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Semash K, Dzhanbekov T, Nasirov M, Monakhov A, Gadzhieva P. Bortezomib as a Potential Treatment for Recurrent Autoimmune Hepatitis Following Pediatric Liver Transplantation. Pediatr Transplant 2025; 29:e70082. [PMID: 40304093 DOI: 10.1111/petr.70082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Revised: 02/04/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can progress to liver cirrhosis and end-stage liver disease, often necessitating liver transplantation (LT). Pediatric LT has significantly improved survival outcomes, but complications such as acute steroid-resistant rejection and AIH recurrence pose serious challenges. CASE PRESENTATION We report the first documented pediatric liver transplantation case in Uzbekistan, performed on a 14-year-old boy with liver cirrhosis secondary to AIH. Despite successful surgery, the patient developed acute steroid-resistant graft rejection and was unresponsive to pulse methylprednisolone therapy and anti-thymocyte globulin (ATG), which also induced adverse effects, including polyneuropathy and hypertension. Further evaluation revealed reactivation of AIH, confirmed by elevated ANA and ANCA titers. Conventional therapies failed to control the disease, prompting the use of bortezomib, a proteasome inhibitor. After the initial dose of bortezomib, significant improvement in bilirubin levels and liver synthetic function was observed. A second dose, administered 7 days later, resulted in the normalization of liver function markers and serological antibodies by postoperative Day 30. The patient was discharged in stable condition under a triple immunosuppressive regimen. To the best of our knowledge, we report the first documented case of using bortezomib for the treatment of recurrent autoimmune hepatitis in a pediatric patient following liver transplantation. CONCLUSION This case emphasizes the effective use of bortezomib as a rescue therapy for steroid-resistant rejection and the recurrence of autoimmune hepatitis following pediatric liver transplantation. It highlights the significance of alternative therapeutic approaches in addressing complex post-transplant immune complications. Furthermore, this case prompts crucial considerations for future research, such as the monitoring of autoimmune disease reactivation and the potential role of drugs like bortezomib in managing immune-related complications after liver transplantation.
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Affiliation(s)
| | | | - Mansur Nasirov
- National Children's Medical Center, Tashkent, Uzbekistan
| | - Artem Monakhov
- V. I. Shumakov Transplantology & Artificial Organs National Medical Research Center, Moscow, Russian Federation
- The First Moscow State Medical University named after I. M. Sechenov (Sechenov University), Moscow, Russia
| | - Patimat Gadzhieva
- V. I. Shumakov Transplantology & Artificial Organs National Medical Research Center, Moscow, Russian Federation
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Kilercik H, Akbulut S, Elsarawy A, Aktas S, Alkara U, Sevmis S. Effect of Complex Venous Outflow Drainage Reconstruction on Postoperative Graft Function in Right-Lobe Living Donor Liver Transplantation. J Clin Med 2025; 14:2005. [PMID: 40142813 PMCID: PMC11942741 DOI: 10.3390/jcm14062005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 03/10/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Living donor liver transplantation (LDLT) is the predominant transplantation technique in regions with low rates of deceased donation. Right-lobe grafting is adopted in most clinical and radiological donor/recipient scenarios. Due to the considerable variations in right-lobe hepatic venous anatomy, many techniques have been used over the years for the purpose of appropriate venous outflow reconstruction during the recipient procedure. In this paper, we present the technical details and consequences of a complex venous outflow reconstruction model (CORM) based on experience, and the long-term patency results obtained using the model. Methods: Data of patients with end-stage liver disease who underwent LDLT between 21 December 2017 and 29 November 2022 were prospectively collected and retrospectively reviewed. The nomenclature of CORM was assigned when three or more hepatic vein anastomoses were performed. Patients with CORM (CORM group; n = 69) were compared with non-CORM patients (non-CORM group; n = 130) in terms of demographic, pre- and postoperative clinical, and follow-up features. Results: Sixty-nine recipients had three or more separate outflow reconstructions (RHV, RIHV, and one or more anterior sectoral veins); these constituted the CORM group. The estimated graft volume of the CORM group was significantly lower than that of the non-CORM group (833 vs. 898; p = 0.022), and the mean GRWR was also significantly lower (1.1 vs. 1.2; p = 0.004). CORM cases showed longer anhepatic phases, as well as longer times for cold and warm ischemia, than non-CORM cases (63 vs. 51 min, 46 vs. 38 min, and 48 vs. 33 min, p < 0.001), though no difference was found with respect to total operative duration. There were no statistical differences between the two groups with respect to rates of in-hospital re-exploration, length of ICU stay, or length of total hospital stay. Graft survival rates at 1 year, 3 years, and 5 years were 88.1%, 83.3%, and 83.3%, respectively, in the CORM group, and 82.9%, 80.2%, and 70.6%, respectively, in the non-CORM group (p = 0.167). Conclusions: Performing three or more CORMs in right-lobe LDLT is not associated with inferior outcomes, either with regard to perioperative variables or to patient and graft outcomes. Right-lobe graft with complex venous anatomy from a living donor should not be a determinant factor for donor exclusion.
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Affiliation(s)
- Hakan Kilercik
- Department of Anesthesiology and Reanimation, Gaziosmanpasa Hospital, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey;
| | - Sami Akbulut
- Department of Surgery and Liver Transplant Institute, Faculty of Medicine, Inonu University, 44280 Istanbul, Turkey
- Department of Surgery and Organ Transplantation, Gaziosmanpasa Hospital, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey; (A.E.); (S.A.); (S.S.)
| | - Ahmed Elsarawy
- Department of Surgery and Organ Transplantation, Gaziosmanpasa Hospital, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey; (A.E.); (S.A.); (S.S.)
| | - Sema Aktas
- Department of Surgery and Organ Transplantation, Gaziosmanpasa Hospital, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey; (A.E.); (S.A.); (S.S.)
| | - Utku Alkara
- Department of Radiology, Gaziosmanpasa Hospital, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey;
| | - Sinasi Sevmis
- Department of Surgery and Organ Transplantation, Gaziosmanpasa Hospital, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey; (A.E.); (S.A.); (S.S.)
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Long J, Dong K, Zhang C, Chen J, Huang K, Su R, Dong C. Graft-to-recipient weight ratio and risk of systemic inflammatory response syndrome early after liver transplantation in children. Dig Liver Dis 2024; 56:2118-2124. [PMID: 38981789 DOI: 10.1016/j.dld.2024.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 06/05/2024] [Accepted: 06/14/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND Systemic inflammatory responses soon after liver transplantation in children can lead to complications and poor outcomes, so here we examined potential risk factors of such responses. METHODS Data were retrospectively analyzed for 69 children who underwent liver transplantation at a single center between July 2017 and November 2019 through follow-up lasting up to one years. Numerous clinicodemographic factors were compared between those who suffered early systemic inflammatory response syndrome (SIRS) or not. RESULTS Of the 69 patients in our analysis, early SIRS occurred in 35 [50.7%, 95% confidence interval (CI), 38.6-62.8%]. Those patients showed significantly higher graft-to-recipient weight ratio (3.69 ± 1.26 vs. 3.12 ± 0.99%, P = 0.042) and lower survival rate at one year (85.7% vs. 100%, P = 0.023). Multivariate analysis found graft-to-recipient weight ratio > 4% to be an independent risk factor for early SIRS [odds ratio (OR) 3.8, 95% CI 1.08-13.371, P = 0.037], and a cut-off value of 4.04% predicted the syndrome in our patients, and area under the receiver operating characteristic curve of 0.656 (95% CI 0.525-0.788, P = 0.026). CONCLUSIONS Graft-to-recipient weight ratio > 4% may predict higher risk of SIRS soon after liver transplantation in children.
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Affiliation(s)
- Junshan Long
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China; Department of General Surgery, Hainan Women and Children's Medical Center, Hainan, PR China
| | - Kun Dong
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China
| | - Cheng Zhang
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China
| | - Junze Chen
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China
| | - Kaiyong Huang
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China
| | - Ruiling Su
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China
| | - Chunqiang Dong
- Department of Organ Transplantation Center, First Affiliated Hospital of Guangxi Medical University, Guangxi, PR China.
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Wang SC, Ting CK, Chen CY, Liu C, Lin NC, Loong CC, Wu HT, Lin YT. Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes. J Clin Monit Comput 2023; 37:1521-1531. [PMID: 37436598 DOI: 10.1007/s10877-023-01047-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 06/13/2023] [Indexed: 07/13/2023]
Abstract
We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology. The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.
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Affiliation(s)
- Shen-Chih Wang
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Kun Ting
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Cheng-Yen Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chinsu Liu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Niang-Cheng Lin
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Che-Chuan Loong
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Transplantation Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hau-Tieng Wu
- Department of Mathematics, Duke University, Durham, NC, USA.
- Department of Statistical Science, Duke University, Durham, NC, USA.
| | - Yu-Ting Lin
- Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan.
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Shinkai T, Kuriyama N, Usui M, Hayasaki A, Fujii T, Iizawa Y, Tanemura A, Murata Y, Kishiwada M, Katoh D, Matsumoto T, Wada H, Yoshida T, Isaji S, Mizuno S. Clinical Significance of Plasma Tenascin-C Levels in Recipients With Prolonged Jaundice After Living Donor Liver Transplantation. Transplant Proc 2023; 55:913-923. [PMID: 36973145 DOI: 10.1016/j.transproceed.2023.01.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 01/26/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Focusing on tenascin-C (TNC), whose expression is enhanced during the tissue remodeling process, the present study aimed to clarify whether plasma TNC levels after living donor liver transplantation (LDLT) could be a predictor of irreversible liver damage in the recipients with prolonged jaundice (PJ). METHODS Among 123 adult recipients who underwent LDLT between March 2002 and December 2016, the subjects were 79 recipients in whom we could measure plasma TNC levels preoperatively (pre-) and on postoperative days 1 to 14 (POD1 to POD14). Prolonged jaundice was defined as serum total bilirubin level >10 mg/dL on POD14, and 79 recipients were divided into 2 groups: 56 in the non-PJ (NJ) group and 23 in the PJ group. RESULTS The PJ group had significantly increased pre-TNC; smaller grafts; decreased platelet counts POD14; increased TB-POD1, -POD7, and -POD14; increased prothrombin time-international normalized ratio on POD7 and POD14; and higher 90-day mortality than the NJ group. As for the risk factors for 90-day mortality, multivariate analysis identified TNC-POD14 as a single significant independent prognostic factor (P = .015). The best cut-off value of TNC-POD14 for 90-day survival was determined to be 193.7 ng/mL. In the PJ group, the patients with low TNC-POD14 (<193.7 ng/mL) had satisfactory survival, with 100.0 % at 90 days, while the patients with high TNC-POD14 (≥193.7 ng/mL) had significantly poor survival, with 38.5 % at 90 days (P = .004). CONCLUSIONS In PJ after LDLT, plasma TNC-POD14 is very useful for diagnosing postoperative irreversible liver damage early.
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Affiliation(s)
- Toru Shinkai
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Department of Disaster and Emergency Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Naohisa Kuriyama
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
| | - Masanobu Usui
- Department of Palliative Medicine, Fujita Health University Faculty of Medicine, Toyoake, Aichi, Japan
| | - Aoi Hayasaki
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Takehiro Fujii
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Yusuke Iizawa
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Akihiro Tanemura
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Yasuhiro Murata
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Masashi Kishiwada
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Daisuke Katoh
- Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Takeshi Matsumoto
- Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Hideo Wada
- Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Toshimichi Yoshida
- Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Shuji Isaji
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Shugo Mizuno
- Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan
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Junger H, Mühlbauer M, Brennfleck FW, Schurr LA, Goetz M, Eggenhofer E, Kirchner G, Evert K, Fichtner-Feigl S, Geissler EK, Schlitt HJ, Brunner SM. Early γGT and bilirubin levels as biomarkers for regeneration and outcomes in damaged bile ducts after liver transplantation. Clin Transplant 2023; 37:e14880. [PMID: 36522802 DOI: 10.1111/ctr.14880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 10/25/2022] [Accepted: 12/03/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Early patient and allograft survival after liver transplantation (LT) depend primarily on parenchymal function, but long-term allograft success relies often on biliary-tree function. We examined parameters related to cholangiocyte damage that predict poor long-term LT outcomes after donation after brain death (DBD). METHODS Sixty bile ducts (BD) were assessed by a BD damage-score and divided into groups with "major" BD-damage (n = 33) and "no relevant" damage (n = 27) during static cold storage. Patients with "major" BD damage were further investigated by measuring biliary excretion parameters in the first 14 days post-LT (followed-up for 60-months). RESULTS Patients who received LT showing "major" BD damage had significantly worse long-term patient survival, versus grafts with "no relevant" damage (p = .03). When "major" BD damage developed, low bilirubin levels (p = .012) and high gamma-glutamyl transferase (GGT)/bilirubin ratio (p = .0003) were evident in the early post-LT phase (7-14 days) in patients who survived (> 60 months), compared to those who did not. "High risk" patients with bile duct damage and low GGT/bilirubin ratio had significantly shorter overall survival (p < .0001). CONCLUSIONS Once "major" BD damage occurs, a high GGT/bilirubin ratio in the early post-operative phase is likely indicator of liver and cholangiocyte regeneration, and thus a harbinger of good overall outcomes. "Major" BD damage without markers of regeneration identifies LT patients that could benefit from future repair therapies.
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Affiliation(s)
- Henrik Junger
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Marco Mühlbauer
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Frank W Brennfleck
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Leonhard A Schurr
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Markus Goetz
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Elke Eggenhofer
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Gabriele Kirchner
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany.,Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany
| | - Katja Evert
- Department of Pathology, University Regensburg, Regensburg, Germany
| | - Stefan Fichtner-Feigl
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany.,Department of Surgery, University Hospital Freiburg, Freiburg, Germany
| | - Edward K Geissler
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany.,Fraunhofer Institute for Experimental Medicine and Toxicology, Regensburg, Germany
| | - Hans J Schlitt
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Stefan M Brunner
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
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Morales Junior R, Telles JP, Kwiatkowski SYC, Juodinis VD, de Souza DC, Santos SRCJ. Pharmacokinetic and pharmacodynamic considerations of antibiotics and antifungals in liver transplantation recipients. Liver Transpl 2023; 29:91-102. [PMID: 35643926 DOI: 10.1002/lt.26517] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/10/2022] [Accepted: 05/18/2022] [Indexed: 01/14/2023]
Abstract
The liver plays a major role in drug metabolism. Liver transplantation impacts the intrinsic metabolic capability and extrahepatic mechanisms of drug disposition and elimination. Different levels of inflammation and oxidative stress during transplantation, the process of liver regeneration, and the characteristics of the graft alter the amount of functional hepatocytes and activity of liver enzymes. Binding of drugs to plasma proteins is affected by the hyperbilirubinemia status and abnormal synthesis of albumin and alpha-1-acid glycoproteins. Postoperative intensive care complications such as biliary, circulatory, and cardiac also impact drug distribution. Renally eliminated antimicrobials commonly present reduced clearance due to hepatorenal syndrome and the use of nephrotoxic immunosuppressants. In addition, liver transplantation recipients are particularly susceptible to multidrug-resistant infections due to frequent manipulation, multiple hospitalizations, invasive devices, and frequent use of empiric broad-spectrum therapy. The selection of appropriate anti-infective therapy must consider the pathophysiological changes after transplantation that impact the pharmacokinetics and pharmacodynamics of antibiotics and antifungal drugs.
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Affiliation(s)
- Ronaldo Morales Junior
- Clinical Pharmacokinetics Center, School of Pharmaceutical Sciences , University of São Paulo , São Paulo , Brazil
- Pediatric Intensive Care Unit, Department of Pediatrics , Hospital Sírio-Libanês , São Paulo , Brazil
| | - João Paulo Telles
- Department of Infectious Diseases , AC Camargo Cancer Center , São Paulo , Brazil
| | | | - Vanessa D'Amaro Juodinis
- Pediatric Intensive Care Unit, Department of Pediatrics , Hospital Sírio-Libanês , São Paulo , Brazil
| | - Daniela Carla de Souza
- Pediatric Intensive Care Unit, Department of Pediatrics , Hospital Sírio-Libanês , São Paulo , Brazil
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Pamecha V, Pattnaik B, Sinha PK, Patil NS, Sasturkar SV, Mohapatra N, Kumar G, Choudhury A, Sarin SK. Early Allograft Dysfunction After Live Donor Liver Transplantation: It's Time to Redefine? J Clin Exp Hepatol 2022; 12:101-109. [PMID: 35068790 PMCID: PMC8766541 DOI: 10.1016/j.jceh.2021.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 03/21/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND An ideal definition of early allograft dysfunction (EAD) after live donor liver transplantation (LDLT) remains elusive. The aim of the present study was to compare the diagnostic accuracies of existing EAD definitions, identify the predictors of early graft loss due to EAD, and formulate a new definition, estimating EAD-related mortality in LDLT recipients. METHODS Consecutive adult patients undergoing elective LDLT were analyzed. Patients with technical (vascular, biliary) complications and biopsy-proven rejections were excluded. RESULTS There were 19 deaths due to EAD of a total of 304 patients. On applying the existing definitions of EAD, we revealed their limitations of being either too broad with low specificity or too restrictive with low sensitivity in patients with LDLT. A new definition of EAD-LDLT (total bilirubin >10 mg/dL, international normalized ratio [INR] > 1.6 and serum urea >100 mg/dL, for five consecutive days after day 7) was derived after doing a multivariate analysis. In receiver operator characteristics analysis, an AUC for EAD-LDLT was 0.86. The calibration and internal cross-validation of the new model confirmed its predictability. CONCLUSION The new model of EAD-LDLT, based on total bilirubin >10 mg/dL, INR >1.6 and serum urea >100 mg/dL, for five consecutive days after day 7, has a better predictive value for mortality due to EAD in LDLT recipients.
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Key Words
- AUC, area under curve
- CIT, cold ischemia time
- DDLT, deceased donor liver transplantation
- DFH, delayed functional hyperbilirubinemia
- EAD, early allograft dysfunction
- GRWR, graft-to-recipient weight ratio
- HDU, high dependency unit
- ICU, intensive care unit
- INR, international normalized ratio
- IR, ischemia-reperfusion
- LDLT, living donor liver transplantation
- MELD, model for end-stage liver disease
- MHV, middle hepatic vein
- PGD, primary graft dysfunction
- PNF, primary non-function
- POD, postoperative day
- PPV, positive predictive value
- ROC, receiver operator characteristics
- SFSS, small for size syndrome
- graft dysfunction
- hyperbilirubinemia
- international normalized ratio
- living donor liver transplantation
- urea
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Affiliation(s)
- Viniyendra Pamecha
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Bramhadatta Pattnaik
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Piyush K. Sinha
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Nilesh S. Patil
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Shridhar V. Sasturkar
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Nihar Mohapatra
- Department of Liver Transplant and Hepato-Pancreato-Biliary Surgery, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India
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Berber I, Cagin YF, Erdogan MA, Ataman E, Gozukara H, Erkurt MA, Yildirim O, Kuku İ, Kaya E, Bilgic Y, Sarici A, Bicim S, Polat A. Early therapeutic plasma exchange may improve treatment outcomes in severe acute toxic Hepatitis. Transfus Apher Sci 2021; 60:103250. [PMID: 34666895 DOI: 10.1016/j.transci.2021.103250] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND OBJECTIVES Acute toxic hepatitis can result in a different clinical course from a completely curable disease to subacute hepatitis, chronic hepatitis, and fulminant hepatitis failure, which is quite mortal. For this purpose, therapeutic plasma exchange (TPE) can be used for improving treatment outcomes by reducing the harmful substances caused with and/or without liver function in acute toxic hepatitis. We aimed to evaluate treatment outcomes in severe acute toxic hepatitis patients who applied early TPE procedure. MATERIALS AND METHODS A total of 335 patients who received TPE between 2010-2021 were retrospectively screened and 59 (male/female, 30/29; min/max-age, 22-84) patients with acute toxic hepatitis who underwent TPE in the first 24 h were included in the study. TPE was performed in patients who had high total bilirubin level (>10 mg/dL). Laboratory parameters of the patients before and after the TPE procedure, number of patients developed complications of acute toxic hepatitis and mortality rates were evaluated for effectiveness of TPE. RESULTS Acute toxic hepatitis was associated with hepatotoxic drugs in 44 (74.5 %), herbal medication 6 (10.2 %), mushroom poisoning 6 (10.2 %) and with substance abuse 3 (5.1 %) in patients. When the patients were compared based on INR, liver function tests, ammonia, lactate and Model For End-Stage Liver Disease (MELD) score at baseline, 48 h after TPE (independently of TPE number) and before final state a statistically significant decrease was observed in all parameters (p < 0.05). Fifty three (90 %) of patients improved without complications, the remaining 6 (10 %) patients were diagnosed with fulminant hepatitis. All these remaining patients died before liver transplantation (LTx) could be performed. CONCLUSION TPE is a safe, tolerable therapy option and early TPE may improve treatment outcomes in severe acute toxic hepatitis.
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Affiliation(s)
- Ilhami Berber
- Inonu University, Faculty of Medicine, Department of Hematology, Malatya, Turkey
| | - Yasir Furkan Cagin
- Inonu University, Faculty of Medicine, Department of Gastroenterology, Malatya, Turkey.
| | - Mehmet Ali Erdogan
- Inonu University, Faculty of Medicine, Department of Gastroenterology, Malatya, Turkey
| | - Engin Ataman
- Inonu University, Faculty of Medicine, Department of Gastroenterology, Malatya, Turkey
| | - Harika Gozukara
- Inonu University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, Malatya, Turkey
| | - Mehmet Ali Erkurt
- Inonu University, Faculty of Medicine, Department of Hematology, Malatya, Turkey
| | - Oguzhan Yildirim
- Inonu University, Faculty of Medicine, Department of Gastroenterology, Malatya, Turkey
| | - İrfan Kuku
- Inonu University, Faculty of Medicine, Department of Hematology, Malatya, Turkey
| | - Emin Kaya
- Inonu University, Faculty of Medicine, Department of Hematology, Malatya, Turkey
| | - Yilmaz Bilgic
- Inonu University, Faculty of Medicine, Department of Gastroenterology, Malatya, Turkey
| | - Ahmet Sarici
- Inonu University, Faculty of Medicine, Department of Hematology, Malatya, Turkey
| | - Soykan Bicim
- Inonu University, Faculty of Medicine, Department of Hematology, Malatya, Turkey
| | - Alaadin Polat
- Inonu University, Faculty of Medicine, Department of Physiology, Malatya, Turkey
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10
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Rodgers SA, Suneja A, Yoshida A, Abouljoud MS, Otrock ZK. Paradoxical embolic strokes in a liver transplant recipient with atrial septal defect undergoing therapeutic plasma exchange. J Clin Apher 2020; 36:206-210. [PMID: 33058311 DOI: 10.1002/jca.21849] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 08/28/2020] [Accepted: 10/02/2020] [Indexed: 11/06/2022]
Abstract
Therapeutic plasma exchange (TPE) is a technique used to separate blood components into layers based on their density difference, thus removing plasma and exchanging it with replacement fluids. A variety of adverse reactions has been described during TPE. Thrombotic events, especially strokes, are extremely rare complications of TPE. Our patient was a 55-year-old female with history of decompensated nonalcoholic steatohepatitis (NASH) liver cirrhosis. She underwent an orthotopic liver transplant (OLT) that was complicated with asystole during reperfusion. Cardiac workup revealed a new atrial septal defect (ASD) with left to right flow. Within the first 5 days after surgery, she developed refractory and persistent hyperbilirubinemia, with total bilirubin levels as high as 42 mg/dL. Our plasmapheresis service was consulted to initiate TPE. Towards the end of the first and only session of TPE, the patient developed hypoxia and left-sided hemiplegia. Stroke response was initiated, and the patient was intubated. MRI done 24 hours after the incident showed multiple acute small embolic infarcts scattered within the bilateral cerebral and cerebellar hemispheres. Bilateral lower and upper extremities venous duplex studies were positive for acute left internal jugular (IJ) vein thrombosis. Patient was treated with anticoagulation and the IJ catheter was removed. Patient also had closure of her ASD. On last follow up, she was doing well with complete reversal of neurologic deficits and stable liver function. Our patient had an uncommon complication of TPE. Her thrombosis manifested with multiple embolic strokes that would not have happened without an ASD with left to right flow.
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Affiliation(s)
- Shannon A Rodgers
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA
| | - Aarushi Suneja
- Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA
| | - Atsushi Yoshida
- Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, Michigan, USA
| | - Marwan S Abouljoud
- Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA
| | - Zaher K Otrock
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA
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11
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Yao S, Kaido T, Yagi S, Uozumi R, Iwamura S, Miyachi Y, Shirai H, Kamo N, Taura K, Okajima H, Uemoto S. Impact of imbalanced graft-to-spleen volume ratio on outcomes following living donor liver transplantation in an era when simultaneous splenectomy is not typically indicated. Am J Transplant 2019; 19:2783-2794. [PMID: 30830721 DOI: 10.1111/ajt.15337] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 02/04/2019] [Accepted: 02/19/2019] [Indexed: 02/06/2023]
Abstract
The impact of an imbalanced graft-to-spleen volume ratio (GSVR) on posttransplant outcomes other than postreperfusion portal hypertension remains unknown. The importance of GSVR might vary according to whether simultaneous splenectomy (SPX) is performed. This retrospective study divided 349 living donor liver transplantation (LDLT) recipients from 2006 to 2017 into 2 groups: low GSVR (≤0.70 g/mL) and normal GSVR (>0.70 g/mL). The cutoff value of GSVR was set based on the first quartile of the distributed data. Graft survival and associations with various clinical factors were investigated between the groups according to whether SPX was performed. Low GSVR did not affect outcomes when SPX was performed. In contrast, it was associated with an increased incidence of early graft loss (EGL) and poor graft survival by presenting posttransplant thrombocytopenia, cholestasis, coagulopathy, and massive ascites when the spleen was preserved. Among patients with a preserved spleen, the multivariable analysis results revealed that older donor age and low GSVR were independent risk factors for graft loss. In conclusion, low GSVR was an independent predictor of graft loss after LDLT when the spleen was preserved. Preserved spleen with extremely low GSVR may be related to persistent hypersplenism, impaired graft function, and consequent EGL.
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Affiliation(s)
- Siyuan Yao
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ryuji Uozumi
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Sena Iwamura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yosuke Miyachi
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hisaya Shirai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naoko Kamo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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12
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Yang J, Yang L, Wu L, Zhao Q, Chen M, He X. Efficacy and Safety of Steroid Therapy for Posttransplant Hyperbilirubinemia Caused by Early Allograft Dysfunction: A Randomized Controlled Trial. Med Sci Monit 2019; 25:1936-1944. [PMID: 30870403 PMCID: PMC6429985 DOI: 10.12659/msm.915128] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Hyperbilirubinemia is a common event that occurs after liver transplantation. Hyperbilirubinemia is usually caused by early allograft dysfunction. Glucocorticoid is widely used for immunosuppression, but few studies have analyzed the effects of steroid therapy on posttransplantation hyperbilirubinemia. The aim of this study was to assess whether glucocorticoid was beneficial in treating hyperbilirubinemia caused by early allograft dysfunction. MATERIAL AND METHODS Patients with postoperative hyperbilirubinemia (those with conditions such as biliary complications and rejections were excluded) were randomly assigned, in a 2: 1 ratio, to the steroid and control groups. Patients in the steroid group were treated with glucocorticoid combined with ursodeoxycholic acid, whereas patients in the control group were only treated with ursodeoxycholic acid. The primary endpoint was decrease in bilirubin and the secondary endpoint was safety. RESULTS From 1st June 2016 to 30th April 2018, 40 patients were enrolled into the steroid group, and 20 were enrolled into the control group. Donor, recipient, and operative data were similar between the 2 groups. The decrease in bilirubin levels in the steroid group was significantly greater than that in the control group on the first day after the intervention was finished (9.25±1.30 mg/dL vs. 3.11±1.45 mg/dL, p=0.005), and after 2 weeks (15.01±1.20 mg/dL vs. 8.88±1.98 mg/dL, p=0.007). The steroid group did not have a higher complication rate but it did have a shorter postoperative hospital stay than in the control group. CONCLUSIONS Low-dose steroid therapy was effective and safe for treating hyperbilirubinemia caused by early graft dysfunction, and it improved liver function.
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Affiliation(s)
- Jie Yang
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Lei Yang
- Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland)
| | - Linwei Wu
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Qiang Zhao
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Maogen Chen
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
| | - Xiaoshun He
- Department of Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).,Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, Guangdong, China (mainland)
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13
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Marubashi S, Ichihara N, Kakeji Y, Miyata H, Taketomi A, Egawa H, Takada Y, Umeshita K, Seto Y, Gotoh M. "Real-time" risk models of postoperative morbidity and mortality for liver transplants. Ann Gastroenterol Surg 2019; 3:75-95. [PMID: 30697613 PMCID: PMC6345648 DOI: 10.1002/ags3.12217] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 08/28/2018] [Accepted: 09/14/2018] [Indexed: 12/23/2022] Open
Abstract
AIM A comprehensive description of morbidity and mortality risk factors for post liver transplant has not been available to date. In this study, we established real-time risk models of postoperative morbidities and mortality in liver transplant recipients using two Japanese nationwide databases. METHODS Data from two Japanese nationwide databases were combined and used for this study. We developed real-time prognostic models for morbidity and mortality from a derivation cohort (n = 1472) and validated the findings with an independent cohort (n = 395). Preoperative variables (C1), preoperative and intraoperative variables (C2), and all variables including postoperative morbidities within 30 days (C3) were analyzed to evaluate the independent risk factors for postoperative morbidity and mortality. RESULTS We established real-time risk models for morbidity and mortality. Areas under the curve (AUC) of C1 and C2 risk models for mortality were 0.74 (0.63-0.82) and 0.79 (0.69-0.86), respectively. Multivariate logistic analysis using C3 showed that hemoglobin <10 g/dL, operative time (hours), and five postoperative morbidities (prolonged ventilation >48 hours, coma >24 hours, renal dysfunction, postoperative systemic sepsis, and serum total bilirubin ≥10 mg/dL) represented independent risk factors for mortality (AUC = 0.87, 95% confidence interval [CI]: 0.78-0.93). CONCLUSIONS Real-time risk models of postoperative morbidities and mortality at various perioperative time points in liver transplant recipients were established. These novel approaches may improve postoperative outcomes of liver transplant recipients. Furthermore, these real-time risk models may be applicable to other surgical procedures.
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Affiliation(s)
- Shigeru Marubashi
- Database Committee of Japanese Society of Gastroenterological SurgeryTokyoJapan
| | | | - Yoshihiro Kakeji
- Database Committee of Japanese Society of Gastroenterological SurgeryTokyoJapan
| | | | - Akinobu Taketomi
- Database Committee of Japanese Society of Gastroenterological SurgeryTokyoJapan
| | | | - Yasutsugu Takada
- Japanese Liver Transplant SocietyTokyoJapan
- Japanese Society of Hepato‐Biliary‐Pancreatic SurgeryTokyoJapan
| | | | - Yasuyuki Seto
- Japanese Society of Gastroenterological SurgeryTokyoJapan
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14
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Kao TL, Chen YL, Kuan YP, Chang WC, Ho YC, Yeh S, Jeng LB, Ma WL. Estrogen-Estrogen Receptor α Signaling Facilitates Bilirubin Metabolism in Regenerating Liver Through Regulating Cytochrome P450 2A6 Expression. Cell Transplant 2018; 26:1822-1829. [PMID: 29338386 PMCID: PMC5784527 DOI: 10.1177/0963689717738258] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND After living donor liver transplantation (LDLT), rising serum bilirubin levels commonly indicate insufficient numbers of hepatocytes are available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450 (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as "bilirubin oxidase." Functional hepatocytes contain abundant CYP2A6, which is considered a marker for hepatocyte function recovery. The aim of our study was to determine the impact of estradiol/estrogen receptor signaling on bilirubin levels during liver function recovery. METHODS We conducted a hospital-based cohort study of bilirubin levels after LDLT surgery in both liver graft donors and recipients, performed a transcriptome comparison of wild-type versus estrogen receptor (ER)α knockout mice and a bioinformatics analysis of transcriptome changes in their regenerating liver after two-third partial hepatectomy (PHx), and assayed in vitro expression of cytochrome (CYP2A6) in human hepatic progenitor cells (HepRG) treated with 17β-estradiol (E2). RESULTS The latency of bilirubin level reduction was shorter in women than in men, suggesting that a female factor promotes bilirubin recovery after liver transplantation surgery. In the PHx mouse model, the expression of the cyp2a4 gene was significantly lower in livers from the knockout ERα mice than in livers from their wild-type littermates; but the expression of other bilirubin metabolism-related genes were similar between these groups. Moreover, E2 or bilirubin treatments significantly promoted CYP2A6 expression in hepatocyte progenitor cells (HepRG cells). Sequence analysis revealed similar levels of aryl hydrocarbon receptor (AhR; bilirubin responsive nuclear receptor) and ESR1 binding to the promoter region of CYP2A6. CONCLUSIONS This is the first report to demonstrate, on a molecular level, that E2/ERα signaling facilitates bilirubin metabolism in regenerating liver. Our findings contribute new knowledge to our understanding of why the latency of improved bilirubin metabolism and thereby liver function recovery is shorter in females than in males.
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Affiliation(s)
- Ta-Lun Kao
- 1 Graduate Institution of Clinical Medical Science and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,2 Department of Trauma and Critical Care, Changhua Christian Hospital, Changhua, Taiwan
| | - Yao-Li Chen
- 3 Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Yu-Ping Kuan
- 4 Department of Obstetrics and Gynecology, Sex Hormone Research Center, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Wei-Chun Chang
- 4 Department of Obstetrics and Gynecology, Sex Hormone Research Center, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Chen Ho
- 1 Graduate Institution of Clinical Medical Science and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,4 Department of Obstetrics and Gynecology, Sex Hormone Research Center, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Shuyuan Yeh
- 5 Department of Urology, University of Rochester Medical Center, Rochester, NY, USA
| | - Long-Bin Jeng
- 1 Graduate Institution of Clinical Medical Science and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,4 Department of Obstetrics and Gynecology, Sex Hormone Research Center, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Lung Ma
- 1 Graduate Institution of Clinical Medical Science and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,4 Department of Obstetrics and Gynecology, Sex Hormone Research Center, Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan.,6 Department of Nursing, Asia University, Taichung, Taiwan
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15
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Coexistence of Bilirubin ≥10 mg/dL and Prothrombin Time-International Normalized Ratio ≥1.6 on Day 7: A Strong Predictor of Early Graft Loss After Living Donor Liver Transplantation. Transplantation 2018; 102:440-447. [PMID: 28968350 DOI: 10.1097/tp.0000000000001959] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Early allograft dysfunction (EAD) defined by serum total bilirubin (TB) of 10 mg/dL or greater or prothrombin time-international normalized ratio (PT-INR) of 1.6 or greater on postoperative day 7 (POD 7) or aminotransferase greater than 2000 IU/L within the first week, is associated with early graft loss after deceased-donor liver transplantation. We aimed to determine the prognostic impact of the EAD definition in living-donor liver transplantation (LDLT). METHODS We analyzed the validity of the EAD definition and its impact on early graft survival in 260 adult recipients who underwent primary LDLT. RESULTS Eighty-four (32.3%) patients met the EAD criteria; 59 (22.7%) and 46 (17.7%) patients had TB of 10 mg/dL or greater and PT-INR of 1.6 or greater on POD 7, respectively, and 22 (8.5%) patients satisfied both criteria. Graft survival differed significantly when stratified according to TB of 10 mg/dL or greater and PT-INR of 1.6 or greater (P < 0.0001). PT-INR of 1.6 or greater resulted in higher graft mortality (risk ratio [RR], 3.87; P < 0.0001 at 90 days; RR, 2.97; P < 0.0001 at 180 days), as did TB of 10 mg/dL or greater (RR, 1.89; P = 0.027 at 90 days; RR, 1.91; P = 0.006 at 180 days). Coexistence of TB of 10 mg/dL or greater and PT-INR of 1.6 or greater was strongly associated with early graft loss (59.1%, RR, 6.97 at 90 days; 68.2%; RR, 5.75 at 180 days). In Cox regression analysis, PT-INR of 1.6 or greater and TB of 10 mg/dL or greater on POD 7 were significant risk factors for early graft loss (hazard ratio, 4.10; 95% confidence interval, 2.35-7.18; P < 0.0001, and hazard ratio, 2.43; 95% confidence interval, 1.39-4.24; P = 0.0018, respectively). CONCLUSIONS TB of 10 mg/dL or greater and/or PT-INR of 1.6 or greater on POD 7 predicted early graft loss after LDLT, and their coexistence worsened patient outcomes.
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16
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Increasing use of therapeutic apheresis as a liver-saving modality. Transfus Apher Sci 2017; 56:385-388. [PMID: 28366590 DOI: 10.1016/j.transci.2017.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Revised: 03/02/2017] [Accepted: 03/02/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Therapeutic plasma exchange (TPE) is used for temporary support of liver function in patients presenting with early graft dysfunction after liver transplantation (LT) or liver surgery. We analyzed the effect of therapeutic apheresis on patients with liver disease. METHODS Between January 2011 and August 2016, 93 apheresis procedures were performed for 26 patients at our institution. Anti-ABO isoagglutination immunoglobulin (Ig) M titer was checked using a type A and type B 3% red blood cell (RBC) suspension in saline with two-fold serial dilutions of patient serum. Anti-ABO isoagglutination IgG titer was checked by a type A and B 0.8% RBC suspension using a low-ionic strength/Coombs card. RESULTS ABO-incompatible (ABOi) LT was the most common (n=10, 38.5%) indication for apheresis; early graft dysfunction after LT (n=8, 30.7%) was the second most common. Median initial IgM and IgG anti-ABO titers for ABOi LT recipients were 1:16 (range, 1:8-1:128) and 1:48 (range, 1:8-1:2048). We performed preoperative TPE in 10 recipients (median number of sessions, 1.5; range, 1-11). Among patients with early graft dysfunction, those who underwent living donor LT had better survival (4/4; 100%) than those who underwent nonliving donor LT (0/3; 0%). Patients who underwent living donor LT first and then additional LT also survived after three TPE sessions. CONCLUSION Therapeutic apheresis is associated with a good survival rate and is essential for liver support in patients with early graft dysfunction after LT or posthepatectomy liver failure and during preparation for ABOi LT.
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17
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Choe W, Kwon SW, Kim SS, Hwang S, Song GW, Lee SG. Effects of therapeutic plasma exchange on early allograft dysfunction after liver transplantation. J Clin Apher 2016; 32:147-153. [PMID: 27306278 DOI: 10.1002/jca.21472] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 03/14/2016] [Accepted: 04/21/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Early allograft dysfunction (EAD) is a serious complication of liver transplantation (LT) and is associated with graft failure, which can result in patient mortality. Due to the shortage of organs for retransplantation, only a small proportion of EAD patients undergo retransplantation. Thus, liver support is needed for most patients with EAD. METHODS We evaluated the effects of therapeutic plasma exchange (TPE) in EAD patients. EAD was defined as a sustained hyperbilirubinemia (≥10 mg/dL) within 30 days of LT without concurrent biliary complications. In a 13-year period, 107 EAD patients underwent TPE while 36 EAD patients did not. We investigated the laboratory and clinical outcomes of TPE and non-TPE groups. RESULTS The TPE group showed 1-month and 1-year survival rates of 82.2% and 53.8%, respectively, whereas the non-TPE group showed 58.3% and 22.2%, respectively. In TPE group, statistically significant decreases (P < 0.05) in total bilirubin (15.2 ± 5.2 to 13.1 ± 5.4 mg/dL), and INR (1.72 ± 1.04 to 1.38 ± 1.14), were seen after the final TPE session. TPE responder groups with age <51 years, total bilirubin <11.1 mg/dL, or INR <1.15 after final TPE showed better prognosis. TPE decreased the hazard risk of death in EAD patients whereas older age, male gender, and higher INR on the day of EAD onset increased the risk. CONCLUSIONS TPE effectively removed plasma bilirubin and improved coagulation function in EAD patients, with higher survival in the TPE group than in the non-TPE group. TPE may be an effective liver support for EAD patients. J. Clin. Apheresis 32:147-153, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Wonho Choe
- Department of Laboratory Medicine, Eulji University School of Medicine, Seoul, Korea.,Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seog-Woon Kwon
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Soo Kim
- Departmnt of Healthcare Management, Cheongju University College of Health Science, Cheongju, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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18
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Marubashi S, Nagano H, Eguchi H, Wada H, Asaoka T, Tomimaru Y, Tomokuni A, Umeshita K, Doki Y, Mori M. Minimum graft size calculated from preoperative recipient status in living donor liver transplantation. Liver Transpl 2016; 22:599-606. [PMID: 26684397 DOI: 10.1002/lt.24388] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 11/10/2015] [Accepted: 12/01/2015] [Indexed: 02/07/2023]
Abstract
Small-for-size graft syndrome is an inevitable complication in living donor liver transplantation (LDLT). We hypothesized that graft weight (GW) measured after graft procurement is one of the variables predicting postoperative graft function. A total of 138 consecutive recipients of adult-to-adult LDLT between March 1999 and October 2014 were included in this study. We investigated the factors associated with small-for-size-associated graft loss (SAGL) to determine the GW required for each patient. Both preoperatively assessed and postoperatively obtained risk factors for SAGL were analyzed in univariate and multivariate logistic regression analysis. Twelve (8.8%) of the transplant recipients had SAGL. In multivariate logistic regression analyses using preoperatively assessed variables, the preoperative Model for End-Stage Liver Disease (MELD) score (P < 0.001) and actual GW/recipient standard liver volume (SLV) ratio (P = 0.008) were independent predictors of SAGL. The recommended graft volume by preoperative computed tomography volumetry was calculated as SLV × (1.616 × MELD + 0.344)/100/0.85 (mL) [MELD ≥ 18.2], or SLV × 0.35 (mL) [MELD < 18.2]. The required allograft volume in LDLT can be determined by the preoperative MELD score of the recipient, and patients with higher MELD scores require larger grafts or deceased donor whole liver transplant to avoid SAGL. Liver Transplantation 22 599-606 2016 AASLD.
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Affiliation(s)
- Shigeru Marubashi
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hiroaki Nagano
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Hiroshi Wada
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Tadafumi Asaoka
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yoshito Tomimaru
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Akira Tomokuni
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Koji Umeshita
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Yuichiro Doki
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
| | - Masaki Mori
- Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
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19
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Wiesen P, Massion PB, Joris J, Detry O, Damas P. Incidence and risk factors for early renal dysfunction after liver transplantation. World J Transplant 2016; 6:220-232. [PMID: 27011921 PMCID: PMC4801799 DOI: 10.5500/wjt.v6.i1.220] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 10/20/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine renal dysfunction post liver transplantation, its incidence and risk factors in patients from a Belgian University Hospital.
METHODS: Orthotopic liver transplantations performed from January 2006 until September 2012 were retrospectively reviewed (n = 187). Patients with no renal replacement therapy (RRT) before transplantation were classified into four groups according to their highest creatinine plasma level during the first postoperative week. The first group had a peak creatinine level below 12 mg/L, the second group between 12 and 20 mg/L, the third group between 20 and 35 mg/L, and the fourth above 35 mg/L. In addition, patients who needed RRT during the first week after transplantation were also classified into the fourth group. Perioperative parameters were recorded as risk factors, namely age, sex, body mass index (BMI), length of preoperative hospital stay, prior bacterial infection within one month, preoperative ascites, preoperative treatment with β-blocker, angiotensin-converting enzyme inhibitor or non steroidal anti-inflammatory drugs, preoperative creatinine and bilirubin levels, donor status (cardiac death or brain death), postoperative lactate level, need for intraoperative vasopressive drugs, surgical revision, mechanical ventilation for more than 24 h, postoperative bilirubin and transaminase peak levels, postoperative hemoglobin level, amount of perioperative blood transfusions and type of immunosuppression. Univariate and multivariate analysis were performed using logistic ordinal regression method. Post hoc analysis of the hemostatic agent used was also done.
RESULTS: There were 78 patients in group 1 (41.7%), 46 in group 2 (24.6%), 38 in group 3 (20.3%) and 25 in group 4 (13.4%). Twenty patients required RRT: 13 (7%) during the first week after transplantation. Using univariate analysis, the severity of renal dysfunction was correlated with presence of ascites and prior bacterial infection, preoperative bilirubin, urea and creatinine level, need for surgical revision, use of vasopressor, postoperative mechanical ventilation, postoperative bilirubin and urea, aspartate aminotransferase (ASAT), and hemoglobin levels and the need for transfusion. The multivariate analysis showed that BMI (OR = 1.1, P = 0.004), preoperative creatinine level (OR = 11.1, P < 0.0001), use of vasopressor (OR = 3.31, P = 0.0002), maximal postoperative bilirubin level (OR = 1.44, P = 0.044) and minimal postoperative hemoglobin level (OR = 0.059, P = 0.0005) were independent predictors of early post-liver transplantation renal dysfunction. Neither donor status nor ASAT levels had significant impact on early postoperative renal dysfunction in multivariate analysis. Absence of renal dysfunction (group 1) was also predicted by the intraoperative hemostatic agent used, independently of the extent of bleeding and of the preoperative creatinine level.
CONCLUSION: More than half of receivers experienced some degree of early renal dysfunction after liver transplantation. Main predictors were preoperative renal dysfunction, postoperative anemia and vasopressor requirement.
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Du Z, Wei Y, Chen K, Chen X, Zhang Z, Li H, Ma Y, Li B. Risk factors and criteria predicting early graft loss after adult-to-adult living donor liver transplantation. J Surg Res 2014; 187:673-82. [DOI: 10.1016/j.jss.2013.10.048] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 10/08/2013] [Accepted: 10/24/2013] [Indexed: 12/11/2022]
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The outcomes of patients with severe hyperbilirubinemia following living donor liver transplantation. Dig Dis Sci 2013; 58:1410-4. [PMID: 23314852 DOI: 10.1007/s10620-012-2519-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2012] [Accepted: 12/03/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Prolonged hyperbilirubinemia (HB) following living donor liver transplantation (LDLT) can be a risk factor for early graft loss and mortality. However, some recipients who present with postoperative hyperbilirubinemia do recover and maintain a good liver function. AIM The purpose of this study was to investigate the risk factors for hyperbilirubinemia following LDLT and to identify predictors of the outcomes in patients with post-transplant hyperbilirubinemia. METHODS A total of 107 consecutive adults who underwent LDLT in Nagasaki University Hospital were investigated retrospectively. The patients were divided into two groups according to postoperative peak serum bilirubin level (HB group: ≥ 30 mg/dl; non-HB group: <30 mg/dl). These two groups of patients and the prognosis of patients in the HB group were analyzed using several parameters. RESULTS Seventeen patients (15.9 %) presented with hyperbilirubinemia, and their overall survival was significantly worse than patients in the non-HB group (n = 90). Donor age was significantly higher in the HB group (P < 0.05). Of the 17 patients in the HB group, nine survived. The postoperative serum prothrombin level at the time when the serum bilirubin level was >30 mg/dl was significantly higher in surviving patients (P < 0.01). CONCLUSIONS The use of a partial liver graft from an aged donor is a significant risk factor for severe hyperbilirubinemia and a poorer outcome. However, those patients who maintain their liver synthetic function while suffering from hyperbilirubinemia may recover from hyperbilirubinemia and eventually achieve good liver function, thus resulting in a favorable survival.
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Ikegami T, Shirabe K, Yoshizumi T, Aishima S, Taketomi YA, Soejima Y, Uchiyama H, Kayashima H, Toshima T, Maehara Y. Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia. Am J Transplant 2012; 12:1886-97. [PMID: 22494784 DOI: 10.1111/j.1600-6143.2012.04052.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The purpose of this study is to propose a new concept of primary graft dysfunction (PGD) after living donor liver transplantation (LDLT), characterized by delayed functional hyperbilirubinemia (DFH) and a high early graft mortality rate. A total of 210 adult-to-adult LDLT grafts without anatomical, immunological or hepatitis-related issues were included. All of the grafts with early mortality (n = 13) caused by PGD in LDLT had maximum total bilirubin levels >20 mg/dL after postoperative day 7 (p < 0.001). No other factors, including prothrombin time, ammonia level or ascites output after surgery were associated with early mortality. Thus, DFH of >20 mg/dL for >seven consecutive days occurring after postoperative day 7 (DFH-20) was used to characterize PGD. DFH-20 showed high sensitivity (100%) and specificity (95.4%) for PGD with early mortality. Among the grafts with DFH-20 (n = 22), those with early mortality (n = 13) showed coagulopathy (PT-INR > 2), compared with those without mortality (p = 0.002). Pathological findings in the grafts with DFH-20 included hepatocyte ballooning and cholestasis, which were particularly prominent in the centrilobular zone. PGD after LDLT is associated with DFH-20 caused by graft, recipient and surgical factors, and increases the risk of early graft mortality.
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Affiliation(s)
- T Ikegami
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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Chen W, Liang L, Ma T, Li J, Xu G, Zhang Y, Bai X, Liang T. Role of hepatic stellate cells on graft injury after small-for-size liver transplantation. J Gastroenterol Hepatol 2011; 26:1659-1668. [PMID: 21592229 DOI: 10.1111/j.1440-1746.2011.06781.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Small-for-size grafts are prone to mechanical injury and a series of chemical injuries that are related to hemodynamic force. Hepatic stellate cells activate and trans-differentiate into contractile myofibroblast-like cells during liver injury. However, the role of hepatic stellate cells on sinusoidal microcirculation is unknown with small-for-size grafts. METHODS Thirty-five percent of small-for-size liver transplantation was performed with rats as donors and recipients. Endothelin-1 levels as well as hepatic stellate cells activation-related protein expression, endothelin-1 receptors, and ultrastructural changes were examined. The cellular localizations of two types of endothelin-1 receptors were detected. Furthermore, liver function and sinusoidal microcirculation were analyzed using two different selective antagonists of endothelin-1 receptor. RESULTS Intragraft expression of hepatic stellate cells activation-related protein such as desmin, crystallin-B and smooth muscle α-actin was upregulated as well as serum endothelin-1 levels and intragraft expression of the two endothelin receptors. The antagonist to endothelin-1 A receptor not to the endothelin-1 B receptor could attenuate microcirculatory disturbance and improve liver function. CONCLUSIONS Small-for-size liver transplantation displayed increased hepatic stellate cells activation and high level of endothelin-1 binding to upregulation of endothelin-1 A receptor on hepatic stellate cells, which contracted hepatic sinusoid inducing graft injury manifested as reduction of sinusoidal perfusion rate and elevation of sinusoidal blood flow.
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Affiliation(s)
- Wei Chen
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Current world literature. Curr Opin Organ Transplant 2009; 14:211-7. [PMID: 19307967 DOI: 10.1097/mot.0b013e32832ad721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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