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.
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Zou, Yu-Hong; Liu, Xin; Khlentzos, Alexander M; Asadian, Peyman; Li, Peng; Thorling, Camilla A; Robertson, Thomas A; Fletcher, Linda M; Crawford, Darrell H G; Roberts, Michael S
This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl(4)-treated rats compared to controls (p<0.05). The extraction ratios (E) for all drugs were significantly lower (p<0.05) in fibrotic than in normal livers and the decrease in E was consistent with the decrease in intrinsic clearance and permeability-surface area product. In addition, other than for furosemide, the mean transit times for all drugs were significantly longer (p<0.01) in the fibrotic livers than in normal livers. Pharmacokinetic model and stepwise regression analyses suggest that these differences arise from a reduction in both the transport of drugs across the basolateral membrane and their metabolic clearance and were in a manner similar to those previously found for another group of drugs.
Zheng, Sheng; Yang, Juan; Yang, Jinhui; Tang, Yingmei; Shao, Qinghua; Guo, Ling; Liu, Qinghua
This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats. hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein. The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (P<0.05). HE staining of the liver showed obvious hepatocyte regeneration and reduced infiltration of inflammatory cells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (P<0.05). The liver function and differentiation of stem cells were comparable between H group and T group (P>0.05). hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection.
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
Schoening, Wenzel; Ariyakhagorn, Veeravorn; Schubert, Thomas; Olschewski, Peter; Andreou, Andreas; Neuhaus, Peter; Pratschke, Johann; Puhl, Gero
Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation. Male inbred Wistar rats (weighing 230-260 g) served as donors and recipients (n=6/group). Donors of treatment groups received i.v. 0.01 mL/g body weight (BW) warm (21 degree centigrade) HTK systemically 15 minutes prior to cold perfusion. Control groups received 0.01 mL/g BW warm (21 degree centigrade) NaCl 0.9%. Following pretreatment, donors were flushed with 4 degree centigrade cold HTK, livers were explanted and stored in 4 degree centigrade HTK for six hours. Thereafter orthotopic liver transplantation was performed. Recipients were harvested four hours, two and five days after reperfusion and blood and liver tissue samples were obtained. Blood samples were analyzed for AST, ALT, lactate dehydrogenase and bilirubin. Liver histological analysis as well as tissue analysis for pro-MMP2, MMP2 and pro-MMP9 using zymography was conducted. Treatment groups showed significantly lower ALT and lactate dehydrogenase levels as well as significantly lower activities of pro-MMP2, MMP2 and pro-MMP9. Histological analysis revealed only minor damage in all groups. The new concept of warm HTK pretreatment significantly reduced ischemia-reperfusion injury. The reduced ischemia-reperfusion injury was due to MMP inhibition. Warm HTK donor pretreatment is easy to handle and could further improve HTK's potency in liver preservation.
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
Zheng, Sheng; Yang, Juan; Yang, Jinhui; Tang, Yingmei; Shao, Qinghua; Guo, Ling; Liu, Qinghua
Objective: This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats. Methods: hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein. Results: The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (P<0.05). HE staining of the liver showed obvious hepatocyte regeneration and reduced infiltration of inflammatory cells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (P<0.05). The liver function and differentiation of stem cells were comparable between H group and T group (P>0.05). Conclusion: hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection. PMID:26884856
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
Chaib, E; Papalois, A; Brons, I G; Calne, R Y
The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control. We have studied isogenic islet transplantation on the rat (WAG-RT1u) liver. The method of isolation and purification of the islets obtained 2.834 +/- 551.64 islets with purity of 83 +/- 2.45%. Diabetes was induced by streptozotocin and seric glucose prior transplantation was 35 mmol/L. The islet transplantation of 2.834 +/- 551.64 islets in the rat liver has normalized glucose test from 9.62 +/- 2.65 mmol/L 10 days after transplantation to 7.43 +/- 0.27 mmol/L later in the follow-up (P < 0.05). The median survival time of the islets was 73 days. In conclusion both the method of isolation and purification of the islets and islet transplantation was effective in the control of the diabetes induced by streptozotocin with median survival time of both islet and rat more than 73 days when rats were sacrified.
Chaib, Eleazar; Papalois, Apostolos; Brons, Ingrid G M; Calne, Roy Y
[corrected] The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control We studied allogenic islet transplantation on the rat liver, Wistar (RT1u) to Lewis (RT1(1)) as a recipient. Control group (n = 8) and nonparenchymal cell group (n = 8) respectively with injection of Hanks solution and nonparenchymal cells in the thymus before islet transplantation. With the method of isolation and purification of the islets we obtained both in the control group 3.637 +/-783,3 islets with purity of 85 +/- 3,52% and nonparenchymal cell group 3.270 +/- 770 islets with purity of 84,25 +/- 2,76%. The nonparenchymal cells were retrieved from the liver and we obtained 2 x 106 cells. Diabetes was induced by i.v. streptozotocin Control group the transplantation of 3.637 +/- 783,3 islets in the rat liver normalized glucose test, 7,21 +/- 0,57 mmol/L in the 2nd postoperative day. Acute rejection came in the 6th postoperative day with significantly increase of glucose test in nonparenchymal cell group, the transplantation of 3.270 +/- 770 islets in the rat liver, almost normalized the glucose test was 17,95 +/- 5,33 mmol/L in the 2nd postoperative day. From the 4th postoperative day to 10th postoperative day. The glucose test increase significantly showing an early acute rejection The injection of nonparenchymal cells in the thymus before allogenic islet transplantation in the rat liver lead to an early acute rejection.
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.
Chaib, Eleazar; Papalois, Apostolos; Brons, Ingrid G M; Calne, Roy Y
The major indication for pancreas or islet transplantation is diabetes mellitus type I. This process has to supply the insulin necessity keeping glucose under control. We studied alogenic islet transplantation on the rat liver, Wistar (RT1u) to Lewis (RT1(1)) as a recipient. Control group (n = 8) and dendritic cell group (n = 9) respectively with injection of Hanks solution and dendritic cells in the thymus before islet transplantation. With the method of isolation and purification of the islets we obtained both in the control group 3637 +/- 783,3 islets with purity of 85 +/- 3,52% and dendritic cell group 3268 +/- 378 islets with purity of 87 +/- 4,47%. The dendritic cells were retrieved from the spleen and we obtained 3,34 x 105+/-1,16 cells. Diabetes was induced by i.v. streptozotocin. Control group the transplantation of 3637 +/- 783,3 islets in the rat liver normalized glucose test, 7,21 +/- 0,57 mmol/L in the second post-operative day. Acute rejection came in the 10 postoperative day with significantly increase of glucose test. Dendritic cell group, the transplantation of 3258 +/- 378 islets in the rat liver, normalized the glucose test was 9,3 +/- 2,85 mmoL/L in the second postoperative day. From the 4th postoperative day to 10th postoperative day the glucose test increase significantly showing an early acute rejection. The injection of dendritic cells in the thymus before alogenic islet transplantation in the rat liver lead to an early acute rejection.
Hori, Tomohide; Nguyen, Justin H; Zhao, Xiangdong; Ogura, Yasuhiro; Hata, Toshiyuki; Yagi, Shintaro; Chen, Feng; Baine, Ann-Marie T; Ohashi, Norifumi; Eckman, Christopher B; Herdt, Aimee R; Egawa, Hiroto; Takada, Yasutsugu; Oike, Fumitaka; Sakamoto, Seisuke; Kasahara, Mureo; Ogawa, Kohei; Hata, Koichiro; Iida, Taku; Yonekawa, Yukihide; Sibulesky, Lena; Kuribayashi, Kagemasa; Kato, Takuma; Saito, Kanako; Wang, Linan; Torii, Mie; Sahara, Naruhiko; Kamo, Naoko; Sahara, Tomoko; Yasutomi, Motohiko; Uemoto, Shinji
AIM: To investigate our learning curves of orthotopic liver transplantation (OLT) in rats and the most important factor for successful surgery. METHODS: We describe the surgical procedures for our rat OLT model, and determined the operator learning curves. The various factors that contributed to successful surgery were determined. The most important surgical factors were evaluated between successful and unsuccessful surgeries. RESULTS: Learning curve data indicated that 50 cases were required for operator training to start a study. Operative time, blood loss, warm ischemic time, anhepatic phase, unstable systemic hemodynamic state, and body temperature after surgery significantly affected surgery success by univariate analysis, while the anhepatic phase was the most critical factor for success by multivariate analysis. CONCLUSION: OLT in rats is the only liver transplantation model that provides clinically relevant and reliable results. Shortened anhepatic phase is key to success in this model. PMID:20593497
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.
Kageyama, Shoichi; Yagi, Shintaro; Tanaka, Hirokazu; Saito, Shunichi; Nagai, Kazuyuki; Hata, Koichiro; Fujimoto, Yasuhiro; Ogura, Yasuhiro; Tolba, Rene; Shinji, Uemoto
Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor. We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group). Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (P<0.001), hyaluronic acid (P<0.05), and malondialdehyde (MDA) (P<0.001), hepatic interleukin-6 expression (IL-6) (P<0.05), and hepatic tumor necrosis factor-alpha (TNF-α) expression (P<0.001). Hepatic eNOS expression (P<0.001) was upregulated, whereas hepatic iNOS (P<0.01) and ET-1 (P<0.001) expressions were downregulated. The damage of hepatocyte and sinusoidal endothelial cells (SECs) were lower in group-VSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (P<0.01). These results suggest that VSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.
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
Okumura, Shinya; Uemura, Tadahiro; Zhao, Xiangdong; Masano, Yuki; Tsuruyama, Tatsuaki; Fujimoto, Yasuhiro; Iida, Taku; Yagi, Shintaro; Bezinover, Dmitri; Spiess, Bruce; Kaido, Toshimi; Uemoto, Shinji
The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.
Rawal, Nidhi; Yazigi, Nada
Excellent outcomes over the last 3 decades have made liver transplantation the treatment of choice for many advanced liver disorders. This success also opened liver transplantation to new indications such as liver tumors and metabolic disorders. The emergence of such new indications for liver transplantation is bringing a new stream of patients along with disease-specific challenges. The cumulative number of liver transplant recipients is peaking, requiring novel systems of health care delivery that meet the needs of this special patient population. This article reviews updates and new development in pediatric liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.
Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A.; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian
Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor. PMID:24651497
Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian
Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.
Zhu, Hong; Marco, Catena; Gianfranco, Ferla
Hepatic reperfusion injury may cause acute inflammatory damage, producing significant organ dysfunction, and is an important problem in liver transplantation. This experiment aimed to study early changes of hepatic function after donor liver denervation and Kupffer cell depletion in rat-to-rat liver transplantation and to evaluate the effect of pre-treatment on liver reperfusion injury. Donor rats were divided into four groups: control group; group G was pre-treated with gadolinium chloride (G), an inhibitor of Kupffer cells; group H with hexamethonium (H), a sympathetic ganglionic blocking agent; and group HG, with combined H and G pre-treatment. Under the same conditions, serum alanine aminotransferase (ALT), arterial ketone body ratio (AKBR), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and superoxide dismutase (SOD) of recipient rats were assessed at 4, 8, 16 and 24 hours after liver transplantation. Histological studies of the grafts were compared. HG pre-treatment significantly decreased ALT, TNF-alpha, and IL-6 levels, increased AKBR and SOD levels, and demonstrated less pathological damage at 8, 16 and 24 hours compared with the control group. Similar trends were also found in the other groups (G and H). However, the differences among them were not significant at 4 post-operative hours. Donor denervation and Kupffer cell depletion had preventive effect on liver reperfusion injury. HG pre-treatment is a feasible and reproducible method to protect grafts from reperfusion injury.
Li, Guo-Lin; Lin, Hao-Ming; Long, Tian-Zhu; Lv, Li-Hong; Yu, Jian-Dong; Huang, Yong-Heng; Min, Jun; Wan, Yun-Le
AIM: To investigate how to reduce the incidence of biliary complications in rat orthotopic liver transplantation. METHODS: A total of 165 male Wistar rats were randomly divided into three groups: Group A, orthotropic liver transplantation with modified “two-cuff” technique; Group B, bile duct was cut and reconstructed without transplantation; and Group C, only laparotomy was performed. Based on the approaches used for biliary reconstruction, Group A was divided into two sub-groups:A1 (n = 30), duct-duct reconstruction, and A2 (n = 30), duct-duodenum reconstruction. To study the influence of artery reconstruction on bile duct complication, Group B was divided into four sub-groups: B1 (n = 10), duct-duct reconstruction with hepatic artery ligation, B2 (n = 10), duct-duct reconstruction without hepatic artery ligation, B3 (n = 10), duct-duodenum reconstruction with hepatic artery ligation, and B4 (n = 10), duct-duodenum reconstruction without hepatic artery ligation. The samples were harvested 14 d after operation or at the time when significant biliary complication was found. RESULTS: In Group A, the anhepatic phase was 13.7 ± 1.06 min, and cold ischemia time was 50.5 ± 8.6 min. There was no significant difference between A1 and A2 in the operation duration. The time for biliary reconstruction was almost the same among all groups. The success rate for transplantation was 98.3% (59/60). Significant differences were found in the incidence of biliary complications in Groups A (41.7%), B (27.5%) and C (0%). A2 was more likely to have biliary complications than A1 (50% vs 33.3%). B3 had the highest incidence of biliary complications in Group B. CONCLUSION: Biliary complications are almost inevitable using the classical “two cuff” techniques, and duct-duodenum reconstruction is not an ideal option in rat orthotopic liver transplantation. PMID:21912457
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.
Zhao, Xin; Shi, Xiaolei; Zhang, Zhiheng; Ma, Hucheng; Yuan, Xianwen; Ding, Yitao
The imbalance of immunity is an important pathogenesis of acute liver failure (ALF). Neutrophils are the hallmark of acute inflammation, which have an essential role in immune regulation. Mesenchymal stem cell (MSC) transplantation is a promising therapy in ALF treatment. Recent studies indicated a considerable connection between MSCs and neutrophils in immune regulation. To investigate changes in neutrophils in ALF rats after MSC transplantation, and to explore the therapeutic effect and mechanism of the combined treatment with MSC transplantation and neutrophil depletion in ALF. We employed monotherapy and the combination therapy with MSCs and anti-PMN serum in D-galactosamine (D-GalN)/lipopolysaccharides (LPS)-induced ALF rats. Rats were sacrificed at 6, 12 and 24h, respectively. Blood samples and liver tissues were collected. Hepatic injury, inflammatory cytokines (TNF-α, IL-1β and IL-10), chemokines (CXCL1 and CXCL2), the number and activity of neutrophils and animal survival were assessed at fixed times. MSC transplantation can effectively improve the liver function of ALF rats and reduce the number and activity of neutrophils in both peripheral blood and liver. Compared with MSC transplantation alone, anti-PMN treatment and co-treatment had a better result in diminishing neutrophils. The co-treatment also exhibited a better therapeutical effect in ALF rats compared with monotherapy. In this process, the expressions of inflammatory cytokines in the liver were consistent with liver function. The regulation of the neutrophil-related microenvironment is affected in D-GalN/LPS-induced ALF rats after MSC transplantation. The combined treatment with MSC transplantation and neutrophil depletion may have a better therapeutic effect in ALF rats. Copyright Â© 2016. Published by Elsevier Masson SAS.
... 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
Following an overview of the data published in the specialized literature in connection with liver transplantation the author presents original experimental studies in this field. One of the first aspects considered is the stage of obtaining the graft of liver tissue. The selective perfusion was used, in situ, of the dog liver, and conditions were achieved which were similar to those obtained in other methods of graft preparation. Two washing solutions were used: a simple one, currently used in the practice, and another one which was enriched with various substrates. Biochemical parameters of tissue sampled by bioptic puncture have demonstrated that the first solution induces a lowering of the glycogen contents of hepatocytes, and this alters the biological qualities or the graft. The fact is stressed that the obtention of the hepatic tissue for grafting should be considered in fact as an in situ conservation. With regard to the liver transplantation proper it is shown that the author has performed the sector heterotopic procedure in the rat. Vascular anastomoses have been made with histoacryl-N-blau by the method of prosthesis with lost tubing. Problems raised by the vascular re-connection of the auxilliary hepatic tissue, and those related to the space where this tissue should be placed are also discussed in detail. The survival time was not longer than 30 hours.
Wolff, M; Kalff, J C; Schwarz, N T; Lauschke, H; Minor, T; Tolba, R H; Hirner, A
As in other western countries the major challenge of liver transplantation in Germany is to expand the number of liver transplantations in respect to the increasing disparity of qualified patients on the waiting list and the still static availability of brain death donor organs. The problem of death on the waiting list has become overt since the German transplantation law has been installed, which has changed the former center-oriented to a patient-oriented allocation weighting waiting time over medical urgency criteria. The more liberal acceptance of so called marginal cadaveric donor livers will probably impair further improvements in the acute and long-term outcome of liver transplantation. This problem can be partially compensated by the use of novel surgical techniques, such as splitting a donor liver to be transplanted into two adult recipients or, more commonly and safe, into an adult and one child. Another alternative to increase the donor pool is living donor liver transplantation, which was first introduced for pediatric recipients but is now increasingly used in adults. In 2001, a constant number of 757 liver transplantations were performed in Germany, including 12.5 % living donor transplantations. Recently, general guidelines for the selection of patients with end-stage liver disease and acute liver failure have been published by the Bundesärztekammer. Additional developments have contributed to improve the results of liver replacement including individualized immunosuppression strategies and novel treatment options to avoid recurrent viral disease following transplantation.
Liu, Y; Luan, X; Li, J; He, Y; Li, M
The aim of this study was to investigate the role of invariant natural killer T (iNKT) cells in liver transplant tolerance in rats. Animals were randomly divided into 3 groups. The α-galactosylceramide (α-GalCer) group underwent injection through the caudal vein; the saline group received the same dose of saline and the control group received no treatment. Ten rats in each group were examined for survival the others were humanely killed on the seventh day posttransplantation. Liver tissues were used to assess histopathologic changes. Real-time polymerase chain reaction (PCR) was performed to determine the relative expressions of messanger RNAs of Th1/Th2-related cytokine (mRNAs) in the liver allograft. The serum levels of related cytokines were determined using enzyme-linked immunosorbent assay (ELISA). Allograft survival was significantly higher among the α-galactosylceramide α-GalCer group than the saline or control groups. The histopathology showed mild changes in the α-galactosylceramide α-GalCer compared with the other 2 groups. Real-time PCR showed the relative expression of Th1-related cytokine interferen (IFN)-γ mRNA to be significantly lower in the α-galactosylceramide α-GalCer compared with the other 2 groups, while the Th2-related cytokine interleukin (IL)-10 mRNA was much higher. The ELISA results confirmed these differential expressions. The iNKT cells may play a pivotal role in liver transplant tolerance due to their regulatory functions on the Th1/Th2 imbalance. iNKT cells should be considered to be significant targets because of their attractive specificity and induction of liver allograft tolerance. Copyright © 2012 Elsevier Inc. All rights reserved.
Ye, Sheng; Dong, Jiahong; Han, Benli
The aim of this study is to explore the protective effect of high-dose reduced glutathione (GSH) preconditioning and venous systemic oxygen persufflation (VSOP) on rat steatotic liver grafts following transplantation. Steatotic liver model was established by feeding rats a high-fat, high-cholesterol diet, and infusing stomach with 50% alcohol (1 mL/100g body weight/d) for 6 wk. In the pretreated group, short-term and high-dose of GSH administration and VSOP were performed. In rat orthotopic liver transplantation model, the recipient survival, liver function, hepatic microcirculation blood flow, hepatic redox, hepatocytes apoptosis and necrosis, and hepatic ultrastructure alteration were observed. In the pretreated rat steatotic grafts, hepatic GSH (from 29.43 +/- 4.83 to 41.56 +/- 8.51mg/mgprot), superoxide dismutase (SOD) (from 48.32 +/- 6.27 to 67.74 +/- 7.68 NU/mgprot), and adenosine triphosphate (ATP) (from 1.61 +/- 0.20 to 2.28 +/- 0.09 micromoles/g) were significantly increased (P < 0.05), whereas malondialdehyde (MDA) was significantly decreased (from 7.20 +/- 2.18 to 4.63 +/- 0.58 nmol/mgprot, P < 0.05). The hepatocyte necrosis of fatty liver graft was significantly reduced in the pretreated group when compared with non-treated fatty ones (37.71% +/- 9.69% versus 16.63% +/- 5.53%; t = 3.777, P = 0.014), and significantly improved liver function and hepatic ultrastructure were observed in the pretreated fatty liver group after operation. The animal survival after transplanted with fatty liver was significantly improved (chi(2) = 4.07, P = 0.0436). A short course pretreatment with high-dose GSH and oxygen persufflation during cold preservation effectively protect steatotic liver grafts from ischemic damage and significantly improve early survival rate in a rat fatty liver transplantation model.
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
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.
Wang, Zhen-Chang; Yang, Shan; Huang, Jing-Jing; Chen, Song-Lin; Li, Quan-Qiang; Li, Yuan
To observe the effect of Rougan Huaqian granules combined with human mesenchymal stem cell (hMSC) transplantation on the liver fibrosis in carbon tetrachloride-induced cirrhosis rats. Sixty SD rats were randomly divided into five groups. The rats in control group received intraperitoneal injection of saline, while those in model control group, treatment group A, group B and group C received intraperitoneal injection of carbon tetrachloride oily solution to induce liver cirrhosis within 8 weeks. Then, the rats in the model control group, treatment group A, treatment group B, treatment group C received vein tail injection of saline, Rougan Huaqian granules, hMSC suspension and Rougan Huaqian granules combined with hMSC suspension. The treatment groups had significantly different liver function (AST levels), liver fibrosis index (laminin and HA), hepatic sinusoidal wallsα-smooth muscle actin, IV collagen and laminin protein expression and I, III collagen from the model group (P<0.05). The transplanted cells showed human hepatocyte-like cells differentiation trend in the liver. The Rougan Huaqian granules combined with hMSC transplantation can alleviate liver fibrosis in cirrhosis rats. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
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.
Yovchev, Mladen I.; Xue, Yuhua; Shafritz, David A.; Locker, Joseph; Oertel, Michael
Background & Aim Considerable progress has been made in developing anti-fibrotic agents and other strategies to treat liver fibrosis; however, significant long-term restoration of functional liver mass has not yet been achieved. Therefore, we investigated whether transplanted hepatic stem/progenitor cells can effectively repopulate the liver with advanced fibrosis/cirrhosis. Methods Stem/progenitor cells derived from fetal livers or mature hepatocytes from DPPIV+ F344 rats were transplanted into DPPIV− rats with thioacetamide (TAA)-induced fibrosis/cirrhosis; rats were sacrificed 1, 2, or 4 months later. Liver tissues were analyzed by histochemistry, hydroxyproline determination, RT-PCR, and immunohistochemistry. Results After chronic TAA administration, DPPIV− F344 rats exhibited progressive fibrosis, cirrhosis and severe hepatocyte damage. Besides stellate cell activation, increased numbers of stem/progenitor cells (Dlk-1+, AFP+, CD133+, Sox-9+, FoxJ1+) were observed. In conjunction with partial hepatectomy (PH), transplanted stem/progenitor cells engrafted, proliferated competitively compared to host hepatocytes, differentiated into hepatocytic and biliary epithelial cells, and generated new liver mass with extensive long-term liver repopulation (40.8 ± 10.3%). Remarkably, more than 20% liver repopulation was achieved in the absence of PH, associated with reduced fibrogenic activity (e.g., expression of α-SMA, PDGFRβ, desmin, vimentin, TIMP1) and fibrosis (reduced collagen). Furthermore, hepatocytes can also replace liver mass with advanced fibrosis/cirrhosis, but to a lesser extent than FLSPCs. Conclusions This study is a Proof of Principle demonstration that transplanted epithelial stem/progenitor cells can restore injured parenchyma in a liver environment with advanced fibrosis/cirrhosis and exhibit anti-fibrotic effects. PMID:23840008
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
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Boehnert, Markus U; Armbruster, Franz Paul; Hilbig, Heidegard
Ischemia reperfusion injury (IRI) is a problem in organ transplantation. Relaxin is known to have a protective effect against liver injury caused by IRI. Using a model of isolated perfused rat liver, the local oxygen supply in liver tissue was investigated by spectrophotometric in vivo imaging and compared to the protective effect of relaxin shown by immunohistochemical measurement of myeloperoxidase and malonyldialdehyde activities as determinants of oxidative stress. In relaxin-treated liver tissue, spectrophotometry showed a better oxygen supply and decreased myeloperoxidase and malonyldialdehyde activities. Our data suggest that relaxin can influence the oxygen distribution in liver tissue and reduce cell damage caused by IRI.
... 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 ...
Zheng, Sheng; Yang, Juan; Tang, Yingmei; Yang, Jinhui; Shao, Qinghua; Guo, Ling; Liu, Qinghua
This study aimed to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of high mobility group box 1 protein (HMGB1) in the serum and liver of rats with acute liver failure (ALF). Healthy male SD rats were randomly divided into control group, ALF group and BMSCs group. ALF was induced by intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS. In BMSCs group, rats received BMSCs (1.0×10(7)) transplantation via the tail vein at 2 h after ALF induction. Intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS was able to induce ALF in rats. In ALF group, serum ALT and AST increased gradually over time. At 72 h, the serum ALT and AST in BMSCs group were significantly different from those in ALF group. HMGB1 expression in the serum and liver remained at a low level at any time point in control group, but increased significantly in ALF group and BMSCs group. The serum and liver HMGB1 expression increased progressively in ALF group, but reduced gradually in BMSCs group. Significant difference in serum and liver HMGB1 expression was observed between ALF group and BMSCs group at 24 h and 72 h. In addition, there was marked difference in the survival rate among three groups at 24 h (χ (2) =21.098, P<0.01). BMSCs transplantation is able to improve the liver function and liver pathology in ALF rats and decrease the serum and liver HMGB1.
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
Makuuchi, M; Kawarazaki, H; Iwanaka, T; Kamada, N; Takayama, T; Kumon, M
Liver transplantation from a brain death donor has not yet been accepted in Japan. The only alternative method at present is transplantation from a living donor. After the first successful living related liver transplantation was performed by Strong in Brisbane, Australia, Japanese hepatic and transplant surgeons also began to perform such operations. As of February 1991, 16 living related liver transplantations had already been performed in Japan, mainly for children with biliary atresia. Five of these patients subsequently died, however, our patient has survived more than 1 year, and she is presently leading a normal school life. The most important issue regarding living related liver transplantation is to ensure the donor's safety. For this purpose, we conducted a preoperative banking of the donor's own blood and plasma. In addition, a selective vascular occlusion was carried out to reduce blood loss during the resection of the liver. Intraoperative color Doppler ultrasonography was introduced for evaluating the circulation of the graft. By using this modality, the following three points were able to be accurately estimated in order to obtain optimal graft perfusion: 1) The most suitable position for the graft to be fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed and 3) the indication for a ligation of the collateral veins to form a porto-systemic shunt. Thanks to these procedures, living related liver transplantations have now become an acceptable transplant method, however, a transplantation from a cadaver that is brain dead but still has a beating heart is still absolutely necessary for adult recipients. Therefore, in the future, both methods should be performed.
Wu, Yakun; Zhang, Wenfeng; Li, Min; Cao, Ding; Yang, Xiaoli; Gong, Jianping
This study aims to explore the protective effects of nobiletin against hepatic ischemia-reperfusion (IR) injury after liver transplantation. Kupffer cells (KCs) were activated and co-cultured with different concentration of nobiletin for 24h in vitro, inflammatory products and activity of TLR4/NF-κB signaling pathway were detected. Sprague-Dawley rats were selected and underwent orthotopic liver transplantation. Donors were injected intravenously with nobiletin (50mg/kg) or saline solution, once a day for 1 week before the surgery. Recipients were randomly paired and sacrificed at the indicated time points (3, 6, and 24h after the surgery), the graft liver tissues and blood samples were collected for analysis. Hepatic function, inflammatory mediators, apoptosis of hepatocytes, histological changes, KCs and CD4+ T-lymphocyte infiltration were assessed. Results showed nobiletin dose-dependently suppressed the expression of inflammatory mediators and the activity of TLR4/NF-κB signaling pathway in activated KCs. Furthermore, nobiletin alleviated liver damage induced by IR in vivo, significantly decreased the serum levels of alanine aminotransferase, aspartate transaminase, inflammatory cytokines and alleviated the histopathology changes. Moreover, liver in the nobiletin treated group exhibited less KCs and CD4+ lymphocyte infiltration and lower hepatocyte apoptosis after operation. In addition, activity of TLR4/NF-κB signaling pathway in KCs was also suppressed, consistent with the results in vitro. Collectively, Nobiletin can ameliorate IR injury after liver transplantation and may be a promising new strategy to protect against liver IR injury.
Shanmugam, Naresh P; Al-Lawati, Tawfiq; Kelgeri, Chaya; Rela, Mohamed
Auxiliary partial orthotopic liver transplantation is a technique where part of diseased native liver is removed and replaced with healthy donor liver so that, the left behind native liver could later regenerate. 2 year 6 month old girl with acute liver failure due to Hepatitis A. She underwent a successful auxiliary partial orthotopic liver transplantation. Successful native liver regeneration and immunosuppression withdrawal after two and half years of surgery. In selective cases of acute liver failure, auxiliary partial orthotopic liver transplantation could provide a chance for native liver regeneration and immunosuppression-free life.
Boehnert, Markus U; Hilbig, Heidegard; Armbruster, Franz P
Reperfusion injury is a problem in organ transplantation. Relaxin causes vessel dilation and inhibition of platelet and mast cell activation. The study investigates the protective effect of relaxin on liver tissue against cell damage during organ preservation and reperfusion. Liver transplantation was simulated in a model of isolated perfused rat liver. Relaxin was applicated during reperfusion and/or preservation. To quantify cell damage, we examined the perfusate for malonyldialdehyde (MDA) and myeloperoxidase activity (MPO), and liver tissue underwent immunohistochemical study. Relaxin as an additional substance in preserving/reperfusion solution decreases MPO and MDA levels in the perfusate and immunohistochemical study. Relaxin seems to have a protective effect against cell damage in ischemia and reperfusion injury.
de la Rosa, Gloria; Fondevila, Constantino; Navasa, Miquel
Liver transplantation (LT) activity started in Spain in 1984 and has exceeded 23,700 interventions, with more than 1000 transplants performed yearly. Every hospital needs official authorization to perform a LT, which implies the obligation to register all patients on the national waiting list. The Spanish National Transplant Organization (ONT) provides essential support for organ procurement, allocation, and management of the waiting list at a national level. Liver allocation is center-oriented as all available organs are referred to the ONT for the whole country. The allocation rules for LT are made according to disease severity after consensus among professionals from every transplant center and ratified by representatives of the regional health authorities. Authorization and location/distribution of transplant centers are regulated by the country (Spain) and by the different regions according to the Real Decreto 1723/2012. For a total population of 47,850,795 inhabitants, there are 24 centers for LT for adults (1 team/2 million people) and 5 for LT for children (1 team/9.5 million people). Nonbiliary cirrhosis, particularly alcohol- and hepatitis C virus-related cirrhosis (60%), and tumors, mainly hepatocellular carcinoma (19%), are the most common indications for LT in Spain. Unusual causes of LT include metabolic diseases like Wilson's disease, familial amyloid polyneuropathy and hyperoxaluria type I, polycystic kidney and liver disease, and some tumors (epithelioid hemangioendothelioma and neuroendocrine tumors). Important efforts are now being undertaken to improve the quality and transplantability of extended criteria livers, in particular those arising from DCD, which represent the greatest opportunity to expand the donor pool. These efforts have to be addressed to adapt the organ preservation procedures, be it through the application of regional perfusion in situ or the use of machine perfusion preservation ex situ. Liver Transplantation 22 1259-1264 2016
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.
Boehnert, M U; Armbruster, F P; Hilbig, H
Reperfusion injury, a well-known problem in organ transplantation, results from multiple pathologic mechanisms, including platelet/mast cell activation and peroxidation of cell membrane lipids. Relaxin was originally described as an insulin-like hormone produced in the ovaries during pregnancy. It causes vessel dilation and inhibition of platelet and mast cell activation. The present study investigated the protective effect of relaxin against reperfusion injury in liver tissue. We used a model of isolated perfused rat liver to simulate liver transplantation. Organ preservation was performed identical to human transplantation in 20 male Wistar rats. During preservation we applied 64 ng/mL relaxin. In contrast controls (n = 10) had no relaxin treatment. To quantify cell damage, we measured malonyldialdehyde (MDA; end product of lipid peroxidation) and myeloperoxidase activity (MPO; marker for accumulation of neutrophil granulocytes) in the perfusates. The livers were examined immunohistochemically for the same parameters. Relaxin as an additional substance in preservation solutions decreased perfusate MPO and MDA levels by up to 30%, as shown by immunohistochemistry. Our preliminary data suggested that relaxin is a promising agent to reduce hepatocyte damage caused by ischemia-reperfusion injury. Quantitative analysis of MDA and MPO levels in the perfusate is the subject of an ongoing study.
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.
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
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
This article addresses postoperative analgesia in patients with end-stage liver disease who have undergone liver transplantation (LT). Postoperative analgesia determines how patients perceive LT. Although important, this topic is underrepresented in the current literature. With an increased frequency of fast tracking in LT, efficient intra- and postoperative analgesia are undergoing changes. We herein review the current literature, compare the benefits and disadvantages of the therapeutic options, and make recommendations based on the current literature and clinical experience. PMID:26413222
... 22, 2002 December 2006 March 2012 Getting A New Liver Facts About Liver Transplants American Society of ... the views of the Society. _________________________________________________________________ 1 Getting a New Liver Facts About Liver Transplants A liver transplant ...
Chen, Geng; Ding, Min; Wang, Meng; Zhang, Yu-Jun; Li, Xiao-Wu; Wang, Shu-Guang; Dong, Jia-Hong
To explore the effect of cold preservation and reperfusion injury (CPRI) on the bile salt spectrum in rat orthotopic liver transplantation (OLT) model. A special analysis method was established to investigate the bile salts in rat by reverse phase high performance liquid chromatography (RP-HPLC). Rats were randomly divided into 3 groups: group A (control group, n = 6), group B (group with 1 h graft preservation pre-OLT, n = 6) and group C (group with 12 h graft preservation pre-OLT, n = 6). The bile samples of 0 - 14 post-transplantation days were analyzed by RP-HPLC. Eleven kinds of bile salts were detected in rat bile. It showed that CPRI could influence the concentration of bile salts significantly in rat model after OLT, the concentration of hydrophobic bile salts (TCA and TCDCA) increased significantly in group B and C. However, the concentration of hydrophilic bile salts (TUDCA and THDCA) just increased in a short-time. The hydrophobicity index (HI) wasn't significantly changed during the first 4 post-transplant days. Thus the HI of bile salts elevated gradually from the 5th day and reached the peak at the 10th day after OLT. The increase of the proportion of hydrophobic bile salts may be one of the major factors leading to the increase of bile toxicity after OLT.
Ramirez, Carlo B; Doria, Cataldo
Women constitute >30% of patients undergoing liver transplantation (orthotopic liver transplantation, OLT) and about 8% are of reproductive age, and 5% are pediatric females who will mostly survive into adulthood and will consider pregnancy. Although pregnancy in OLT recipients is associated with an increased incidence of hypertension, preeclampsia, anemia, preterm deliveries, and cesarean section, acute rejection and liver allograft loss do not appear to be increased and pregnancy-related maternal death is uncommon. The incidence of structural malformations in the newborn of liver transplant recipients is reported to be 4.4%, which is similar to the rate of 3-5% in the US general population. Patients are advised to defer conception for at least 1-2 years after OLT, while maintaining effective contraception. Pregnancy after OLT usually results in a favorable maternal and neonatal outcome when there is coordinated pre- and perinatal care by a multidisciplinary team composed of obstetric-gynecologists, and a transplant team. Copyright © 2014 Elsevier Ltd. All rights reserved.
Hessheimer, Amelia J; Nacif, Lucas; Flores Villalba, Eduardo; Fondevila, Constantino
Before liver transplantation became widely applicable as a treatment option, the mortality rate for acute liver failure was as high as 85%. Today, acute liver failure is a relatively common transplant indication in some settings, but the results of liver transplantation in this context appear to be worse than those for chronic forms of liver disease. In this review, we discuss the indications and contraindications for urgent liver transplantation. In particular, we consider the roles of auxiliary, ABO-incompatible, and urgent living donor liver transplantation and address the management of a «status 1» patient with total hepatectomy and portocaval shunt for toxic liver syndrome. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Yagi, S; Nagai, K; Kadaba, P; Afify, M; Teramukai, S; Uemoto, S; Tolba, R H
The prognosis for recipients of small liver grafts is poor. The aim of this study was to determine the impact of venous systemic oxygen persufflation (VSOP) with nitric oxide (NO) gas for 30% partial liver preservation and transplantation in rats. After we determined optimal NO concentration as 40 ppm in vitro with the isolated perfused rat liver model, we assessed liver injury and regeneration in vivo at 1, 3, 24 and 168 h after transplantation in the following three groups after 3 h-cold storage (n = 20 per group): control group = static storage; VSOP group = oxygen persufflation and VSOP+NO group = oxygen with NO persufflation. The liver graft persufflation was achieved with medical gas via the suprahepatic vena cava; In comparison with control group after transplantation, VSOP+NO preservation (1) increased portal circulation, (2) reduced AST and ALT release, (3) upregulated hepatic endothelial NO synthase, (4) reduced hepatocyte and bileductule damage and (5) improved liver regeneration. These results suggest that gaseous oxygen with NO persufflation is a novel and safe preservation method for small partial liver grafts, not only alleviating graft injury but also improve liver regeneration after transplantation. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
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.
Putnam, Charles W.; Halgrimson, Charles G.; Koep, Lawrence; Starzl, Thomas E.
Since the first clinical orthotopic liver transplant was performed 13 years ago, approximately 275 patients have undergone this procedure. The Denver series constitutes about 40% of this total experience. In our series, the overall 1-year survival has been 29%; the longest survivor is now 62/3 years posttransplantation. Most of the early deaths have been caused by technical complications, frequently related to difficulties in establishing and maintaining adequate biliary drainage. The late deaths have been from a variety of causes, including recurrent tumor, hepatitis, bile duct obstruction, and chronic rejection. Favorable indications for liver transplantation include biliary atresia, chronic aggressive hepatitis, inborn errors of metabolism, and certain other benign hepatic diseases. Alcoholic cirrhosis is a less favorable indication and primary hepatic malignancy is a relative contraindication. The immunologic criteria for donor-recipient selection are much less rigid than for renal transplantation. Biliary reconstruction is the principal technical problem encountered with orthotopic liver transplantation. Guidelines for the establishment of biliary drainage, its evaluation, and the management of postoperative biliary complications are discussed. PMID:325920
Monti, L; Soglia, G; Tomà, P
Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors.
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.
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.
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.
The transplantation of hepatocytes could be an alternative therapeutic option to the whole organ transplantation for the treatment of end-stage liver diseases. However, this cell-based therapy needs the understanding of the molecular mechanisms to improve efficacy. This chapter includes a detailed method of a rat model for liver regeneration studies after age-dependent hepatocyte 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
Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin
A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.
Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha
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. 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. 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. The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature.
Suraweera, Duminda; Saab, Elena G; Choi, Gina; Saab, Sammy
Obesity is an important public health and medical concern in the United States. The rate of obesity has steadily risen for the past several decades. Obesity is associated with the development of nonalcoholic steatohepatitis, which is one of the leading indications for liver transplantation. After liver transplantation, recipients tend to gain weight and develop recurrent fatty liver. Over time, recurrent fatty liver may impact patient and graft survival. A bariatric surgical approach may be beneficial in select patients.
Suraweera, Duminda; Saab, Elena G.; Choi, Gina
Obesity is an important public health and medical concern in the United States. The rate of obesity has steadily risen for the past several decades. Obesity is associated with the development of nonalcoholic steatohepatitis, which is one of the leading indications for liver transplantation. After liver transplantation, recipients tend to gain weight and develop recurrent fatty liver. Over time, recurrent fatty liver may impact patient and graft survival. A bariatric surgical approach may be beneficial in select patients. PMID:28539844
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
Nagai, Kazuyuki; Yagi, Shintaro; Afify, Mamdouh; Bleilevens, Christian; Uemoto, Shinji; Tolba, Rene H
Steatotic livers are associated with poor graft function after transplantation. We investigated the effects of venous-systemic oxygen persufflation with nitric oxide gas (VSOP-NO) on steatotic partial livers after transplantation. Steatotic livers induced by fasting for 2 days and subsequent refeeding for 3 days with a fat-free, carbohydrate-rich diet were reduced in size by 50% and transplanted into Lewis rats after 3 hr of cold storage in histidine-tryptophan-ketoglutarate solution. Gaseous oxygen with nitric oxide (40 ppm) was insufflated into the grafts through the suprahepatic vena cava during cold storage (VSOP-NO group; n=20). Transplantation of cold-static stored steatotic and normal grafts served as controls (Steatotic-Control and Normal-Control, respectively; n=20 for each group). The graft microcirculation and portal venous flow were increased by VSOP-NO compared with Steatotic-Control (P<0.001 for both). Serum alanine aminotransferase and interleukin-6 levels were lower in VSOP-NO versus Steatotic-Control group (P=0.03 for both). Messenger RNA expression for inducible nitric oxide synthase, which was increased in Steatotic-Control livers 3 hr after transplantation (P=0.02 vs. that at 1 hr), was suppressed by VSOP-NO. Although serum nitrite levels were decreased 1 hr after transplantation in Steatotic-Control (P=0.06 vs. Normal-Control), the VSOP-NO group showed increased levels comparable to Normal-Control. In livers 24 hr after transplantation, moderate vacuolization of hepatocytes by histology with the immunohistochemical expression of nitrotyrosine, indicative of nitrative stress, was found in Steatotic-Control, whereas these findings were less apparent in VSOP-NO-treated livers. Application of VSOP-NO for steatotic partial livers reduces hepatocellular damage and improves graft viability and microcirculation after transplantation.
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.
Fukazawa, Kyota; Nishida, Seigo
Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
Benson, Merrill D
Liver transplantation as a specific treatment of transthyretin amyloidosis was first performed in 1990. The rationale for this treatment was that removal of the source (liver) of the amyloid precursor protein (mutated transthyretin) would stop progression of the disease. Indeed, after orthotopic liver transplantation (OLT), mutant transthyretin (TTR) is rapidly cleared from circulation. In the last 20 years, >2000 familial amyloidotic polyneuropathy (FAP) patients have received liver transplants. For these patients, prospective monitoring has shown prolongation of life compared with FAP patients who have not undergone liver transplantation. The most favorable results have been for FAP patients with the Val30Met TTR mutation. Less favorable results have been seen for patients with other TTR mutations where progression of amyloid tissue deposition has been documented as the result of amyloid fibril formation from normal (wild-type) TTR. Although it is obvious that OLT has benefited many FAP patients, there remains a need for further therapies. Copyright © 2012 Wiley Periodicals, Inc.
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.
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
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
Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro
Summary Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108
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
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.
Moreno, A; Meneu, J C; Moreno, E; Garcia, I; Loinaz, C; Jimenez, C; Gómez, R; Abradelo, M; Calvo, J; Fundora, Y; Ortiz, C
The shortage in cadaveric grafts has prompted the development of alternative surgical techniques to expand the donor pool. To evaluate the feasibility of split liver transplantation using an observational, retrospective, and longitudinal study. Between April 1986 and October 2002 we performed 875 liver transplants. From April 1991 to date, we performed 18 split liver transplantations in patients of mean age 42.27+/-25.65 years; five children and 13 adults; and 83.3% women. Urgent transplants accounted for 38.9%. Mean patient weight was 52.29+/-20.87 kg. Ex situ splitting was performed in 33%. The mean cold ischemia time was 460+/-265.69 minutes with a mean warm time of 64.33+/-11.78 minutes. Mean consumption of packed blood was 5.59+/-4.87 units; of frozen fresh plasma, 11.56+/-7.42 units; and of platelets 4.89+/-4.99 units. After a mean follow-up of 10.83+/-12.51 months, 55.56% of the recipients are alive. Actuarial patient and graft survival rates at 1 year are 55.6% and 44.12%, respectively. Actuarial patient and graft survival rates at 1 year, excluding operative mortality were 77% and 68%, respectively. Actuarial patient and graft survival rates at 1 year, comparing urgent and elective transplantations are: 14.29 and 14%, respectively, for urgent cases and 90.91 and 90% for elective ones. Operative mortality was 16.6% while mortality during follow-up was 26.6%. The late complications included arterial thrombosis (n=2): of whom the first needed liver retransplantation 4 months after split liver transplantation; chronic rejection (n=2), recurrence of hepatitis (n=1). Split liver transplantation is a useful way to expand the graft pool and shows better results in elective liver transplantation.
Markin, R S; Stratta, R J; Woods, G L
Infections occurring in liver transplant recipients result in significant morbidity and mortality. Factors influencing the frequency of posttransplant infections include pretransplant nutritional status, latent viral infections, and the degree of immunosuppression used to modulate the immune response to the allograft. Infectious agents may be introduced into the patient via the allograft, through infusion of blood products, and through intravenous lines, catheters, and drains. Infections also develop as a result of reactivation of latent viruses or by overgrowth or invasion by endogenous organisms. The intensity of the immunosuppressive regimen directly affects the frequency of infection. Infection may be categorized as bacterial, viral, fungal, or protozoal. The most frequent organisms include bacterial--enterobacteriaceae; viral--cytomegalovirus; fungal--Candida species and Aspergillus species; and protozoal--Pneumocystis carinii. Diagnosing infection requires the use of many different methods in combination, including routine bacterial culture, viral culture, and fungal culture. Histologic and cytologic examination may lead to rapid identification of some organisms. Specialized collection procedures such as bronchoalveolar lavage provide rapid access to material for culture and cytologic examination. Serum serology in conjunction with histotopic or cytologic evaluation is useful in diagnosing some infections, such as Epstein-Barr virus. New technology such as polymerase chain reaction allows detection of all types of infection at or before the onset of clinical symptoms. Rapid and early diagnosis of infection in this patient population can reduce infection-related morbidity and mortality.
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.
Shukla, Akash; Vadeyar, Hemant; Rela, Mohamed; Shah, Samir
Liver transplantation (LT) has evolved rapidly since the first successful liver transplant performed in1967. Despite a humble beginning, this procedure gained widespread acceptance in the western world as a suitable option for patients with end stage liver disease (ESLD) by the beginning of the 1980s. At present, approximately 25,000 liver transplants are being performed worldwide every year with approximately 90% one year survival. The techniques of living donor liver transplantation (LDLT) developed in East Asia in the 1990s to overcome the shortage of suitable grafts for children and scarcity of deceased donors. While deceased donor liver transplantation (DDLT) constitutes more than 90% of LT in the western world, in India and other Asian countries, most transplants are LDLT. Despite the initial disparity, outcomes following LDLT in eastern countries have been quite satisfactory when compared to the western programs. The etiologies of liver failure requiring LT vary in different parts of the world. The commonest etiology for acute liver failure (ALF) leading to LT is drugs in the west and acute viral hepatitis in Asia. The most common indication for LT due to ESLD in west is alcoholic cirrhosis and hepatitis C virus (HCV), while hepatitis B virus (HBV) predominates in the east. There is a variation in prognostic models for assessing candidature and prioritizing organ allocation across the world. Model for end–stage liver disease (MELD) is followed in United States and some European centers. Other European countries rely on the Child–Turcotte–Pugh (CTP) score. Some parts of Asia still follow chronological order of listing. The debate regarding the best model for organ allocation is far from over. PMID:25755506
Cui, Yi-Yao; Qian, Jian-Ming; Yao, Ai-Hua; Ma, Zhen-Yu; Qian, Xiao-Feng; Zha, Xiao-Min; Zhao, Yi; Ding, Qiang; Zhao, Jia; Wang, Shui; Wu, Jian
BACKGROUND Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and an increased mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted. AIMS The present study aims to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase (SOD) mimetic, MnTBAP, on graft function, growth and survival in the recipient rats. METHODS Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP). RESULTS Serum ALT levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of TNF-α and IL-1β and DNA binding activity of NF-κB in the grafts were increased significantly in SSGLT recipients compared to sham-operated controls. Both phosphorylated p38 MAPK and nuclear c-jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum SOD activity. Moreover, in situ bromo-deoxyuridine incorporation demonstrated that graft regeneration in SSGLT+MnTBAP group was much profound than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved. CONCLUSIONS Enhanced oxidant stress with activation of the p38-c-Jun-NF-κB signaling pathway contributes to SFS-associated graft failure, retarded graft growth and poor survival. MnTBAP effectively reversed the pathologic changes in SFS-associated graft failure. PMID:22955229
Jia, Lili; Wang, Fei; Gu, Xiangqian; Weng, Yiqi; Sheng, Mingwei; Wang, Gang; Li, Shipeng; Du, Hongyin; Yu, Wenli
Liver transplantation has been a routine treatment for the end stage liver diseases. Severe changes in circulation system and internal environment may occur during transplant surgery and cause injury to many organs including brain. Specific mechanisms of brain injury associated with liver transplantation are not yet elucidated. Previous studies have shown that the JAK/STAT signal transduction pathways are involved in the development of the central nervous system, such as nerve cell proliferation, survival, differentiation, and it also have a role in the disease processes, including brain tumor, brain ischemia and other diseases of the central nervous system. In this study we investigate whether propofol plays an important role in protecting the hippocampus through JAK2/STAT3 pathway. Thirty-two healthy male Sprague-Dawley rats, were randomly divided into four groups (n=8). Sham operation group (group S), autogenous orthotropic liver transplantation group (group I), autogenous orthotropic liver transplantation+propofol treatment group (group P) and autogenous orthotropic liver transplantation+propofol+AG490 treatment group (group A). We evaluated histological damage, inflammation, oxidative stress and apoptosis in hippocampus using HE staining, light microscope, real-time PCR and western blot. The results showed that there was a significant damage of hippocampus in group I compared to the sham group as demonstrated by increased serum levels of S100β, NSE and the histological changes. However, an induction of propofol reduced the levels of MDA, TNFα, S100β, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3, meanwhile. Consistently, pretreatment with JAK2/STAT3 pathway inhibitor AG490, decreased the levels of MDA, TNFα, S100β, NSE and increased activity of SOD, IL-10, and attenuated the expression of JAK2 and STAT3. These results reveal that autogenous orthotropic liver transplantation induces the activation of JAK2/STAT3
... 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.
Mottershead, Marcus; Neuberger, James
Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms. The shortage of organs for transplantation has resulted in the need for rationing. A variety of approaches to selection and allocation have been developed and vary from country to country. The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs; these include splitting grafts, use of extended criteria livers, livers from non-heart-beating donors and from living donors. Post transplantation, most patients will need life-long immunosuppression, although a small proportion can have immunosuppression successfully withdrawn. Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in side-effects and so improve the patient and graft survival. For autoimmune diseases, transplantation is associated with significant improvement in the quality and length of life. Disease may recur after transplantation and may affect patient and graft survival. PMID:18528936
Akamatsu, Nobuhisa; Sugawara, Yasuhiko
Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompensation. The use of poor quality organs, particularly from older donors, has a highly negative impact on the severity of recurrence and patient/graft survival. Although immunosuppressive regimens have a considerable impact on the outcome, the optimal regimen after liver transplantation for HCV-infected patients remains unclear. Disease progression monitoring with protocol biopsy and new noninvasive methods is essential for predicting patient/graft outcome and starting antiviral treatment with the appropriate timing. Antiviral treatment with pegylated interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. Living-donor liver transplantation is now widely accepted as an established treatment for HCV cirrhosis and the results are equivalent to those of deceased donor liver transplantation. PMID:22900194
Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe
Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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
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
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.
Testino, Gianni; Patussi, Valentino; Scafato, Emanuele
Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT) in Europe and in the United States. The outcome of patients transplanted for ALD is at least as good as that for most other diagnoses and better than that for hepatitis C virus. In case of severe acute alcoholic hepatitis (AAH) non-responders to medical therapy, the reason for denying LT is that it requires abstinence from alcohol for six months before consideration for a transplant. A strict application of a period of abstinence as a policy for transplant eligibility is unfair to non-responder patients, as most of them will have died prior to the end of the six-month sober period. In our opinion, in severe AAH subjects with a good social support, with the frequency of self-help groups (alcoholics anonymous or association of clubs of alcoholics in treatment), with the frequency of Alcohol Unit and without severe psychotic or personality disorders, the lack of pre-LT abstinence alone should not be a barrier against being listed.
Jiménez-Castro, Mónica B; Meroño, Noelia; Mendes-Braz, Mariana; Gracia-Sancho, Jordi; Martínez-Carreres, Laia; Cornide-Petronio, Maria Eugenia; Casillas-Ramirez, Araní; Rodés, Juan; Peralta, Carmen
Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. Copyright © 2014 European Association for the Study of the Liver. Published by
Lorente, Laureano; Aller, Maria Angeles; Ispizua, José Ignacio; Rodriguez, José; Durán, Hipólito
One of the causes of auxiliary liver transplantation failure is the inter-liver competition between the host liver and the graft for the hepatotrophic factors of the portal blood. We have developed an experimental model of heterotopic partial (30%) liver isotransplant using Wistar rats so as to study this competition. Splenoportography and dissection demonstrate the existence of collateral circulation. The collaterals at 90 days post-transplant (PT) consisted of veins from the portal vein to the host liver (PR), paraesophageal veins (PE) and splenorenal veins (SR). At 60 days P.T., PR and SR veins but not PE ones appeared, and at 30 days P.T., there were only PR veins. Graft atrophy at 90 days P.T. was associated with a severe degree of bile duct proliferation. The gradual development of portal hypertension causes porto-systemic collateral circulation and the graft loses the portal hepatotrophic factors. The late development of the portal hypertension and the biliary proliferation could be caused by the hepatic arterial ischemia in this experimental model. Thus, as has been described in the orthotopic liver tansplantation, the heterotopic one might require a double vascularization, both portal and arterial. PMID:2278927
... 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 ...
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
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. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.
Suraweera, Duminda; Dutson, Erik; Saab, Sammy
Obesity has become increasingly prevalent, and the number of obese patients in need of liver transplant is expected to continue to increase. In addition, liver disease due to nonalcoholic fatty liver disease is expected to become the leading cause of liver transplantation in the near future. However, obesity remains a relative contraindication in liver transplant. New strategies in managing this patient population are clearly needed. To this end, the authors review the current literature on the efficacy of bariatric surgery in the setting of liver transplantation in obese patients. Copyright © 2016 Elsevier Inc. All rights reserved.
Carbone, Marco; Neuberger, James M
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune
Catana, Andreea M; Medici, Valentina
The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450
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
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.
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 a powerful research tool for 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, since 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 has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in 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. 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 liver and other diseases. PMID:26709949
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.
Hagness, Morten; Foss, Aksel; Line, Pål-Dag; Scholz, Tim; Jørgensen, Pål Foyn; Fosby, Bjarte; Boberg, Kirsten Muri; Mathisen, Oystein; Gladhaug, Ivar P; Egge, Tor Skatvedt; Solberg, Steinar; Hausken, John; Dueland, Svein
The objective of this pilot study was to investigate the potential for long-term overall survival (OS) after liver transplantation for colorectal liver metastases (CLMs). Patients with nonresectable CLMs have poor prognosis, and few survive beyond 5 years. CLMs are currently considered an absolute contraindication for liver transplantation, although liver transplantation for primary and some secondary liver malignancies shows excellent outcome in selected patients. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%) and liver transplantation for CLMs was abandoned. Since then, the survival rate after liver transplantation in general has improved by almost 30%. On the basis of this, a 5-year survival rate of about 50% after liver transplantation for CLMs could be anticipated. In a prospective pilot study, liver transplantation for nonresectable CLMs was performed (n = 21). Main inclusion criteria were liver-only CLMs, excised primary tumors, and at least 6 weeks of chemotherapy. Kaplan-Meier estimates of the OS rate at 1, 3, and 5 years were 95%, 68%, and 60%, respectively. Metastatic recurrence of disease was common (mainly pulmonary). However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after median of 27 months; range, 8-60), 33% had no evidence of disease. Hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy were identified as significant prognostic factors. OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).
Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen
Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of
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
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.
Saab, Sammy; Zhou, Kali; Chang, Edward K; Busuttil, Ronald W
Liver transplantation is the definitive therapy for patients with advanced liver disease and its complications. Patients who are transplanted with a diagnosis of hepatocellular carcinoma (HCC) are at risk of recurrent cancer, and these patients are monitored on a regular basis for recurrence. In contrast, de novo HCC following liver transplantation is a very rare complication, and recipients without HCC at the time of transplantation are not screened. We describe the clinical features of de novo HCC over a decade after achieving a sustained viral response with treatment of hepatitis C and two decades after liver transplantation. Our case highlights the necessity of screening for HCC in the post-transplant patient with advanced liver disease even after viral clearance. PMID:26807385
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
Kim, Jong Man; Kim, Kyung Mo; Yi, Nam-Joon; Choe, Yon Ho; Kim, Myung Soo; Suh, Kyung Suk; Kim, Soon I I; Lee, Suk-Koo; Lee, Sung-Gyu
Pediatric liver transplantation is the standard of care for treatment of liver failure in children. The aim of this study was to identify the characteristics of pediatric liver transplantation in centers located in Korea and determine factors that influence outcomes. This retrospective study was performed using data from between 1988 and 2010 and included all recipients 18 yr old and younger who underwent pediatric liver transplantation in Korea during that period. Our data sources were hospital medical records and the outcome measure was overall patient survival. Univariate and multivariate statistical analyses were undertaken using the Cox proportional hazards model. Five hundred and thirty-four pediatric liver transplantations were performed in 502 children. Median age and average pediatric end-stage liver disease (PELD) score were 20 months and 18 point, respectively. Biliary atresia (57.7%, 308/534) was the most common cause of liver disease. Eighty-two (15.3%) were deceased donor liver transplantations and 454 (84.7%) were living donor liver transplantations. Retransplantation was performed in 32 cases (6%). Overall, 1-, 5-, and 10-yr patient survival rates were 87.8%, 82.2%, and 78.1%, respectively. In multivariate analysis, independent significant predictors of poor patient survival were chronic rejection and retransplantation. This study presents the epidemiologic data for nearly all pediatric liver transplantation in Korea and shows that the independent prognostic factors in patient survival are chronic rejection and retransplantation.
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.
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
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
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.
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
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
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
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
Liver transplantation (LT) services in the United Kingdom are provided by 7 designated transplant centers for a population of approximately 64 million. The number of deceased organ donors has grown, and in 2014-2015 it was 1282 (570 donation after circulatory death and 772 donation after brain death). Donor risk is increasing. In 2014-2015, there were 829 LTs from deceased and 38 from living donors. The common causes for transplantation are liver cell cancer, viral hepatitis, and alcohol-related liver disease. Livers are allocated first nationally to super-urgent listed patients and then on a zonal basis. The United Kingdom will be moving toward a national allocation scheme. The median interval between listing and transplantation is 152 days for adults awaiting their first elective transplant. Of the adults listed for the first elective transplant, 68% underwent transplantation at < 1 year; 17% are waiting; and 4% and 11% were removed or died, respectively. The 1- and 5-year adult patient survival rate from listing is 81% and 68%, respectively, and from transplantation is 92% and 80%, respectively. The transplant program is funded through general taxation and is free at the point of care to those who are eligible for National Health Service (NHS) treatment; some have to pay for medication (up to a maximum payment of US $151/year). The competent authority is the Human Tissue Authority which licenses donor characterization, retrieval, and implantation; transplant units are commissioned by NHS England and NHS Scotland. National Health Service Blood and Transplant (NHSBT) promotes organ donation, maintains the organ donor register, obtains consent, and undertakes donor characterization and offering. NHSBT also maintains the national waiting list, develops and applies selection and allocation policies, monitors outcomes, and maintains the UK National Transplant Registry and commissions a national organ retrieval service. Liver Transplantation 22 1129-1135 2016 AASLD
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.
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.
Saidi, Reza F; Razavi, Moaven; Cosimi, A Benedict; Ko, Dicken S C
Improved outcomes of liver transplantation have led to increases in the numbers of US transplant centers and candidates on the list. The resultant and ever-expanding organ shortage has created competition among centers, especially in regions with multiple liver transplant programs. Multiple reports now document that competition among the country's transplant centers has led to the listing of increasingly high-risk patients and the utilization of more marginal liver allografts. The transplant and medical communities at large should carefully re-evaluate these practices and promote innovative approaches to restoring trust in the allocation of donor organs and confirming that there is nationwide conformity in the guidelines used for evaluating and listing potential candidates for this scarce resource. © 2014 American Association for the Study of Liver Diseases.
Putnam, Charles W.; Porter, Kendrick A.; Well, Richard; Reid, H. A. S.; Starzl, Thomas E.
Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiarl syndrome. She Is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. PMID:781334
Jara, Paloma; Hierro, Loreto; Martínez-Fernández, Pilar; Alvarez-Doforno, Rita; Yánez, Francisca; Diaz, María C; Camarena, Carmen; De la Vega, Angela; Frauca, Esteban; Muñoz-Bartolo, Gema; López-Santamaría, Manuel; Larrauri, Javier; Alvarez, Luis
Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion. 2009 Massachusetts Medical Society
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
Rana, Abbas; Pallister, Zachary; Halazun, Karim; Cotton, Ronald; Guiteau, Jacfranz; Nalty, Courtney C; O'Mahony, Christine A; Goss, John A
Low case volume has been associated with poorer surgical outcomes in a multitude of surgical procedures. We studied the association among low case volume, outcomes, and the likelihood of pediatric liver transplantation. We studied a cohort of 6628 candidates listed in the Organ Procurement and Transplantation Network for primary pediatric liver transplantation between 2002 and 2012; 4532 of the candidates went on to transplantation. Candidates were divided into groups according to the average volume of yearly transplants performed in the listing center over 10 years: >15, 10 to 15, 5 to 9, and <5. We used univariate and multivariate Cox regression analyses with bootstrapping on transplant recipient data and identified independent recipient and donor risk factors for wait-list and posttransplant mortality. 38.5% of the candidates were listed in low-volume centers, those in which <5 transplants were performed annually. These candidates had severely reduced likelihood of transplantation with only 41% receiving a transplant. For the remaining candidates, listed at higher volume centers, the transplant rate was 85% (P < .001). Being listed at a low-volume center was a significant risk factor in multivariate Cox regression analysis for both wait-list mortality (hazard ratio, 3.27; confidence interval, 2.53-4.23) and posttransplant mortality (hazard ratio, 2.21; confidence interval, 1.43-3.40). 38.5% of pediatric transplant candidates are listed in low-volume transplant centers and have lower likelihood of transplantation and poorer outcomes. If further studies substantiated these findings, we would advocate consolidating pediatric liver transplantation in higher volume centers. Copyright © 2015 by the American Academy of Pediatrics.
Giusto, Michela; Lattanzi, Barbara; Di Gregorio, Vincenza; Giannelli, Valerio; Lucidi, Cristina; Merli, Manuela
Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades, a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass (sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected, dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolic disorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation.
Giusto, Michela; Lattanzi, Barbara; Di Gregorio, Vincenza; Giannelli, Valerio; Lucidi, Cristina; Merli, Manuela
Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades, a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass (sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected, dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolic disorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation. PMID:25152572
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.
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.
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.
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
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
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
Living donor liver transplant (LDLT) accounts for a small volume of the transplants in the USA. Due to the current liver allocation system based on the model for end-stage liver disease (MELD), LDLT has a unique role in providing life-saving transplantation for patients with low MELD scores and significant complications from portal hypertension, as well as select patients with hepatocellular carcinoma (HCC). Donor safety is paramount and has been a topic of much discussion in the transplant community as well as the general media. The donor risk appears to be low overall, with a favorable long-term quality of life. The latest trend has been a gradual shift from right-lobe grafts to left-lobe grafts to reduce donor risk, provided that the left lobe can provide adequate liver volume for the recipient. PMID:27115007
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
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.
Diana, Restrepo B; Marle, Duque G; Carlos, Cardeño C
Liver transplantation is a treatment available for many patients with liver cirrhosis who find in this treatment a way to improve life expectancy and quality of life. Paranoid schizophrenia affects 1% of the general population, produces psychotic symptoms, and runs a chronic course in some cases with significant deterioration in all areas of life. To discuss the case of a patient with liver cirrhosis diagnosed with paranoid schizophrenia during the evaluation protocol for liver transplantation. Case report. We report the case of a 47-year-old woman with liver cirrhosis whose only alternative to improve life expectancy and quality of life was access to liver transplantation. During routine evaluations the liaison psychiatrist observed first-order psychotic symptoms and documented a life story that confirmed the presence of paranoid schizophrenia. Paranoid schizophrenia is a psychiatric disorder common in the general population that can be a part of the medical comorbidities of patients requiring liver transplantation and is not an absolute contraindication to its completion. We are unaware of similar cases of liver transplantation in patients with schizophrenia in our country. We believe this is a big step on the road to overcome the stigma that mental illness imposes on patients. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.
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
García-Sesma, A; Jiménez, C; Loinaz, C; Meneu, J C; Colina, F; Marqués, E; Gómez, R; Abradelo, M; Garcia, J I; Moreno González, E
We report three cases of Kaposi's sarcoma after orthotopic liver transplantation performed for cirrhosis related to hepatitis C virus (one case), ethanol (one case), or both (one case). All patients displayed disease within the first year after liver transplantation, and only in one case was the diagnosis obtained before the patient died. All three patients were on tacrolimus-steroid therapy, and in one case mycophenolate mofetil was added to treat acute persistent rejection.
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
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.
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
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.
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.
Villa, Nicolas A.
Strictures of the bile duct are a well-recognized complication of liver transplant and account for more than 50% of all biliary complications after deceased donor liver transplant and living donor liver transplant. Biliary strictures that develop after transplant are classified as anastomotic strictures or nonanastomotic strictures, depending on their location in the bile duct. The incidence, etiology, natural history, and response to therapy of the 2 types vary greatly, so their distinction is clinically important. The imaging modality of choice for the diagnosis of biliary strictures is magnetic resonance cholangiopancreatography because of its high rate of diagnostic accuracy and limited risk of complications. Biliary strictures that develop after liver transplant may be managed with endoscopic retrograde cholangiography (ERC), percutaneous transhepatic cholangiography (PTC), or surgical revision, including retransplant. The initial treatment of choice for these strictures is ERC with progressive balloon dilation and the placement of increasing numbers of plastic stents. PTC and surgery are generally reserved for failures of endoscopic therapy or for anatomic variants that are not suitable for ERC. In this article, we discuss the classification of biliary strictures, their diagnosis, and the therapeutic strategies that can be used to manage these common complications of liver transplant. PMID:27482175
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.
Pillai, Anjana A; Levitsky, Josh
Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate peri- and post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon. PMID:19750565
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.
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.
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
Fonseca-Neto, Olival Cirilo Lucena da; Lima, Heloise Caroline de Souza; Melo, Paulo Sérgio Vieira de; Lemos, Roberto; Leitão, Laércio; Amorim, Américo Gusmão; Lacerda, Cláudio Moura
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. To report the occurrence of acute appendicitis in a cohort of liver transplant recipients. Retrospective analysis in a period of 12 years among 925 liver transplants, in witch five cases of acute appendicitis were encountered. 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. 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.
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
Mattila, Mirjami; Kemppainen, Helena; Isoniemi, Helena; Polo-Kantola, Päivi
Pregnancy after liver transplantation is possible but associated with increased risk of obstetrical complications. We report here for the first time the pregnancy outcomes after liver transplantation in Finland. All of the 25 pregnancies ending in deliveries after liver transplantation in Finland in 1998-2015 were analyzed. The data were collected from the mothers' medical records. The main outcome measures included pregnancy complications and the mode of delivery. Neonatal outcome measures were birthweight, 5-min Apgar score and umbilical artery pH. Twenty-six infants were born. Of all deliveries, 76% occurred at the ≥37 weeks of gestation and the average birthweight was 3040 g. Apgar scores were ≥7 in 25/26 (96%) of the infants and cases of birth asphyxia (umbilical artery pH ≤ 7.05) were not detected. Cesarean section rate was 32%. Preeclampsia occurred in 12% of the women and the preterm delivery rate was 24%. Co-morbidities (hypertension, intrahepatic cholestasis of pregnancy, Hodgkin's disease, colitis ulcerosa, epileptic attacks, cholangitis, splenic artery rupture, renal insufficiency and graft rejection) complicated 52% of pregnancies. Pregnancies after liver transplantation in Finland result in good perinatal outcome with healthy, mostly full-term, normally grown offspring; however, serious maternal complications related to underlying liver pathology, transplant surgery and immunosuppressive medication occur frequently. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.
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.
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
Carbone, Marco; Neuberger, James
End-stage liver disease due to hepatitis C (HCV) and cirrhosis from alcohol (ALD) are the commonest indications for liver transplantation in the western countries. Up to one third of HCV-infected transplant candidates have a history of significant alcohol intake prior to transplantation. However, there are few data available about the possible interaction between alcohol and HCV in the post-transplant setting. Patients with both HCV and alcohol are more likely to die on the waiting list than those with ALD and HCV alone. However, after transplantation, non-risk adjusted graft and patient survival of patients with HCV + ALD are comparable to those of patients with HCV cirrhosis or ALD cirrhosis alone. In the short and medium term HCV recurrence after transplant in patients with HCV + ALD cirrhosis does not seem more aggressive than that in patients with HCV cirrhosis alone. A relapse in alcohol consumption in patients with HCV + ALD cirrhosis does not have a major impact on graft survival. The evidence shows that, as is currently practiced, HCV + ALD as an appropriate indication for liver transplantation. However, these data are based on retrospective analyses with relatively short follow-up so the conclusions must be treated with caution. PMID:21209701
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.
BIZOLLON, T; DUCERF, C; TREPO, C; MUTIMER, D
Hepatology and Liver Transplantation Unit,Hôtel-Dieu Croix-Rousse,Lyon,France D MUTIMER Cirrhosis due to hepatitis C virus (HCV) is now the most common indication of liver transplantation in Western Europe and the United States. In the absence of effective prophylaxis, recurrent HCV infection is almost inevitable. Though the natural history and intermediate term outcome of recurrent HCV are now better documented, those factors which may influence the recurrence of hepatitis and consequent progression of graft disease remain unclear. Interferon (IFN) as a sole agent for the treatment of recurrent infection has proved unsatisfactory. Early intervention with a combination of IFN and ribavirin seems promising, and this approach may prevent or delay progression of HCV related graft disease after liver transplantation. PMID:10075968
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.
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
Moreno, A; Meneu, J C; Moreno, E; Fraile, M; García, I; Loinaz, C; Abradelo, M; Jiménez, C; Gomez, R; García-Sesma, A; Manrique, A; Gimeno, A
Describe the results of liver transplantation after installing Transjugular Intrahepatic Portosystemic Shunt (TIPS) and compare them with those of a control group in a comparative, longitudinal, retrospective study. Between April 1986 and October 2002, we performed 875 liver transplantations. Between January 1996 and October 2002, 26 transplantations were performed on TIPS carriers. This group was compared with a control cohort of 50 randomly selected patients who underwent transplantation in this period (non-TIPS carriers). Both groups were homogeneous with no significant differences between age, sex United Network for Organ Sharing (UNOS) score, Child stage, or etiology. Actuarial survival rates at 1 and 3 years: TIPS group 96.15% and 89.29% versus control cohort 87.8% and 81%, respectively. In 73.9%, the TIPS was clearly effective; in 88.9%, a postoperative Doppler revealed normal flow. There were no statistically significant differences compared with time on the waiting list for transplant, duration of the operation, ischemia times, intraoperative consumption of hemoderivates, vascular or nonvascular postoperative complications, duration of stay in the intensive care unit, hospital stay, or retransplantation rate. In our experience, TIPS insertion does not affect either the intraoperative or postoperative evolution and is not associated with an increased time on the liver transplant waiting list.
Ranney, D N; Acker, W B; Al-Holou, S N; Ehrlichman, L; Lee, D S; Lewin, S A; Nguyen, C; Peterson, S F; Sell, K; Kubus, J; Reid, D; Englesbe, M J
Concern exists that liver transplant center substance abuse policies may have an inappropriate and disproportionate impact on marijuana users. Our hypothesis is that patients with chronic liver disease who were marijuana users will have inferior survival. This is a retrospective (1999-2007) cohort study. The primary outcome measure is time-dependent, adjusted patient survival from the time of liver transplant evaluation. The primary exposure variable is a positive cannabinoid toxicology screen during the liver transplant evaluation period. Overall, 155 patients qualified as marijuana users while 1334 patients were marijuana non-users. Marijuana users were significantly (p < 0.05) younger (48.3 vs. 52.1), more likely to be male (78.1% vs. 63.0%), have hepatitis C (63.9% vs. 40.6%) and were less likely to receive a transplant (21.8% vs. 14.8%). Marijuana users were more likely to use tobacco, narcotics, benzodiazepines, amphetamines, cocaine or barbiturates (p < 0.05). Unadjusted survival rates were similar between cohorts. Upon multivariate analysis, MELD score, hepatitis C and transplantation were significantly associated with survival, while marijuana use was not (HR 1.09, 95% CI 0.78-1.54). We conclude that patients who did and did not use marijuana had similar survival rates. Current substance abuse policies do not seen to systematically expose marijuana users to additional risk of mortality.
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
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.
Chan, See Ching; Fan, Sheung Tat
Living donor liver transplantation (LDLT) has gone through its formative years and established as a legitimate treatment when a deceased donor liver graft is not timely or simply not available at all. Nevertheless, LDLT is characterized by its technical complexity and ethical controversy. These are the consequences of a single organ having to serve two subjects, the donor and the recipient, instantaneously. The transplant community has a common ground on assuring donor safety while achieving predictable recipient success. With this background, a reflection of the development of LDLT may be appropriate to direct future research and patient-care efforts on this life-saving treatment alternative. PMID:18176956
Koike, Shuhei; Kobayashi, Takashi; Okada, Yoshiyuki; Shibuya, Shinsuke; Sakai, Kaoru; Tanaka, Yukari; Akamatsu, Shusuke; Negoro, Hiromitsu; Terada, Naoki; Yamasaki, Toshinari; Matsui, Yoshiyuki; Inoue, Takahiro; Kamba, Tomomi; Umeya, Yumi; Kaido, Toshimi; Ogawa, Osamu
We report a 40-year-old man with end-stage renal disease due to IgA nephropathy who underwent deceased donor kidney transplantation. The donor was diagnosed to be brain-dead due to cerebral hemorrhage after her second liver transplantation for non-viral liver cirrhosis. Intraoperative 1-hour biopsy of the graft kidney revealed moderate global glomerular sclerosis (22%) and interstitial fibrosis (40%) consistent with underlying nephrosclerosis or calcineurin inhibitor nephrotoxicity. Although hemodialysis was needed until the graft began functioning several days after the kidney transplantation, the postoperative clinical course thereafter was uneventful and the graft functioned well with stable serum creatinine levels around 2.4 mg/dl at 6 monthspos toperatively.
Acar, S; Gencdal, G; Tokac, M; Eren, E; Alkara, U; Tellioglu, G; Dinckan, A; Akyildiz, M
Polycystic liver disease is characterized by multiple cystic lesions on the liver. It is an uncommon autosomal dominant disease. The cysts' diameters range from 20 to 30 cm to small microscopic nodules. Generally, more than half of the liver parenchyma is covered. The mass effect of the liver created by the large cysts can cause life-threatening symptoms such as weight loss, reduction of oral intake, and malnutrition. Liver transplantation is the best treatment option in symptomatic patients. We present a patient who had polycystic liver and kidney disease, and we performed liver transplantation because of his life-threatening symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.
Ramanathan, Rajesh; Pettinato, Giuseppe; Beeston, John T; Lee, David D; Wen, Xuejun; Mangino, Martin J; Fisher, Robert A
Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF. Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF. A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen. Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.
Chan, Edie Y; Bhattacharya, Renuka; Eswaran, Sheila; Hertl, Martin; Shah, Nikunj; Fayek, Sameh; Cohen, Eric B; Hollinger, Edward F; Olaitan, Oyedolamu; Jensik, Stephen C; Perkins, James D
The decision for isolated kidney transplant (KT) vs. combined liver-kidney transplant (CLKT) in patients with end-stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT. Our dataset included the United Network for Organ Sharing (UNOS)/Standard Transplant and Analysis and Research (STAR) kidney files from 1987 to 2012 after being joined with the liver files from 2002 to 2012. Outcomes of patients who received a CLKT with an international normalized ratio (INR) ≤1 and total bilirubin ≤1 were compared to patients who received a primary KT and subsequently required listing for LT between zero and five yr or after five yr. For the three groups, 244 patients had a CLKT, 216 were wait-listed for LT between zero and five yr after KT (0-5 WL), and 320 were wait-listed five yr after KT (+5 WL). From the time of KT, the 0-5 WL group had significantly worse survival than the CLKT group and the +5 WL group. The +5 WL had the best survival of all groups. For the 0-5 WL group, 45% underwent LT and 40% died while waiting compared to the +5 WL group with 53% having LT and 26% died while waiting. At the time of LT, the 0-5 WL group had a higher model for end-stage liver disease (MELD) score, higher incidence of being in the ICU at the time of transplant, and higher incidence of requiring life support. From the time of LT, the CLKT trended toward better survival (p = 0.0549) than both the 0-5 WL and +5 WL groups, which had equivalent survival. The 0-5 WL group is a higher risk group with poorer survival due to a higher incidence of dying on the waitlist. Better identification of patients with a high risk for hepatic decompensation following KT and agreement for regional exception for LT in the event of decompensation may improve utilization of organs and
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.
Miller, Charles M; Quintini, Cristiano; Dhawan, Anil; Durand, Francois; Heimbach, Julie K; Kim-Schluger, Hyung Leona; Kyrana, Eirini; Lee, Sung-Gyu; Lerut, Jan; Lo, Chung-Mau; Pomfret, Elizabeth Anne
Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients.
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
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.
Kaltenborn, Alexander; Schrem, Harald
Liver transplantation is the only live-saving, curative treatment for various end-stage liver diseases, and it has excellent survival rates. Mycophenolate mofetil is widely used as co-medication for immunosuppression after liver transplantation, especially to allow a sparing effect on calcineurin-inhibitors, thus reducing their numerous adverse effects. It improves both graft and patient survival. The properties of its active metabolite, mycophenolic acid, are diverse: inhibition of de novo purine synthesis and selective lymphocyte inhibition, anti-tumoral, antiviral, anti-angioneoplastic, and vasculoprotective mechanisms are described and summarized in this review. The most common adverse effects of mycophenolate mofetil are gastrointestinal complaints such as diarrhea, which often lead to dose-reduction or withdrawal of mycophenolate mofetil. A newer, enteric-coated formulation is available, which is meant to reduce the gastrointestinal adverse effects. Mycophenolate mofetil does not relevantly interact with other common drugs. The question of whether therapeutic drug monitoring allows optimized dosing strategies cannot be satisfyingly answered yet. The optimal partner-immunosuppressant seems to be tacrolimus, especially in low doses. This tutorial review provides an overview of recent studies exploring the role of mycophenolate mofetil in liver transplantation with regards to its development, mechanism of action, and actual controversies such as therapeutic drug monitoring or de novo malignancy after transplantation.
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
Schroeder, Rebecca A; Collins, Bradley H; Tuttle-Newhall, Elizabeth; Robertson, Kerri; Plotkin, Jeffrey; Johnson, Lynt B; Kuo, Paul C
To assess clinical safety of a low central venous pressure (CVP) fluid management strategy in patients undergoing liver transplantation. Retrospective record review comparing 2 transplant centers, one using the low CVP method and the other using the normal CVP method. University-based, academic, tertiary care centers. Patients undergoing orthotopic cadaveric liver transplantation. Each center practiced according to its own standard of care. Center 1 maintained an intraoperative CVP <5 mmHg using fluid restriction, nitroglycerin, forced diuresis, and morphine. If pressors were required to maintain systolic arterial pressure >90 mmHg, phenylephrine or norepinephrine was used. At center 2, CVP was kept 7 to 10 mmHg and mean arterial pressure >75 mmHg with minimal use of vasoactive drugs. Data collected included United Network for Organ Sharing status, surgical technique, intraoperative transfusion rate, preoperative and peak postoperative creatinine, time spent in intensive care unit and hospital, incidence of death, and postoperative need for hemodialysis. Principal findings include an increased rate of transfusion in the normal CVP group but increased rates of postoperative renal failure (elevated creatinine and more frequent need for dialysis) and 30-day mortality in the low CVP group. Despite success in lowering blood transfusion requirements in liver resection patients, a low CVP should be avoided in patients undergoing liver transplantation.
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.
Mandell, Mercedes Susan; Lindenfeld, JoAnn; Tsou, Mei-Yung; Zimmerman, Michael
Physicians previously thought that heart disease was rare in patients with end stage liver disease. However, recent evidence shows that the prevalence of ischemic heart disease and cardiomyopathy is increased in transplant candidates compared to most other surgical candidates. Investigators estimate that up to 26% of all liver transplant candidates have at least one critical coronary artery stenosis and that at least half of these patients will die perioperatively of cardiac complications. Cardiomyopathy also occurs in greater frequency. While all patients with advanced cardiac disease have defects in cardiac performance, a larger than expected number of patients have classical findings of dilated, restrictive and hypertrophic cardiomyopathy. This may explain why up to 56% of patients suffer from hypoxemia due to pulmonary edema following transplant surgery. There is considerable controversy on how to screen transplant candidates for the presence of heart disease. Questions focus upon, which patients should be screened and what tests should be used. This review examines screening strategies for transplant candidates and details the prognostic value of common tests used to identify ischemic heart disease. We also review the physiological consequences of cardiomyopathy in transplant candidates and explore the specific syndrome of “cirrhotic cardiomyopathy”. PMID:18567069
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
Urbach, Andrew H.; Gartner, J. Carlton; Malatack, J. Jeffrey; Zitelli, Basil J.; Iwatsuki, Shunzaburo; Shaw, Byers W.; Starzl, Thomas E.
The linear growth of 29 patients was evaluated from two to 4⅓ years after liver transplantation. All patients received cyclosporine and low-dose prednisone, light patients (28%) displayed acceleration of linear growth velocity and were above the fifth percentile at the end of the evaluation period. Four patients (14%) grew normally prior to transplantation and continued to grow normally after the surgical procedure. Only four patients (14%) dropped from higher levels to below the fifth percentile. Thirteen patients (45%) were less than the fifth percentile before and after surgery; ten of these 13 patients have attained normal or accelerated growth velocity. Good linear growth has been achieved in more than three fourths of patients who underwent liver transplantation. PMID:3554981
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.
Pan, Heng-Chih; Chen, Ying-Jen; Lin, Jhe-Ping; Tsai, Ming-Jung; Jenq, Chang-Chyi; Lee, Wei-Chen; Tsai, Ming-Hung; Fan, Pei-Chun; Chang, Chih-Hsiang; Chang, Ming-Yang; Tian, Ya-Chung; Hung, Cheng-Chieh; Fang, Ji-Tseng; Yang, Chih-Wei; Chen, Yung-Chang
Proteinuria is a manifestation of renal dysfunction and it has been demonstrated to be a significant prognostic factor in various clinical situations. The study was designed to analyze prognosis of patients receiving liver transplantation as well as to determine predictive performance of perioperative proteinuria. We retrospectively reviewed data of patients who had received a liver transplant in a medical center between 2002 and 2010. Demographic information and clinical characteristic parameters were recorded on the day of intensive care unit admission before operation and on postoperative days 1, 7, and 14. Among a total of 323 patients, in-hospital mortality and 90-day mortality rates were 13.0 % (42/323) and 14.2 % (46/323), respectively. Patients with proteinuria on admission had higher rates of acute kidney injury (26.8 % vs. 8.8 %, p < 0.001), severe infection episodes (48.8 % vs. 30.7 %, p = 0.023), hospital death (31.1 % vs. 10.1 %, p < 0.001), and 90-day mortality (37.7 % vs. 10.9 %, p < 0.001). Multivariate analysis showed that proteinuria on admission and Sequential Organ Failure Assessment (SOFA) score were independent predictors of in-hospital mortality. The discriminatory ability of proteinuria plus SOFA was even better than that of SOFA alone, especially on postoperative day 1. The presence of proteinuria before liver transplantation is supposed to be recognized as a negative predictor for in-hospital survival. Moreover, the presence of proteinuria after liver transplantation can assist in the early prediction of poor short-term prognosis for patients receiving liver transplantation.
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.
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.
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
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
Manowski, Z; Silver, M M; Roberts, E A; Superina, R A; Phillips, M J
Two cases of hereditary tyrosinemia presented with ascites and coagulopathy in infancy. Both patients underwent liver transplantation at the age of 25 and 36 mo, respectively. Both cases had normal liver function 37 and 24 mo later. The native liver in each case showed mixed micro- and macronodular cirrhosis with hepatocellular dysplasia, including both the large and small cell varieties. One of the subjects had also shown dysplasia in a prior liver biopsy. We compared the hepatic morphology with that from two other cases from our autopsy files. One of these (a female, 9 mo old) showed dysplasia, and the other (her male sibling, 4 yr old) had a liver cell carcinoma with lung metastases. These observations confirm prior reports that neoplastic transformation occurs early in the natural history of hereditary tyrosinemia despite meticulous dietary management and other supportive treatment. With the detection of liver cell dysplasia, efforts should be intensified to find an appropriate donor. Liver transplantation cures the hepatic disease and should be performed before malignancy develops.
Foss, Aksel; Adam, Rene; Dueland, Svein
Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1- and 5-year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5-year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.
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
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. Published by Elsevier Inc.
Elola-Olaso, A Moreno; Gonzalez, E Moreno; Diaz, J C Meneu; Garcia García, I; Usera, M Abradelo; Romero, J; Perez-Saborido, B; Fraile, M; Manrique, A
Living donor liver transplantation has emerged as a response to the cadaveric graft shortage, especially for adult recipients. Both right and left liver grafts are widely used, although some technical problems remain unresolved. Herein we describe our technique for reconstruction of the venous outflow in living donor liver transplantation. From April 1986 to September 2004, 1012 liver transplantations were performed including 30 living donor liver transplantations between April 1995 and September 2004. We have selected the first 28 cases to ensure a mean follow-up of 21.07 +/- 13.11 months. We transplanted 18 right lobe grafts, 7 left lobe grafts, and 3 left lateral segment grafts. A surgical technique is described herein. No venous outflow obstruction developed among living donor liver transplantation recipients. We recommend reconstruction of the hepatic veins in living donor liver transplantation including joining together the three hepatic veins in the recipient to avoid venous outflow obstruction.
THE ONLY TREATMENT: Liver transplantation (LT) is currently the final treatment for most types of end-stage liver diseases including alcoholic cirrhosis, so far alcoholic cirrhosis has become the first indication for LT in France and other western countries, accounting for 25% of all procedures. However due to ethical issues and also the discrepancy between the theoretical number of candidates and available organs, indications for LT in alcoholic cirrhosis must be rigorously defined. On the average, candidates are 50 years old, males in two-thirds of the cases, with pre-terminal liver disease combining advanced-stage liver dysfunction (PT < 40%, bilirubin > 50 mumol/l, albumin < 30 g/l) and intractable ascitis. The gain in survival being best in patients with severe cirrhosis (Child-Pugh grade C), these patients should be given priority when liver function fails to improve despite prolonged abstention. For less advanced diseases (Child-Pugh B or A), LT can be considered after failure of symptomatic medical treatments or in case a small hepatocellular carcinoma develops. The list includes presence of extrahepatic organ failure, generally related to alcohol-tobacco abuse (cardiomyopathy, pancreatitis, neuropathy, squamous cell carcinoma ...) and precarious psychosocial situations exposing the patient to the risk of recurrent alcoholism and non-compliance after transplantation. Predictive factors of after recidivism after transplantation are preoperative abstinence of less than 6 months duration, denial of alcoholism, lack of familial and occupational support, antisocial behavior and a history of psychiatric disorders or drug abuse. Patients with several of these risk factors cannot reasonably be considered as candidates for LT. Inversely, transplantation should be proposed for patients with no or few risk factors due to the excellent physical and social outcome observed. Generally, a full 6 months of preoperative abstinence is required by most transplantation centers
Lilly, L B; Grant, D
Our understanding of cyclosporine (CsA) administration for liver transplantation has significantly improved over the past decade. Cyclosporine is a highly lipophilic molecule, and the original galenic formulation, Sandimmune, was highly dependent on bile flow and gut motility for its absorption. Sandimmune's poor absorption profile produced erratic CsA levels after liver transplantation. A new microemulsification formulation of CsA, Neoral (CsA-ME), was developed to overcome these limitations. The NOF-1 study confirmed the superiority of CsA-ME's absorption compared with Sandimmune; CsA-ME had a more consistent and reliable absorption, with lower intrapatient variability and improved dose linearity with drug exposure as measured by area under the concentration-time curve (AUC). These advantages translated into more reliable CsA predose concentrations and less toxicity. An analysis of the pharmacokinetic data showed that 2-hour postdose CsA levels (C2) provided a better measure of immune suppression than did trough levels (C0). The LIS2T study recently confirmed and extended these data by showing equivalent efficacy between CsA-ME using C2 monitoring or tacrolimus in liver transplant patients, with a similar incidence of adverse events except for a higher rate of diabetes mellitus and diarrhea with tacrolimus. These data confirmed that the improved CsA-ME formulation, when used in conjunction with optimized drug-monitoring protocols, is well tolerated after transplantation and provides low rates of graft rejection.
Huda, A; Newcomer, R; Harrington, C; Keeffe, E B; Esquivel, C O
Return to productive employment is often an important milestone in the recovery and rehabilitation process after liver transplantation (OLT). This literature review identifies factors associated with employment in patients who underwent OLT. We searched PubMed for articles that addressed the various factors affecting employment after OLT. The studies demonstrated improvement in the quality of life and examined factors that predicted whether patients would return to work after OLT. Demographic variable associated with posttransplant employment included young age, male sex, college degree, Caucasian race, and pretransplant employment. Patients with alcohol-related liver disease had a significantly lower rate of employment than did those with other etiologies of liver disease. Recipients who were employed after transplantation had a significantly better posttransplant functional status than did those who were not employed. Economic pressures are increasing the expectation that patients who undergo successful OLT will return to work. Thus, transplant teams need to have a better understanding of posttransplant work outcomes for this vulnerable population, and greater attention must be paid to the full social rehabilitation of transplant recipients. Specific interventions for OLT recipients should be designed to evaluate and change their health perceptions and encourage their return to work. Published by Elsevier Inc.
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.
Burckart, Gilbert J.; Venkataramanan, Raman; Ptachcinski, Richard J.; Starzl, Thomas E.; Gartner, J. Carlton; Zitelli, Basil J.; Malatack, Jeffrey J.; Shaw, Byers W.; Iwatsuki, Shunzaburo; Van Thiel, David H.
Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9–21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2–7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: (1) cyclosporine clearance is highly variable between patients, (2) pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, (3) cyclosporine is poorly and variably absorbed in liver transplant patients, and (4) cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation. PMID:3540030
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.
Halldorson, Jeffrey B; Paarsch, Harry J; Dodge, Jennifer L; Segre, Alberto M; Lai, Jennifer; Roberts, John Paul
In the United States, livers for transplantation are distributed within donation service areas (DSAs). In DSAs with multiple transplant centers, competition among centers for organs and recipients may affect recipient selection and outcomes in comparison with DSAs with only 1 center. The objective of this study was to determine whether competition within a DSA is associated with posttransplant outcomes and variations in patients wait-listed within the DSA. United Network for Organ Sharing data for 38,385 adult cadaveric liver transplant recipients undergoing transplantation between January 1, 2003 and December 31, 2009 were analyzed to assess differences in liver recipients and donors and in posttransplant survival by competition among centers. The main outcome measures that were studied were patient characteristics, actual and risk-adjusted graft and patient survival rates after transplantation, organ quality as quantified by the donor risk index (DRI), wait-listed patients per million population by DSA, and competition as quantified by the Hirschman-Herfindahl index (HHI). Centers were stratified by HHI levels as no competition or as low, medium (or mid), or high competition. In comparison with DSAs without competition, the low-, mid-, and high-competition DSAs (1) performed transplantation for patients with a higher risk of graft failure [hazard ratio (HR) = 1.24, HR = 1.26, and HR = 1.34 (P < 0.001 for each)] and a higher risk of death [HR = 1.21, HR = 1.23, and HR = 1.34 (P < 0.001 for each)] and for a higher proportion of sicker patients as quantified by the Model for End-Stage Liver Disease (MELD) score [10.0% versus 14.8%, 20.1%, and 28.2% with a match MELD score of 31-40 (P < 0.001 for each comparison)], (2) were more likely to use organs in the highest risk quartile as quantified by the DRI [18.3% versus 27.6%, 20.4%, and 31.7% (P ≤ 0.001 for each)], and (3) listed more patients per million population [18 (median) versus 34 (P = not significant), 37 (P
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.
Gupta, Eva; Finn, Laura; Johns, Gretchen; Pruthi, Rajiv K; Roy, Vivek
Orthotopic liver transplantation for other diseases typically results in a coincidental cure for hemophilia A and B; however, long-term outcomes of liver transplant in hemophilia C are not very well described. Herein, the authors report a patient of severe congenital factor XI (FXI) deficiency who received an orthotopic liver transplant. The authors discuss the perioperative management and long-term outcomes. The normalization of his FXI levels confirms that the liver is the most clinically relevant site of synthesis of FXI.
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
Kerkar, Nanda; Lakhole, Arathi
Liver transplantation (LT) is an important component in the therapeutic armamentarium of managing end-stage liver disease. In North American children, biliary atresia remains the most common indication for LT compared to hepatitis C in adults, while hepatoblastoma is the most common liver tumor requiring LT, versus Hepatocellular carcinoma in adults. Rejection, lymphoproliferative disease, renal insufficiency, metabolic syndrome, recurrent disease, 'de novo' autoimmune hepatitis and malignancy require careful surveillance and prompt action in adults and children after LT. In children, specific attention to EBV viremia, growth, development, adherence and transition to the adult services is also required. Antibody mediated rejection and screening for donor specific antibodies is becoming important in managing liver graft dysfunction. Biomarkers to identify and predict tolerance are being developed. Machine perfusion and stem cells (iPS) to synthesize organs are generating interest and are a focus for research.
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
Halldorson, Jeffrey B.; Paarsch, Harry J.; Dodge, Jennifer L.; Segre, Alberto M.; Lai, Jennifer; Roberts, John Paul
In the United States, livers for transplantation are distributed within donation service areas (DSAs). In DSAs with multiple transplant centers, competition among centers for organs and recipients may affect recipient selection and outcomes in comparison with DSAs with only 1 center. The objective of this study was to determine whether competition within a DSA is associated with posttransplant outcomes and variations in patients wait-listed within the DSA. United Network for Organ Sharing data for 38,385 adult cadaveric liver transplant recipients undergoing transplantation between January 1, 2003 and December 31, 2009 were analyzed to assess differences in liver recipients and donors and in posttransplant survival by competition among centers. The main outcome measures that were studied were patient characteristics, actual and risk-adjusted graft and patient survival rates after transplantation, organ quality as quantified by the donor risk index (DRI), wait-listed patients per million population by DSA, and competition as quantified by the Hirschman-Herfindahl index (HHI). Centers were stratified by HHI levels as no competition or as low, medium (or mid), or high competition. In comparison with DSAs without competition, the low-, mid-, and high-competition DSAs (1) performed transplantation for patients with a higher risk of graft failure [hazard ratio (HR) = 1.24, HR = 1.26, and HR = 1.34 (P < 0.001 for each)] and a higher risk of death [HR = 1.21, HR = 1.23, and HR = 1.34 (P < 0.001 for each)] and for a higher proportion of sicker patients as quantified by the Model for End-Stage Liver Disease (MELD) score [10.0% versus 14.8%, 20.1%, and 28.2% with a match MELD score of 31-40 (P < 0.001 for each comparison)], (2) were more likely to use organs in the highest risk quartile as quantified by the DRI [18.3% versus 27.6%, 20.4%, and 31.7% (P ≤ 0.001 for each)], and (3) listed more patients per million population [18 (median) versus 34 (P = not significant), 37 (P
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
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
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
Adams, David; Slama, Michel; Samuel, Didier
Familial amyloid polyneuropathy (FAP) is the most serious of the hereditary neuropathies in adults and is due to endoneurial amyloid deposits. These sensorimotor and autonomic diseases are very progressive and disabling. A "typical" patient with FAP is 30-years-old, of Portuguese origin, and has insidiously developed pains or sensory loss in the feet and digestive disorders, such as diarrhea, and has lost weight. Clinical examination shows sensory polyneuropathy of the distal small fibers (with sensory loss prevailing over sensations of temperature and pain). Cardiac disorders are frequent. One parent will have died prematurely from this disease. FAP are fatal 10.8 years after the first symptoms, on average. Neuropathy is usually associated with cardiac manifestations, weight loss, and more rarely renal or eye complications. FAP are secondary to a point mutation of the transthyretin (TTR) or prealbumin gene (18q11.2-q12.1), of which there are 40 variants. In France, the variant TTRMet30 is present in half of all cases and one third of FAP patients present with sporadic disease. Liver transplantation has been proposed as a treatment for FAP because the liver is the main source of variant amyloidogenic TTR. Transplantation makes it possible to eliminate 98% of the variant TTR in the serum, doubles median survival for variant TTRMet30 carriers, and halts the progress of the sensorimotor neuropathy over the long term in 62% of cases. No regression or recurrence has been observed. Poor prognostic factors after liver transplantation are a mutation other than the TTRMet30 variant, severe neuropathy, and late onset. Liver transplantation must be proposed to the symptomatic patients as early as possible. It should be performed in a center specialized in FAP. After LT, periodic follow-up in such a center is essential. Copyright 2009 Elsevier Masson SAS. All rights reserved.
Acosta Martínez, J; López-Herrera Rodríguez, D; González Rubio, D; López Romero, J L
Despite the importance of haemodynamic management in patients undergoing liver transplantation, there is currently no consensus on the most appropriate type of monitoring to use. In this context, transoesophageal echocardiography can provide useful information to professionals, although their use constraints prevent further spread today. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
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
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.
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.
Riva, Natalia; Schaiquevich, Paula; Cáceres Guido, Paulo; Halac, Esteban; Dip, Marcelo; Imventarza, Oscar
AEs during immunosuppressive treatment with tacrolimus are very common. We retrospectively evaluated FK safety and efficacy in a large pediatric liver transplant cohort in Latin America. During 2-year follow-up, we analyzed data from patients who underwent liver transplantation over the period 2010-2012 and recorded FK exposure, AEs, and AR episodes. AEs were classified according causality and severity. Tacrolimus exposure before and during AE was compared using Wilcoxon matched-pairs test. Kaplan-Meier curves were used for survival analysis. In total, 46 patients (out of 72 patients) experienced 69 AEs, such as hypomagnesemia (49%), PTLD (6%), hypertension (6%), and/or nephrotoxicity (22%). 43% of AEs were classified as moderate or serious, and 89% were assigned as probable or definitive. Patients who had one or more AR episodes accounted for 65%. The 12-month acute rejection-free survival was 41% (95% CI, 30.1%-53.1%). A significant difference was observed in FK trough concentrations before and during hypomagnesemia and nephrotoxicity (P<.05). This study is the first report of FK safety in a large group of pediatric liver transplant patients in Latin America. Children experience AEs, even in protocols with low FK doses. Therapeutic monitoring is an important tool to manage immunosuppressive schemes containing tacrolimus in vulnerable populations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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.
Bolte, Fabian Johannes; Schmidt, Hartmut H-J; Becker, Thomas; Braun, Felix; Pascher, Andreas; Klempnauer, Jürgen; Schmidt, Jan; Nadalin, Silvio; Otto, Gerd; Barreiros, Ana Paula
A retrospective multicenter study has been conducted to evaluate domino liver transplantations (DLTs) in Germany. The study provides insight into survival and features having an impact on the assessment of neuropathy after DLT. In addition, a neurologic follow-up program with a scheme to estimate the likelihood of de novo amyloidosis is presented. A series of 61 DLTs at seven transplant centers in Germany was enrolled. The mean age of domino recipients at the time of transplantation was 58 years, 46 of them being men, and 15 being women. The median follow-up was 46 months. The overall 1-, 3-, and 5-year survival of domino recipients was 81.6%, 70.8% and 68.8%, respectively. Causes of death were primarily not related to familial amyloidosis. The main indication of DLT was hepatocellular carcinoma. Two of the reported domino recipients developed symptoms and signs of de novo amyloidosis within 10 years after transplantation. A total of 30 domino graft recipients (49.18%) presented with diabetes post transplantation. In conclusion, an advanced follow-up program is crucial to evaluate the risk of transmitting familial amyloidosis by DLT and to establish more strict selection criteria for domino recipients. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.
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
Xie, Yan; Wu, Yang; Xin, Kang; Wang, Jiao-Jing; Xu, Hong; Ildstad, Suzanne T; Leventhal, Joseph; Yang, Guang-Yu; Zhang, Zheng; Levitsky, Josh
Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell-depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls. Three experimental allogeneic LT groups were treated with tacrolimus (TAC) for 3 to 4 weeks and then underwent: (1) TAC withdrawal alone; (2) nonmyeloablative conditioning (anti-αβTCR mAb + total body irradiation [300 cGy]) followed by TAC withdrawal; (3) Nonmyeloablative conditioning + donor BMI (100 × 10 T cell-depleted bone marrow cells) followed by TAC withdrawal. All group 1 recipients developed chronic rejection. Group 2 had long-term survival but impaired liver function and high donor-specific antibody (DSA) levels. In contrast, group 3 (conditioning + BMI) had long-term TAC-free survival with preserved liver function and histology, high mixed chimerism and blood/liver/spleen CD4 + CD25 + Foxp3+ regulatory T cells, and low DSA titers, similar to syngeneic grafts. While donor-specific tolerance was observed post-BMI, graft-versus-host disease was not. These results support that donor-specific tolerance can be achieved with BMI even when delayed after LT and this tolerance correlates with increased mixed chimerism, regulatory T cell generation, and diminished DSA.
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.
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. 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. © 2014 by the American Association for the Study of Liver Diseases.
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
Alvarez, Fernando; Mitchell, Grant A
Tyrosinemia is a disease of the tyrosine metabolism, affecting mainly liver, kidney and peripheral nerves. Two forms of liver disease caused by a deficiency of FAH are recognised: (1) acute liver failure; (2) chronic liver disease. Since the introduction of NTBC [2-(2-nitro-4-trifluoromethyl benzoyl)-1-3-cyclohexanedione] (nitisinone(R)) in the treatment of tyrosinemia, no liver disease has been observed when started in the first weeks of life. Liver transplantation is a good option for the treatment of tyrosinemic patients developing liver nodules, with high suspicion of hepatocarcinoma. In the long-term outcome of the liver transplant, survival was of 90% in tyrosinemic patients.
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
Zarrinpar, Ali; Kaldas, Fady; Busuttil, Ronald W
Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with multiple etiologies, high incidence, and high mortality. The standard surgical management for patients with HCC consists of locoregional ablation, surgical resection, or liver transplantation, depending on the background state of the liver. Eighty percent of patients initially presenting with HCC are unresectable, either due to the extent of tumor or the level of underlying hepatic dysfunction. While in patients with no evidence of cirrhosis and good hepatic function resection has been the surgical treatment of choice, it is contraindicated in patients with moderate to severe cirrhosis. Liver transplantation is the optimal surgical treatment. PubMed search of recent articles (from January 2000 to March 2011) was performed looking for relevant articles about hepatocellular carcinoma and its treatment. Additional articles were identified by evaluating references from selected articles. Here we review criteria for transplantation, the types, indications, and role of locoregional therapy in treating the cancer and in downstaging for possible later transplantation. We also summarize the contribution of immunosuppression and adjuvant chemotherapy in the management and prevention of HCC recurrence. Finally we discuss recent advances in imaging, tumor biology, and genomics as we delineate the remaining challenges for the diagnosis and treatment of this disease. Much can be improved in the diagnosis and treatment of HCC. A great challenge will be to improve patient selection to criteria based on tumor biology. Another will be to incorporate systemic agents post-operatively in patients at high risk for recurrence, paying close attention to efficacy and safety. The future direction of the effort in treating HCC will be to stimulate prospective trials, develop molecular imaging of lymphovascular invasion, to improve recipient selection, and to investigate biomarkers of tumor biology.
Krawczyk, Marek; Grąt, Michał; Adam, Rene; Polak, Wojciech G; Klempnauer, Jurgen; Pinna, Antonio; Di Benedetto, Fabrizio; Filipponi, Franco; Senninger, Norbert; Foss, Aksel; Rufián-Peña, Sebastian; Bennet, William; Pratschke, Johann; Paul, Andreas; Settmacher, Utz; Rossi, Giorgio; Salizzoni, Mauro; Fernandez-Selles, Carlos; Martínez de Rituerto, Santiago T; Gómez-Bravo, Miguel A; Pirenne, Jacques; Detry, Olivier; Majno, Pietro E; Nemec, Petr; Bechstein, Wolf O; Bartels, Michael; Nadalin, Silvio; Pruvot, Francois R; Mirza, Darius F; Lupo, Luigi; Colledan, Michele; Tisone, Giuseppe; Ringers, Jan; Daniel, Jorge; Charco Torra, Ramón; Moreno González, Enrique; Bañares Cañizares, Rafael; Cuervas-Mons Martinez, Valentin; San Juan Rodríguez, Fernando; Yilmaz, Sezai; Remiszewski, Piotr
Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.
Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don
Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.
Mohan, Neelam; Karkra, Sakshi; Rastogi, Amit; Dhaliwal, Maninder S; Raghunathan, Veena; Goyal, Deepak; Goja, Sanjay; Bhangui, Prashant; Vohra, Vijay; Piplani, Tarun; Sharma, Vivek; Gautam, Dheeraj; Baijal, S S; Soin, A S
To describe our experience of pediatric living donor liver transplantation from India over a period of 12 year. A retrospective analysis of 200 living donor liver transplantation in children (18 years or younger) was done for demographic features, indications, donor and graft profile and outcome. Between September 2004 and July 2016, 200 liver transplants were performed on 197 children. Fifty transplants were done in initial 6 years and 150 in next 6 years. All donors (51% mothers) were discharged with a mean stay of 7 days. The leading indications of liver transplants were cholestatic liver disease (46%) followed by metabolic liver disease (33%) and acute liver failure /acute on chronic liver failure (28.5%). Biliary leakage (8.5%), biliary stricture (9%), hepatic artery thrombosis (4.5%) and portal vein thrombosis (4%) were the most common surgical complications; all could be managed by surgical or interventional radiological measures, except in one child who died. Sepsis, acute rejection and CMV hepatitis in first 6 months were seen in 14.5%, 25% and 17% cases, respectively. Post-transplant lymphoproliferative disease was seen in only 1.5%. Re-transplant rate was 1.5%. The overall 1 year survival rate was 94% and 5 year actuarial survival was 87% with no statistically significant difference between children weight < 10 kg vs. > 10 kg. Outcome in acute liver failure did not differ significantly between those with acute on chronic liver failure vs. those with chronic liver disease. Advances in medical and surgical techniques associated with multidisciplinary teams including skilled pediatric liver transplant surgeons, anesthetists, dedicated pediatric hepatologists, pediatric intensivists, interventional radiologists and pathologists resulted in an excellent outcome of living related liver transplants in children. Low age and weight of the baby does not seem to be a contraindication for liver transplantation as outcome were comparable in our experience.
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.
Lladó, Laura; Fabregat, Joan; Ramos, Emilio; Baliellas, Carme; Roca, Josep; Casasnovas, Carlos
Combined heart and liver transplantation for familial amyloid polyneuropathy (FAP) is currently the best treatment for patients with cardiomyopathy related to FAP. However, its optimal timing and the possibility of domino liver transplantation in this setting remain under discussion. Most such cases in the medical literature have been performed simultaneously, although many of them have required the use of veno-venous bypass and the majority have not used the liver as a graft for domino liver transplantation. We report 3 cases of non-Val30Met mutation that underwent sequential heart and domino liver transplantation at our institution. We describe the 3 cases and the medical literature, with special attention to the reason for sequential heart and liver transplantation, the role of transient elastography in this setting, and the feasibility of domino liver transplantation. In our experience, combined heart and liver transplantation is a feasible but challenging procedure for patients with FAP. Performing the procedure sequentially rather than simultaneously seems safer and easier, both technically and hemodynamically. More importantly, such an approach allows the use of livers from FAP patients as grafts for domino liver transplantation. Copyright © 2013 Elsevier España, S.L. All rights reserved.
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
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.
Rana, A; Hardy, M A; Halazun, K J; Woodland, D C; Ratner, L E; Samstein, B; Guarrera, J V; Brown, R S; Emond, J C
It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21,673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30,321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures.
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
Bilhartz, Jacob L; Shieck, Victoria L
Liver transplantation originated in children more than 50 years ago, and these youngest patients, while comprising the minority of liver transplant recipients nationwide, can have some of the best and most rewarding outcomes. The indications for liver transplantation in children are generally more diverse than those seen in adult patients. This diversity in underlying cause of disease brings with it increased complexity for all who care for these patients. Children, still being completely dependent on others for survival, also require a care team that is able and ready to work with parents and family in addition to the patient at the center of the process. In this review, we aim to discuss diagnoses of particular uniqueness or importance to pediatric liver transplantation. We also discuss the evaluation of a pediatric patient for liver transplant, the system for allocating them a new liver, and also touch on postoperative concerns that are unique to the pediatric population.
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
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
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. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.
Cisneros-Garza, Laura E; López-Hernández, Pedro A; Muñoz-Ramírez, M del Rosario; Castilla-Valdéz, Martha Patricia; Sebastián-Ruiz, M José; Carmona-Martínez, Juan Gerardo; Alvarez-Treviño, Guillermo Alberto; Martínez-Flores, José Guillermo; Olavide-Aguilar, Ramón
Liver transplantation is the best treatment for end stage liver diseases. In April 2003, our institution started a Liver Transplantation Program for both pediatric and adults population. Shown the results of the Liver Transplantation Program in the UMAE 25 Monterrey N.L. This is a retrospective cohort study of patients with liver transplantation. A total of 51 liver transplantations have been done in 49 patients with two retrasplantation, 15 in children and 36 in adults. The principal indication for liver transplantation in children was biliary atresia and hepatitis C cirrhosis in adults. The acute renal failure was the main early complication, the acute cellular rejection in the mediate period, and the cardiovascular diseases as late complication related to obesity, metabolic syndrome, diabetes mellitus and hypertension. Overall survival at 1 and 5 years was 57.1 and 54.2%, respectively. During the first three years post-transplantation, the quality of life was good or very good. Although still a young and perfectible program, the effort of a multidisciplinary team has made possible to perform liver transplantation in two patient populations, pediatric and adults.
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
Marqués, E; Jiménez, C; Manrique, A; Vallejo, G H; Clemares, M; Ortega, P; Moreno, E
Malignancies are a serious long-term complication among liver transplant recipients, with an overall incidence of 4.5%-15%. Posttransplantation lymphoproliferative disease (PTLD) is one of the leading causes of late death. Its development is related to complex interactions between immunosuppressive drugs and environmental agents. The aim of this study was to analyze risk factors for PTLD and survival after orthotopic liver transplantation (OLT) compared with solid tumors. We undertook a retrospective review of the clinical histories of adult patients who underwent OLT between July 1986 and February 2001, and who had been followed until 2005. This study comprised 528 adult recipients who survived more than 2 months after OLT. We excluded pediatric, partial-organ, and multiorgan recipients. No differences were observed concerning gender, viral etiology of hepatitis, calcineurin inhibitor regimen, or steroid maintenance period. Treated acute rejection episodes accounted for 53.3% of patients who developed PTLD compared with 47.3% in the control group (P = .787). Patients with solid tumors were older at the time of diagnosis than those with PTLD (57.5 +/- 8.13 years vs 48.8 +/- 13.9; P = .002). The overall mortality rate for PTLD was 55.5%, which did not differ significantly from solid tumors. PTLD develops in younger patients after OLT. Various immunosuppressive regimens do not seem to influence the incidence of PTLD or other solid tumors.
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
Stock, P G; Estrin, J A; Fryd, D S; Payne, W D; Belani, K G; Elick, B A; Najarian, J S; Ascher, N L
The purpose of this study was to analyze data from all adult and pediatric liver transplants performed between January 1, 1983 and January 15, 1986 at the University of Minnesota Hospital and identify perioperative variables that predict patient survival and could aid in patient selection. Charts, intraoperative anesthesia records, blood bank records, flow sheets, outpatient records, and autopsy reports were examined in 45 pediatric and 15 adult patients who underwent primary orthotopic liver transplantation. Analysis of the data can be summarized as follows: (1) Pediatric patients whose coagulation parameters could not be corrected prior to operation and who consequently required preoperative exchange transfusion had poorer outcomes than those not requiring an exchange to correct coagulation parameters. (2) The rapid infusion technique for massive blood transfusion resulted in significantly decreased blood loss and intraoperative blood product replacement. (3) Twenty-four hour postoperative factor V levels were good predictors of survival. Patients with poor factor V levels required rigorous replacement of coagulation factors. (4) Pediatric patients with uncorrectable coagulopathies requiring immediate postoperative exchange transfusion had extremely high mortality.
Uribe, M; Hunter, B; Alba, A; Calabrán, L; Flores, L; Soto, P; Herzog, C
The success rate of pediatric liver transplantation has improved in recent years. Advances in immunosuppression have reduced the risk of rejection, but have enhanced the risk of posttransplant lymphoproliferative disorder (PTLD). Since 1994, we have performed 197 orthotopic liver transplantations in 157 recipients younger than 15 years. Herein we have performed a retrospective study to review the incidence and clinical characteristics, along with the treatment and outcomes of PTLD diagnosed over this 14-year experience. We documented 8 cases of PTLD (5%), half of which occurred during the first 2 years posttransplantation; 5 presented with abdominal involvement and 2 with thoracic masses. The histological findings showed lymphoma in 6 cases. All were treated with reduction of immunosuppression and 2 received Rituximab. Three patients died, a mortality rate of 37.5%. One subject experienced rejection, and the others responded to treatment. PTLD is a life-threatening condition that requires a high index of suspicion, appropriate imaging, biopsy diagnosis, and prompt treatment to achieve positive results. Quantitative monitoring of Epstein-Barr virus load may be useful to detect a high-risk population.
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.
Calne, R. Y.; Williams, Roger; Dawson, J. L.; Ansell, I. D.; Evans, D. B.; Flute, P. T.; Herbertson, P. M.; Joysey, V.; Keates, G. H. W.; Knill-Jones, R. P.; Mason, S. A.; Millard, P. R.; Pena, J. R.; Pentlow, B. D.; Salaman, J. R.; Sells, R. A.; Cullum, P. A.
Two patients with primary hepatic malignancy were treated by hepatectomy and orthotopic liver transplantation. In both cases the donor liver was infused with cold solutions and kept chilled without continuous perfusion. There was immediate satisfactory hepatic function in both transplants. The first patient died after 11 weeks from overwhelming bacterial and fungal infections probably secondary to hepatic infarction due to thrombosis of the recipient hepatic artery. The thrombus occurred at the site of the arterial clamp. In an attempt to control the growth before transplantation, the patient had been treated with large doses of chlorambucil, which resulted in extreme marrow depression and septicaemia. The second patient developed cholestatic jaundice during the second and third weeks after transplantation, with histological evidence of mild rejection, which was controlled by increasing the dose of immunosuppressive agents. He is now well, having returned to work six weeks after the operation. Though the first patient showed no evidence of rejection, it is concluded that patients receiving liver allografts should receive immunosuppressive therapy. ImagesFig. 2Fig. 8Fig. 2Fig. 3A and BFig. 4Fig. 6Fig. 1Fig. 5Fig. 7 PMID:4881064
Ling, Qi; Xu, Xiao; Xie, Haiyang; Wang, Kai; Xiang, Penghui; Zhuang, Runzhou; Shen, Tian; Wu, Jian; Wang, Weilin; Zheng, Shusen
New-onset diabetes after transplantation (NODAT) is a serious complication of liver transplantation (LT). The present study aimed to investigate the risk factors of NODAT by a national survey using the China Liver Transplant Registry database. A total of 10 204 non-pre-existing diabetic patients undergone primary LT between January 2000 and December 2013 were included. Risk factors were identified by logistic regression analysis. NODAT occurred in 24.3% of liver recipients with a median follow-up time of 2.6 years, and was associated with a significantly lower patient survival. NODAT increased not only diabetes related complications (e.g., infection, kidney failure) but also biliary stricture and cholangitis. NODAT patients who received hypoglycaemic treatment had a worse prognosis and a higher hepatocellular carcinoma recurrence compared with those without treatment. New-onset hyperglycaemia (<30 days) was the major predictor of NODAT. Other risk factors included cold ischaemia time >9 h, recipient age >50 years, body mass index >25 kg/m(2) , other hepatitis (mainly hepatitis C), post-transplant intensive care unit stay >15 days, cytomegalovirus infection and corticosteroid at discharge. The incidence of NODAT in China is similar to that in Western countries. However, the NODAT-related complications are more common and severer in China compared with those in Western countries. The major risk factors are different. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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.
Hashemi Goradel, Nasser; Eghbal, Mohammad Ali; Darabi, Masoud; Roshangar, Leila; Asadi, Maryam; Zarghami, Nosratollah; Nouri, Mohammad
Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen (APAP)-induced liver damage. Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y (SRY) primers. The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver injury were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats. Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury.
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.
Wasson, Nicholas R; Deer, Jeremy D; Suresh, Santhanam
Pediatric patients with liver dysfunction and renal failure may exhibit many comorbidities. There are often associated congenital syndromes to be taken into account. Liver and renal transplantation offer a solution and substantial improvement in quality of life. Anesthetic management of pediatric liver and renal transplantation has not been well described. There are key differences between adults and children undergoing these procedures, and acknowledgment of some key principles provide a solid foundation to optimize perioperative outcomes. This article provides an overview of the perioperative management and considerations in pediatric patients undergoing liver and renal transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.
Capone, Kristin; Amirikian, Karine; Azzam, Ruba K
Pediatric liver transplantation is a state-of-the-art treatment for children with end-stage liver disease. Over the past few decades, the advent of new surgical techniques using split liver grafts and living donors has drastically increased the organ availability for pediatric patients, while advances in immunosuppression have improved overall outcomes. The pediatrician is a key player in the multidisciplinary team that cares for these children starting with the timely referral of children who require liver transplantation to the active participation in optimizing the child's overall health before and after transplantation. [Pediatr Ann. 2016;45(12):e439-e445.]. Copyright 2016, SLACK Incorporated.
Thornburg, Bartley; Katariya, Nitin; Riaz, Ahsun; Desai, Kush; Hickey, Ryan; Lewandowski, Robert; Salem, Riad
Liver transplantation (LT) is commonly used to treat patients with end-stage liver disease. The evolution of surgical techniques, endovascular methods, and medical care has led to a progressive decrease in posttransplant morbidity and mortality. Despite these improvements, a multidisciplinary approach to each patient remains essential as the early diagnosis and treatment of the complications of transplantation influence graft and patient survival. The critical role of interventional radiology in the collaborative approach to the care of the LT patient will be reviewed. Liver Transplantation 23 1328-1341 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.
Mehta, K D; Ragni, M V
Hepatitis C is the major cause of end-stage liver disease and the major indication for orthotopic liver transplantation (OLTx) in individuals with haemophilia. To assess the epidemiology and outcomes of OLTx in U.S. haemophilia patients. We investigated haemophilia liver transplant recipients between 1993 and 2012, using the Nationwide Inpatient Sample, identified by ICD9 code 50.59. Of the 11 267 (weighted n = 54 691) patients undergoing OLTx, 44 (0.4%; weighted n = 213) had haemophilia. Those with haemophilia were more likely than non-haemophilic OLTx recipients to have bleeding complications (45.3% vs. 31.5%, P = 0.009) and hypovolemic shock (7.0% vs. 1.1%, P < 0.0001). They also had a significantly higher incidence of HIV (24.8% vs. 0.5%, P < 0.005), hepatitis B (16.2% vs. 7.9%, P = 0.04) and vitamin K deficiency (2.1% vs. 0.02%, P < 0.001). In spite of these differences, there was no difference in in-hospital mortality between haemophilic and non-haemophilic recipients (6.8% vs. 6.2%, P = 0.9). In multivariate logistic regression, bleeding complications in haemophilia increased the risk of in-hospital mortality by more than 3-fold (P < 0.0001), and disseminated intravascular coagulation increased the risk of bleeding complications in haemophilic recipients by over 10-fold (P < 0.0001). Bleeding complications are common in haemophilia OLTx recipients. Thus, aggressive correction of coagulation defects in this group may be a medically sound approach to reduce complications and mortality associated with OLTx. © 2016 John Wiley & Sons Ltd.
Lu, Tian Fei; Hua, Xiang Wei; Cui, Xiao Lan; Xia, Qiang
Orthotopic liver transplantation is currently the best treatment option for selected patients with hepatocellular carcinoma (HCC). From 1980 to 2011, 8874 patients with HCC in China underwent liver transplantation. The organ donation classification criteria of China (China criteria), which are established by the Government of China, are divided into three parts: China criteria I, donation after brain death; China criteria II, donation after cardiac death and China criteria III, donation after dual brain-cardiac death. Data from the China Liver Transplant Registry(CLTR) System shows that patients within the Milan criteria have higher survival rates than those who are beyond these criteria. Based on CLTR data, altogether 416 patients received living-donor liver transplantation(LDLT) in China. Their 1-year and 3-year survival rates were significantly higher than those of the non-LDLT recipients. The most common early stage(<30 days after liver transplantation) complications include pleural effusion, diabetes, peritoneal effusion or abscess, postoperative infection, hypertension and intraperitoneal hemorrhage; while the most common late stage (≥ 30 days after liver transplantation) complications were diabetes, hypertension, biliary complications,postoperative infection, tacrolimus toxicity and chronic graft rejection. The incidence of vascular complication, which is the main reason for acute graft failure and re-transplantation, was 2.4%. Liver transplantation is an effective treatment for patients with HCC in China.
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.
Scholz, T; Gallimore, M J; Bäckman, L; Mathisen, O; Bergan, A; Klintmalm, G B; Aasen, A O
In this study, we evaluated the role of proteolytic enzymes belonging to the coagulation, fibrinolytic, and plasma contact systems in the early postoperative phase after orthotopic liver transplantation (OLT). Twenty-nine patients were studied at the time of OLT and during the first 2 postoperative weeks. Blood samples were collected daily after OLT and analyzed for kallikrein-like activity (KK), functional kallikrein inhibition (KKI), plasmin-like activity (PL), and alpha2-antiplasmin (AP). In addition, prekallikrein (PKK), prothrombin (PTH), antithrombin III (AT III), plasminogen (PLG), prothrombin/antithrombin III complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), and plasmin/alpha2-antiplasmin complexes (PAP) were measured. Nineteen patients experienced biopsy-verified acute rejections (AR) and ten patients had uneventful courses and served as controls. Plasma analyses showed that the contact, coagulation, and fibrinolytic systems were activated during OLT. Following OLT, continuous thrombin and plasmin generation was observed, and these effects were more pronounced in the group having an uneventful course than in patients with AR. Factors that could possibly affect plasma proteolytic activity, such as blood product usage during and after OLT and cold ischemia time of the liver graft, did not differ between the groups, nor did the routine liver function tests, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
DiMartini, Andrea; Cruz, Ruy J; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Kim, Kevin H; Fontes, Paulo
For patients with end-stage liver disease, commonly used indices of nutritional status (ie, body weight and body mass index) are often inflated because of fluid overload (ie, ascites and peripheral edema), and this results in an underdiagnosis of malnutrition. Because muscle is the largest protein reservoir in the body, an estimate of the muscle mass may be a more reliable and valid estimate of nutritional status. Therefore, we used pretransplant computed tomography data for 338 liver transplantation (LT) candidates to identify muscle and fat mass on the basis of a specific abdominal transverse section commonly used in body composition analyses, and we investigated the contribution of this measure to specific post-LT outcomes. We found that the majority of our patients (68%) could be defined as cachectic. For men, muscle mass predicted many important posttransplant outcomes, including intensive care unit (ICU) stay, total length of stay (LOS), and days of intubation. Muscle mass was a significant predictor of survival and also predicted disposition to home versus another facility. For women, muscle mass predicted ICU stay, total LOS, and days of intubation, but the effect was modest. Muscle mass did not predict survival or disposition for women. In conclusion, because pretransplant muscle mass is associated with many important postoperative outcomes, we discuss these findings in the context of possible pretransplant interventions for either improving or sustaining muscle mass before surgery. © 2013 American Association for the Study of Liver Diseases.
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.
Roche, Bruno; Samuel, Didier
Liver transplantation is the only therapy for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to hepatitis D virus (HDV) and hepatitis B virus (HBV) coinfection or superinfection. Patients chronically coinfected with HDV are less at risk of HBV recurrence and have a better survival rate than patients infected with HBV alone. Patients coinfected with HDV generally do not require pretransplant antiviral therapy. Rates of recurrent HBV-HDV infection are lower than 5% using low-dose intramuscular (IM) HBIg and antiviral prophylaxis in combination. Few studies have evaluated the possibility of using shorter-term HBIg (12-24 months) then switching to antiviral therapy. Although HBV replication can be controlled by potent HBV-polymerase inhibitors, reappearance of HBsAg and/or the persistence of HBV DNA in serum, liver, or peripheral blood mononuclear cells might have deleterious consequences in the setting of HBV-HDV coinfection as they may provide the biologic substrate to the reactivation of HDV. No effective antiviral drug is available for the treatment of graft infection with HDV. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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
Aby, Elizabeth; Jimenez, Melissa A; Grotts, Jonathan F; Agopian, Vatche; French, Samuel W; Busuttil, Ronald W; Saab, Sammy
Background and Aims: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality. Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy. The introduction of direct-acting antiviral agents (DAAs) has changed the management of recurrent HCV infection. This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs. Methods: A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV. The analysis included 475 adult liver transplants for hepatitis C performed at the University of California, Los Angeles from January 1, 2006 to October 1, 2015. Patients were divided into two eras, pre- and post-introduction of DAAs on December 1, 2013. Results: In the era before the introduction of DAAs, the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs. 26.9%, p < 0.001). Conclusions: The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV. Given that DAAs are well tolerated and have high efficacy, liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation.
Aby, Elizabeth; Jimenez, Melissa A.; Grotts, Jonathan F.; Agopian, Vatche; French, Samuel W.; Busuttil, Ronald W.; Saab, Sammy
Abstract Background and Aims: Hepatitis C virus (HCV) cirrhosis is the leading indication for liver transplantation in the United States and recurrent HCV following liver transplantation is a major cause of allograft loss and mortality. Liver biopsies are commonly used to identify recurrent HCV and determine the need for antiviral therapy. The introduction of direct-acting antiviral agents (DAAs) has changed the management of recurrent HCV infection. This study aimed to describe the role of liver biopsies in liver transplant recipients with HCV after the introduction of DAAs. Methods: A retrospective analysis was performed looking at the rate of liver biopsies post-liver transplantation for HCV. The analysis included 475 adult liver transplants for hepatitis C performed at the University of California, Los Angeles from January 1, 2006 to October 1, 2015. Patients were divided into two eras, pre- and post-introduction of DAAs on December 1, 2013. Results: In the era before the introduction of DAAs, the percentage of patients biopsied was significantly higher compared to the era after the introduction of DAAs (56.1% vs. 26.9%, p < 0.001). Conclusions: The introduction of DAAs has changed the management of liver biopsy following liver transplantation and the management of recurrent HCV. Given that DAAs are well tolerated and have high efficacy, liver biopsies are no longer routinely used to justify the use antiviral therapy following liver transplantation. PMID:28936400
Hori, Tomohide; Uemoto, Shinji; Gardner, Lindsay B.; Sibulesky, Lena; Ogura, Yasuhiro; Nguyen, Justin H.
Background A small-for-size graft is important in living-donor liver transplantation (LDLT) and deceased-donor liver transplantation (DDLT). Subjects and methods First, we confirmed the effect of initial graft volume on survival using a rat model of liver transplantation (LT). We then evaluated the actual long-term survival based on graft type in 1421 LTs (including 1364 LDLTs) at Kyoto University and 2000 DDLTs at the Mayo Clinic, to evaluate donor safety in LDLT and the possibility of shifting to split orthotopic liver transplantation (SOLT) in DDLT. Results In the rat model, SOLTs with 40%- and 20%-grafts had a poor survival. A total of 697 pediatric LTs showed good long-term outcomes (survival rate was 0.764 at 21.2 years). The survival rate of 724 adult LTs was 0.664 at 17.8 years. The survival rates of auxiliary partial orthotopic liver transplantation with a left-sided graft (0.421 at 15.0 years) and SOLT with a left-sided graft (0.000 at 0.8 years) need to be improved. Although the survival rate of 1965 adult DDLTs with a whole-liver graft in the Mayo Clinic was 0.727 at 12.8 years, that of adult SOLT was 0.595 at 11.0 years. Conclusion From the viewpoint of greater donor safety and expanded donor candidates in LDLT, the choice of a left-sided graft still remains controversial. A shift to SOLT to achieve excellent results should be established to resolve a donor shortage in DDLT. PMID:21955515
Xinias, Ioannis; Mavroudi, Antigoni; Vrani, Olga; Imvrios, Georgios; Takoudas, Dimitrios; Spiroglou, Kleomenis
Liver transplantation (LT) is the only available live-saving procedure for children with irreversible liver failure. This paper reports our experience from the follow-up of 16 Greek children with end-stage liver failure who underwent a LT. Over a period of 15 years, 16 pediatric liver recipients received follow up after being subjected to OLT (orthotopic liver transplantation) due to end-stage liver failure. Nine children initially presented with extrahepatic biliary atresia, 2 with acute liver failure after toxic mushroom ingestion, 2 with intrahepatic cholestasis, 2 with metabolic diseases and one with hepatoblastoma. Ten children received a liver transplant in the Organ Transplantation Unit of Aristotle University of Thessaloniki and the rest in other transplant centers. Three transplants came from a living-related donor and 13 from a deceased donor. Six children underwent immunosuppressive treatment with cyclosporine, mycophenolate mofetil and corticosteroids, and 7 with tacrolimus, mycophenolate mofetil and corticosteroids. Three out of 16 children died within the first month after the transplantation due to post-transplant complications. Three children presented with acute rejection and one with chronic organ rejection which was successfully managed. Five children presented with cytomegalovirus infection, 5 with Epstein-Barr virus, 2 with HSV1,2, 2 with ParvoB19 virus, 2 with varicella-zoster virus and one with C. Albicans infection. One child presented with upper gastrointestinal hemorrhage and one with small biliary paucity. A satisfying outcome was achieved in most cases, with good graft function, except for the patient with small biliary paucity who required re-transplantation. The long-term clinical course of liver transplanted children is good under the condition that they are attended in specialized centers. PMID:21589827
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.
Gao, Peng Ji; Gao, Jie; Li, Zhao; Hu, Zhi Ping; Leng, Xi Sheng; Zhu, Ji Ye
Portal vein thrombosis (PVT) is a common complication in patients with liver cirrhosis. During liver transplantation (LT), PVT may complicate the procedure and lead to a poor prognosis. The aim of this study is to evaluate patients enrolled in the China Liver Transplant Registry, to understand the influence of PVT to the LT recipients. We collected data from patients who underwent LT and were entered into the China Liver Transplant Registry. All data of medical records and follow-up were retrospectively reviewed. The preoperative condition, duration of surgery, intraoperative blood loss, postoperative early and late PVT, and survival rates were compared between patients with PVT and those without PVT. Multivariate Cox analysis and survival analysis were used to determine the influence of PVT. A total of 20,524 cases were recruited into the study. In all, 1810 (8.82%) patients were diagnosed with preoperative PVT of various severities. All patients were followed up for an average of 30.25±33.25months (up to a maximum of 171.68months). Patients with PVT had a significantly longer operating time, more intraoperative blood loss and a higher rate of post-LT PVT (P<0.001). Multivariate Cox analysis showed that PVT did not reduce the recipients' survival rate (HR=0.89, 95% CI: 0.774-1.024, P=0.103). There was no significant difference in cumulative survival rate (P=0.059) between patients without PVT, and patients with PVT. PVT increases the difficulty of LT, but doesn't reduce the survival rate. Therefore, PVT is not an absolute contraindication for LT in experienced transplantation centers. Copyright © 2016. Published by Elsevier Masson SAS.
Zitelli, Basil J.; Miller, Joanne W.; Gartner, J. Carlton; Malatack, J. Jeffrey; Urbach, Andrew H.; Belle, Steven H.; Williams, Laurel; Kirkpatrick, Beverly; Starzl, Thomas E.
Sixty-five pediatric patients who received liver transplants between May 1981 and May 1984 were observed for as many as 5 years and examined for changes in lifestyle. Children were less frequently hospitalized, spent less time hospitalized, required fewer medications, and generally had excellent liver and renal function after hepatic transplantation as compared with their pre-transplantation status. Most children were in age-appropriate and standard school classes or were only 1 year behind. Cognitive abilities remained unchanged. Children improved in gross motor function and patients’ behavior significantly improved according to parents’ perceptions. Enuresis was more prevalent, however, than in the population of children who had not received liver transplants. Parental divorce rates were no greater than those reported for other families with chronically ill children. Overall, objective changes in life-style as well as parents’ perceptions of behavior of children appear to be improved after liver transplantation. PMID:3041361
Liver transplantation is believed to reverse the clinical and metabolic abnormalities of cirrhosis. Reduced skeletal muscle mass or sarcopenia contributes to increased mortality and adverse consequences of cirrhosis. Failure of reversal of sarcopenia of cirrhosis after liver transplantation is not well recognized. Six temporally, geographically, and methodologically distinct follow-up studies in 304 cirrhotics reported conflicting data on changes in indirect measures of skeletal muscle mass after transplantation. Distinct measures of body composition but not skeletal muscle mass were used and did not focus on the clinical consequences of sarcopenia after transplantation. A number of studies reported an initial rapid postoperative loss of lean mass followed by incomplete recovery with a maximum follow-up of 2 years. Posttransplant sarcopenia may be responsible for metabolic syndrome and impaired quality of life after liver transplantation. Potential reasons for failure to reverse sarcopenia after liver transplantation include use of immunosuppressive agents [mammalian target of rapamycin (mTOR) and calcineurin inhibitors] that impair skeletal muscle growth and protein accretion. Repeated hospitalizations, posttransplant infections, and renal failure also contribute to posttransplant sarcopenia. Finally, recovery from muscle deconditioning is limited by lack of systematic nutritional and physical-activity-based interventions to improve muscle mass. Despite the compelling data on sarcopenia before liver transplantation, the impact of posttransplant sarcopenia on clinical outcomes is not known. There is a compelling need for studies to examine the mechanisms and consequences of sarcopenia post liver transplantation to permit development of therapies to prevent and reverse this disorder. PMID:23912247
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.
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
Molina Raya, A; García Navarro, A; San Miguel Méndez, C; Domínguez Bastante, M; Villegas Herrera, M T; Granero, K; Becerra Massare, A; Villar Del Moral, J M; Expósito, M; Fundora Suárez, Y
The aim of this work was to determine the impact of obesity on the morbidity and mortality of liver transplantation (LT) recipients. A single-center, observational-cohort, retrospective study was conducted in patients undergoing LT from January 2008 to December 2014 to compare complications and survival between those with body mass index (BMI) <35 kg/m(2) and those with BMI ≥35 kg/m(2). The study included 170 patients: 162 (95.3%) with BMI <35 kg/m(2) and 8 (4.7%) with BMI ≥35 kg/m(2). The groups significantly differed in overall mortality and graft survival: The risk of death was 3.54-fold higher (95% confidence interval, 1.39-9.03) and the mean graft survival was shorter (61 vs 21 mo; P = .001) in the group with BMI ≥35 kg/m(2). The groups did not significantly differ in rates of biliary complications, arterial and portal vein thrombosis, retransplantation or reintervention, intraoperative requirement for blood products, length of intensive care unit stay, or post-reperfusion syndrome or rejection rates. Although no significant differences were found between these groups in post-transplantation complications, BMI ≥35 kg/m(2) emerged as a mortality risk factor in these patients. Copyright © 2016. Published by Elsevier Inc.
Heffron, TG; Pillen, T; Smallwood, GA; Rodriguez, J; Sekar, S; Henry, S; Vos, M; Casper, K; Gupta, N; Fasola, C; Romero, R
Children transplanted for acute liver failure (ALF) urgently require an optimal graft. Lower post-transplant survival compared to children transplanted for chronic liver disease. Over 10 years, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type (ABO incompatible grafts (ABOI), Large for size grafts(XL)(GRWR>5%),deceased donor segmental liver transplantation(DDSLT), living donor liver transplantation (LDLT) and whole liver transplant (WLT) were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. 12/33 received ABOI, 5 XL grafts, 18 DDSLT, and 3 LDLT. Waiting time pre-transplant was 2.1 days. 1 and 3 year patient survival ALF group was 93% and 93% and graft survivals were 93 and 78.6%. Median follow-up was 1452 days. ABOI one and three year patient and graft survival in the ALF was 92 and 75%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group nor the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, large for size grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival not significantly different than that for non-acute liver disease. PMID:19519799
Ye, Hui; Zhao, Qiang; Wang, Yufang; Wang, Dongping; Zheng, Zhouying; Schroder, Paul Michael; Lu, Yao; Kong, Yuan; Liang, Wenhua; Shang, Yushu; Guo, Zhiyong; He, Xiaoshun
To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation. To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model. The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61). Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation.
Wang, Dongping; Zheng, Zhouying; Schroder, Paul Michael; Lu, Yao; Kong, Yuan; Liang, Wenhua; Shang, Yushu; Guo, Zhiyong; He, Xiaoshun
Objective To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation. Methods To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model. Results The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61). Conclusions Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation. PMID:26368552
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.
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
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
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.
Adams, Leon A; Arauz, Oscar; Angus, Peter W; Sinclair, Marie; MacDonald, Graeme A; Chelvaratnam, Utti; Wigg, Alan J; Yeap, Sze; Shackel, Nicholas; Lin, Linda; Raftopoulos, Spiro; McCaughan, Geoffrey W; Jeffrey, Gary P
Diabetes at time of liver transplantation is associated with reduced post-transplant survival. We aimed to assess whether additional metabolic conditions such as obesity or hypertension had additive prognostic impact on post-transplantation survival. A multi-center cohort study of 617 adult subjects undergoing liver transplantation between 2003 and 2009 has been used. Dry body mass index was calculated following adjustment for ascites. After a median follow-up of 5.8 years (range 0-10.5), 112 (18.2%) patients died. Diabetes was associated with reduced post-transplant survival (hazard ratio 1.89, 95% confidence interval [CI] 1.25-2.86, P = 0.003), whereas obesity, hypertension, dyslipidemia, and the metabolic syndrome itself were not (P > 0.3 for all). Patients with concomitant diabetes and obesity had lower survival (adjusted Hazard Ratio [aHR] 2.40, 95%CI 1.32-4.38, P = 0.004), whereas obese non-diabetic patients or diabetic non-obese patients had similar survival compared with non-diabetic, non-obese individuals. The presence of hypertension or dyslipidemia did not impact on survival in patients with diabetes (P > 0.1 for both). Obese diabetic patients had longer intensive care and hospital stays than non-obese diabetic or obese, non-diabetic patients (P < 0.05). The impact of concomitant obesity and diabetes on survival was greater in subjects aged 50+ years (52.6% 5-year survival, aHR 3.04, 95% CI 1.54-5.98) or those transplanted with hepatocellular carcinoma (34.1% 5-year survival, aHR 3.35, 95% CI 1.31-5.57). Diabetes without obesity was not associated with an increased mortality rate in these sub-groups. Concomitant diabetes and obesity but not each condition in the absence of the other is associated with reduced post-liver transplant survival. The impact of diabetes and obesity is greater in older patients and those with hepatocellular carcinoma. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons
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
Liu, Song; Miao, Ji; Shi, Xiaolei; Wu, Yafu; Jiang, Chunping; Zhu, Xinhua; Wu, Xingyu; Ding, Yitao; Xu, Qingxiang
In spite of the increasing success of liver transplantation, there remains inevitable risk of postoperative complications, re-operations, and even death. Risk factors that correlate with post-transplant death have not been fully identified. We performed a retrospective analysis of 65 adults that received donation after circulatory death liver transplantation. Binary logistic regression and Cox's proportional hazards regression were employed to identify risk factors that associate with postoperative death and the length of survival period. Twenty-two recipients (33.8%) deceased during 392.3 ± 45.6 days. The higher preoperative Child-Pugh score (p = .007), prolonged postoperative ICU stay (p = .02), and more postoperative complications (p = .0005) were observed in deceased patients. Advanced pathological staging (p = .02) with more common nerve invasion (p = .03), lymph node invasion (p = .02), and para-tumor satellite lesion (p = .01) were found in deceased group. The higher pre-transplant Child-Pugh score was a risk factor for post-transplant death (OR = 4.38, p = .011), and was correlated with reduced post-transplant survival period (OR = 0.35, p = .009). Nerve invasion was also a risk factor for post-transplant death (OR = 13.85, p = .014), although it failed to affect survival period. Our study emphasizes the impact of recipient's pre-transplant liver function as well as pre-transplant nerve invasion by recipient's liver cancer cells on postoperative outcome and survival period in patients receiving liver transplantation.
Kiuchi, Tetsuya; Oike, Fumitaka; Yamamoto, Hidekazu
Controversies on small-for-size (SFS) graft in liver transplantation have evolved in parallel with the history of living donor liver transplantation for adults. It is true that the liver regenerates rapidly within a limited threshold. But 'normal' liver weight itself is variable and the influences of variable liver graft and extrahepatic factors are not negligible in pathological condition. Clinical features of 'SFS syndrome' are neither specific nor inevitable in low-weight liver and many other factors than actual graft weight contribute to their occurrence. Among them, early elevation of portal venous pressure highly probably plays a key role. In the clinical trials of surgical modification and local pharmacological manipulation targeting portal hemodynamics and tissue congestion, it may be the time to discard an excessive fear for SFS grafts and to minimize unnecessary withdrawal from the opportunity of transplantation.
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
Bayrakci, Umut Selda; Baskin, Esra; Ozcay, Figen; Gulleroglu, Kaan; Ozbay, Ferda; Sevmis, Sinasi; Karakayali, Hamdi; Haberal, Mehmet
HT is a frequent cardiovascular risk factor in liver transplant recipients. However, there are only few studies in the literature regarding the risk of HT in liver transplanted children. The aim of this study was to assess the 24 h BP profiles of liver transplanted patients and to compare the results with healthy children. ABPM was performed on 20 liver transplanted patients and 27 healthy children aged 7.1 ± 4.8 and 8.5 ± 2.9 yr, respectively. HT was defined as SDS > 1.64 (i.e., >95th percentile) adjusted for gender and height. The mean duration of post-transplant follow-up was 32 ± 19 months. Six (30%) patients were found to be hypertensive. The physiological nocturnal BP fall was attenuated significantly in the study group for diastolic BP (11.5 ± 6.1 mmHg vs. 17.7 ± 7.1 mmHg, p = 0.006). Specifically, the number of patients with high nighttime systolic and diastolic BP SDS (p = 0.02 and p = 0.004, respectively) as well as elevated nighttime systolic (p = 0.03) and diastolic (p = 0.003) BPLs was found to be significantly higher than those in the controls. Alteration of the "normal" circadian rhythm is very frequent in liver transplant recipients. Thus, it is recommended to perform ABPM on all liver transplanted children not to underdiagnose HT. © 2012 John Wiley & Sons A/S.
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.
Howell, Jessica; Balderson, Glenda; Hellard, Margaret; Gow, Paul; Strasser, Simone; Stuart, Katherine; Wigg, Alan; Jeffrey, Gary; Gane, Ed; Angus, Peter W
Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the
Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems. Copyright © 2015 Elsevier Ltd. All rights reserved.
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.
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
Wong, Wendy; Merker, Jason D; Nguyen, Christine; Berquist, William; Jeng, Michael; Viele, Maurene; Glader, Bertil; Fontaine, Magali J
Anemia is a common finding in post-liver transplant patients. Causes for the anemia include nutritional deficiencies, red cell aplasia as well as immune-mediated hemolysis. One of the immunologic causes of hemolytic anemia is drug-induced hemolysis. Tacrolimus is a common immunosuppressant used in post-liver transplant patients to prevent graft rejection. There have been reports of tacrolimus-associated hemolytic anemia secondary to hemolytic uremic syndrome as well as autoimmune hemolysis. There are also case-reports of severe hemolytic anemia related to cold agglutinin production in post-liver transplant patients. We described in this paper three cases of severe cold agglutinin hemolytic anemia in three pediatric liver transplant patients. Steroid therapy, plasmapheresis and withdrawal of tacrolimus led to resolution of the severe hemolytic process in each case. Whether the immune-mediated hemolysis is related to tacrolimus is not clear and needs to be characterized further.
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.
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.
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.
Mendoza-Sánchez, Federico; Javier-Haro, Francisco; Mendoza-Medina, Diego Federico; González-Ojeda, Alejandro; Cortés-Lares, José Antonio; Fuentes-Orozco, Clotilde
Liver transplantation in patients with liver cirrhosis, portal vein thrombosis, and cavernous transformation of the portal vein, is a complex procedure with high possibility of liver graft dysfunction. It is performed in 2-19% of all liver transplants, and has a significantly high mortality rate in the post-operative period. Other procedures to maintain portal perfusion have been described, however there are no reports of liver graft perfusion using right gastroepiploic vein. A 20 year-old female diagnosed with cryptogenic cirrhosis, with a Child-Pugh score of 7 points (class "B"), and MELD score of 14 points, with thrombosis and cavernous transformation of the portal vein, severe portal hypertension, splenomegaly, a history of upper gastrointestinal bleeding due to oesophageal varices, and left renal agenesis. The preoperative evaluation for liver transplantation was completed, and the right gastroepiploic vein of 1-cm diameter was observed draining to the infrahepatic inferior vena cava and right suprarenal vein. An orthotopic liver transplantation was performed from a non-living donor (deceased on January 30, 2005) using the Piggy-Back technique. Portal vein perfusion was maintained using the right gastroepiploic vein, and the outcome was satisfactory. The patient was discharged 13 days after surgery. Liver transplantation was performed satisfactorily, obtaining an acceptable outcome. In this case, the portal perfusion had adequate blood flow through the right gastroepiploic vein. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.
Lerut, Jan P; Orlando, Giuseppe; Sempoux, Christine; Ciccarelli, Olga; Van Beers, Bernard E; Danse, Etienne; Horsmans, Yves; Rahier, Jacques; Roggen, Francine
Hepatic epithelioid haemangioendotheliomas (HEHEs) are rare, low-grade vascular tumours. Five adults with HEHEs and one adult with a vascular tumour showing combined features of haemangioma and haemangioendothelioma underwent liver transplantation. Two HEHE patients had extrahepatic metastases at the time of transplantation. Median survival time following diagnosis was 10.7 years (range 40 months to 195 months). One patient needed resection of a HEHE in the breast 13 years post-transplantation. All six patients are surviving free from disease 22 to 166 months after transplantation (median 77 months). One HEHE-patient who had been treated for 8 years for vertebral and cerebral localisations is free of disease without immunosuppression 56 months after transplantation. We can conclude that liver transplantation is a valuable treatment for hepatic haemangioendothelioma, even in cases of extrahepatic localisation of the disease.
Levy, M F; Greene, L; Ramsay, M A; Jennings, L W; Ramsay, K J; Meng, J; Hein, H A; Goldstein, R M; Husberg, B S; Gonwa, T A; Klintmalm, G B
We undertook this study to understand the factors at our transplant center that contribute to patients' return to the ICU after their liver transplant and their initial discharge from that unit. Patients who, after liver transplantation, fail discharge from the Intensive Care Unit (ICU) and must be readmitted to that unit may well utilize many more resources than those patients who are well enough to stay out of the ICU. A retrospective review of a prospectively maintained liver transplant research database followed by a retrospective review of (a subgroup) patient charts and contemporaneous controls. A large metropolitan tertiary care center and adult liver transplant center. A total of 1,197 consecutive adult patients who underwent their initial liver transplantation from 1984 to 1996. Readmission to the intensive care unit after adult liver transplantation and discharge from that unit. Only recipient age, pretransplant synthetic function labs (protime and albumin), bilirubin levels, and intraoperative blood product requirements could be statistically linked to the group requiring ICU readmission. The primary etiology for ICU readmission was cardiopulmonary deterioration. Readmission was associated with significantly lower patient and graft survivals. A detailed review of 23 patients transplanted from October 1994 to June 1996 was made, with special emphasis on cardiopulmonary status (hemodynamics, respiratory variables, and chest radiograph findings). This subgroup was compared with 30 temporally matched controls who were not readmitted to the ICU. Intravascular fluid overload and lower inspiratory capacity were significant factors related to ICU readmission. Readmitted patients had a longer hospitalization with higher hospital charges than the control group. We conclude that the most important means of preventing ICU readmission in liver transplantation patients is to optimize cardiopulmonary function and status. Close monitoring of fluid balance to avoid
Breil, Thomas; Wenning, Daniel; Teufel, Ulrike; Hoffmann, Georg F; Ries, Markus
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. 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. 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. 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 should serve as a baseline for future
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.
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
Bourdeaux, Christophe; Pire, Aurore; Janssen, Magda; Stéphenne, Xavier; Smets, Francoise; Sokal, Etienne; de Magnée, Catherine; Fusaro, Fabio; Reding, Raymond
pT, under mono- and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS-related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus-based regimens (median follow-up post-LT: 6.0 yr, range: 0.8-9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow-up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus-steroid regimen. Beyond April 2001, 105 patients received steroid-free tacrolimus-basiliximab or tacrolimus-daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS-free operational tolerance (n = 6), 27 of them belonging to the 43 steroid-free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid-free tacrolimus-based IS seems to promote long-term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT. © 2012 John Wiley & Sons A/S.
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
Delaune, Vaihere; Berney, Thierry; Lacotte, Stéphanie; Toso, Christian
The portal vein remains the preferred site for pancreatic islet transplantation due to its easy access and low morbidity. However, despite great progress in isolation and transplantation protocols over the past few years, it is still associated with the early loss of some 50-70% of transplanted islets. The complex liver microenvironment itself presumably plays an important role in this loss. The present review focuses on the specifics of the liver microenvironment, notably the localized hepatic ischemia/reperfusion injury following transplantation, the low oxygenation of the portal vein, the instant blood-mediated inflammatory reaction, the endogenous liver immune system, and the gut-liver axis, and how they can each have an impact on the transplanted islets. It identifies the potential, or already applied, clinical interventions for improving intraportal islet survival, and pinpoints those promising areas still lacking preclinical research. Future interventions on clinical intraportal islet transplantation need to take into account the global context of the liver microenvironment, with multi-point interventions being most likely to improve early islet survival and engraftment. © 2017 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.
One of the most important problems after solid organ transplantation including liver, remains infections. Multiple risk factors play a role among which the most important are: general patients health before transplantation, prolong operative time, graft function and type of immunosuppression. The most important problems with bacterial, fungal and viral infections was described as well as treatment and profilaxis.
Climov, M; Măciuceanu Zarnescu, M B; Stefănescu, A; Zamfirescu, D; Lascăr, I
The aim of this study was to emphasize the learning curve of hemifacial transplantation in rats by comparison between 2 operators: medical student trained in basic microsurgery and an experienced microsurgeon. A total number of 15 hemifacial transplants between Brown Norway as donors and Wistar as receiver rats were performed by two operators: experienced microsurgeon (group II, n=5) and the medical student (group III, n=10). Warm ischemia time and operative time were used as instrument for comparison. All the rats received immunosuppressive treatment with cyclosporine A in monotherapy for 30 days. Results were processed statistically using Microsoft Excel. Transplantation procedure duration time performed by experienced microsurgeon began from 420 min and decreased to 330 min after 5 transplantations, with confidence interval (95% probability)382 ± 37.9 min and the warm ischemia time decreased from 140 min to 50 min, confidence interval of the warm ischemia time being 90 ± 33.52 min. After transplantation the rats were treated with cyclosporine A and monitored for 30 days. Medical student tended to equalize the operative time and warm ischemia time, approximately, after 9 transplantations, from 660 min to 330 min and warm ischemia time from 190 min to 60 min. The confidence interval (95%) of the procedure by duration of the surgery was 467 ± 80.66 min and 133.5 ± 31.44 min for the warm ischemia time. Most of the rats (n=11) survived in both transplanted groups (group II and group III) performed by microsurgeon and student. By analyzing learning curves using two parameters (operative time and warm ischemia time) and survival rates no statistically significant difference was found (p 0.05). Hemifacial transplantation model in rats is a useful tool for preparing experimental and clinical application of the facial transplantation. It is a good model for training young specialists for future transplantation surgery. It is important to notice that the medical
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
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
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
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
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.
Wong, Linda L; Truong, Hung P; Seto, Todd; Lacar, Lea; Naugler, Willscott E
Approximately 5% of liver transplants annually are performed urgently with "status-1" designation. This study aims to determine if the demand, characteristics and outcome for status-1 liver transplantation has changed over time. We utilized the Scientific Registry of Transplant Patients (2003-2015) to characterize 2352 adult patients who underwent 2408 status-1 liver transplants and compared them between Era1 (2003-6/2009) and Era2 (7/2009 -2015). Overall, there were fewer liver transplants performed with the Status-1 designation in Era2 than Era1 (1099 vs 1309). Although the number of urgent liver transplants was relatively constant with successive years, the proportion transplanted with Status-1 designation decreased markedly over time. Era2 patients were older (43.2 vs 41.7 years, p=0.01) and less likely be ABO-incompatible (1.1% vs 2.4%, p=0.01) or re-transplant (77 vs 124, p=0.03). In terms of disease etiology, the largest group was "ALF, nonspecified" (43.4%). There was no difference in proportion with drug-induced liver injury (DILI), but the subset of herbal/dietary supplements increased in Era2 (1.3% vs 0.46 %, p=0.04). Survival was increased in Era2 in the overall cohort and for patients with autoimmune disease (p <0.05), despite longer waiting-times for this etiology (186 vs 149 days). DILI or nonspecified ALF had shorter waiting-times and 90% were transplanted within 7 days. LT for the most urgent indications (Status-1) is decreasing, while survival remains excellent. Fewer incidences of acute liver failure are classified as indeterminate, mostly as a result of increasing awareness of Autoimmune Hepatitis and DILI as causes of the syndrome.
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.
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.
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
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
Gilbo, N; Mirabella, S; Strignano, P; Ricchiuti, A; Lupo, F; Giono, I; Sanna, C; Fop, F; Salizzoni, M
During orthotopic liver transplantation (OLT), various situations may occur in which biliary reconstruction is neither technically feasible nor recommended. One bridge to a delayed anastomosis can be an external biliary fistula (EBF). This procedure allows the surgeon to execute hemostatic maneuvers, such as abdominal packing; therefore, biliary reconstruction can be subsequently performed in a bloodless operative field without edematous tissues. EBF can be made by placing in the donor biliary tract a cannula that is fixed to the bile duct using 2-0 silk ties and secured outside the abdominal wall. The biliary anastomosis will be performed within 2 days after the OLT. The aim of this study was to examine the safety of EBF in terms of the incidence of biliary complications compared with a direct anastomosis. Among 1,634 adult OLTs performed in 17 years in our center, 1,322 were carried out with termino-terminal hepaticocholedochostomy (HC-TT); two with side-to-side hepaticocholedochostomy; 208 with hepaticojejunostomy (HJ); 31 with EBF and delayed HC-TT, and 71 with EBF and delayed HJ. Biliary complication rates in the EBF group were 24.5%, including 23.9% in the delayed HJ and 25.8% in the delayed HC-TT. Biliary complication incidence among all OLTs was 24.6% (P = NS). No complications related to the procedure were observed. Therefore, EBF is a safe technique without a higher biliary complication rate. It may be useful when a direct biliary anastomosis is dangerous.
Nemes, Balázs; Gelley, Fanni; Dabasi, Eszter; Gámán, György; Fehérvári, Imre; Görög, Dénes; Kóbori, László; Fazakas, János; Vitális, Eszter; Doros, Attila; Gálffy, Zsuzsanna; Máthé, Zoltán
The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. The aim of this study was to analyse risk factors and colonisations of bacterial infections. The files of 408 patients (281 bacterium cultures) were reviewed. Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.
Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah; Molinari, Michele
Studies on patients' societal reintegration following orthotopic liver transplantation (OLT) are scarce. 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. 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. 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.
Larralde, Margarita; Giachetti, Ana; Kowalczuk, Alicia; D'Agostino, Daniel; Galimberti, Ricardo
We report the occurrence of calcinosis cutis in a 3-year-old girl after liver transplantation. The cutaneous lesions consisted of 5 mm white papules on an erythematous base in linear and rosette configurations that developed in the abdominal and lumbar areas 10 days after transplantation. The patient had received calcium chloride solution intravenously during surgery. We excluded other causes of ectopic calcification such as hyperparathyroidism, renal failure, and extravasation of calcium solution. We discuss the etiology of calcinosis cutis after liver transplantation. This sequence of events has not been previously described in pediatric patients.
Jiménez Pérez, Miguel; Olmedo Martín, Raúl; Marín García, David; Lozano Rey, Juan Miguel; de la Cruz Lombardo, Jesús; Rodrigo López, Juan Miguel
Sirolimus is a potent immunosuppressive drug that began to be used in the last few years. This drug was initially used in renal transplantation but its use in other solid organ transplantations such as liver, heart, lung and pancreas, has been increasing. Sirolimus is indicated in rescue therapies and to reduce the secondary toxic effects of calcineurin inhibitors. However, this drug has been associated with infrequent but severe pulmonary toxicity and cases of interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, and alveolar proteinosis have been described. We present the case of a male liver transplant recipient who developed interstitial pneumonitis associated with sirolimus use.
Khanna, A; Gish, R; Winter, S C; Nyhan, W L; Barshop, B A
Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but long-term outcome is controversial. Many patients with other approved indications for liver transplantation die before donor grafts are available. A 28-year-old man with MMA underwent cadaveric liver transplantation. His liver was used as a domino graft for a 61-year-old man with primary sclerosing cholangitis, who had low priority on the transplant waiting list. Surgical outcome was successful, and after transplantation both patients have excellent graft function. The patient with MMA showed substantial decrease in methylmalonate in urine (from 5,277 ± 1,968 preoperatively to 1,068 ± 384 mmol/mol creatinine) and plasma (from 445.9 ± 257.0 to 333.3 ± 117.7 μmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 ± 0.33 g/kg/day. The domino recipient maintained near-normal levels of plasma amino acids but did develop elevated methylmalonate in blood and urine while receiving an unrestricted diet (peak plasma methylmalonate 119 μmol/l and urine methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein). Neither patient demonstrated any apparent symptoms of MMA or metabolic decompensation during the postoperative period or following discharge. Liver transplantation substantially corrects methylmalonate metabolism in MMA and greatly attenuates the disease. In this single patient experience, a liver from a patient with MMA functioned well as domino graft although it did result in subclinical methylmalonic acidemia and aciduria in the recipient. Patients with MMA can be considered as domino liver donors for patients who might otherwise spend long times waiting for liver transplantation.
Reddi, D M; Barbas, A S; Castleberry, A W; Rege, A S; Vikraman, D S; Brennan, T V; Ravindra, K V; Collins, B H; Sudan, D L; Lagoo, A S; Martin, A E
The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15-yr-old male from pre-B-cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre-B-cell acute lymphoblastic leukemia. He is currently alive 31 months post-transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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
Cordone, Gabriella; Zingone, Fabiana; Cardillo, Giuseppe; Martinelli, Vincenzo; Pugliese, Novella; Pellegrini, Lucienne; Ciacci, Carolina; Parrilli, Gianpaolo
The prevalence and causes of erythrocytosis after liver transplantation have never been studied, even though this condition is known to predispose patients to thrombosis leading to graft failure or death. Erythrocytosis after orthotopic liver transplantation (OLT) can be defined as an increase in the red cell mass >125% in patients without a pre-OLT history of this condition. The study population was composed of 96 patients: 33 had undergone transplantation for a hepatitis B virus (HBV) infection (18 had a hepatitis D virus coinfection), 43 had undergone transplantation for a hepatitis C virus infection, 9 had undergone transplantation for alcohol abuse, and 11 had undergone transplantation for other causes [autoimmune liver disease (6), Wilson's syndrome (1), or cryptogenetic liver cirrhosis (4)]. Idiopathic erythrocytosis was reported in 11 male patients with a history of HBV infection. Patients with the diagnosis of erythrocytosis underwent phlebotomy every 3 weeks until the hematocrit level reached 45%, and this was repeated if the level exceeded 49%, so no patient presented with cardiovascular accidents during the follow-up. In conclusion, a history of HBV infection, male sex, and hepatitis B immune globulin therapy are all possible cofactors for an increased risk of erythrocytosis in OLT patients. Copyright © 2013 American Association for the Study of Liver Diseases.
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.
Rana, Abbas; Kaplan, Bruce; Jie, Tun; Porubsky, Marian; Habib, Shahid; Rilo, Horacio; Gruessner, Angelika C; Gruessner, Rainer W G
The 15% mortality rate of liver transplant recipients at one yr may be viewed as a feat in comparison with the waiting list mortality, yet it nonetheless leaves room for much improvement. Our aim was to critically examine the mortality rates to identify high-risk periods and to incorporate cause of death into the analysis of post-transplant survival. We performed a retrospective analysis on United Network for Organ Sharing data for all adult recipients of liver transplants from January 1, 2002 to October 31, 2011. Our analysis included multivariate logistic regression where the primary outcome measure was patient death of 49,288 recipients. The highest mortality rate by day post-transplant was on day 0 (0.9%). The most significant risk factors were as follows: for one-d mortality from technical failure, intensive care unit admission odds ratio (OR 3.2); for one-d mortality from graft failure, warm ischemia >75 min (OR 5.6); for one-month mortality from infection, a previous transplant (OR 3.3); and for one-month mortality from graft failure, a previous transplant (OR 3.7). We found that the highest mortality rate after liver transplantation is within the first day and the first month post-transplant. Those two high-risk periods have common, as well as different, risk factors for mortality. © 2013 John Wiley & Sons A/S.
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.
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.
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.
Kabiling, Catherine S; Chen, Chao-Long; Concejero, Allan; Wang, Chih-Chi; Wang, Shih-Ho; Lin, Chih-Che; Liu, Yueh-Wei; Yong, Chee-Chien; Jawan, Bruno; Cheng, Yu-Fan
Liver transplantation (LT) in overseas patients is a sensitive issue because of the possibility of organ trafficking and transplant tourism. In the Istanbul Summit, there was a call to develop standardized professional frameworks to prevent these practices. Our objectives are three-fold, to critically evaluate our professional framework, to study the demographic profiles, and to identify the outcome and impact of LT in overseas patients. Recipient and donor case records, e-mail communications, and medico-legal records were collected and analyzed for management strategy, demographic profile, donor and recipient characteristics, and outcome. Only 5% of our total LT operations were for overseas patients. Forty-two (79%) were pediatric cases for which 39 (93%) were due to biliary atresia (P<0.001). Sixty-eight percent were from the Philippines. Thirty-seven (70%) of the donors were first-degree relative. The average hospital days of a pediatric living donor liver transplant (LDLT) recipient was 65.48±28.7, and average cost was 44,602 USD. An adult LDLT recipient stayed for 52.09±11.3 days and spent around 75, 013 USD. A donor of pediatric LDLT stayed in the hospital for 17.42±5 days and spent round 8,176 USD. A donor for adult LDLT was admitted for 15.5±4 days and spent an average 9,612 USD. The total cost for recipient and donor were 56,615 USD (range, 28,976-82,056) for pediatric LDLT and 84,483 USD (range, 64,851-108,467) for adult LDLT. Actuarial survival rates were 91% at 1 year, 88% at 3 years, and 86% at 5 years and 10 years. Travelling for LDLT may be a wise and cost-effective step for patients with end-stage liver disease seeking alternative ways from their country. Our professional framework is effective to prevent practice of organ trafficking and transplant tourism. It may be useful to develop international guidelines for the practice of LT in overseas patients.
This review aims to outline the delivery of liver transplant services in the UK. Liver transplantation in the UK is based on seven designated transplant units serving a population of just over 60 million people. Nearly 900 liver transplants were done in 2013/2014. Potential deceased donors are identified and referred to centrally employed specialist nurses for obtaining family consent and for donor characterisation. Organs are retrieved by a National Organ Retrieval Service, based on seven abdominal and six cardiothoracic retrieval teams providing a 24/7 service which has shown to be capable of retrieving organs from up to ten donors a day. Donated organs are allocated first nationally to those who qualify for super-urgent listing. The next priority is for splitting livers, and if there is no suitable recipient or the liver is not suitable for splitting, then livers are offered first to the local centre; each centre has a designated donor zone, adjusted annually to ensure equity between the number of patients listed and the number of donors. The allocation scheme is being reviewed, and national schemes based on need, utility and benefit are being assessed. Outcomes are monitored by National Health Service Blood and Transplant (NHSBT), and if there is a possibility of adverse deviation, then further inquiries are made. Outcomes, both from listing and from transplantation, are published by the centre on the NHSBT website ( www.odt.nhs.uk ). NHSBT works closely with stakeholders primarily through the advisory groups with clinicians, patients, lay members and professional societies and aims to provide openness and transparency. The system for organ donation and delivery of liver transplant in the UK has developed and is now providing an effective and efficient service, but there remains room for improvement.
Özbilgin, M; Ünek, T; Egeli, T; Ağalar, C; Özbilgin, Ş; Hancı, V; Ellidokuz, H; Astarcıoğlu, I
We investigated the liver transplantation literature since 1975 and found the most frequently cited 100 articles and assessed the distribution of authors and journals of these articles. Using the advanced mode of the Institute for Scientific Information (ISI) Web of Science (WOS) search engine, the words "SU = transplantation AND TI = liver OR SU = transplantation AND TS = liver" were used to scan articles and determine the most-cited 100 articles on July 18, 2016. From 1975 to date, it appears a total of 43,369 articles were published in the field of liver transplantation in the WOS. Although the most cited article had 677 citations, the least cited article had 180 citations. The mean citation number for the 100 articles was 252.31 ± 96.75. The mean annual citation number for the articles varied from 61.55 to 5 and the mean was 15.31 ± 8.63. The most cited article was by Feng et al "Characteristics Associated With Liver Graft Failure: The Concept of a Donor Risk Index" published in the American Journal of Transplantation (677 citations). Bibliometric analysis highlights the key topics and publications that have shaped the understanding and management of liver transplantation. According to our research, this is the first study to investigate articles with most citations in the field of liver transplantation. In our study the article with the most citations was cited 677 times, whereas the 100th article was cited 180 times with a mean citation number for the 100 articles of 252.31 ± 96.75. Copyright © 2017 Elsevier Inc. All rights reserved.
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.
Got'e, S V; Shagidulin, M Iu; Onishchenko, N A; Krasheninnikov, M E; Il'inskiĭ, I M; Mozheĭko, N P; Liundup, A V; Volkova, E A; Petrakov, K I; Avramov, P V; Perova, N V; Sevast'ianov, V I
On an experimental model of chronic fibrotic liver damage (male rats Wistar (n-60), damage of CCl4, the duration of the experiment 90 days) it was studied the effectiveness of cell therapy for the correction of chronic liver failure. These rats were divided into 3 experimental groups: in the Ist-group (control, n=10) isotonic saline (650 mkl.) was injected; in the IInd-group (n=20) suspension of liver cells was applicated in a dose 8 - l0 x 10(6) cells; in the IIIrd-group (n=30) suspension of liver cells and bone marrow cells (mesenchymal stromal cells) in ratio 5:1 were used as cell associates on microparticles intjectable heterogeneous biopolymer hydrogel "SpheroGEL" (cell-engineering design) in common dose 8 - l0 x 10(6) It was ascertained that in the 2nd and in the 3rd groups the accelerated normalization of disturbed liver functional indices (ALT, AST, ALP) took place - to 30 days, but in the control group only to 90 days. The reliable differences in rats ofnormalization offunctional indices were absent between the IInd and the IIIrd groups. But in 90 days by using special histological dyeing it was found out that defibrotic processes in liver tissue were more expressed in the IIIrd group in comparison with the IIIrd group. Received results were consequence of prolonged vital activity of cells (liver cells and mesenchymal stromal bone marrow cells) into cell-engineering designs, which were transplanted in the IIIrd group. The obtained effect can be explained by that the developed cell-engineering designs provide adequate conditions for prolonged vital activity of the transplanted cells.
Chiu, King-Wah; Nakano, Toshiaki; Chen, Kuang-Den; Hsu, Li-Wen; Lai, Chia-Yun; Huang, Ching-Yin; Cheng, Yu-Fan; Goto, Shigeru; Chen, Chao-Long
Cytochrome P450 metabolizes many drugs in the liver. Three genotypes of CYP2C19 with extensive, intermediate, and poor metabolizing activity, respectively, have been identified in peripheral blood of transplant recipients and new liver grafts in living donor liver transplantation (LDLT). The expression of the final genotype in liver graft biopsies depends on the donor, whereas the expression in peripheral blood mononuclear cells depends on the recipient. The metabolizing isoenzyme of the major anti-rejection agents passes through CYP3A4, CYP3A5 and MDR1, which have also been identified to have similar biological characteristics as genotype of CYP2C19 in liver tissue. Recently, pyrosequencing has been used to investigate the expressions of different genotypes in liver grafts in LDLT. This review focuses on recent findings regarding the biological expressions of the CYP2C19, CYP3A4, CYP3A5 and MRD1 genotypes in liver grafts before and after LDLT. The application of pyrosequencing may be beneficial in further research on liver transplantation. Laser capture microdissection of hepatocytes in liver grafts may be a direction for future research.
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.
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)
Ghosh, Partha S; Hupertz, Vera; Ghosh, Debabrata
We studied neurological complications (NCs) after liver transplantation (LT) in children. We performed an institutional review board-approved retrospective review of patients with LT ≤21 years during a period of 30 years (1980-2010). NCs were classified as early (within 3 months post-LT) and delayed (beyond 3 months post-LT). Of 65 children with LT, 20 (30.7%) had NCs; 16 were girls. Mean age was 11.8±5.9 years. Early NCs were found in 13.8% (9/65) of the patients: seizures in 7 and encephalopathy in 2. Abnormal neuroimaging findings were posterior reversible leukoencephalopathy syndrome (1), intracranial hemorrhage (1), mild cerebral edema (1), and bilateral basal ganglia T1W hyperintensities in magnetic resonance imaging (1). On follow-up, there were 3 deaths (unrelated to NCs). One with intracranial hemorrhage had residual hemiparesis and was taking a long-term antiepileptic drug. Late NCs are found in 16.9% (11/65) of the patients: seizures in 4, headache in 4, encephalopathy in 3 (1 had seizures in addition), and paresthesias caused by possible small-fiber neuropathy in 1. Abnormal neuroimaging findings were hypoxic-ischemic encephalopathy (1), encephalomalacia caused by old hemorrhage (1), and hyperintensity of the posterior periventricular white matter in magnetic resonance imaging (1). On follow-up, all of the patients survived; 1 had papilledema with secondary optic atrophy requiring optic nerve sheath fenestration and 1 needed long-term antiepileptic drug. NCs are common in children after LT, seizures being the most common. In contrary to the previous studies, we found delayed complications more often than early complications. Early detection and appropriate management of NCs is important.
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
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
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. 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. 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. 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).
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.
Jackson, Elizabeth W; Zacks, Steven; Zinn, Sandra; Ryan, John; Johnson, Mark W; Gerber, David A; Andreoni, Kenneth; Fair, Jeffrey H; Shrestha, Roshan; Fried, Michael W
Although several studies have identified posttransplant neurologic sequelae in patients with acute liver failure (ALF), the effects of these sequelae on neuropsychologic functioning after transplant is unknown. This study compared neuropsychologic functioning of ALF patients with chronic liver disease patients after liver transplantation. After liver transplantation, seven ALF patients were compared with a matched control group of patients who had been transplanted for chronic liver disease. The patients were matched by gender, age (within 5 years), and time since transplantation (within 2 years). Patients completed a 2-hour battery of tests, which included measures of attention, memory, motor performance, abstract conceptualization, and visuospatial perception. There were no significant differences between the groups on measures of socioeconomic status or education. Significant differences were found on three separate tests: WAIS-III Vocabulary, WAIS-III Similarities, and WMS-III Paired Associate Learning II. Although these tests measure distinct functions (vocabulary knowledge, abstract conceptualization, and delayed verbal recall), they may be influenced by broader verbal functions, such as verbal fluency, conceptualization, and the ability to articulate ideas. When patients were asked what functions had noticeably deteriorated since transplantation, nearly all complained of memory difficulties, and there was no difference between groups. However, more ALF than chronic liver disease (CLD) patients complained of concentration difficulties. The results of this study suggest that ALF patients may experience more neuropsychologic dysfunction after transplant. Further studies are required to expand on these initial observations with the potential to improve patient care and referral to appropriate rehabilitative services.
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.
Wettstein, M; Häussinger, D
Taurine, betaine, and inositol were recently identified as osmolytes in liver cells interfering with cell volume regulation and cell function. In this study, the effect of osmolytes on cold ischemia-reoxygenation injury was investigated in rat liver. Isolated rat livers were flushed for 15 min with Krebs-Henseleit buffer (KHB), then stored for 16 hr in KHB at 4 degrees C, and thereafter reperfused with oxygenated KHB for 180 min. When taurine, betaine, and inositol (2 mmol/L, each) were added to the preperfusion and storage buffer, lactate dehydrogenase, aspartate amino transferase, and glutathione S-transferase leakage into the effluent perfusate during the reoxygenation period were less than half compared to controls without osmolytes and bile flow was higher. The effect of taurine (2 mmol/L) was similar to a mixture of all three osmolytes, indicating that taurine is the most important constituent. When livers were stored for 24 hr in University of Wisconsin solution, osmolyte addition to the storage solution also decreased lactate dehydrogenase and aspartate aminotransferase leakage during reoxygenation. Increasing liver taurine content by a 7-day taurine supplementation of drinking water attenuated reoxygenation injury in cold and warm ischemia in rat livers, whereas taurine depletion by beta-alanine feeding had the opposite effect. The data show that taurine protects livers from ischemia-reoxygenation. Taurine addition to perfusion and storage solutions in low millimolar concentrations or taurine supplementation of the donor may be useful to protect transplanted organs.
Kawano, Y; Mizuta, K; Sanada, Y; Urahashi, T; Ihara, Y; Okada, N; Yamada, N; Sasanuma, H; Sakuma, Y; Taniai, N; Yoshida, H; Kawarasaki, H; Yasuda, Y; Uchida, E
Cytomegalovirus (CMV) infection is known to be the most frequently viral infection among patients after liver transplantation. This is especially true in pediatric living-donor liver transplantation because the recipients have often not been infected with CMV and postoperative primary infection with CMV frequently occurs. Of 93 patients who underwent pediatric liver transplantation at our department, 33 patients (36.3%) were diagnosed with CMV infection using the antigenemia method (C7-HRP). Retrospective review and statistical analysis were conducted to confirm risk factors of post-transplantation CMV infection. Positive lymphocytes were diagnosed between postoperative days 8 and 111 after transplantation. Ganciclovir or foscavir were administrated to 21 patients. The other 10 patients who had one positive lymphocyte were observed and the cell disappeared on follow-up examination. We did not observe any cases of positive lymphocytes with C7-HRP in patients who received a graft from a CMV antibody-negative donor. Independent predictors associated with CMV infection in the multivariable analysis were administration of OKT3 and grafts from CMV antibody-positive donors. In CMV infection after pediatric liver transplantation, cases with CMV antibody-positive donors and with OKT3 administration for acute rejection are considered high risk, and cases with CMV antibody-negative donors are considered low risk. Copyright © 2014 Elsevier Inc. All rights reserved.
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
Schrem, Harald; Volz, Sophia; Koch, Hans-Friedrich; Gwiasda, Jill; Kürsch, Priscila; Goldis, Alon; Pöhnert, Daniel; Winny, Markus; Klempnauer, Jürgen; Kaltenborn, Alexander
This study investigated the utility of retrospective two one-sided cumulative sum (CUSUM) charts combined with multivariable regression analysis in liver transplantation for transplant center benchmarking. One thousand seven hundred and forty-nine consecutive adult primary liver transplants (January 1, 1983 to December 31, 2012) were analyzed retrospectively with two one-sided CUSUM chart analysis of 90-day mortality. Three eras and two subseries in latest era 3 were identified due to graphically delineated relevant shifts in mean 90-day mortality. Delineation of eras 1, 2, and 3 coincided with relevant changes in allocation policies. CUSUM analysis detected a resurgence of higher mean 90-day mortality in era 3 after results had improved continuously over 25 years. In era 3, two subseries were identified with improving mean 90-day mortality rates from 15.4% in subseries 1 to 8.9% in the following subseries 2. The quantitative influence of independent risk factors on 90-day mortality differed markedly between all identified eras and subseries as assessed with multivariable regression analysis deployed on era-specific subcohorts. The assessed methodology is able to identify meaningful center-specific eras and subseries of liver transplantation with striking alterations of the significance and weight of outcome drivers for post-transplant 90-day mortality over time. This warrants the introduction of prospective risk-adjusted two one-sided CUSUM chart analysis into quality management in liver transplantation in Germany with the goal to obtain alarm signals as early as possible.
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
Bruminhent, Jackrapong; Razonable, Raymund R
Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression
Modi, Rohan M; Patel, Nishi; Metwally, Sherif N; Mumtaz, Khalid
Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m2 may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community. PMID:27648152
Lau, Lawrence; Kankanige, Yamuna; Rubinstein, Benjamin; Jones, Robert; Christophi, Christopher; Muralidharan, Vijayaragavan; Bailey, James
The ability to predict graft failure or primary nonfunction at liver transplant decision time assists utilization of scarce resource of donor livers, while ensuring that patients who are urgently requiring a liver transplant are prioritized. An index that is derived to predict graft failure using donor and recipient factors, based on local data sets, will be more beneficial in the Australian context. Liver transplant data from the Austin Hospital, Melbourne, Australia, from 2010 to 2013 has been included in the study. The top 15 donor, recipient, and transplant factors influencing the outcome of graft failure within 30 days were selected using a machine learning methodology. An algorithm predicting the outcome of interest was developed using those factors. Donor Risk Index predicts the outcome with an area under the receiver operating characteristic curve (AUC-ROC) value of 0.680 (95% confidence interval [CI], 0.669-0.690). The combination of the factors used in Donor Risk Index with the model for end-stage liver disease score yields an AUC-ROC of 0.764 (95% CI, 0.756-0.771), whereas survival outcomes after liver transplantation score obtains an AUC-ROC of 0.638 (95% CI, 0.632-0.645). The top 15 donor and recipient characteristics within random forests results in an AUC-ROC of 0.818 (95% CI, 0.812-0.824). Using donor, transplant, and recipient characteristics known at the decision time of a transplant, high accuracy in matching donors and recipients can be achieved, potentially providing assistance with clinical decision making.
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
Sugawara, Yasuhiko; Tamura, Sumihito; Kokudo, Norihiro
A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary. PMID:21151523
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
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
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 imm