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BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation. APPROACH AND RESULTS: This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: -3.7 (-6.4, -0.96) mm Hg/year for partial pressure of arterial oxygen (PaO 2 ); -26 (-96, 44) m/year for 6-minute walk distance, and 3.3% (-6.6, -0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO 2 decline by 0.88 (0.36, 1.4) mm Hg/month. We identified 2 PaO 2 deterioration classes-"very severe disease, slow decliners" (PaO 2 45.0 mm Hg; -1.0 mm Hg/year); and "moderate disease, steady decliners" (PaO 2 65.5 mm Hg; -2.5 mm Hg/year). PaO 2 increased by 6.5 (5.3, 7.7) mm Hg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO 2 was 2.5 (0.1, 4.9) mm Hg/month faster for every 10 mm Hg greater pretransplant orthodeoxia. CONCLUSIONS: We present a large and long longitudinal data analysis in HPS. In addition to rates of physiological decline and improvement before and after liver transplantation, we present novel predictors of PaO 2 decline and improvement rates. Our findings enhance our understanding of the natural history of HPS and provide pathophysiologic clues. Importantly, they may assist providers in prognostication and prioritization before and after transplant.
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Síndrome Hepatopulmonar , Transplante de Fígado , Humanos , Síndrome Hepatopulmonar/diagnóstico , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Canadá , PulmãoRESUMO
AIM: To investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors in liver transplant (LT) recipients with diabetes. METHODS: A single-centre, retrospective analysis of prospectively collected data from an LT recipient database (1990-2023) was conducted. We included adults with pre-existing diabetes and post-transplant diabetes, newly started on GLP-1RAs and/or SGLT2 inhibitors after LT. Metabolic and biochemical parameters and outcomes were collected for up to 12 months after starting medications and were compared to those in patients receiving dipeptidyl peptidase-4 (DPP-4) inhibitors. Statistical analysis included descriptive statistics and linear mixed models. RESULTS: We included participants on GLP-1RAs (n = 46), SGLT2 inhibitors (n = 87), combination therapy (n = 12), and a DPP-4 inhibitor comparator (n = 217). Both GLP-1RAs and combination therapy decreased mean glycated haemoglobin (HbA1c) levels, and combination therapy remained significant when adjusted for DPP-4 inhibitor treatment (-3.5%, 95% CI [-6.1, -0.95]; p = 0.0089) at 12 months. All three groups had significant decreases in mean weight and body mass index, but these remained significant in the GLP-1RA (-5.2 kg, 95% CI [-8.7, -1.7], p = 0.0039 and 1.99 kg/m2, 95% CI [-3.4, -0.6], p = 0.0048) and combination therapy groups (-5.4 kg, 95% CI [-10.5, -0.36], p = 0.04 and -3.4 kg/m2, 95% CI [-5.5, -1.3], p = 0.0015) when adjusted for DPP-4 inhibitor treatment at 12 months. Alanine aminotransferase levels decreased with GLP-1RA and combination therapy. There were two (1.4%) cases of graft rejection. CONCLUSION: We found that GLP-1RAs, SGLT2 inhibitors, and their combination, led to significant weight loss in LT recipients with diabetes. Combination therapy, in particular, lowered HbA1c and alanine aminotransferase levels compared to DPP-4 inhibitors. Further studies are needed to assess long-term safety and efficacy.
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INTRODUCTION AND OBJECTIVES: Recurrent cirrhosis complicates 10-30% of Liver transplants (LT) and can lead to consideration for re-transplantation. We evaluated the trajectories of relisted versus primary listed patients on the waitlist using a competing risk framework. MATERIALS AND METHODS: We retrospectively examined 1,912 patients listed for LT at our centre between from 2012 to 2020. Cox proportional hazard models were used to assess overall survival (OS) by listing type and competing risk analysis Fine-Gray models were used to assess cumulative incidence of transplant by listing type. RESULTS: 1,731 patients were included (104 relisted). 44.2% of relisted patients received exception points vs. 19.8% of primary listed patients (p<0.001). Patients relisted without exceptions, representing those with graft cirrhosis, had the worst OS (HR: 4.17, 95%CI 2.63 - 6.67, p=<0.0001) and lowest instantaneous rate of transplant (HR: 0.56, 95%CI 0.38 - 0.83, p=0.006) than primary listed with exception points. On multivariate analysis listing type, height, bilirubin and INR were associated with cumulative incidence of transplant, while listing type, bilirubin, INR, sodium, creatinine were associated with OS. Within relisted patients, there was a trend towards higher mortality (HR: 1.79, 95%CI 0.91 - 3.52, p=0.08) and low transplant incidence (HR: 0.51, 95%CI 0.22 - 1.15, p=0.07) for graft cirrhosis vs other relisting indications. CONCLUSIONS: Patients relisted for LT are carefully curated and comprise a minority of the waitlist population. Despite their younger age, they have worse liver/kidney function, poor waitlist survival, and decreased transplant incidence suggesting the need for early relisting, while considering standardized exception points.
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Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/cirurgia , Modelos de Riscos Proporcionais , Listas de Espera , BilirrubinaRESUMO
OBJECTIVE: To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA: In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS: All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS: Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION: With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Fígado/métodos , Doadores Vivos , Sobrevivência de Enxerto , Estudos Retrospectivos , Doadores de Tecidos , Morte , Morte Encefálica , FígadoRESUMO
BACKGROUND: Non-alcoholic Steatohepatitis (NASH) cirrhosis is the second most common indication for liver transplantation (LT) in the US and often is associated with significant co-morbidities. We validated a model and risk prediction score that reflects the benefit derived from LT for NASH cirrhosis by predicting 5-year survival post-LT. METHODS: We developed a prediction score utilizing 6515 NASH deceased donor LT (DDLT) recipients from 2002 to 2019 from the Scientific Registry of Transplant Recipients (SRTR) database to identify a parsimonious set of independent predictors of survival. Coefficients of relevant recipient factors were converted to weighted points to construct a risk scoring system that was then externally validated. RESULTS: The final risk score includes the following independent recipient predictors and corresponding points: recipient age (5 points for age ≥70 years), functional status (3 points for total assistance), presence of TIPSS (2 points), hepatic encephalopathy (1 point), serum creatinine (5 points if >1.45 mg/dl), need for mechanical ventilation (3 points), and dialysis within 1 week prior to LT (7 points). Diabetes is a stratifying variable for baseline risk. Scores range from 0 to 20 with scores above 13 having an overall survival of <65% at 5 years post-LT. Internal and external validation indicated good predictive ability. CONCLUSION: Our practically useable and validated risk score helps to identify and stratify candidates who will derive the most long-term benefit from LT for NASH cirrhosis.
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Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Idoso , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Cirrose Hepática/cirurgia , Cirrose Hepática/complicações , Fatores de Risco , Medição de Risco , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). This study aimed to determine whether living donor LT (LDLT) recipients experienced less recurrent NASH, cirrhosis, and cardiometabolic complications compared to deceased donor LT (DDLT). METHOD: Patients with LDLT and DDLT for NASH between February 2002 and May 2018 at University Health Network (UHN) were compared. Cox Proportional Hazard model was used to analyze overall survival (OS), Fine and Gray's Competing Risk models were conducted to analyze cumulative incidence of post LT outcomes. RESULTS: One hundred and ninety-nine DDLTs and 66 LDLTs were performed for NASH cirrhosis. Time and rate of recurrence of NAFLD and NASH were comparable in both groups. Graft cirrhosis was more common in DDLT recipients (n = 14) versus LDLT (n = 0) (p < .0001). Significant fibrosis (Fibrosis ≥ F2) developed in 50 recipients (12 LDLT and 38 DDLT) post LT (DDLT vs. LDLT: HR = 1.00, 95% CI = (.52-1.93), p = .91) and there was no difference in time to significant fibrosis (p = .57). There was no difference in development of post-transplant diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, and cancers. LDLT group had better renal function at 10 years (MDRD eGFR of 57.0 mL/min vs. 48.5 mL/min, p = .047). Both groups had a comparable OS (HR = 1.83 (95% CI = .92-3.62), p = .08). CONCLUSION: Overall, LDLT recipients had significantly better renal function by virtue of having early transplantation in their disease course. LDLT was also associated with significantly less graft cirrhosis, although OS and cardiometabolic outcomes were comparable between LDLT and DDLT.
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Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Doadores Vivos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Estudos Retrospectivos , Fibrose , Resultado do Tratamento , Sobrevivência de EnxertoRESUMO
BACKGROUND: Advanced donor age paired with donation after cardiac death (DCD) increases the risk of transplantation, precluding widespread use of grafts from such donors worldwide. Our aim was to analyze outcomes of liver transplantation using grafts from older DCD donors and donation after brain death (DBD) donors. METHODS: Patients who underwent liver transplantation using grafts from deceased donors between January 2016 and December 2021 were included in the study. Short-and long-term outcomes were analyzed for 4 groups of patients: those who received DCD and DBD grafts from younger (< 50 yr) and older (≥ 50 yr) donors. RESULTS: Of the 807 patients included in the analysis, 44.7% (n = 361) of grafts were received from older donors, with grafts for older DCD donors comprising 4.7% of the total cohort (n = 38). Patients who received grafts from older donors had a lower incidence of biliary strictures than those who received grafts from younger donors (7.9% v. 20.0% for DCD donation, p = 0.14, and 4.9% v. 6.8% for DBD donation, p = 0.34), with a significantly lower incidence of ischemic-type biliary strictures in patients who received grafts from older versus younger DCD donors (2.6% v. 18.0%, p = 0.04). There was no difference in 1- and 3-year graft survival rates among patients who received grafts from older and younger DCD donors (92.1% v. 90.8% and 80.2% v. 80.9%, respectively) and those who received grafts from older and younger DBD donors (90.1% v. 93.2% and 85.3% v. 84.4%, respectively) (p = 0.85). Pretransplantation admission to the intensive care unit (hazard ratio [HR] 9.041, p < 0.001) and nonalcoholic steatohepatitis (HR 2.197, p = 0.02) were found to significantly affect survival of grafts from older donors. CONCLUSION: Donor age alone should not be the criterion to determine the acceptability of grafts in liver transplantation. With careful selection criteria, older DCD donors could make a valuable contribution to expanding the liver donor pool, with grafts that produce comparable results to those obtained with standard-criteria grafts.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Humanos , Constrição Patológica , Estudos Retrospectivos , Doadores Vivos , Doadores de Tecidos , Morte , Morte EncefálicaRESUMO
Nonalcoholic steatohepatitis (NASH) cirrhosis is the second most common indication for liver transplantation (LT) in the United States.1 Patients are increasingly older at presentation, with higher rates of metabolic syndrome, obesity, hyperlipidemia, diabetes mellitus, and renal failure.2 They are also at higher risk of cardiovascular events and mortality while on the waiting list1 and in the post-transplant period.3,4 We sought to identify predictors of long-term benefit based on 5-year survival post-LT in NASH cirrhosis, thereby delineating those patients that derive a clear benefit from LT versus those in whom LT may be futile.
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Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Listas de EsperaRESUMO
LITMUS was a single-centre, Phase 2a study designed to investigate whether the gene biomarker FGL2/IFNG previously reported for the identification of tolerance in murine models could identify operationally tolerant liver transplant recipients. Multiplex RT-PCR was used to amplify eight immunoregulatory genes in peripheral blood mononuclear cells (PBMC) from 69 adult liver transplant recipients. Patients with PBMC FGL2/IFNG ≥ 1 and a normal liver biopsy underwent immunosuppression (IS) withdrawal. The primary end point was the development of operational tolerance. Secondary end points included correlation of tolerance with allograft gene expression and immune cell markers. Twenty-eight of 69 patients (38%) were positive for the PBMC tolerance biomarker and 23 proceeded to IS withdrawal. Nine of the 23 patients had abnormal baseline liver biopsies and were excluded. Of the 14 patients with normal biopsies, eight (57%) have achieved operational tolerance and are off IS (range 12-57 months). Additional studies revealed that all of the tolerant patients and only one non-tolerant patient had a liver gene ratio of FOXP3/IFNG ≥ 1 prior to IS withdrawal. Increased CD4+ T regulatory T cells were detected both in PBMC and livers of tolerant patients following IS withdrawal. Higher expression of SELE (gene for E-selectin) and lower expression of genes associated with inflammatory responses (GZMB, CIITA, UBD, LSP1, and CXCL9) were observed in the pre-withdrawal liver biopsies of tolerant patients by RNA sequencing. These results suggest that measurement of PBMC FGL2/IFNG may enrich for the identification of operationally tolerant liver transplant patients, especially when combined with intragraft measurement of FOXP3/IFNG. Clinical Trial Registration: ClinicalTrials.gov (LITMUS: NCT02541916).
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Leucócitos Mononucleares , Transplante de Fígado , Adulto , Biomarcadores/metabolismo , Fibrinogênio , Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Humanos , Tolerância Imunológica/genética , Imunossupressores , Leucócitos Mononucleares/metabolismo , Transplante de Fígado/métodos , Tolerância ao Transplante/genéticaRESUMO
BACKGROUND: Despite the current highly effective therapies with direct-acting antiviral agents (DAAs), some patients with chronic hepatitis C virus (HCV) infection still do not achieve sustained virological response (SVR) and require retreatment. Sofosbuvir/velpatasvir/voxilaprevir (SVV) is recommended as the first-line retreatment option for most patients. The aim of this study was to evaluate the efficacy of SVV as salvage therapy after at least one course of DAA. METHODS: Data were collected on all HCV-infected patients who failed DAAs and were prescribed SVV from a prospective Canadian registry (CANUHC) including 17 sites across Canada. Factors associated with failure to achieve SVR with SVV therapy and the utility of RAS testing and ribavirin use were evaluated. RESULTS: A total of 128 patients received SVV after non-SVR with DAA treatment: 80% male, median age 57.5 (31-86), 44% cirrhotic, and 17 patients post liver transplant. First line regimens included: sofosbuvir/velpatasvir (27.3%), sofosbuvir/ledipasvir (26.5%), grazoprevir/elbasvir (12.5%), other (33.5%). Ribavirin was added to SVV in 26 patients due to past sofosbuvir/velpatasvir use (nâ =â 8), complex resistance associated substitution profiles (nâ =â 16) and/or cirrhosis (nâ =â 9). Overall SVR rate was 96% (123/128). Of 35 patients who previously failed sofosbuvir/velpatasvir, 31 (88.5%) achieved SVR compared to 92 of 93 (99%) among those receiving any other regimen (Pâ =â .01). CONCLUSIONS: Similar to reports from phase 3 clinical trials, SVV proved highly effective as salvage therapy for patients who failed a previous DAA therapy. Those who failed SVV had at least 2 of the following factors: genotype 3, presence of cirrhosis, past liver transplantation, past exposure to sofosbuvir/velpatasvir and/or complex resistance profiles.
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Antivirais , Hepatite C Crônica , Ácidos Aminoisobutíricos , Antivirais/uso terapêutico , Canadá , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Estudos Prospectivos , Quinoxalinas , Sistema de Registros , Terapia de Salvação , Sofosbuvir/uso terapêutico , SulfonamidasRESUMO
BACKGROUND & AIMS: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3â¯cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy. METHODS: We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3â¯cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70â¯years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2â¯cm vs. HCC >2â¯cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria. RESULTS: We included 301 patients (167 HCC ≤2â¯cm and 134 HCC >2â¯cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2â¯cm and the HCC >2â¯cm groups, respectively (pâ¯=â¯0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2â¯cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2â¯cm group (pâ¯=â¯0.01). Tumor size >2â¯cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000â¯ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria. CONCLUSION: RFA for single HCC ≤3â¯cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA. LAY SUMMARY: Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2â¯cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.
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Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , alfa-Fetoproteínas/análiseRESUMO
The management of severe aplastic anaemia is particularly challenging when it occurs in the context of recent liver transplantation. Rapid identification of a suitable donor followed by allogeneic haematopoietic stem cell transplantation is the only curative option. This scenario is often complicated by potentially life-threatening infections that develop as a consequence of immunosuppression. Alternative donor transplantation using suitably matched unrelated donors can be potentially life-saving when suitably matched sibling donors are unavailable. Above all, a dedicated interdisciplinary approach with seamless communication between hepatology, transplant surgery, haematology, and stem cell transplant services is essential to achieving optimal outcomes. Herein, we describe a case of severe hepatitis leading to hepatic failure who was treated with liver transplantation from a deceased donor, and later received an allogeneic haematopoietic stem cell transplantation from a matched unrelated donor for hepatitis-associated aplastic anaemia.
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Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas , Falência Hepática Aguda/terapia , Transplante de Fígado , Anemia Aplástica/diagnóstico , Biomarcadores , Diagnóstico por Imagem , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Falência Hepática Aguda/complicações , Falência Hepática Aguda/diagnóstico , Masculino , Transplante Homólogo , Adulto JovemRESUMO
Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult-to-adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no-PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t-PVT]; n = 28). Ten patients had early portal vein thrombosis (e-PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l-PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t-PVT (hazard ratio [HR], 3.55; P = 0.01), e-PVT (HR, 4.96; P = 0.04), and l-PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l-PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e-PVT and l-PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no-PVT, 2% versus e-PVT, 10%; P = 0.15). No significant differences were found regarding 1-year (89% versus 92%), 5-year (79% versus 82%), and 10-year (69% versus 79%) graft survival between the t-PVT and no-PVT groups, respectively (P = 0.24). The 1-year (89% versus 96%), 5-year (82% versus 86%), and 10-year (79% versus 83%) patient survival was similar for the patients in the no-PVT and t-PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.
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Transplante de Fígado/efeitos adversos , Doadores Vivos , Veia Porta , Esplenectomia/efeitos adversos , Trombose Venosa/etiologia , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Circulação Hepática , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Ontário , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Esplenectomia/mortalidade , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/mortalidade , Trombose Venosa/fisiopatologiaRESUMO
BACKGROUND: Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT). METHODS: All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival. RESULTS: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p = 0.02) and tumor burden (p < 0.001). The majority of those listed underwent LT (n = 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599-15.464; p = 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660-12.768; p = 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (n = 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p = 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%. CONCLUSION: Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.
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Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Seleção de Pacientes , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga TumoralRESUMO
Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy-seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol-related liver disease (ALD) was the underlying etiology in the majority (n = 47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end-stage liver disease (MELD) score <20 and serum albumin ≥32 g/l at listing were the only independent predictors of recompensation/delisting in ALD. The probability of recompensation was 70% when both factors were present at listing. Interestingly, about a tenth of decompensated ALD patients who died on the waiting list (median duration on waiting list 11 months) and a quarter of decompensated ALD patients who underwent living donor liver transplantation (median duration on waiting list 2 months) also had both factors at listing. In conclusion, ALD seems to be the most favorable etiology for recompensation beyond the need for transplantation. Both MELD and serum albumin at listing independently predict recompensation/delisting in ALD. It seems advisable to implement a period of observation for ALD patients with both favorable factors, before embarking on living donor liver transplantation.
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Hepatopatias Alcoólicas , Transplante de Fígado/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Remissão Espontânea , Estudos Retrospectivos , Listas de EsperaRESUMO
Trichodysplasia spinulosa (TS) is a rare dermatologic complication associated with the immunosuppressive therapy used in solid organ transplantation. The distinctive clinical manifestation of this condition is spiny follicular papules on the face, ears, extremities, and trunk. Histopathologically, abnormally maturing hair follicles with hyperkeratotic material are noted. The condition is produced by the trichodysplasia spinulosa-associated polyomavirus. Treatment of this condition in the past has entailed a reduction in immunosuppression, topical agents such as cidofovir or retinoids, or oral valganciclovir. Herein, we report a case of generalized TS treated successfully with leflunomide.
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Doenças do Cabelo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Isoxazóis/uso terapêutico , Transplante de Fígado/efeitos adversos , Infecções por Polyomavirus/tratamento farmacológico , Prurido/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Diagnóstico Diferencial , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/patologia , Doenças do Cabelo/virologia , Folículo Piloso/patologia , Humanos , Terapia de Imunossupressão , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Leflunomida , Masculino , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Prurido/diagnóstico , Prurido/patologia , Prurido/virologiaRESUMO
INTRODUCTION: Recurrence of HCV infection in patients with chronic hepatitis C virus (HCV) at the time of liver transplantation is nearly universal and reduces the likelihood of graft and patient survival. MATERIALS AND METHODS: We evaluated outcomes of 17 patients (16 with HCV genotype 1 and 1 with genotype 4) who received up to 12 or 24 weeks of ledipasvir/sofosbuvir plus ribavirin prior to or up to the time of liver transplant in the SOLAR-1 and SOLAR-2 trials. In all patients, HCV RNA was < 15 IU/mL prior to transplant. At screening, 6 patients were Child-Pugh-Turcotte (CPT) class B and 11 were CPT class C. Seven patients underwent transplant prior to completing assigned treatment, with 4 treated for < 12 weeks. The primary endpoint was posttransplant virologic response 12 weeks after transplant (pTVR12) in patients with HCV RNA < 15 IU/mL at their last measurement prior to transplant. RESULTS: Overall, 94% (16/17) achieved pTVR12. All who achieved pTVR12 received at least 11 weeks of treatment. The single patient who did not achieve pTVR12 discontinued study drug on day 21 and underwent liver transplant the following day. The patient had HCV RNA < 15 IU/mL at post-transplant week 2 but died 15 days post-transplant because of multi-organ failure and septic shock. CONCLUSION: Among a small population of HCV patients with decompensated cirrhosis, virologic response to ledipasvir / sofosbuvir plus ribavirin prior to liver transplantation was maintained after transplantation, even if treatment was stopped early. Administration of ledipasvir / sofosbuvir plus ribavirin before liver transplant can prevent post-transplant HCV recurrence.
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Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Cirrose Hepática/cirurgia , Transplante de Fígado , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Idoso , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribavirina/efeitos adversos , Sofosbuvir/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340-580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56-1.74 mmol/L) and produced bile (61 mL; 14-146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP-preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1-3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1-1.56] versus 1.1 [1-1.3]; P = 0.5) and bilirubin (1.5; 1-7.7 mg/dL versus 2.78; 0.4-15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0-8 versus 0-23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8-17 versus 7-89 days; P = 0.23). Major complications (Dindo-Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501-1508 2016 AASLD.
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Aloenxertos/fisiologia , Transplante de Fígado , Fígado/fisiologia , Soluções para Preservação de Órgãos/uso terapêutico , Preservação de Órgãos/métodos , Perfusão/métodos , Traumatismo por Reperfusão/prevenção & controle , Adolescente , Adulto , Idoso , Isquemia Fria , Dextranos/uso terapêutico , Eritrócitos , Estudos de Viabilidade , Humanos , Tempo de Internação , Pessoa de Meia-Idade , América do Norte , Soluções para Preservação de Órgãos/química , Perfusão/instrumentação , Projetos Piloto , Poligelina/uso terapêutico , Estudos Retrospectivos , Albumina Sérica/uso terapêutico , Temperatura , Adulto JovemRESUMO
Because of a persistent discrepancy between the demand for liver transplantation (LT) and the supply of deceased donor organs, there is an interest in increasing living donation rates at centers trained in this method of transplantation. We examined a large socioeconomically heterogeneous cohort of patients listed for LT to identify recipient factors associated with living donation. We retrospectively reviewed 491 consecutive patients who were listed for LT at our center over a 24-month period. Demographic, medical, and socioeconomic data were extracted from electronic records and compared between those who had a potential living donor (LD) volunteer for assessment and those who did not; 245 patients (50%) had at least 1 potential LD volunteer for assessment. Multivariate logistic regression analysis identified that patients with a LD were more likely to have Child-Pugh C disease (odds ratio [OR], 2.44; P = 0.02), and less likely to be older (OR, 0.96; P = 0.002), single (OR, 0.34; P = 0.006), divorced (OR, 0.53; P = 0.03), immigrants (OR, 0.38; P = 0.049), or from the lowest income quintile (OR, 0.44; P = 0.02). In conclusion, this analysis has identified several factors associated with access to living donation. More research is warranted to define and overcome barriers to living donor liver transplantation through targeted interventions in underrepresented populations.