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Dulcetta L, Marra P, Carbone FS, Bonaffini PA, Sallemi C, Sansotta N, Colledan M, D'Antiga L, Sironi S. Biliary complications in pediatric liver transplantation: findings of percutaneous transhepatic cholangiography in a large single-center cohort. Pediatr Radiol 2022; 52:1061-1074. [PMID: 35107594 DOI: 10.1007/s00247-021-05278-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 12/09/2021] [Accepted: 12/27/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Although biliary complications after orthotopic liver transplantation represent a common source of morbidity and mortality, decreasing graft survival, consensus is lacking on their management in the pediatric population. OBJECTIVE The aim of this study was to present the prevalence of such biliary complications and their interventional radiologic management with representative images. MATERIALS AND METHODS This retrospective study reports our experience with percutaneous transhepatic cholangiography in the management of biliary complications after orthotopic liver transplantation in pediatric patients. This study enrolled all pediatric patients (<18 years old) who underwent percutaneous transhepatic cholangiography for the management of biliary complications after orthotopic liver transplantation at a tertiary care center between January 2010 and December 2020. Diagnosis of biliary complications and indication to perform percutaneous transhepatic cholangiography were based on clinical, laboratory or radiologic data. RESULTS Among the 301 orthotopic liver transplantations, 78 (26%) developed biliary complications that were managed by interventional radiology: these included 52 (17.3%) biliary strictures, 19 (6.3%) bile leaks, 5 (1.7%) biliary stones, 1 (0.3%) iatrogenic biliary obstruction and 1 (0.3%) vanishing syndrome. The median time interval between orthotopic liver transplantation and the diagnosis of biliary complications was 6.0 years (interquartile range [IQR] 8.2 years). Percutaneous transhepatic cholangiography and biliary duct catheterization were successful in all cases, with low rates of complications that were variable among subgroups. CONCLUSION A wide spectrum of biliary complications can occur after pediatric orthotopic liver transplantation. In this large single-center experience, we highlight the value of percutaneous transhepatic cholangiography in their diagnosis and management. Percutaneous treatments in pediatric patients are safe and effective, providing resolution or serving as a bridge to surgery, including re-transplantation.
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Affiliation(s)
- Ludovico Dulcetta
- Department of Radiology, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Paolo Marra
- Department of Radiology, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy. .,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
| | - Francesco Saverio Carbone
- Department of Radiology, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Pietro Andrea Bonaffini
- Department of Radiology, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Claudio Sallemi
- Department of Radiology, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy
| | - Naire Sansotta
- Department of Paediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Michele Colledan
- School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.,Department of Organ Failure and Transplantation, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Lorenzo D'Antiga
- Department of Paediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Sandro Sironi
- Department of Radiology, ASST Papa Giovanni XXIII Hospital, 24127, Bergamo, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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Alnagar A, Daradka K, Kyrana E, Mtegha M, Palaniswamy K, Rajwal S, Mulla J, O'meara M, Karam M, Shawky A, Hakeem AR, Upasani V, Dhakshinamoorthy V, Prasad R, Attia M. Predictors of patient and graft survival following pediatric liver transplantation: Long-term analysis of more than 300 cases from single centre. Pediatr Transplant 2022; 26:e14139. [PMID: 34545678 DOI: 10.1111/petr.14139] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 08/04/2021] [Accepted: 08/28/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Pediatric liver transplant (PLT) activity has flourished over time although with limited expansion in the graft pool. The study aims to identify pre-transplant factors that predict post-transplant patient and graft survival in the PLT population. METHODS Retrospective review of PLTs at a single tertiary transplant unit from 2000 to 2019. Univariate and multivariate analyses of pre-transplant factors were performed to identify predictors of patient and graft survival. RESULTS Two hundred and seventy-six patients received 320 PLTs. The most common cause of graft loss was hepatic artery thrombosis (n = 13, 29.6%). The most common cause of mortality was sepsis (n = 11, 29.7%). Univariate analysis showed that the following variables had a significant (p < .05) impact on patient survival: recipient age, weight, height, graft type (technical variant graft), transplant category (acute liver failure), the era of transplant, and invasive ventilation. The following variables had a significant (p < .05) impact on graft survival: recipient age, weight, height, transplant category (acute liver failure), and the era of transplant. Multivariate analysis precluded the era of transplant as the only significant factor for patient survival; patients transplanted after 2005 had significantly higher patient survival. No independent factor predicting graft survival was identified. For children transplanted after 2005, the only factor that predicted patient survival was pre-transplant invasive ventilation. CONCLUSIONS Our study suggests that the learning curve and pre-transplant invasive ventilation in the recipient have a significant impact on patient survival. The traditional view of worse outcomes of smaller PLT candidates should be changed.
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Affiliation(s)
- Amr Alnagar
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK.,General Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Khaled Daradka
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK.,Department of General Surgery, Jordan University Hospital, The University of Jordan- Queen Rania Street, Amman, Jordan
| | - Eirini Kyrana
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | - Marumbo Mtegha
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | | | - Sanjay Rajwal
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | - Jamila Mulla
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | - Moira O'meara
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | - Mohamed Karam
- General Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed Shawky
- General Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | | | - Vivek Upasani
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | | | - Raj Prasad
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
| | - Magdy Attia
- The Leeds Teaching Hospitals, NHS Foundation Trust, Leeds, UK
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3
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Bersani I, Auriti C, Piersigilli F, Dotta A, Diomedi-Camassei F, Di Pede A, Buttinelli G, Danhaive O. Neonatal acute liver failure due to enteroviruses: a 14 years single NICU experience. J Matern Fetal Neonatal Med 2019; 33:2576-2580. [PMID: 30513031 DOI: 10.1080/14767058.2018.1555806] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Background: Neonatal acute liver failure (ALF) is a severe condition with a mortality rate up to 70%. Human enterovirus (HEV) infections are associated with serious diseases in newborns, including myocarditis, meningoencephalitis and, more rarely, ALF with a fulminant course.Methods: Cases of neonatal-onset ALF were identified using the institutional clinical database. The history and clinical data of infants with HEV infection were collected by medical record revision. Viral testing by nested real- time PCR (nRT-PCR) was performed by the Bambino Gesù Children's Hospital Clinical Laboratory and by National Institute of Public Health in Rome.Results: Among ten infants referred to our Institution with neonatal-onset ALF in the 2004-2018 period, we identified five cases due to HEV. In three of these, the mother reported an episode of mild fever and diarrhea during the last trimester of gestation, suggesting fetal-maternal transmission. All were late preterm infants (32-36 weeks). Two infants died as a result of ALF; the other three survived with full normalization of liver function. In four, the causing agents were coxsackie B serotypes 3 (n = 1), 4 (n = 1) and 5 (n = 2), in the fifth case we identified echovirus serotype 11.Conclusions: Human enterovirus (HEV) are a rare but relevant cause of ALF in neonates. HEV testing should be systematically performed in cases of neonatal ALF for diagnostic and management purposes.
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Affiliation(s)
- Iliana Bersani
- Department of Neonatology, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
| | - Cinzia Auriti
- Department of Neonatology, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
| | | | - Andrea Dotta
- Department of Neonatology, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
| | | | - Alessandra Di Pede
- Department of Neonatology, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
| | | | - Olivier Danhaive
- Department of Neonatology, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy.,Division of Neonatology, St-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium
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Lanjuan L, Qian Y, Jianrong H, Xiaowei X, Yuemei C, Yagang C, Weihang M, Zhi C, Suzhen F. Severe hepatitis treated with an artificial liver support system. Int J Artif Organs 2018. [DOI: 10.1177/039139880102400508] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We designed an artificial liver support system (ALSS) including plasma exchange, charcoal hemoperfusion, plasma bilirubin absorption, charcoal plasma perfusion, hemofiltration and hemodialysis. We chose different methods or their combinations according to the patients’ conditions. We investigated the effect of ALSS in 154 patients with severe hepatitis, 72 of whom survived. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared at different stages (i.e. early, middle and end stages). After each ALSS treatment, the liver function of these patients greatly improved, serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while BCAA/AAA ratio increased. Patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. Thus, we concluded that ALSS is a reliable therapy for advanced liver diseases and treatment in early or middle stages is appropriate.
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Affiliation(s)
- L. Lanjuan
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - Y. Qian
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - H. Jianrong
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - X. Xiaowei
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - C. Yuemei
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - C. Yagang
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - M. Weihang
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - C. Zhi
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
| | - F. Suzhen
- Department of Infectious Disease, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang - China
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Hori T, Uemoto S, Walden LB, Chen F, Baine AMT, Hata T, Kogure T, Nguyen JH. Matrix metalloproteinase-9 as a therapeutic target for the progression of fulminant liver failure with hepatic encephalopathy: A pilot study in mice. Hepatol Res 2014; 44:651-662. [PMID: 23672352 DOI: 10.1111/hepr.12161] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Revised: 05/08/2013] [Accepted: 05/09/2013] [Indexed: 12/13/2022]
Abstract
AIM If progressive liver injury and subsequent hepatic encephalopathy can be prohibited in fulminant liver failure (FLF), it would be ideal for intensive care of FLF and provide an expanded opportunity for liver transplantation (LT). We hypothesized that matrix metalloproteinase (MMP)-9 plays an important role in FLF progression, and investigated MMP-9 behaviors in a murine FLF model, especially at the coma stage. METHODS The murine FLF model with azoxymethane recapitulates FLF in humans. The detailed coma status was evaluated, on the assumption that LT is indicated at early, but not late, stage 3. To investigate whether MMP-9 deletion or reduction has beneficial effects, an MMP-9 inhibitor (GM6001) and transfection of tissue inhibitor of metalloproteinases (TIMP)-1 cDNA were used. Mice were divided into five groups: control; FLF; FLF with GM6001 pretreatment; FLF with TIMP-1 plasmid transfection 24 h before disease onset; and FLF with TIMP-1 plasmid transfection 48 h before disease onset. Neurological findings, including survival, were followed. Samples were obtained at early and late stage 3. Biochemical examinations and histopathological assessments were performed. The expression and function of MMP-9 and TIMP-1 were evaluated by western blotting and zymography. A brain permeability study was also performed. RESULTS MMP-9 was strongly increased in FLF. The MMP-9 inhibitions worked well, and prolonged the survival, interval to stage 3 and duration of early stage 3. MMP-9 inhibition improved the liver and subsequent brain injuries at early stage 3, with no remarkable improvements at late stage 3. CONCLUSION MMP-9 has therapeutic potential for FLF progression.
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Affiliation(s)
- Tomohide Hori
- Department of Neuroscience, Mayo Clinic in Florida; Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto
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Vasanthan KS, Subramanian A, Krishnan UM, Sethuraman S. Role of biomaterials, therapeutic molecules and cells for hepatic tissue engineering. Biotechnol Adv 2012; 30:742-52. [PMID: 22265845 DOI: 10.1016/j.biotechadv.2012.01.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2011] [Revised: 12/28/2011] [Accepted: 01/05/2012] [Indexed: 12/18/2022]
Abstract
Current liver transplantation strategies face severe shortcomings owing to scarcity of donors, immunogenicity, prohibitive costs and poor survival rates. Due to the lengthy list of patients requiring transplant, high mortality rates are observed during the endless waiting period. Tissue engineering could be an alternative strategy to regenerate the damaged liver and improve the survival and quality of life of the patient. The development of an ideal scaffold for liver tissue engineering depends on the nature of the scaffold, its architecture and the presence of growth factors and recognition motifs. Biomimetic scaffolds can simulate the native extracellular matrix for the culture of hepatocytes to enable them to exhibit their functionality both in vitro and in vivo. This review highlights the physiology and pathophysiology of liver, the current treatment strategies, use of various scaffolds, incorporation of adhesion motifs, growth factors and stem cells that can stabilize and maintain hepatocyte cultures for a long period.
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7
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Margarit C, Asensio M, Dávila K, Ortega J, Iglesias J, Tormo R, Charco R. Analysis of risk factors following pediatric liver transplantation. Transpl Int 2011. [DOI: 10.1111/j.1432-2277.2000.tb02008.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Miloh T, Kerkar N, Parkar S, Emre S, Annunziato R, Mendez C, Arnon R, Suchy F, Rodriguez-Laiz G, Del Rio Martin J, Sturdevant M, Iyer K. Improved outcomes in pediatric liver transplantation for acute liver failure. Pediatr Transplant 2010; 14:863-9. [PMID: 20609170 DOI: 10.1111/j.1399-3046.2010.01356.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
UNLABELLED OLT is a life-saving option for ALF. AIM To evaluate our outcomes in pediatric OLT for ALF. METHODS Retrospective review of our data between 1992 and 2007. RESULTS Of 142 children with ALF, 126 were listed, of which 40 spontaneously improved, nine died, and 77 underwent OLT (median waiting time four days). Fifty-three children received deceased donor grafts (34 whole and 19 split grafts), and there were 24 living donor grafts. The one- and five-yr patient survival was 87% and 80%, and graft survival 83% and 79%, respectively. Thirteen patients died after OLT, and there were nine retransplants in seven patients. Patient weight, length of stay, creatinine, and infection were significantly associated with death; increased weight and black ethnicity were associated with graft loss on univariate analysis, but not on multivariate analysis. There were no significant differences in patient survival (one and five yr), graft loss, or other complications between the groups. CONCLUSION We report the largest single-center study of OLT in pediatric ALF, demonstrating no difference in outcomes between different graft types. Our liberal use of segmental grafts may allow earlier OLT in this high-risk cohort and contribute to our excellent outcomes.
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Affiliation(s)
- Tamir Miloh
- Department of Pediatrics and Recanati Miller Transplant Institute, Department of Surgery, Mount Sinai Hospital, New York, NY, USA.
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9
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Guo C, Zhang M. Successful Treatment of Biliary Atresia in Very Small Infants through Living Related Liver Transplantation. Case Rep Gastroenterol 2010; 4:158-167. [PMID: 20805938 PMCID: PMC2929409 DOI: 10.1159/000314195] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Improving outcomes in very small children is a major goal of pediatric liver transplantation. This report describes our experience of living related liver transplantation in an infant weighing 3.98 kg. The recipient, a 80-day-old male infant with congenital biliary atresia, was treated with living donor liver transplantation and then followed up for 6 months. The left lateral segment (segment II, III) with reduced size from the donor, his 26-year-old mother, was used as the graft. The graft weighed 200 g. The graft weight to recipient body weight ratio was 5.025%. The donor regained her liver function within 3 days and was discharged on day 8. The patient showed good results. Liver function returned to normal 9 days after the operation with bilirubin level almost decreased to normal. Cyclosporin, mycophenolate mofetil and prednisone were used for postoperative immunosuppression. No bleeding, thrombosis, infection or bile leakage occurred. The patient had slight fever because of a little collection in the abdomen and recovered after paracentesis and drainage. He was discharged on day 16. The donor and recipient are in satisfactory condition at present. Improvement of technique in hepatic surgery, microsurgical technique in vascular surgery and postoperative intensive care are the keys to ensure the success of the procedure.
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Affiliation(s)
- Chunbao Guo
- Department of Hepatobiliary Surgery, Children's Hospital, Chongqing Medical University, Chongqing, P.R. China
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10
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Heffron TG, Pillen T, Smallwood G, Rodriguez J, Sekar S, Henry S, Vos M, Casper K, Gupta NA, Fasola CG, Romero R. Pediatric liver transplantation for acute liver failure at a single center: a 10-yr experience. Pediatr Transplant 2010; 14:228-32. [PMID: 19519799 PMCID: PMC4380080 DOI: 10.1111/j.1399-3046.2009.01202.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Children transplanted for ALF urgently require an optimal graft and have lower post-transplant survival compared with children transplanted for chronic liver disease. Over 10 yr, 33 consecutive children transplanted for ALF were followed. Demographics, encephalopathy, intubation, dialysis, laboratory values, graft type ABOI, XL (GRWR > 5%), DDSLT, LDLT and WLT were evaluated. Complications and survival were determined. ALF accounted for 33/201 (16.4%) of transplants during this period. Twelve of 33 received ABOI, five XL grafts, 18 DDSLT, and three LDLT. Waiting time pretransplant was 2.1 days. One- and three-yr patient survival in the ALF group was 93.4% and 88.9%, and graft survivals were 86.4% and 77.7%. Median follow-up was 1452 days. ABOI one- and three yr patient and graft survival in the ALF was 91.6% and 78.6%. No difference in graft or patient survival was noted in the ALF and chronic liver disease group or the ABOI and the ABO compatible group. A combination of ABO incompatible donor livers, XL grafts, DDSLT, LDLT and WLT led to a short wait time and subsequent graft and patient survival comparable to patients with non-acute disease.
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11
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Mohamed El Moghazy W, Ogura Y, Mutsuko M, Harada K, Koizumi A, Uemoto S. Pediatric living-donor liver transplantation for acute liver failure: analysis of 57 cases. Transpl Int 2010; 23:823-30. [PMID: 20158695 DOI: 10.1111/j.1432-2277.2010.01059.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
We reviewed 57 pediatric patients admitted with acute liver failure to Kyoto University Hospital in Japan over a period of 15 years to compare the etiology and the long-term outcome of infants and children after living donor liver transplantation (LDLT). Patients were divided into two groups according to age at the time of liver transplantation, infants group (<1 year, n = 20), and children group (1-18 years, n = 37). The overall survival rates were 73.6%, 69.5% and 67.2% at 1, 5, and 10 years after LDLT respectively. Age of recipients at the time of LDLT had a strong impact on their outcome, Children had significantly better outcome than infants (P = 0.001). Surgical complications were comparable between both groups. Infants had higher rates of acute cellular rejection (ACR), which was associated with features of hepatitis in many cases. Refractory ACR was the leading cause of death in eight out of 12 infants, while it resulted in loss of one child only. Cox's proportional hazard regression model was used to examine potential risk factors for graft loss and it shows that age <1 year was associated with high risk of graft loss [hazard ratio (HR) = 11.393; CI = 1.961-76.1763] (P < 0.05). In conclusion, Infants had poorer prognosis than children and refractory ACR was the leading cause of death. Using additional immunosuppressant for cases with severe and atypical rejections is recommended.
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12
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Fulminant hepatic failure in children: superior and durable outcomes with liver transplantation over 25 years at a single center. Ann Surg 2009; 250:484-93. [PMID: 19730179 DOI: 10.1097/sla.0b013e3181b480ad] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE(S) Death occurs in half of all children with fulminant hepatic failure (FHF). Although liver transplantation (LT) is potentially life-saving, there are only a few published series with limited experience. The aim was to examine predictors of survival after LT for FHF. METHODS Between 1984 and 2008, all LT for FHF performed in recipients less than or equal to 18 years of age were analyzed from a prospectively maintained database using 35 demographic, laboratory, and operative variables. Unique calculated variables included creatinine clearance (cCrCl) and Pediatric End-Stage Liver Disease score (PELD). Study end-points were patient and death censored graft survival. Median follow-up was 98 months. Statistical analysis involved the log-rank test and Cox proportional hazards model. RESULTS A total of 122 children underwent 159 LTx. Cryptogenic was the primary etiology (70%) and the median age was 53 months. The significant (P < 0.05) univariate predictors of worse graft survival were: recipient age <24 months, cCrCl <60 mL/min/1.73m, PELD >25 points, and warm ischemia time >60 minutes. The significant (P < 0.05) univariate predictors of worse patient survival were: recipient African-American and Asian race, recipient age <24 months, cCrCl <60 mL/min/1.73m, and time from onset jaundice to encephalopathy <7 days. On multivariate analysis, survival was significantly impacted by 4 variables: cCrCl <60 mL/min/1.73m (GRAFT and PATIENT), PELD >25 points (GRAFT), recipient age <24 months (GRAFT), and time from onset jaundice to encephalopathy <7 days (PATIENT). While overall 5- and 10-year survival was 73% and 72% (GRAFT) and 77% and 73% (PATIENT), these were significantly worse when a combination of multivariate risk-factors were present. CONCLUSIONS This data from a large, single-center experience demonstrates that LT is the treatment of choice for FHF and results in durable survival. Analysis revealed 4 novel outcome predictors. Young children with rapid onset acute liver failure are a high-risk subpopulation. Unique to this study, cCrCl and PELD accurately predicted the end-points. This analysis identifies patient subpopulations requiring early aggressive intervention with LT.
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13
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Abstract
1. Establishing the cause of fulminant hepatitis is an important determinant in outcomes after liver transplantation. 2. Liver transplantation is an integral part of the management of ALF. 3. In addition to generic posttransplant care, neurologic, septic, and hematologic issues need to be addressed. 4. Outcomes after liver transplantation are poorer than those for elective transplantation but superior to those found for comparably ill patients being transplanted for chronic liver disease. 5. Multiple factors have an influence on outcome, and risk stratification is beginning to emerge.
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Affiliation(s)
- John G O'Grady
- King's College Hospital, Denmark Hill, London, United Kingdom. john.o'
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14
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Soltys KA, Mazariegos GV, Squires RH, Sindhi RK, Anand R. Late graft loss or death in pediatric liver transplantation: an analysis of the SPLIT database. Am J Transplant 2007; 7:2165-71. [PMID: 17608834 DOI: 10.1111/j.1600-6143.2007.01893.x] [Citation(s) in RCA: 111] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Late graft loss (LGL) and late mortality (LM) following liver transplantation (LT) in children were analyzed from the studies of pediatric liver transplantation (SPLIT) database. Univariate and multivariate associations between pre- and postoperative factors and LGL and LM in 872 patients alive with their primary allografts 1 year after LT were reviewed. Thirty-four patients subsequently died (LM) and 35 patients underwent re-LT (LGL). Patients who survive the first posttransplant year had 5-year patient and graft survival rates of 94.2% and 89.2%, respectively. Graft loss after the first year was caused by rejection in 49% of the cases with sequelae of technical complications accounting for an additional 20% of LGL. LT for tumor, steroid resistant rejection, reoperation in the first 30 days and >5 admissions during the first posttransplant year were independently associated with LGL in multivariate analysis. Malignancy, infection, multiple system organ failure and posttransplant lymphoproliferative disease accounted for 61.8% of all late deaths after LT. LT performed for FHF and tumor were associated with LM. Patients who are at or below the mean for weight at the time of transplant were also at an increased risk of dying. Frequent readmission was also found to be associated with LM.
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Affiliation(s)
- K A Soltys
- Hillman Center for Pediatric Transplantation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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15
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Nadalin S, Heuer M, Wallot M, Auth M, Schaffer R, Sotiropoulos GC, Ballauf A, van der Broek MAJ, Olde-Damink S, Hoyer PF, Broelsch CE, Malagò M. Paediatric acute liver failure and transplantation: The University of Essen experience. Transpl Int 2007; 20:519-27. [PMID: 17355244 DOI: 10.1111/j.1432-2277.2007.00474.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
To report our experience with 17 children who underwent a liver transplantation (LT) for acute liver failure (ALF). All LT procedures (deceased and living donor) were offered. Since 2003 Molecular Adsorbents Recycling System (MARS) was proposed as bridging procedure. We monitored the perioperative course and the short- and long-term outcomes. All children developed pretransplant hepatic encephalopathy (mostly grades II and III); six needed ventilator support and three haemodialysis. Median PELD/MELD score was 30. MARS was used in five children with poor pretransplant prognostic factors: all five survived the LT without sequelae. We performed 13 deceased donor LT (seven whole, five split and onr reduced) and four left lateral LDLT. Postoperative complications were observed in 10 children, requiring re-operation in seven. Two children developed irreversible neurological disorders. After a median follow up of 45 months, 16 children are still alive. About 1- and 5-year cumulative patient survival rates are 94% with a corresponding graft survival of 88% and 81%, respectively. The combination of experienced paediatric ICU management, the application of new liver support devices, and the capacity to offer both living and deceased donor transplant alternatives in a timely fashion represent the best formula to achieve optimal results in children with ALF.
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Affiliation(s)
- Silvio Nadalin
- Department of General-, Visceral- and Transplantation Surgery, University Hospital Essen, Essen, Germany.
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16
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17
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Abstract
BACKGROUND This study examines the results of liver transplantation (LT) in children 5 kg or less. Reports suggest an increased morbidity and mortality in children weighing 5 kg or less as compared to larger children. However, over half of all children needing LT are <1 year old. Improving outcomes in very small children is a major goal of liver transplantation. METHODS All children under 21 years of age transplanted from January 1990 to June 2005 were included in this study. One hundred sixty-eight primary liver transplants were done: 61 in children less than one year of age and 20 in infants weighing 5 kg or less at LT (2 to 5 kg). These 20 infants underwent 23 transplants. Whole organs were used in 39% of transplants, and reduced or split grafts were used in 61%. Arterial reconstruction using aortic conduits was done in 22%. Analysis included Fischer's exact or Chi square test for non-parametric analysis while patient survival was calculated using the Kaplan-Meier method test with differences in survival assessed using the log rank test. RESULTS Five-year survival for infants 5 kg or less was 74%, and graft survival was 60%, which was not different from patients transplanted that were >5 kg. There were three perioperative deaths, one from primary graft non-function, and two from portal vein thrombosis. There were no bile leaks or hepatic artery thromboses. Bacterial, fungal, and viral infections made up the vast majority of the postoperative complications (65%), with viral infections resulting in two graft losses requiring re-transplantation. Rejection occurred in 25% of patients, of which one required OKT3. Five of the 23 liver transplants in infants less than 5 kg were done prior to 1996, with a five-year graft survival of only 20%. Improvements in technique and postoperative care after 1996 led to improved graft and patient survival of 77% and 86% respectively. CONCLUSIONS Liver transplantation for infants weighing less than 5 kilograms can be technically challenging but can have equivalent graft and patient survival when compared to larger children requiring liver transplantation. Infants should not be denied liver transplantation based on weight alone.
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Affiliation(s)
- Kristin L Mekeel
- Division of Transplantation and Hepatobiliary Surgery, University of Florida, Gainesville, FL 32410, USA
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18
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Rhee C, Narsinh K, Venick RS, Molina RA, Nga V, Engelhardt R, Martín MG. Predictors of clinical outcome in children undergoing orthotopic liver transplantation for acute and chronic liver disease. Liver Transpl 2006; 12:1347-56. [PMID: 16741901 DOI: 10.1002/lt.20806] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The current United Network for Organ Sharing (UNOS) policy is to allocate liver grafts to pediatric patients with chronic liver disease based on the pediatric end-stage liver disease (PELD) scoring system, while children with fulminant hepatic failure may be urgently listed as Status 1a. The objective of this study was to identify pre-transplant variables that influence patient and graft survival in those children undergoing LTx (liver transplantion) for FHF (fulminant hepatic failure) compared to those patients transplanted for extrahepatic biliary atresia (EHBA), a chronic form of liver disease. The UNOS Liver Transplant Registry was examined for pediatric liver transplants performed for FHF and EHBA from 1987 to 2002. Variables that influenced patient and graft survival were assessed using univariate and multivariate analysis. Kaplan-Meier analysis of FHF and EHBA groups revealed that 5 year patient and graft survival were both significantly worse (P < 0.0001) in those patients who underwent transplantation for FHF. Multivariate analysis of 29 variables subsequently revealed distinct sets of factors that influenced patient and graft survival for both FHF and EHBA. These results confirm that separate prioritizing systems for LTx are needed for children with chronic liver disease and FHF; additionally, our findings illustrate that there are unique sets of variables which predict survival following LTx for these two groups.
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Affiliation(s)
- Chris Rhee
- Department of Pediatrics, Division of Gastroenterology, Mattel Children's Hospital at UCLA, Los Angeles, CA 90095, USA
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19
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Yamamoto S, Steers JL, Wharen RE, Eckman CB, Nguyen JH. Cerebrospinal fluid drainage and cranial decompression prolong survival in rats with fulminant hepatic failure. Transpl Int 2006; 19:675-82. [PMID: 16827685 PMCID: PMC2676324 DOI: 10.1111/j.1432-2277.2006.00322.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Fulminant hepatic failure (FHF) is a devastating disease. Liver transplantation is the definitive treatment. However, a third of these patients die due to brain edema before a donor becomes available. Cerebrospinal fluid (CSF) drainage and decompressive craniectomy have been used to treat brain edema in brain trauma and hemispheric stroke. However, their role in brain edema associated with FHF has not been examined. In this study we evaluated the potential effects of CSF drainage and decompressive craniectomy on survival in FHF using an experimental model in rats. In CSF drainage experiments all animals had ventriculostomy placed. Five days later FHF was induced with d-galactosamine. Those FHF rats that progressed into comatose stages either received CSF aspiration or did not. In separate experiments the study rats had either a decompressive craniectomy or a sham procedure. FHF was induced 5 days later. We found that both CSF drainage and decompressive craniectomy significantly increased survival of FHF rats compared with the controls: 53.2 +/- 1.1 vs. 48.7 +/- 1.5 h (P = 0.031), and 69.4 +/- 3.9 vs. 53.7 +/- 3.2 h (P = 0.009), respectively. In conclusion, these findings suggest that CSF drainage and decompressive craniectomy may increase the window of opportunity for liver transplantation.
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Affiliation(s)
- Satoshi Yamamoto
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Jeffery L. Steers
- Department of Transplantation, Division of Transplant Surgery, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | - Robert E. Wharen
- Department of Neurosurgery, Mayo Clinic College of Medicine, Jacksonville, FL, USA
| | | | - Justin H. Nguyen
- Department of Transplantation, Division of Transplant Surgery, Mayo Clinic College of Medicine, Jacksonville, FL, USA
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20
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Li LJ, Du WB, Zhang YM, Li J, Pan XP, Chen JJ, Cao HC, Chen Y, Chen YM. Evaluation of a bioartificial liver based on a nonwoven fabric bioreactor with porcine hepatocytes in pigs. J Hepatol 2006; 44:317-324. [PMID: 16356580 DOI: 10.1016/j.jhep.2005.08.006] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2005] [Revised: 07/26/2005] [Accepted: 08/12/2005] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIMS We developed a bioartificial liver (BAL) based on a direct hemoperfusion typed nonwoven fabric bioreactor containing porcine hepatocytes. In this study, the efficacy of our BAL was evaluated with a pig fulminant hepatic failure (FHF) model. METHODS FHF was induced with intravenous administration of D-galactosamine (1.3 g/kg) in each pig. Twelve hours post D-galactosamine injection, fifteen pigs were divided into: a BAL group (n = 5), in which pigs received the BAL treatment with 1.0 to 1.3 x 10(9) hepatocytes for 6 h, a sham BAL group (n = 5), in which pigs received the BAL treatment without hepatocytes, and a FHF group (n = 5), in which pigs only received intensive care. Parameters related to liver function and animal survival up to 168 h were determined. RESULTS In the BAL group, blood ammonia and plasma lactate levels were lower, and serum glucose levels and Fischer index were higher than those in the other two groups. Survival time of pigs in the BAL group was significantly prolonged as compared with the sham BAL and the FHF group. CONCLUSIONS The BAL based on a nonwoven fabric bioreactor containing porcine hepatocytes appears to be effective in the treatment of FHF in pigs.
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Affiliation(s)
- Lan Juan Li
- Key Laboratory of Infectious Diseases, Ministry of Public Health, Department of Infectious Diseases, The 1st Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
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21
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Du WB, Li LJ, Huang JR, Yang Q, Liu XL, Li J, Chen YM, Cao HC, Xu W, Fu SZ, Chen YG. Effects of artificial liver support system on patients with acute or chronic liver failure. Transplant Proc 2005; 37:4359-4364. [PMID: 16387120 DOI: 10.1016/j.transproceed.2005.11.044] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIMS Acute on chronic liver failure (AoCLF) is associated with a high mortality rate. Artificial liver support system (ALSS) is useful to bridge patients with liver failure to liver transplantation or to regenerate their own livers. The aims of this prospective study were to investigate the effects of ALSS on clinical manifestations, liver function, and 30-day survival to probe the factors related to mortality in patients with AoCLF. METHODS In this study, 338 enrolled patients with AoCLF who received ALSS treatment for 1 to 8 sessions, were compared with 312 patients treated with conventional medications. RESULTS Clinical manifestations and liver functions were significantly improved, namely, decreased levels of serum transaminases, total bilirubin, and bile acid, as well as increased levels of serum albumin following ALSS treatment. The 30-day survival rates of the patients who received ALSS versus controls were 47.9% versus 34.6%, respectively (P = .01). The MELD score and the stage of hepatic encephalopathy were highly associated with mortality (P < .001), but the sessions of ALSS showed a positive relation to the 30-day survival (P < .05). CONCLUSIONS ALSS appears to be efficacious and safe for the treatment of patients with AoCLF. Both model for end-stage liver disease (MELD) score and hepatic encephalopathy are useful to predict the mortality of patients.
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Affiliation(s)
- W B Du
- Key Laboratory of Infectious Diseases, Ministry of Public Health of China, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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22
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Chan PC, Chen HL, Kong MS, Huang FC, Lee HC, Lin CC, Liu CC, Lee IH, Wu TC, Wu SF, Ni YH, Hsu HY, Chang MH. Factors affecting the mortality of pediatric fulminant hepatic failure in relation to hepatitis B virus infection. J Gastroenterol Hepatol 2005; 20:1223-1227. [PMID: 16048570 DOI: 10.1111/j.1440-1746.2005.03923.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
AIM To investigate the factors affecting the outcome of fulminant hepatic failure (FHF) in children in relation to hepatitis B virus (HBV) infection. METHODS Retrospective review of a total of 94 cases (61 males and 33 females, aged from 1 month to 15 years) recruited from nine tertiary referral centers in Taiwan from 1985 to 1999. RESULTS The overall mortality rate was 75%. Patients in the mortality group were of an older age, had higher peak total bilirubin levels, a longer prothrombin time, and a lower percentage of HBV positivity (P < 0.001, P = 0.003, P = 0.0027 and P = 0.042, respectively). Mortality was 65% in the HBV positive (n = 42) and 83% in the HBV negative (n = 52) group (P = 0.05). In the HBV positive group, the prothrombin time was noted to be the single factor affecting outcome (P = 0.036). In the HBV negative group, older age and higher peak value of total serum bilirubin were suggestive of poor survival rate (P < 0.001 and P = 0.006, respectively). Multivariate analysis revealed that total bilirubin was the single factor affecting outcome in the HBV-negative group. The mortality rate of HBV positive children in three consecutive time periods without liver transplantation (1985-1989, 1990-1994, 1995-1999) decreased gradually (91, 67 and 38%, respectively, with P = 0.027). This change was not observed in HBV-negative cases. CONCLUSIONS Hepatitis B virus positive FHF had a lower mortality rate than HBV negative FHF, with each group having different factors affecting mortality.
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Affiliation(s)
- Pei-Chun Chan
- Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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23
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Baliga P, Alvarez S, Lindblad A, Zeng L. Posttransplant survival in pediatric fulminant hepatic failure: the SPLIT experience. Liver Transpl 2004; 10:1364-71. [PMID: 15497159 DOI: 10.1002/lt.20252] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Pediatric patients with fulminant hepatic failure (FHF) tend to be the sickest and have the most urgent need for a liver transplant. The purpose of this analysis was to identify factors associated with posttransplant survival in this subset of patients. Data on all FHF patients registered in the Studies of Pediatric Liver Transplantation (SPLIT) registry from 1995 to 2002 were analyzed. Demographics such as age, gender, race, weight, and etiology of liver disease were recorded. Pretransplant degree of encephalopathy; intubation; dialysis; laboratory parameters such as serum bilirubin and international normalized ratio of coagulopathy (INR); and type of graft: cadaveric whole, cadaveric technical variant, or living donor were analyzed to determine effects on patient survival. Overall, FHF accounted for 12.9% (141 / 1,092) of primary transplants performed between 1995 and 2002. The etiology of liver disease was unknown in the vast majority of children (126 / 141; 89.4%). Mortality while on the waiting list for FHF children is significantly higher than for children with other liver disease (P < .0001). Six-month survival posttransplant for patients with FHF (74.5%) is significantly lower (P < .0001) than those with chronic liver disease (88.9%). A multivariate model demonstrates that the highest risk group includes those children with grade 4 encephalopathy (P < .0001), infants less than 1 year of age (P = .018), and children requiring dialysis prior to transplantation (P = .002). Pretransplant bilirubin and INR were not significant predictors of posttransplant survival after controlling for the other significant factors. Living donor and split / reduced grafts did not have a significantly increased risk of posttransplant death compared to whole grafts. In conclusion, despite advances in the surgical techniques and changes in organ allocation, pediatric patients with FHF continue to have a high pretransplant mortality and less successful posttransplant survival compared to children with chronic liver disease.
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Affiliation(s)
- Prabhakar Baliga
- Division of Transplant Surgery, Medical University of South Carolina, Charleston, SC, USA
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24
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Li LJ, Yang Q, Huang JR, Xu XW, Chen YM, Fu SZ. Effect of artificial liver support system on patients with severe viral hepatitis: A study of four hundred cases. World J Gastroenterol 2004; 10:2984-8. [PMID: 15378778 PMCID: PMC4576257 DOI: 10.3748/wjg.v10.i20.2984] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To assess the effect of artificial liver support system (ALSS) on patients with severe viral hepatitis, who were divided into treatment group and control group.
METHODS: Four hundred in-hospital patients enrolled during 1995-2003 who received ALSS therapy were studied as the treatment group. Four hundred in-hospital patients enrolled during 1986-1994 who received other medical therapies served as the control group. The methods of ALSS used included plasma exchange, hemoperfusion, hemofiltration, continuous hemodiafiltration (CHDF). The effect of ALSS treatment was studied in patients at different stages of the disease.
RESULTS: The cure rate of acute and subacute severe hepatitis in the treatment group was 78.9% (30/38), and was 11.9% (5/42) in the control group. The improved rate of chronic severe hepatitis in the treatment group was 43.4% (157/362), and was 15.4% (55/358) in the control group. We found that patients treated with ALSS in the early or middle stage of the disease had much higher survival rates than patients in the end stage of the disease.
CONCLUSION: ALSS is an effective and safe therapy for severe viral hepatitis.
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Affiliation(s)
- Lan-Juan Li
- Department of Infectious Disease, First Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
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25
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Rubik J, Pietraszek-Jezierska E, Kamiński A, Skarzynska A, Jóźwiak S, Pawłowska J, Drewniak T, Prokurat S, Grenda R, Kaliciński P. Successful treatment of a child with fulminant liver failure and coma caused by Amanita phalloides intoxication with albumin dialysis without liver transplantation. Pediatr Transplant 2004; 8:295-300. [PMID: 15176968 DOI: 10.1111/j.1399-3046.2004.00170.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
FLF is a life-threatening disease. Hepatic coma exerts dramatic impact on patient survival. At present, LTx is the treatment modality of choice that provides significant improvement in outcome of most patients with FLF. Multiple attempts have been made to reduce mortality and improve the patient's condition. One of the new options is AD - MARS. We present the case of a 11-yr-old boy with FLF and hepatic coma who avoided the scheduled LTx because of rapid neurological and biochemical improvement immediately after three MARS sessions.
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Affiliation(s)
- Jacek Rubik
- Department of Nephrology and Kidney Transplantation, Children's Memorial Health Institute, Warsaw, Poland.
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26
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Humar A, Khwaja K, Glessing B, Larson E, Asolati M, Durand B, Lake J, Payne WD. Regionwide sharing for status 1 liver patients--beneficial impact on waiting time and pre- and posttransplant survival. Liver Transpl 2004; 10:661-5. [PMID: 15108258 DOI: 10.1002/lt.20161] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
On August 21, 1999, Region 7 of the United Network for Organ Sharing (UNOS) adopted a policy of regionwide sharing of cadaver livers for UNOS Status 1 recipients. We examined what impact this policy had at our center on their waiting times, waiting list mortality, and outcomes. From January 1, 1995, through December 31, 2002, our center listed 39 patients for an emergent (Status 1) transplant, according to the current criteria for Status 1 listing: patients (adult and pediatric) with fulminant hepatic failure (FHF), hepatic artery thrombosis, or primary nonfunction early after a liver transplant, or critically ill pediatric patients with chronic liver disease. These 39 candidates were analyzed in 2 groups: those listed before regionwide sharing (Group I, n = 19) and those listed after (Group II, n = 20). Patient characteristics did not differ significantly between the 2 groups, including mean donor and recipient age, proportion of pediatric patients, and type of graft used (i.e., living or deceased donor, segmental or whole-organ). FHF was the most common cause of liver failure in both groups-74% versus 70% (P = ns). The next most common cause in both groups was hepatic artery thrombosis, followed by primary nonfunction. Most transplants used deceased donors; however, 2 of the transplants in Group I versus only 1 in Group II used living donors. Waiting list mortality (the patient death rate before a transplant could take place) was 32% in Group I versus only 5% in Group II (P =.03). The mean number of days on the waiting list was also substantially lower in Group II (2.9 days) than in Group I, (5.8 days) (P =.04). For patients who underwent a transplant, graft and patient survival rates at 6 months posttransplant were 69.2% in Group I versus 89.5% in Group II (P =.03). In conclusion, the introduction of regionwide sharing seems to have been of benefit for Status 1 patients at our center. They have a significantly lower risk of dying while waiting for a transplant and undergo one in a much shorter period of time.
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Affiliation(s)
- Abhinav Humar
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
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27
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Abstract
Liver transplantation is accepted therapy for acute or chronic liver failure. Survival after LT has improved significantly in developed countries and this has increased the awareness of this treatment modality in the developing world. Successful LT in both children and adults have now been reported from India. Chronic liver failure secondary to cholestatic liver disease in the most frequent indication for LT, with biliary with atresia as the single commonest cause. Innovative techniques such as reduced size, splint, and living donor liver transplantation are being applied more often to decrease long waiting times and reduce associated morbidity and mortality. Early postoperative complications include primary graft failure, venous thrombosis, rejection, biliary complications and infections. Late complication includes CMV or EBV infections, side effects of immunosuppression, post transplantation lymphoproliferative disease and late biliary strictures. Most children achieve good quality of life. There are still many lessons to learn and there are future challenges such as the ever increasing problems of donor scarcity and the search for potent but less toxic immunosuppressive agents.
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Affiliation(s)
- Deirdre Kelly
- The Liver Unit, Birmingham Children's Hospital, Steelhouse Lane, Birmingham
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28
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Qian Y, Lanjuan L, Jianrong H, Jun L, Hongcui C, Suzhen F, Xia Y, Shuhong Y. Study of severe hepatitis treated with a hybrid artificial liver support system. Int J Artif Organs 2003; 26:507-13. [PMID: 12866656 DOI: 10.1177/039139880302600609] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Artificial liver support system (ALSS) has been used to treat hepatic failure and has significantly decreased the mortality. TECA hybrid artificial liver support system (TECA-HALSS), which combines the hollow fiber bioreactor with a plasma exchange circuit, was used to assess the efficacy, safety and feasibility in treating severe hepatitis patients. The hybrid artificial liver support system (HALSS) consists of a bioreactor containing more than 5 x10(9) porcine hepatocytes and plasma exchange device. Fifteen patients with severe hepatitis were treated with this hybrid system. All patients experienced a reduction in symptoms such as fatigue, abdominal distention or ascites. After each treatment serum total bilirubin decreased markedly while prothrombin activity increased. There were ten patients whose progress of hepatocyte necrosis was stopped after HALSS treatment, and finally they recovered completely. One patient received liver transplantation after HALSS therapy and survived. No serious adverse events were noted in the fifteen patients.
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Affiliation(s)
- Y Qian
- Department of Infectious Disease,The First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, China.
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29
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Farmer DG, Anselmo DM, Ghobrial RM, Yersiz H, McDiarmid SV, Cao C, Weaver M, Figueroa J, Khan K, Vargas J, Saab S, Han S, Durazo F, Goldstein L, Holt C, Busuttil RW. Liver transplantation for fulminant hepatic failure: experience with more than 200 patients over a 17-year period. Ann Surg 2003; 237:666-75; discussion 675-6. [PMID: 12724633 PMCID: PMC1514517 DOI: 10.1097/01.sla.0000064365.54197.9e] [Citation(s) in RCA: 123] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome. SUMMARY BACKGROUND DATA FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT. METHODS A retrospective review was undertaken of all patients undergoing LT for FHF at a single transplant center. The median follow-up was 41 months. Thirty-five variables were analyzed by univariate and multivariate analysis to determine their impact on patient and graft survival. RESULTS Two hundred four patients (60% female, median age 20.2 years) required urgent LT for FHF. Before LT, the majority of patients were comatose (76%), on hemodialysis (16%), and ICU-bound. The 1- and 5-year survival rates were 73% and 67% (patient) and 63% and 57% (graft). The primary cause of patient death was sepsis, and the primary cause of graft failure was primary graft nonfunction. Univariate analysis of pre-LT variables revealed that 19 variables predicted survival. From these results, multivariate analysis determined that the serum creatinine was the single most important prognosticator of patient survival. CONCLUSIONS This study, representing one of the largest published series on LT for FHF, demonstrates a long-term survival of nearly 70% and develops a clinically applicable and readily measurable set of pretransplant factors that determine posttransplant outcome.
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Affiliation(s)
- Douglas G Farmer
- Department of Surgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
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30
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Green DW, Ashley EMC. The choice of inhalation anaesthetic for major abdominal surgery in children with liver disease. Paediatr Anaesth 2002; 12:665-73. [PMID: 12472701 DOI: 10.1046/j.1460-9592.2002.00724.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Many children with liver disease undergo major abdominal surgery. Maintenance of anaesthesia is thus an important consideration in this surgical population. Despite a comprehensive and painstaking review of the literature, a sound evidence base, on which a choice of inhalation anaesthetic may be made, is lacking due to limited research in these patients. Differences between the more recent agents such as isoflurane, sevoflurane and desflurane are minor. Sevoflurane is favoured in paediatric practice for gaseous induction, but desflurane or isoflurane are marginally the preferred agents for maintenance of anaesthesia in children with liver disease undergoing major abdominal surgery. However, on the evidence that exists, much of it admittedly in animals and in adults, all three are preferable to halothane in this group of patients. More work is needed in this area before sound conclusions can be drawn and one agent proved to be definitely superior to the others.
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Affiliation(s)
- D W Green
- Department of Anaesthetics, King's College Hospital, London, UK
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31
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Centeno MA, Bes DF, Sasbón JS. Mortality risk factors of a pediatric population with fulminant hepatic failure undergoing orthotopic liver transplantation in a pediatric intensive care unit. Pediatr Crit Care Med 2002; 3:227-233. [PMID: 12780961 DOI: 10.1097/00130478-200207000-00004] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVES: To determine risk factors of mortality in the preoperative, perioperative, and immediate postoperative period of a pediatric population that has undergone orthotopic liver transplantation for fulminant hepatic failure in a pediatric intensive care unit. DESIGN: Retrospective review of medical records. SETTING: A pediatric intensive care unit in a children's hospital. PATIENTS: Sixty patients with fulminant hepatic failure who fulfilled King's College criteria for liver transplantation. INTERVENTION: Orthotopic liver transplantation was performed according to standard techniques. Before transplantation, patients were admitted to a pediatric intensive care unit when intensive care was required, and patients were always admitted to a pediatric intensive care unit after the operation. Measurements: A total of 20 variables were studied via univariate and multivariate analysis; statistical significance was accepted when p </=.05. MAIN RESULTS: A total of 70 orthotopic liver transplantations were performed in 60 children (mean age, 64.11 +/- 40.97 months; range, 11 months to 14 yrs) for fulminant hepatic failure. Fulminant hepatic failure was caused by hepatitis A virus in 60% of cases, and non-A non-B non-C hepatitis was responsible in 40% of cases. Univariate analysis showed that the complications of infectious, hemodynamic, renal, and gastrointestinal bleeding are significant variables. Posttransplant respiratory support was also a significant variable. When the same variables were calculated with a multivariate analysis, no significant results were obtained. Multivariate analysis showed that mortality risk factors in this population were: etiology of liver failure (p <.002), liver size (p <.014), ischemia time (p <.041), ventilatory support before transplantation (p <.048), neurologic complications after orthotopic liver transplantation (p <.003), and acute rejection (p <.021). CONCLUSIONS: Hepatitis A virus is the major cause of fulminant liver failure in Argentina, but non-A non-B non-C hepatitis is an independent risk factor of mortality. Reduced-size graft, longer ischemia time, ventilatory support before orthotopic liver transplantation, neurologic complications, and acute rejection after transplantation are independent predictive factors of mortality. Better sanitary conditions and universal immunization for hepatitis A virus should reduce hepatitis A virus and hepatitis A virus-induced fulminant hepatic failure.
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Affiliation(s)
- Mónica A. Centeno
- Pediatric Intensive Care Unit (MAC, JSS) and the Intermediate and Moderate Care Ward, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," Buenos Aires, Argentina
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Jain A, Mazariegos G, Kashyap R, Kosmach-Park B, Starzl TE, Fung J, Reyes J. Pediatric liver transplantation. A single center experience spanning 20 years. Transplantation 2002; 73:941-7. [PMID: 11923697 PMCID: PMC2975975 DOI: 10.1097/00007890-200203270-00020] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Survival after liver transplantation has improved significantly over the last decade with pediatric recipients faring better than adults. The 20-year experience of pediatric liver transplantation at Children's Hospital of Pittsburgh is reported in terms of patient survival; graft survival in relation to age, gender, and immunosuppressive protocols; causes of death; and indications for retransplantation. METHOD From March 1981 to April 1998, 808 children received liver transplants at Children's Hospital of Pittsburgh. All patients were followed until March 2001, with a mean follow-up of 12.2+/-3.9 years (median=12.6; range=2.9-20). There were 405 female (50.2%) and 403 male (49.8%) pediatric recipients. Mean age at transplant was 5.3+/-4.9 years (mean=3.3; range 0.04-17.95), with 285 children (25.3%) being less than 2 years of age at transplant. Cyclosporine (CsA)-based immunosuppression was used before November 1989 in 482 children (50.7%), and the subsequent 326 recipients (40.3%) were treated with tacrolimus-based immunosuppression. Actuarial survival was calculated using the Kaplan-Meier statistical method. Differences in survival were calculated by log-rank analysis. RESULTS Overall patient survival at 1, 5, 10, 15, and 20 years was 77.1%, 72.6%, 69.4%, 65.8%, and 64.4%, respectively. There was no difference in survival for male or female patients at any time point. At up to 10 years posttransplant, the survival for children greater than 2 years of age (79.5%, 75.7%, and 71.6% at 1, 5, and 10 years, respectively) was slightly higher than those at less than 2 years of age (72.6%, 66.9%, and 65.3% at 1, 5, and 10 years, respectively). However, at 15 and 20 years posttransplant, survival rates were similar (>2 years=67.3% and 65.8%; <2 years=64.1% and 64.1%). A significant difference in survival was seen in CsA-based immunosuppression (71.2%, 68.1%, 65.4%, and 61%) versus tacrolimus-based immunosuppression (85.8%, 84.7%, 83.3%, and 82.9%) at 1, 3, 5, and 10 years, respectively (P=0.0001). The maximum difference in survival was noted in the first 3 months between CsA and tacrolimus; thus, indicating there may have been other factors (nonimmunological factors) involved in terms of donor and recipient selection and technical issues. The mean annual death rate beyond 2 years posttransplant was 0.47%, with the mean annual death rate for patients who received tacrolimus-based immunosuppression being significantly lower than those who received CsA-based immunosuppression (0.14% vs. 0.8%; P=0.001). The most common etiologies of graft loss were hepatic artery thrombosis (33.4%), acute or chronic rejection (26.6%), and primary nonfunction (16.7%). Of note, retransplantation for graft loss because of acute or chronic rejection occurred only in those patients who received CsA-based immuno-suppression. CONCLUSION The overall 20-year actuarial survival for pediatric liver transplantation is 64%. Survival has increased by 20% in the last 12 years with tacrolimus-based immunosuppression. Although this improvement may be the result of several factors, retransplantation as a result of acute or chronic rejection has been completely eliminated in patients treated with tacrolimus.
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Affiliation(s)
- Ashok Jain
- Department of Surgery, Thomas E. Starzl Transplantation Institute, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA
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Noujaim HM, Mayer DA, Buckles JA, Beath SV, Kelly DA, McKiernan PJ, Mirza DF, de Ville De Goyet J. Techniques for and outcome of liver transplantation in neonates and infants weighing up to 5 kilograms. J Pediatr Surg 2002; 37:159-64. [PMID: 11819191 DOI: 10.1053/jpsu.2002.30242] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
BACKGROUND Neonates and small infants represent less than 5% of paediatric candidates for liver replacement. Most cases present under urgent conditions and receive grafts from large donors. Surgical techniques must be adapted for adequate graft preparation, vascular reconstruction, and abdominal closure. METHODS Technical aspects and outcome of 15 liver transplantations in infants weighing less than 5 kg performed at our unit were analysed retrospectively. RESULTS Liver transplantation was performed under urgent or highly urgent condition in 13 cases. Reduced or split liver grafts were used in all cases (median donor to recipient weight ratio, 9), including a monosegmental graft in 2 cases. In 10 cases, vascular reconstruction was done using a vascular conduit (5, 4, and 1 for artery, portal, and hepatic veins, respectively) and a delayed closure of the abdomen was necessary in 7 children. Postoperative complications were as follows: thrombosis of hepatic artery (n = 1) or portal vein (n = 1), gastrointestinal haemorrhage (n = 2), intraperitoneal bleeding (n = 1), biliary stricture (n = 2), septicaemia (n = 1). Two infants died of brain damage with a functioning graft. One child underwent retransplant for chronic rejection. CONCLUSIONS Overall, survival rate is 60% (median follow-up, 34 months), which compares favourably with older patient groups when case mix is comparable.
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Lu A, Monge H, Drazan K, Millan M, Esquivel CO. Liver transplantation for fulminant hepatitis at Stanford University. J Gastroenterol 2002; 37 Suppl 13:82-7. [PMID: 12109673 DOI: 10.1007/bf02990106] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND To review the clinical characteristics and outcomes of 26 patients evaluated for liver transplantation for fulminant hepatic failure at Stanford University and Lucile Packard Children's Hospital in an attempt to identify risk factors and prognostic predictors of survival. METHODS A retrospective review of the records of 26 consecutive patients who were evaluated for possible liver transplantation for acute liver failure from May 1, 1995, to January 1, 2000. Pretransplant patient demographics and clinical characteristics were collected, and the data were analyzed by univariate and multivariate analysis. RESULTS Clinical assessment of encephalopathy did not predict outcome. Patients with abnormal computed tomography (CT) of the brain had a twofold increase in mortality compared with those patients with normal studies (p = 0.03). Patients requiring mechanical ventilation and continuous venovenous hemofiltration (CVVH) also had a poor prognosis. CONCLUSION Predictors of poor outcome after fulminant hepatic failure include abnormal CT scan, mechanical ventilation, and requirement for hemofiltration.
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Affiliation(s)
- Amy Lu
- Division of Transplantation, Stanford University Medical Center, Palo Alto, CA 94304, USA
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Sieders E, Peeters PMJG, TenVergert EM, de Jong KP, Porte RJ, Zwaveling JH, Bijleveld CMA, Gouw ASH, Slooff MJH. Graft loss after pediatric liver transplantation. Ann Surg 2002; 235:125-32. [PMID: 11753051 PMCID: PMC1422404 DOI: 10.1097/00000658-200201000-00016] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To describe the epidemiology and causes of graft loss after pediatric liver transplantation and to identify risk factors. SUMMARY BACKGROUND DATA Graft failure after transplantation remains an important problem. It results in patient death or retransplantation, resulting in lower survival rates. METHODS A series of 157 transplantations in 120 children was analyzed. Graft loss was categorized as early (within 1 month) and late (after 1 month). Risk factors were identified by analyzing recipient, donor, and transplantation variables. RESULTS Kaplan-Meier 1-month and 1-, 3-, and 5-year patient survival rates were 85%, 82%, 77%, and 71%, respectively. Graft survival rates were 71%, 64%, 59%, and 53%, respectively. Seventy-one of 157 grafts (45%) were lost: 18 (25%) by death of patients with functioning grafts and 53 (75%) by graft-related complications. Forty-five grafts (63%) were lost early after transplantation. Main causes of early loss were vascular complications, primary nonfunction, and patient death. Main cause of late graft loss was fibrosis/cirrhosis, mainly as a result of biliary complications or unknown causes. Child-Pugh score, anhepatic phase, and urgent transplantation were risk factors for early loss. Donor age, donor/recipient weight ratio, blood loss, and technical-variant liver grafts were risk factors for late loss. CONCLUSIONS To prevent graft loss after pediatric liver transplantation, potential recipients should be referred early so they can be transplanted in an earlier phase of their disease. Technical-variant liver grafts are risk factors for graft survival. The logistics of the operation need to be optimized to minimize the length of the anhepatic phase.
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Affiliation(s)
- Egbert Sieders
- Liver Transplant Group of the University Hospital Groningen, Department of Surgery, Office for Medical Technology Assessment, Pediatrics, and Pathology and Laboratory Medicine, Groningen, The Netherlands
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Affiliation(s)
- F J Kirkham
- Neurosciences Unit, Institute of Child Health (University College London), 30 Guilford Street, London WC1N 1EH.
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Yasutomi M, Uemoto S, Inomata Y, Tanaka K. Liver failure following living donor liver transplantation for fulminant hepatic failure. Transplant Proc 2000; 32:2133. [PMID: 11120101 DOI: 10.1016/s0041-1345(00)01602-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- M Yasutomi
- Department of Transplantation Surgery, Kyoto University Hospital, Kyoto, Japan
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Abstract
Increased survival for young liver transplant recipients has greatly improved. Increasing success has led to broader indications, thereby increasing the number of potential recipients. Pediatric liver centers are developing new strategies to cope with the ever-increasing demands for suitable size appropriate grafts. UNOS is in the process of updating guidelines to regulate the sharing of organs which become available from new surgical techniques. In the future, alternative therapies, such as artificial liver assist devices and techniques of cellular transplantation and genetic modification of hepatocytes, may decrease the number of children who die while waiting for a suitable organ or even obviate the need for the liver transplantation.
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Affiliation(s)
- O Abramson
- Departments of Pediatrics, Gastroenterology, Hepatology, and Nutrition, University of California San Francisco, San Francisco, California, USA
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Abstract
Severe hepatitis A infection is an infrequent but well-recognized cause of acute liver failure that can now be effectively prevented with vaccination against hepatitis A virus. Bromfenac and troglitazone hepatotoxicity as well as various herbal remedies are some of the newly identified causes of acute liver failure. The recently identified transfusion-transmitted virus has been implicated in some cases of idiopathic acute liver failure whereas hepatitis G virus does not appear to be a causative agent. Recognizing, monitoring, and treating patients with life-threatening cerebral edema remain critically important but difficult aspects of the clinical care of acute liver failure. Hypothermia and N-acetylcysteine are promising experimental approaches to cerebral edema but emergency liver transplantation is the only proven means of improving patient survival. Although recent changes in organ allocation may reduce waiting time to transplantation, more reliable and validated markers of liver regeneration and prognosis are needed to triage patients. The potential application and limitations of novel technologies including bioartificial liver devices and auxiliary liver transplantation continue to evolve from pioneering work in animal models and human subjects.
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Affiliation(s)
- R J Fontana
- University of Michigan Medical Center, Ann Arbor, Michigan, USA
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