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Giri S, Sahu SK, Mohapatra V, Chaudhary M, Panigrahi M, Nath P, Mallick B, Praharaj DL. Comparison of Biliary Complications Between Living and Deceased Donor Liver Transplantations: A Systematic Review and Meta-analysis. Cureus 2024; 16:e69019. [PMID: 39385910 PMCID: PMC11463893 DOI: 10.7759/cureus.69019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
To understand if the risk of biliary complications is higher with living donor liver transplantation (LDLT) compared to deceased donor liver transplantation (DDLT), the present meta-analysis was conducted to analyze the differences between these two types of liver transplantations. Three databases were searched from inception to September 2023 for comparative studies reporting biliary complications with LDLT and DDLT. Odds ratios (OR) with 95% confidence intervals were calculated for all the dichotomous outcomes. Twenty-eight studies were included in the final analysis. LDLT was associated with a significantly higher incidence of biliary complications than DDLT (OR 1.96, 95% CI: 1.56-2.47). However, on subgroup analysis, only studies published in or before 2014 reported a higher incidence of biliary complications with LDLT, but not with studies published after 2014. An analysis of individual adverse events showed that LDLT was associated with a higher incidence of both bile leak (OR 3.38, 95% CI: 2.52-4.53) and biliary stricture (OR 1.75, 95% CI: 1.20-2.55). LDLT was associated with a higher incidence of overall biliary complications, including bile leak and biliary stricture. With advances in surgical techniques, there has been a reduction in the risk of biliary complications.
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Affiliation(s)
- Suprabhat Giri
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Saroj K Sahu
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Vedavyas Mohapatra
- Surgical Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Mansi Chaudhary
- Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, IND
| | - Manas Panigrahi
- Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, IND
| | - Preetam Nath
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Bipadabhanjan Mallick
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
| | - Dibya L Praharaj
- Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, IND
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Goto T, Ivanics T, Cattral MS, Reichman T, Ghanekar A, Sapisochin G, McGilvray ID, Sayed B, Lilly L, Bhat M, Selzner M, Selzner N. Superior Long-Term Outcomes of Adult Living Donor Liver Transplantation: A Cumulative Single-Center Cohort Study With 20 Years of Follow-Up. Liver Transpl 2022; 28:834-842. [PMID: 34870890 DOI: 10.1002/lt.26386] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 10/21/2021] [Accepted: 11/17/2021] [Indexed: 12/31/2022]
Abstract
Living donor liver transplantation (LDLT) is an attractive alternative to deceased donor liver transplantation (DDLT). Although both modalities have similar short-term outcomes, long-term outcomes are not well studied. We compared the 20-year outcomes of 668 adults who received LDLT with1596 DDLTs at the largest liver transplantation (LT) program in Canada. Recipients of LDLT were significantly younger and more often male than DDLT recipients (P < 0.001). Autoimmune diseases were more frequent in LDLT, whereas viral hepatitis and alcohol-related liver disease were more frequent in DDLT. LDLT recipients had lower Model for End-Stage Liver Disease scores (P = 0.008), spent less time on the waiting list (P < 0.001), and were less often inpatients at the time of LT (P < 0.001). In a nonadjusted analysis, 1-year, 10-year, and 20-year patient survival rates were significantly higher in LDLT (93%, 74%, and 56%, respectively) versus DDLT (91%, 67%, and 46%, respectively; log-rank P = 0.02) as were graft survival rates LDLT (91%, 67%, and 50%, respectively) versus (90%, 65%, and 44.3%, respectively, for DDLT; log-rank P = 0.31). After multivariable adjustment, LDLT and DDLT were associated with a similar hazard of patient and graft survival. Our data of 20 years of follow-up of LDLT from a single, large Western center demonstrates excellent long-term outcomes for recipients of LDLT.
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Affiliation(s)
- Toru Goto
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery & Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tommy Ivanics
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Henry Ford Hospital, Detroit, MI.,Department of Surgical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden
| | - Mark S Cattral
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Trevor Reichman
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Anand Ghanekar
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Ian D McGilvray
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Blayne Sayed
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Les Lilly
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Mamatha Bhat
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Markus Selzner
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
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Tang W, Qiu JG, Cai Y, Cheng L, Du CY. Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1320830. [PMID: 32908865 PMCID: PMC7468609 DOI: 10.1155/2020/1320830] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/19/2020] [Accepted: 08/07/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. METHOD A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. RESULTS Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. CONCLUSIONS LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.
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Affiliation(s)
- Wei Tang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jian-Guo Qiu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yang Cai
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Luo Cheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Cheng-You Du
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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Assessment of Fibrosis in Liver Transplant Recipients: Diagnostic Performance of Shear Wave Elastography (SWE) and Correlation of SWE Findings With Biopsy Results. AJR Am J Roentgenol 2019; 213:W264-W271. [PMID: 31573849 DOI: 10.2214/ajr.19.21160] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE. Liver transplant patients are monitored for rejection and hepatic fibrosis and often undergo liver biopsies. The purpose of the present study is to determine whether noninvasive shear wave elastography (SWE) can quantify fibrosis in liver transplant recipients, with the aim of decreasing and possibly eliminating unnecessary biopsies for patients with suspected or progressive hepatic fibrosis. MATERIALS AND METHODS. Between May 1, 2015, and December 31, 2017, our prospective study evaluated 111 adult liver transplant patients (age range, 23-79 years) who underwent 147 ultrasound (US) SWE examinations of the right hepatic lobe followed by biopsies. SWE values were compared with the histologic fibrosis (Metavir) scores of the biopsy samples. SWE threshold values were determined using classification and regression tree analysis by anchoring to the degree of fibrosis. The sensitivity, specificity, positive predictive value, and negative predictive value (with 95% CIs) were calculated on the basis of the threshold value. Overall prediction accuracy was estimated using the AUC value from the ROC curve. RESULTS. From the 147 US SWE examinations and liver biopsies, consistent threshold values were identified for patients with no or minimal fibrosis (Metavir scores of F0 and F1, respectively) compared with significant fibrosis (Metavir scores of F2, F3, or F4). A median SWE value of 1.76 m/s or less denoted no or minimal fibrosis, whereas a value greater than 1.76 m/s denoted significant fibrosis. The sensitivity of US SWE examinations in classifying fibrosis was 0.77 (95% CI, 0.5-0.93). The specificity, positive predictive value, and negative predictive value were 0.79 (95% CI, 0.71-0.86), 0.33 (95% CI, 0.19-0.49), and 0.96 (95% CI, 0.91-0.99), respectively. CONCLUSION. Liver transplant patients may avoid liver biopsy if US SWE examination shows a median shear wave velocity of 1.76 or less, which corresponds to a Metavir score of F0 or F1, denoting no or minimal fibrosis.
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Kling CE, Perkins JD, Reyes JD, Montenovo MI. Living Donation Versus Donation After Circulatory Death Liver Transplantation for Low Model for End-Stage Liver Disease Recipients. Liver Transpl 2019; 25:580-587. [PMID: 29637730 DOI: 10.1002/lt.25073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 03/31/2018] [Indexed: 02/07/2023]
Abstract
In this era of organ scarcity, living donor liver transplantation (LDLT) is an alternative to using deceased donors, and in Western countries, it is more often used for recipients with low Model for End-Stage Liver Disease (MELD) scores. We sought to compare the patient survival and graft survival between recipients of liver transplantation from living donors and donation after circulatory death (DCD) donors in patients with low MELD scores. This is a retrospective cohort analysis of adult liver transplant recipients with a laboratory MELD of ≤20 who underwent transplantation between January 1, 2003 and March 31, 2016. Recipients were categorized by donor graft type (DCD or LDLT), and recipient and donor characteristics were compared. Ten-year patient and graft survival curves were calculated using Kaplan-Meier analyses, and a mixed-effects model was performed to determine the contributions of recipient, donor, and center variables on patient and graft survival. There were 36,705 liver transplants performed: 32,255 (87.9%) from DBD donors, 2166 (5.9%) from DCD donors, and 2284 (6.2%) from living donors. In the mixed-effects model, DCD status was associated with a higher risk of graft failure (relative risk [RR], 1.27; 95% confidence interval [CI], 1.16-1.38) but not worse patient survival (RR, 1.27; 95% CI, 0.96-1.67). Lower DCD center experience was associated with a 1.21 higher risk of patient death (95% CI, 1.17-1.25) and a 1.13 higher risk of graft failure (95% CI, 1.12-1.15). LDLT center experience was also predictive of patient survival (RR, 1.03; 95% CI, 1.02-1.03) and graft failure (RR, 1.05; 95% CI, 1.05-1.06). In conclusion, for liver transplant recipients with low laboratory MELD, LDLT offers better graft survival and a tendency to better patient survival than DCD donors.
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Affiliation(s)
- Catherine E Kling
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
| | - James D Perkins
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
| | - Jorge D Reyes
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
| | - Martin I Montenovo
- Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, WA
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Goldaracena N, Barbas AS, Galante A, Sapisochin G, Al-Adra D, Selzner N, Galvin Z, Cattral MS, Greig PD, Lilly L, Bhat M, McGilvray ID, Ghanekar A, Levy G, Grant DR, Selzner M. Live donor liver transplantation with older donors: Increased long-term graft loss due to HCV recurrence. Clin Transplant 2018; 32:e13304. [PMID: 29947154 DOI: 10.1111/ctr.13304] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 05/20/2018] [Indexed: 12/20/2022]
Abstract
Using our prospectively collected database all adult hepatitis C virus (HCV)-positive patients receiving an adult-to-adult LDLT between October 2000 and May 2014 were identified. Outcome of LDLT with grafts from younger (<50 years=128) vs older donors (≥50 years=31) was compared. Post-transplant graft function, postoperative complications and incidence of HCV recurrence were evaluated. Long-term graft and patient survival was calculated. No difference in graft function was observed between younger and older grafts. Overall complications were similar between both groups. The severity of complications determined by the Dindo-Clavien score was similar. Graft loss from HCV recurrence was significantly less frequent in younger grafts (18% vs 62%, P = 0.001). Young vs older livers had a trend toward improved 1-, 5-, and 10-year graft survival (89% vs 87%, 77% vs 69%, 70% vs 55%, P = 0.096), while patient survival was comparable between both groups (91% vs 90%, 78% vs 69%, 71% vs 60%, P = 0.25). In conclusion, LDLT with older vs younger grafts are more frequently associated with long-term graft loss due to HCV recurrence. Differences in graft survival might be more prominent with prolonged (≥5-year) follow-up. Living donor-recipient matching is particularly important for younger HCV-positive recipients.
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Affiliation(s)
- Nicolas Goldaracena
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Andrew S Barbas
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Antonio Galante
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - David Al-Adra
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Nazia Selzner
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Zita Galvin
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Mark S Cattral
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Paul D Greig
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Les Lilly
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Mamatha Bhat
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Ian D McGilvray
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Anand Ghanekar
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Gary Levy
- Department of Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - David R Grant
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
| | - Markus Selzner
- Department of Surgery, Multi Organ Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada
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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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8
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Kim JM, Lee KW, Song GW, Jung BH, Lee HW, Yi NJ, Kwon CHD, Hwang S, Suh KS, Joh JW, Lee SK, Lee SG. Increased survival in hepatitis c patients who underwent living donor liver transplant: a case-control study with propensity score matching. Ann Surg Treat Res 2017; 93:293-299. [PMID: 29250507 PMCID: PMC5729122 DOI: 10.4174/astr.2017.93.6.293] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 04/19/2017] [Accepted: 05/10/2017] [Indexed: 12/18/2022] Open
Abstract
Purpose There is no consensus regarding the difference in outcomes of HCV in patients who receive living donor liver transplantation (LDLT) or compared to deceased donor liver transplantation (DDLT). The aims of this study were to compare characteristics between LDLT and DDLT groups and to identify risk factors affecting patient survival. Methods We retrospectively reviewed the multicenter records of 192 HCV RNA-positive patients who underwent liver transplantation. Results Thirty-five patients underwent DDLT, and 146 underwent LDLT. The 1-, 3-, and 5-year patient survival rates were 66.7%, 63.0%, and 63.0% in the DDLT group and 86.1%, 82.3%, and 79.5% in the LDLT group (P = 0.024), respectively. After propensity matching, the patient survival curve of the LDLT group was higher than that of the DDLT group. However, there was no statistically significant difference in patient survival between the 2 groups (P = 0.061). Recipient age ≥ 60 years, LDLT, and use of tacrolimus were positively associated with patient survival in multivariate analyses. Conclusion LDLT appears to be suitable for HCV-infected patients if appropriate living donor is available.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bo-Hyun Jung
- Department of Surgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hae Won Lee
- Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Suk-Koo Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Gambato M, Crespo G, Torres F, LLovet L, Carrión J, Londoño M, Lens S, Mariño Z, Bartres C, Miquel R, Navasa M, Forns X. Simple prediction of long-term clinical outcomes in patients with mild hepatitis C recurrence after liver transplantation. Transpl Int 2017; 29:698-706. [PMID: 26661662 DOI: 10.1111/tri.12730] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 08/20/2015] [Accepted: 12/01/2015] [Indexed: 01/11/2023]
Abstract
Little is known about the long-term outcomes of mild hepatitis C recurrence after liver transplantation (LT). In an era where most patients request treatment with direct acting antivirals (DAAs), data on the natural history in these patients are relevant. We have prospectively assessed the clinical outcomes of 173 patients with mild hepatitis C recurrence 1 year after LT. The endpoints were cirrhosis development (F = 4, HVPG ≥10 mmHg, liver stiffness measurement ≥14 kPa) and HCV-related graft loss. After a median follow-up of 80 months, the cumulative probability (CP) of HCV-related graft loss 5 and 10 years after LT were only 3% and 10%, respectively. Graft cirrhosis developed in 26 (15%) patients over time, with a CP of 13% and 30% at 5 and 10 years after LT, respectively. The CP of cirrhosis 5 years after LT was only 8% in patients with a donor <50 years and AST <60 IU/l 1 year after LT (n = 67), compared with 46% in those 24 individuals with both risk factors. Our data support an excellent long-term outcome of patients with mild hepatitis C recurrence 1 year after LT. There are, however, some patients progressing to cirrhosis who can be easily identified and who should receive prompt antiviral therapy.
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Affiliation(s)
- Martina Gambato
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Ferran Torres
- Medical Statistics Core Facility, Hospital Clinic, IDIBAPS, Barcelona, Spain.,Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Laura LLovet
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - José Carrión
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - María Londoño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Sabela Lens
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Zoe Mariño
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Concepció Bartres
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Rosa Miquel
- Pathology Department, Hospital Clínic, Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain
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10
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Kitajima T, Kaido T, Hamaguchi Y, Yagi S, Taura K, Fujimoto Y, Hatano E, Okajima H, Haga H, Uemoto S. Validation of the FIB-4 index for evaluation of fibrosis in patients with recurrent hepatitis C after living donor liver transplantation: A single center experience. Hepatol Res 2016; 46:752-7. [PMID: 26583748 DOI: 10.1111/hepr.12617] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 10/19/2015] [Accepted: 10/31/2015] [Indexed: 12/13/2022]
Abstract
AIM The FIB-4 index has been proposed as a simple, non-invasive surrogate marker of liver fibrosis in patients with hepatitis C virus (HCV). However, the utility of FIB-4 in HCV positive patients after living donor liver transplantation (LDLT) has not been assessed. The aim of this study was to evaluate the efficacy of FIB-4 in the detection of significant liver graft fibrosis caused by recurrent HCV infection after LDLT compared with other simple fibrosis markers. METHODS A total of 259 liver biopsies (LB) with evidence of recurrent HCV were taken from 110 HCV positive LDLT patients who had undergone concomitant splenectomy before administration of antiviral therapy. In LB performed at 3 months or later after LT (n = 202, subject group), FIB-4 was compared between fibrosis stages and the accuracy of FIB-4 in predicting significant fibrosis (METAVIR, F ≥ 2) was assessed compared with aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, age-platelet index, and AST to platelet ratio index (APRI). RESULTS FIB-4 was significantly different between all fibrosis stages (F0 and F1-F4, P = 0.022; F0/1 and F2-F4, P < 0.0005; and F0-F2 and F3F4, P = 0.034) and provided the best area under the receiver-operator curve (AUROC) compared with other markers (FIB-4, 0.711; APRI, 0.693; age-platelet index, 0.663; and AST to ALT ratio, 0.562). The optimal cut-off value to identify significant fibrosis was 2.20 with 65% sensitivity and 69% specificity. CONCLUSION FIB-4 is a more reliable marker for diagnosing significant liver fibrosis than APRI, age-platelet index, and AST to ALT ratio in LDLT patients with HCV.
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Affiliation(s)
- Toshihiro Kitajima
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuhei Hamaguchi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shintaro Yagi
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yasuhiro Fujimoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hideaki Okajima
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hironori Haga
- Department of Diagnostic Pathology, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Nadalin S, Capobianco I, Panaro F, Di Francesco F, Troisi R, Sainz-Barriga M, Muiesan P, Königsrainer A, Testa G. Living donor liver transplantation in Europe. Hepatobiliary Surg Nutr 2016; 5:159-75. [PMID: 27115011 DOI: 10.3978/j.issn.2304-3881.2015.10.04] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Living donor liver transplantation (LDLT) sparked significant interest in Europe when the first reports of its success from USA and Asia were made public. Many transplant programs initiated LDLT and some of them especially in Germany and Belgium became a point of reference for many patients and important contributors to the advancement of the field. After the initial enthusiasm, most of the European programs stopped performing LDLT and today the overall European activity is concentrated in a few centers and the number of living donor liver transplants is only a single digit fraction of the overall number of liver transplants performed. In this paper we analyse the present European activities and highlight the European contribution to the advancement of the field of LDLT.
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Affiliation(s)
- Silvio Nadalin
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Ivan Capobianco
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Fabrizio Panaro
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Fabrizio Di Francesco
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Roberto Troisi
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Mauricio Sainz-Barriga
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Paolo Muiesan
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Alfred Königsrainer
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
| | - Giuliano Testa
- 1 Department of General and Transplant Surgery, University Hospital Tübingen, Germany ; 2 Department of General and Liver Transplant Surgery, Saint Eloi Hospital, University of Montpellier, Montpellier, France ; 3 Department of Paediatric Surgery and Transplantation Centre, Bambino Gesù Children's Hospital, Rome, Italy ; 4 Department of General, Hepato-Biliary and Transplantation Surgery, Gent University Hospital, Gent, Belgium ; 5 Department of HPB & Liver Transplant Surgery, CHU Tours University Hospital & Medical School Chambray-lès-Tours, France ; 6 Liver Surgery and Transplant Unit, Queen Elizabeth Hospital, Birmingham, UK ; 7 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center at Dallas, Dallas, TX, USA
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12
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Burra P, De Martin E, Zanetto A, Senzolo M, Russo FP, Zanus G, Fagiuoli S. Hepatitis C virus and liver transplantation: where do we stand? Transpl Int 2016; 29:135-152. [PMID: 26199060 DOI: 10.1111/tri.12642] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 03/06/2015] [Accepted: 07/15/2015] [Indexed: 12/14/2022]
Abstract
The hepatitis C virus (HCV) infects more than 180 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to liver cirrhosis leading to liver transplantation or death, and HCV recurrence still constitutes a major challenge for the transplant team. Antiviral therapy is the only available instrument to slow down this process, although its actual impact on liver histology, in responders and nonresponders, is still controversial. We are now facing a "new era" of direct antiviral agents that is already changing the approach to HCV burden both in the pre- and in the post-liver transplantation settings. Available data on sofosbuvir/ledipasvir and sofosbuvir/simeprevir in patients with decompensated cirrhosis sustain a SVR12 of 89% , but one-third of patients do not clinically improved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with HCC before liver transplantation is associated with 2% recurrence rate if liver transplantation is performed at least one month after undetectable HCV-RNA is achieved. The treatment of recurrence with the new antiviral drugs is associated with a SVR that ranges between 60 and 90%. In this review, we have focused on the evolution of antiviral therapy for HCV recurrence from the "old" interferon-based therapy to the "new" interferon-free regimens, highlighting useful information to aid the transplant hepatologist in the clinical practice.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Eleonora De Martin
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Centre Hepato-Biliaire Paul Brousse, Villejuif, France
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Giacomo Zanus
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
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13
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Grassi A, Ballardini G. Post-liver transplant hepatitis C virus recurrence: an unresolved thorny problem. World J Gastroenterol 2014; 20:11095-11115. [PMID: 25170198 PMCID: PMC4145752 DOI: 10.3748/wjg.v20.i32.11095] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 02/15/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV)-related cirrhosis represents the leading cause of liver transplantation in developed, Western and Eastern countries. Unfortunately, liver transplantation does not cure recipient HCV infection: reinfection universally occurs and disease progression is faster after liver transplant. In this review we focus on what happens throughout the peri-transplant phase and in the first 6-12 mo after transplantation: during this crucial period a completely new balance between HCV, liver graft, the recipient's immune response and anti-rejection therapy is achieved that will deeply affect subsequent outcomes. Nearly all patients show an early graft reinfection, with HCV viremia reaching and exceeding pre-transplant levels; in this setting, histological assessment is essential to differentiate recurrent hepatitis C from acute or chronic rejection; however, differentiating the two patterns remains difficult. The host immune response (mainly cellular mediated) appears to be crucial both in the control of HCV infection and in the genesis of rejection, and it is also strongly influenced by immunosuppressive treatment. At present no clear immunosuppressive strategy could be strongly recommended in HCV-positive recipients to prevent HCV recurrence, even immunotherapy appears to be ineffective. Nonetheless it seems reasonable that episodes of rejection and over-immunosuppression are more likely to enhance the risk of HCV recurrence through immunological mechanisms. Both complete prevention of rejection and optimization of immunosuppression should represent the main goals towards reducing the rate of graft HCV reinfection. In conclusion, post-transplant HCV recurrence remains an unresolved, thorny problem because many factors remain obscure and need to be better determined.
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14
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Akamatsu N, Sugawara Y, Kokudo N, Eguchi S, Fujiwara T, Ohdan H, Nagano H, Taketomi A, Kitagawa Y, Shimada M, Ku Y, Yanaga K, Shirabe K, Ikegami T, Mizokami M, Takeuchi M, Maehara Y. Outcomes of living donor liver transplantation for hepatitis C virus-positive recipients in Japan: results of a nationwide survey. Transpl Int 2014; 27:767-774. [PMID: 24684710 DOI: 10.1111/tri.12329] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Revised: 02/17/2014] [Accepted: 03/28/2014] [Indexed: 02/06/2023]
Abstract
A nationwide survey of living donor liver transplantation (LDLT) for hepatitis C virus (HCV)-positive recipients was performed in Japan. A total of 514 recipients are reported and included in the study. The cumulative patient survival rate at 5 and 10 years was 72% and 63%, respectively. Of the 514 recipients, 142 patients (28%) died until the end of the observation, among which the leading cause was recurrent hepatitis C (42 cases). According to Cox regression multivariate analysis, donor age (>40), non-right liver graft, acute rejection episode, and absence of a sustained virologic response were independent prognostic factors. Of the 514 recipients, 361 underwent antiviral treatment mainly with pegylated-interferon and ribavirin (preemptive treatment in 150 patients and treatment for confirmed recurrent hepatitis in 211). The dose reduction rate and discontinuation rate were 40% and 42%, respectively, with a sustained virologic response rate of 43%. In conclusion, patient survival of HCV-positive recipients after LDLT was good, with a 10-year survival of 63%. Right liver graft might be preferable for HCV-positive recipients in an LDLT setting.
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Affiliation(s)
- Nobuhisa Akamatsu
- Division of Artificial Organ and Transplantation, Department of Surgery, University of Tokyo, Tokyo, Japan
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15
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Mariño Z, Mensa L, Crespo G, Miquel R, Bruguera M, Pérez-Del-Pulgar S, Bosch J, Forns X, Navasa M. Early periportal sinusoidal fibrosis is an accurate marker of accelerated HCV recurrence after liver transplantation. J Hepatol 2014; 61:270-7. [PMID: 24703854 DOI: 10.1016/j.jhep.2014.03.029] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 03/18/2014] [Accepted: 03/26/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Significant liver fibrosis (F ⩾ 2) and portal hypertension (hepatic venous pressure gradient [HVPG] ⩾ 6 mmHg) 1 year after liver transplantation (LT) are predictors of severe hepatitis C recurrence. Periportal sinusoidal fibrosis (SF) is an early expression of the fibrogenic process in response to liver injury. We aimed to evaluate whether SF in early liver biopsies represents an early and accurate marker for identifying patients with severe HCV recurrence after LT. METHODS A total of 101 HCV LT patients with early biopsy (<6 months), and HVPG measurement and/or liver biopsy one year after LT were included. Early biopsies were stained with Sirius Red and SF was graded semi-quantitatively. Results were compared between groups (significant SF vs. non-significant SF) and correlated with the development of severe HCV recurrence one year after LT. RESULTS Patients with early significant SF had older donor age and higher necroinflammatory activity (NIA). The presence of early significant SF enabled identification of 78.9% and 90.6% of patients with F ⩾ 2 and HVPG ⩾ 6 mmHg, respectively, one year after LT. Donor age and NIA were independent predictors of significant fibrosis (F ⩾ 2) one year after LT, whereas donor age, ALT (3 months), NIA, and SF grade were independent predictors of portal hypertension (HVPG ⩾ 6). CONCLUSIONS Significant SF in early biopsies is a good predictor of severe hepatitis C recurrence. This histological finding, when combined with simple variables, may be useful to select the best candidates for early antiviral therapy after LT.
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Affiliation(s)
- Zoe Mariño
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Laura Mensa
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Gonzalo Crespo
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Rosa Miquel
- Pathology Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Miquel Bruguera
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Sofía Pérez-Del-Pulgar
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Jaume Bosch
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Xavier Forns
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
| | - Miquel Navasa
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain.
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16
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Dhanasekaran R, Firpi RJ. Challenges of recurrent hepatitis C in the liver transplant patient. World J Gastroenterol 2014; 20:3391-3400. [PMID: 24707122 PMCID: PMC3974506 DOI: 10.3748/wjg.v20.i13.3391] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 11/22/2013] [Accepted: 03/10/2014] [Indexed: 02/06/2023] Open
Abstract
Cirrhosis secondary to hepatitis C virus (HCV) is a very common indication for liver transplant. Unfortunately recurrence of HCV is almost universal in patients who are viremic at the time of transplant. The progression of fibrosis has been shown to be more rapid in the post-transplant patients than in the transplant naïve, hence treatment of recurrent HCV needs to be considered for all patients with documented recurrent HCV. Management of recurrent HCV is a challenging situation both for patients and physicians due to multiple reasons as discussed in this review. The standard HCV treatment with pegylated interferon and Ribavarin can be considered in these patients but it leads to a lower rate of sustained virologic clearance than in the non-transplanted population. Some of the main challenges associated with treating recurrent HCV in post-transplant patients include the presence of cytopenias; need to monitor drug-drug interactions and the increased incidence of renal compromise. In spite of these obstacles all patients with recurrent HCV should be considered for treatment since it is associated with improvement in survival and a delay in fibrosis progression. With the arrival of direct acting antiviral drugs there is renewed hope for better outcomes in the treatment of post-transplant HCV recurrence. This review evaluates current literature on this topic and identifies challenges associated with the management of post-transplant HCV recurrence.
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17
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Terrault NA, Stravitz RT, Lok ASF, Everson GT, Brown RS, Kulik LM, Olthoff KM, Saab S, Adeyi O, Argo CK, Everhart JE, Rodrigo DR. Hepatitis C disease severity in living versus deceased donor liver transplant recipients: an extended observation study. Hepatology 2014; 59:1311-1319. [PMID: 24677192 PMCID: PMC4118586 DOI: 10.1002/hep.26920] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 09/20/2013] [Accepted: 10/28/2013] [Indexed: 12/23/2022]
Abstract
UNLABELLED Donor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage ≥3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23). CONCLUSION Donor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT.
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18
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Wan P, Yu X, Xia Q. Operative outcomes of adult living donor liver transplantation and deceased donor liver transplantation: a systematic review and meta-analysis. Liver Transpl 2014; 20:425-36. [PMID: 24478109 DOI: 10.1002/lt.23836] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 01/05/2014] [Indexed: 12/11/2022]
Abstract
Living donor liver transplantation (LDLT) has emerged as an alternative to deceased donor liver transplantation (DDLT) because of the increasing number of patients waiting for liver transplantation (LT). However, whether it can achieve operative outcomes similar to those achieved with DDLT for adult patients remains controversial. We conducted this meta-analysis to compare the operative outcomes of LDLT and DDLT recipients. A literature search was performed to identify clinical controlled studies comparing LDLT and DDLT that were published before October 2013. Four perioperative outcomes [duration of the recipient operation (DRO), red blood cell (RBC) transfusion requirement, length of the hospital stay, and cold ischemia time (CIT)] and 5 postoperative complication outcomes (biliary complications, vascular complications, intra-abdominal bleeding, perioperative death, and retransplantation) were the main outcomes assessed. Nineteen studies with a total of 5450 patients were included in the meta-analysis. In comparison with DDLT, LDLT was associated with a significantly longer DRO and a shorter CIT. We found that biliary complications [odds ratio (OR) = 3.08, 95% confidence interval (CI) = 1.97-4.81, P < 0.001], vascular complications (OR = 2.16, 95% CI = 1.32-3.54, P = 0.002), and retransplantation (OR = 1.76, 95% CI = 1.09-2.83, P = 0.02) occurred more frequently for LDLT recipients, and the subgroup analysis indicated that the biliary complication rate decreased dramatically with greater LDLT experience. No significant difference was observed in RBC transfusion requirements, the lengths of hospital stays, intra-abdominal bleeding rates, or perioperative mortality between LDLT and DDLT recipients. In conclusion, LDLT is associated with a higher rate of surgical complications after transplantation. A reduction of postoperative complication rates can be achieved as centers gain greater experience with LDLT. However, LDLT is still an excellent alternative to DDLT because it facilitates access to LT.
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Affiliation(s)
- Ping Wan
- Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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19
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Walzer N, Flamm SL. Pegylated IFN-α and ribavirin: emerging data in the treatment of special populations. Expert Rev Clin Pharmacol 2014; 2:67-76. [PMID: 24422772 DOI: 10.1586/17512433.2.1.67] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Hepatitis C virus (HCV) is one of the most common causes of chronic liver disease and is currently the leading indication for liver transplantation in the USA. Pegylated IFN-α (PEG-IFN-α) and ribavirin comprise the standard of care for the treatment of chronic HCV. The expansion of antiviral therapy to include special populations that were not well represented or excluded from registration trials has occurred in recent years. Data have emerged that demonstrate that these groups have variable responses to therapy and, in some cases, different side-effect profiles. The etiologies for the varied response rates remain under investigation. This review will address the clinical efficacy and safety profiles of PEG-IFN-α and ribavirin in populations of patients coinfected with HIV, obese patients, liver transplant recipients, children and African-Americans.
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Affiliation(s)
- Natasha Walzer
- Northwestern Feinberg School of Medicine, 675 N St Clair Galter 15-250, Chicago, IL 60611, USA
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20
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Ohdan H. Is living donor liver transplantation really equivalent to deceased donor liver transplantation? Transpl Int 2013; 26:778-9. [PMID: 23855656 DOI: 10.1111/tri.12141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2013] [Accepted: 06/10/2013] [Indexed: 11/27/2022]
Affiliation(s)
- Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan
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21
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Ciria R, Pleguezuelo M, Khorsandi SE, Davila D, Suddle A, Vilca-Melendez H, Rufian S, de la Mata M, Briceño J, Cillero PL, Heaton N. Strategies to reduce hepatitis C virus recurrence after liver transplantation. World J Hepatol 2013; 5:237-50. [PMID: 23717735 PMCID: PMC3664282 DOI: 10.4254/wjh.v5.i5.237] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2012] [Revised: 11/16/2012] [Accepted: 12/01/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not re-transplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pre-transplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of post-transplant HCV recurrence and strategies to reduce its impact on our patients.
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Affiliation(s)
- Ruben Ciria
- Ruben Ciria, Shirin Elizabeth Khorsandi, Diego Davila, Abid Suddle, Hector Vilca-Melendez, Nigel Heaton, Institute of Liver Studies, King's College Hospital, London SE5 9RS, United Kingdom
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New insights in recurrent HCV infection after liver transplantation. Clin Dev Immunol 2013; 2013:890517. [PMID: 23710205 PMCID: PMC3655463 DOI: 10.1155/2013/890517] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2012] [Revised: 03/17/2013] [Accepted: 03/31/2013] [Indexed: 12/15/2022]
Abstract
Hepatitis C virus (HCV) is a small-enveloped RNA virus belonging to the Flaviviridae family. Since first identified in 1989, HCV has been estimated to infect 170 million people worldwide. Mostly chronic hepatitis C virus has a uniform natural history, from liver cirrhosis to the development of hepatocellular carcinoma. The current therapy for HCV infection consists of a combination of Pegylated interferon and ribavirin. On the other hand, HCV-related liver disease is also the leading indication for liver transplantation. However, posttransplant HCV re-infection of the graft has been reported to be universal. Furthermore, the graft after HCV re-infection often results in accelerated progression to liver failure. In addition, treatment of recurrent HCV infection after liver transplantation is often compromised by enhanced adverse effects and limited efficacy of interferon-based therapies. Taken together, poor outcome after HCV re-infection, regardless of grafts or recipients, poses a major issue for the hepatologists and transplant surgeons. The aim of this paper is to review several specific aspects regarding HCV re-infection after transplant: risk factors, current therapeutics for HCV in different stages of liver transplantation, cellular function of HCV proteins, and molecular mechanisms of HCV entry. Hopefully, this paper will inspire new strategies and novel inhibitors against recurrent HCV infection after liver transplantation and greatly improve its overall outcome.
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23
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Schepis F, Vukotic R, Berzigotti A, Carrión JA, Forns X, Abraldes JG, García-Valdecasas JC, Navasa M, García-Pagán JC, Bosch J. Hemodynamic response to propranolol in patients with recurrent hepatitis C virus-related cirrhosis after liver transplantation: a case-control study. Liver Transpl 2013; 19:450-6. [PMID: 23408436 DOI: 10.1002/lt.23614] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 01/13/2013] [Indexed: 02/07/2023]
Abstract
Cirrhosis recurrence is frequent after orthotopic liver transplantation for hepatitis C virus (HCV). Because transplantation causes liver denervation, we hypothesized that the response to propranolol might differ in transplant patients versus nontransplant patients with cirrhosis and portal hypertension. Twenty-one patients with cirrhosis recurrence after orthotopic liver transplantation with portal hypertension were compared to 20 nontransplant patients with cirrhosis, HCV, and portal hypertension, and they were matched by sex, age, presence of varices, and Child-Pugh score. The patients underwent systemic and hepatic hemodynamic measurements at the baseline and 20 minutes after intravenous propranolol (0.15 mg/kg). At the baseline, the transplant patients with cirrhosis had a lower hepatic venous pressure gradient (HVPG) than the nontransplant patients with cirrhosis (14.8 ± 2.9 versus 17.3 ± 4.4 mm Hg, P = 0.03) but a higher mean arterial pressure (MAP; 100.3 ± 12.3 versus 91.8 ± 11.6 mm Hg, P = 0.04) and higher systemic vascular resistance (2253 ± 573 versus 1883 ± 525 dyn/second/cm(-5) , P = 0.03). There were no differences in the cardiac index (CI). Propranolol significantly decreased HVPG to similar extents in transplant patients and nontransplant patients with cirrhosis (-14.1% ± 8.0% versus -16.9% ± 9.5%, P > 0.99). MAP tended to increase in transplant patients with cirrhosis, whereas it slightly decreased in nontransplant patients (5.1% ± 14.2% versus -4.8% ± 6.4%, P = 0.007); however, the reduction in CI was less marked in transplant patients with cirrhosis (-18.6% ± 7.6% versus -26.9% ± 9.0%, P = 0.005). In conclusion, patients with HCV-related cirrhosis and portal hypertension after orthotopic liver transplantation have lower baseline HVPG values but similar HVPG responses to propranolol infusions in comparison with nontransplant patients with cirrhosis. In contrast to nontransplant patients, propranolol increases the systemic vascular resistance and arterial pressure in transplant patients with cirrhosis and attenuates the fall in CI.
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Affiliation(s)
- Filippo Schepis
- Hepatic Hemodynamic Laboratory and Liver Transplantation Section, Barcelona, Spain
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24
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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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25
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Ikegami T, Shirabe K, Yoshiya S, Yoshizumi T, Yamashita YI, Harimoto N, Toshima T, Uchiyama H, Soejima Y, Maehara Y. A high MELD score, combined with the presence of hepatitis C, is associated with a poor prognosis in living donor liver transplantation. Surg Today 2013; 44:233-40. [DOI: 10.1007/s00595-013-0523-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Accepted: 11/05/2012] [Indexed: 02/07/2023]
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Akamatsu N, Sugawara Y. 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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Affiliation(s)
- Nobuhisa Akamatsu
- Department of Hepato-Biliary-Pancreatic Surgery, Saitama Medical Center, Saitama Medical University, 1981 Tsujido-cho, Kamoda, Kawagoe, Saitama 350-8550, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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27
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Living donor liver transplantation for HCV: will the true outcomes stand up? J Hepatol 2012; 57:1166-7. [PMID: 22989566 DOI: 10.1016/j.jhep.2012.09.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2012] [Accepted: 09/04/2012] [Indexed: 12/04/2022]
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Hu A, Liang W, Zheng Z, Guo Z, He X. Living donor vs. deceased donor liver transplantation for patients with hepatitis C virus-related diseases. J Hepatol 2012; 57:1228-43. [PMID: 22820490 DOI: 10.1016/j.jhep.2012.07.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2012] [Revised: 06/23/2012] [Accepted: 07/12/2012] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS Living donor liver transplantation (LDLT) provides a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatitis C virus-related (HCV-related) diseases in the circumstances of severe organ dearth. However, the patient and graft outcomes, and recurrence of HCV after LDLT remain controversial. Here we sought to compare the post-transplant outcomes after LDLT and DDLT. METHODS A systematic review and meta-analysis were performed. PubMed/MEDLINE, EMBASE, and the Cochrane database were searched for eligible literatures. The major end points were patient survival, graft survival, recurrence rate, and acute rejection. The pooled odds ratio (OR) was calculated using random-effects model to synthesize the results. Heterogeneity and publication bias were quantitatively evaluated. RESULTS Fourteen studies with a total of 2024 participants were included in this analysis. We found comparable patient survival between groups (1-year: OR, 0.78, 95% CI, 0.48-1.26, p=0.31; 2-year: OR, 0.71, 95% CI, 0.41-1.23, p=0.23; 3-year: OR, 0.79, 95% CI, 0.5-1.12, p=0.18; 4-year: OR, 0.92, 95% CI, 0.43-1.95, p=0.83; 5-year: OR, 1.06, 95% CI, 0.53-2.14, p=0.86, respectively). Although 1- and 3-year graft survivals were inferior in LDLT, 2-, 4- and 5-year graft survivals were similar. HCV recurrence rates and acute rejection rates were equivalent. CONCLUSIONS LDLT was equivalent to DDLT in terms of patient survival, long-term graft survival, HCV recurrence, and acute rejection rates, with potentially lower short-term patient and graft survival.
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Affiliation(s)
- Anbin Hu
- Department of General Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
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29
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Takada Y, Uemoto S. Living donor liver transplantation for hepatitis C. Surg Today 2012; 43:709-14. [PMID: 23052749 DOI: 10.1007/s00595-012-0361-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 07/05/2012] [Indexed: 12/20/2022]
Abstract
Liver cirrhosis and hepatocellular carcinoma related to chronic hepatitis C virus (HCV) infection are currently the most common indications for liver transplantation. The number of living donor liver transplantation (LDLT) procedures has increased given the shortage of donor organs from deceased donors. However, recurrence of HCV infection is universal and affects graft survival. This mini-review compared the outcomes for HCV-positive recipients after LDLT with those after deceased donor liver transplantation.
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Affiliation(s)
- Yasutsugu Takada
- Department of Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, 791-0295, Japan.
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30
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Quintini C, Hashimoto K, Uso TD, Miller C. Is there an advantage of living over deceased donation in liver transplantation? Transpl Int 2012; 26:11-9. [PMID: 22937787 DOI: 10.1111/j.1432-2277.2012.01550.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Living donor liver transplantation (LDLT) is a well-established strategy to decrease the mortality in the waiting list and recent studies have demonstrated its value even in patients with low MELD score. However, LDLT is still under a high level of scrutiny because of its technical complexity and ethical challenges as demonstrated by a decline in the number of procedures performed in the last decade in Western Countries. Many aspects make LDLT different from deceased donor liver transplantation, including timing of transplantation, procedure-related complications as well as immunological factors that may affect graft outcomes. Our review suggests that in selected cases, LDLT offers significant advantages over deceased donor liver transplantation and should be used more liberally.
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31
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Carbone M, Lenci I, Baiocchi L. Prevention of hepatitis C recurrence after liver transplantation: An update. World J Gastrointest Pharmacol Ther 2012; 3:36-48. [PMID: 22966482 PMCID: PMC3437445 DOI: 10.4292/wjgpt.v3.i4.36] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 06/20/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C related liver failure and hepatocarcinoma are the most common indications for liver transplantation in Western countries. Recurrent hepatitis C infection of the allograft is universal and immediate following liver transplantation, being associated with accelerated progression to cirrhosis, graft loss and death. Graft and patient survival is reduced in liver transplant recipients with recurrent Hepatitis C virus (HCV) infection compared to HCV-negative recipients. Many variables may impact on recurrent HCV liver disease. Overall, excess immunosuppression is believed to be a key factor; however, no immunosuppressive regimen has been identified to be more beneficial or less harmful. Donor age limitations, exclusion of moderately to severely steatotic livers and minimization of ischemic times could be a potential strategy to minimize the severity of HCV disease in transplanted subjects. After transplantation, antiviral therapy based on pegylated IFN alpha with or without ribavirin is associated with far less results than that reported for immunocompetent HCV-infected patients. New findings in the field of immunotherapy and genomic medicine applied to this context are promising.
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Affiliation(s)
- Marco Carbone
- Marco Carbone, Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, United Kingdom
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32
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Akamatsu N, Sugawara Y. Liver transplantation and hepatitis C. Int J Hepatol 2012; 2012:686135. [PMID: 22900194 PMCID: PMC3412106 DOI: 10.1155/2012/686135] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Accepted: 05/21/2012] [Indexed: 02/07/2023] Open
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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Affiliation(s)
- Nobuhisa Akamatsu
- Department of Hepato-Biliary-Pancreatic Surgery, Saitama Medical Center, Saitama Medical University, 1981 Tsujido-cho, Kamoda, Kawagoe, Saitama 350-8550, Japan
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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33
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Germani G, Tsochatzis E, Papastergiou V, Burroughs AK. HCV in liver transplantation. Semin Immunopathol 2012; 35:101-10. [PMID: 22829333 DOI: 10.1007/s00281-012-0329-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 07/01/2012] [Indexed: 12/23/2022]
Abstract
HCV-related cirrhosis represents the leading indication for liver transplantation in the Western countries. HCV reinfection after liver transplantation occurs in virtually all patients transplanted for HCV-related liver disease Histological evidence of chronic HCV infection develops in 50 to 90 % of patients by 12 months after liver transplantation, and cirrhosis occurs in about 20 % of patients within 5 years after transplant. Several studies have evaluated host, viral, and transplant-related factors that might be associated with the severity of HCV recurrence. Among host factors, immunosuppression is one of the major factors that accounts for accelerated HCV recurrence and it has been an area of extensive research and controversy. Donor age, steatosis, and immunogenetic factors are also relevant in determining the outcome in patients transplanted for HCV-related cirrhosis. A major step to prevent complications of HCV recurrence related to the rapid fibrosis is the posttransplant antiviral treatment. Two strategies have been tried: pre-emptive or other strategies as soon as possible after liver transplantation or elective therapy once there is histological evidence of recurrent hepatitis C. Retransplantation due to graft failure from recurrent hepatitis C is rarely an option in the era of organ shortage as it is associated with poor outcome, but many case needs to be considered early in the evolution of disease. New antivirals may change the outcome dramatically of patients transplanted for HCV cirrhosis.
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Affiliation(s)
- Giacomo Germani
- The Royal Free Sheila Sherlock Liver Centre and University Department of Surgery, Royal Free Hospital and UCL, London, UK
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34
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Taki-Eldin A, Zhou L, Xie HY, Zheng SS. Liver regeneration after liver transplantation. ACTA ACUST UNITED AC 2012; 48:139-53. [PMID: 22572792 DOI: 10.1159/000337865] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2011] [Accepted: 02/07/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND/PURPOSE The liver has a remarkable capacity to regenerate after injury or resection. The aim of this review is to outline the mechanisms and factors affecting liver regeneration after liver transplantation. METHODS Relevant studies were reviewed using Medline, PubMed and Springer databases. RESULTS A variety of cytokines (such as interleukin-6 and tumor necrosis factor-α), growth factors (like hepatocyte growth factor and transforming growth factor-α) and cells are involved in liver regeneration. Several factors affect liver regeneration after transplantation such as ischemic injury, graft size, immunosuppression, steatosis, donor age and viral hepatitis. CONCLUSION Liver regeneration has been studied for many years. However, further research is essential to reveal the complex processes affecting liver regeneration, which may provide novel strategies in the management of liver transplantation recipients and donors.
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Affiliation(s)
- A Taki-Eldin
- Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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35
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Marubashi S, Umeshita K, Asahara T, Fujiwara K, Haga H, Hashimoto T, Hatakeyama K, Ichida T, Kanematsu T, Kitajima M, Kiyosawa K, Makuuchi M, Miyagawa S, Satomi S, Soejima Y, Takada Y, Tanaka N, Teraoka S, Monden M. Steroid-free living donor liver transplantation for HCV--a multicenter prospective cohort study in Japan. Clin Transplant 2012; 26:857-67. [PMID: 22507465 DOI: 10.1111/j.1399-0012.2012.01627.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2012] [Indexed: 12/29/2022]
Abstract
This prospective, non-randomized, multicenter cohort study analyzed the safety and efficacy of a steroid-free immunosuppressive (IS) protocol for hepatitis C virus (HCV)-positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assigned the steroid-free IS protocol (Fr group) and 29 the traditional steroid-containing IS protocol (St group). Serum HCV RNA levels increased over time and were higher in the St group until postoperative day 90 (POD 14, p=0.013). Preemptive anti-HCV therapy was started in a higher percentage of recipients (59.3%) in the Fr group than in the St group (31.0%, p=0.031), mainly due to early HCV recurrence. The incidence of HCV recurrence at one yr was lower in the Fr group (22.2%) than in the St group (41.4%; p=0.066). The incidence of acute cellular rejection was similar between groups. New onset diabetes after transplant, cytomegalovirus infection, and renal dysfunction were significantly less frequent in the Fr group than in the St group (p=0.022, p<0.0001, p=0.012, respectively). The steroid-free IS protocol safely reduced postoperative morbidity and effectively suppressed both the HCV viral load in the early post-transplant period and HCV recurrence in HCV-positive LDLT recipients.
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Affiliation(s)
- Shigeru Marubashi
- Department of Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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36
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Sikka S. Treatment of hepatitis C in liver transplant patient. APOLLO MEDICINE 2012. [DOI: 10.1016/s0976-0016(12)60121-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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37
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Adebajo CO, Talwalkar JA, Poterucha JJ, Kim WR, Charlton MR. Ultrasound-based transient elastography for the detection of hepatic fibrosis in patients with recurrent hepatitis C virus after liver transplantation: a systematic review and meta-analysis. Liver Transpl 2012; 18:323-31. [PMID: 22140010 DOI: 10.1002/lt.22460] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Ultrasound-based transient elastography (TE) is a promising noninvasive alternative to liver biopsy for the detection of hepatic fibrosis due to recurrent hepatitis C virus (HCV) after liver transplantation (LT). However, its overall test performance in various settings remains unknown. The aim of this study was to perform a systematic review and diagnostic accuracy meta-analysis of studies comparing ultrasound-based TE to liver biopsy for the detection of hepatic fibrosis due to a recurrent HCV infection after LT. Electronic and manual bibliographic searches (including scientific abstracts) were performed to identify potential studies. A meta-analysis was conducted to generate pooled estimates of the sensitivity values, specificity values, likelihood ratios, and diagnostic odds ratios of individual studies. The extent of the heterogeneity and the reasons for it were assessed. Six fully published studies were identified for analysis. Five studies that evaluated significant fibrosis were identified. Among these studies, the pooled estimates were 83% for sensitivity [95% confidence interval (CI) = 77%-88%], 83% for specificity (95% CI = 77%-88%), 4.95 for the positive likelihood ratio (95% CI = 3.4-7.2), 0.17 for the negative likelihood ratio (95% CI = 0.09-0.35), and 30.5 for the diagnostic odds ratio (95% CI = 12.8-72.4). For the 5 studies that assessed cirrhosis, the pooled estimates were 98% for sensitivity (95% CI = 90%-100%), 84% for specificity (95% CI = 80%-88%), 7 for the positive likelihood ratio (95% CI = 2.8-17.3), 0.06 for the negative likelihood ratio (95% CI = 0.02-0.19), and 130 for the diagnostic odds ratio (95% CI = 36.5-462.1). A diagnostic threshold (or cutoff value) bias was identified as an important cause of heterogeneity for the pooled results of both patient groups. In conclusion, ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis due to a recurrent HCV infection after LT. The detection of significant fibrosis is more accurate for these patients versus patients whose native liver is chronically infected with HCV.
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Affiliation(s)
- Corlan O Adebajo
- Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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38
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Jonge JD, Olthoff KM. Liver regeneration. BLUMGART'S SURGERY OF THE LIVER, PANCREAS AND BILIARY TRACT 2012:87-101.e6. [DOI: 10.1016/b978-1-4377-1454-8.00005-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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39
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Sher L, Jennings L, Rudich S, Alexopoulos SP, Netto G, Teperman L, Kinkhabwala M, Brown RS, Pomfret E, Klintmalm G. Results of live donor liver transplantation in patients with hepatitic C virus infection: the HCV 3 trial experience. Clin Transplant 2011; 26:502-9. [DOI: 10.1111/j.1399-0012.2011.01561.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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40
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Evaluation of a portable hemoglobinometer (HemoCue) to control anemia in hepatitis C liver transplant recipients undergoing antiviral therapy. Eur J Gastroenterol Hepatol 2011; 23:942-7. [PMID: 21772147 DOI: 10.1097/meg.0b013e328348f9c2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Monitoring of anemia, the most frequent side-effect of antiviral therapy in hepatitis C virus (HCV)-infected liver transplant recipients, requires frequent blood tests and medical visits. AIMS The primary aim of this study was to assess the usefulness and the accuracy of a portable hemoglobinometer (HemoCue) in patients receiving antiviral therapy after liver transplantation due to severe hepatitis C recurrence in the graft. The secondary aim was to evaluate the usefulness of this device in terms of cost-saving and time-saving benefits. METHODS Multiple simultaneous hemoglobin measurements were obtained in venous blood by the reference method (ADVIA 120) and in capillary blood using HemoCue in 16 patients receiving antiviral therapy after liver transplantation. In addition, paired HemoCue measurements were taken to assess the reproducibility of this method, and correlation coefficients (CC) were calculated between them. Time requirements and cost of both procedures were recorded and compared. RESULTS HemoCue showed an excellent reproducibility (CC 0.92) and very high correlation with the standard method (CC 0.89). Its accuracy in detecting anemia (hemoglobin ≤10 mg/dl) was excellent as well (area under the receiver operator characteristic curve, 0.96). The application of HemoCue in this cohort of patients resulted in a significant reduction in the economical expense and labor (i.e., time) per patient during follow-up. CONCLUSION HemoCue is accurate and reproducible in measuring hemoglobin levels, and could be effectively used in this cohort of patients to control anemia during antiviral therapy. It could also help to reduce both overall costs and displacements, thereby improving the quality of life of these patients.
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Comparative Analysis of Hepatitis C Recurrence and Fibrosis Progression Between Deceased-Donor and Living-Donor Liver Transplantation: 8-Year Longitudinal Follow-Up. Transplantation 2011; 92:453-60. [DOI: 10.1097/tp.0b013e3182259282] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Deshpande R, O'Reilly D, Sherlock D. Improving Outcomes with Surgical Resection and Other Ablative Therapies in HCC. Int J Hepatol 2011; 2011:686074. [PMID: 21994867 PMCID: PMC3170839 DOI: 10.4061/2011/686074] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Revised: 03/24/2011] [Accepted: 04/10/2011] [Indexed: 12/13/2022] Open
Abstract
With rising incidence and emergence of effective treatment options, the management of hepatocellular carcinoma (HCC) is a complex multidisciplinary process. There is still little consensus and uniformity about clinicopathological staging systems. Resection and liver transplantation have been the cornerstone of curative surgical treatments with recent emergence of ablative techniques. Improvements in diagnostics, surgical techniques, and postoperative care have lead to dramatically improved results over the years. The most appropriate treatment plan has to be individualised and depends on a variety of patient and tumour-related factors. Very small HCCs discovered on surveillance have the best outcomes. Patients with advanced cirrhosis and tumours within Milan criteria should be offered transplantation. Resection is best for small solitary tumours with preserved liver function. Ablative techniques are suitable for low volume tumours in patients unfit for either resection or transplantation. The role of downstaging and bridging therapy is not clearly established.
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Affiliation(s)
- Rahul Deshpande
- Department of Hepatobiliary Surgery, North Manchester General Hospital, Crumpsall, Manchester M8 5RB, UK
| | - Derek O'Reilly
- Department of Hepatobiliary Surgery, North Manchester General Hospital, Crumpsall, Manchester M8 5RB, UK
| | - David Sherlock
- Department of Hepatobiliary Surgery, North Manchester General Hospital, Crumpsall, Manchester M8 5RB, UK
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Abstract
A perception that living donor liver transplantation can be accomplished with an acceptable donor complication rate and recipient survival rate has led to the acceptance of living donor liver transplantation as a viable alternative to decreased deceased donor transplantation. Careful candidate evaluation and selection has been crucial to the success of this procedure. Advancements in the understanding of the lobar nature of the liver and of liver regeneration have advanced the surgical technique. Initial attempts at adult-to-adult donation utilized the left hepatic lobe, but now have evolved into use of the right hepatic lobe. Size matching is very important to successful graft function in the recipient. There is great concern regarding morbidity and mortality in donors. Biliary complications and infections continue to be among the most highly reported complications, although rates vary among centers and countries. Reports of single center complications have ranged from 9% to 67%. A survey of centers in the United States in 2003 reported complications of 10%. A series from our institution reported complications arising in 13 (33%) of 39 patients. A review focused on documenting donor deaths found 33 living liver donor deaths worldwide. The much publicized immediate postoperative mishap of 2002 that resulted in a donor’s death resulted in a drop in the utilization of living donor liver transplantation in the United States, from which this procedure has never fully recovered. The future development and expansion of living donor liver transplantation depends on open communication regarding donor complications and deaths. Close immediate postoperative monitoring and meticulous management will remain an essential aspect in limiting donor complications and deaths.
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Affiliation(s)
- Bhargavi Gali
- Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA
| | - Charles B. Rosen
- Department of Surgery, Transplant Center, Mayo Clinic, Rochester, MN, USA
| | - David J. Plevak
- Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA
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Narang TK, Ahrens W, Russo MW. Post-liver transplant cholestatic hepatitis C: a systematic review of clinical and pathological findings and application of consensus criteria. Liver Transpl 2010; 16:1228-35. [PMID: 21031537 DOI: 10.1002/lt.22175] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation is currently the only definitive modality for the treatment of end-stage liver disease due to chronic hepatitis C. However, recurrent hepatitis C after liver transplantation is nearly universal. Cirrhosis may develop in 20% of recipients within 5 years, and recurrent hepatitis C may lead to graft failure, retransplantation, and even death. A subset of recipients may develop post-liver transplant cholestatic hepatitis C (PLTCHC), which is characterized by cholestasis, hepatocyte ballooning, and rapid progression to graft failure. We present a systematic review of PLTCHC that is focused on hepatitis C-infected liver transplant recipients. We compare the pathological definitions of PLTCHC, clinical factors, management strategies, and outcomes reported in studies. We found differences among studies in the types of histological criteria used to diagnose PLTCHC during liver biopsy and in the types of clinical information provided. Three of the 12 studies published after 2003 used the definition of PLTCHC published by the first International Liver Transplantation Society expert panel consensus conference on liver transplantation and hepatitis C. We propose that studies on PLTCHC use the consensus criteria for diagnosis and suggest clinical information that should be provided in future studies with the goal of improving our understanding and management of this deadly disease.
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Affiliation(s)
- Tarun K Narang
- Department of Medicine, Carolinas Medical Center, Charlotte, NC 28203, USA
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Sugawara Y, Tamura S, Kokudo N. Antiviral treatment for hepatitis C virus infection after liver transplantation. HEPATITIS RESEARCH AND TREATMENT 2010; 2010:475746. [PMID: 21151523 PMCID: PMC2989693 DOI: 10.1155/2010/475746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/21/2010] [Revised: 08/13/2010] [Accepted: 10/06/2010] [Indexed: 12/16/2022]
Abstract
A significant proportion of patients with chronic hepatitis C virus (HCV) infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary.
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Affiliation(s)
- Yasuhiko Sugawara
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Sumihito Tamura
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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46
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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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Acute hepatitis after autologous stem cell transplantation and rapid progression to liver cirrhosis. Eur J Gastroenterol Hepatol 2010; 22:1141-4. [PMID: 20463583 DOI: 10.1097/meg.0b013e32833a064a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
A 51-year-old woman was diagnosed with a diffuse cerebral large cell lymphoma. During the period of a combined chemotherapy followed by autologous stem cell transplantation with multiple blood donations, an acute hepatitis without hepatitis C antibodies was diagnosed. Liver biopsy showed steatohepatitis, initially thought to be related to chemotherapy. Sixteen months after the transplantation, liver cirrhosis appeared with circulatory bypass. Retrospectively, testing of serum samples showed a hepatitis C infection. Infection with the hepatitis C virus (HCV) from a blood donation was excluded through retrospective testing for HCV-RNA of blood donors. Finally, the cause of infection remained elusive. Hepatitis serology is not a reliable test under immunosuppressive therapy. The course of progression to liver cirrhosis in the presented short period of 22 months after HCV infection is remarkable and has - to our knowledge - not been reported in literature before.
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Tamura S, Sugawara Y, Yamashiki N, Kaneko J, Kokudo N, Makuuchi M. Pre-emptive antiviral therapy in living donor liver transplantation for hepatitis C: observation based on a single-center experience. Transpl Int 2010; 23:580-588. [PMID: 20028490 DOI: 10.1111/j.1432-2277.2009.01023.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Reports of large series in living donor liver transplantation (LDLT) for hepatitis C virus infection (HCV) are scarce. Between 1996 and 2008, 105 LDLTs were performed at the University of Tokyo for HCV. Rapid induction of antiviral treatment with interferon (IFN) and ribavirin (RBV) was attempted per protocol regardless of the clinical presentation of recurrent HCV (pre-emptive treatment approach). Treatment was continued for 12 months after serum HCV-RNA became negative (ETR: end-of-treatment response) and judged as a sustained viral response (SVR) after another 6 months of negative results without treatment. A fixed treatment period was not defined unless an ETR was achieved (no-stopping approach). Flexible dose adjustments were allowed. Ninety-five patients were eligible for pre-emptive therapy. Forty-three (45%) patients experienced an ETR, and 32 (34%) achieved SVR. Nonadherence to full-dose INF and RBV had little impact on the viral response. Evaluation using the Kaplan-Meier method to incorporate the cumulative time-dependent nature of the no-stopping approach estimated SVR rate at 53% by the fifth year. Survival rate at 5 years was 79% for the HCV recipients and did not differ significantly from our non-HCV series. In LDLT for HCV, pre-emptive IFN-RBV-based treatment with the application of no-stopping approach is feasible and effective.
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Affiliation(s)
- Sumihito Tamura
- Artificial Organ and Transplantation Division, University of Tokyo, Tokyo, Japan
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Masuzaki R, Yamashiki N, Sugawara Y, Yoshida H, Tateishi R, Tamura S, Kaneko J, Hasegawa K, Kokudo N, Makuuchi M, Omata M. Assessment of liver stiffness in patients after living donor liver transplantation by transient elastography. Scand J Gastroenterol 2010; 44:1115-20. [PMID: 19562623 DOI: 10.1080/00365520903078810] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Recurrence of hepatitis and progression of fibrosis are major problems in liver transplantation (LT) for patients with hepatitis C. Liver stiffness measurement (LSM) by transient elastography correlates well with histologic liver fibrosis stages in chronic liver diseases. The aim of this study was to evaluate the usefulness of transient elastography for the assessment of fibrosis in patients after living donor LT. MATERIAL AND METHODS Seventy-nine patients who visited our institution, and in whom LSM was successfully evaluated, were enrolled in the study. The patients were divided into three groups according to positivity for hepatitis C antibody and hepatitis B surface antigen as the hepatitis C virus (HCV) group (n=37), the hepatitis B virus (HBV) group (n=10), and the NBNC (negative for both hepatitis B and C) group (n=32). The correlation between LSM and histologic fibrosis stage was assessed in 36 patients. LSM was also compared with regard to the effect of interferon therapy in HCV patients. RESULTS The median value for liver stiffness was 6.8 kPa and the median time from LT was 3.1 years. In patients who underwent liver biopsy, stiffness was significantly correlated with the stages of fibrosis (p<0.001, rho = 0.848). In patients who received interferon therapy after LT, the LSM decreased over time in those with a sustained virological response, whereas LSM increased in patients without a response. CONCLUSION Transient elastography may be an appropriate non-invasive procedure to sequentially assess the progression of liver fibrosis in patients after LT.
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Affiliation(s)
- Ryota Masuzaki
- Department of Gastroenterology, University of Tokyo, Japan
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50
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Carrión JA, Torres F, Crespo G, Miquel R, García-Valdecasas JC, Navasa M, Forns X. Liver stiffness identifies two different patterns of fibrosis progression in patients with hepatitis C virus recurrence after liver transplantation. Hepatology 2010; 51:23-34. [PMID: 19839063 DOI: 10.1002/hep.23240] [Citation(s) in RCA: 109] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Significant liver fibrosis (F >or= 2) and portal hypertension (hepatic venous pressure gradient [HVPG] >or= 6 mmHg) at 1 year after liver transplantation (LT) identify patients with severe hepatitis C recurrence. We evaluated whether repeated liver stiffness measurements (LSM) following LT can discriminate between slow and rapid "fibrosers" (fibrosis stage F2-F4 at 1 year after LT). Eighty-four patients who had undergone LT and who were infected with hepatitis C virus (HCV) and 19 LT controls who were not infected with HCV underwent LSM at 3, 6, 9, and 12 months after LT. All HCV-infected patients underwent liver biopsy 12 months after LT (paired HVPG measurements in 74); 31 (37%) were rapid fibrosers. Median LSM (in kilopascal) at months 6, 9, and 12 were significantly higher in rapid fibrosers (9.9, 9.5, 12.1) than in slow fibrosers (6.9, 7.5, 6.6) (P < 0.01 all time points). The slope of liver stiffness progression (kPa x month) in rapid fibrosers (0.42) was significantly greater than in slow fibrosers (0.05) (P < 0.001), suggesting two different speeds of liver fibrosis progression. Figures were almost identical for patients with HVPG >or= 6 mmHg or HVPG < 6 mmHg at 1 year after LT. Multivariate analysis identified donor age, bilirubin level, and LSM as independent predictors of fibrosis progression and portal hypertension in the estimation group (n = 50) and were validated in a second group of 34 patients. The areas under the receiver operating characteristic curve that could identify rapid fibrosers and patients with portal hypertension as early as 6 months after LT were 0.83 and 0.87, respectively, in the estimation group and 0.75 and 0.80, respectively, in the validation group. CONCLUSION Early and repeated LSM following hepatitis C recurrence in combination with clinical variables discriminates between rapid and slow fibrosers after LT.
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Affiliation(s)
- José A Carrión
- Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
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