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Intraoperative dialysis with the use of a mobile dialysis system during liver transplantation. Adv Med Sci 2022; 67:208-215. [PMID: 35568010 DOI: 10.1016/j.advms.2022.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 03/22/2022] [Accepted: 04/29/2022] [Indexed: 11/23/2022]
Abstract
PURPOSE Over the last few years, transplant centers have started to use various intraoperative renal replacement therapy (ioRRT) modalities during liver transplantation (LT) in patients with pre-existing renal impairment. Here, we present a study on the safety and clinical outcomes of intraoperative hemodialysis (ioHD) performed using a mobile dialysis system during LT. PATIENTS AND METHODS We retrospectively analyzed 102 adult patients undergoing LT with ioHD; pre-existing renal failure and/or intraoperative metabolic derangement were ioHD treatment indications. RESULTS Our study cohort consisted of three groups: LT with preoperative serum creatinine (sCr) < 2 mg/dL (Group 1:n = 22), LT with preoperative sCr ≥2 mg/dL (Group 2:n = 73), and simultaneous liver-kidney transplantation (Group 3:n = 7). Among the procedures, 30% were re-transplantations. The mean calculated Model for End-stage Liver Disease score in Group 2 was 39.2, and 67% of patients were hospitalized in the intensive care unit. Patients in Group 1 were less acutely ill but developed severe intraoperative derangements and, therefore, underwent urgent ioHD intraoperatively. However, it was delayed when compared to Group 2. All groups achieved post-reperfusion potassium levels <4 mmol/L and a decrease in central venous pressure. No serious procedural complications occurred. Post-reperfusion syndrome occurred in 12.7% of patients. Elevated mortality was likely due to the high illness severity in the cohort. CONCLUSIONS Performing ioHD with a mobile dialysis system during LT was safe and effective, while being easier to perform than continuous techniques. Its effect on intra- and postoperative outcomes should be addressed in a study with a control group.
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2
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Outcomes of Adult Liver Retransplantation: A Canadian National Database Analysis. Can J Gastroenterol Hepatol 2022; 2022:9932631. [PMID: 35360444 PMCID: PMC8964213 DOI: 10.1155/2022/9932631] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 02/12/2022] [Accepted: 02/16/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Liver retransplantation remains as the only treatment for graft failure. This investigation aims to assess the incidence, post-transplant outcomes, and risk factors in liver retransplantation recipients in Canada. MATERIALS AND METHODS The Canadian Organ Replacement Register was used to obtain and analyse data on all adult liver retransplant recipients, matched donors, transplant-specific variables, and post-transplant outcomes from January 2000 to December 2018. RESULTS 377 (6.5%) patients underwent liver retransplantation. Autoimmune liver disease and hepatitis C virus (HCV) were the most common underlying diagnoses. Graft failure was 7.9% and 12.5%, and overall survival was 77.1% and 65.6% at 1 year and 5 years, respectively. In contrast to recipients receiving their first graft transplant, the retransplantation group had a significantly higher incidence of graft failure (p < 0.001) and lower overall survival (p < 0.001). The graft failure and patient survival rates were comparable between second transplant and repeat retransplant recipients. Furthermore, there were no differences in graft failure and patient survival when stratified according to time to retransplantation. Recipient and donor age (HR = 1.12, p=0.011; HR = 1.09, p=0.008), recipient HCV status (HR = 1.81, p=0.014), and donor cytomegalovirus status (HR = 4.10, p=0.006) were predictors of patient mortality. CONCLUSION This analysis of liver retransplantation demonstrates that this is a safe treatment for early and late graft failure. Furthermore, even in patients requiring more than two grafts, similar outcomes to initial retransplantation can be achieved with careful selection.
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3
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Oh SY, Jang EJ, Kim GH, Lee H, Yi NJ, Yoo S, Kim BR, Ryu HG. Association between hospital liver transplantation volume and mortality after liver re-transplantation. PLoS One 2021; 16:e0255655. [PMID: 34351979 PMCID: PMC8341477 DOI: 10.1371/journal.pone.0255655] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 07/21/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The relationship between institutional liver transplantation (LT) case volume and clinical outcomes after liver re-transplantation is yet to be determined. METHODS Patients who underwent liver re-transplantation between 2007 and 2016 were selected from the Korean National Healthcare Insurance Service database. Liver transplant centers were categorized to either high-volume centers (≥ 64 LTs/year) or low-volume centers (< 64 LTs/year) according to the annual LT case volume. In-hospital and long-term mortality after liver re-transplantation were compared. RESULTS A total of 258 liver re-transplantations were performed during the study period: 175 liver re-transplantations were performed in 3 high-volume centers and 83 were performed in 21 low-volume centers. In-hospital mortality after liver re-transplantation in high and low-volume centers were 25% and 36% (P = 0.069), respectively. Adjusted in-hospital mortality was not different between low and high-volume centers. Adjusted 1-year mortality was significantly higher in low-volume centers (OR 2.14, 95% CI 1.05-4.37, P = 0.037) compared to high-volume centers. Long-term survival for up to 9 years was also superior in high-volume centers (P = 0.005). Other risk factors of in-hospital mortality and 1-year mortality included female sex and higher Elixhauser comorbidity index. CONCLUSION Centers with higher case volume (≥ 64 LTs/year) showed lower in-hospital and overall mortality after liver re-transplantation compared to low-volume centers.
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Affiliation(s)
- Seung-Young Oh
- Critical Care Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Eun Jin Jang
- Department of Information Statistics, Andong National University, Gyeongsangbuk-do, Korea
| | - Ga Hee Kim
- Department of Statistics, Kyungpook National University, Daegu, Korea
| | - Hannah Lee
- Critical Care Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Seokha Yoo
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Bo Rim Kim
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Ho Geol Ryu
- Critical Care Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
- * E-mail:
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4
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Current management & future directions in post-liver transplant recurrence of viral hepatitis. JOURNAL OF LIVER TRANSPLANTATION 2021. [DOI: 10.1016/j.liver.2021.100027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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5
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Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol 2020; 46-47:101689. [PMID: 33158469 PMCID: PMC7519014 DOI: 10.1016/j.bpg.2020.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]
Abstract
Survival following liver transplantation has changed dramatically owing to improvement in surgical techniques, peri-operative care and optimal immunosuppressive therapy. Post-Liver transplant (LT) de novo or recurrent viral infection continues to cause major allograft dysfunction, leading to poor graft and patient survival in untreated patients. Availability of highly effective antiviral drugs has significantly improved post-LT survival. Patients transplanted for chronic hepatitis B infection should receive life-long nucleos(t)ide analogues, with or without HBIg for effective viral control. Patients with chronic hepatitis C should be commenced on directly acting antiviral (DAA) drugs prior to transplantation. DAA therapy for post-LT recurrent hepatitis C infection is associated with close to 100% sustained virological response (SVR), irrespective of genotype. De novo chronic Hepatitis E infection is an increasingly recognised cause of allograft dysfunction in LT recipients. Untreated chronic HEV infection of the graft may lead to liver fibrosis and allograft failure. CMV and EBV can reactivate leading to systemic illness following liver transplantation. With COVID-19 pandemic, post-transplant patients are at risk of SARS-Co-V2 infection. Majority of the LT recipients require hospitalization, and the mortality in this population is around 20%. Early recognition of allograft dysfunction and identification of viral aetiology is essential in the management of post-LT de novo or recurrent infections. Optimising immunosuppression is an important step in reducing the severity of allograft damage in the treatment of post-transplant viral infections. Viral clearance or control can be achieved by early initiation of high potency antiviral therapy.
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Affiliation(s)
- Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.
| | - Radhika Venugopal
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mukul Vij
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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6
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Tronina O, Ślubowska K, Mikołajczyk-Korniak N, Komuda-Leszek E, Wieczorek-Godlewska R, Łągiewska B, Pacholczyk M, Lisik W, Kosieradzki M, Durlik M. Fibrosing Cholestatic Hepatitis C After Liver Transplantation: Therapeutic Options Before and After Introduction of Direct-Acting Antivirals: Our Experience and Literature Review. Transplant Proc 2018; 49:1409-1418. [PMID: 28736015 DOI: 10.1016/j.transproceed.2017.01.077] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 01/24/2017] [Indexed: 12/26/2022]
Abstract
BACKGROUND Cirrhosis caused by hepatitis C is the most common indication for liver transplantation. The most aggressive form of hepatitis C virus (HCV) relapse after liver transplantation is fibrosing cholestatic hepatitis C, which can be observed in 2% to 15% of recipients. METHODS Double therapy with peg-interferon and ribavirin was characterized by low antiviral response, rapid fibrosis, and frequent graft failure within 1 year after surgery. RESULTS Introduction of direct-acting antivirals for HCV treatment allows for more efficient therapy with less adverse reactions, including patients with fibrosing cholestatic hepatitis C. CONCLUSIONS We present 4 (2.5%) cases of cholestatic viral hepatitis C recurrence in patients undergoing transplantation between 2006 and 2015 at the Transplantation Institute of Warsaw; during this period, 158 liver transplants were performed in patients with cirrhosis caused by HCV infection.
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Affiliation(s)
- O Tronina
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
| | - K Ślubowska
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - N Mikołajczyk-Korniak
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - E Komuda-Leszek
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - R Wieczorek-Godlewska
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
| | - B Łągiewska
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Pacholczyk
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - W Lisik
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Kosieradzki
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
| | - M Durlik
- Department of Transplantation Medicine, Nephrology, and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
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7
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International Liver Transplantation Society Consensus Statement on Hepatitis C Management in Liver Transplant Recipients. Transplantation 2018; 101:956-967. [PMID: 28437388 DOI: 10.1097/tp.0000000000001704] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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8
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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9
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Cholankeril G, Yoo ER, Hu M, Gadiparthi C, Khan MA, Perumpail RB, Bonham CA, Ahmed A. Rates of liver retransplantation in the United States are declining in the era of direct-acting antiviral agents. J Viral Hepat 2017; 24:1194-1195. [PMID: 28685914 DOI: 10.1111/jvh.12750] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Accepted: 05/30/2017] [Indexed: 12/09/2022]
Affiliation(s)
- G Cholankeril
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - E R Yoo
- Department of Medicine, University of Illinois College of Medicine, Chicago, IL, USA
| | - M Hu
- Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA
| | - C Gadiparthi
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - M A Khan
- Division of Gastroenterology and Hepatology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - R B Perumpail
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - C A Bonham
- Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - A Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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10
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Abstract
Hepatic retransplantation has been surgically challenging since the beginning of liver transplant. Outcomes have improved over time, but patient survival with retransplant continues to be significantly worse than that of primary transplant. Many studies have focused on factors to predict outcomes. Models have been developed to help predict risk, but the decision for retransplant must be a multidisciplinary transplant team decision. The question of "when is too much?" can be guided by recipient and donor factors but is an ethical decision that must be made by the liver transplant team.
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Affiliation(s)
- Jennifer Berumen
- Department of Abdominal Transplantation and Hepatobiliary Surgery, University of California, San Diego, La Jolla, CA 92037, USA.
| | - Alan Hemming
- Department of Abdominal Transplantation and Hepatobiliary Surgery, University of California, San Diego, La Jolla, CA 92037, USA
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11
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Jesudian A, Desale S, Julia J, Landry E, Maxwell C, Kallakury B, Laurin J, Shetty K. Donor Factors Including Donor Risk Index Predict Fibrosis Progression, Allograft Loss, and Patient Survival following Liver Transplantation for Hepatitis C Virus. J Clin Exp Hepatol 2016; 6:109-14. [PMID: 27493458 PMCID: PMC4963323 DOI: 10.1016/j.jceh.2015.10.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 10/26/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The utilization of liver transplantation (LT) is limited by the availability of suitable organs. This study aimed to assess the impact of the donor risk index (DRI) and other donor characteristics on fibrosis progression, graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients. METHODS HCV-infected LT recipients who had at least 2 post-LT protocol liver biopsy specimens available were included. Hazard ratio for bivariate analysis was computed using Cox proportional hazard regression analysis. RESULTS Of 312 recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5-67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was significantly associated with patient and graft survival (P = 0.04). Of the subset of 104 individuals who underwent histological analysis, 67.3% progressed to ≥F2. On multivariate analysis, significant donor-specific predictors of fibrosis progression were: donor age >50 years and DRI >1.7. CONCLUSIONS (1) Fibrosis progression in HCV-infected LT recipients is strongly associated with donor characteristics, specifically donor age and DRI. (2) DRI, an objective measure of donor quality, appears to correlate both with rate of histological progression and overall patient/graft survival.
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Key Words
- AA, African-American
- CDA, corrected donor age
- CI, confidence interval
- CIT, cold ischemic time
- DCD, donation after cardiac death
- DM, diabetes mellitus
- DRI, donor risk index
- HBV, hepatitis B virus
- HCV, hepatitis C virus
- HIV, human immunodeficiency virus
- HL, hyperlipidemia
- HTN, hypertension
- Hepatitis C
- LBx, liver biopsy
- LT, liver transplantation
- MMF, mycophenolate mofetil
- OPTN, Organ Procurement and Transplantation Network
- OTTR, organ transplant tracking record
- REDCap, Research Database Capture
- TAC, tacrolimus
- UNOS, United Network for Organ Sharing
- donor risk index
- liver transplantation
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Affiliation(s)
- Arun Jesudian
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, United States
| | | | | | | | | | - Bhaskar Kallakury
- Department of Pathology, MedStar Georgetown University Hospital, United States
| | - Jacqueline Laurin
- Division of Gastroenterology and Hepatology, Johns Hopkins University, United States
| | - Kirti Shetty
- Division of Gastroenterology and Hepatology, Johns Hopkins University, United States,Address for correspondence: Kirti Shetty, Sibley Medical Building, 5215 Loughboro Road, #320, Washington, DC 20016, United States. Tel.: +1 202 660 5584; fax: +1 202 660 7359.Sibley Medical Building, 5215 Loughboro Road, #320WashingtonDC20016United States
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12
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Song ATW, Sobesky R, Vinaixa C, Dumortier J, Radenne S, Durand F, Calmus Y, Rousseau G, Latournerie M, Feray C, Delvart V, Roche B, Haim-Boukobza S, Roque-Afonso AM, Castaing D, Abdala E, D’Albuquerque LAC, Duclos-Vallée JC, Berenguer M, Samuel D. Predictive factors for survival and score application in liver retransplantation for hepatitis C recurrence. World J Gastroenterol 2016; 22:4547-4558. [PMID: 27182164 PMCID: PMC4858636 DOI: 10.3748/wjg.v22.i18.4547] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 01/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify risk factors associated with survival in patients retransplanted for hepatitis C virus (HCV) recurrence and to apply a survival score to this population.
METHODS: We retrospectively identified 108 patients retransplanted for HCV recurrence in eight European liver transplantation centers (seven in France, one in Spain). Data collection comprised clinical and laboratory variables, including virological and antiviral treatment data. We then analyzed the factors associated with survival in this population. A recently published score that predicts survival in retransplantation in patients with hepatitis C was applied. Because there are currently no uniform recommendations regarding selection of the best candidates for retransplantation in this setting, we also described the clinical characteristics of 164 patients not retransplanted, with F3, F4, or fibrosing cholestatic hepatitis (FCH) post-first graft presenting with hepatic decompensation.
RESULTS: Overall retransplantation patient survival rates were 55%, 47%, and 43% at 3, 5, and 10 years, respectively. Patients who were retransplanted for advanced cirrhosis had survival rates of 59%, 52%, and 49% at 3, 5, and 10 years, while those retransplanted for FCH had survival rates of 34%, 29%, and 11%, respectively. Under multivariate analysis, and adjusting for the center effect and the occurrence of FCH, factors associated with better survival after retransplantation were: negative HCV viremia before retransplantation, antiviral therapy after retransplantation, non-genotype 1, a Model for End-stage Liver Disease (MELD) score < 25 when replaced on the waiting list, and a retransplantation donor age < 60 years. Although the numbers were small, in the context of the new antivirals era, we showed that outcomes in patients who underwent retransplantation with undetectable HCV viremia did not depend on donor age and MELD score. The Andrés score was applied to 102 patients for whom all score variables were available, producing a mean score of 43.4 (SD = 6.6). Survival rates after the date of the first decompensation post-first liver transplantation (LT1) in the liver retransplantation (reLT) group (94 patients decompensated) at 3, 5, and 10 years were 62%, 59%, and 51%, respectively, among 78 retransplanted individuals with advanced cirrhosis, and 42%, 32%, and 16% among 16 retransplanted individuals with FCH. In the non-reLT group with hepatic decompensation, survival rates were 27%, 18%, and 9% at 3, 5, and 10 years, respectively (P < 0.0001). Compared with non-retransplanted patients, retransplanted patients were younger at LT1 (mean age 48 ± 8 years compared to 53 ± 9 years in the no reLT group, P < 0.0001), less likely to have human immunodeficiency virus (HIV) co-infection (4% vs 14% among no reLT patients, P = 0.005), more likely to have received corticosteroid bolus therapy after LT1 (25% in reLT vs 12% in the no reLT group, P = 0.01), and more likely to have presented with sustained virological response (SVR) after the first transplantation (20% in the reLT group vs 7% in the no reLT group, P = 0.028).
CONCLUSION: Antiviral therapy before and after retransplantation had a substantial impact on survival in the context of retransplantation for HCV recurrence, and with the new direct-acting antivirals now available, outcomes should be even better in the future.
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13
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Hung K, Gralla J, Dodge JL, Bambha KM, Dirchwolf M, Rosen HR, Biggins SW. Optimizing repeat liver transplant graft utility through strategic matching of donor and recipient characteristics. Liver Transpl 2015; 21:1365-73. [PMID: 25865434 DOI: 10.1002/lt.24138] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/27/2015] [Accepted: 04/01/2015] [Indexed: 02/07/2023]
Abstract
Repeat liver transplantation (LT) is controversial because of inferior outcomes versus primary LT. A minimum 1-year expected post-re-LT survival of 50% has been proposed. We aimed to identify combinations of Model for End-Stage Liver Disease (MELD), donor risk index (DRI), and recipient characteristics achieving this graft survival threshold. We identified re-LT recipients listed in the United States from March 2002 to January 2010 with > 90 days between primary LT and listing for re-LT. Using Cox regression, we estimated the expected probability of 1-year graft survival and identified combinations of MELD, DRI, and recipient characteristics attaining >50% expected 1-year graft survival. Re-LT recipients (n = 1418) had a median MELD of 26 and median age of 52 years. Expected 1-year graft survival exceeded 50% regardless of MELD or DRI in Caucasian recipients who were not infected with hepatitis C virus (HCV) of all ages and Caucasian HCV-infected recipients <50 years old. As age increased in HCV-infected Caucasian and non-HCV-infected African American recipients, lower MELD scores or lower DRI grafts were needed to attain the graft survival threshold. As MELD scores increased in HCV-infected African American recipients, lower-DRI livers were required to achieve the graft survival threshold. Use of high-DRI livers (>1.44) in HCV-infected recipients with a MELD score > 26 at re-LT failed to achieve the graft survival threshold with recipient age ≥ 60 years (any race), as well as at age ≥ 50 years for Caucasians and at age < 50 years for African Americans. Strategic donor selection can achieve >50% expected 1-year graft survival even in high-risk re-LT recipients (HCV infected, older age, African American race, high MELD scores). Low-risk transplant recipients (age < 50 years, non-HCV-infected) can achieve the survival threshold with varying DRI and MELD scores.
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Affiliation(s)
- Kenneth Hung
- Division of Gastroenterology and Hepatology, Anschutz Medical Campus, University of Colorado, Aurora, CO
| | - Jane Gralla
- Departments of Pediatrics, University of Colorado, Aurora, CO.,Biostatistics and Informatics, Anschutz Medical Campus, University of Colorado, Aurora, CO
| | - Jennifer L Dodge
- Department of Surgery, University of California, San Francisco, CA
| | - Kiran M Bambha
- Division of Gastroenterology and Hepatology, Anschutz Medical Campus, University of Colorado, Aurora, CO
| | - Melisa Dirchwolf
- Unidad de Hepatopatias Infecciosas, Hospital Francisco J. Muñiz, Buenos Aires, Argentina
| | - Hugo R Rosen
- Division of Gastroenterology and Hepatology, Anschutz Medical Campus, University of Colorado, Aurora, CO
| | - Scott W Biggins
- Division of Gastroenterology and Hepatology, Anschutz Medical Campus, University of Colorado, Aurora, CO
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14
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Dueland S, Hagness M, Line PD, Guren TK, Tveit KM, Foss A. Is Liver Transplantation an Option in Colorectal Cancer Patients with Nonresectable Liver Metastases and Progression on All Lines of Standard Chemotherapy? Ann Surg Oncol 2015; 22:2195-2200. [PMID: 25297902 DOI: 10.1245/s10434-014-4137-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2014] [Indexed: 02/11/2025]
Abstract
BACKGROUND About 50 % of patients with metastatic colorectal cancer (CRC) will develop metastatic disease with liver as primary metastatic site. The majority of CRC patients has nonresectable disease and receives palliative chemotherapy. Overall survival (OS) from time of progression on last line of chemotherapy in metastatic CRC is about 5 months. CLM have been considered a contraindication for liver transplantation. However, we have previously reported 5-year OS of 60 % after liver transplantation for nonresectable CLM. There were six patients who had progressive disease (PD) on last line of standard chemotherapy at the time of liver transplantation; here we report the outcome for these six patients. METHODS Patients with nonresectable liver-only CLM received liver transplantation in the SECA study, a subgroup of six patients whose disease had progressed on all standard lines of chemotherapy. RESULTS These patients with nonresectable disease and PD on the last line of standard chemotherapy at time of liver transplantation had 8-35 metastatic lesions in the liver with the largest diameter at 2.8-13.0 cm. All patients had a relapse within 2.1-12.4 months after liver transplantation. Some patients received treatment with curative intent at the time of relapse, and median OS after transplantation was 41 months with a Kaplan-Meier calculated 5-year OS of 44 %. CONCLUSIONS Liver transplantation in nonresectable CLM patients with extensive tumor load and PD on the last line of chemotherapy had extended OS compared with any other treatment option reported in the literature.
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Affiliation(s)
- Svein Dueland
- Department of Oncology, Oslo University Hospital, Oslo, Norway,
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15
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Abstract
Liver transplantation has become the treatment of choice for nearly all causes of end-stage liver disease, fulminant liver failure, and selected primary hepatic malignancies. The demand for liver transplantation has persistently outmatched the availability of donor organs leading to the development of novel strategies to expand the donor pool. The authors review the process of liver transplant evaluation, methods used to address the donor shortage, and disease-specific outcomes and challenges and discuss posttransplant care.
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Affiliation(s)
- Ming-Ming Xu
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH14, New York, NY 10032, USA
| | - Robert S Brown
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians & Surgeons, 622 West 168th Street, PH14, New York, NY 10032, USA.
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16
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Abstract
Chronic HCV infection is the leading indication for liver transplantation. However, as a result of HCV recurrence, patient and graft survival after liver transplantation are inferior compared with other indications for transplantation. HCV recurrence after liver transplantation is associated with considerable mortality and morbidity. The development of HCV-related fibrosis is accelerated after liver transplantation, which is influenced by a combination of factors related to the virus, donor, recipient, surgery and immunosuppression. Successful antiviral therapy is the only treatment that can attenuate fibrosis. The advent of direct-acting antiviral agents (DAAs) has changed the therapeutic landscape for the treatment of patients with HCV. DAAs have improved tolerability, and can potentially be used without PEG-IFN for a shorter time than previous therapies, which should result in better outcomes. In this Review, we describe the important risk factors that influence HCV recurrence after liver transplantation, highlighting the mechanisms of fibrosis and the integral role of hepatic stellate cells. Indirect and direct assessment of fibrosis, in addition to new antiviral therapies, are also discussed.
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17
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Dumortier J, Boillot O, Scoazec JY. Natural history, treatment and prevention of hepatitis C recurrence after liver transplantation: Past, present and future. World J Gastroenterol 2014; 20:11069-11079. [PMID: 25170196 PMCID: PMC4145750 DOI: 10.3748/wjg.v20.i32.11069] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 03/07/2014] [Accepted: 06/23/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related liver disease, including cirrhosis and hepatocellular carcinoma is the main indication for liver transplantation (LT) worldwide. Post-transplant HCV re-infection is almost universal and results in accelerated progression from acute hepatitis to chronic hepatitis, and liver cirrhosis. Comprehension and treatment of recurrent HCV infection after LT have been major issues for all transplant hepatologists and transplant surgeons for the last decades. The aim of this paper is to review the evolution of our knowledge on the natural history of HCV recurrence after LT, including risk factors for disease progression, and antiviral therapy. We will focus our attention on possible ways (present and future) to improve the final long-term results of LT for HCV-related liver disease.
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18
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deLemos AS, Schmeltzer PA, Russo MW. Recurrent hepatitis C after liver transplant. World J Gastroenterol 2014; 20:10668-81. [PMID: 25152571 PMCID: PMC4138448 DOI: 10.3748/wjg.v20.i31.10668] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Revised: 01/25/2014] [Accepted: 04/02/2014] [Indexed: 02/06/2023] Open
Abstract
End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.
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19
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Abstract
Hepatic retransplant accounts for 5% to 15% of liver transplants in most series and is associated with significantly increased hospital costs and inferior patient survival when compared with primary liver transplant. Early retransplants are usually due to primary graft nonfunction or vascular thrombosis, whereas later retransplants are most commonly necessitated by chronic rejection or recurrent primary liver disease. Hepatic retransplant remains the sole option for survival in many patients facing allograft failure after liver transplant. With improved techniques to match retransplant candidates with appropriate donor grafts, it is hoped that the outcomes of retransplant will continue to improve in future.
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20
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Joshi D, Carey I, Foxton M, Al-Freah M, Bruce M, Heaton N, Quaglia A, O'Grady J, Aluvihare V, Agarwal K. CXCL10 levels identify individuals with rapid fibrosis at 12 months post-transplant for hepatitis C virus and predict treatment response. Clin Transplant 2014; 28:569-78. [DOI: 10.1111/ctr.12354] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2014] [Indexed: 01/14/2023]
Affiliation(s)
- Deepak Joshi
- Institute of Liver Studies; King's College Hospital; London UK
| | - Ivana Carey
- Institute of Liver Studies; King's College Hospital; London UK
| | - Matthew Foxton
- Institute of Liver Studies; King's College Hospital; London UK
| | | | - Matthew Bruce
- Institute of Liver Studies; King's College Hospital; London UK
| | - Nigel Heaton
- Institute of Liver Studies; King's College Hospital; London UK
| | - Alberto Quaglia
- Institute of Liver Studies; King's College Hospital; London UK
| | - John O'Grady
- Institute of Liver Studies; King's College Hospital; London UK
| | | | - Kosh Agarwal
- Institute of Liver Studies; King's College Hospital; London UK
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21
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Younossi ZM, Kanwal F, Saab S, Brown KA, El-Serag HB, Kim WR, Ahmed A, Kugelmas M, Gordon SC. The impact of hepatitis C burden: an evidence-based approach. Aliment Pharmacol Ther 2014; 39:518-31. [PMID: 24461160 DOI: 10.1111/apt.12625] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2013] [Revised: 10/11/2013] [Accepted: 12/30/2013] [Indexed: 12/08/2022]
Abstract
BACKGROUND Infection with the hepatitis C virus (HCV) has been considered a major cause of mortality, morbidity and resource utilisation in the US. In addition, HCV is the main cause of hepatocellular cancer (HCC) in the US. Recent developments in the diagnosis and treatment of HCV, including new recommendations pertaining to screening for HCV by the Centers for Disease Control and Prevention and newer treatment regimens with high efficacy, short duration and the potential for interferon-free therapies, have energised the health care practitioners regarding HCV management. AIM To assess the full impact of HCV burden on clinical, economic and patient-reported outcomes. METHODS An expert panel was convened to assess the full impact of HCV burden on a number of important outcomes using an evidence-based approach predicated on Grading of Recommendations Assessment, Development and Evaluation methodology. The literature was summarised, graded using an evidence-based approach and presented during the workshop. Workshop presentations were intended to review recent, relevant evidence-based literature and provide graded summary statements pertaining to HCV burden on topics including the relationships between HCV and the development of important outcomes. RESULTS The associations of HCV with cirrhosis, HCC, liver-related mortality, type 2 diabetes mellitus, rheumatological diseases and quality of life impairments are supported by strong evidence. Also, there is strong evidence that sustained viral eradication of HCV can improve important outcomes such as mortality and quality of life. CONCLUSIONS The current evidence suggests that HCV has been associated with tremendous clinical, economic and quality of life burden.
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Affiliation(s)
- Z M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA
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22
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Oniscu GC, Diaz G, Levitsky J. Meeting report of the 19th Annual International Congress of the International Liver Transplantation Society (Sydney Convention and Exhibition Centre, Sydney, Australia, June 12-15, 2013). Liver Transpl 2014; 20:7-14. [PMID: 24136728 DOI: 10.1002/lt.23767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2013] [Accepted: 09/24/2013] [Indexed: 12/21/2022]
Abstract
The International Liver Transplantation Society held its annual meeting from June 12 to 15 in Sydney, Australia. More than 800 registrants attended the congress, which opened with a conference celebrating 50 years of liver transplantation (LT). The program included series of featured symposia, focused topic sessions, and oral and poster presentations. This report is by no means all-inclusive and focuses on specific abstracts on key topics in LT. Similarly to previous reports, this one presents data in the context of the published literature and highlights the current direction of LT.
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Affiliation(s)
- Gabriel C Oniscu
- Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
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23
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Duarte-Rojo A, Budhraja V, Veldt BJ, Goldstein DD, Watt KD, Heimbach JK, McHutchison JG, Tillman HL, Poterucha JJ, Charlton MR. Interleukin-28B and fibrosing cholestatic hepatitis in posttransplant hepatitis C: a case-control study and literature review. Liver Transpl 2013; 19:1311-7. [PMID: 24039107 DOI: 10.1002/lt.23733] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Accepted: 07/26/2013] [Indexed: 12/14/2022]
Abstract
Chronic hepatitis C (CHC)-related cirrhosis is the leading indication for liver transplantation (LT). However, the recurrence of a hepatitis C virus (HCV) infection after transplantation is universal and is associated with worse outcomes. Fibrosing cholestatic hepatitis (FCH) is a particularly severe manifestation of a recurrent HCV infection and frequently results in graft failure and death. The identification of risk factors for FCH is important but has been limited by the low frequency of FCH. The interleukin-28B (IL-28B) genotype is important in an HCV infection: it is related to the clinical severity of an acute infection and may play a role in the development of FCH as well. Two hundred seventy-two consecutive LT cases for CHC were studied at a single institution. Consensus criteria were used to define an FCH cohort. The remainder of the study population served as a control group. The IL-28B genotype (at the rs12979860 locus) from both the donor and the recipient was determined, and other clinically relevant data were tabulated. A nonparametric statistical analysis was performed. Twelve cases of FCH were identified, and they were compared to a control group of 260 LT cases without FCH. A detailed analysis of clinical characteristics, including treatment responses and outcomes, was tabulated. FCH was associated with the earlier recurrence of HCV infections, higher HCV viral loads, and lower levels of immunosuppressive medications. There was a nonsignificant increase in recipient IL-28B non-CC genotypes in cases developing FCH. In conclusion, a high HCV viral load and earlier recurrence were identified as risk factors for FCH. It is still unclear what role immunosuppression plays in the pathogenesis of FCH and whether IL-28B polymorphisms constitute a risk factor. Collaborative studies with larger numbers of study subjects are needed in order to define these issues.
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Affiliation(s)
- Andres Duarte-Rojo
- Divisions of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; University of Arkansas for Medical Sciences, Little Rock, AR
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24
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Campsen J, Zimmerman M, Trotter J, Hong J, Freise C, Brown RS, Cameron A, Ghobrial M, Kam I, Busuttil R, Saab S, Holt C, Emond JC, Stiles JB, Lukose T, Chang MS, Klintmalm G. Multicenter review of liver transplant for hepatitis B-related liver disease: disparities in gender and ethnicity. Clin Transplant 2013; 27:829-37. [PMID: 24033475 DOI: 10.1111/ctr.12224] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/29/2013] [Indexed: 12/15/2022]
Abstract
Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected.
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Affiliation(s)
- Jeffrey Campsen
- Baylor University Medical Center at Dallas, Dallas, TX, USA; University of Utah Health Sciences Center, Salt Lake City, UT, USA
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25
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Kressel A, Therapondos G, Bohorquez H, Borg B, Bruce D, Carmody I, Cohen A, Girgrah N, Joshi S, Reichman T, Loss GE. Excellent liver retransplantation outcomes in hepatitis C-infected recipients. Clin Transplant 2013; 27:E512-20. [DOI: 10.1111/ctr.12182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2013] [Indexed: 12/15/2022]
Affiliation(s)
- A. Kressel
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - G. Therapondos
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - H. Bohorquez
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - B. Borg
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - D. Bruce
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - I. Carmody
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - A. Cohen
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - N. Girgrah
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - S. Joshi
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - T. Reichman
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
| | - G. E. Loss
- Multi-organ Transplant Institute; Ochsner Medical Center; New Orleans; LA; USA
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26
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Karnik GS, Shetty K. Management of recurrent hepatitis C in orthotopic liver transplant recipients. Infect Dis Clin North Am 2013; 27:285-304. [PMID: 23714341 DOI: 10.1016/j.idc.2013.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
End-stage liver disease and hepatocellular carcinoma from chronic hepatitis C are the most common indications for orthotopic liver transplantation and the incidence of both are projected to increase over the next decade. Recurrent hepatitis C virus infection of the allograft is associated with an accelerated progression to cirrhosis, graft loss, and death. This article presents an overview of the natural history of hepatitis C virus recurrence in liver transplant recipients and guidance on optimal management strategies.
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Affiliation(s)
- Geeta S Karnik
- Department of Infectious Diseases, Georgetown University Hospital, Washington, DC 20007, USA.
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27
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Levitsky J, Doucette K. Viral hepatitis in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:147-68. [PMID: 23465008 DOI: 10.1111/ajt.12108] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- J Levitsky
- Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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28
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Living-donor liver transplantation and hepatitis C. HPB SURGERY : A WORLD JOURNAL OF HEPATIC, PANCREATIC AND BILIARY SURGERY 2013; 2013:985972. [PMID: 23401640 PMCID: PMC3564275 DOI: 10.1155/2013/985972] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Accepted: 01/01/2013] [Indexed: 12/19/2022]
Abstract
Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompression. In areas with low deceased-donor organ availability like Japan, living-donor liver transplantation (LDLT) is similarly indicated for HCV cirrhosis as deceased-donor liver transplantation (DDLT) in Western countries and accepted as an established treatment for HCV-cirrhosis, and the results are equivalent to those of DDLT. To prevent graft failure due to recurrent hepatitis C, antiviral treatment with pegylated-interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. In contrast to DDLT, many Japanese LDLT centers have reported modified treatment regimens as best efforts to secure first graft, such as aggressive preemptive antiviral treatment, escalation of dosages, and elongation of treatment duration.
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29
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Shetty S, Stefanovic S, Mihailescu MR. Hepatitis C virus RNA: molecular switches mediated by long-range RNA-RNA interactions? Nucleic Acids Res 2012; 41:2526-40. [PMID: 23275555 PMCID: PMC3575821 DOI: 10.1093/nar/gks1318] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Multiple conserved structural cis-acting regulatory elements have been recognized both in the coding and untranslated regions (UTRs) of the hepatitis C virus (HCV) genome. For example, the cis-element 5BSL3.2 in the HCV-coding region has been predicted to use both its apical and internal loops to interact with the X RNA in the 3'-UTR, with the IIId domain in the 5'-UTR and with the Alt sequence in the coding region. Additionally, the X RNA region uses a palindromic sequence that overlaps the sequence required for the interaction with 5BSL3.2, to dimerize with another HCV genome. The ability of the 5BSL3.2 and X RNA regions to engage in multi-interactions suggests the existence of one or more molecular RNA switches which may regulate different steps of the HCV life cycle. In this study, we used biophysical methods to characterize the essential interactions of these HCV cis-elements at the molecular level. Our results indicate that X RNA interacts with 5BSL3.2 and another X RNA molecule by adopting two different conformations and that 5BSL3.2 engages simultaneously in kissing interactions using its apical and internal loops. Based on these results, we propose a mode of action for possible molecular switches involving the HCV RNA.
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Affiliation(s)
- Sumangala Shetty
- Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282, USA
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30
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Abstract
Recurrent HCV disease is the most common cause of graft loss and patient mortality in HCV-infected liver transplant (LT) recipients. Risk factors for more severe recurrence that are potentially modifiable are older donor age, prolonged cold ischaemia time, prior treated acute rejection, CMV hepatitis, IL28B donor genotype, and post-LT insulin resistance. The most effective means of preventing HCV recurrence is eradicating HCV prior to LT. Select wait-list candidates with compensated or mildly decompensated disease can be considered for antiviral treatment with peginterferon, ribavirin (and protease inhibitor if genotype 1). For the majority of LT patients, HCV treatment must be delayed until post-transplant. Treatment is generally undertaken if histologic severity reaches grade 3 or 4 necroinflammation or stage ≥2 fibrosis, or if cholestatic hepatitis. Achievement of sustained viral response (SVR) post-LT is associated with stabilization of fibrosis and improved graft survival. SVR is attained in ~30% of patients treated with peginterferon and ribavirin. Poor tolerability of therapy is a limitation. Combination therapy with telaprevir or boceprevir added to peginterferon and ribavirin is anticipated to increase efficacy but with higher rates of adverse effects and challenges in managing drug-drug interactions between the protease inhibitors and calcineurin inhibitors/sirolimus.
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31
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Abstract
Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompensation. The use of poor quality organs, particularly from older donors, has a highly negative impact on the severity of recurrence and patient/graft survival. Although immunosuppressive regimens have a considerable impact on the outcome, the optimal regimen after liver transplantation for HCV-infected patients remains unclear. Disease progression monitoring with protocol biopsy and new noninvasive methods is essential for predicting patient/graft outcome and starting antiviral treatment with the appropriate timing. Antiviral treatment with pegylated interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. Living-donor liver transplantation is now widely accepted as an established treatment for HCV cirrhosis and the results are equivalent to those of deceased donor liver transplantation.
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32
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Moroso V, van der Meer A, Tilanus HW, Kazemier G, van der Laan LJW, Metselaar HJ, Joosten I, Kwekkeboom J. Donor and recipient HLA/KIR genotypes do not predict liver transplantation outcome. Transpl Int 2011; 24:932-42. [PMID: 21672051 DOI: 10.1111/j.1432-2277.2011.01286.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Whether or not Natural Killer (NK) cells affect the immune response to solid organ allografts is still controversial. Main determinants of NK-cell activation are specific HLA/killer-cell immunoglobulin-like receptors (KIR) interactions that, in transplantation, may induce NK-cell alloreactivity. So far, in liver transplantation (LTX) donor-versus-recipient alloreactivity has not been investigated; in addition, studies of predicted recipient-versus-donor NK-cell alloreactivity have led to contradicting results. We typed a cohort of LTX donors and recipients for HLA-C/Bw4 and KIRs. We estimated the effect of NK-cell alloreactivity, as predicted by classically used models, in the donor-versus-recipient direction. The results indicate that HLA/KIR mismatches in the donor-versus-recipient direction do not predict graft rejection nor graft or patient survival, suggesting that donor-derived NK cells do not play a major role in LTX outcome. In addition, when considering predicted NK-cell alloreactivity in the reverse direction (recipient-versus-donor), we first confirmed that donor HLA-C genotype was not associated with acute rejection, graft or patient survival and secondly we found that none of the models describing NK-cell alloreactivity could predict LTX outcome. Overall our observations suggest that, in contrast to what is shown in haematopoietic stem cell transplantation, donor-derived NK cells may not contribute in preventing liver graft rejection, and that recipient-versus-donor NK-cell alloreactivity does not predict LTX outcome.
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Affiliation(s)
- Viviana Moroso
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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Abstract
The treatment for cholangiocarcinoma (CCA) remains a challenge because of the aggressive nature of the disease and the absence of effective treatments besides surgical resection (HR) and liver transplantation (LT). In intrahepatic CCA, HR remains the treatment of choice whereas with concomitant liver disease such as cirrhosis or primary sclerosing cholangitis (PSC), LT is the only option. Hilar CCA or Klatskin tumours have in recent decades been managed with a more aggressive surgical approach to achieve R0 resection. This approach usually involves preoperative portal embolisation, followed by liver resection – sometimes extensive and even with portal vein resection. The recent protocols that combine preoperative neoadjuvant chemoirridation and LT show promising results that need to be confirmed. The development of diagnostic modalities (tumour markers, cytology and radiology) are of the utmost importance to identify these patients at an early stage to preserve radical surgery possible. Cholangiocarcinoma (CCA) is a malignant disease of the epithelial cells in the intra- and extrahepatic bile ducts. While still a rare malignant disease, CCA is the second most common primary malignancy of the liver. The incidence is increasing; especially the incidence of intrahepatic CCA (1). The treatment of CCA is challenging as it is usually difficult to diagnose when radical surgical treatment, resection (HR) or liver transplantation (LT) is possible. The lack of effective medical treatment makes a radical surgical resection or hepatectomy the only therapeutic option. Most of the CCAs are unresectable at presentation and the prognosis for these patients is dismal.
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Affiliation(s)
- S Friman
- Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
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34
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Findlay JY, Fix OK, Paugam-Burtz C, Liu L, Sood P, Tomlanovich SJ, Emond J. Critical care of the end-stage liver disease patient awaiting liver transplantation. Liver Transpl 2011; 17:496-510. [PMID: 21506240 DOI: 10.1002/lt.22269] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Patients with end-stage liver disease awaiting liver transplantation frequently require intensive care admission and management due to either complications of liver failure or to intercurrent illness, particularly infection. Mortality in such patients is high and the development of an illness necessitating intensive care unit management can influence transplant candidacy. Specialized support frequently requires hemodynamic support, mechanical ventilation, and renal support. In this review, areas of management of particular importance to patients with end-stage liver disease in the intensive care unit are discussed. These areas are hepatic encephalopathy, infectious diseases, cardiovascular support, mechanical ventilation, renal support and combined transplantation, and decisions regarding delisting. Current knowledge specific to these patients, when available, is discussed, current practice is described, and areas of uncertainty in the evidence are discussed.
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Affiliation(s)
- James Y Findlay
- Department of Anesthesiology and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
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35
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Friman S, Foss A, Isoniemi H, Olausson M, Höckerstedt K, Yamamoto S, Karlsen TH, Rizell M, Ericzon BG. Liver transplantation for cholangiocarcinoma: selection is essential for acceptable results. Scand J Gastroenterol 2011; 46:370-5. [PMID: 21073376 DOI: 10.3109/00365521.2010.533384] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS Cholangiocarcinoma (CCA) is considered a contraindication for liver transplantation by most liver transplant centers. The aim of this study has been to report our results as well as to explore factors that influence patient survival after liver transplantation for CCA. PATIENTS All transplant patients with CCA in Norway, Sweden and Finland during 1984-2005 were included (n = 53). Thirty-three patients (62%) had intrahepatic CCA. Twenty-one patients (40%) had a more advanced tumor (>TNM stage 2). Thirty-four of the 53 recipients (64%) had primary sclerosing cholangitis (PSC). RESULTS Patients with TNM stage ≤ 2 transplanted after 1995 had a 5-year survival rate of 48%. The overall 5-year patient survival rate was 25%. There was no difference in survival between patients with extrahepatic and intrahepatic CCA. The 5-year survival rate among patients with TNM stage ≤ 2 was 36%. Patients with TNM stage >2 had a 10% 5-year survival rate; the difference was significant at p < 0.01. Patients transplanted after 1995 had a significantly better 5-year survival rate than pre-1995 patients (38% vs. 0%, p < 0.01). Patients transplanted after 1995 with TNM ≤ 2 and CA 19-9 ≤ 100 had the 5-year survival of 58%. CONCLUSION By selecting CCA patients with TNM stage ≤ 2 and a CA 19-9 ≤ 100 a reasonable 5-year survival rate is possible. We think that CCA in selected cases can be an acceptable indication for liver transplantation.
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Affiliation(s)
- Styrbjörn Friman
- Transplant Institute, Sahlgrenska University Hospital, Göteborg, Sweden.
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36
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Retransplantation in patients with hepatitis C recurrence after liver transplantation. J Hepatol 2010; 53:962-70. [PMID: 20800307 DOI: 10.1016/j.jhep.2010.06.006] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2009] [Revised: 06/08/2010] [Accepted: 06/10/2010] [Indexed: 12/11/2022]
Abstract
Hepatitis C virus (HCV) infection recurs universally after liver transplantation (LT) and fibrosis progression is accelerated in the graft. Retransplantation (RT) is the only therapeutic option to achieve long-term survival in patients with decompensated cirrhosis after LT. Patient and graft survival rates after RT are inferior to those after primary LT. It is generally accepted that severe hepatitis C recurrence (cholestatic hepatitis) and forms with rapid fibrosis progression have a poor survival after RT. However, it is not clear whether rapid fibrosis progression in the first graft will be followed by the same rate of fibrosis progression in the second graft. The use of prognostic scores as screening tools has shown an improvement in survival in HCV-infected patients after RT, reaching similar survival rates as those obtained in non HCV-infected patients. Moreover, these scores can identify candidates with a high risk of mortality in whom the use of a new organ would be unreasonable. Prevention of severe hepatitis C recurrence could be the first step to avoid RT. Thus, antiviral treatment on the waiting list (if possible) and early identification and treatment of patients with severe hepatitis C recurrence may be a good strategy to avoid RT. In addition, active management of factors which can accelerate fibrosis progression (donor age, post-transplant diabetes, high dose of corticosteroids) might reduce the incidence of severe forms of hepatitis C recurrence.
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37
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Rowe IA, Barber KM, Birch R, Curnow E, Neuberger JM. Retransplantation for graft failure in chronic hepatitis C infection: a good use of a scarce resource? World J Gastroenterol 2010; 16:5070-6. [PMID: 20976844 PMCID: PMC2965284 DOI: 10.3748/wjg.v16.i40.5070] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2010] [Revised: 06/16/2010] [Accepted: 06/23/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the outcome of patients with hepatitis C virus (HCV) infection undergoing liver retransplantation. METHODS Using the UK National Registry, patients undergoing liver transplantation for HCV-related liver disease were identified. Data on patient and graft characteristics, as well as transplant and graft survival were collected to determine the outcome of HCV patients undergoing retransplantation and in order to identify factors associated with transplant survival. RESULTS Between March 1994 and December 2007, 944 adult patients were transplanted for HCV-related liver disease. At the end of follow-up, 617 of these patients were alive. In total, 194 (21%) patients had first graft failure and of these, 80 underwent liver retransplantation, including 34 patients where the first graft failed due to recurrent disease. For those transplanted for HCV-related disease, the 5-year graft survival in those retransplanted for recurrent HCV was 45% [95% confidence interval (CI): 24%-64%] compared with 80% (95% CI: 62%-90%) for those retransplanted for other indications (P = 0.01 log-rank test); the 5-year transplant survival after retransplantation was 43% (95% CI: 23%-62%) and 46% (95% CI: 31%-60%), respectively (P = 0.8, log-rank test). In univariate analysis of all patients retransplanted, no factor analyzed was significantly associated with transplant survival. CONCLUSION Outcomes for retransplantation in patients with HCV infection approach agreed criteria for minimum transplant benefit. These data support selective liver retransplantation in patients with HCV infection.
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Abstract
Recurrence of the primary disease has become a major focus for transplant hepatologists both when investigating graft dysfunction and when tailoring immunosuppression to maximize graft survival. However, disease recurrence varies in penetrance, can be predictable or random, and does not always conform to the expected pattern of disease. The cholestatic hepatitis syndromes associated with hepatitis B and C are the most dramatic examples of phenotypic change. Being on immunosuppressive drugs may intensify the progression of infectious and malignant diseases, but this effect is not predictable. A significant minority of patients with each of the autoimmune diseases, counter-intuitively, get recurrent disease despite immunosuppression of a potency that is adequate to prevent rejection of the liver graft. Disease patterns emerge after liver transplantation for cryptogenic cirrhosis that shed light on the cause of the native liver disease, for example, nonalcohol-related fatty liver disease and autoimmune hepatitis. The phenotypic expression of disease recurrence can be modified by specific drugs used for immunosuppression and by HLA-antigen matching profiles. Understanding and modifying the phenotypic expression of recurrent disease after liver transplantation is a fertile area for research and continued refinement of clinical care.
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Affiliation(s)
- J G O'Grady
- Institute of Liver Studies, King's College Hospital, London, UK.
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39
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Foss A, Adam R, Dueland S. Liver transplantation for colorectal liver metastases: revisiting the concept. Transpl Int 2010; 23:679-85. [PMID: 20477993 DOI: 10.1111/j.1432-2277.2010.01097.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1- and 5-year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5-year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.
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Affiliation(s)
- Aksel Foss
- Department of Transplantation, Oslo University Hospital - Rikshospitalet, Oslo, Norway
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40
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R753Q single-nucleotide polymorphism impairs toll-like receptor 2 recognition of hepatitis C virus core and nonstructural 3 proteins. Transplantation 2010; 89:811-5. [PMID: 20090572 DOI: 10.1097/tp.0b013e3181cbac18] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) core and nonstructural (NS) 3 proteins induce inflammation and immunity through a toll-like receptor (TLR) 2-dependent pathway. Individuals with the R753Q single-nucleotide polymorphism (SNP) in the TLR2 gene have increased the risk of allograft failure after liver transplantation for chronic hepatitis C. METHODS To test the hypothesis that R753Q SNP impairs TLR2 recognition of HCV proteins, a series of in vitro experiments were performed wherein stable clones of wild-type TLR2-deficient human embryonic kidney (HEK) 293 cells and HEK293 cells transfected with wild-type (HEK293-TLR2) or variant TLR2 genes (HEK293-TLR2-R753Q) were stimulated with HCV core and NS3 proteins. Cellular activation was assessed by nuclear factor-kappa B-driven luciferase activity, cytokine secretion, and gene upregulation. RESULTS Compared with TLR2-deficient HEK293 cells, HEK293-TLR2 cells had marked nuclear factor-kappa B-driven luciferase activity, had modest to marked upregulation in TLR2 signaling-associated genes, and secreted large quantities of interleukin-8 during exposure to HCV core and NS3 proteins. In contrast, HEK293-TLR2-R753Q cells did not respond to stimulation with HCV and behaved similarly like TLR2-deficient HEK293 cells. CONCLUSION R753Q SNP impairs TLR2-mediated immune recognition of HCV core and NS3 proteins. This biologic defect may account for the predisposition of patients to develop allograft failure after liver transplantation for chronic hepatitis C.
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Abstract
BACKGROUND Transplantation of more than two livers for recurring graft failure has not been specifically addressed in the literature. METHODS A retrospective analysis was conducted from a total of 2527 overall liver transplants at our institution. Main indications for multiple retransplant included primary nonfunction, chronic rejection, hepatic artery thrombosis, and recurrent disease. RESULTS We identified 39 patients who received more than two grafts (32 received 3 grafts, 5 received 4 grafts, and 2 received 5 grafts). All patients required interposition arterial grafts from the aorta and hepatojejunostomy for the biliary reconstruction. Seventeen patients are still alive at last follow-up. Perioperative mortality rates after 3rd, 4th, and 5th liver graft were 25%, 14%, and 50%, respectively. Patient and graft survival rates were 72% and 56% at 1 year, respectively. Median length of stay was 27 days and median graft survival was 2.9 years. CONCLUSIONS Selection of patients and a significant use of available resources are some of the important factors that clinicians need to take into account when dealing with multiple retransplantations. With such conditions, however, liver retransplantation of more than two grafts can be a life-saving procedure.
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Affiliation(s)
- J Levitsky
- Division of Hepatology and Organ Transplantation, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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Sung RS, Pomfret EA, Andreoni KA, Baker TB, Peters TG. The high-risk recipient: the Eighth Annual American Society of Transplant Surgeons' State-of-the-Art Winter Symposium. Clin Transplant 2009; 24:23-8. [PMID: 19919609 DOI: 10.1111/j.1399-0012.2009.01156.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The evolution of organ transplantation has produced results so successful that many transplant programs commonly see recipients with medical risks, which in the past, would have prohibited transplantation. The Eighth Annual American Society of Transplant Surgeons State-of-the-Art Winter Symposium focused on the high-risk recipient. The assessment of risk has evolved over time, as transplantation has matured. The acceptance of risk associated with a given candidate today is often made in consideration of the relative value of the organ to other candidates, the regulatory environment, and philosophical notions of utility, equity, and fairness. In addition, transplant programs must balance outcomes, transplant volume, and the costs of organ transplantation, which are impacted by high-risk recipients. Discussion focused on various types of high-risk recipients, such as those with coronary artery disease, morbid obesity, and hepatitis C; strategies to reduce risk, such as down-staging of hepatocellular carcinoma and treatment of pulmonary hypertension; the development of alternatives to transplantation; and the degree to which risk can or should be used to define candidate selection. These approaches can modify the impact of recipient risk on transplant outcomes and permit transplantation to be applied successfully to a greater variety of patients.
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Affiliation(s)
- Randall S Sung
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
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Firpi RJ, Clark V, Soldevila-Pico C, Morelli G, Cabrera R, Levy C, Machicao VI, Chaoru C, Nelson DR. The natural history of hepatitis C cirrhosis after liver transplantation. Liver Transpl 2009; 15:1063-71. [PMID: 19718647 DOI: 10.1002/lt.21784] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis C after liver transplantation leads to graft cirrhosis in up to 30% of patients within 5 years, but limited data exist regarding the clinical course of cirrhosis after transplantation. The aims of this study were to report the natural history of hepatitis C cirrhosis after liver transplantation and to identify risk factors for decompensation and survival. Hepatitis C patients underwent protocol liver biopsies yearly after liver transplantation. After cirrhosis was identified by biopsy, the outcomes of interest were the development of decompensation, death, or retransplantation for hepatitis C. Kaplan-Meier and Cox regression analysis was used to determine survival and risk factors for decompensation and mortality. Out of 502 liver transplants performed for hepatitis C, 88 patients (18%) had cirrhosis within 3.7 years. Seventy-one patients were compensated at diagnosis. The cumulative probability of decompensation 1 year after cirrhosis was 30%. A Model for End-Stage Liver disease score >or= 16 was predictive of decompensation and poor survival, whereas successful interferon treatment was found to reduce this risk (relative risk = 0.05). Once decompensation occurred, 1-year survival was 46%. In conclusion, the results confirm an accelerated natural history of hepatitis C cirrhosis after liver transplantation and demonstrate poor survival after decompensation. The Model for End-Stage Liver Disease can stratify risk for decompensation and survival, whereas successful antiviral therapy may be protective.
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Affiliation(s)
- Roberto J Firpi
- Section of Hepatobiliary Diseases, Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32610-0214, USA.
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Shankar A, Alexander G. Liver transplantation for liver disease caused by hepatitis C virus infection. Br J Hosp Med (Lond) 2009; 70:95-100. [PMID: 19229150 DOI: 10.12968/hmed.2009.70.2.38908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Hepatitis C is an important problem that often requires liver transplantation. However, outcomes have not improved in line with liver transplants for other indications. This article explores the issues surrounding this difficult area of transplant hepatology.
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Affiliation(s)
- Arun Shankar
- Department of Hepatology, Addenbrooke's Hospital, Cambridge
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Schmitt TM, Kumer SC, Pruett TL, Argo CK, Northup PG. Advanced recipient age (>60 years) alone should not be a contraindication to liver retransplantation. Transpl Int 2009; 22:601-5. [PMID: 19220825 DOI: 10.1111/j.1432-2277.2009.00845.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Advanced age has been shown to be a risk factor for survival in primary liver transplantation. We sought to determine the independent influence of recipient age on retransplantation survival. The UNOS dataset was analyzed for adult, nonstatus 1, liver retransplantations since February 27, 2002. The univariate effect of age on 90-day and 1-year survival was analyzed. Multivariate survival models were used to determine 90-day, 1-year, and overall survival. Recipient age, donor age, model for end-stage liver disease (MELD) score, and hepatitis C status were used to construct multivariable survival models. Some 2141 liver retransplantations were analyzed. Overall, increasing recipient age was independently predictive of increasing mortality after liver retransplantation. In recipients between 18 and 60, there remained a direct relationship between age and mortality. However, in recipients aged over 60, increasing age was not independently associated with 90-day mortality (P = 0.88) and 1-year mortality (P = 0.74), despite adjusting for donor age, MELD score, and viral hepatitis status, suggesting that their original liver condition, their co-morbidities or perioperative condition plays an important role in retransplantation survival. Increasing recipient age up to 60, adversely affects liver retransplantation survival. After 60, there are no additional risks. Advanced age alone should not be an exclusionary factor when considering liver retransplantation; only the overall ability of the patient to tolerate a major surgery should be the determining factor.
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Affiliation(s)
- Timothy M Schmitt
- Department of Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA.
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Fibrosing cholestatic hepatitis with hepatitis C virus treated by double filtration plasmapheresis and interferon plus ribavirin after liver transplantation. Clin J Gastroenterol 2009; 2:125-130. [DOI: 10.1007/s12328-008-0057-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2008] [Accepted: 11/24/2008] [Indexed: 01/16/2023]
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48
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Qasim A, Zaman BM, Geoghegan J, Maguire D, Traynor O, Hegarty J, McCormick PA. Significant influence of the primary liver disease on the outcomes of hepatic retransplantation. Ir J Med Sci 2008; 178:47-51. [PMID: 18982406 DOI: 10.1007/s11845-008-0234-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2007] [Accepted: 09/25/2008] [Indexed: 10/21/2022]
Abstract
BACKGROUND There are many indications for hepatic retransplantation. AIM To identify factors influencing retransplantation needs and outcomes. PATIENTS AND METHODS Retransplantation records from January 1993 to March 2005 were analysed. Patient and disease characteristics and survival outcomes for retransplantation were compared between various groups. RESULTS Totally, 286 primary and 42 hepatic retransplantations were performed. Retransplantation indications included primary sclerosing cholangitis (PSC), primary biliary cirrhosis, chronic hepatitis C (HCV), chronic active hepatitis (CAH), and alcohol-related disease. Mean follow-up post-retransplantation was 31 +/- 9 months. Actuarial patient survival at 3 months, 1 year, 3 years, 5 years, and at the end of study was 71.4, 69, 59.5, 54.7, and 50%, respectively. Early and late retransplantation had 1-year survival of 73 and 68.5%, respectively. Retransplantation need was significantly higher for PSC, HCV, and CAH. CONCLUSIONS Hepatic retransplantation remains a successful salvage option for transplant complications; however, its need is significantly influenced by the primary liver disease.
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Affiliation(s)
- A Qasim
- Liver Transplant Unit, St Vincent's University Hospital, Dublin, Ireland.
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49
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Abstract
1. Liver failure and liver cancer from chronic hepatitis C are the most common indications for liver transplantation and numbers of both are projected to double over the next 20 years. 2. Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation and associated with accelerated progression to cirrhosis, graft loss and death. 3. Graft and patient survival is reduced in liver transplant recipients with recurrent HCV infection compared to HCV-negative recipients. 4. The natural history of chronic hepatitis C is accelerated following liver transplantation compared C, with 20% progressing to cirrhosis by 5 years. However, the rate of fibrosis progression is not uniform and may increase over time. 5. The rates of progression from cirrhosis to decompensation and from decompensation to death are also accelerated following liver transplantation. 6. Multiple host, donor and viral factors are associated with rapid fibrosis progression and HCV-related graft failure. 7. Over the last decade, graft and patient survival rates have improved following liver transplantation for non-HCV disease but not for HCV-cirrhosis. This may reflect worsening donor quality and changes in immunosuppression strategies over recent years. 8. Viral eradication by antiviral therapy prevents disease progression and improves survival. 9. The severity of recurrent hepatitis C at one year post-transplant predicts subsequent progression to cirrhosis. Annual protocol biopsies are recommended to help determine need for antiviral therapy. 10. The projected impact of recurrent hepatitis C on graft and patient survival can only be avoided by the development of safe and effective antiviral strategies which can both prevent initial graft infection and eradicate established hepatitis C recurrence.
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Affiliation(s)
- Edward J Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
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50
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Verna EC, Brown RS. Hepatitis C and liver transplantation: enhancing outcomes and should patients be retransplanted. Clin Liver Dis 2008; 12:637-59, ix-x. [PMID: 18625432 DOI: 10.1016/j.cld.2008.03.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis C (HCV)-related end-stage liver disease is the most common indication for liver transplantation. Safe expansion of the donor pool with improved rates of deceased donation and more widespread use of living and extended criteria donation are likely to decrease wait list mortality. In addition, improved antiviral treatments and a better understanding of the delicate balance between under- and over-immunosuppression in this population are needed. Finally, when recurrent advanced fibrosis occurs, the criteria for patient selection for retransplantation remain widely debated. This article reviews the literature on these topics and the work being done in each area to maximize outcomes in patients receiving transplants for HCV-related cirrhosis.
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Affiliation(s)
- Elizabeth C Verna
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
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