Adult living donor liver transplantation: Who is the ideal donor and recipient?
2005; Elsevier BV; Volume: 43; Issue: 1 Linguagem: Inglês
10.1016/j.jhep.2005.05.002
ISSN1600-0641
AutoresHenkie P. Tan, Kusum Patel-Tom, Amadeo Marcos,
Tópico(s)Organ Donation and Transplantation
ResumoEfforts to increase the number of deceased donors (DD) for liver transplantation have been unsuccessful to meet the demands for end stage liver disease (ESLD). Living donors represent a large pool of organs and seem to be the only immediately available alternative. However, there is a significant cost to drawing from this pool, and it is not measured monetarily but rather in lives and morbidities. Living donor surgery is the only major surgery performed on an individual for whom it is not medically indicated. The risk for the donor is balanced by the great benefit to the recipient, as well as the donor's psychological benefit. However, every effort must be taken to minimize morbidities, making this procedure the most challenging in the field of surgery. Selection of the ideal donor for adult living donor liver transplantation (LDLT) is guided by two key principals: (1) donor safety with unavoidable minimal but never acceptable morbidity and no mortality, and (2) identifying the optimal partial liver allograft with resultant graft and recipient survival at least equivalent to that of DD liver transplantation. Because of these reasons, frequently not more than one-third of potential donors are accepted as candidates for this procedure [1Trotter J.F. Wachs M. Everson G.T. Kam I. Adult-to-adult transplantation of the right hepatic lobe from a living donor.N Engl J Med. 2002; 346: 1074-1082Crossref PubMed Scopus (414) Google Scholar, 2Valentin-Gamazo C. Malago M. Karliova M. Lutz J.T. Frilling A. Nadalin S. et al.Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center.Liver Transpl. 2004; 10: 1087-1096Crossref PubMed Scopus (147) Google Scholar]. The evaluation of a potential donor is a complex and expensive process costing about $5500/donor [[2]Valentin-Gamazo C. Malago M. Karliova M. Lutz J.T. Frilling A. Nadalin S. et al.Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center.Liver Transpl. 2004; 10: 1087-1096Crossref PubMed Scopus (147) Google Scholar]. The costs of evaluation of potential donors who are rejected during the selection process are not covered by the donors' or recipients' insurance. Several guidelines for donor selection and evaluation have been published: (1) authors for the live organ donor consensus group have published practice guidelines about the well-being of the live organ donor [[3]Authors for the live organ donor consensus group Consensus statement on the live organ donor.J Am Med Assoc. 2000; 284: 2919-2926Crossref Scopus (416) Google Scholar], (2) the American Society of Transplant Surgeons (ASTS) has published a position paper on LDLT [[4]American society of transplant surgeons: ethics committee American society of transplant surgeons' position paper on adult-to-adult living donor liver transplantation.Liver Transpl. 2000; 6: 815-817Crossref PubMed Scopus (49) Google Scholar], and (3) a summary of the conference at the National Institute of Health on LDLT is available [[5]Shiffman M.L. Brown R.S. Olthoff K.M. Everson G. Miller C. Siegler M. et al.Living donor liver transplantation: summary of a conference at the National Institute of Health.Liver Transpl. 2002; 8: 174-188Crossref PubMed Scopus (133) Google Scholar]. The published donor evaluation protocols are all very similar. The protocol performed at the University of Pittsburgh Medical Center Thomas E. Starzl Transplantation Institute (UPMC STI) is listed in Table 1 (modification of [[6]Marcos A. Right lobe living donor liver transplantation: a review.Liver Transpl. 2000; 6: 3-20PubMed Google Scholar]). In brief, most potential donors are excluded based on the initial studies to rule out underlying conditions that represent increased surgical risk, such as diabetes, severe or uncontrolled hypertension, and hepatic, cardiac, pulmonary, renal, and occult infectious disease. Immediate exclusion criteria include donors who are currently pregnant, less than 18-year-old or older than 55-years old with co-morbidities. Selection criteria are rigid to ensure donor safety with no exception to accommodate the needs of the recipients.Table 1Evaluation protocol for potential adult living liver donors (UPMC STI)Step 1Clinical evaluation: history and physical. First informed consentLaboratory: ABO, hematology, chemistry (including liver function tests) and coagulation profiles, drug screen, hypercoagulable workup (Factor V Leiden, prothrombin mutation G20210A, antithrombin III and protein C&S deficiencies), factors V, VII, VIII, antiphospholipid or cardiolipin antibodies, ceruloplasmin, α-1-antitrypsinSerology: hepatitis A, B, and C; HIV PCRImaging studies: chest X-ray, EKGStep 2Multidisciplinary team clinical evaluation: hepatology, psychology, etc, consultsLaboratory: HLA, cross-match, tumor markers (AFP, CEA), UA C&S, pregnancy test (female)Serology: CMV, HSV, EBV, RPRImaging studies: helical CT-angiogram with portal phase and 3D reconstruction with liver volumetricSpecial studies when indicated: echocardiogram, cardiac stress test, pulmonary function test, glucose tolerance test, colonoscopy, mammographyHistology: liver biopsyStep 3Clinical evaluations: update history and physical. Second informed consentAnesthesiology consultsLaboratory: cross-match, and blood consentFinal approval at the multidisciplinary transplantation conference prior to surgery Open table in a new tab Donors with positive hepatitis B and C, and human immunodeficiency virus (HIV) serologies are absolute contraindications for living donations even to positive hepatitis and HIV recipients, with the exception of donor positive hepatitis B core antibody in the presence of a negative hepatitis B surface antigen for hepatitis B positive recipients. These donors, in addition, should have a non-detectable hepatitis B quantitative polymerase chain reaction, have normal liver enzymes and histology. Hypercoagulable states (Factor V Leiden [[7]Tan H.P. Markowitz J.S. Maley W.R. Merritt W.T. Klein A.S. Successful liver transplantation in a patient with Budd–Chiari syndrome caused by homozygous factor V Leiden.Liver Transpl. 2000; 6: 654-656Crossref PubMed Scopus (20) Google Scholar], prothrombin mutation G20210A, antithrombin III and protein C&S deficiencies, Factor VIII elevation, antiphospholipid or cardiolipin antibodies) are relative contraindications for donation for fear of increase donor mortality from pulmonary emboli. Smokers are strongly encouraged to quit and oral contraceptive cessation is encouraged 4 weeks prior to surgery. Donors should never be compelled to donate. The psychological or psychiatric evaluation focuses on the emotional stability of the potential donor and is used to verify and reaffirm the informed consent. Donors should be permitted to change their mind up until the induction of general anesthesia, and they should be given every opportunity to withdraw at any time if they have any reservations. Psychological counseling can be very helpful, and multiple consents encourage donors to reconsider their decision [[8]Marcos A. Fisher R. Ham J. Olzinski A. Shiffman M. Sanyal A. et al.Selection and outcome of living donors for right lobe liver transplantation.Transplantation. 2000; 69: 2410-2415Crossref PubMed Scopus (266) Google Scholar]. A spiral or helical CT-angiogram with portal phase and 3D reconstruction liver volumetric is used in our center to determine the donor's vascular anatomy and accurate measurement of the graft and liver volume. An ideal graft to recipient body weight ratio (GRBW) of 0.8 corrected for the degree of steatosis is a safe lower limit for adult recipients [[9]Marcos A. Fisher R. Ham J. Shiffman M. Sanyal A. Luketic V. et al.Liver regeneration and function in donors and recipients after right lobe adult-to-adult living donor liver transplantation.Transplantation. 2000; 69: 1375-1379Crossref PubMed Scopus (293) Google Scholar] with a maximal 60% resection of the donor liver volume to ensure consistent donor safety. The left hemiliver will almost always be adequate for the donor if the plane of transaction is to the right of the midhepatic vein, with the segments IV representing approximately 40% of graft mass [9Marcos A. Fisher R. Ham J. Shiffman M. Sanyal A. Luketic V. et al.Liver regeneration and function in donors and recipients after right lobe adult-to-adult living donor liver transplantation.Transplantation. 2000; 69: 1375-1379Crossref PubMed Scopus (293) Google Scholar, 10Marcos A. Fisher R. Ham J. Shiffman M. Sanyal A. Luketic V. et al.Right lobe living donor liver transplantation.Transplantation. 1999; 68: 798-803Crossref PubMed Scopus (360) Google Scholar]. Its devascularization could be catastrophic, and protection of significant portal and arterial tributaries is essential. For this reason the right hemiliver (segments V–VIII) is preferred. We do not routinely perform a magnetic resonance cholangiopancreatography to evaluate the biliary ducts pre-operatively but an intra-operative cholangiogram is performed routinely. Biliary complications in both donors and recipients are potentially highly morbid, and their prevention is a priority (see article by S Todo, H Furukawa and T Kaminiyama in this Forum). Optimal management requires knowledge of both primary and secondary biliary drainage. Recently, Schroeder et al. [[11]Schroeder T. Nadalin S. Stattaus J. Debatin J.F. Malago M. Ruehm S.G. Potential living liver donors: evaluation with an all-in-one protocol with multi-detector row CT.Radiology. 2002; 224: 586-591Crossref PubMed Scopus (84) Google Scholar] have concluded in a preliminary study that the three-phase dual-enhancement multi-detector row CT, which includes CT cholangiography and CT angiography, has the potential to replace the combinations of various partially invasive diagnostic procedures. We have always made mandatory the performance of a liver biopsy pre-operatively. We previously demonstrated in 100 consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation, body mass index (BMI) correlated only weakly with biopsy, with 73% of overweight (BMI>25) donors having little or no hepatic fat [[12]Ryan K.R. Johnson L.A. Germin B.I. Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation.Liver Transpl. 2002; 8: 1114-1122Crossref PubMed Scopus (269) Google Scholar]. Imaging was only 12% sensitive to small amounts (5–10%) of fat. Moreover, three candidates were denied surgery because biopsy detected an occult liver disease. Screening liver biopsy has a low complication rate and may actually serve to increase donor safety. This issue is exemplified in the recent first living-related liver donor death in Japan [[13]Akabayashi A. Slingsby B.T. Fujita M. The first donor death after living-related liver transplantation in Japan.Transplantation. 2004; 77 (letter): 634Crossref PubMed Scopus (126) Google Scholar]. The healthy donor had undiagnosed nonalcoholic steatohepatitis. A liver biopsy is also mandatory in the Essen group after the loss of a donor due to congenital lipodystrophy [[2]Valentin-Gamazo C. Malago M. Karliova M. Lutz J.T. Frilling A. Nadalin S. et al.Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center.Liver Transpl. 2004; 10: 1087-1096Crossref PubMed Scopus (147) Google Scholar]. Eight to 22% of potential donors evaluated were rejected because of abnormal liver biopsy [2Valentin-Gamazo C. Malago M. Karliova M. Lutz J.T. Frilling A. Nadalin S. et al.Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center.Liver Transpl. 2004; 10: 1087-1096Crossref PubMed Scopus (147) Google Scholar, 14Marcos A. Ham J. Fisher R. Olzinski A. Posner M. Single-center analysis of the first forty living donor transplants using the right lobe.Liver Transpl. 2000; 6: 296-301Crossref PubMed Scopus (264) Google Scholar, 15Pomfret E.A. Pomposelli J.J. Gordon F.D. Erbay N. Lyn Price L. Lewis W.D. et al.Liver regeneration and surgical outcome in donors of right-lobe liver grafts.Transplantation. 2003; 76: 5-10Crossref PubMed Scopus (147) Google Scholar]. We consider >20% steatosis a relative contraindication for donation and highly recommend a diet to decrease this, and we proceed with repeat liver biopsy to confirm decrease steatosis. Emergency LDLT for fulminant hepatic failure should be perform only on a case by case basis as the donor is placed in a very compromised medical and emotional/psychological position with ethical, medical, logistic and economic concerns [[16]Marcos A. Ham J.M. Fisher R.A. Olzinski A.T. Shiffman M.L. Sanyal A.J. et al.Emergency adult-to-adult living donor liver transplantation for fulminant hepatic failure.Transplantation. 2000; 69: 2202-2205Crossref PubMed Scopus (54) Google Scholar]. Poor outcomes that cannot be blamed on underlying medical conditions can often be traced to intra-operative events, suggesting that most of the risk to healthy donors can be controlled and minimized. Even with refinement of surgical technique, risk will never be eliminated completely and an ethical dilemma will, therefore, always remain. This risk must be offset by beneficence to the recipient, and the continued use of these organs can only be justified if the outcome is consistently good for both the healthy donor and sick recipient. Using continuous intra-operative cell-saver, maintenance of low central venous pressure, and meticulous parenchymal transaction using a combination technique including Tissue Link, helix hydro-jet, cavitron ultrasonic dissector, and selective use of the endovascular GIA stapler, in 155 consecutive right lobe living donor hepatectomies at the University of Rochester and UPMC STI, we have minimized blood loss from 554+395 mL to about 250 mL. Operative time for liver parenchymal dissection has also dropped from about 200 min to about 90 min. Donor morbidities were less than 10%, with bile leak from cut liver edges less than 5% (all managed conservatively). There were no re-exploration or take back to the operating room. Table 2 summarizes the ideal LDLT donor profile. It is important that the ideal donors have the ability and willingness to comply with long-term follow-up. Furthermore, informed consent should include the risk for death, liver failure, infection, need for blood transfusion, disability, and the ability to withdraw anytime prior to surgery.Table 2The ideal LDLT donor profileParametersIdeal criteriaGenderNo difference PregnancyNot pregnantAge21–55 years oldBMI 40%GRBW>0.8Health statusNo significant cardiac, pulmonary, renal or metabolic (e.g. HTN, IDDM) diseasePrevious infectionsNo HIV +, active hepatitis, viral infections, (positive EBV and CMV Abs Ok)Hypercoagulable stateRelative to absolute contraindicationsAttitudesNo coercion, emotionally stable SmokingRecommend cessation, not mandatory AlcoholAt most social drinker Oral contraceptivesRecommend cessation 4 weeks priorHistology Steatosis 25 [[20]New York State Health Department. New York State Committee on quality improvement in living liver donation 2002.Google Scholar]. It is thought that smaller grafts are unable to meet the needs of patients experiencing severe and prolonged illness. It is important that the recipients understand and accept that the donation will put the donor at significant risk. One-year graft and recipient survival after LDLT has improved to at least 80 and 86%, respectively [21Marcos A. Ham J.M. Fisher R.A. Olzinski A.T. Posner M.P. Surgical management of anatomical variations of the right lobe in living donor liver transplantation.Ann Surg. 2000; 231: 824-831Crossref PubMed Scopus (185) Google Scholar, 22Gondolesi G.E. Varotti G. Florman S. Munoz L. Fishbein T.M. Emre S.H. et al.Biliary complications in 96 consecutive right lobe living donor transplant recipients.Transplantation. 2004; 77: 1842-1848Crossref PubMed Scopus (209) Google Scholar, 23Lo C.M. Fan S.T. Liu C.L. Yong B.H. Wong Y. Lau G.K. et al.Lessons learned from one hundred right lobe living donor liver transplants.Ann Surg. 2004; 240: 151-158Crossref PubMed Scopus (125) Google Scholar]. Hepatic artery thrombosis occurs in about 5% [[17]Marcos A. Killackey M. Orloff M.S. Mieles L. Bozorgzadeh A. Tan H.P. Hepatic arterial reconstruction in 95 adult right lobe living donor liver transplants: evolution of anastomotic technique.Liver Transpl. 2003; 9: 570-574Crossref PubMed Scopus (55) Google Scholar] and biliary complications has improved to less than 20% [21Marcos A. Ham J.M. Fisher R.A. Olzinski A.T. Posner M.P. Surgical management of anatomical variations of the right lobe in living donor liver transplantation.Ann Surg. 2000; 231: 824-831Crossref PubMed Scopus (185) Google Scholar, 23Lo C.M. Fan S.T. Liu C.L. Yong B.H. Wong Y. Lau G.K. et al.Lessons learned from one hundred right lobe living donor liver transplants.Ann Surg. 2004; 240: 151-158Crossref PubMed Scopus (125) Google Scholar, 24Brown Jr, R.S. Russo M.W. Lai M. Shiffman M.L. Richardson M.C. Everhart J.E. et al.A survey of liver transplantation from living adult donors in the United States.N Engl J Med. 2003; 348: 818-825Crossref PubMed Scopus (456) Google Scholar], but can be as high as 40% [[22]Gondolesi G.E. Varotti G. Florman S. Munoz L. Fishbein T.M. Emre S.H. et al.Biliary complications in 96 consecutive right lobe living donor transplant recipients.Transplantation. 2004; 77: 1842-1848Crossref PubMed Scopus (209) Google Scholar]. There are two specific groups of patients who are ideally suited for LDLT. The first group of patients with hepatocellular carcinoma (HCC) could benefit substantially from rapid (fast track) LDLT transplantation prior to metastases, even with increased UNOS priority. Data from Japan demonstrates that LDLT for HCC is feasible with satisfactory results, even when liver function is markedly impaired, or HCC is uncontrolled by conventional anti-tumor treatments [[25]Todo S. Furukawa H. Japanese study group on organ transplantation. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan.Ann Surg. 2004; 240: 451-459Crossref PubMed Scopus (356) Google Scholar]. With 316 LDLT recipients, 1- and 3-year patient survivals were 78 and 69%, respectively. One- and three-year recurrence-free survivals were 73 and 65%, respectively. Another group of potential recipients are patients whose severity of illness that is not accurately reflected by their MELD score [[26]Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar]. These include patients with complicated cholestatic liver disease or patients with ascites, uncontrolled encephalopathy and/or severe cachexia. Since hepatitis C viral infection (HCV) is the most common indication for liver transplantation in the United States, the issue of recurrent HCV in LDLT is of paramount importance [[27]Garcia-Retortillo M. Forns X. Llovet J.M. Navasa M. Feliu A. Massauer A. et al.Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation.Hepatology. 2004; 40: 699-707Crossref PubMed Scopus (168) Google Scholar]. Although some early reports have shown earlier and more severe recurrence of HCV following LDLT compared to DD recipients [[28]Sugawara Y, Makuuchi M. Should living donor liver transplantation be offered to patients with hepatitis C virus cirrhosis? J Hepatol 2005; in press.Google Scholar], this issue is still highly controversial [27Garcia-Retortillo M. Forns X. Llovet J.M. Navasa M. Feliu A. Massauer A. et al.Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation.Hepatology. 2004; 40: 699-707Crossref PubMed Scopus (168) Google Scholar, 29Shiffman M.L. Stravitz R.T. Cantos M.J. Mills A.S. Sterling R.K. Luketic V.A. et al.Histologic recurrence of chronic hepatitis C virus in patients after living donor and deceased donor liver transplantation.Liver Transpl. 2004; 10: 1248-1255Crossref PubMed Scopus (124) Google Scholar]. Recent data [27Garcia-Retortillo M. Forns X. Llovet J.M. Navasa M. Feliu A. Massauer A. et al.Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation.Hepatology. 2004; 40: 699-707Crossref PubMed Scopus (168) Google Scholar, 30Russo M.W. Shrestha R. Is severe recurrent hepatitis C more common after living donor liver transplantation?.Hepatology. 2004; 40: 524-526Crossref PubMed Scopus (18) Google Scholar, 31Bozorgzadeh A. Jain A. Ryan C. Ornt D. Zand M. Mantry P. et al.Impact of hepatitis C viral infection in primary cadaveric liver allograft versus primary living-donor allograft in 100 consecutive liver transplant recipients receiving tacrolimus.Transplantation. 2004; 77: 1066-1070Crossref PubMed Scopus (55) Google Scholar], including data from our patients [[32]Tan HP, Madeb R, Kovach SJ, Orloff M, Mieles L, Johnson LA, et al. Hypophosphatemia after 95 right-lobe living donor hepatectomies for liver trasplantation is not a significant source of morbidity. Trasplantation 2003;76:1085–1088.Google Scholar], have shown that this may not be true. Given the current decrease in waiting list mortality with LDLT, we strongly feel that HCV cirrhosis potential recipients should be treated like any other potential recipients on the waiting list for LDLT. The ideal LDLT recipient profile is listed in Table 3.Table 3The ideal LDLT recipient profileParametersIdeal criteriaListingMust first be listed on the standard DD waiting listMELD score<25 [20]New York State Health Department. New York State Committee on quality improvement in living liver donation 2002.Google ScholarRecipient risk factorsNo thrombosis of multiple visceral veins, multiple medical problems, multiple significant abdominal surgeries; advanced age [26]Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google ScholarSpecific recipient subgroups HCCBenefit substantially from rapid live donor transplantation as DD transplantation may allow for metastasis [25]Todo S. Furukawa H. Japanese study group on organ transplantation. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan.Ann Surg. 2004; 240: 451-459Crossref PubMed Scopus (356) Google Scholar Severity of illness not accurately reflected by MELD scoreComplicated cholestatic liver disease, patients with ascites, uncontrolled encephalopathy and/or severe cachexia [26]Trotter J.F. Living donor liver transplantation: is the hype over?.J Hepatol. 2005; 42: 20-25Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Open table in a new tab In conclusion, the main objectives of the donor evaluation process is to assure the safety of the donor with the least morbidity and no mortality but yet identifying the optimal donor allograft for the recipient. This is achieved through a thorough medical and psychological evaluation. The precise size, vascular and biliary anatomy and quality of the liver allograft is determined by the mandatory pre-operative liver biopsy and helical CT-angiogram with portal phase and 3D reconstruction with liver volumetric, and intra-operative vascular ultrasound and cholangiogram. An ideal GRBW of 0.8 corrected for the degree of steatosis is a safe lower limit for adult recipients with a maximal 60% resection of the donor liver volume to ensure consistent donor safety. A ratio of 1% is probably safer if uncorrected. With improvement of surgical techniques, organs from living donors might give superior results with decreased vascular and biliary complications, and improved graft and recipient survival [[23]Lo C.M. Fan S.T. Liu C.L. Yong B.H. Wong Y. Lau G.K. et al.Lessons learned from one hundred right lobe living donor liver transplants.Ann Surg. 2004; 240: 151-158Crossref PubMed Scopus (125) Google Scholar]. Table 4 list the key points in LDLT. We implore the ASTS to continue to take the leadership and initiative in the USA in establishing an immediate long-term national registry to track the outcome of all living donors and recipientsFig. 1.Table 4Key points in LDLT1. More than 1605 (see Fig. 1) LDLT (http://www.optn.org, accessed Nov 29, 2004) were performed in at least 42 centers (Brown et al., 2003) in the United States. Fourteen centers had performed more than 10 such transplantations each and together accounted for 80% of such transplantations2. Selection of the ideal donor for LDLT is guided by 2 key principals: (1) donor safety with minimal acceptable morbidity and no mortality, and (2) identifying optimal donor partial hepatic allograft with resultant graft and recipient survival at least equivalent to that of DD liver allograft3. We prefer right lobe over left lobe donation in LDLT4. An ideal GRBW of 0.8, corrected for degree of steatosis, is a safe lower limit with maximal 60% resection of the donor liver volume. Otherwise, a ratio of 1% is probably safer if uncorrected5. The mortality rate is about 0.2%. Total major and minor donor morbidities are currently reduced to less than 10–15%. Donor biliary complications are less than 5% in our experiences and others. Majority were managed nonoperatively and resolved spontaneously6. One-year graft and recipient survival after LDLT has improved to at least 80 and 86%, respectively. Hepatic artery thrombosis occurs in about 5% and biliary complications have improved to less than 20%7. HCV recurrence post LDLT is still highly controversialWith improvement of surgical techniques, organs from living donors might give superior results with decrease vascular and biliary complications, and improved graft and recipient survival Open table in a new tab
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