismatch in diameter exists between the donor and recipient bile ducts. PMID:28331447
Donohue, Ciara I; Mallett, Susan V
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
Levitsky, Josh; Kalil, Andre C; Meza, Jane L; Hurst, Glenn E; Freifeld, Alison
Previous case series have reported serious complications of chicken pox (CP) after pediatric liver transplantation (PLT), mainly due to visceral dissemination. The goal of our study was to determine the incidence, risk factors, and outcomes of CP after PLT. A case-control study of all CP infections in pediatric transplant recipients followed at our center from September 1993 to April 2004 was performed. Data were collected before and after infection and at the same time points in age-, gender-, and transplant year-matched controls. Potential risk factors prior to CP and adverse outcomes after infection were compared between cases and controls. Twenty (6.2%) developed CP at a median of 1.8 yr (0.6-4.8) after PLT. All CP infections were cutaneous, with no evidence of organ involvement. Twelve were hospitalized: 9 only to receive intravenous acyclovir and 3 stayed > or =2 weeks for other complications. Risk factors were not statistically different among cases and controls. Of the outcomes analyzed, cases were significantly more likely to develop non-CP infections within one year of CP than controls (Hazard Ratio = 12.6, 95% confidence interval = 3.1-51.7; P < 0.001). These infections were often bacterial and occurred long after CP infection. In conclusion, CP is uncommon after PLT and has a low likelihood of organ dissemination. No risk factors were identified. Some cases required prolonged hospitalizations. Close monitoring for the development of late bacterial infections is warranted.
Guggenheimer, James; Eghtesad, Bijan; Close, John M; Shay, Christine; Fung, John J
A prerequisite dental evaluation is usually recommended for potential organ transplant candidates. This is based on the premise that untreated dental disease may pose a risk for infection and sepsis, although there is no evidence that this has occurred in organ transplant candidates or recipients. The purpose of this study was to assess the prevalence of dental disease and oral health behaviors in a sample of liver transplant candidates (LTCs). Oral examinations were conducted on 300 LTCs for the presence of gingivitis, dental plaque, dental caries, periodontal disease, edentulism, and xerostomia. The prevalence of these conditions was compared with oral health data from national health surveys and examined for possible associations with most recent dental visit, smoking, and type of liver disease. Significant risk factors for plaque-related gingivitis included intervals of more than 1 yr since the last dental visit (P = 0.004), smoking (P = 0.03), and diuretic therapy (P = 0.005). Dental caries and periodontal disease were also significantly associated with intervals of more than 1 yr since the last dental visit (P = 0.004). LTCs with viral hepatitis or alcoholic cirrhosis had the highest smoking rate (78.8%). Higher rates of edentulism occurred among older LTCs who were less likely to have had a recent dental evaluation (mean 88 months). In conclusion, intervals of more than 1 yr since the last dental visit, smoking, and diuretic therapy appear to be the most significant determinants of dental disease and the need for a pretransplantation dental screening evaluation in LTCs. Edentulous patients should have periodic examinations for oral cancer.
Naik, Pradeep; Premsagar, B; Mallikarjuna, M
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.
Pais, Raluca; Barritt, A. Sidney; Calmus, Yvon; Scatton, Olivier; Runge, Thomas; Lebray, Pascal; Poynard, Thierry; Ratziu, Vlad; Conti, Filomena
Summary Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of preand post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities. PMID:27486010
Van Schalkwyk, McI; Westbrook, R H; O'Beirne, J; Wright, A; Gonzalez, A; Johnson, M A; Kinloch-de Loës, S
We are not aware of a report detailing the complex obstetrical and medical management of twin pregnancy in the context of HIV infection and early post-liver transplantation period. Here we describe the successful outcome of a twin pregnancy in a 28-year-old HIV-positive female receiving antiretroviral therapy and immunosuppressive therapy who was the recipient of a liver transplant for previous drug-induced liver failure.
Sahota, Amandeep; Zaghla, Hassan; Adkins, Rodney; Ramji, Alnoor; Lewis, Susan; Moser, Jennifer; Sher, Linda S; Fong, Tse-Ling
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.
Orman, Eric S.; Mayorga, Maria E.; Wheeler, Stephanie B.; Townsley, Rachel M.; Toro-Diaz, Hector H.; Hayashi, Paul H.; Barritt, Sidney A.
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
Feldman, Amy G.; Neighbors, Katie; Mukherjee, Shubra; Rak, Melanie; Varni, James W.; Alonso, Estella M.
Objective Investigate the spectrum of physical function of pediatric liver transplant (LT) recipients 12–24 months post-LT. Study design Review data collected through the Functional Outcomes Group, an ancillary study of Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12–24 months. Children ≥ 8 years and parents completed the Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales, which includes 8 questions assessing physical function. Scores were compared to a matched healthy child population (n=1658), and between survivors with optimal versus non-optimal health. Results A total of 263 patients were included. Median age at transplant and survey was 4.8 years (IQR 1.3–11.4) and 5.9 years (IQR 2.6–13.1), respectively. The mean Physical Functioning Score on child and parent reports were 81.2± 17.3 and 77.1± 23.7, respectively. Compared to a matched healthy population, transplant survivors and their parents reported lower physical function scores (p<0.01). 32.9% of patients and 35.0% of parents reported a physical function score <75, which is >1 SD below the mean of a healthy population. Physical Function Scores were significantly higher in survivors with optimal health than those with non-optimal health (p<0.01). There was a significant relationship between Emotional Functioning and Physical Functioning Scores for LT recipients (r=0.69, p<0.001). In multivariate analysis, primary disease, height Z score<−1.64 at long term follow-up (LTF) visit, ≥4 days of hospitalization since LTF visit, and not listed as Status 1 were predictors of poor physical function. Conclusions Pediatric LT recipients 1–2 years post-LT and their parents report lower physical function than a healthy population. Findings suggest practitioners need to routinely assess physical function, and development of rehabilitation programs may be important. PMID:26850789
Lin, Chih-Hsiang; Chen, Chao-Long; Lin, Tsu-Kung; Chen, Nai-Ching; Tsai, Meng-Han; Chuang, Yao-Chung
After liver transplantation, patients may develop seizures or epilepsy due to a variety of etiologies. The ideal antiepileptic drugs for these patients are those with fewer drug interactions and less hepatic toxicity. In this study, we present patients using levetiracetam to control seizures after liver transplantation. We retrospectively enrolled patients who received levetiracetam for seizure control after liver transplantation. We analyzed the etiology of liver failure that required liver transplantation, etiology of the seizures, outcomes of seizure control, and the condition of the patient after follow-up at the outpatient department. Hematological and biochemical data before and after the use of levetiracetam were also collected. Fifteen patients who received intravenous or oral levetiracetam monotherapy for seizure control after liver transplantation were enrolled into this study. All of the patients remained seizure-free during levetiracetam treatment. Two patients died during the follow-up, and the other 13 patients were alive at the end of the study period and all were seizure-free without neurological sequelae that interfered with their daily activities. No patients experienced liver failure or rejection of the donor liver due to ineffective immunosuppressant medications. The dosage of immunosuppressants did not change before and after levetiracetam treatment, and there were no changes in hematological and biochemical data before and after treatment. Levetiracetam may be a suitable antiepileptic drug for patients who undergo liver transplantation due to fewer drug interactions and a favorable safety profile.
Malhi, Harmeet; Gorla, Giridhar R.; Irani, Adil N.; Annamaneni, Pallavi; Gupta, Sanjeev
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.
Durán, F G; Piqueras, B; Romero, M; Carneros, J A; de Diego, A; Salcedo, M; Santos, L; Ferreiroa, J; Cos, E; Clemente, G
Pulmonary complications after orthotopic liver transplant (OLT) are frequent, involving high morbidity and mortality. We have determined the pulmonary complication incidence in 187 patients submitted to OLT at the General University Hospital "Gregorio Marañón" in the last 4 years, analyzing the type of infection, evolution, diagnostic and therapeutic measures and their influence on OLT mortality. A total of 120 patients had pulmonary complications, the most frequent being pleural effusion (61.94%), pneumonia (43.36%), and pneumothorax (11.5%). Serious pulmonary hypertension was diagnosed by invasive methods in two patients at the time of surgery (unidentified before OLT); both died at early post postoperative times. Pleural effusion was noted in 70 patients, 31.42% of them requiring thoracic tube drainage, complications developing in 22.72%. Thirteen patients were diagnosed of pneumothorax, the most frequent etiologies being percutaneous liver biopsy, thoracic tube drainage for pleural effusion, and postoperative complications in 41.6, 33.3, and 23.3%, respectively. Pneumonia was diagnosed in the 1st month after OLT in 45 patients. Tests to diagnose and identify the etiological agent were made in 71.1% of diagnosed pneumonia patients, identification being obtained in 62.5%. Telescope catheter culture identified the agent in 48%, fiber optic bronchoscopy in 50%, and lung or pleural biopsy in 100%. Respiratory insufficiency was noted in 64 patients (34.22% of transplanted patients). Factors involved in their development were pneumonia (42.18%), graft dysfunction (39.06%, pleural effusion (34.37%), sepsis (28.18%), and poor nutritional status (7.81%). Fifty patients (41.66%) died, pulmonary pathology being the determinant factor in 28.8%. Patient mortality with respiratory insufficiency was greater, especially in those with three factors involved the development of respiratory insufficiency.
Dierickx, Daan; Cardinaels, Nina
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
Mito, M; Ebata, H; Kusano, M; Onishi, T; Saito, T; Sakamoto, S
Hepatocytes isolated by the collagenase digestive method were transplanted into the spleens of syngeneic rats. Morphology and function of the hepatocytes in the spleen were investigated for 12 to 17 months after transplantation. The transplanted hepatocytes proliferated and reconfigured in the spleen without direct perfusion of portal venous blood and with the presence of an intact host liver. Fourteen to 17 months after transplantation, the hepatocytes which had formed a demarcated nodule occupied approximately 40% of the area of the splenic parenchyma without undifferentiation on microscopic examination. However, the weight of the hepatized spleen did not increase beyond the weight of a normal spleen and the weight of the host liver that had normal morphology also did not differ from a normal liver. Light and electron microscopic studies demonstrated differentiated cord structure and normal architecture for each heptocyte. Furthermore, the hepatized spleen synthesized albumin and glycogen as demonstrated by immunofluorescence and histochemical studies. Ammonia tolerance and indocyanine green clearance tests revealed functioning hepatocytes in the spleen proper. These results indicate that our experimental model lends itself well to investigations in cell growth mechanism and that hepatocellular transplantation has potential clinical application to compensate for impaired hepatic function.
Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C
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
Jiménez-Castro, M B; Gracia-Sancho, J; Peralta, C
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.
Maiwall, Rakhi; Kumar, Manoj
Chronic hepatitis B is a global health problem that leads to development of various complications, such as cirrhosis, liver cancer, and liver failure requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction, cirrhosis of the allograft, and graft failure. Patients with high viral load at the time of transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation, while patients with low viral load, including HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation. Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and, therefore, all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence. Even, marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients. In this article, we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection PMID:27047773
Takagi, Kosei; Yagi, Takahito; Shinoura, Susumu; Umeda, Yuzo; Yoshida, Ryuichi; Nobuoka, Daisuke; Watanabe, Nobuyuki; Kuise, Takashi; Fuji, Tomokazu; Araki, Hiroyuki; Fujiwara, Toshiyoshi
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an extremely rare cause of hyponatremia post-liver transplantation. A 15-year-old Japanese girl with recurrent cholangitis after Kasai surgery for biliary atresia underwent successful living donor liver transplantation. Peritonitis due to gastrointestinal perforation occurred. Hyponatremia gradually developed but improved after hypertonic sodium treatment. One month later, severe hyponatremia rapidly recurred. We considered the hyponatremia's cause as SIADH. We suspected that tacrolimus was the disease's cause, so we used cyclosporine instead, plus hypertonic sodium plus water intake restriction, which improved the hyponatremia. Symptomatic hyponatremia manifested by SIADH is a rare, serious complication post-liver transplantation.
Katsura, Emi; Ichikawa, Tatsuki; Taura, Naota; Miyaaki, Hisamitsu; Miuma, Satoshi; Shibata, Hidetaka; Honda, Takuya; Hidaka, Masaaki; Soyama, Akihiko; Takeshima, Fuminao; Eguchi, Susumu; Nakao, Kazuhiko
Background The risk of liver cirrhosis is higher among individuals with diabetes mellitus, and a cirrhotic patient with diabetes may have a poorer prognosis after liver transplantation compared to a patient without diabetes. Thus, we evaluated whether fasting plasma glucose prior to receiving a liver transplant was a prognostic factor for post-transplant survival. Material/Methods Ninety-one patients received a living donor liver transplant between November 2005 and December 2012. Patients were considered diabetic if they were prescribed diabetes medications or had impaired glucose tolerance as measured by an oral glucose tolerance test. Each patient was monitored through December 31, 2013, to evaluate prognosis. Results Fasting plasma glucose of at least 100 mg/dL significantly decreased survival following transplant (52% in the high FPG group compared to 78% in the control group, p=0.04), while postprandial hyperglycemia had no effect on survival. Additionally, overall mortality and the incidence of vascular disease were significantly higher among patients with uncontrolled plasma glucose. Impaired fasting plasma glucose was significantly and inversely associated with overall survival in the univariate and multivariate analyses, while creatinine (at least 1 mg/dL) was inversely associated with survival in the univariate analysis. Conclusions Elevated fasting plasma glucose prior to liver transplantation was inversely associated with post-transplant survival. This effect may be due to underlying microangiopathy as a result of uncontrolled diabetes before transplantation. Our data demonstrated the importance of controlled blood glucose prior to liver transplantation. PMID:27909287
Patel, Yuval A.; Berg, Carl L.
Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease in developed countries and is on trajectory to become the leading indication for liver transplantation in the USA and much of the world. Patients with NAFLD cirrhosis awaiting liver transplant face unique challenges and increased risk for waiting list stagnation and dropout due to burdensome comorbidities including obesity, diabetes, cardiovascular disease, and kidney disease. Thus far, patients transplanted for NAFLD cirrhosis have excellent mid- and long-term patient and graft survival, but concerns regarding short-term morbidity and mortality continue to exist. Post-liver transplantation, NAFLD occurs as both a recurrent and de novo manifestation, each with unique outcomes. NAFLD in the donor population is of concern given the growing demand for liver transplantation and mounting pressure to expand the donor pool. This review addresses key issues surrounding NAFLD as an indication for transplantation, including its increasing prevalence, unique patient demographics, outcomes related to liver transplantation, development of post-liver transplantation NAFLD, and NAFLD in the liver donor population. It also highlights exciting areas where further research is needed, such as the role of bariatric surgery and preconditioning of marginal donor grafts. PMID:26815171
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.
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.
NACIF, Lucas Souto; PINHEIRO, Rafael Soares; PÉCORA, Rafael Antônio de Arruda; DUCATTI, Liliana; ROCHA-SANTOS, Vinicius; ANDRAUS, Wellington; D'ALBUQUERQUE, Luiz Carneiro
Introduction: Late acute rejection leads to worse patient and graft survival after liver transplantation. Aim: To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method: Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were analyzed demographics, immunosuppression, rejection, infection and graft and patient survival rates. Results: Late acute rejection in liver transplantation showed poor results mainly regarding patient and graft survival. Almost all of these cohort studies were retrospective and descriptive. The incidence of late acute rejection varied from 7-40% in these studies. Late acute rejection was one cause for graft loss and resulted in different outcomes with worse patient and graft survival after liver transplant. Late acute rejection has been variably defined and may be a cause of chronic rejection with worse prognosis. Late acute rejection occurs during a period in which the goal is to maintain lower immunosuppression after liver transplantation. Conclusion: The current articles show the importance of late acute rejection. The real benefit is based on early diagnosis and adequate treatment at the onset until late follow up after liver transplantation. PMID:26537150
Lee, Mary R.; Leggio, Lorenzo
Alcoholic liver disease is the second most common indication for orthotopic liver transplantation in western countries. The majority of patients with alcoholic liver disease, however, are not referred for transplant evaluation. If evaluated, a 6 month period of sobriety is required before waitlisting for transplant. The consequences of relapse to alcohol use in patients on the waitlist are usually removal from the list. Therefore, identification and treatment of alcohol use disorder in patients with end-stage liver disease greatly impacts quality of life, treatment options and survival in patients’ course with this grave illness. Psychosocial and behavioral interventions prior to transplant appear to reduce drinking in the period before the surgery as well as reduce relapse rates post-transplant. Only one of the three medications approved by the Food and Drug Administration, acamprosate, seems feasible for use in patients with end-stage liver disease, while several other medications currently under investigation for the treatment of alcohol use disorder can be considered for use in this population. While only baclofen has been formally studied in alcoholic patients with end-stage liver disease with positive results for safety and efficacy, other medications also hold promise to treat alcohol use disorder in this population. Transplant programs with addictions specialists who function as an integral part of the treatment team may offer better outcomes to patients in terms of success of maintaining sobriety both pre- and post-transplant. PMID:26619772
Weinrieb, Robert M; Lucey, Michael R
Very little addiction treatment research has been done concerning smoking cessation, illicit drugs, or even alcohol abuse in liver transplant patients. Our data suggest that a surprising number of patients who are awaiting a liver transplant for alcohol-related end-stage liver disease will return to drinking before transplantation. We found that motivational enhancement therapy afforded no marked benefit over treatment as usual for drinking, smoking, mood, or general health outcomes in alcoholics awaiting liver transplantation. Stably abstinent methadone-maintained opiate-dependent patients should not be tapered off methadone; are generally good candidates for liver transplant; show low relapse rates into illicit use of opiates; and may be at risk for more medical complications than their counterparts. Pre- and posttransplantation smoking rates are high and cause marked morbidity and mortality. Transplant teams should encourage smoking cessation treatments.Marijuana use in liver transplant recipients is not uncommon, and apart from the risk of developing aspergillosis, additional health risks have not yet been identified.
Dorsch, Martina; Wedekind, Dirk
The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required.
Miloh, Tamir; Barton, Andrea; Wheeler, Justin; Pham, Yen; Hewitt, Winston; Keegan, Tara; Sanchez, Christine; Bulut, Pinar; Goss, John
Pediatric liver transplantation has experienced improved outcomes over the last 50 years. This can be attributed in part to establishing optimal use of immunosuppressive agents to achieve a balance between minimizing the risks of allograft rejection and infection. The management of immunosuppression in children is generally more complex and can be challenging when compared with the use of these agents in adult liver transplant patients. Physiologic differences in children alter the pharmacokinetics of immunosuppressive agents, which affects absorption, distribution, metabolism, and drug excretion. Children also have a longer expected period of exposure to immunosuppression, which can impact growth, risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood of nonadherence. This review discusses immunosuppressive options for pediatric liver transplant recipients and the unique issues that must be addressed when managing this population. Further advances in the field of tolerance and accommodation are needed to relieve the acute and cumulative burden of chronic immunosuppression in children. Liver Transplantation 23 244-256 2017 AASLD.
Descheemaeker, P-N; Compagnon, P; Lavoué, V; Seguin, P; Lechaux, D; Renaud-Giono, A; Camus, C; Meunier, B; Malledant, Y
The hepatic rupture of a subcapsular haematoma during HELLP syndrome is a rare complication carrying a high mortality. There is no clear guideline management in the literature. We report here a case of a subcapsular haematoma which required liver transplantation.
Llovet, Laura-Patricia; Rodríguez-Tajes, Sergio; Londoño, María-Carlota
Hepatitis C recurrence after liver transplantation is universal and increases morbidity and mortality in these patients. The development of new direct antiviral agents against the hepatitis C virus is a major treatment advance. Pre-transplant treatment avoids graft infection and sometimes improves liver function, allowing the patient to be withdrawn from the transplant waiting list. Delaying treatment until the postpostransplant period may be advisable in patients with advanced cirrhosis. Generally, antiviral therapy after liver transplantation is provided in patients with histological evidence of the disease. In these patients, treatment is more effective in the initial stages of the disease. The choice of antiviral therapy in these patients is based on the degree of liver function, the presence of renal failure, and potential drug-drug interactions.
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
Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 ± 251 g (mean ± SD), and percentage 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 ± 267 g, and percentage reconstitution was 93% ± 18%. Predictors of greater 3-month liver volume included larger patient size (donors and 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). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed 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
Breil, Thomas; Wenning, Daniel; Teufel, Ulrike; Hoffmann, Georg F.
Introduction Pediatric liver transplantation is a highly specialized, challenging field. Selective reporting may introduce bias into evidence based clinical decision making, but the precise extent of unpublished data in pediatric liver transplantation is unknown today. We therefore assessed the public availability of completed clinical trials in pediatric liver transplantation. Methods We determined the proportion of published and unpublished pre-registered, completed pediatric liver transplantation studies on ClinicalTrials.gov. The major trial and literature databases, i.e., clinicaltrials.gov, Pubmed, and Google Scholar were searched for publications. In addition, principal investigators or sponsors were contacted directly. STROBE criteria were applied for the descriptive analysis. Results Out of N = 33 studies focusing on pediatric liver transplantation registered as completed until March 2014 on clinicaltrials.gov, N = 19 (58%) studies were published until February 2015, whereas N = 14 (42%) studies remained unpublished. The unpublished trials contain data from N = 2105 (35%) patients out of a total population of N = 6044 study participants. Median time-to-publication, i.e., the period from completion of the trial until public availability of the data was 23 IQR 10 to 28 months. Most pertinent key questions in pediatric liver transplantation, i.e., surgical procedures, immunosuppression, concomitant infections, and graft rejection were addressed in 48% of studies (N = 16/33), half of which were published. Conclusion Half of the clinical trials in pediatric liver transplantation focused on key questions such as surgical procedures, immunosuppression, concomitant infections, and graft rejection. There is still a considerable amount of unpublished studies results in pediatric liver transplantation. Time from study completion to publication was almost twice as long as the 12 months mandatory FDAAA-timeline with a trend towards acceleration over time. The data
Bacchella, T; Machado, M C C
The first clinical orthotopic liver transplantation in Brazil was performed on August 5, 1968. The patient was awake after surgery and died on the seventh postoperative day due to subdural hematoma, bronchopneumonia, renal failure, and graft rejection. The report of this case is important to understand the evolution of clinical liver transplantation in Brazil, where this procedure is now routinely carried out in many medical centers.
Kallwitz, Eric R; Loy, Veronica; Mettu, Praveen; Von Roenn, Natasha; Berkes, Jamie; Cotler, Scott J
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
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
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
RIBEIRO-JR, Marcelo Augusto Fontenelle; MEDRADO, Melina Botelho; ROSA, Otto Mauro; SILVA, Ana Júlia de Deus; FONTANA, Mariana Prado; CRUVINEL-NETO, José; FONSECA, Alexandre Zanchenko
Background : The liver is the most injured organ in abdominal trauma. Currently, the treatment in most cases is non-operative, but surgery may be necessary in severe abdominal trauma with blunt liver damage, especially those that cause uncontrollable bleeding. Despite the damage control approaches in order to achieve hemodynamic stability, many patients develop hypovolemic shock, acute liver failure, multiple organ failure and death. In this context, liver transplantation appears as the lifesaving last resource Aim : Analyze the use of liver transplantation as a treatment option for severe liver trauma. Methods : Were reviewed 14 articles in the PubMed, Medline and Lilacs databases, selected between 2008-2014 and 10 for this study. Results : Were identified 46 cases undergoing liver transplant after liver trauma; the main trauma mechanism was closed/blunt abdominal trauma in 83%, and severe trauma (>grade IV) in 81 %. The transplant can be done, in this context, performing one-stage procedure (damaged organ removed with immediate transplantation), used in 72% of cases. When the two-stage approach is performed, end-to-side temporary portacaval shunt is provided, until new organ becomes available to be transplanted. If two different periods are considered - from 1980 to 2000 and from 2000 to 2014 - the survival rate increased significantly, from 48% to 76%, while the mortality decreased from 52% to 24%. Conclusion : Despite with quite restricted indications, liver transplantation in hepatic injury is a therapeutic modality viable and feasible today, and can be used in cases when other therapeutic modalities in short and long term, do not provide the patient survival chances. PMID:26734803
Bejarano, Pablo A; Garcia, Monica T; Rodriguez, Maria M; Ruiz, Phillip; Tzakis, Andreas G
Ground-glass hepatocytes have been described in Lafora's disease, fibrinogen deposition, hepatitis B, type IV glycogenosis, and alcohol aversion (cyanamide) therapy. We encountered ground-glass hepatocytes with intracytoplasmic inclusions in four liver biopsies from three transplanted patients who had none of the above-mentioned underlying diseases. One patient was a 4-year-old boy who had a kidney transplant for severe ureterovesical reflux. Patient 2 was a 52-year-old man who had two liver transplants because of hepatitis C. The third patient was a 7-month-old girl who underwent a multivisceral transplant because of necrotizing enterocolitis and liver failure induced by total parenteral nutrition. The patients developed liver abnormalities from 45 days to 4 years after their transplants. The livers showed conspicuous ground-glass hepatocytes in 90% of the children's samples and 30% of the adult liver cells. The cytoplasmic bodies stained strongly for Gomori methenamine-silver; they were positive for periodic acid-Schiff without diastase, but negative after diastase digestion. They were negative for colloidal iron and hepatitis B core and surface antigens. Electron microscopy revealed non-membrane bound aggregates of glycogen. Idiopathic ground-glass hepatocytes occur in transplanted patients and represent accumulation of altered glycogen. However, their clinical significance and cause are not entirely elucidated.
Lauterio, Andrea; Di Sandro, Stefano; Concone, Giacomo; De Carlis, Riccardo; Giacomoni, Alessandro; De Carlis, Luciano
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
Sureka, Binit; Bansal, Kalpana; Rajesh, S; Mukund, Amar; Pamecha, Viniyendra; Arora, Ankur
The liver is the second most-often transplanted solid organ after the kidney, so it is clear that liver disease is a common and serious problem around the globe. With the advancements in surgical, oncological and imaging techniques, orthotopic liver transplantation has become the first-line treatment for many patients with end-stage liver disease. Ultrasound, and Doppler are the most economical and cost-effective imaging modalities for evaluating postoperative fluid collections and vascular complications. Computed tomography (CT) is used to confirm the findings of ultrasound and look for pulmonary complications. Magnetic resonance imaging (MRI) is used for the diagnosis of biliary complications, bile leaks and neurological complications. This article illustrates the imaging options for diagnosing the various complications that can be encountered in the postoperative period after liver transplantation. PMID:26534929
Lysy, Philippe A; Najimi, Mustapha; Stéphenne, Xavier; Bourgois, Annick; Smets, Françoise; Sokal, Etienne M
Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives. PMID:18567072
Kobayashi, N; Miyazaki, M; Fukaya, K; Inoue, Y; Sakaguchi, M; Noguchi, H; Matsumura, T; Watanabe, T; Totsugawa, T; Tanaka, N; Namba, M
Primary human hepatocytes are an ideal source of hepatic function in bioartficial liver (BAL), but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, primary human fetal hepatocytes were immortalized using simian virus 40 large T antigen. One of the immortal cell lines, OUMS-29, showed highly differentiated liver functions. Intrasplenic transplantation of OUMS-29 cells protected 90% hepatectomized rats from hyperammonemia and significantly prolonged their survival. Essentially unlimited availability of OUMS-29 cells supports their clinical use for BAL treatment.
Hofer, Ira; Spivack, John; Yaport, Miguel; Zerillo, Jeron; Reich, David L; Wax, David; DeMaria, Samuel
The anesthesiologist has been recognized as an integral member of the liver transplant team, and previous studies have demonstrated that inter-anesthesiologist variability can be a driver of outcomes for high-risk patients. We hypothesized that anesthesiologist experience, defined as the number of previous liver transplants performed at our institution, the Icahn School of Medicine at Mount Sinai, would be independently associated with outcomes for liver transplant patients. Eight hundred forty-nine liver transplants performed between January 2003 and January 2013 with a total of 22 anesthesiologists were analyzed. Each transplant was assigned an incremental case number that corresponded to the number of transplants that the attending anesthesiologist had already performed at our institution. Several perioperative covariates were controlled for in the context of a generalized linear mixed effects model to detail the influence of threshold levels of the incremental case number on the primary outcome, 30-day mortality, and a secondary outcome, 30-day graft failure. Sensitivity analyses were conducted to confirm the robustness of these findings. An incremental case number ≤ 5 was associated with a significantly greater risk of 30-day mortality (odds ratio = 2.24, 95% confidence interval = 1.11-4.54, P = 0.025), and there was evidence suggestive of a greater risk of 30-day graft failure (odds ratio = 1.93, 95% confidence interval = 0.95-3.93, P = 0.071). Sensitivity analyses ruled out threats to the validity of these findings, including dropout effects and time trends in the overall performance of the transplantation unit. In conclusion, this study shows that an anesthesiologist's level of experience has a significant effect on outcomes for liver transplant recipients, with increased mortality and possibly graft failure during a provider's first 5 cases. These findings may indicate the need for increased training and supervision for
Wang, Y-G; Wu, J-S; Jiang, B; Wang, J-H; Liu, C-P; Peng, C; Tian, B-Z
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.
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide. In the last decade it has become the third most common indication for liver transplantation in the United States. Increasing prevalence of NAFLD in the general population also poses a risk to organ donation, as allograft steatosis can be associated with non-function of the graft. Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease, although long term outcomes beyond 10 year are lacking. NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted. De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Predictors for NAFLD post-transplant recurrence include obesity, hyperlipidemia and diabetes as well as steroid dose after liver transplantation. A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk. Although immunosuppression side effects potentiate obesity and the metabolic syndrome, studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population. Based on pre-transplant data, sustained weight loss through diet and exercise is the most effective therapy for NAFLD. Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents. Studies of these therapies are lacking in the post-transplant population. A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD. PMID:24409043
Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah
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
Lee, Soo Young; Kim, Han Joon; Choi, Dongho
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
Lee, Soo Young; Kim, Han Joon; Choi, Dongho
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.
Melendez, H. V.; Rela, M.; Baker, A.; Ball, C.; Portmann, B.; Mieli-Vergani, G.; Heaton, N.
Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease. PMID:9370907
Chin, Jun Liong; Hisamuddin, Syafiah Hanis; O'Sullivan, Aoife; Chan, Grace; McCormick, P Aiden
Thrombocytopenia affects patients undergoing liver transplantation. Intraoperative platelet transfusion has been shown to independently influence survival after liver transplantation at 1 and 5 years. We examined the impact of thrombocytopenia and intraoperative platelet transfusion on short-term graft and overall survival after orthotopic liver transplantation (OLT). A total of 399 patients undergoing first OLT were studied. Graft and overall survival in patients with different degrees of thrombocytopenia and with or without intraoperative platelet transfusion were described. The degree of thrombocytopenia prior to OLT did not affect graft or overall survival after transplant. However, graft survival in patients receiving platelets was significantly reduced at 1 year (P= .023) but not at 90 days (P= .093). Overall survival was significantly reduced at both 90 days (P= .040) and 1 year (P= .037) in patients receiving platelets. We conclude that a consistently lower graft and overall survival were observed in patients receiving intraoperative platelet transfusion.
Faybush, Elisa; Mulligan, David C; Birch, Barry D; Sirven, Joseph I; Balan, Vijayan
There are no published accounts of patients with ventriculoperitoneal shunts undergoing liver transplantation in the literature. Because patients with ventriculoperitoneal shunts are prone to infections, this may be a theoretical contraindication to transplantation. We present a case of a patient with cirrhosis who had a ventriculoperitoneal shunt placed many years prior to transplantation. The patient had no neurological complications and the shunt was intact and functioning. Prior to transplantation, the patient underwent a ventriculoperitoneal to ventriculopleural shunt conversion that was reversed posttransplantation. Apart from some minor complications, the patient has done remarkably well from a graft and neurological perspective. In conclusion, patients who have ventriculoperitoneal shunts may be considered for liver transplantation as the risk of infectious and neurological complications is low and there are no deleterious effects on graft survival.
Sá, Amanda Silva; Ziviani, Luciana Costa; Castro-E-Silva, Orlando; Galvão, Cristina Maria; Mendes, Karina Dal Sasso
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.
Tan-Tam, Clara C; Frassetto, Lynda A; Stock, Peter G
HIV infection has evolved into a chronic condition as a result of improvements in therapeutic options. Chronic exposure with HIV and associated co-pathogens as well as toxicities from prolonged therapy with antiviral medications has resulted in increased morbidity and mortality rates from end-stage liver and kidney disease in the HIV-infected population. Since the definitive treatment for end-stage organ failure is transplantation, demand has increased among HIV-infected patients. Although the transplant community has been slow to recognize HIV as a chronic condition, many transplant centers have eliminated HIV infection as a contraindication to transplantation as a result of better patient management and demand. This review examines the current clinical strategies and issues surrounding liver and kidney transplantation in HIV-infected patients.
Sauer, Vanessa; Siaj, Ramsi; Stöppeler, Sandra; Bahde, Ralf; Spiegel, Hans-Ullrich; Köhler, Gabriele; Zibert, Andree; Schmidt, Hartmut H J
The outcome of consecutive hepatocyte transplants was explored in a rat model of Wilson's disease before the onset of fulminant hepatitis without preconditioning regimens. Rats received a high-copper diet in order to induce a rapid induction of liver failure. Sham-operated rats (15/15) developed jaundice and fulminant hepatitis, and they died within 4 weeks of first transplantation. Despite the continuation of a high dietary copper challenge, long-term survival was observed for a notable proportion of the transplanted animals (7/18). All survivors displayed normalized levels of hepatitis-associated serum markers and ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively. The liver copper concentrations, the liver histology, and the expression of marker genes were significantly restored within 4 months of transplantation in comparison with the control group. The high expression of a copper transporter gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors indicated a high rate of repopulation by donor hepatocytes. Our data suggest that repeated cell transplantation can overcome the limitations of a single therapy session in rats with severe hepatic disease by functionally restoring the host liver without preconditioning.
Gedik, Ender; Bıçakçıoğlu, Murat; Otan, Emrah; İlksen Toprak, Hüseyin; Işık, Burak; Aydın, Cemalettin; Kayaalp, Cüneyt; Yılmaz, Sezai
The main goal of 2-stage liver transplant is to provide time to obtain a new liver source. We describe our experience of 3 patients with 3 different clinical conditions. A 57-year-old man was retransplanted successfully with this technique due to hepatic artery thrombosis. However, a 38-year-old woman with fulminant toxic hepatitis and a 5-year-old-boy with abdominal trauma had poor outcome. This technique could serve as a rescue therapy for liver transplant patients who have toxic liver syndrome or abdominal trauma. These patients required intensive support during long anhepatic states. The transplant team should decide early whether to use this technique before irreversible conditions develop.
Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.
Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.
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.
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
Lallier, M; St-Vil, D; Dubois, J; Paradis, K; Laberge, J M; Bensoussan, A L; Guttman, F M; Blanchard, H
From February 1986 to July 1994, 81 hepatic transplantations were performed in 73 children, with an overall patient survival rate of 83%. Forty-two patients received whole-liver grafts (WLG) and 39 had reduced-size grafts (RSG). The mean patient weight was 19.7 kg, with 29 patients weighing less than 10 kg. Seventeen vascular complications (21%) occurred in 13 children: 8 (10%) had hepatic artery thrombosis (HAT), 5 (6%) had portal vein thrombosis (PVT), 1 had both HAT and PVT (1%), and 3 (4%) had aortic conduit perforation (ACP). There was no significant difference in the incidence of HAT between RSG (5%) and WLG (14%) or between children weighing less than 10 kg (10%) and those weighing more than 10 kg (10%). The site of arterial reconstruction, end-to-end to the recipient common hepatic artery or end-to-side to the infrarenal aorta, had no significant effect on the occurrence of HAT (7% v 8%), but HAT occurred in 2 of 6 cases (33%) in which an aortic conduit was used. PVT documented in 5 cases (6%) was associated with technical complications (2), preduodenal portal vein (2), and a circulating cardiolipid antibody (1), and required thrombectomy, with no graft loss. Combined HAT and PVT was found in one patient 2 years postretransplantation for HAT. Although graft function is normal, portal hypertension persists. The aortic conduit, used in six patients, led to arterial perforation (3), HAT (2), and death (2). Of the 8 cases of HAT, 1 was diagnosed during autopsy and 7 occurred within 30 days and required retransplantation (6) or thrombectomy with rearterialization (1).(ABSTRACT TRUNCATED AT 250 WORDS)
Gitto, Stefano; Villa, Erica
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.
Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito
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
Joshi, Deepak; Agarwal, Kosh
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
Fagiuoli, Stefano; Daina, Erica; D'Antiga, Lorenzo; Colledan, Michele; Remuzzi, Giuseppe
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
Vacanti, Joseph P; Kulig, Katherine M
Liver transplantation remains the only definitive treatment for liver failure and is available to only a tiny fraction of patients with end-stage liver diseases. Major limitations for the procedure include donor organ shortage, high cost, high level of required expertise, and long-term consequences of immune suppression. Alternative cell-based liver therapies could potentially greatly expand the number of patients provided with effective treatment. Investigative research into augmenting or replacing liver function extends into three general strategies. Bioartificial livers (BALs) are extracorporeal devices that utilize cartridges of primary hepatocytes or cell lines to process patient plasma. Injection of liver cell suspensions aims to foster organ regeneration or provide a missing metabolic function arising from a genetic defect. Tissue engineering recreates the organ in vitro for subsequent implantation to augment or replace patient liver function. Translational models and clinical trials have highlighted both the immense challenges involved and some striking examples of success.
Starzl, Thomas E.; Lakkis, Fadi G.
Liver transplantation radically changed the philosophy of hepatology practice, enriched multiple areas of basic science, and had pervasive ripple effects in law, public policy, ethics, and theology. Why organ engraftment was feasible remained enigmatic, however, until the discovery in 1992 of donor leukocyte microchimerism in long-surviving liver, and other kinds of organ recipients. Following this discovery, the leukocyte chimerism-associated mechanisms were elucidated that directly linked organ and bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. We describe here how the initially controversial paradigm shift mandated revisions of cherished dogmas. With the fresh insight, the reasons for numerous inexplicable phenomena of transplantation either became obvious or have become susceptible to discriminate experimental testing. The therapeutic implications of the “new immunology” in hepatology and in other medical disciplines, have only begun to be explored. Apart from immunology, physiologic investigations of liver transplantation have resulted in the discovery of growth factors (beginning with insulin) that are involved in the regulation of liver size, ultrastructure, function, and the capacity for regeneration. Such studies have partially explained functional and hormonal relationships of different abdominal organs, and ultimately they led to the cure or palliation by liver transplantation of more than 2 dozen hepatic-based inborn errors of metabolism. Liver transplantation should not be viewed as a purely technologic achievement, but rather as a searchlight whose beams have penetrated the murky mist of the past, and continue to potentially illuminate the future. PMID:16447295
Aguirre-Avalos, Guadalupe; Covarrubias-Velasco, Marco Antonio; Rojas-Sánchez, Antonio Gerardo
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
Zhang, M; Uhanova, J; Minuk, GY
BACKGROUND: A higher incidence of autoimmune disorders may predispose First Nations (FN) individuals to higher rates and more severe episodes of rejection, graft loss and mortality following liver transplantation for advanced liver disease. METHODS: A retrospective review of patient outcomes in a single centre providing long-term follow-up care for FN and non-FN patients transplanted for advanced liver disease was conducted. RESULTS: A total of 20 FN and 129 non-FN charts were available for review. FN subjects were younger at transplantation (mean [± SD] age 32.4±4.1 years versus 46.3±1.4 years; P=0.00005), less often male (35% versus 58%; P=0.05), more commonly transplanted for autoimmune hepatitis (30% versus 4.7%; P=0.006), less often from urban residences (25% versus 74%; P=0.0001) and less compliant with medical care (20% versus 80%; P=0.007). After a mean follow-up period of 11.0±1.5 years and 8.4±0.5 years in FN and non-FN subjects, respectively, the incidence and severity of rejection, graft and patient survival were similar between cohorts. CONCLUSION: Although demographic profiles, nature of the underlying disease and compliance differed, the rates and severity of rejection, graft and patient survival were similar in FN and non-FN patients who underwent liver transplantation for advanced liver disease. PMID:21766089
Zamberlan, Patrícia; Leone, Cláudio; Tannuri, Uenis; de Carvalho, Werther Brunow; Delgado, Artur Figueiredo
OBJECTIVE: To analyze the nutritional status of pediatric patients after orthotopic liver transplantation and the relationship with short-term clinical outcome. METHOD: Anthropometric evaluations of 60 children and adolescents after orthotopic liver transplantation, during the first 24 hours in a tertiary pediatric intensive care unit. Nutritional status was determined from the Z score for the following indices: weight/age, height/age or length/age, weight/height or weight/length, body mass index/age, arm circumference/age and triceps skinfold/age. The severity of liver disease was evaluated using one of the two models which was adequated to the patients' age: 1. Pediatric End-stage Liver Disease, 2. Model for End-Stage Liver Disease. RESULTS: We found 50.0% undernutrition by height/age; 27.3% by weight/age; 11.1% by weight/height or weight/length; 10.0% by body mass index/age; 61.6% by arm circumference/age and 51.0% by triceps skinfold/age. There was no correlation between nutritional status and Pediatric End-stage Liver Disease or mortality. We found a negative correlation between arm circumference/age and length of hospitalization. CONCLUSION: Children with chronic liver diseases experience a significant degree of undernutrition, which makes nutritional support an important aspect of therapy. Despite the difficulties in assessment, anthropometric evaluation of the upper limbs is useful to evaluate nutritional status of children before or after liver transplantation. PMID:23295591
Goldberg, David S.; Reese, Peter P.; Amaral, Sandra; Abt, Peter L.
Simultaneous heart-liver transplantation, although rare, has become more common in the U.S. When the primary organ is a heart or liver, patients receiving an offer for the primary organ automatically receive the second, non-primary organ from that donor. This policy raises issues of equity—i.e. whether liver transplant-alone candidates bypassed by heart-liver recipients are disadvantaged. No prior published analyses have addressed this issue, and few methods have been developed as a means to measure the impact of such allocation policies. We analyzed OPTN match run data from 2007-2013 to determine whether this combined organ allocation policy disadvantages bypassed liver transplant waitlist candidates in a clinically meaningful way. Among 65 heart-liver recipients since May 2007, 42 had substantially higher priority for the heart relative to the liver, and bypassed 268 liver-alone candidates ranked 1-10 on these match runs. Bypassed patients had lower risk of waitlist removal for death or clinical deterioration compared to controls selected by match MELD score (HR: 0.56, 95% CI: 0.40-0.79), and similar risk as controls selected by laboratory MELD score (HR: 0.91, 95% CI: 0.63-1.33) or on match runs of similar graft quality (HR: 0.97, 95% CI: 0.73-1.37). The waiting time from bypass to subsequent transplantation was significantly longer among bypassed candidates versus controls on match runs of similar graft quality (median: 87 (IQR: 27-192) days versus 24 (5-79) days; p<0.001). Although transplant is delayed, liver transplant waitlist candidates bypassed by heart-liver recipients do not have excess mortality compared to three sets of matched controls. These analytic methods serve as a starting point to consider other potential approaches to evaluate the impact of multi-organ transplant allocation policies PMID:25044621
Thudi, Kavitha R; Kreikemeier, Jeffrey T; Phillips, Nancy J; Salvalaggio, Paolo R; Kennedy, Donald J; Hayashi, Paul H
Hepatic cat scratch disease is rarely reported in liver transplant recipients and has never been reported with discrete liver lesions in the graft. A 52-year-old woman was transplanted for hepatitis C cirrhosis and hepatocellular carcinoma. Her posttransplant course was uneventful. She presented 2.7 years after transplantation with fever of unknown origin and went on to develop multiple and diffuse discrete liver lesions. Despite an extensive work-up including percutaneous and laparoscopic biopsies, a subsegmental resection that included one of these masses was required to make the diagnosis of Bartonella henselae infection. Serologic tests were equivocal. Histology was consistent with cat scratch disease of the liver, and polymerase chain reaction (PCR) testing of the resected tissue confirmed the diagnosis. Response to doxycycline was rapid. Fevers resolved within 7 days. Repeat abdominal CT scan showed reduction of the liver masses. Cat scratch disease should be considered in postliver transplant patients presenting with fever and liver lesions, especially if close contact with cats has occurred. Diagnosis by PCR testing of involved tissue is preferred when serologies are equivocal due to immunosuppression.
Qi, Ziping; Li, Lu; Wang, Xuefu; Gao, Xiang; Wang, Xin; Wei, Haiming; Zhang, Jian; Sun, Rui; Tian, Zhigang
Liver immunopathologic mechanisms during hepatotropic infection, malignant transformation, and autoimmunity are still unclear. Establishing a chimeric mouse with a reconstituted liver and immune system derived from a single donor across species is critical to study regional donor immune responses in recipient liver. Using a strain of mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah-/-) and bone marrow transplantation (BMT), we reconstituted the donor's hepatocytes and immune cells across host species barrier. Syngeneic, allogeneic or even xenogeneic rat BMT rescued most recipient fah-/- mice against liver failure by donor BM-derived FAH+ hepatocytes. Importantly, immune system developed normally in chimeras, and the immune cells together with organ architecture were intact and functional. Thus, donor BM can across host species barrier and concurrently reconstitutes MHC-identical response between immune cells and hepatocytes, giving rise to a new simple and convenient small animal model to study donor's liver immune response in mice.
Qi, Ziping; Li, Lu; Wang, Xuefu; Gao, Xiang; Wang, Xin; Wei, Haiming; Zhang, Jian; Sun, Rui; Tian, Zhigang
Liver immunopathologic mechanisms during hepatotropic infection, malignant transformation, and autoimmunity are still unclear. Establishing a chimeric mouse with a reconstituted liver and immune system derived from a single donor across species is critical to study regional donor immune responses in recipient liver. Using a strain of mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah-/-) and bone marrow transplantation (BMT), we reconstituted the donor's hepatocytes and immune cells across host species barrier. Syngeneic, allogeneic or even xenogeneic rat BMT rescued most recipient fah-/- mice against liver failure by donor BM-derived FAH+ hepatocytes. Importantly, immune system developed normally in chimeras, and the immune cells together with organ architecture were intact and functional. Thus, donor BM can across host species barrier and concurrently reconstitutes MHC-identical response between immune cells and hepatocytes, giving rise to a new simple and convenient small animal model to study donor's liver immune response in mice. PMID:25191899
Ling, Qi; Dai, Haojiang; Zhuang, Runzhou; Shen, Tian; Wang, Weilin; Xu, Xiao; Zheng, Shusen
To compare the performance of eight score systems (MELD, uMELD, MELD-Na. iMELD, UKELD, MELD-AS, CTP, and mCTP) in predicting the post-transplant mortality, we analyzed the data of 6,014 adult cirrhotic patients who underwent liver transplantation between January 2003 and December 2010 from the China Liver Transplant Registry database. In hepatitis B virus (HBV) group, MELD, uMELD and MELD-AS showed good predictive accuracies at 3-month mortality after liver transplantation; by comparison with other five models, MELD presented the best ability in predicting 3-month, 6-month and 1-year mortality, showing a significantly better predictive ability than UKELD and iMELD. In hepatitis C virus and Alcohol groups, the predictive ability did not differ significantly between MELD and other models. Patient survivals in different MELD categories were of statistically significant difference. Among patients with MELD score >35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one. In conclusion, MELD is superior to other score systems in predicting short-term post-transplant survival in patients with HBV-related liver disease. Among patients with MELD score >35, a new prognostic model can identify the sickest patients who should be excluded from waiting list to prevent wasteful transplantation. PMID:28198820
Noble-Jamieson, G; Valente, J; Barnes, N D; Friend, P J; Jamieson, N V; Rasmussen, A; Calne, R Y
Five children with cystic fibrosis complicated by hepatic cirrhosis received liver grafts. They all had portal hypertension with varices and three had variceal bleeding; respiratory function was only moderately impaired, but four were colonised with pseudomonas and one with aspergillus. Liver transplantation was well tolerated and there was no increase in respiratory or other early postoperative complications. Four of the children were fully well from 14 to 35 months after transplantation; the most recently transplanted had problems from a biliary stricture. In spite of the need for immunosuppression there was no increase in infection and respiratory function improved or remained stable. Once the children were stabilised after transplantation their nutrition and general health were greatly improved. PMID:7979532
Nutritional status is significantly altered in patients with end-stage liver disease (cirrhosis). Malnutrition is a common complication of cirrhosis and is known to be associated with a greater risk of post-operative complications and mortality, especially following liver transplantation. Neurological complications occur frequently after transplant and the nature and extent of these complications may relate to nutritional deficits such as protein-calorie malnutrition as well as vitamin and micronutrient deficiencies. A consensus document from the International Society on Hepatic Encephalopathy and Nitrogen metabolism (ISHEN) has been established in order to address these concerns. Careful assessment of nutritional status followed by prompt treatment of nutritional deficits has the potential to impact on transplant outcome and, in particular, on post-transplant neurological disorders in patients with cirrhosis.
Noble-Jamieson, G; Barnes, N; Jamieson, N; Friend, P; Calne, R
About 10% of children with CF develop hepatic cirrhosis and progressive portal hypertension. As the portal hypertension worsens these children are likely to develop serious variceal bleeding and other complications including malnutrition and a decline in respiratory function. Indices of lung function may fall as much as 50% in a year and chest infections may require frequent admissions to hospital. The respiratory symptoms are often attributed to CF related lung disease and affected children may therefore be considered unsuitable for liver transplantation. We propose a simple scoring system which can help to select patients who should be referred for assessment of liver transplantation. After careful assessment and preparation children with lung function indices as low as 30% predicted can have a successful outcome after liver transplantation. With good graft function portal hypertension is relieved and absorption, nutrition and respiratory function all improve. The improved quality of life of these children is remarkable. PMID:8778448
Op den Dries, Sanna; Sutton, Michael E; Lisman, Ton; Porte, Robert J
Biliary complications, especially nonanastomotic biliary strictures (NAS), are a major cause of morbidity after orthotopic liver transplantation. Of all donor and recipient characteristics known to increase the risk of developing NAS, the role of prolonged ischemia times is most extensively described in the literature. However, there is increasing evidence that several other, non-ischemia-related factors play a critical role in the pathogenesis of NAS as well. The clinical presentation of NAS may vary considerably among liver transplant recipients, including large variations in time of occurrence, and in location and severity of the strictures. Additional underlying causes such as bile salt toxicity and immune-mediated injury are believed to explain the wide spectrum of biliary strictures after orthotopic liver transplantation. Current and emerging insight in the pathogenesis of NAS and potential targets to reduce biliary injury and preserve bile ducts are discussed in this overview.
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
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.
Toker, A; Salzer, L
Allocation of medical resources, especially resources with absolute scarcity such as organs for transplant, is a difficult task. Medical, surgical, and ethical considerations should be evaluated. In solid organ transplantation, ethics committees are the gate keepers that deal with moral philosophy when moral values are in conflict. Often, no good solution to a dilemma in these medical ethics exists. Our case presents split living liver donation for retransplantation in a mentally disabled girl, with few medical ethics principles at stake.
Rodríguez-Castro, Kryssia Isabel; De Martin, Eleonora; Gambato, Martina; Lazzaro, Silvia; Villa, Erica; Burra, Patrizia
The evolution of liver diseases to end-stage liver disease or to acute hepatic failure, the evaluation process for liver transplantation, the organ allocation decision-making, as well as the post-transplant outcomes are different between female and male genders. Women’s access to liver transplantation is hampered by the use of model for end-stage liver disease (MELD) score, in which creatinine values exert a systematic bias against women due to their lower values even in the presence of variable degrees of renal dysfunction. Furthermore, even when correcting MELD score for gender-appropriate creatinine determination, a quantifiable uneven access to transplant prevails, demonstrating that other factors are also involved. While some of the differences can be explained from the epidemiological point of view, hormonal status plays an important role. Moreover, the pre-menopausal and post-menopausal stages imply profound differences in a woman’s physiology, including not only the passage from the fertile age to the non-fertile stage, but also the loss of estrogens and their potentially protective role in delaying liver fibrosis progression, amongst others. With menopause, the tendency to gain weight may contribute to the development of or worsening of pre-existing metabolic syndrome. As an increasing number of patients are transplanted for non-alcoholic steatohepatitis, and as the average age at transplant increases, clinicians must be prepared for the management of this particular condition, especially in post-menopausal women, who are at particular risk of developing metabolic complications after menopause. PMID:25540733
Cheng, Yu-Fan; Yu, Chun-Yen; Ou, Hsin-You; Tsang, Leo Leung-Chit; Huang, Tung-Liang; Chen, Tai-Yi; Concejero, Allan; Wang, Chih-Chi; Wang, Shih-Ho; Lin, Tsan-Shiun; Liu, Yueh-Wei; Yang, Chin-Hsiang; Yong, Chee-Chien; Chiu, King-Wah; Jawan, Bruno; Eng, Hock-Liew; Chen, Chao-Long
Preoperative evaluation of donors for living-donor liver transplantation aims to select a suitable donor with optimal graft quality and to ensure donor safety. Hepatic steatosis, a common finding in living liver donors, not only influences the outcome of liver transplantation for the recipient but also affects the recovery of the living donor after partial hepatectomy. Histopathologic analysis is the reference standard to detect and quantify fat in the liver, but it is invasive, and results are vulnerable to sampling error. Imaging can be repeated regularly and allows assessment of the entire liver, thus avoiding sampling error. Selection of appropriate imaging methods demands understanding of their advantages and limitations and the suitable clinical setting. This article describes potential clinical applications for liver fat quantification of imaging methods for fat detection and quantification, with an emphasis on the advantages and limitations of ultrasonography, computed tomography, and magnetic resonance imaging for quantifying liver fat.
Eguchi, S; Lilja, H; Hewitt, W R; Middleton, Y; Demetriou, A A; Rozga, J
We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased
Wen, Jessica W; Furth, Susan L; Ruebner, Rebecca L
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.
Teegen, Eva Maria; Denecke, Timm; Eisele, Robert; Lojewski, Christian; Neuhaus, Peter; Chopra, Sascha Santosh
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.
Intraoperative thromboembolism is a well-documented complication associated with orthotopic liver transplantation (OLT) but its identification and intraoperative treatment are still an emerging topic in anesthesia. Intracardiac thrombus during OLT is associated with a high mortality rate. There are only a few reports describing the successful management of thromboembolism during OLT. We describe a case where routine intraoperative transesophageal echocardiography during a live donor liver transplantation enabled early detection of an intracardiac thrombus with subsequent successful heparin treatment. Our case suggests that if an intracardiac thrombus is identified early (before hemodynamic instability occurs), the use of IV heparin may be a safe therapeutic option. PMID:28070442
Rossi, Ana P; Vella, John P
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.
Huang, Yi; MacQuillan, Gerry; Adams, Leon A; Garas, George; Collins, Megan; Nwaba, Albert; Mou, Linjun; Bulsara, Max K; Delriviere, Luc; Jeffrey, Gary P
AIM To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. RESULTS One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time (CIT) (mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance (r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver (P = 0.027). CONCLUSION Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation. PMID:27895402
Mora, N P; Turrión, V S; Pereira, F; Herrera, J; Murcia, J; Vázquez, J; De Vicente, E; Ardaiz, J
Extraction and preservation are of special interest in any liver transplant program. The viability and correct early function of the graft are determinant factors of the success or failure of the transplant. Application of a restrictive criterion in the acceptance of donor livers has allowed us to achieve an optimal viability (96.7%) in our first 60 cases of liver transplant.
Cantisani, G P C; Zanotelli, M L; Gleisner, A L M; de Mello Brandão, A; Marroni, C A
Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.
Clayton, Erica F; Malik, Saloni; Bonnel, Alexander; Mu, Yifei; Olthoff, Kim; Shaked, Abraham; Abt, Peter L; Peterman, Heather; Reddy, K. Rajender; Ottmann, Shane; Furth, Emma E; Levine, Matthew H
Background & Aims Liver transplantation has become the standard of care treatment for hepatocellular carcinoma (HCC) that falls within size and numeric criteria in cirrhotic patients. Cirrhotomimetic (CMM) hepatocellular carcinoma is an uncommon growth pattern that infiltrates cirrhotic parenchyma, can become extensive in size, and can evade detection via radiologic studies. Liver transplant outcomes for this type of HCC is not well reported but generally considered to be poor. We wished to better describe this variant of HCC in explanted livers, derive a classification system for this tumor type, and assess the outcomes of liver transplantation for this tumor variant. Methods Upon retrospective analysis of all patients transplanted at a single center for HCC in 1996–2009 (358 patients) a series of 26 patients exhibiting CMM growth pattern were identified. We developed a classification system for this tumor growth pattern variant and determined patient and tumor-specific outcomes. Results We derived a classification schema of CMM HCC based upon tumor extent and cellular histopathology with clear cell pathology being associated with favorable outcome. We note a 100% 3-year and 58.3% 5-year recurrence free survival after transplant in those with tumor confined to one lobe who have clear cell pathology versus 16.2% 3- and 5-year recurrence free survival in those who do not meet these criteria. Conclusion Cirrhotomimetic HCC features are noted in 7% of patients transplanted for HCC in our center with favorable outcomes inpatients with clear cell histology and growth involving less than 50% of the liver. PMID:24668931
Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim
Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options.
Talabiska, D G; Komar, M J; Wytock, D H; Rubin, R A
Early infectious complications within the first 3 months of orthotopic liver transplantation are common and are associated with significant morbidity and mortality. Here we report the first case of transfusion-acquired malaria in an orthotopic liver transplantation recipient. The patient was found to have Plasmodium ovale malaria during evaluation of a severe febrile illness. The infection was traced to a platelet transfusion and responded to treatment with chloroquine. Risk factors associated with the development of malaria infection are identifiable and should be reviewed from the recipient and donor when possible. Routes of infection in the liver transplant patient would include blood products, the organ itself, and resurgence of latent infection. Theoretically, immunosuppression may have an impact on the disease process. Clinicians caring for these patients need to have a high index of suspicion in order to diagnose and treat malaria effectively in the post-transplant setting. Although rare, malaria should be added to the list of pathogens that can infect organ transplant recipients.
Azzam, Ayman Zaki
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has a poor prognosis if untreated. It is ranked the third among the causes of cancer-related death. There are multiple etiologic factors that can lead to HCC. Screening for early HCC is challenging due to the lack of well specific biomarkers. However, early diagnosis through successful screening is very important to provide cure rate. Liver transplantation (LT) did not gain wide acceptance until the mid-1980s, after the effective immunosuppression with cyclosporine became available. Orthotopic LT is the best therapeutic option for early, unresectable HCC. It is limited by both, graft shortage and the need for appropriate patient selection. It provides both, the removal of tumor and the remaining cirrhotic liver. In Milan, a prospective cohort study defined restrictive selection criteria known as Milan criteria (MC) that led to superior survival for transplant patients in comparison with any other previous experience with transplantation or other options for HCC. When transplantation occurs within the established MC, the outcomes are similar to those for nonmalignant liver disease after transplantation. The shortage of organs from deceased donors has led to the problems of long waiting times and dropouts. This has led to the adoption of extended criteria by many centers. Several measures have been taken to solve these problems including prioritization of patients with HCC, use of pretransplant adjuvant treatment, and living donor LT. PMID:26052380
Douzdjian, V; Filos, D; Okorodudu, A O
Alterations in magnesium (Mg) homeostasis during and after orthotopic liver transplantation are common. The purpose of this study is to compare total Mg (TMg), calculated ionized Mg (cMg++) and measured ionized Mg (mMg++) during and immediately following liver transplantation. The newly developed first generation ion selective electrode analyzer, AVL 988-4, was used to measure mMg++ in 63 serum samples from 3 transplant recipients and 48 serum samples from 48 healthy volunteers. Analysis was divided into intraoperative (stages 1 to 3) and postoperative periods. Decreased TMg, cMg++ and mMg++ levels were observed intraoperatively and > 2 weeks postoperatively. The cMg++ levels were consistently higher than mMg++, presumably owing to the fact that the equation used for the calculation does not take complex-Mg++ into account. A better correlation was observed between mMg++ and cMg++ in the transplant group (r = 0.87 to 0.99) compared to controls (r = 0.74). The usefulness of direct measurement of Mg++ in liver transplantation remains to be determined.
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
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
Salcedo, M; Alvarez, E; Clemente, G; Bañares, R; Robles, J; Asanza, C G; Sabrido, J L; Calleja, J; Ferreiroa, J; Cos, E
A clinical case of epithelioid hemangioendothelioma without extrahepatic involvement treated with liver transplantation is presented. The patient remains alive 42 months thereafter without tumor recurrence. A review of cases reported to date was carried out with special reference being made to the therapy undertaken and the follow-up.
Braegger, C P; Belli, D C; Mentha, G; Steinmann, B
A 16-year-old girl is described with abetalipoproteinaemia who underwent liver transplantation for hepatic cirrhosis. After this procedure her serum lipoprotein profile was corrected; however, fat malabsorption and steatorrhea persisted because the primary defect, a mutant microsomal triglyceride-transfer protein, remains expressed in the intestine.
Adams, Jason Y.; Luo, Robert; Banaei, Niaz; Concepcion, Waldo; Ho, Dora Y.
We report a fatal case of disseminated Emmonsia sp. infection in a 55-year-old man who received an orthotopic liver transplant. The patient had pneumonia and fungemia, and multisystem organ failure developed. As human habitats and the number of immunocompromised patients increase, physicians must be aware of this emerging fungal infection. PMID:28098544
Andraus, Wellington; D’Alburquerque, Luiz A. C.
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
Fakhar, Nasir; Nikeghbalian, Saman; Kazemi, Kourosh; Shamsayeefar, Ali Reza; Gholami, Siavash; Kasraianfard, Amir; Malek-Hosseini, Seyed Ali
Background The current organ shortage has prompted the use of marginal organs. We conducted this retrospective study to present our experience with transplanting deceased donor livers with elevated levels of serum transaminases and to explain whether elevated levels of serum transaminases in donors affect allograft function and survival of the recipients. Methods Data of deceased donor livers and patients, who underwent liver transplantation from March 2013 to March 2015 at Shiraz center for organ transplantation, was reviewed. Liver donors with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level of more than 500 IU/l and their related recipients were considered as the case group (n = 24) and the others were considered as the control group (n = 834). Results In the case group, the medians of levels of serum AST and ALT of donors were 834 ± 425 IU/L (range: 250 - 2285) and 507 ± 367 IU/L (range: 100 - 1600), respectively. Recipients were followed for a median of 13.6 ± 9 months (range: 7 - 28.4). Post-transplant complications were acute rejection (n = 5), infection (n = 3), portal vein thrombosis (n = 3), bile duct stricture (n = 1), and hepatic artery stenosis (n = 1). The one-year survival rate of the patients was 91.7%. Demographics, post-transplant complications and one-year survival rates were not significantly different between the two study groups. Conclusions Transplanting deceased donor livers with markedly elevated liver enzymes may be an acceptable choice for expanding the donor pool. PMID:27882068
Isik, F. F.; McDonald, T. O.; Ferguson, M.; Yamanaka, E.; Gordon, D.
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
Cucchetti, Alessandro; Ross, Lainie Friedman; Thistlethwaite, J Richard; Vitale, Alessandro; Ravaioli, Matteo; Cescon, Matteo; Ercolani, Giorgio; Burra, Patrizia; Cillo, Umberto; Pinna, Antonio Daniele
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.
Houssin, D; Charpentier, B; Gugenheim, J; Baudot, P; Tamisier, D; Lang, P; Gigou, M; Bismuth, H
In several combinations of inbred rats, liver allografts are spontaneously tolerated, and after a few weeks liver tolerant rats are in a state of donor-specific transplantation tolerance. In vivo and in vitro experiments were conducted to analyze the immunological status of LEW or BN rats with spontaneously tolerated (LEW X BN) F1 liver allografts several months after transplantation. Acute rejection of secondary donor-specific heart allografts retransplanted from liver-tolerant rats to normal syngeneic hosts suggests that the state of tolerance in liver-tolerant rats is related to an active modification of the immune system of the rat and not to a reduced immunogenicity of the graft. No cytotoxic antibodies or cells were found in liver-tolerant rats. Reactivity in mixed lymphocyte culture was normal or slightly reduced. Arguments for the presence of splenic suppressor cells were found in LEW tolerant rats using a local graft-versus-host assay, but these could not be found in BN rats, or when attempting to transfer or to break the tolerance state. A nonspecific humoral blocking factor was found in vitro in liver-tolerant rats but transfer of serum from liver-tolerant rats to normal syngeneic hosts did not permit a significant prolongation of donor-specific heart allografts. These results suggest that more than one mechanism may be involved at the maintenance phase of liver allograft tolerance.
Esquivel, C O
Outcomes after liver transplantation are outstanding; however, the limiting factor is the shortage of organs. Recently, the utilization of donors after cardiac death has been encouraged; however, such transplants are associated with a high complication rate, mainly a high incidence of biliary complications, particularly ischemic cholangiopahty, a serious complication that often leads to retransplantation. The second problem is the morbidity associated with the use of immunosuppressive drugs. In this manuscript, the current status of clinical protocols for induction of tolerance is briefly discussed. Furthermore, the future of research in transplantation will involve basic scientists and clinical scholars working in concert as has been developed at Stanford School of Medicine with the creation of the Institute for Immunity, Transplantation and Infection.
Moreno González, E; García García, I; González Pinto, I; Gómez Sanz, R; Loinaz Segurola, C; Riaño Carrera, D; Bercedo Martínez, J; Pérez Cerdá, F; Ibáñez Aguirre, J; Moral Gutiérrez, P
The authors report their experience on 132 liver transplants performed on 111 patients. Eighteen have a re-transplantation and in 3 of them a second retransplantation (total re-transplanted patients 21 = 15.9%). Hepatic cirrhosis was the most common indication (57.65%) for transplantation (34.37% of alcoholic etiology). The authors report briefly their operative techniques and the results of their experience. The per-operative mortality (30 days) was 16.21% (18/111). The most important complications were: 9 hepatic arterial thromboses (6.8%), 4 arterial strictures (3.03%), 1 portal stricture (0.75%), 4 portal vein thromboses (3.03%), 5 biliary fistulae (3.78%) (3 following biliary duct-to-duct anastomosis and 2 following hepatic-jejunoanastomosis) and 2 strictures of the choledocus (1.51%). The actuarial survival rate (48 months) is 80%.
Burra, Patrizia; Rodriguez-Castro, Kryssia I
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
Chen, Hong; Wang, Xu; Fan, Tieyan; Li, Jun; Wang, Letian; Shen, Zhongyang
The present case report describes the diagnosis and treatment of a patient with veno-occlusive disease (VOD) following liver transplantation. Combining the clinical data and relevant literature, the study aimed to consider the causes of VOD following liver transplantation, and the pathogenesis, clinical diagnosis and auxiliary examination features of VOD. A 42-year-old man who had a long history of taking traditional Chinese medicine (essential components unknown) underwent an orthotropic liver transplantation on January 14, 2011, due to small venous occlusion disease of the liver. The patient was treated with tacrolimus as an antirejection therapy following the surgery, and gradually developed right upper quadrant pain and fatigue. The examination results were consistent with the diagnostic standards for VOD. Following treatment with methylprednisolone, the patient was treated with alprostadil and Danhong injections. Forty days later, the patient's total bilirubin (TBIL) level was observed to have decreased significantly, the liver function had returned to normal and the ascites had decreased, but had not completely disappeared. The patient then underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure, following which the ascites were shown to have completely disappeared.
Herden, Uta; Ganschow, Rainer; Briem-Richter, Andrea; Helmke, Knut; Nashan, Bjoern; Fischer, Lutz
Nowadays, most paediatric liver transplant recipients receive a split or other technical variant graft from adult deceased or live donors, because of a lack of available age- and size matched paediatric donors. Few data are available, especially for liver grafts obtained from very young children (<6 years). We analysed all paediatric liver transplantations between 1989 and 2009. Recipients were divided into five groups (1-5) depending on donor age (<1, ≥1 to <6, ≥6 to <16, ≥16 to <45, ≥45 years). Overall, 413 paediatric liver transplantations from deceased donors were performed; 1- and 5-year graft survival rates were 75%, 80%, 78%, 81%, 74% and 75%, 64%, 70%, 67%, 46%, and 1- and 5-year patient survival rates were 88%, 91%, 90%, 89%, 78% and 88%, 84%, 84%, 83%, 63% for groups 1-5, respectively, without significant difference. Eight children received organs from donors younger than 1 year and 45 children received organs from donors between 1 and 6 years of age. Overall, vascular complications occurred in 13.2% of patients receiving organs from donors younger than 6 years. Analysis of our data revealed that the usage of liver grafts from donors younger than 6 years is a safe procedure. The outcome was comparable with grafts from older donors with excellent graft and patient survival, even for donors younger than 1 year.
Griesemer, Adam D.; Parsons, Ronald F.; Graham, Jay A.; Emond, Jean C.; Samstein, Benjamin
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
The referral of a patient with cirrhosis to a liver transplant center for evaluation is usually made by a local gastroenterologist. The role of the referring gastroenterologist begins with early identification and modification of high-risk behaviors, which may delay listing a patient for liver transplantation. The local gastroenterologist must also fully appreciate what constitutes a timely referral of a patient to a liver transplant center and the consequences of late referral. Although patients experience the inevitable deterioration of their liver function, which in turn advances their priority on the liver transplant waiting list, the referring gastroenterologist must also anticipate medical complications of cirrhosis, and should initiate appropriate surveillance and prophylaxis programs to detect and prevent these complications. Finally, the referring gastroenterologist constitutes a vital link of information between the patient and the transplant center. Adherence to these guidelines will increase the probability that a patient with chronic liver failure will undergo successful liver transplantation and will decrease post-transplant morbidity.
Jung, Dong-Hwan; Song, Gi-Won; Ha, Tae-Yong; Jwa, Eun-Kyeong; Lee, Sung-Gyu
Portal hypertension induces congestion of the liver and spleen, thus any capsular or parenchymal injury to these organs can produce intractable bleeding which generally is not easily controlled. To cope with intractable bleeding such as being encountered during liver transplantation, we developed an infiltrating hemostasis technique as a conceptual shift from conventional application methods, in which fibrin glue is locally injected into the bleeding area on the liver or spleen. This technique, which uses a fibrin glue kit (2 ml kit; Greenplast, Green Cross, Seoul, Korea), consists of inserting the needle 0.5-1 cm deep at the bleeding point, forcefully injecting 1 ml of fibrin glue contained in the fibrin glue kit, and then slowly withdrawing the needle with continuous forceful injection of the remaining 1 ml of fibrin glue. We have successfully performed this procedure in 6 cases of living donor liver transplantation and in 2 cases of non-transplant resection of the cirrhotic livers with hepatocellular carcinoma. This technique was also successfully applied to one liver transplant recipient in which intractable bleeding occurred from a small laceration at the spleen. Our fibrin glue-infiltrating hemostasis would be indicated to intractable bleeding from the hepatic or splenic cut surface. In such a situation, it would be applicable as a second-line rescue method for hemostasis. PMID:28261700
Hwang, Shin; Jung, Dong-Hwan; Song, Gi-Won; Ha, Tae-Yong; Jwa, Eun-Kyeong; Lee, Sung-Gyu
Portal hypertension induces congestion of the liver and spleen, thus any capsular or parenchymal injury to these organs can produce intractable bleeding which generally is not easily controlled. To cope with intractable bleeding such as being encountered during liver transplantation, we developed an infiltrating hemostasis technique as a conceptual shift from conventional application methods, in which fibrin glue is locally injected into the bleeding area on the liver or spleen. This technique, which uses a fibrin glue kit (2 ml kit; Greenplast, Green Cross, Seoul, Korea), consists of inserting the needle 0.5-1 cm deep at the bleeding point, forcefully injecting 1 ml of fibrin glue contained in the fibrin glue kit, and then slowly withdrawing the needle with continuous forceful injection of the remaining 1 ml of fibrin glue. We have successfully performed this procedure in 6 cases of living donor liver transplantation and in 2 cases of non-transplant resection of the cirrhotic livers with hepatocellular carcinoma. This technique was also successfully applied to one liver transplant recipient in which intractable bleeding occurred from a small laceration at the spleen. Our fibrin glue-infiltrating hemostasis would be indicated to intractable bleeding from the hepatic or splenic cut surface. In such a situation, it would be applicable as a second-line rescue method for hemostasis.
Pillai, Vinod G; Chen, Chao-Long
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.
Barnard, Abbey; Konyn, Peter
Improved short- and long-term survival of liver transplant recipients has led to increased focus on complications of both the early and late posttransplant periods. A variety of metabolic complications have been observed in the post–orthotopic liver transplant population, including hypertension, hyperlipidemia, obesity, diabetes mellitus, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis. Although only a small proportion of patients experience metabolic complications prior to transplantation, the prevalence of these complications posttransplantation reaches or exceeds that of the general population. This is of particular concern, as cardiovascular disease is the second leading cause of death in the late transplant period. A number of mechanisms mediate these metabolic complications, including reversal of cirrhosis pathophysiology, patient lifestyle factors, and immunosuppressive medications. Titration and modification of immunosuppression have been demonstrated to improve and sometimes even eliminate these conditions. Therefore, given the multiple etiologies contributing to the metabolic derangements, an effective management approach must incorporate lifestyle modifications, immunosuppression titration, and medical management. Best practices and understanding of the mechanisms underlying these complications allow for discussion of initial therapies and strategies; however, further study is necessary to determine the optimal management of metabolic complications over time. PMID:27917074
Vogels, B A; Maas, M A; Bosma, A; Chamuleau, R A
The effect of intrasplenic hepatocyte transplantation (HTX) was studied in an experimental model of acute liver failure in rats with chronic liver atrophy. Rats underwent a portacaval shunt operation on Day -14 to induce liver atrophy, and underwent total hepatectomy on Day 0 as a start of acute liver failure. Intrasplenic hepatocyte or sham transplantation was performed on Day -7,-3, or -1 (n = 4 to 6 per group). During the period following hepatectomy, mean arterial blood pressure was maintained above 80 mm Hg and hypoglycaemia was prevented. Severity of hepatic encephalopathy was assessed by clinical grading and EEG spectral analysis, together with determination of blood ammonia and plasma amino acid concentrations, and "survival" time. Histological examination of the spleen and lungs was performed after sacrifice. Intrasplenic hepatocyte transplantation resulted in a significant improvement in clinical grading in all transplanted groups (p < 0.05), whereas a significant improvement in EEG left index was seen only in the group with transplantation on Day -1 (p < 0.05). In contrast to hepatocyte transplantation 1 day before total hepatectomy, rats with hepatocyte transplantation 3 and 7 days before total hepatectomy showed a significant 3- and 2-fold increase in "survival" time compared to sham transplanted controls: HTX at Day -1: 7.5 +/- 0.3 h vs. 5.9 +/- 0.6 h (p > 0.05), HTX at Day -3: 19.7 +/- 3.7 h vs. 6.5 +/- 0.3 h (p < 0.05), and HTX at Day -7: 13.8 +/- 3.2 h vs. 6.3 +/- 0.3 h (p < 0.05). Furthermore, rats with hepatocyte transplantation on Day -3 and -7 showed significantly lower blood ammonia concentrations after total hepatectomy (p < 0.0001). Histological examination of the spleens after sacrifice showed clusters of hepatocytes in the red pulp. Hepatocytes present in the spleen for 3 and 7 days showed bile accumulation and spots of beginning necrosis. The present data show that in a hard model of complete liver failure in portacaval shunted rats
Cárdenas, Andrés; Crespo, Gonzalo; Balderramo, Domingo; Bordas, Josep P; Sendino, Oriol; Llach, Josep
Endoscopic Retrograde Cholangiopancreatography (ERCP) is commonly performed in patients after liver transplantation. The most common indications for ERCP include treatment of bile leaks and anastomotic and nonanastomotic biliary strictures. In this report we describe an unusual complication of ERCP in a liver transplant recipient with a bile leak two months after orthotopic liver transplantation (OLT). After confirming a bile leak, a hydrophilic guide wire was placed in the intrahepatic duct, an endoscopic sphincterotomy was performed, and a biliary plastic stent was successfully placed over the wire across the bile leak. Within the following 24 hours the patient developed a sharp right-sided upper quadrant pain and a drop in his hemoglobin level. An abdominal CT scan demonstrated a subcapsular hepatic hematoma that was successfully managed conservatively.
Zhou, Jian; Ju, Weiqiang; Yuan, Xiaopeng; Jiao, Xingyuan; Zhu, Xiaofeng; Wang, Dongping; He, Xiaoshun
Effect of ABO-incompatible liver transplantation on patients with severe hepatitis B (SHB) remains unclear. Herein, we summarized 22 cases with SHB in whom were performed emergency liver transplantation from ABO-incompatible donors. The immunosuppressive protocol consisted basiliximab, tacrolimus, steroids and mycophenolate mofetil. The mean MELD score was 35.2 ± 7.1. Major complications included rejection, infections, biliary complications, hepatic artery thrombosis or stenosis and portal vein thrombosis. Patient survival rates were 40.9%, 78.9% and 82.3% in 1 year, 29.2%, 66.8% and 72.9% in 3 years, and 21.9%, 60.1% and 62.5% in 5 years for ABO-incompatible, ABO-compatible and ABO-identical groups. Graft survival rates were 39%, 78.9% and 82.3% in 1 year, 27.8%, 66.4% and 71.1% in 3 years, and 20.9%, 57.9% and 61.0% in 5 years for incompatible, compatible and identical ABO graft-recipient match. The 1-, 3-, 5-year graft and patient survival rates of ABO-incompatible were distinctly lower than that of ABO-compatible group (P < 0.05). Our results suggested that ABO-incompatible liver transplantation might be a life-saving procedure for patients with SHB as a promising alternative operation when ABO-compatible donors are not available and at least bridges the second opportunity for liver retransplantation.
Stirkat, Falk; Croner, Roland S.; Vassos, Nikolaos; Raptis, Dimitrios; Yedibela, Süleyman; Hohenberger, Werner; Müller, Volker
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
Polat, K Y; Tosun, M S; Ertekin, V; Aydinli, B; Emre, S
Brucellosis is considered the most widespread zoonosis in the world. It has been reported that the prevalence of seropositivity among the Turkish population varies from 3% to 14%. We present a case of brucellosis after pediatric liver transplantation. A 15-year-old boy with the diagnosis of neuro Wilson's disease underwent deceased-donor liver transplantation. The postoperative immunosuppressive protocol consisted of steroids and tacrolimus. Two months after the operation the patient experienced fever to 40°C. The patient complained of poor appetite, headache, and diarrhea. He had had pancytopenia. Despite administration of appropriate antibiotics, antiviral and antifungal agents, fever persisted for > 1 month. Multiple blood, urine, stool, and sputum cultures were negative. Bone marrow aspirate revealed hypocellularity. Liver biopsy was performed, but rejection was not observed on biopsy specimen. Brucella serology was positive and Brucella agglutination titer was 1:320. Bone marrow culture was positive for Brucella but blood culture was negative. The patient was then treated with oral doxycycline and rifampin for 8 weeks. No previous case report about Brucella infection after liver transplantation has appeared in the literature, to our knowledge; our case is presented as the first. Bone marrow hypoplasia is a rare feature of Brucella infection. Our patient with brucellosis and pancytopenia had had hypocellular bone marrow. The clinical and hematologic findings resolved with treatment of the infection. Brucella infection should be suspected in liver transplanted recipients with fever of unknown origin, especially in a recipient who has lived in an endemic area. Brucella also should be considered as a possible diagnosis in patients with pancytopenia.
Manas, Derek; Burnapp, Lisa; Andrews, Peter Antony
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.
Baskin, E; Ozçay, F; Sakalli, H; Agras, P I; Karakayali, H; Canan, O; Haberal, M
An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty-six children (9 girls, 17 boys; mean age, 7.66 +/- 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilson's disease in one, and alpha-1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 +/- 3.49 yr, which was significantly lower than in those without UTI (9.75 +/- 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60
Woodle, E.S.; Ward, R.E.; Vera, D.R.; Stadalnik, R.C.
Tc-NGA is a new liver imaging agent which binds to hepatic binding protein (HBP), a hepatocyte-specific membrane receptor. The purpose of the present study was to evaluate the potential role of Tc-NGA imaging in liver transplantation. The molar Tc-NGA dose was standardized according to patient weight (0.7 nmole/kg). After a 30 minute dynamic imaging study (5 mCi, IV), kinetic analysis of time activity data (heart, liver), provided values for receptor concentration, (HBP), and hepatic blood flow, Q. Eleven Tc-NGA imaging studies were performed in transplant candidates and 22 studies were performed in seven transplant recipients. Preservation damage was manifested by diffuse patchiness in tracer distribution which resolved during the following two weeks. Histologically proven, localized hepatic infarcts were demonstrated in three recipients. Lobar infarction was demonstrated in one recipient. Hepatic regeneration was later demonstrated in this patient after hepatic lobectomy. Hepatic blood flow was markedly decreased in the early postoperative period, but improved with time. Increased (HBP) was demonstrated with regeneration. Markedly decreased (HBP) and Q were obtained in several candidates who died awaiting transplantation. These studies indicate that TC-NGA liver imaging provides a valuable new means for: (1) evaluation of preservation damage, (2) early demonstration of hepatic infarction, (3) evaluation of hepatic rejection, and (4) selection of patients for hepatic transplantation.
Vennarecci, Giovanni; Miglioresi, Lucia; Guglielmo, Nicola; Pelle, Fabio; Santoro, Roberto; Andreuccetti, Jacopo; Ceribelli, Cecilia; Stella, Pietro; Angelo, Corrado; Ettorre, Giuseppe Maria
We report the first case of a liver transplant in a patient with epidermolysis bullosa acquisita and associated hepatitis B virus-hepatitis D virus cirrhosis and its inherent technical issues. Epidermolysis bullosa acquisita is an autoimmune multisystem disorder involving skin and mucosa characterized by the appearing of blisters and erosions. The more severe forms may result in nutritional compromise, anemia, osteopenia, dilated cardiomyopathy, laryngeal mucosal involvement, esophageal strictures, bladder, and kidney involvement requiring surgical intervention. Epidermolysis bullosa acquisita has become recognized as a multisystem disorder that poses several surgical challenges. This case shows that liver transplant is a feasible procedure in patients affected by epidermolysis bullosa acquisita. Patients with epidermolysis bullosa acquisita require a particular pretransplant assessment and a dedicated intra- and postoperative management of every invasive procedure that can traumatize the skin and mucosal epithelium to achieve an uneventful liver transplant. Epidermolysis bullosa acquisita does not represent a contraindication to liver transplant, and immunosuppression after transplant may favor a good systemic control of this immunologic disorder.
Mehl, Ashley; Bohorquez, Humberto; Serrano, Maria-Stella; Galliano, Gretchen; Reichman, Trevor W
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
Mehl, Ashley; Bohorquez, Humberto; Serrano, Maria-Stella; Galliano, Gretchen; Reichman, Trevor W
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.
Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro
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
Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando
We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.
Pirenne, Jacques; Deloose, Koen; Coosemans, Willy; Aerts, Raymond; Van Gelder, Frank; Kuypers, Dirk; Maes, Bart; Verslype, Chris; Yap, Paul; Van Steenbergen, Werner; Roskams, Tania; Mathieu, Chantal; Fevery, Johan; Nevens, Frederik
Liver disease alters the glucose metabolism and may cause diabetes, but this condition is potentially reversible with liver transplantation (LTx). Type 1 diabetes mellitus may be coincidentally present in a LTx candidate and immunosuppressive drugs will aggravate diabetes and make its management more difficult for posttransplant. In addition, diabetes negatively influences outcome after LTx. Therefore, the question arises as to why not transplanting the pancreas in addition to the liver in selected patients suffering from both liver disease and Type 1 diabetes. We report two cases of en bloc combined liver and pancreatic transplantation, a technique originally described a decade ago in the treatment of upper abdominal malignancies but rarely used for the treatment of combined liver disease and Type 1 diabetes. Both recipients are currently liver disease-free and insulin-free more than 2 and 4 years posttransplant, respectively. Surgical, medical and immunological aspects of combined liver-pancreas transplantation are discussed in the light of the existing relevant literature.
Shirota, Tomoki; Ikegami, Toshihiko; Sugiyama, Satoshi; Kubota, Kouji; Shimizu, Akira; Ohno, Yasunari; Mita, Atsuyoshi; Urata, Koichi; Nakazawa, Yuichi; Kobayashi, Akira; Iwaya, Mai; Miyagawa, Shinichi
A 20-year-old woman was admitted to an emergency hospital after ingesting 66 g of acetylsalicylic acid in a suicide attempt. Although she was treated with gastric lavage, oral activated charcoal, and intravenous hydration with sodium bicarbonate, her hepatic and renal function gradually deteriorated and serum amylase levels increased. Steroid pulse therapy, plasma exchange, and continuous hemodiafiltration did not yield any improvement in her hepatic or renal function, and she was transferred to our hospital for living donor liver transplantation. Nine days after drug ingestion, she developed hepatic encephalopathy: thus, we diagnosed the patient with acute liver failure with hepatic coma accompanied by acute pancreatitis due to the overdose of acetylsalicylic acid. Living donor liver transplantation was immediately performed using a left lobe graft from the patient's mother. Following transplantation, the patient's renal and hepatic function and consciousness improved, and she was discharged. In this report, we describe a rare case of acetylsalicylic acid-induced acute liver failure with acute hepatic coma and concomitant acute pancreatitis and acute renal failure, which were treated successfully with emergency living donor liver transplantation.
Carvalho, Andreia; Rocha, Ana; Lobato, Luísa
Hereditary transthyretin amyloidosis (ATTR) is a rare worldwide autosomal dominant disease caused by the systemic deposition of an amyloidogenic variant of transthyretin (TTR), which is usually derived from a single amino acid substitution in the TTR gene. More than 100 mutations have been described, with V30M being the most prevalent. Each variant has a different involvement, although peripheral neuropathy and cardiomyopathy are the most common. Orthotopic liver transplantation (OLT) was implemented as the inaugural disease-modifying therapy because the liver produces the circulating unstable TTR. In this review, we focus on the results and long-term outcomes of OLT for ATTR after more than 2063 procedures and 23 years of experience. After successful OLT, neuropathy and organ impairment are not usually reversed, and in some cases, the disease progresses. The overall 5-year survival rate is approximately 100% for V30M patients and 59% for non-ATTR V30M patients. Cardiac-related death and septicemia are the main causes of mortality. Lower survival is related to malnutrition, a longer duration of disease, cardiomyopathy, and a later onset (particularly for males). Deposits, which are composed of a mixture of truncated and full-length TTR (type A) fibrils, have been associated with posttransplant myocardial dysfunction. A higher incidence of early hepatic artery thrombosis of the graft has also been documented for these patients. Liver-kidney/heart transplantation is an alternative for patients with advanced renal disease or heart failure. The sequential procedure, in which ATTR livers are reused in patients with liver disease, reveals that neuropathy in the recipient may appear as soon as 6 years after OLT, and ATTR deposits may appear even earlier. Long-term results of trials with amyloid protein stabilizers or disrupters, silencing RNA, and antisense oligonucleotides will highlight the value and limitations of liver transplantation.
Doblecki-Lewis, S; Palaios, E; Bejarano, P A; Tzakis, A G; Selvaggi, G; Morris, M I
Gas gangrene is a rare and devastating infectious process that can occur after liver transplantation, most often following hepatic artery thrombosis. We here report 3 cases of gas gangrene following orthotopic liver transplantation. Blood cultures were positive for Clostridium clostridiiforme in one case. In 2 other cases liver tissue from explanted specimens was positive for Enterobacter cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed tomography imaging revealed diffuse liver necrosis with gas formation in each case. All 3 patients were successfully treated with a combination of antibiotics and emergent re-transplantation. We review previously published cases of gas gangrene after liver transplant and emphasize the importance of hepatic artery thrombosis in the development of this syndrome as well as the frequent involvement of non-clostridial organisms. Early diagnosis and aggressive combined medical and surgical treatment including re-transplantation are essential for successful treatment of these rare and catastrophic infections.
Lim, Tiong Y; Considine, Aisling; Quaglia, Alberto; Shawcross, Debbie L
The use of herbal medications is increasing significantly in the UK and there is a perception that herbal preparations are without adverse effects. This case report highlights the potential risks of black cohosh, which is one of the most commonly used herbal products. This is a case report of a 60-year-old Caucasian lady who presented with subacute liver failure secondary to taking black cohosh. This was further confirmed by liver biopsy and she subsequently deteriorated and underwent liver transplantation. Available evidence supports an association between black cohosh and risk of hepatotoxicity. In current literature, there have only been four previously reported cases of hepatotoxicity associated with black cohosh, which required liver transplantation. We submit that our patient represents the fifth case. We recommend that patients taking this supplement should have close monitoring of their hepatic function, especially in the presence of other risk factors. PMID:23833086
Suraweera, Duminda; Sundaram, Vinay
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
Ascha, Mustafa S; Ascha, Mona L; Hanouneh, Ibrahim A
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
Ramos, Hector C.; Todo, Satoru; Kang, Yoogoo; Felekouras, Evangelos; Doyle, Howard R.; Starzl, Thomas E.
Objectives To examine the techniques and the outcome of liver transplantation with maximal conservation of blood products and to analyze the potential benefits or drawbacks of blood conservation and salvage techniques. Design Case series survey. Setting Tertiary care, major university teaching hospital. Patients and Methods Four patients with religious objections to blood transfusions who were selected on the basis of restrictive criteria that would lower their risk for fatal hemorrhage, including coagulopathy, a thrombosed splanchnic venous system requiring extensive reconstruction, active bleeding, and associated medical complications. All patients were pretreated with erythropoietin to increase production of red blood cells. All operations were performed at the same institution, with a 36-month follow-up. Interventions Orthotopic liver transplantation that used blood salvage, plateletpheresis, and autotransfusion and the withholding of the use of human blood products with the exception of albumin. Main Outcome Measures Survival and postoperative complications, with the effectiveness of erythropoietin and plateletpheresis as secondary measures. Results All patients are alive at 36 months after orthotopic liver transplantation. One patient, a minor (13 years of age), was transfused per a state court ruling. Erythropoietin increased the production of red blood cells as shown by a mean increase in hematocrit levels of 0.08. Plateletpheresis allowed autologous, platelet-rich plasma to be available for use after allograft reperfusion. Three major complications were resolved or corrected without sequelae. Only one patient developed postoperative hemorrhage, which was corrected surgically. The mean charge for bloodless surgery was $174 000 for the three patients with United Network for Organ Sharing (UNOS) status 3 priority for transplantation. This result was statistically significant when these patients were compared with all the patients with UNOS status 3 priority
Alsina, Angel E.; Franco, Edson; Nakshabandi, Ahmad; Albers, Christopher; Kemmer, Nyingi; Finan, Jon
Fibrolamellar hepatocellular carcinoma is a rare hepatocellular tumor usually arising in noninfected and noncirrhotic livers. Only 2 cases accompanied by hyperammonemia due to intrahepatic shunting have been reported. A 23-year-old white woman presented with a 2-week history of nausea, vomiting, generalized weakness, and intermittent right upper quadrant pain. Abdominal computerized tomography revealed a 13 x 9-cm hepatic mass. Core-needle biopsy revealed fibrolamellar hepatocellular carcinoma. She presented with coma due to hyperammonemia levels (peak at 437 mcg/dL) but without metastatic disease. She was urgently transplanted, started on daily sorafenib 8 weeks after transplantation, and was free of disease at 1 year after transplantation. PMID:27807568
Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen
Background De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. Aims To describe the overall pattern of de novo cancers in liver transplant recipients. Methods Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Results Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. Conclusions De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention. PMID:27171501
Ikegami, Toshihiko; Masuda, Yuichi; Ohno, Yasunari; Mita, Atsushi; Kobayashi, Akira; Urata, Koichi; Nakazawa, Yuichi; Miwa, Shirou; Hashikura, Yasuhiko; Miyagawa, Shinichi
We have previously reported that a graft volume (GV) > 30% of the recipient's standard liver volume (SLV) can meet the recipient's metabolic demands. Here we report our experience with adult-to-adult living donor liver transplantation using left side grafts < 35% of the recipient's SLV. Of 143 adult living donor liver transplants, 13 auxiliary partial orthotopic liver transplants, 8 right side grafts, and 2 retransplantation cases were excluded. The resulting 120 cases were divided into 2 groups: group S consisted of 33 patients who received liver grafts < 35% of their SLV, and group L consisted of 87 patients who received liver grafts > or = 35% of their SLV. Patient characteristics, postoperative liver function, duration of hospital stay, and recipient survival rates were compared between the 2 groups. There were no significant differences between groups in recipient or donor background characteristics. The mean GV/SLV ratio of group S was 31.8%, whereas that of group L was 42.5%. There were no significant differences in the postoperative serum total bilirubin levels, prothrombin time international normalized ratio, daily ascites volume, or duration of postoperative hospital stay between the groups. The 1- and 5-year survival rates in group S were 80.7% and 64.2%, respectively, whereas those of group L were 90.8% and 84.9%, respectively, with no significant difference between groups. In conclusion, graft size was not considered to be the only cause of so-called small-for-size graft syndrome, and left side grafting appears to be the procedure of choice for adult-to-adult living donor liver transplantation because of the lower risk to donors in comparison with right lobe grafting.
Finch, Christopher K; Eason, James; Usery, Justin B
A 41-year-old male with a previous orthotopic liver transplant began experiencing insomnia, anxiety, diaphoresis, headaches, and palpitations that progressed over a 2-day period. As part of his home medication regimen, the patient was taking gabapentin for peripheral neuropathy. His acute onset of increasing symptoms coincided with an inadvertent discontinuation of gabapentin. After reinitiation of gabapentin therapy, the symptoms slowly improved over the next 24 hours and the episode of gabapentin withdrawal syndrome resolved.
Prigent, Gwénolé; Aït-Ammar, Nawel; Levesque, Eric; Fekkar, Arnaud; Costa, Jean-Marc; El Anbassi, Sarra; Foulet, Françoise; Duvoux, Christophe; Merle, Jean-Claude
ABSTRACT Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in Candida spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of Candida isolates to echinocandins were tested by Etest and the EUCAST reference method. Isolates were analyzed by FKS sequencing and genotyped based on microsatellites or multilocus sequence typing (MLST) profiles. Ninety-four patients were included, and 39 patients were colonized or infected and treated with echinocandin. Echinocandin resistance appeared in 3 (8%) of the treated patients within 1 month of treatment. One patient was colonized by resistant Candida glabrata, one by resistant Candida dubliniensis, and one by resistant Candida albicans. Molecular analysis found three mutations in FKS2 HS1 (F659S, S663A, and D666E) for C. glabrata and one mutation in FKS1 HS1 (S645P) for C. dubliniensis and C. albicans. Susceptible and resistant isolates belonged to the same genotype. To our knowledge, this is the first study on echinocandin resistance in Candida spp. in a liver transplant population. Most resistant isolates were found around/in digestive sites, perhaps due to lower diffusion of echinocandin in these sites. This work documents the risk of emergence of resistance to echinocandin, even after short-term treatment. PMID:27855078
Kusne, S; Dummer, J S; Singh, N; Iwatsuki, S; Makowka, L; Esquivel, C; Tzakis, A G; Starzl, T E; Ho, M
We studied infections in 101 consecutive patients who underwent liver transplantation between July 1984 and September 1985. The mean length of follow-up was 394 days. Eighty-three percent of population had 1 or more episodes of infection and 67% of the population had severe infections. The overall mortality was 26/101 (26%) and 23 of 26 deaths (88%) were associated with infection. Seventy percent of severe infections occurred in the first 2 months after transplantation. The most frequent severe infections were abdominal abscess, bacterial pneumonia, invasive candidiasis, Pneumocystis pneumonia, and symptomatic cytomegalovirus infection. Patients with more than 12 hours of cumulative surgical time had a higher rate of severe infections (P less than 0.001), particularly fungal (P less than 0.001) and bacterial (P less than 0.01) infections. Also, the use of choledocho-jejunostomy was associated with a higher rate of infection in patients who had more than 1 transplant operation (P less than 0.02). No increase in infection was found in patients who received azathioprine, or more than the median number of steroid boluses or "recycles"; but patients who received OKT3 therapy had a higher rate of protozoal infections (P less than 0.05). A result similar to that of our previous studies was a strong relation between the number of severe fungal infections and prolonged courses of antibiotics after transplant operation (P less than 0.001). Pretransplant manifestations of severe liver disease such as ascites, encephalopathy, and gastrointestinal bleeding were not associated with higher rates of infection after transplantation, but high serum levels of ALT were. Patients with lower ratios of T-helper to T-suppressor lymphocytes had more severe viral (P less than 0.02) and fungal (P less than 0.01) infections after transplantation.
Liver transplantation (LT) for hepatocellular carcinoma (HCC) at Kaohsiung Chang Gung Memorial Hospital mainly relies on live donor LT (LDLT). Owing to taking the risk of LD, we are obligated to adopt strict selection criteria for HCC patients and optimize the pre-transplant conditions to ensure a high disease-free survival similar to those without HCC, even better than deceased donor LT (DDLT). Better outcomes are attributed to excellent surgical results and optimal patient selection. The hospital mortality of primary and salvage LDLT are lower than 2% in our center. Although Taiwan Health Insurance Policy extended the Milan to University of California, San Francisco (UCSF) criteria in 2006, selection criteria will not be consolidated to take into account only by the morphologic size/number of tumors but also by their biology. The criteria are divided into modifiable image morphology, alpha fetoprotein (AFP), and positron emission tomography (PET) scan with standard uptake value (SUV) and unmodifiable unfavorable pathology such as HCC combined with cholangiocarcinoma (CC), sarcomatoid type, and poor differentiation. Downstaging therapy is necessary for HCC patients beyond criteria to fit all modifiable standards. The upper limit of downstaging treatment seems to be extended by more effective drug eluting transarterial chemoembolization in cases without absolute contraindications. In contrast, the pitfall of unmodifiable tumor pathology should be excluded by the findings of pretransplant core biopsy/resection if possible. More recently, achieving complete tumor necrosis in explanted liver could almost predict no recurrence after transplant. Necrotizing therapy is advised if possible before transplant even the tumor status within criteria to minimize the possibility of tumor recurrence. LDLT with low surgical mortality in experienced centers provides the opportunities of optimizing the pre-transplant tumor conditions and timing of transplant to achieve better
Muder, Robert R; Agarwala, Sangeeta; Mirani, Aja; Gayowski, Timothy; Venkataramanan, Raman
The authors evaluated the pharmacokinetics of cefoperazone and sulbactam in 9 liver transplant patients. Cefoperazone and sulbactam were administered as an intravenous infusion over 30 minutes every 12 hours for six doses, and multiple blood samples were collected immediately after the first dose (administered during the surgery) and after the last dose. The concentrations of cefoperazone and sulbactam in serum and, when possible, in urine and bile collected over one dosing interval were measured by high-pressure liquid chromatography. The concentration of cefaperazone ranged from 436 to 4118 microg/ml, and sulbactam ranged from 3.3 to 8.7 microg/ml in the bile samples. The intraoperative clearance of cefoperazone (0.53+/-0.18 ml/min/kg) was significantly higher than the postoperative clearance (0.21+/-0.23 ml/min/kg). The half-life of cefaperazone, although not statistically significantly different, was prolonged in all patients during the postoperative period. The clearance of sulbactam (1.51+/-0.51 ml/min/kg) was lower than what is reported in patients with normal renal function but was comparable to what has been reported in patients with renal impairment and in critically ill patients. There were no significant differences in any of the pharmacokinetic parameters of sulbactam during and after surgery. The pharmacokinetic parameters of cefoperazone and sulbactam were significantly altered in liver transplant patients compared to what has been reported in normal subjects but were similar to what has been reported in patients with liver and renal impairment. There was a significant impairment in the biliary excretion of cefoperazone during the postoperative period in liver transplant patients. Although the percentage of the dose of cefoperazone excreted in the bile was drastically reduced, the biliary concentrations were generally high and above the MIC for most organisms. Given that both renal and hepatic elimination of cefoperazone is decreased, leading to a
Aggarwal, Shushma; Bane, Brian C; Boucek, Charles D; Planinsic, Raymond M; Lutz, John W; Metro, David G
Anesthesia for liver transplantation (ALT) requires extensive preparation and rapid recognition of changing clinical conditions. Owing to the proliferation of transplant centers, greater number of anesthesia providers need training in specific skills required to treat these patients. These cases are no longer limited to few transplant centers; therefore, reduction of cases in individual centers has created a need for simulation training to prepare and supplement clinical experience. We have developed an ALT simulation course for senior anesthesia residents which combines didactic sessions with live-patient-based and mannequin-based simulation. Outcomes have been measured using pre- and post-simulation course quizzes as well as a survey given at the end of the month-long ALT rotation. Twenty-four senior anesthesiology residents (n = 24) have completed the ALT simulation course. Residents had an average score of 75% ± 10% on the pre-simulation quiz, which increased to 92% ± 6.5% on the post-simulation quiz (p < 0.001). Furthermore, survey scores indicated that residents noted that the course provided an improvement in their preparedness, confidence, anticipation, and understanding of the importance of communication skills in the care of this patient population. The ALT simulation course provided a standardized in-depth exposure to clinical issues involved in the perioperative care of liver transplant patients.
Yoo, Hwan Y; Galabova, Violetta; Edwin, David; Thuluvath, Paul J
The outcome of liver transplantation is dependent on many factors. It was suggested that racial disparities in outcome may be related to differences in socioeconomic status (SES). In this retrospective study, we analyzed the effect of SES on graft and patient survival. Two hundred seventy-six adult patients who underwent liver transplantation at our institution from July 1988 to June 2001 were included in the analysis. Educational and occupation statuses were coded using established criteria (Hollingshead Index of Social Status [HI]). SES then was calculated using the HI formula: SES = education level x 3 + occupation x 5, and categorized into four groups: group 1, score less than 29 (n = 71); group 2, score of 29 to 42 (n = 82); group 3, score of 42 to 53 (n = 69); and group 4, score greater than 53 (n = 54). Kaplan-Meier analysis was used for graft and patient survival, and Cox regression analysis was used to determine the effect of confounding factors. Demographics of all four groups were similar. One-, 2-, and 5-year graft and patient survival did not differ significantly across groups by Kaplan-Meier and Cox regression survival analysis. In conclusion, SES did not predict graft and patient survival after liver transplantation.
Yang, Po-Chih; Ho, Cheng-Maw; Hu, Rey-Heng; Ho, Ming-Chih; Wu, Yao-Ming; Lee, Po-Huang
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. Radical treatment of HCC in early stages results in a long disease-free period and improved overall survival. The choice of optimal management strategy for HCC mainly depends on the severity of the underlying liver disease. For patients with decompensated liver cirrhosis and HCC within Milan criteria (MC), liver transplant (LT) is the choice of treatment. However, for patients with good residual liver reserve and HCC within MC, selection of other curative treatments such as liver resection (LR) or radiofrequency ablation may be a reasonable alternative. For patients without cirrhosis, LR can result in an overall survival similar to that provided by LT. Therefore, it is an accepted alternative to LT especially in areas with organ shortage. However, the cumulative 5-year recurrence rate of HCC post LR might be as high as 70%. For initial transplant-eligible (within MC) patients with recurrent HCC post LR, salvage liver transplant (SLT) was first proposed in 2000. However, most patients with recurrent HCC considered for SLT are untransplantable cases due to HCC recurrence beyond MC or comorbidity. Thus, the strategy of opting for SLT results in the loss of the opportunity of LT for these patients. Some authors proposed the concept of “de principe liver transplant” (i.e., prophylactic LT before HCC recurrence) to prevent losing the chance of LT for these potential candidates. Factors associated with the failure of SLT will be dissected and discussed in three parts: Patient, tumor, and underlying liver disease. Regarding patient-related factors, the rate of transplantability depends on patient compliance. Patients without regular follow-up tend to develop HCC recurrence beyond MC at the time of tumor detection. Advancing age is another factor related to severe comorbidities when LT is considered for HCC recurrence, and these elderly candidates become ineligible as
Taner, Timucin; Park, Walter D; Stegall, Mark D
Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms.
Anand, Anil C
Treatment of hepatitis C virus (HCV) with newer directly acting antivirals (DAAs) and lead to sustained viral response (SVR) in majority of patients and SVR has been documented to be associated with reversal of liver cirrhosis. The improved SVR rates and safety profiles of DAAs have led to the treatment of patients with decompensated cirrhosis awaiting liver transplantation (LT). Several clinical trials of DAAs in decompensated HCV patients have recently demonstrated SVR rates above 80%, which have been associated with significant improvements, in the Child-Pugh-Turcotte scores/or model for end-stage liver disease scores in a proportion of patients. Moreover, it has been shown that HCV RNA becomes negative after 2-4 weeks of treatment, and those who are transplanted after becoming HCV RNA negative will be have very low the risk of HCV recurrence after transplantation. Some of the patients may have reached the "point of no return" and may proceed to worsening of decomposition over time. To avoid the risk of worsening, there is an additional option of treating these patients after LT should they develop recurrent HCV infection. Currently there are no guidelines as to select patients who would benefit from treatment prior to LT as opposed to those who will be better off being treated after the transplant surgery. The article discusses a possible approach for such selection.
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
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.
Zhang, Bo; Liu, Qiu-Hua; Zhou, Cui-Jie; Hu, Ming-Zheng; Qian, Hai-Xin
Ischemia/reperfusion (I/R) injury can occur during small-for-size liver transplantation, resulting in delayed graft function and decreased long-term graft survival. The aim of the present study was to evaluate the effects of genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting hepatocytes against I/R injury in a rat model of small-for-size liver transplantation. L02 liver cells were transfected with the eNOS gene using an adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase chain reaction and western blot analysis. To evaluate the effect of eNOS overexpression, L02 cells were placed in a hypoxic environment for 12 h and immediately transferred to an oxygen-enriched atmosphere. For in vivo testing, rats pretreated with Ad-eNOS or control underwent small-for-size liver transplantation. At 6 h after reperfusion, the bile quantity, serum transaminase and nitric oxide (NO) levels, and histological outcomes were evaluated. Cell apoptosis was assessed by flow cytometry or TUNEL assay. In vitro, Ad-eNOS prevented apoptosis in L02 cells with an increase in the level of NO in culture supernatant. In vivo, Ad-eNOS pre-treatment significantly increased bile production, improved abnormal transaminase levels, diminished apoptosis among liver cells, and decreased hepatocellular damage at 6 h after I/R injury. The eNOS-mediated renal protective effects might be associated with the downregulation of tumor necrosis factor-α and a reduction in macrophage activation in the early stage of reperfusion in small-for-size liver allografts. eNOS-derived NO production significantly attenuates hepatic I/R injury. Thus, eNOS overexpression constitutes a promising therapeutic approach to prevent liver I/R injury following small-for-size liver transplantation. PMID:27882135
Rummler, Silke; Bauschke, Astrid; Bärthel, Erik; Jütte, Heike; Maier, Katrin; Ziehm, Patrice; Malessa, Christina; Settmacher, Utz
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
Telles-Correia, Diogo; Barbosa, António; Mega, Inês; Monteiro, Estela
Nonadherence is considered as determinant for the increase of morbility and mortality, reduction of quality of life, increase of medical costs and excess health services utilization in transplanted patients, and it can be direct cause of 21% of the fails of transplants and 26% of the mortality after transplantation. It was demonstrated that patient description obtained by means of an interview with a good questionnaire is the best way to access to adherence. In transplanted patients, non adherence with a more extended sense, is much more prevalent than adherence related only with medication intake, and therefore the instrument that should be used to measure adherence in this population should be a questionnaire that accesses adherence in a more extended sense. There wasn't found in literature any instrument to evaluate multidimensional adherence in liver transplanted patients. Based on an extended review of literature and with supervision of hepatologists the authors elaborated a questionnaire that mentions 3 adherence dimensions: presence in medical appointments and exams, medication intake and alcohol ingestion, with three questions to each dimension. This questionnaire has passed threw several steps to be validated: cognitive debriefing, liability tests, concept validity, construct validity, and criterium validity.
Rogal, Shari S.; Mankaney, Gautham; Udawatta, Viyan; Chinman, Matthew; Good, Chester B.; Zickmund, Susan; Bielefeldt, Klaus; Chidi, Alexis; Jonassaint, Naudia; Jazwinski, Alison; Shaikh, Obaid; Hughes, Christopher; Fontes, Paulo; Humar, Abhinav; DiMartini, Andrea
Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort. PMID:27820828
Tovikkai, Chutwichai; Charman, Susan C; Praseedom, Raaj K; Gimson, Alexander E; van der Meulen, Jan
AIM To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS. PMID:28058226
Chen, C L; Wang, K L; Hui, Y L; Shieh, W B
Between March 1984 and February 1991, six orthotopic liver transplantations were performed at the Chang Gung Memorial Hospital in Taiwan. The indications for transplantation were Wilson's disease (5 patients) and biliary atresia (1 patient). Donors and recipients were matched only for size and ABO blood group compatibility, and the recipient operations were performed without the use of a venovenous bypass. Arterial reconstruction was carried out by end-to-end hepatic artery anastomosis (4), thoracic aortic conduit (1), or interposition of an iliac artery graft (1), whereas biliary reconstruction was accomplished by a choledochocholedochostomy using a T-tube stent (4) or a choledochocholedochostomy using an external cholecystostomy without stenting (2). Biliary complications occurred in three patients, and all required additional surgery. The average duration of donor-liver cold ischemia, operating time, and blood loss during surgery were 7 h and 50 min (range, 4.5-9 h), 13.5 h (range, 11.8-17 h), and 4,385 ml (range, 750-12,000 ml), respectively. The immunosuppressive regimens included a cyclosporin-steroid combination (n = 2) and a triple-drug combination (n = 4). All except one of the surviving patients experienced at least one rejection episode that was reversed by a methyl-prednisolone bolus and/or recycle. One patient developed a primary cytomegalovirus (CMV) infection that responded well to Ganciclovir treatment. Two of the patients died, one of injuries sustained in a traffic accident 3 years after transplantation, and the other of massive upper gastrointestinal bleeding. The overall survival value at 3 months was 83%, and the follow-up period ranged from 3 months to 7 years. All of the survivors have achieved complete rehabilitation and currently enjoy an excellent quality of life with normal liver function. Although the present study involved a small number of cases, our results indicate that liver transplantation can be successfully achieved in a high
Zhu, Yingwei; Miao, Zongning; Gong, Lei; Chen, Weichang
This study was to investigate the therapeutic effect of intravenous transplantation of TIMP-1-silencing mesenchymal stem cells (MSCs) in a rat model of liver fibrosis. MSCs were transduced with a lentiviral vector expressing tissue inhibitor of metalloproteinase 1 (TIMP-1)-shRNA, and the liver cirrhosis model was established by injection of CCl4 (1 ml/kg body weight twice a week for 4 weeks) in Sprague Dawley rats. The survived 36 rats were randomly divided into 3 groups: control group, MSCs group, and TIMP-1-shRNA group. At 4 weeks after establishment of animal model, 3×106 MSCs were intravenously injected. In TIMP-1-shRNA group, MSCs expressing TIMP-1-shRNA were transplanted. Animals were sacrificed 4 weeks later. Blood was collected for the detection of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The livers were harvested for histological examination. At 5 days after transfection, strong fluorescence was detectable in each group. TIMP-1-shRNA group had the lowest TIMP-1 expression. Following MSCs transplantation, serum ALT and AST reduced in rats with hepatic cirrhosis, and histology showed less fibrotic areas and collagens, as compared to control group. These improvements were more obvious in the TIMP-1-shRNA group. Our study indicates that transplantation of MSCs expressing TIMP-1-shRNA is able to inhibit the progression of liver fibrosis and possibly restore the liver function in a rat model. PMID:26464632
Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena
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
Mancuso, Andrea; Perricone, Giovanni
Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in chronic liver disease and cirrhosis. The incidence of HCC is growing worldwide. With respect to any other available treatment for liver cancer, liver transplantation (LT) has the highest potential to cure. LT allows for removal at once of both the tumor (“seed”) and the damaged-hepatic tissue (“soil”) where cancerogenesis and chronic liver disorders have progressed together. The Milan criteria (MC) have been applied worldwide to select patients with HCC for LT, yielding a 4-year survival rate of 75%. These criteria represent the benchmark for patient selection and are the basis for comparison with any other suggested criteria. However, MC are often considered to be too restrictive, and recent data show that between 25% and 50% of patients with HCC are currently transplanted beyond conventional indications. Consequently, any unrestricted expansion of selection criteria will increase the need for donor organs, lengthen waiting periods, increase drop-out rates, and impair outcomes on intention-to-treat analysis. Management of HCC recurrence after LT is challenging. There are a few reports available regarding the safety and efficacy of sorafenib for HCC recurrence after LT, but the data are heterogeneous. A multi-center prospective randomized controlled trial comparing placebo with sorafenib is advised. Alternatively, a meta-analysis of patient survival with sorafenib for HCC recurrence after LT could be helpful to characterize the therapeutic benefit and safety of sorafenib. Here, we review the use of LT for HCC, with particular emphasis on the selection criteria for transplantation in patients with HCC and management of HCC recurrence after LT. PMID:26357625
Kato, Karin; Nagao, Miki; Miyamoto, Kentaro; Oka, Kentaro; Takahashi, Motomichi; Yamamoto, Masaki; Matsumura, Yasufumi; Kaido, Toshimi; Uemoto, Shinji; Ichiyama, Satoshi
Background Increasing evidence suggests that the intestinal microbiota plays an important role in liver diseases. However, the dynamics of the intestinal microbiota during liver transplantation (LT) and its potential role in clinical course remain unknown. Methods We prospectively analyzed the intestinal microbiota of 38 patients who underwent LT in Kyoto University Hospital. We characterized the microbial compositions of fecal specimens from LT patients using a metagenomics approach by an Illumina MiSeq platform. We analyzed the diversity of microbiota sequentially from pretransplantation until 2 months after LT and also compared the microbiota during an episode of acute cellular rejection (ACR) and bloodstream infections (BSI) to the microbial composition of time-matched fecal specimens obtained from patients who did not experience ACR or BSI, respectively. Results Three hundred twenty fecal specimens were analyzed. Dynamic changes were observed in the microbial composition of LT recipients during the perioperative period. Over the course of LT, the mean diversity index decreased during the first 3 weeks after LT and gradually increased during our observation period. The loss of intestinal microbiota diversity was associated with high Child-Pugh scores, high model for end-stage liver disease scores, ACR, and BSI. At the family level, Bacteroides, Enterobacteriaceae, Streptococcaceae, and Bifidobacteriaceae were increased whereas Enterococcaceae, Lactobacillaceae, Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae were decreased in ACR patients. Conclusions The microbiota of LT patients was associated with the severity of liver diseases and the presence of ACR and BSI. These results lay the groundwork for more comprehensive investigations of microbiota characteristics to identify diagnostic markers for transplant health and to guide intervention strategies to improve transplant outcomes.
Muralidharan, Vijayaragavan; Imber, Charles; Leelaudomlipi, Surasak; Gunson, Bridget K; Buckels, John A C; Mirza, Darius F; Mayer, A David; Bramhall, Simon R
Arterial complications after orthotopic liver transplantation (OLT), including hepatic artery thrombosis (HAT), are important causes of early graft failure. The use of an arterial conduit is an accepted alternative to the utilisation of native recipient hepatic artery for specific indications. This study aims to determine the efficacy of arterial conduits and the outcome in OLT. We retrospectively reviewed 1,575 cadaveric adult OLTs and identified those in which an arterial conduit was used for hepatic revascularisation. Data on the primary disease, indication for using arterial conduit, type of vascular graft, operative technique and outcome were obtained. Thirty-six (2.3%) patients underwent OLT in which arterial conduits were used for hepatic artery (HA) revascularisation. Six of these were performed on the primary transplant, while the rest (n=30) were performed in patients undergoing re-transplantation, including six who had developed hepatic artery aneurysms. The incidence of arterial conduits was 0.4% (6/1,426 cases) in all primary OLTs and 20.1% (30/149 cases) in all re-transplants. Twenty-nine procedures utilised iliac artery grafts from the same donor as the liver, six used iliac artery grafts from a different donor, and a single patient underwent a polytetrafluoroethylene (PTFE) graft. Two techniques were used: infra-renal aorto-hepatic artery conduit and interposition between the donor and recipient native HAs, or branches of the HAs. The 30-day mortality rate for operations using an arterial conduit was 30.6%. Three conduits thrombosed at 9, 25 and 155 months, respectively, but one liver graft survived without re-transplantation. The arterial conduits had 1- and 5-year patency rates of 88.5% and 80.8%. The 1- and 5-year patient survival rates were 66.7% and 44%. We can thus conclude that an arterial conduit is a viable alternative option for hepatic revascularisation in both primary and re-transplantation. Despite a lower patency rate than that of
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
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
Wadhawan, Manav; Kumar, Ajay
Biliary complications are common after living donor liver transplant (LDLT) although with advancements in surgical understanding and techniques, the incidence is decreasing. Biliary strictures are more common than leaks. Endoscopic retrograde cholangiopancreatography (ERCP) is the first line modality of treatment of post LDLT biliary strictures with a technical success rate of 75%-80%. Most of ERCP failures are successfully treated by percutaneous transhepatic biliary drainage (PTBD) and rendezvous technique. A minority of patients may require surgical correction. ERCP for these strictures is technically more challenging than routine as well post deceased donor strictures. Biliary strictures may increase the morbidity of a liver transplant recipient, but the mortality is similar to those with or without strictures. Post transplant strictures are short segment and soft, requiring only a few session of ERCP before complete dilatation. Long-term outcome of patients with biliary stricture is similar to those without stricture. With the introduction of new generation cholangioscopes, ERCP success rate may increase, obviating the need for PTBD and surgery in these patients. PMID:27057304
Sapisochín, Gonzalo; Fernández de Sevilla, Elena; Echeverri, Juan; Charco, Ramón
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
Edmunds, Catherine; Ekong, Udeme D
Autoimmune liver diseases (AILD) are rare diseases with a reported prevalence of less than 50 per 100 000 population. As the research landscape and our understanding of AILDs and liver transplantation evolves, there remain areas of unmet needs. One of these areas of unmet needs is prevention of disease recurrence after liver transplantation. Disease recurrence is not an insignificant event because allograft loss with the need for retransplantation can occur. Patients transplanted for AILD are more likely to experience acute rejection compared to those transplanted for non-AILD, and the reason(s) behind this observation is unclear. Tasks for the future include a better understanding of the pathogenesis of AILD, definition of the precise pathogenetic mechanisms of recurrent AILD, and development of strategies that can identify recipients at risk for disease recurrence. Importantly, the role of crosstalk between alloimmune responses and autoimmune responses in AILD is an important area that needs further study.This article reviews the relevant literature of de novo autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary sclerosing cholangitis, and recurrent primary biliary cirrhosis in terms of the clinical entity, the scientific advancements, and future scientific goals to enhance our understanding of these diseases.
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. PMID:26605281
Zhang, Qi-Kun; Wang, Meng-Long
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.
Guasch Arévalo, E; Alcantarilla Martín, C; López López, M A; Suárez Cobián, A; Gilsanz, F
We describe the case of a woman with a functioning orthotopic liver transplant who was receiving cyclosporine treatment. An emergency cesarean section was performed, with epidural analgesia, for prolonged pregnancy and an unfavorable cervix. No complications were recorded either during or after surgery. She gave birth to a healthy boy and both were discharged on the fifth day after delivery. Organ transplantation is an increasingly common procedure, and Spain, which has a large number of organ donors, is the country where the largest number of transplants in Europe is performed. Immunosuppressive therapy has advanced greatly, allowing patients to survive longer and enjoy good quality of life. Many transplanted women in their childbearing years consider pregnancy, which can lead to medical problems, a worsened clinical picture or complications related to pregnancy, putting the lives of both mother and fetus at risk. Perioperative management by an anesthesiologist is necessary, whether delivery is vaginal or cesarean. Whenever immunosuppressive therapy is involved, the use of general or regional anesthetics carries risk, as do pregnancy and delivery themselves.
Hori, T; Ogura, Y; Okamoto, S; Nakajima, A; Kami, K; Iwasaki, J; Yonekawa, Y; Ogawa, K; Oike, F; Takada, Y; Egawa, H; Nguyen, J H; Uemoto, S
Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.
Triulzi, D J; Shirey, R S; Ness, P M; Klein, A S
Transplantation of ABO-unmatched livers has been associated with the development of donor-derived antibody (DDAb) and hemolysis. Nine (22%) of 41 consecutive patients undergoing liver transplantation at our institution received 10 ABO-unmatched livers. Five (56%) of nine patients developed DDAbs and hemolysis. All five patients were group A1 and received group O livers. DDAbs appeared a mean of 9.2 +/- 2.8 (1 SD) days after surgery and persisted for 15.2 +/- 10.3 days. All patients with DDAbs developed hemolysis. During the period when DDAbs were demonstrable, the hemoglobin dropped by a mean of 4.8 g per dL (48 g/L), and the patients were transfused with a mean of 7.8 +/- 2.3 units of group O red cells. One patient with hemolysis underwent exchange transfusion for acute renal failure. Patients with hemolysis required significantly more red cells postoperatively (15.0 vs. 6.9 units, p = 0.04) than did ABO-matched patients. None of the parameters examined (age, recipient or donor gender, secretor status, rejection, or donor isoagglutinin titers) were predictive of DDAb or hemolysis, although hemolysis occurred in three of four cases in which donor serum IgG anti-A titers were > or = 128, as opposed to one of four cases in which titers were < 128. Because recipients of ABO-unmatched livers are at high risk for transiently developing DDAb and hemolysis with associated morbidity, the prophylactic use of donor-type red cells for surgery and after operation is justified.
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
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
Katchman, Helena; Tal, Orna; Eventov-Friedman, Smadar; Shezen, Elias; Aronovich, Anna; Tchorsh, Dalit; Cohen, Sivan; Shtabsky, Alexander; Hecht, Gil; Dekel, Benjamin; Freud, Enrique; Reisner, Yair
Cell therapy as an alternative to orthotopic liver transplantation represents a major challenge, since negligible proliferation of isolated hepatocytes occurs after transplantation because of the stringent homeostatic control displayed by the host liver. Thus, different modalities of liver injury as part of the pretransplant conditioning are a prerequisite for this approach. The major objective of the present study was to test whether xenotransplantation of pig fetal liver fragments, in which potential cell-cell and cell-stroma interactions are spared, might afford more robust growth and proliferation compared with isolated pig fetal hepatoblasts. After transplantation into SCID mice, fetal liver tissue fragments exhibited marked growth and proliferation, in the setting of a quiescent host liver, compared with isolated fetal hepatoblasts harvested at the same gestational age (embryonic day 28). The proliferative advantage of fetal pig liver fragments was clearly demonstrated by immunohistochemical and morphometric assays and was observed not only after implantation into the liver but also into extrahepatic sites, such as the spleen and the subrenal capsule. The presence of all types of nonparenchymal liver cells that is crucial for normal liver development and regeneration was demonstrated in the implants. Preservation of the three-dimensional structure in pig fetal liver fragments enables autonomous proliferation of transplanted hepatic cells in the setting of a quiescent host liver, without any requirement for liver injury in the pretransplant conditioning. The marked proliferation and functional maturation exhibited by the pig fetal liver fragments suggests that it could afford a preferable source for transplantation.
Raczyńska, Joanna; Habior, Andrzej; Pączek, Leszek; Foroncewicz, Bartosz; Pawełas, Andrzej; Mucha, Krzysztof
Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver, characterized by the presence of antimitochondrial antibodies (AMA) and progressive immune-mediated destruction of biliary ductules, which lead to cirrhosis. Theories of the PBC etiopathogenesis assume that the disease develops secondarily as an improper immunological reaction to undefined environmental and/or infectious factors in genetically predisposed individuals. Ursodeoxycholic acid (UDCA) is the only drug recommended to treat PBC; it delays the progression of liver disease, but remains only a symptomatic treatment. In the advanced stage of PBC, the treatment of choice is liver transplantation (LTx). Nowadays, PBC is the third indication for LTx, after viral-related and alcoholic liver cirrhosis. Unfortunately, PBC recurs in 21-37% of patients at 10 years after LTx, and in 43% at 15 years after LTx, with the median time to recurrence of 3-5.5 years. Diagnosis of recurrent PBC (rPBC) is based on the liver histopathology. Although various risk factors of rPBC have been investigated, the cause of the recurrence is not clear. There is no specific treatment of rPBC. Together with immunosuppression after LTx, UDCA remains the treatment of choice. New diagnostic technologies (e.g., genomics, proteomics, cell-based therapy, and clinical study of the rPBC patients) may be helpful in understanding the pathogenesis of PBC and the development of new treatment modalities.
Uemura, Tadahiro; Nikkel, Lucas E; Hollenbeak, Christopher S; Ramprasad, Varun; Schaefer, Eric; Kadry, Zakiyah
Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score.
Andersen, Kasper Jarlhelt; Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Sasanuma, Hideki; Nyengaard, Jens Randel; Hamilton-Dutoit, Stephen; Ladekarl, Morten; Mortensen, Frank Viborg
Background Sorafenib is a multikinase inhibitor with antiangiogenic and antiproliferative properties, approved for the treatment of hepatocellular carcinoma. The effect of Sorafenib on liver regeneration in healthy rats was investigated. Methods Sixty Wistar rats received either Sorafenib (group S; 15 mg/kg) or placebo for 14 days prior to resection and until sacrifice. After a 70% partial hepatectomy, the rats were euthanized on post-operative days (POD) 2, 4 or 8. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using stereological methods on sections prepared by systematic uniform random sampling. Results Seven animals (12%) died after surgery. Death rates were similar in treated rats and controls. At hepatectomy, the body weight was significantly lower in group S rats. The liver weight and regeneration rates were lower in group S rats on PODs 2, 4 and 8. Hepatocyte proliferation was significantly lower in group S animals on PODs 2 and 4. Alanine aminotransferase ALAT was significantly higher in the Sorafenib-treated group on PODs 2, 4 and 8. Alkaline phosphatase ALP and bilirubin levels were similar in the two groups, although bilirubin was elevated in group S rats on POD 8. Conclusion In this rat model, Sorafenib did not increase post-hepatectomy mortality, but was associated with a significant impaired liver weight gain, regeneration rates and hepatocyte proliferation. PMID:23461776
Kluger, Michael D; Memeo, Riccardo; Laurent, Alexis; Tayar, Claude; Cherqui, Daniel
Background There has been little focus lately on operative techniques for full graft liver transplantation, and the standard technique is unclear. Methods An internet survey addressing the key technical issues was e-mailed to programme directors. Results Responses were obtained from 93 out of 128 (73%) directors contacted. Programmes performed a median of 60 (8–240) transplants per year. Maximum mean cold time of 13 ± 3 h and maximum median steatosis of 40% (15–90%) were tolerated. The inferior vena cava was preserved by 48% of centres all the time and 43% selectively. European centres used temporary portacaval shunting (42%) four times more often than USA programmes. Venous bypass was always used when not preserving the inferior vena cava by less than 25%, and used selectively by approximately 40% of centres. Portal vein anastomosis with room for expansion (88%), graft hepatic artery to native gastroduodenal/common hepatic artery bifurcation (57%) and bile duct-to-duct (47%) were the favoured techniques. Discussion A standard international operative technique for deceased donor liver transplantation does not exist, although there is a trend towards inferior vena cava preservation. Donor selection criteria were more homogenous across programmes. As suggested by the high response rate, there likely exists interest to investigate technical variations on an international scale. PMID:21929669
Verma, Suman; Hand, Fiona; Armstrong, Matthew J; de Vos, Marie; Thorburn, Douglas; Pan, Terry; Klinck, John; Westbrook, Rachel H; Auzinger, Georg; Bathgate, Andrew; Masson, Steven; Holt, Andrew; Houlihan, Diarmaid D; Ferguson, James W
Liver transplantation (LT) in patients with portopulmonary hypertension (PoPH) has historically resulted in unpredictable and often poor outcomes. The United Kingdom experience for the period 1992-2012 is reported in this article. A retrospective analysis of patients, preoperatively fulfilling the PoPH European Respiratory Society Task Force on Pulmonary-Hepatic Vascular Disorders diagnostic criteria was conducted across all UK LT centers. Data collection included comorbidities, use of preoperative and postoperative pharmacotherapy, patient survival, and cause of death. To enable survival stratification, PoPH was classified as mild, moderate, or severe based on mean pulmonary pressure of <35 mm Hg, 35-49 mm Hg, and ≥50 mm Hg, respectively. Of 127 patients reported to have PoPH, just 28 fulfilled the diagnostic criteria (14 mild, 9 moderate, 5 severe). Twenty (71.4%) patients were male with median age and Model for End-Stage Liver Disease of 50 years (range, 23-62 years) and 18 (range, 6-43), respectively. Twelve (42.9%) patients died within 5 years of LT. The majority of deaths (10 of 12; 83%) occurred within the first 6 months after LT, aetiologies of which included right heart failure (n = 3), progressive PoPH (n = 2), and sepsis (n = 2). Of those receiving preoperative pharmacotherapy (n = 8), 5 are currently alive and were classified as mild to moderate PoPH. Both severe PoPH patients optimized preoperatively with pharmacotherapy died within a year of LT. Development of effective vasodilatory therapies in the setting of pulmonary arterial hypertension has led to a dramatic improvement in patient survival. The available data indicate that in this era of pharmacotherapy, PoPH in isolation no longer represents a valid consideration to transplant. Liver Transplantation 22 1637-1642 2016 AASLD.
Teixeira, H R S; Marques, D M; Lopes, A R F; Ziviani, L C; Magro, J T J; Mente, Ênio D; Castro-E-Silva, O; Galvão, C M; Mendes, K D S
The objective of the present study was to determine the anxiety and stress levels of liver transplant candidates during the preoperative period. A cross-sectional, prospective study was conducted on 52 liver transplantation candidates seen at a specialized public hospital outpatient clinic in the interior of the state of São Paulo, Brazil. Data were collected from November 2014 to April 2015 using a self-applicable questionnaire for the assessment of anxiety (State-Trait Anxiety Inventory, short version) and stress (Perceived Stress Scale), in addition to sociodemographic and clinic characterization. The mean (±SD) anxiety level detected was 23.06 ± 5.51 points, with 1.92% of the subjects showing minimum levels (0 to 12 points), 59.62% a medium level (12 to 24 points), 36.54% a moderate level (24 to 36 points), and 1.92% a severe level (36 to 48 points) of anxiety. The mean level on the stress scale was 12.10 ± 5.62 points, with 7.69% of the subjects showing high stress levels. When individuals with good and poor stress levels were compared, a significant difference was observed between them (P = .0004). The Spearman correlation test showed that the higher the stress, the higher the levels of anxiety (r = 0.4258), P < .0001. The present study contributes to the analysis of the mental health of liver transplantation candidates in view of the need for interventions for the improvement of anxiety and stress levels since the waiting period for the organ generates emotional changes that can affect the quality of life of the patient and the success of this complex therapeutic modality.
Aydınlı, Bahar; Karadeniz, Ümit; Demir, Aslı; Güçlü, Çiğdem Yıldırım; Kazancı, Dilek; Koçulu, Rabia; Haytural, Candan; Özgök, Ayşegül; Bostancı, Erdal Birol; Zorlu, Ali
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
Rinaldi, Luca; Valente, Giovanna; Piai, Guido
Background Liver transplanted patients need close surveillance for early signs of graft disease. Objectives Transient elastography can safely be repeated over time, offering serial liver stiffness measurement values. Serial stiffness measurements were compared to single baseline stiffness measurements in predicting the appearance of liver-related clinical events and guiding subsequent clinical decisions. Methods One hundred and sixty liver transplanted patients were observed for three years in our real-life practice. Results Liver stiffness measurements were stable in 75% of patients, decreased in 4% of patients, and increased in 21% of patients. The pattern of increased stiffness measurements was associated with both HCV-RNA positive status and the presence of an active biliary complication of liver transplantation and was more predictive of a clinically significant event resulting from any disease of the transplanted liver when compared to a stable pattern or to a single liver stiffness measurement. The procedures that were consequently performed were often diagnostic for unexpected situations, both in HCV-RNA positive and HCV-RNA negative patients. Conclusions The pattern of longitudinally increased liver stiffness measurements efficiently supported clinical decisions for individualized management strategies. Repeated transient elastography in real-life clinical practice appears to have a practical role in monitoring liver transplanted patients. PMID:28123442
Miura, K; Sato, Y; Kokai, H; Hara, Y; Kobayashi, T; Oya, H; Yamamoto, S; Hatakeyama, K
A case of a 71-year-old man with a huge retroperitoneal tumor situated behind the liver, which strongly compressed the liver inferior vena cava (IVC), and gastrointestinal tract is described. With the techniques of whole liver extraction and autologous orthotopic liver transplantation, we successfully removed the tumor. We have the surgical techniques, essential elements, and indications for this procedure.
Zaouali, Mohamed Amine; Panisello, Arnau; Lopez, Alexandre; Castro, Carlos; Folch, Emma; Carbonell, Teresa; Rolo, Anabela; Palmeira, Carlos Marques; Garcia-Gil, Agustin; Adam, René; Roselló-Catafau, Joan
We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention. PMID:28282906
Russo, Francesco Paolo; Ferrarese, Alberto; Zanetto, Alberto
Liver transplantation (LT) has been established as the most effective treatment modality for end-stage liver disease over the last few decades. Currently, patient and graft survival after LT are excellent, with 1- and 5-year survival of 90% and 80%, respectively. However, the timing of referral to LT is crucial for improving survival benefit and outcome. The current shortage of donors and the increasing demand for LT currently lengthen the waiting time. Thus, waiting list mortality is about 10–15%, according to the geographical area. For this reason, over the last several years, alternatives to deceased donor LT and new options for prioritizing patients on the waiting list have been proposed. PMID:28105300
Jakobovich, E.; Koplewitz, B.; Marva, E.; Granot, E.
We describe a 14-year-old girl, who was 13 y after liver transplantation for biliary atresia with an unremarkable postoperative course. She presented with fever of up to 40°C, extreme fatigue, malaise, anorexia, and occasional vomiting. On physical examination the only finding was splenomegaly. Lab results showed hyperglobulinemia and an elevated sedimentation rate. Liver function tests were normal except for mild elevation of γGTP. Abdominal U/S and CT demonstrated an enlarged spleen with retroperitoneal and mesenteric lymph nodes enlargement. An exhaustive evaluation for infectious causes, autoimmune conditions, and malignancy was negative. A full recovery after 5 months prompted testing for self-limited infectious etiologies. Yersinia enterocolitica infection was diagnosed. PMID:25126442
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
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
Hoyos, Sergio; Guzmán, Carlos; Correa, Gonzalo; Restrepo, Juan Carlos; Franco, Hernán; Cárdenas, Andrés
Situs inversus (SI) is a rare congenital disorder with a complete mirror image of thoracic and abdominal organs. In adults with SI and decompensated cirrhosis experience with liver transplantation is limited. Orthotopic liver transplantation (OLT) in an adult with cirrhosis using a technique where the recipient liver was placed using a 90-degree rotation of the graft was previously reported by Klintmalm et al, however no other reports using this technique have been described. We report a case of a 41 year-old man with situs inversus and decompensated cirrhosis who successfully underwent OLT using this technique. The donor liver was rotated 90-degrees towards the left and easily fitted into the recipients'fossa with the left lobe pointing toward the left lower quadrant. The patient had an uneventful recovery and has been followed for 21 months without any complications. This technique has the advantage of preventing compromise of the size of the donor liver, permits an easy reconstruction of vascular and biliary tree and in this case was associated with an excellent outcome.
Li, Hao; Fan, Ming-Qi; Men, Tong-Yi; Wang, Yun-Peng; Xing, Tong-Hai; Fan, Jun-Wei; Peng, Zhi-Hai; Zhong, Lin
Background The number and survival rate of simultaneous liver-kidney transplant (SLKT) recipients have increased dramatically since 2002. However, the long-term effectiveness of SLKT in patients with hepatitis B is unknown. Material/Methods Forty-six patients who visited the Organ Transplant Center of the Shanghai First People’s Hospital between January 2001 and May 2005 had hepatitis B virus infection and renal failure (any degree), and underwent organ transplantation: 21 patients underwent SLKT and 25 patients underwent liver transplant (LT) alone. Results The 1-, 3-, and 5-year survival rates of SLKT recipients were 90.5%, 81.0%, and 81.0%, respectively. Incidence of acute hepatic allograft rejection between SLKT recipients and LT recipients (33% vs. 16%) did not reach significance (P=0.170). Despite higher infection rate, more prevalent hepatitis B relapse, and longer stay in the intensive care unit, SLKT recipients experienced significantly higher 1-year survival rate (90.5%) compared with LT recipients (60%, P=0.019). Multivariate regression analysis revealed that postoperative renal failure (odds ratio (OR)=48, P=0.003) and Risk/Injury/Failure/Loss/End-stage (RIFLE) stage (OR=8, P=0.012) were independent risk factors for postoperative death after LT. Conclusions SLKT in patients with hepatitis B had higher early-stage infection rate, but had a higher long-term survival rate compared with the LT group. Although the incidence of postoperative hepatitis B relapse in SLKT recipients was higher, timely and reasonable treatment can ensure long-term survival of patients. Worsening RIFLE stage of recipients can predict high mortality when only given LT. SLKT might be a better choice for RIFLE stage 2 or 3 patients than LT alone. PMID:26828767
Fox, Rena K
The decision to perform liver transplantation for a particular patient is never the decision of one single individual, although a single individual could preclude transplant as an option if the opportunity for referral is missed. Every physician treating patients with cirrhosis, including primary care physicians and primary gastroenterologists, should watch for the essential turning points at which a patient may become eligible for a transplant referral. Timing of referral could be assessed according to either the type of liver disease or non–disease-specific measures of disease severity. Although the MELD score is an easily accessible and convenient tool it is not as well known as CTP classification, and many cirrhotic patients under long-term management may not be being allocated a MELD score regularly calculated by their primary physicians. Because a slow progression in MELD score may occur without a change in symptoms, reaching the MELD score acceptable for transplant referral may go unrecognized. As generalists face the rising prevalence of NAFLD and the rising prevalence of cirrhosis and HCC from HCV, there will be an increasing need for education in the management of liver disease. It will be necessary for specialists and health care systems to better inform primary care physicians about the recommendations on criteria for transplant referral and the critical windows of opportunity within which they can act. Although there is a recognized knowledge gap that needs to be addressed, once a patient is in medical care, inadequate physician knowledge should never be the cause for late timing or missing the opportunity for referral.
Englert, Cornelia; Grabhorn, Enke; Richter, Andrea; Rogiers, Xavier; Burdelski, Martin; Ganschow, Rainer
Progressive familial intrahepatic cholestasis (PFIC) is caused by mutations of the bile salt export pump or the multidrug resistance P-glycoprotein, resulting in chronic hepatic failure. Partial external diversion of bile or ileal bypass is effective in some cases and, in others, liver transplantation (OLT) is necessary. Forty-two children were included in this study. Twenty-six children suffered from PFIC type 2 and 16 from PFIC type 3. Symptoms included pruritus, cholestasis, liver cirrhosis, and growth retardation. Seventeen patients received external biliary diversion. Ten had to undergo OLT in the following course. As of this report, three of the remaining patients were on the wait list for OLT. Twenty-three children received a liver graft primarily with excellent outcome. Our data show that OLT is the option of choice in symptomatic PFIC and whenever liver cirrhosis is present. We suggest a very restrictive recommendation of external biliary diversion. However, gene therapy may be a future option for children with PFIC.
Dionissios, Neofytos; Shmuel, Shoham; Kerry, Dierberg; Katharine, Le; Simon, Dufresne; Sean, Zhang X; Kieren, Marr A
This is a case report of central nervous system (CNS) invasive aspergillosis (IA) in a liver transplant recipient, which illustrates the utility of enzyme-based diagnostic tools for the timely and accurate diagnosis of IA, the treatment challenges and poor outcomes associated with CNS IA in liver transplant recipients. PMID:22676861
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
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.…
ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro
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
Pavel, Mihai-Calin; Fondevila Campo, Constantino; Calatayud Mizrahi, David; Ferrer Fabrega, Joana; Sanchez Cabus, Santiago; Molina Santos, Víctor; Fuster Obregon, Josep; Garcia-Valdecasas Salgado, Juan Carlos
The increasing difference between the number of patients in waiting lists for liver transplantation and the number of available donors has generated a great interest in the use of non-ideal organs, like grafts obtained from cardiac death donors (DCD). However, the extreme sensibility to ischemia of these livers results in a low utilization rate and a high percentage of post-transplant complications and re-transplantation. Normothermic perfusion machines (NMP) emerged as an alternative that tries to maintain the viability of the organ and even to improve its function. This review focuses on current results of DCD liver transplantation and on the role that NMP may have in this field.
Sakamoto, Seisuke; Nosaka, Shunsuke; Shigeta, Takanobu; Uchida, Hajime; Hamano, Ikumi; Karaki, Chiaki; Kanazawa, Hiroyuki; Fukuda, Akinari; Nakazawa, Atsuko; Kasahara, Mureo
Cystic lesions in the liver are often found through the evaluation of liver donors. Multiple cysts are worrisome, and donor candidates with multiple cysts may be unacceptable as liver donors, especially when their recipients have fibrocystic disease (FCD), which is an inherited disorder. This study reviewed 183 cases of living donor liver transplantation. We collected clinical and radiological data associated with donors with cystic lesions and with donors without cystic lesions, and we evaluated the outcomes of these donors and their recipients. As part of the preoperative radiological assessment of grafts, magnetic resonance cholangiography (MRC) was performed to evaluate the biliary anatomy of donor candidates with multiple cysts. Thirty-four donors (18.6%) had 1 or more cystic lesions in the liver, and 6 of these donors had multiple cysts (ie, >10). Donors with multiple cysts were older and heavier, and there was a significant relationship between these donors and recipients whose original disease was FCD. During the follow-up (median = 3.1 years), all donors with cystic lesions were found to be doing well without any major postoperative complications. Fifteen recipients who received grafts with cystic lesions (12 left-sided lobes and 3 right-sided lobes) had no complications related to the cystic lesions. In conclusion, donors with cystic lesions may be acceptable as liver donors, although our data are limited mostly to left-sided lobe donation with a short follow-up period. MRC should be preoperatively performed to rule out any biliary anomalies, especially in donor candidates whose recipients have FCD.
Kim, Dean Y; Kwon, David S; Salem, Riad; Ma, Chan K; Abouljoud, Marwan S
We report a case of a patient with end-stage liver disease secondary to hepatitis C, complicated by a large hepatocellular carcinoma. Because of the size of the tumor exceeded the Milan criteria, he was not a candidate for liver transplantation. However, after two treatments with yttrium-90 glass microsphere infusions, the tumor became smaller and the patient's alpha-fetoprotein level dropped to normal range. He was listed for transplantation and subsequently received a deceased donor liver transplant. Two years after his transplantation, he remains tumor free and has normal alpha-fetoprotein levels. This is the first reported case in the literature of using yttrium-90 microspheres as a bridge to liver transplantation in a patient with a large hepatocellular carcinoma. This therapy should be considered in patients with cirrhosis and large hepatocellular carcinomas exceeding current size criterion, who would otherwise be good candidates for transplantation.
Miraglia, Roberto Maruzzelli, Luigi; Caruso, Settimo; Riva, Silvia; Spada, Marco; Luca, Angelo; Gridelli, Bruno
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.
Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Parrilla, Pascual; Martínez-Alarcón, Laura; Ramírez, Pablo; Pons, José Antonio
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
Matevossian, Edouard; Doll, Dietrich; Weirich, Gregor; Burian, Maria; Knebel, Carolin; Thorban, Stefan; Hüser, Norbert
Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative. PMID:21490847
Carraro, Amedeo; Montin, Umberto; Violi, Paola; Soldani, Fabio; Mazzi, Romualdo; Merighi, Mara; Kanani, Faheem; Concia, Ercole; Tedeschi, Umberto
We report a case of successfully treated multiple liver abscesses in a liver-transplanted patient, sustained by combined multidrug-resistant infections. Two months after a liver transplant, a computed tomography scan revealed the presence of multiple abscesses in the liver graft. Blood cultures and abscessual liver fluid were both positive for acquired colistin- and carbapenem- resistant Klebsiella pneumoniae and an extended-spectrum of beta-lactamases-producing Enterobacter aerogenes. The treatment strategy consisted of different prolonged antimicrobial combinations and draining of the abscesses with complete recovery of the liver lesions.
Nadim, Mitra K; Annanthapanyasut, Wanwarat; Matsuoka, Lea; Appachu, Kari; Boyajian, Mark; Ji, Lingyun; Sedra, Ashraf; Genyk, Yuri S
Liver transplantation (LT) for patients with renal dysfunction is frequently complicated by major fluid shifts, acidosis, and electrolyte and coagulation abnormalities. Continuous renal replacement therapy (CRRT) has been previously shown to ameliorate these problems. We describe the safety and clinical outcomes of intraoperative hemodialysis (IOHD) during LT for a group of patients with high Model for End-Stage Liver Disease (MELD) scores. We performed a retrospective study at our institution of patients who underwent IOHD from 2002 to 2012. Seven hundred thirty-seven patients underwent transplantation, and 32% received IOHD. The mean calculated MELD score was 37, with 38% having a MELD score ≥ 40. Preoperatively, 61% were in the intensive care unit, 19% were mechanically ventilated, 43% required vasopressor support, and 80% were on some form of renal replacement therapy at the time of transplantation, the majority being on CRRT. Patients on average received 35 U of blood products and 4.8 L of crystalloids without significant changes in hemodynamics or electrolytes. The average urine output was 450 ml, and the average amount of fluid removal with dialysis was 1.8 L. The 90-day patient and dialysis-free survival rates were 90% and 99%, respectively. One-year patient survival rates based on the pretransplant renal replacement status and the MELD status were not statistically different. This is the first large study to demonstrate the safety and feasibility of IOHD in a cohort of critically ill patients with high MELD scores undergoing LT with good patient and renal outcomes.
Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro
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
N., Selvakumar; Goyal, Neerav; Nayeem, Mohammed; Vohra, Sandeep; Gupta, Subash
Introduction Liver transplantation (LT) is the gold standard for decompensated Chronic Liver Disease (CLD) in individuals satisfying the selection criteria. Organ scarcity is the rate limiting step in liver transplantation across the globe. Expanding the donor pool is practiced by transplant surgeons across the globe in view of perennial donor organ scarcity and ever increasing organ demand. Presentation of case We have presented series of 3 cases of liver transplantation (LT) with modified left lobe (conventional right) graft from a situs inversus donor and implanting it as a conventional right lobe with a modified technique. The grafts had Type 1, Type 2 and Type 3 biliary anatomies. One graft had inferior hepatic veins also. All three patients had uneventful recoveries. The follow up period range is 4 years to 8 months. Discussion There are multiple case reports in the literature involving situs inversus donors in liver transplantation. Various techniques have also been described. We describe simple and effective technique which has proved successful to our patients. Conclusion SIT donors can be safely accepted for living donor liver transplantation. It is a technically challenging procedure both for donor liver harvesting and implantation in recipient. This is the first case series of LT using modified left lobe graft (conventional right) from a SIT donor with 2 different techniques. Biliary anastomosis is the tricky part of the operation. PMID:26895114
Saraf, Vivek; Pande, Supriya; Gopalakrishnan, Unnikrishnan; Balakrishnan, Dinesh; Menon, Ramachandran N; Sudheer, O V; Dhar, Puneet; Sudhindran, S
Zinc phosphide (ZnP) containing rodenticide poisoning is a recognized cause of acute liver failure (ALF) in India. When standard conservative measures fail, the sole option is liver transplantation. Records of 41 patients admitted to a single centre with ZnP-induced ALF were reviewed to identify prognostic indicators for requirement of liver transplantation. Patients were analyzed in two groups: group I (n = 22) consisted of patients who either underwent a liver transplant (n = 14) or died without a transplant (n = 8); group II (n = 19) comprised those who survived without liver transplantation. International normalized ratio (INR) in group I was 9 compared to 3 in group II (p < 0.001). Encephalopathy occurred only in group I. Model for End-Stage Liver Disease (MELD) score in group I was 41 compared to 24 in group II (p < 0.001). MELD score of 36 (sensitivity of 86.7 %, specificity of 90 %) or a combination of INR of 6 and encephalopathy (sensitivity of 100 %, specificity of 83 %) were the best indicators of mortality. Such patients should undergo urgent liver transplantation.
Linton, M F; Gish, R; Hubl, S T; Bütler, E; Esquivel, C; Bry, W I; Boyles, J K; Wardell, M R; Young, S G
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
Sharma, Pratima; Shu, Xu; Schaubel, Douglas E.; Sung, Randall S.; Magee, John C.
Survival benefit of simultaneous liver-kidney transplant (SLKT) over liver transplant alone (LTA) is unclear from the current literature. Additionally, the role of donor kidney quality, measured by kidney donor risk index (KDRI), in survival benefit of SLKT is not studied. We compared survival benefit after SLKT and LTA among recipients with similar pre-transplant renal dysfunction using novel methodology, specifically with respect to survival probability and area under the survival curve by dialysis status and KDRI. Methods Data were obtained from the Scientific Registry of Transplant Recipients. The study cohort included patients with pre-LT renal dysfunction who were waitlisted and received either a SLKT (n=1,326) or a LTA (n=4,283) between 3/1/02–12/31/09. Inverse Probability of Treatment Weighted (IPTW) – SLKT and LTA survival curves, along with the 5-year area under the survival curve were computed by dialysis status at transplant. The difference in the area under the curve represents the average additional survival time gained via SLKT over LTA. Results For patients not on dialysis, SLKT resulted in a significant 3.7 month gain in 5-year mean post-transplant survival time. The decrease in mortality rate differs significantly by KDRI, and an estimated 76% of SLKT recipients received a kidney with KDRI sufficiently low for mortality. The mortality decrease for SLKT was concentrated in the first year post-transplant. The difference between SLK and LTA 5-year mean post-transplant survival time was 1.4 months and non-significant for patients not on dialysis. Conclusion The propensity score-adjusted survival among SLKT and LTA recipients was similar for those who were dialysis at LT. Although statistically significant, the survival advantage of SLKT over LTA was of marginal clinical significance among patients not on dialysis; and occurred only if the donor kidney was of sufficient quality. These results should be considered in the ongoing debate regarding the
Uzunova, Yordanka; Prodanova, Krasimira; Spassov, Lubomir
Orthotopic liver transplantation (OLT) is the only curative treatment for end-stage liver disease. Early diagnosis and treatment of infections after OLT are usually associated with improved outcomes. This study's objective is to identify reliable factors that can predict postoperative infectious morbidity. 27 children were included in the analysis. They underwent liver transplantation in our department. The correlation between two parameters (the level of blood glucose at 5th postoperative day and the duration of the anhepatic phase) and postoperative infections was analyzed, using univariate analysis. In this analysis, an independent predictive factor was derived which adequately identifies patients at risk of infectious complications after a liver transplantation.
Aydinli, Bulent; Ozturk, Gurkan; Arslan, Sukru; Kantarci, Mecit; Tan, Onder; Ahıskalioglu, Ali; Özden, Kemalettin; Colak, Abdurrahim
Alveolar echinococcosis (AE) is a chronic disease caused by ingestion of the eggs of the parasitic cestode Echinococcosis multilocularis (EM). In severe cases, liver transplantation (LT) may represent the only possibility of survival and cure. Patients undergoing LT associated with hepatic AE at our institution between April 2011 and October 2014 were investigated retrospectively. The clinical findings of the 27 patients who participated in the study were noted. Kaplan-Meier and chi-square tests were used to investigate the effect of these characteristics on survival and mortality. Living donor LT was performed on 20 patients (74.1%), and deceased donor LT was performed on 7 patients (25.9%). Hilar invasion was the most common indication (14 patients, 51.9%) for transplantation. The patient follow-up was 16.1 ± 11.4 months, and the overall survival rate was 77.8%. Primary nonfunction developed only in 2 patients in the posttransplantation period. Six patients died during monitoring, the most common cause of death being sepsis (3 patients). The relationship between the mortality rate of the patients and the invasion of the bile duct and/or portal vein by alveolar lesions was found to be statistically significant (P = 0.024 and P = 0.043, respectively). According to PNM staging, when the AE disease exceeds the resectability limits, the only alternative for the treatment of the disease is LT. However, different from LT due to cirrhosis, it is extremely difficult to perform a transplantation for AE disease because of the invasive characteristics of it. In order to decrease the difficulty of the operation and the postoperative mortality, the intracystic abscess and cholangitis which occur because of AE must be treated via medical and percutaneous methods before transplantation.
Bahirwani, Ranjeeta; Forde, Kimberly A.; Mu, Yifei; Lin, Fred; Reese, Peter; Goldberg, David; Abt, Peter; Reddy, K Rajender; Levine, Matthew
Renal dysfunction prior to liver transplantation has a marked impact on post-transplant kidney outcomes. The aim of this study was to assess post-transplant renal function in patients with chronic kidney disease (CKD) receiving orthotopic liver transplantation (OLT) alone. METHODS Retrospective review of 40 OLT recipients with pre-transplant CKD (serum creatinine ≥ 2 mg/dl for at least 3 months) at the University of Pennsylvania from February 2002 to July 2010. Primary outcome was estimated glomerular filtration rate (eGFR) up to 3 years post-transplant. Secondary outcomes included incidence of stage 4 CKD (eGFR < 30 ml/min), need for renal replacement therapy (RRT), meeting criteria for kidney transplant listing (eGFR ≤ 20 ml/min), and mortality. RESULTS Median patient age was 56.5 years and 48% patients had pre-transplant diabetes. Median serum creatinine at transplant was 2.7 mg/dl (eGFR 24 ml/min). Median eGFR at 1, 2, and 3 years post-transplant was 35, 34, and 37 ml/min respectively. Twelve patients (30%) required RRT at a median of 1.21 years posttransplant and 16 (40%) achieved an eGFR ≤ 20 ml/min at 1.09 years post-transplant. Mortality was 35% at a median of 1.60 years post-transplant. CONCLUSIONS OLT recipients with pre-transplant CKD have a substantial burden of post-transplant renal dysfunction and high short-term mortality, questioning the rationale for OLT alone in this population. PMID:24382253
Meng, Xueqin; Wu, Liming
The overuse of glucocorticoid may cause the metabolic disorders affecting the long term outcome of liver transplantation. This study aims to investigate the immune adjustment strategy by decreasing use of glucocorticoid after liver transplantation. The follow-up study was carried out on liver function and lipid metabolism. This study included adult recipients of liver transplantation. There were 3 groups according to their use of glucocorticoid: long term (>3 months, n = 18), short term (<3 months, n = 20), and control group (no use of glucocorticoid, radical hepatic resection, n = 22). The laboratory results of liver function (AST/ALT ratio) and serum lipid were compared 6 months after liver transplantation. AST/ALT ratio, the marker of liver function, showed no significant difference between long and short term group (P > 0.05). The acute rejection had no significant difference between short and long term groups, while TG, HDL, LDL, and glucose showed significant change in the long term group (P < 0.05). At 6 months after liver transplantation, the long term group showed higher metabolic disorders (P < 0.05). The proper immune adjustment strategy should be made to avoid overuse of glucocorticoid. It can decrease hyperlipidemia and other metabolic disorders after liver transplantation without increasing the acute rejection or liver function damage. PMID:28194427
Zardi, Enrico Maria; Zardi, Domenico Maria; Chin, Diana; Sonnino, Chiara; Dobrina, Aldo; Abbate, Antonio
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.
Tangri, Navdeep; Alam, Ahsan; Edwardes, Michael D; Davidson, Ashley; Deschênes, Marc; Cantarovich, Marcelo
Background. Serum creatinine (Scr)-based equations lack accuracy in predicting glomerular filtration rate (GFR) in patients with liver disease. Cimetidine has been shown to improve the performance of Scr-based GFR formulae. Methods. We evaluated the use of cimetidine on the performance of GFR-estimating equations in 39 liver transplant recipients. The patients received oral cimetidine (800 mg tid) during a 24-h urine collection. The next day, the patients underwent radionucleotide GFR (rGFR) determination and Scr was measured for creatinine clearance (CrCl) and GFR estimation using the Cockcroft-Gault, Nankivell and modified diet in renal disease (MDRD) equations. Data were analysed using the Pearson correlation statistic and Bland-Altman plots. Results. The mean rGFR was 65 +/- 26.4 mL/min. The use of cimetidine increased the bias between rGFR and the Nankivell and MDRD equations. The combined root mean square error for the CrCl, Cockcroft-Gault, Nankivell and MDRD equations without cimetidine were 20.2, 15.6, 17.0 and 15.5 and cimetidine-aided were 28.2, 23.2, 23.7 and 24.3, respectively. Conclusions. All the tested equations without using cimetidine predicted GFR with modest accuracy. The addition of cimetidine decreased the precision and increased the bias of all the GFR-estimating equations. In the absence of accurate GFR-estimating equations, rGFR should be used to monitor kidney function in liver transplant recipients.
Rodrigo, L; de Francisco, R; Pérez-Pariente, J M; Cadahia, V; Tojo, R; Rodriguez, M; Lucena, Ma I; Andrade, R J
We present the case of a 63-year-old woman who had undergone 7 months of treatment with Nimesulide (100 mg/b.i.d.) for symptomatic osteoarthritis. The patient was admitted to our unit with a clinical picture of progressive jaundice over 3 weeks. Clinical and analytical studies revealed acute liver failure, this being confirmed by liver biopsy, which showed submassive necrosis. Serological tests for different viral agents causing hepatitis were all negative. In addition, she presented a picture of severe haemolytic anaemia resistant to several treatments and needed multiple transfusions. Twenty-three days after admission, the patient presented hepatic encephalopathy and received an orthotopic liver transplant on day 25. The evolution after transplantation was good and the patient continues in good health with no evidence of haemolysis almost 2 years later. Liver toxicity due to Nimesulide is well known, but to our knowledge the occurrence of haemolytic anaemia has not been related to this drug previously. For these reasons, Nimesulide has been restricted or removed from the market in several countries in recent months.
More than ten years after the initial description of the humoral theory of transplantation by Dr. Paul I. Terasaki, the significance of humoral alloimmunity in liver transplantation has yet to be clearly defined. The liver allograft has an inherent tolerogenic capacity which confers its resistance to cell-mediated as well as antibody-mediated rejection. Nevertheless, the protection against alloimmunity is not complete, and antibody-mediated tissue injury can occur in the liver graft under specific circumstances. In this article the evidence on the clinicopathologic effects of donor-specific alloantibodies in liver transplantation will be examined and interpreted in parallel with lessons learned from renal transplantation. The unique anatomic and immunologic features of the liver will be reviewed to gain new insights into the complex interactions between humoral immune system and the liver allograft. PMID:28164136
Colombo, Carla; Costantini, Diana; Rocchi, Alessia; Romano, Giovanna; Rossi, Giorgio; Bianchi, Maria Luisa; Bertoli, Simona; Battezzati, Alberto
The long-term effects of liver transplantation on nutritional status, body composition and pulmonary function in patients with liver disease associated with cystic fibrosis (CF) are poorly defined. We studied 15 patients with CF-associated biliary cirrhosis and severe portal hypertension. Seven underwent liver transplantation (age: 14.8 +/- 6.2 years), and eight were treated conservatively (age: 15.9 +/- 6.7 years). All patients were evaluated at baseline and thereafter yearly for a median duration of 5 years. During follow-up, transplanted patients gained weight and showed a significant increment in body mass index (P < 0.004), whereas patients without transplantation remained stable (P = 0.063). Baseline bone mineral content (dual energy X-ray absorptiometry scan) was lower than normal in all patients (more in transplanted patients) and increased in transplanted patients (P < 0.05), but not in patients without transplantation. In both groups percent body fat did not change, whereas fat free mass increased only in the transplant group (P = 0.06) (P < 0.03 versus nontransplanted patients). Only in transplanted patients' plasma concentrations of vitamin E and A increased (P < 0.05 versus nontransplanted patients). Forced espiratory volume in 1 s and forced vital capacity showed similar deterioration in transplanted and in nontransplanted patients. Liver transplantation is associated with long-term beneficial effects on the nutritional status of CF patients and seems to favor bone mineralization.
Eshraghian, Ahad; Imanieh, Mohammad Hadi; Dehghani, Seyed Mohsen; Nikeghbalian, Saman; Shamsaeefar, Alireza; Barshans, Frouzan; Kazemi, Kourosh; Geramizadeh, Bita; Malek-Hosseini, Seyed Ali
AIM To investigate incidence and survival of post-transplant lymphoproliferative disorder (PTLD) patients after liver transplantation. METHODS A cross-sectional survey was conducted among patients who underwent liver transplantation at Shiraz Transplant Center (Shiraz, Iran) between August 2004 and March 2015. Clinical and laboratory data of patients were collected using a data gathering form. RESULTS There were 40 cases of PTLD in the pediatric age group and 13 cases in the adult group. The incidence of PTLD was 6.25% in pediatric patients and 1.18% in adult liver transplant recipients. The post-PTLD survival of patients at 6 mo was 75.1% ± 6%, at 1 year was 68.9% ± 6.5% and at 5 years was 39.2% ± 14.2%. Higher serum tacrolimus level was associated with lower post-PTLD survival in pediatric patients (OR = 1.07, 95%CI: 1.006-1.15, P = 0.032). A serum tacrolimus level over 11.1 ng/mL was predictive of post PTLD survival (sensitivity = 90%, specificity = 52%, area under the curve = 0.738, P = 0.035). CONCLUSION Incidence of PTLD in our liver transplant patients is comparable to other centers. Transplant physicians may consider adjustment of tacrolimus dose to maintain its serum level below this cutoff point. PMID:28275302
Fiegel, Henning C; Kaufmann, Peter M; Bruns, Helge; Kluth, Dietrich; Horch, Raymund E; Vacanti, Joseph P; Kneser, Ulrich
Today, liver transplantation is still the only curative treatment for liver failure due to end-stages liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, e.g. liver tissue engineering, are under investigation with the aim, that in future an artificial liver tissue could be created and be used for the replacement of the liver function in patients. Using cells instead of organs in this setting should permit (i) expansion of cells in an in vitro phase, (ii) genetic or immunological manipulation of cells for transplantation, (iii) tissue typing and cryopreservation in a cell bank, and (iv) the ex vivo genetic modification of patient's own cells prior re-implantation. Function and differentiation of liver cells are influenced by the three-dimensional organ architecture. The use of polymeric matrices permits the three dimensional formation of a neo-tissue and specific stimulation by adequate modification of the matrix-surface which might be essential for appropriate differentiation of transplanted cells. Additionally, culturing hepatocytes on three dimensional matrices permits culture in a flow bioreactor system with increased function and survival of the cultured cells. Based on bioreactor technology, bioartificial liver devices (BAL) are developed for extracorporeal liver support. Although BALs improved clinical and metabolic conditions, increased patient survival rates have not been proven yet. For intra-corporeal liver replacement, a concept which combines Tissue Engineering using three-dimensional, highly porous matrices with cell transplantation could be useful. In such a concept, whole liver mass transplantation, long term engraftment and function as well as correction of a metabolic defect in animal models could be achieved with a principally reversible procedure. Future studies have to
Fayek, S A; Quintini, C; Chavin, K D; Marsh, C L
This article is a review of the salient points and a future prospective based on the 2014 Organ Procurement and Transplantation Network (OPTN)/Scientific Registry of Transplant Recipients (SRTR) liver donation and transplantation data report recently published by the American Journal of Transplantation. Emphasis of our commentary and interpretation is placed on data relating to waitlist dynamics, organ utilization rates, the impact of recent advances in the treatment of hepatitis C, and the increases in end-stage renal disease among liver transplant candidates. Finally, we share our vision on potential areas of innovation that are likely to significantly improve the field of liver transplantation in the near future.
Singh, Ajay K; Nachiappan, Arun C; Verma, Hetal A; Uppot, Raul N; Blake, Michael A; Saini, Sanjay; Boland, Giles W
Liver transplantation is now frequently used in the treatment of end-stage liver disease. Therefore, it is important that radiologists be aware of common anastomotic techniques and expected postoperative imaging findings. Imaging is most useful in evaluating for posttransplantation complications, which are broadly classified into vascular, biliary, and other complications. Hepatic artery thrombosis is the most significant complication and is often associated with graft failure. Radiologists have multiple modalities at their disposal for optimal evaluation. Doppler ultrasonography (US) is the preliminary imaging modality for gross evaluation of the liver parenchyma, biliary tree, and vasculature for abnormalities. When US findings are indeterminate or there is persistent clinical suspicion for an abnormality, computed tomography (CT) is often performed. The major indications for CT are detection of bile leak, hemorrhage, and abscess, but CT is also useful in the assessment of the vasculature. T-tube cholangiography and magnetic resonance cholangiopancreatography are the best noninvasive imaging tools for evaluating for biliary stricture. Some investigators would argue that endoscopic retrograde cholangiopancreatography (ERCP) is a better diagnostic imaging modality; however, ERCP is invasive. Hepatobiliary scintigraphy is optimal for the evaluation of biliary leakage. Early detection of posttransplantation complications will help lower morbidity rates and will likely allow graft salvage in selected cases.
Caicedo, Luis A.; Villegas, Jorge I.; Serrano, Oscar; Millán, Mauricio; Sepúlveda, Mauricio; Jiménez, Diego; García, Jairo; Posada, Juan G.; Mesa, Liliana; Duran, Carlos; Schweineberg, Johanna; Dávalos, Diana; Manzi, Eliana; Sabogal, Angie; Aristizabal, Ana María; Echeverri, Gabriel J.
Case series Patient: Male, 38 • Male, 48 Final Diagnosis: En-bloc transplantation (liver, kidney, pancreas) Symptoms: Encephalopathy • adynamia • ascites • asthenia Medication: — Clinical Procedure: En-bloc transplantation Specialty: Transplantology Objective: Unusual setting of medical care Background: En-bloc transplantation is a surgical procedure in which multiple organs are transplanted simultaneously. It has some similarities with multi-organ transplantation but offers certain advantages. This report highlights the experience of our interdisciplinary group regarding the treatment and follow-up of patients who received en-bloc transplantation, with the aim of encouraging the development of this surgical technique. Case Report: The first case is a 38-year-old patient with type 1 diabetes mellitus, liver cirrhosis, and chronic kidney failure who received an en-bloc transplant of the liver, pancreas, and kidney with no intraoperative complications. He had a prolonged hospital stay due to anemia and systemic inflammatory response syndrome, which were resolved successfully. At follow-up, he had no requirement for insulin or for dialysis, or for new interventions. The second case describes a 48-year-old patient with type 2 diabetes mellitus, renal failure, and liver cirrhosis who received an en-bloc transplant of the liver, pancreas, and kidney with no complications. During the postoperative period, the patient suffered a possible episode of acute tubular necrosis, which evolved towards improvement, with a tendency to normal metabolic and renal functioning, with no additional events. The patient is currently in follow-up and is insulin-independent. Conclusions: En-bloc transplantation is a safe procedure, which is technically simple and which achieves excellent results. This procedure is indicated in patients with end-stage renal disease, cirrhosis, and diabetes mellitus that is difficult to control. PMID:28148909
Bismuth, H; Samuel, D; Castaing, D; Adam, R; Saliba, F; Johann, M; Azoulay, D; Ducot, B; Chiche, L
OBJECTIVE: The authors report on the experience of orthotopic liver transplantation in fulminant hepatitis at Paul Brousse Hospital. SUMMARY BACKGROUND DATA: Liver transplantation is a breakthrough in the treatment of patients with fulminant hepatitis. However, the indications, the timing for transplantation, the type of transplantation, and the use of ABO incompatible grafts in this setting still are debated. METHODS: Transplantation was indicated in patients with confusion or coma and factor V less than 20%, younger than 30 years of age, and confusion or coma and factor V less than 30% older than 30 years of age. RESULTS: Among 139 patients who met the aforementioned criteria for transplantation, 1 recovered, 22 died before transplantation, and 116 underwent transplants with a 1-year survival of 68%. Survival was 83% in patients with grade 1 and 2 comas at transplantation versus 56% (p < 0.001) in those with grade 3 comas; it was 51% versus 81% (p < 0.001) in those transplanted with high risk (ABO-incompatible, split, or steatotic) and low-risk grafts, respectively. In a multivariate analysis, steatotic and partial grafts were predictive of poorer patient survival, and ABO incompatibility was predictive of poorer graft survival. CONCLUSIONS: Orthotopic liver transplantation is an effective treatment in fulminant hepatitis. Use of high-risk grafts permitted transplantation of 83% of patients, but was responsible for higher mortality. PMID:7639578
Luzar, B; Ferlan-Marolt, V; Poljak, M; Sojar, V; Stanisavljević, D; Bukovac, T; Markovic, S
The infrequent occurrence of herpes simplex virus (HSV) hepatitis in healthy women in comparison with the high prevalence of HSV infections suggests that, in addition to deranged immunity, an underlying condition in the liver might be necessary to develop HSV hepatitis. We report the case of a 28-year-old pregnant woman in the 28 (th) week of gestation. Following HSV type 2 infection of the uterine cervix, acute liver failure developed, necessitating urgent liver transplantation. In addition to fulminant HSV type 2 hepatitis, the explanted liver also showed the histological features of acute fatty liver of pregnancy. The presented case suggests a possible pathogenetic role of acute fatty liver of pregnancy in the development of fulminant HSV hepatitis following recurrent infection with HSV in healthy pregnant women. We believe that early histopathological diagnosis, followed by specific antiviral treatment and liver transplantation in selected patients may improve the clinical outcome of otherwise almost uniformly fatal HSV hepatitis.
Liver transplant is the criterion standard for patients with end-stage liver disease. Yet there is no liver transplant in Syria. Traveling abroad for a liver transplant is a luxury few Syrians can afford. There is currently an on-going debate whether to start a liver transplant program using living or deceased donors. In 2003, a new law was enacted, authorizing the use of organs from volunteer strangers and deceased donors. Despite the positive aspects of this law (allowing unrelated donors to increase the number of transplants in the country); the negative aspects also were obvious. The poor used the law to sell their organs to the rich, and this model is in violation of the Istanbul Declaration. To better document transplant communities' perceptions on organ donation, an e-mail survey was sent to a nationally representative sample of physicians (n = 115) that showed that 58% of respondents did not support the start of liver transplant from live donors, as they fear a considerable risk for the donor and the recipient. Seventy-one percent of respondents believe that unrelated kidney donation has contributed to tarnishing the reputation of transplant, and 56% believe that a deceased-donor program can run in parallel with unrelated organ donations. The interest in deceased-donor program has been affected negatively by the systematic approach of using poor persons as the source of the organ. This lack of interest has affected starting a liver program that relies on deceased donors; especially the need for kidneys is more than livers. Health authorities in Syria were inclined to initiate a liver transplant program from live donors, despite the risks of serious morbidities and mortality. In conclusion then, paid kidney donation in actual effect is actually a hindrance to establishing a deceased-donor liver program.
Dom, Geert; Peuskens, Hendrik
Although liver transplantation (LT) is performed increasingly for patients with end-stage alcoholic liver disease (ALD), the topic remains controversial. Traditionally, the role of an addiction specialist focused on the screening and identification of patients with a high risk on relapse in heavy alcohol use. These patients were in many cases subsequently excluded from a further LT procedure. Recently, awareness is growing that not only screening of patients but also offering treatment, helping patients regain and maintain abstinence is essential, opening up a broader role for the addiction specialist (team) within the whole of the transplant procedure. Within this context, high-risk assessment is proposed to be an indication of increasing addiction treatment intensity, instead of being an exclusion criterion. In this review we present an overview regarding the state of the art on alcohol relapse assessment and treatment in patients with alcohol use disorders, both with and without ALD. Screening, treatment and monitoring is suggested as central roles for the addiction specialist (team) integrated within transplant centers. PMID:26301051
He, Jinjun; Hao, Shuai; Zhang, Hao; Guo, Fuzheng; Huang, Lingyun; Xiao, Xueyuan; He, Dacheng
Liver regeneration has been studied for decades; however, its regulation remains unclear. In this study, we report a dynamic tracing of protein synthesis in rat regenerating liver with a new proteomic technique, (35) S in vivo labeling analysis for dynamic proteomics (SiLAD). Conventional proteomic techniques typically measure protein alteration in accumulated amounts. The SiLAD technique specifically detects protein synthesis velocity instead of accumulated amounts of protein through (35) S pulse labeling of newly synthesized proteins, providing a direct way for analyzing protein synthesis variations. Consequently, protein synthesis within short as 30 min was visualized and protein regulations in the first 8 h of regenerating liver were dynamically traced. Further, the 3.5-5 h post partial hepatectomy (PHx) was shown to be an important regulatory turning point by acute regulation of many proteins in the initiation of liver regeneration.
Shellmer, D. A.; Dabbs, A. DeVito; Dew, M. A.; Noll, R. B.; Feldman, H.; Strauss, K.; Morton, D. H.; Vockley, G.; Mazariegos, G. V.
MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one year and/or three years post-liver transplantation. Findings show either no significant change or improvement in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced either no significant change or improvement in adaptive scores. In general, findings may indicate that liver transplantation curtails additional central nervous system damage and neurocognitive decline providing an opportunity for stabilization or improvement in functioning. PMID:20946191
Kallwitz, Eric R
Loss of muscle mass and function is a common occurrence in both patients with decompensated cirrhosis and those undergoing liver transplantation. Sarcopenia is associated with morbidity and mortality before and after liver transplantation. The ability of skeletal muscle mass to recover after transplant is questionable, and long term adverse events associated with persistent sarcopenia have not been well studied. Limited data is available examining mechanisms by which decreased muscle mass might develop. It is not clear which interventions might reduce the prevalence of sarcopenia and associated health burdens. However, measures to either decrease portal hypertension or improve nutrition appear to have benefit. Research on sarcopenia in the liver transplant setting is hampered by differing methodology to quantify muscle mass and varied thresholds determining the presence of sarcopenia. One area highlighted in this review is the heterogeneity used when defining sarcopenia. The health consequences, clinical course and potential pathophysiologic mechanisms of sarcopenia in the setting of cirrhosis and liver transplantation are further discussed.
Jamil, K M; Hydes, T J; Cheent, K S; Cassidy, S A; Traherne, J A; Jayaraman, J; Trowsdale, J; Alexander, G J; Little, A-M; McFarlane, H; Heneghan, M A; Purbhoo, M A; Khakoo, S I
Objective Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. Design Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing. Results NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p<0.05) and NKp30 (p<0.001), reduced cytotoxicity (p<0.001) and interferon (IFN)-γ secretion (p<0.025). There was no segregation of this effect with HLA-C, and these functional changes were not observed in individuals with HCV. Microarray and RT-qPCR analysis demonstrated downregulation of STAT4 in NK cells from LT recipients (p<0.0001). Changes in the expression levels of the transcription factors Helios (p=0.06) and Hobit (p=0.07), which control NKp46 and IFNγ expression, respectively, were also detected. Hypofunctionality of NK cells was associated with impaired STAT4 phosphorylation and downregulation of the STAT4 target microRNA-155. Conversely in HCV-LT NK cell tolerance was reversed, consistent with the more aggressive outcome of LT for HCV. Conclusions LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. NK cell tolerance occurs upstream of major histocompatibility complex (MHC) class I mediated education, and is associated with deficient STAT4 phosphorylation. STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease. PMID:26887815
Lee, Chen-Fang; Cheng, Chih-Hsien; Wang, Yu-Chao; Soong, Ruey-Shyang; Wu, Tsung-Han; Chou, Hong-Shiue; Wu, Ting-Jung; Chan, Kun-Ming; Lee, Ching-Song; Lee, Wei-Chen
The objective of this study was to evaluate the results of adult ABO-incompatible living donor liver transplantation (LDLT).ABO-incompatible LDLT is an aggressive treatment that crosses the blood-typing barrier for saving lives from liver diseases. Although graft and patient survival have been improved recently by various treatments, the results of adult ABO-incompatible LDLT require further evaluation.Two regimens were designed based on isoagglutinin IgG and IgM titers and the time course of immunological reactions at this institute. When isoagglutinin IgG and IgM titers were ≤64, liver transplantation was directly performed and rituximab (375 mg/m) was administrated on postoperative day 1 (regimen I). When isoagglutinin titers were >64, rituximab (375 mg/m) was administered preoperatively with or without plasmapheresis and boosted on postoperative day 1 (regimen II). Immunosuppression was achieved by administration of mycophenolate mofetil, tacrolimus, and steroids.Forty-six adult ABO-incompatible and 340 ABO-compatible LDLTs were performed from 2006 to 2013. The Model for End-Stage Liver Disease scores for ABO-incompatible recipients ranged from 7 to 40, with a median of 14. The graft-to-recipient weight ratio ranged from 0.61% to 1.61% with a median of 0.91%. The 1-, 3-, and 5-year survival rates were 81.7%, 75.7%, and 71.0%, respectively, for ABO-incompatible LDLT recipients, compared to 81.0%, 75.2%, and 71.5% for ABO-C recipients (P = 0.912). The biliary complication rate was higher in ABO-incompatible LDLT recipients than in the ABO-compatible recipients (50.0% vs 29.7%, P = 0.009).In the rituximab era, the blood type barrier can be crossed to achieve adult ABO-incompatible LDLT with survival rates comparable to those of ABO-compatible LDLT, but with more biliary complications.
Pereira, F; Herrera, J; Mora, N P; Nuño, J; Turrión, V S; Vicente, E; Ardaiz, J
Twenty piggy-back (PB) liver transplantations (LT) were compared with 20 LT performed by the standard technique in order to evaluate whether or not the theoretical haemodynamic advantages of the preservation of the inferior vena cava (IVC) have any impact on the final results of the LT. Statistically significant differences were observed in the duration of the hepatectomy, which was longer for PB LT (192 min vs. 146 min), and in the duration of the anhepatic phase, which was shorter in that group (52 min vs. 76 min). There were no differences in the duration of the complete surgical procedure, consumption of blood products, incidence of postoperative acute renal failure, number of reoperations or survival.
We report a unique case of a 3-mo-old female with consumptive hypothyroidism and liver hemangioendothelioma who required pharmacological doses of thyroid hormones and was cured following liver transplantation. Liver hemangioendotheliomas are capable of producing an excess of the thyroid hormone inac...
Sańko-Resmer, J; Paczek, L; Wyzgał, J; Ziółkowski, J; Ciszek, M; Alsharabi, A; Grzelak, I; Paluszkiewicz, R; Patkowski, W; Krawczyk, M
As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.
Robles, Ricardo; Figueras, Joan; Turrión, Victor S.; Margarit, Carlos; Moya, Angel; Varo, Evaristo; Calleja, Javier; Valdivieso, Andres; Valdecasas, Juan Carlos G.; López, Pedro; Gómez, Manuel; de Vicente, Emilio; Loinaz, Carmelo; Santoyo, Julio; Fleitas, Manuel; Bernardos, Angel; Lladó, Laura; Ramírez, Pablo; Bueno, F S.; Jaurrieta, Eduardo; Parrilla, Pascual
Objective: To assess the real utility of orthotopic liver transplantation (OLT) in patients with cholangiocarcinoma, we need series with large numbers of cases and long follow-ups. The aim of this paper is to review the Spanish experience in OLT for hilar and peripheral cholangiocarcinoma and to try to identify the prognostic factors that could influence survival. Summary Background Data: Palliative treatment of nondisseminated irresectable cholangiocarcinoma carries a zero 5-year survival rate. The role of OLT in these patients is controversial, due to the fact that the survival rate is lower than with other indications for transplantation and due to the lack of organs. Methods: We retrospectively reviewed 59 patients undergoing OLT in Spain for cholangiocarcinoma (36 hilar and 23 peripheral) over a period of 13 years. We present the results and prognostic factors that influence survival. Results: The actuarial survival rate for hilar cholangiocarcinoma at 1, 3, and 5 years was 82%, 53%, and 30%, and for peripheral cholangiocarcinoma 77%, 65%, and 42%. The main cause of death, with both types of cholangiocarcinoma, was tumor recurrence (present in 53% and 35% of patients, respectively). Poor prognosis factors were vascular invasion (P < 0.01) and IUAC classification stages III–IVA (P < 0.01) for hilar cholangiocarcinoma and perineural invasion (P < 0.05) and stages III-IVA (P < 0.05) for peripheral cholangiocarcinoma. Conclusions: OLT for nondisseminated irresectable cholangiocarcinoma has higher survival rates at 3 and 5 years than palliative treatments, especially with tumors in their initial stages, which means that more information is needed to help better select cholangiocarcinoma patients for transplantation. PMID:14745336
Kasahara, Mureo; Kozaki, Koichi; Yoshida, Toru; Yamamoto, Hidekazu; Ogawa, Kohei; Ogura, Yasuhiro; Tanaka, Koichi
Because right-lobe living-donor liver transplantation was introduced in adult-to-adult liver transplantation to mitigate the problems of small-for-size grafts, some technical controversies have been reported. This report describes a case of graft subcapsular hematoma due to parenchymal injury. A 53-year-old woman underwent a right-lobe living-donor liver transplantation for acute-on-chronic liver failure due to primary biliary cirrhosis. A huge subcapsular hematoma was discovered by routine Doppler echogram examination on the first posttransplantation day. Relaparotomy findings revealed that rotation of the graft for the hemostasis procedure during the transplant operation had induced a compression injury to the graft by the xiphoid process. It was speculated that a small laceration in the graft parenchyma led to the major subcapsular hematoma. This experience suggests that the graft liver must be handled with special care to prevent potential mechanical injury.
Stickel, Felix; Inderbitzin, Daniel; Candinas, Daniel
Patients with end-stage liver disease often reveal significant protein-energy malnutrition, which may deteriorate after listing for transplantation. Since malnutrition affects post-transplant survival, precise assessment must be an integral part of pre- and post-surgical management. While there is wide agreement that aggressive treatment of nutritional deficiencies is required, strong scientific evidence supporting nutritional therapy is sparse. In practice, oral nutritional supplements are preferred over parenteral nutrition, but enteral tube feeding may be necessary to maintain adequate calorie intake. Protein restriction should be avoided and administration of branched-chain amino acids may help yield a sufficient protein supply. Specific problems such as micronutrient deficiency, fluid balance, cholestasis, encephalopathy, and comorbid conditions need attention in order to optimize patient outcome.
Naranjo, J; Poniachik, J; Cisco, D; Contreras, J; Oksenberg, D; Valera, J M; Díaz, J C; Rojas, J; Cardemil, G; Mena, S; Castillo, J; Rencoret, G; Godoy, J; Escobar, J; Rodríguez, J; Leyton, P; Fica, A; Toledo, C
Oral ulcers are a frequent problem in transplant medicine. It is important to consider infectious etiologies, exacerbated by the immunosuppressive treatment, but other etiologies are also possible, like adverse drug reactions. Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used in combination with calcineurin inhibitors and steroids. Reports of renal transplant patients with oral ulcers related to MMF have appeared lately and herein we have described 2 cases in liver transplant patients. Their oral ulcers resolved quickly after suspension of the medication. Our 2 cases in liver transplant patients represented a unique setting for this type of complication.
Tanikella, Rajasekhar; Kawut, Steven M.; Brown, Robert S.; Krowka, Michael J.; Reinen, Jenna; Dinasarapu, Chandrasekhar R.; Trotter, James F.; Roberts, Kari E.; Mohd, Mustafa A.; Arnett, Donna K.; Fallon, Michael B.
Health-related quality of life (HRQOL) is an important measure of the effects of chronic liver disease in affected patients that helps guide interventions to improve well-being. However, the relationship between HRQOL and survival in liver transplant candidates remains unclear. We examined whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the Short Form 36 (SF-36) Health Survey were associated with survival in liver transplant candidates. We administered the SF-36 questionnaire (version 2.0) to patients in the Pulmonary Vascular Complications of Liver Disease study, a multicenter prospective cohort of patients evaluated for liver transplantation in 7 academic centers in the United States between 2003 and 2006. Cox proportional hazards models were used with death as the primary outcome and adjustment for liver transplantation as a time-varying covariate. The mean age of the 252 participants was 54 ± 10 years, 64% were male, and 94% were white. During the 422 person years of follow-up, 147 patients (58%) were listed, 75 patients (30%) underwent transplantation, 49 patients (19%) died, and 3 patients were lost to follow-up. Lower baseline PCS scores were associated with an increased mortality rate despite adjustments for age, gender, Model for End-Stage Liver Disease score, and liver transplantation (P for the trend = 0.0001). The MCS score was not associated with mortality (P for the trend = 0.53). In conclusion, PCS significantly predicts survival in liver transplant candidates, and interventions directed toward improving the physical status may be helpful in improving outcomes in liver transplant candidates. PMID:20104497
Orlando, G; De Luca, L; Toti, L; Zazza, S; Angelico, M; Casciani, C U; Tisone, G
Portal vein thrombosis (PVT) is a frequent finding in liver transplantation, the management of which depends mainly on its extent. In cases of mild to moderate PVT, a low dissection of the portal trunk, a jump graft, or direct implantation of graft portal vein into large venous collaterals or thrombectomy offer alternatives. For severe PVT anecdotal reports suggest that cavoportal hemitransposition, portal arterialization, or combined liver and intestine transplantation may be attempted, although the results to date are not satisfactory. When extensive perivenous and venous inflammatory changes reach the infrapancreatic region, liver transplantation probably should not be performed due to the high mortality rate.
Perito, Emily Rothbaum; Rhee, Sue; Glidden, Dave; Roberts, John Paul; Rosenthal, Philip
In adult liver transplant recipients, the donor body mass index (dBMI) is associated with posttransplant obesity but not with graft or patient survival. Because of the obesity epidemic in the United States and the already limited supply of liver donors, clarifying whether the dBMI affects pediatric outcomes is important. United Network for Organ Sharing data for pediatric liver transplants in the United States (1990-2010) were evaluated. Data on transplants performed between 2004 and 2010 (n = 3788) were used for survival analyses with Kaplan-Meier and Cox proportional hazards models and for posttransplant obesity analyses with generalized estimating equations. For children receiving adult donor livers, a dBMI of 25 to <35 kg/m(2) was not associated with graft or patient survival in univariate or multivariate analyses. A dBMI ≥ 35 kg/m(2) increased the risk of graft loss [hazard ratio (HR) = 2.54, 95% confidence interval (CI) = 1.29-5.01, P = 0.007] and death (HR = 3.56, 95% CI = 1.64-7.72, P = 0.001). For pediatric donors, the dBMI was not associated with graft loss or mortality in a univariate or multivariate analysis. An overweight or obese donor was not a risk factor for posttransplant obesity. Overweight and obesity are common among liver transplant donors. This analysis suggests that for adult donors, a body mass index (BMI) of 25 to <35 kg/m(2) should not by itself be a contraindication to liver donation. Severe obesity (BMI ≥ 35 kg/m(2)) in adult donors increased the risk of graft loss and mortality, even after adjustments for recipient, donor, and transplant risk factors. Posttransplant obesity was not associated with the dBMI in this analysis. Further research is needed to clarify the impact of donor obesity on pediatric liver transplant recipients.
Fernández del Río, R.; O'Hara, M.E.; Holt, A.; Pemberton, P.; Shah, T.; Whitehouse, T.; Mayhew, C.A.
Background The burden of liver disease in the UK has risen dramatically and there is a need for improved diagnostics. Aims To determine which breath volatiles are associated with the cirrhotic liver and hence diagnostically useful. Methods A two-stage biomarker discovery procedure was used. Alveolar breath samples of 31 patients with cirrhosis and 30 healthy controls were mass spectrometrically analysed and compared (stage 1). 12 of these patients had their breath analysed after liver transplant (stage 2). Five patients were followed longitudinally as in-patients in the post-transplant period. Results Seven volatiles were elevated in the breath of patients versus controls. Of these, five showed statistically significant decrease post-transplant: limonene, methanol, 2-pentanone, 2-butanone and carbon disulfide. On an individual basis limonene has the best diagnostic capability (the area under a receiver operating characteristic curve (AUROC) is 0.91), but this is improved by combining methanol, 2-pentanone and limonene (AUROC curve 0.95). Following transplant, limonene shows wash-out characteristics. Conclusions Limonene, methanol and 2-pentanone are breath markers for a cirrhotic liver. This study raises the potential to investigate these volatiles as markers for early-stage liver disease. By monitoring the wash-out of limonene following transplant, graft liver function can be non-invasively assessed. PMID:26501124
Onoe, Takashi; Tahara, Hiroyuki; Tanaka, Yuka; Ohdan, Hideki
Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed. PMID:26755868
Massarollo, P C B; Shiroma, M E; Rodrigues, A J; Mies, S
Subcapsular hematoma of the graft is an underreported complication of liver transplantation (LT). Among 408 LT performed from September 1, 1985, to September 1, 2000, eight patients developed a subcapsular hematoma within 30 days after LT (8/408 = 2.0%). Among the six early cases observed, five required further surgical approaches due to hematoma progression, rupture, and hemorrhage. One patient underwent liver retransplantation due to uncontrollable hepatic hemorrhage. The two more recent cases were successfully treated by early opening of the Glisson's capsule with hemostasis of the hepatic raw bleeding surface. The five patients who developed acute renal failure required dialysis. Three patients died during hospitalization. Among the survivors, two were discharged on the postoperative (PO) day 15; the others on PO day 37, 38, and 56. In conclusion, subcapsular hematoma of the graft is a potentially serious complication of LT that may produce severe hemorrhage, shock, and in extreme cases, graft loss or even death. The severity of the complication is related to the extension of the decapsulated area of the graft. An early surgical approach with intentional opening of the hematoma before progression of the lesion seems to facilitate hemostasis and improve results.
Margarit, C.; Murio, E.; Lazaro, J. L.; Charco, R.; Vidal, M. T.; Bonnin, J.
Caroli's disease is characterized by congenital cystic dilatation of the intrahepatic bile ducts. In 7% of casea a malignant tumor develops complicating the course of the disease. We report the case of a 25 year-old woman in whom Caroli's disease was diagnosed at the age of 11. From that time on, she had several episodes of cholangitis. In 1989, the abdominal ultrasound and CT scan showed dilatation of the intrahepatic bile ducts, intracystic lithiasis and a solid mass. FNA cytology showed a papillary adenocarcinoma. At laparotomy a tumor was found occupying both hepatic lobes, and intraoperative US showed another two nodules in the left lobe. The tumor was considered unresectable. Examination of the hilar lymph nodes was tumor-negative. Two weeks later, the patient underwent an ortothopic liver transplantation (OLT). The pathological examination confirmed Caroli's disease with adenocarcinoma. Two years after OLT, the patient is alive with normal liver function and no evidence of disease. To our knowledge this is the first case report of adenocarcinoma in Caroli's disease treated by OLT. PMID:8260439
Mendizabal, Manuel; Reddy, K Rajender; Cassuto, James; Olthoff, Kim M; Faust, Thomas W; Makar, George A; Rand, Elizabeth B; Shaked, Abraham; Abt, Peter L
The improved life expectancy of patients with cystic fibrosis (CF) has led to a change in the impact of liver disease on the prognosis of this population. Liver transplantation has emerged as the procedure of choice for patients with CF and features of hepatic decompensation and for intractable variceal bleeding as a major manifestation. We retrospectively reviewed the United Network for Organ Sharing database to analyze the outcomes of 55 adults and 148 children with CF who underwent liver transplantation, and we compared them to patients who underwent transplantation for other etiologies. We additionally compared the benefits of liver transplantation among patients who underwent transplantation for cystic fibrosis-related liver disease (CFLD) and those who remained on the waiting list. The 5-year survival rates for children and adults undergoing liver transplantation were 85.8% and 72.7%, respectively (P = 0.016). A multivariate Cox regression analysis comparing pediatric and adult CF patients to patients who underwent transplantation for other etiologies noted lower 5-year survival rates (P < 0.0001). However, compared to those remaining on the waiting list, pediatric transplant recipients with CF (hazard ratio = 0.33, 95% confidence interval = 0.16-0.70, P = 0.004) and adult transplant recipients with CF (hazard ratio = 0.25, 95% confidence interval = 0.11-0.57, P = 0.001) gained a significant survival benefit. In conclusion, long-term outcomes in patients with CFLD are acceptable but are inferior in comparison with the outcomes of those undergoing transplantation for other etiologies. Despite such observations, a survival benefit was noted in transplant patients versus those who remained on the waiting list.
Salvalaggio, Paolo R; Seda Neto, João; Alves, Jefferson Andre; Fonseca, Eduardo A; Carneiro de Albuquerque, Luiz; Andraus, Wellington; Massarollo, Paulo B; Duro Garcia, Valter; Maurette, Rafael J; Ruf, Andrés E; Pacheco-Moreira, Lucio F; Caicedo Rusca, Luis A; Osorio, Veronica Botero; Matamoros, Maria Amalia; Varela-Fascinetto, Gustavo; Jarufe, Nicolas P
We reviewed the history, volume, outcomes, uniqueness, and challenges of living donor liver transplantation (LDLT) in Latin America. We used the data from the Latin American and Caribbean Transplant Society, local transplant societies, and opinions from local transplant experts. There are more than 160 active liver transplant teams in Latin America, but only 30 centers have used LDLT in the past 2 years. In 2014, 226 LDLTs were done in the region (8.5% of liver transplant activities). Living donor liver transplantation is mainly restricted to pediatric patients. Adult-to-adult LDLT activities decreased after the implementation of the model for end-stage liver disease score and a concomitant increase on the rate of deceased donors per million population. Posttransplant outcome analysis is not mandatory, transparent or regulated in most countries. More experienced teams have outcomes comparable to international expert centers, but donor and recipient morbidity might be underreported. Latin America lags behind in terms of the number of adult LDLT and the rate of living donor utilization in comparison with other continents with similar donation rates. Local alliances and collaborations with major transplant centers in the developed world will contribute to the development of LDLT in Latin America.
Nacoti, Mirco; Corbella, Davide; Fazzi, Francesco; Rapido, Francesca; Bonanomi, Ezio
Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, “developmental hemostasis”, demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the “cell based model of coagulation”, takes into account the interaction between plasma proteins and cells. In the last, the concept of “rebalanced coagulation” highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation
Heits, N; Guenther, R; Kuechler, T; Becker, T; Braun, F
The shortage of postmortem donor organs is a well-known problem in Germany. Willingness in the general population is 80%, but less than 14% have an organ donor card. We evaluated the free decision of liver transplant candidates who filled out a donor card before signing the informed consent for the transplant procedure. We analyzed 122 patients of mean age 55.9 years (range, 15.4-74.1) who signed an informed consent for liver transplantation between January 10, 2007, and January 24, 2012. The patients received the original text of the German organ donor card with tick boxes on the informed consent form for liver transplantation. All patients were informed that their decision had no impact on further management. Patients were able to choose between (1) becoming a donor, (2) refusal, (3) transfer of the decision to another person, or (4) no decision. All patients signed the informed consent to be listed for liver transplantation: 73.8% (n = 90) chose to become a donor; 5.7% (n = 7) refused; 5.7% (n = 7) transferred the decision to another person; and 14.8% (n = 18) did not come to a decision. Interestingly, not all candidates for liver transplantation were willing to become an organ donor in the time of expressed consent. However, willingness to sign the donor card was much higher among liver transplant candidates compared with the general population.
Pardo, Fernando; Pons, José Antonio; Briceño, Javier
With the aim to promote the elaboration of consensus documents on state of the art topics in liver transplantation with multidisciplinary management, the Spanish Society for Liver Transplantation (SETH) organized the V Consensus Meeting with the participation of experts from all the Spanish liver transplant programs. In this edition, the following topics were revised, and we present the summary: 1. High-risk receptors; 2. Immunosuppression scenarios; and 3. Management of the patient with hepatocarcinoma in the waiting list.
Pardo, Fernando; Pons, José Antonio; Briceño, Javier
With the aim to promote the elaboration of consensus documents on state of the art topics in liver transplantation with multidisciplinary management, the Spanish Society for Liver Transplantation (SETH) organized the V Consensus Meeting with the participation of experts from all the Spanish liver transplant programs. In this edition, the following topics were revised, and we present the summary: 1. High-risk receptors; 2. Immunosuppression scenarios; and 3. Management of the patient with hepatocarcinoma in the waiting list.
Wong, Yik Chun; McCaughan, Geoffrey W; Bowen, David G; Bertolino, Patrick
Both experimental and clinical studies have shown that the liver possesses unique tolerogenic properties. Liver allografts can be spontaneously accepted across complete major histocompatibility mismatch in some animal models. In addition, some liver transplant patients can be successfully withdrawn from immunosuppressive medications, developing ‘operational tolerance'. Multiple mechanisms have been shown to be involved in inducing and maintaining alloimmune tolerance associated with liver transplantation. Here, we focus on CD8 T-cell tolerance in this setting. We first discuss how alloreactive cytotoxic T-cell responses are generated against allografts, before reviewing how the liver parenchyma, donor passenger leucocytes and the host immune system function together to attenuate alloreactive CD8 T-cell responses to promote the long-term survival of liver transplants. PMID:27867515
Galvão, Flávio Henrique Ferreira; Bacchella, Telesforo; Cerqueira Machado, Marcel
Technical difficulties hamper the widespread use of intestinal transplantation in rats. We evaluated the feasibility in training this microsurgical model for medical students. Thirty eight students were assessed. After information about intestinal transplantation in rats, they spontaneously agreed to be trained for this procedure. The course consisted of 4-h weekly lessons during 4-month period. The teaching process includes assessment in four phases: I) conception of intestinal transplantation and rat anatomy; II) basic microsurgery training; III) donor operation; IV) donor/recipient operation. Wistar rats were used as donors and recipients in one-step small bowel transplantation. All students (100%) reached phase II, seven students (18.42%) reached phase III and two students (5.26%) reached phase IV. Decreased interest about the theme, lack of time and patience, frustration and/or inability were all reasons given by the student that may have contributed to the low rate of success. Medical students achieved a low rate of completion for training in rat intestinal transplantation microsurgical procedures.
Kireev, Roman; Bitoun, Samuel; Cuesta, Sara; Tejerina, Alejandro; Ibarrola, Carolina; Moreno, Enrique; Vara, Elena; Tresguerres, Jesus A F
Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35 min of warm hepatic ischemia and 36 h of reperfusion. One experimental group remained untreated and 2 were given 10mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation.
Ding, Fan; Tang, Hui; Xu, Chi; Jiang, Zai-Bo; Yi, Shu-Hong; Li, Hua; Jiang, Nan; Chen, Wen-Jie; Yang, Qing; Yang, Yang; Chen, Gui-Hua
Biliary stenosis is a common complication after liver transplantation, and has an incidence rate ranging from 4.7% to 12.5% based on our previous study. Three types of biliary stenosis (anastomotic stenosis, non-anastomotic peripheral stenosis and non-anastomotic central hilar stenosis) have been identified. We report the outcome of two patients with anastomotic stricture after liver transplantation who underwent successful cutting balloon treatment. Case 1 was a 40-year-old male transplanted due to subacute fulminant hepatitis C. Case 2 was a 57-year-old male transplanted due to hepatitis B virus-related end-stage cirrhosis associated with hepatocellular carcinoma. Both patients had similar clinical scenarios: refractory anastomotic stenosis after orthotopic liver transplantation and failure of balloon dilation of the common bile duct to alleviate biliary stricture. PMID:28104994
Vollet Filho, José D.; da Silveira, Marina R.; Castro-e-Silva, Orlando; Bagnato, Vanderlei S.; Kurachi, Cristina
Evaluating transplantation grafts at harvest is essential for its success. Laser-induced fluorescence spectroscopy (LIFS) can help monitoring changes in metabolic/structural conditions of tissue during transplantation. The aim of the present study is to correlate LIFSobtained spectra of human hepatic grafts during liver transplantation with post-operative patients' mortality rate and biochemical parameters, establishing a method to exclude nonviable grafts before implantation. Orthotopic liver transplantation, piggyback technique was performed in 15 patients. LIFS was performed under 408nm excitation. Collection was performed immediately after opening donor's abdominal cavity, after cold perfusion, end of back-table period, and 5 min and 1 h after warm perfusion at recipient. Fluorescence information was compared to lactate, creatinine, bilirubin and INR levels and to survival status. LIFS was sensitive to liver changes during transplantation stages. Study-in-progress; initial results indicate correlation between fluorescence and life/death status of patients.
Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E
In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213
Pham, Thomas A; Enns, Gregory M; Esquivel, Carlos O
Inborn metabolic diseases of the liver can be life-threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver.
Parent, Brendan; Caplan, Arthur L
The 11 original regions for organ allocation in the United States were determined by proximity between hospitals that provided deceased donors and transplant programs. As liver transplants became more successful and demand rose, livers became a scarce resource. A national system has been implemented to prioritize liver allocation according to disease severity, but the system still operates within the original procurement regions, some of which have significantly more deceased donor livers. Although each region prioritizes its sickest patients to be liver transplant recipients, the sickest in less liver-scarce regions get transplants much sooner and are at far lower risk of death than the sickest in more liver-scarce regions. This has resulted in drastic and inequitable regional variation in preventable liver disease related death rate.A new region districting proposal - an eight district model - has been carefully designed to reduce geographic inequities, but is being fought by many transplant centers that face less scarcity under the current model. The arguments put forth against the new proposal, couched in terms of fairness and safety, will be examined to show that the new system is technologically feasible, will save more lives, and will not worsen socioeconomic disparity. While the new model is likely not perfect, it is a necessary step toward fair allocation.
Honoré, P; Detry, O; Meurisse, M; Jacquet, N
The orthotopic liver transplantation (OLT) program of the University of Liège was initiated in 1986. Between 1986 and December 1998, 150 adult OLT have been performed in our institution, including 18 liver retransplantations, 1 combined heart and liver transplantation and 3 combined liver and kidney transplantations. The aim of this study was to report the last 3 years of our experience. From January 1996 to November 1998, we performed 50 OLT on 49 patients. Three were retransplantations and two were combined liver and kidney transplantations. Fourty-three patients were transplanted for chronic liver disease and 6 for acute or subacute hepatopathy. Mean waiting time on the list was 4 weeks. Immunosuppression was based on triple therapy (cyclosporin A/tacrolimus, steroids, azathioprine), with steroid and azathioprine withdrawal in most of the patients after 3 months. In the chronic liver disease group, operative (< 30 days) survival was 95% (peroperative myocardial infarction in 2 patients). In the acute liver disease group, postoperative survival was 66%. No perioperative death occurred in 1997 and 1998. Actuarial one year survival was 87%. In our experience, OLT has become a safe procedure.
Naitik, Pandya; Prakash, Tigari; Kotresha, Dupadahalli; Rao, Nadendla Rama
To evaluate the effect of an antitumor activity of Terminalia catappa on lipid lowering activity in transplanted fibrosarcoma in Wistar albino rats. Methylcholantherene-induced fibrosarcoma was transplanted in rats. After 30(th) day when tumor became palpable, started the treatment of ethanolic extract of Terminalia catappa by orally (250 and 500 mg/kg) for a period of 20 days. The blood sample was collected on 21(st) day, and the liver and the kidney were also removed for studying the lipid profile in serum and the tissues. The levels of total cholesterol, triglycerides and very low density lipoprotein (VLDL) were markedly elevated and high density lipoprotein (HDL) was markedly decreased in the serum of tumor bearing rats. Significant alterations were also observed in the lipid profile of liver and kidney. These changes were significantly reversed in Terminalia catappa (500 mg/kg) treated animals. The reversal of altered lipid levels to normal values in rats with experimentally induced tumor was showed antitumor activity by Terminalia catappa.
Guex, E; Cheseaux, M; Bertrand, P Coti; Piquet, M A; Bouvry, S; Pilon, N; Halkic, N; Pascual, M; Roulet, M
The prevalence of undernutrition was prospectively studied in 143 patients before liver transplantation between 1997 and 2005. Nutritional assessment is a particularly tricky problem in cirrhosis and mid-arm muscle circumference is considered as the best reliable anthropometric tool. In this prospective study, prevalence rate is very high (61%) and undernutrition is more frequent in alcoholic cirrhotic patients. In conclusion, these patients should benefit from an early dietician intervention before liver transplantation.
Lai, Ming-chun; Zhang, Wei; Yang, Zhe; Zhang, Wu; Owusu-Ansah, K G; Yu, Song-feng; Geng, Lei; Xie, Hai-yang; Zhou, Lin; Zheng, Shu-sen
Mucormycosis is a rare but potentially lethal complication of liver transplantation. Most reported cases have involved rhinocerebral, pulmonary, gastrointestinal, or disseminated forms. We present herein the case of a 61-year-old male patient with hepatocellular carcinoma who developed isolated penile mucormycosis after orthotopic liver transplantation. Such a case has not been reported in the literature to date. Early diagnosis and timely surgical intervention combined with comprehensive treatment are the key factors for improving the survival rate in patients with mucormycosis.
López-Herrera Rodríguez, D; Guerrero Domínguez, R; Mellado Miras, P; Gómez Sosa, L
Familial amyloid polyneuropathy (FAP) is a systemic amyloidosis caused by mutated transthyretin. Cardiac amyloidosis, the major prognostic determinant in systemic amyloidosis, is characterized by infiltration of the myocardium, leading to cardiomyopathy and conduction disturbances. Liver transplantation is the only curative option for patients with FAP. The case is presented of a 36-year-old patient with type i FAP with cardiac involvement, proposed for liver transplant surgery, which was successfully performed without any preoperative event of interest.
Hwang, Hong Pil; Yang, Jae Do; Bae, Sang In; Hwang, Si Eun; Cho, Baik Hwan; Yu, Hee Chul
Severe portal vein thrombosis (PVT) is often considered a relative contraindication for living donor liver transplantation due to high associated risks and morbidity. Meanwhile, improvement in operative techniques, resulting in higher success rates has removed PVT from the list of contraindications in deceased donor liver transplantation (DDLT). In this report, we describe a surgical technique for DDLT using polytetrafluoroethylene graft from the inferior mesenteric vein for portal inflow in patient with portomesenteric thrombosis.
Rostron, Anthony; Carter, Vaughan; Mutunga, Mbithe; Cavanagh, Gary; O'Suilleabhain, Criostoir; Burt, Alistair; Jaques, Bryon; Talbot, David; Manas, Derek
We present a case of a 23-year-old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.
Olthoff, Kim M.; Smith, Abigail R.; Abecassis, Michael; Baker, Talia; Emond, Jean C.; Berg, Carl L.; Beil, Charlotte A.; Burton, James R.; Fisher, Robert A.; Freise, Christopher E.; Gillespie, Brenda W.; Grant, David R.; Humar, Abhi; Kam, Igal; Merion, Robert M.; Pomfret, Elizabeth A.; Samstein, Benjamin; Shaked, Abraham
Objective To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers to outcomes of deceased donor liver transplant (DDLT) and identify key variables impacting patient and graft survival. Summary Background Data The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) is a prospective multicenter NIH study comparing outcomes of LDLT and DDLT and associated risks. Methods Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in A2ALL transplanted between 1/1/1998 and 1/31/2014 at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. Results Survival probability at 10 years was 70% for LDLT and 64% for DDLT. Unadjusted survival was higher with LDLT (HR=0.76, p=0.02) but attenuated after adjustment (HR=0.98, p=0.90) as LDLT recipients had lower mean MELD (15.5 vs 20.4) and fewer were transplanted from ICU, inpatient, on dialysis, ventilated, or with ascites. Post-transplant ICU days were less for LDLT. For all recipients female gender and primary sclerosing cholangitis were associated with improved survival, while dialysis and older recipient/donor age were associated with worse survival. Higher MELD score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. Conclusions LDLT provides significant long-term transplant benefit resulting in transplantation at a lower MELD score, decreased death on waitlist, and excellent post-transplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision-making regarding timing of transplant and donor options. Clinical Trials ID NCT00096733. PMID:26258315
Iida, T; Sawada, N; Takahashi, M; Zendejas, I R; Kayler, L K; Magliocca, J F; Kim, R D; Hemming, A W; Fujita, S
Mucormycosis is an uncommon but frequently fatal infectious complication after solid organ transplantation. We describe successful treatment of invasive mucormycosis in a liver transplant recipient by wound debridement, a right above-elbow arm amputation, and antifungal medications. Early recognition, prompt operative intervention, and initiation of an appropriate antifungal treatment are very important in the management of mucormycosis, a potentially life-threatening infection.
Bardet, Valérie; Junior, Alcindo Pissaia; Coste, Joël; Lecoq-Lafon, Carinne; Chouzenoux, Sandrine; Bernard, Denis; Soubrane, Olivier; Lacombe, Catherine; Calmus, Yvon; Conti, Filoména
Anemia is common following liver transplantation. Because cyclosporine inhibits erythropoietin (Epo) production in experimental models, we investigated whether Epo production was impaired in liver transplant recipients receiving a cyclosporine- or tacrolimus-based immunosuppressive regimen. First, serum Epo levels were measured before and 1 year after transplantation in 35 liver transplant recipients. Second, serum Epo levels were compared in a large series of liver transplant recipients with stable graft and renal functions: 27 receiving a cyclosporine-based and 31 receiving a tacrolimus-based immunosuppressive regimen. A reference group was made up of 22 blood donors and 21 nontransplanted subjects with iron-deficiency anemia. Serum Epo levels were significantly lower after than before liver transplantation, especially in cyclosporine-treated patients. Serum Epo concentrations correlated with hematocrit values in both transplant recipients and control subjects. Using multiple linear regression models, the polynomial relationship between hematocrit and serum Epo values was similar to the control group in patients under tacrolimus, whereas Epo production was significantly reduced in patients under cyclosporine-based immunosuppression. Hematocrit values and the type of calcineurin inhibitor were the only parameters independently related to Epo levels. In conclusion, cyclosporine, but not tacrolimus, inhibits Epo production at the doses used in clinical practice.
Higashi, Hisanobu; Obara, Hideaki; Miyakoshi, Kei; Shinoda, Masahiro; Kitago, Minoru; Shimojima, Naoki; Abe, Yuta; Hibi, Taizo; Yagi, Hiroshi; Matsubara, Kentaro; Yamada, Yohei; Itano, Osamu; Hoshino, Ken; Kuroda, Tatsuo; Kitagawa, Yuko
Many papers have reported on pregnancy and delivery after liver transplantation, but there have been no reports on pregnancy after ABO-incompatible liver transplantation. This paper reports the first successful pregnancy and delivery of a newborn after ABO-incompatible liver transplantation for fulminant hepatic failure. The patient was a 39-year-old female. She had an ABO-incompatible liver transplantation, donated from her husband, due to subacute fulminant hepatitis of unknown etiology. She was taking tacrolimus, methylprednisolone, and mizoribine orally for the maintenance of immunosuppression at the time of discharge. She was discharged uneventfully on postoperative day 38 without any rejection episodes. At 1 year and 6 mo after transplantation, she indicated a wish to become pregnant. Therefore, treatment with mycophenolate mofetil was interrupted at that time. After two miscarriages, she finally became pregnant and delivered transvaginally 3 years after the transplantation. All of the pregnancies were conceived naturally. The newborn was female with a birth weight of 3146 g; the Apgar scores were 9 and 10. Delivery was performed smoothly, and the newborn exhibited no malformations. The mother and the newborn were discharged uneventfully. We suggest that pregnancy is possible for recipients after ABO-incompatible liver transplantation. PMID:28210092
Aydogdu, Sema; Cakir, Murat; Arikan, C; Tumgor, Gokhan; Yuksekkaya, Hasan Ali; Yilmaz, Funda; Kilic, Murat
In this study, we analyze the demographic features, clinical and histopathological findings in patients who underwent liver transplantation for progressive familial intrahepatic cholestasis. We also analyze outcome and impact of liver transplantation on growth and bone mineral content. Most of the patients were presented with jaundice mainly beginning within the first six months. At the time of initial admission; eight patients had short stature (height SD score<2), and four patients had weight SD score<2. Liver transplantation were performed at the age of 43.2+/-27 months (range 9 to 96 months), 6.5+/-3.5 months later after the first admission. Infection, surgical complications and osmotic diarrhea associated with severe metabolic acidosis were noted in 41.4%, 16.6% and 33.3%, respectively. One patient developed posttransplant lymphoproliferative disorder. Overall; 1 year graft and patient survival was 69.2% and 75%, respectively. At the end of the 1st year only 2 patients had height SD score<2. Linear regression of height gain against increase in total body BMD measured at the time of transplantation and 1 year after liver transplantation gave a coefficient r=0.588 (p=0.074). No correlation was found between the height gain and age and PELD score at time of transplantation, and no difference was noted between the sexes and donor type. Liver transplantation is effective treatment modality with good outcome and little morbidity, and increases the growth acceleration in patients with PFIC associated with cirrhosis.
Tokunaga, Y; Wicomb, W N; Concepcion, W; Nakazato, P; Collins, G M; Esquivel, C O
We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing