RESUMO
Liver transplantation is a technically demanding surgical procedure with known complications, and the optimal approach to addressing vascular and biliary complications requires a coordinated effort between surgical and interventional radiology teams. Vascular complications involving the hepatic artery, portal vein, or hepatic veins can be characterized by their mechanism, chronicity, and timing of presentation. These factors help determine whether the optimal therapeutic approach is surgical or endovascular. Very early presentation in the perioperative period favors surgical revision, while later presentation is best addressed endovascularly. Biliary complications can be categorized as leaks or strictures, and coordinated surgical, endoscopic, and percutaneous management is needed to address these types of complications. Through advances in technique and the management of complications, outcomes after liver transplantation continue to improve.
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Doenças Biliares , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Doenças Biliares/terapia , Artéria Hepática , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Split liver transplantation (SLT), where a single donor liver is divided for transplantation to 2 recipients, has the potential to increase the availability of size-matched livers for pediatric candidates and expand the supply of donor organs available for adult candidates. Although SLT is a well-established technique, the number of SLTs has remained flat during the past 2 decades, partly due to concerns about the posttransplant survival of SLT recipients compared with whole liver transplantation (WLT) recipients. Prior work on SLT versus WLT survival analysis had limitations because, for pediatric recipients, it did not consider the correlations between donor age/weight and the allograft type, and for adult recipients, it may have included records where the donor livers did not meet the split liver criteria (splittable). METHODS: Using the Organ Procurement and Transplantation Network's database (2003-2019), this study analyzes and compares (i) key characteristics of donors and recipients, (ii) donor-recipient match dynamics (organ offers and accept/decline decisions), and (iii) recipient posttransplant survival, for SLT and WLT. RESULTS AND CONCLUSIONS: The results in this study show that the posttransplant survival of SLT and WLT recipients is similar (controlling for other confounding factors that may impact posttransplant survival), highlighting the importance of SLT for increasing the liver supply and potential benefits for both pediatric and adult candidates.
Assuntos
Transplante de Fígado , Adulto , Humanos , Criança , Doadores Vivos , Fígado/cirurgia , Transplante Homólogo , Ácido LácticoRESUMO
OBJECTIVE: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons. BACKGROUND: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC. METHODS: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers. RESULTS: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001). CONCLUSION: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Transplante de Fígado , Benchmarking , Colangiocarcinoma/cirurgia , Humanos , Tumor de Klatskin/patologia , Tumor de Klatskin/cirurgia , Padrão de CuidadoRESUMO
Despite the increase in deceased organ donation over the past ten years, the gap between patients awaiting transplant and available organs continues to widen. Deceased donors secondary to acute fatal poisonings represent less than 1% of all organ donors. Organs from poisoned donors have largely been discarded due to concerns of toxin transmission and poor organ function as well as the paucity of data that exists regarding this donor population. Here, we report a case of a 40-year-old male who underwent successful liver re-transplantation from a donor who died following ethylene glycol ingestion. To our knowledge this case report is the first to describe successful re-transplantation from an ethylene glycol-poisoned donor. We also provide a comprehensive review of the literature describing organ donation from poisoned donors.
Assuntos
Transplante de Fígado , Transplante de Órgãos , Venenos , Obtenção de Tecidos e Órgãos , Adulto , Ingestão de Alimentos , Etilenoglicol , Humanos , Masculino , Doadores de TecidosRESUMO
Biliary leaks and anastomotic strictures comprise the majority of biliary complications (BCs) following liver transplantation (LT). Currently, there are few large contemporary case series of BCs in adult deceased donor liver transplant (DDLT) recipients in the literature. The purpose of this study was to examine the pretransplant and intraoperative risk factors associated with BCs at a high-volume tertiary care center and determine the impact of these BCs on their posttransplant course and long-term transplant outcomes. METHODS: We retrospectively reviewed all adult patients undergoing a DDLT from a donor after brain death (DBD) at Emory University between January 2015 and December 2019. RESULTS: A total of 647 adult patients underwent DDLT from a DBD during the study period and were included in analyses. The median length of follow-up posttransplant was 2.5 y. There were a total of 27 bile leaks (4.2%) and 69 biliary strictures (10.7%). Recipient age and cold ischemic time were identified as risk factors for biliary leak, whereas alcoholic cirrhosis as transplant indication was a risk factor for biliary stricture. Placement of a biliary stent was associated with the development of both biliary leaks and anastomotic strictures. Posttransplant, biliary leaks were a significant risk factor for future episodes of acute rejection but did not impact overall survival. In contrast, biliary strictures were associated with a significantly reduced overall survival at 1- and 4-y post DDLT. CONCLUSIONS: BCs are a major source of morbidity and mortality following DDLT, with strictures and leaks associated with distinct posttransplant complications.
RESUMO
OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3âmonths post-LT, and ≥3âmonths post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3âmonths post-LT, and ≥3âmonths post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3âmonths after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.
Assuntos
Antivirais/administração & dosagem , Carcinoma Hepatocelular/cirurgia , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Idoso , Benzimidazóis/administração & dosagem , Carbamatos/administração & dosagem , Carcinoma Hepatocelular/virologia , Esquema de Medicação , Combinação de Medicamentos , Feminino , Fluorenos/administração & dosagem , Hepatite C Crônica/complicações , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Pirrolidinas/administração & dosagem , Quinoxalinas/administração & dosagem , Estudos Retrospectivos , Sofosbuvir/administração & dosagem , Sulfonamidas/administração & dosagem , Resposta Viral SustentadaRESUMO
BACKGROUND: Pediatric acute liver failure (PALF) remains an enigmatic process of rapid end-organ dysfunction associated with a variety of pathologic conditions though the predominant cause is indeterminate. A growing body of research has identified mutations in the NBAS gene to be associated with recurrent acute liver failure and multi-systemic disease including short stature, skeletal dysplasia, facial dysmorphism, immunologic abnormalities, and Pelger-Huët anomaly. METHODS AND RESULTS: Here, we describe a 4-year-old girl who presented with dehydration in the setting of acute gastroenteritis and fever but went on to develop PALF on day 2 of hospitalization. She clinically recovered with supportive measures, but after discharge, had at least 2 additional episodes of PALF. Ultimately, she underwent liver transplant and her recurrent episodes of PALF did not recur throughout a 6-year follow-up period. Whole-exome sequencing post-liver transplant initially revealed two variants of uncertain significance in the NBAS gene. Parental studies confirmed the c.1549C > T(p.R517C; now likely pathogenic) variant from her mother and a novel c.4646T > C(p.L1549P) variant from her father. In silico analyses predicted these variants to have a deleterious effect on protein function. Consistent with previously characterized NBAS mutation-associated disease (NMAD), our patient demonstrated the following features: progeroid facial features, hypoplasia of the 12th ribs, Pelger-Huët anomaly on peripheral blood smear, and abnormal B and NK cell function. CONCLUSION: Altogether, we describe a novel pathogenic variant in the NBAS gene of a patient with NMAD and report the resolution of recurrent PALF secondary to NMAD following liver transplantation.
Assuntos
Falência Hepática Aguda/genética , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Proteínas de Neoplasias/genética , Pré-Escolar , Feminino , Humanos , Mutação , RecidivaRESUMO
Adenovirus infection is commonly associated with self-limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life-threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation.
Assuntos
Infecções por Adenoviridae , Abscesso Hepático , Transplante de Fígado , Adenoviridae , Infecções por Adenoviridae/complicações , Adulto , Febre , Humanos , Abscesso Hepático/etiologia , TransplantadosRESUMO
OBJECTIVE: To describe the assessment of Fontan-associated liver disease and determine the clinical and imaging measures that may identify hepatic morbidity risk in isolated heart transplantation candidates and trend those measures post-isolated heart transplantation. STUDY DESIGN: Retrospective analysis of pre-isolated heart transplantation and post-isolated heart transplantation Fontan-associated liver disease (FALD) status using blood tests, magnetic resonance imaging (MRI), and liver biopsy analysis within 6 months before isolated heart transplantation and 12 months after isolated heart transplantation in 9 consecutive patients with Fontan. Pre- and post-isolated heart transplantation standard laboratory values; varices, ascites, splenomegaly, thrombocytopenia (VAST) score; Fontan liver MRI score; liver biopsy scores; Model for End-stage Liver Disease (MELD); MELD excluding the International Normalized Ratio (MELD-XI); AST to platelet ratio index, and cardiac catheterization data were compared. RESULTS: Pretransplantation maximum MELD and MELD-XI was 15 and 16, respectively. Central venous pressures and VAST scores decreased significantly post-transplantation. In 5 paired studies, Fontan liver MRI score maximum was 10 pretransplantation and decreased significantly post-transplantation. Arterially enhancing nodules on MRI persisted in 2 patients post-transplantation. Pretransplantation and post-transplantation liver biopsy scores did not differ in 4 paired biopsy specimens. CONCLUSIONS: Patients with FALD and MELD <15, MELD-XI <16, Fontan liver MRI score <10, and VAST score ≤2 can have successful short-term isolated heart transplantation outcomes. Liver MRI and VAST scores improved post-transplantation. Post-transplantation liver biopsy scores did not change significantly. Pretransplantation liver biopsy demonstrating fibrosis alone should not exclude consideration of isolated heart transplantation. The persistence of hepatic vascular remodeling and fibrosis post-isolated heart transplantation suggests that continued surveillance for hepatic complications post-transplantation for patients with Fontan is reasonable.
Assuntos
Técnica de Fontan/efeitos adversos , Transplante de Coração , Hepatopatias/diagnóstico , Seleção de Pacientes , Adolescente , Ascite/diagnóstico por imagem , Biópsia , Pressão Venosa Central , Criança , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/patologia , Hepatopatias/etiologia , Testes de Função Hepática , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias , Estudos Retrospectivos , Esplenomegalia/diagnóstico por imagem , Trombocitopenia , Varizes/diagnóstico por imagem , Remodelação Vascular , Adulto JovemRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Y90 radiation segmentectomy (RS) vs. percutaneous microwave ablation (MWA) in patients with solitary HCC ≤ 4 cm. METHODS: From 2014 to 2017, 68 consecutive treatment naïve patients were included (34 per treatment arm). Chi-square and t-test were used to evaluate differences in baseline demographics between groups. Objective response was evaluated using mRECIST and toxicity using CTCAE. Overall survival (OS) and progression free survival (PFS) in the targeted tumor and the remainder of liver from initial treatment was calculated using Kaplan-Meier estimation. Propensity score matching was then performed with n = 24 patients matched in each group. Similar outcome analysis was then pre-formed. RESULTS: In the overall study population, both groups had similar baseline characteristics with the exception of larger lesions in the RS group. There was no difference in toxicity, objective tumor response, OS and non-target liver PFS between the MWA and RS group (p's > 0.05). In the matched cohort, the objective tumor response was 82.6% in MWA vs. 90.9%% in RS (p = 0.548). The mean OS in the MWA group (44.3 months) vs RS (59.0 months; p = 0.203). The targeted tumor mean PFS for the MWA groups was 38.6 months vs. 57.8 months in RS group (p = 0.005). There was no difference overall PFS and toxicity between the 2 matched groups. CONCLUSIONS: Our data suggest Y90 RS achieves similar tumor response and OS with a similar safety compared to MWA in the management of HCC lesions ≤ 4 cm. Additionally, targeted tumor PFS appears to be prolonged in the RS group with similar non-target liver PFS between RS and MWA group.
Assuntos
Técnicas de Ablação/métodos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Radioisótopos de Ítrio/uso terapêutico , Feminino , Humanos , Fígado/cirurgia , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Defects in biliary transport proteins, MDR3 in humans and Mdr2 in mice, can lead to a spectrum of cholestatic liver disorders. Although B cell disorders and the aberrant Ab production are the leading extrahepatic manifestations of cholestatic liver diseases, the mechanism underlying this phenomenon is incompletely understood. Using mice with deficiency of Mdr2 that progressively develop cholestatic liver disease, we investigated the contributions of BAFF to aberrant IgG autoantibody production and hepatic fibrosis. In Mdr2-/- mice, hepatic B lymphocytes constitutively produced IgG during fibrosis progression, which correlated with elevated serum levels of BAFF, antinuclear Abs (ANA) and immune complexes. The elevated BAFF and ANA titers were also detected in human patients with primary sclerosing cholangitis and hepatobiliary cholangiopathies. Consistent with the higher BAFF levels, liver-specific selection of the focused BCR IgH repertoire was found on hepatic B cells in Mdr2-/- mice. Interestingly, the administration of anti-BAFF mAb in Mdr2-/- mice altered the BCR repertoire on hepatic B lymphocytes and resulted in reduced ANA and immune complex titers. However, anti-BAFF treatment did not attenuate hepatic fibrosis as measured by collagen deposition, hepatic expressions of collagen-1a, α-smooth muscle actin, and mononuclear cell infiltration (CD11b+ Ly-6chi monocytes and CD11b+ Gr1+ neutrophils). Importantly, depletion of B cells by anti-CD20 mAb reduced both hepatic fibrosis and serum levels of ANA and immune complexes. Our findings implicate B cells as the potential therapeutic targets for hepatic fibrosis and targeting BAFF specifically for attenuating the autoantibody production associated with cholestatic liver disease.
Assuntos
Fator Ativador de Células B/imunologia , Colestase/imunologia , Cirrose Hepática/imunologia , Fígado/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Animais , Autoanticorpos/imunologia , Fibrose/imunologia , Células Estreladas do Fígado/imunologia , Humanos , Imunoglobulina G/imunologia , CamundongosRESUMO
Generalized lymphadenopathy after organ transplant is a concerning finding, often indicating the devel-opment of lymphoma. We describe a 52-year-old liver transplant recipient who had clinical symptoms and imaging concerning for posttransplant lymphoproliferative disease. However, histologic evaluation of a lymph node biopsy revealed that the patient actually had a much rarer but relatively benign condition, Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis). We discuss the epidemiology, clinical symptoms, diagnosis, histologic features, and treatment of this uncommon mimic of posttransplant lymphoproliferative disease.
Assuntos
Doença Hepática Terminal/cirurgia , Linfadenite Histiocítica Necrosante/diagnóstico , Transplante de Fígado/efeitos adversos , Linfadenopatia/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Antirreumáticos/uso terapêutico , Diagnóstico Diferencial , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Feminino , Glucocorticoides/uso terapêutico , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Linfadenite Histiocítica Necrosante/etiologia , Humanos , Cirrose Hepática Biliar/complicações , Linfadenopatia/tratamento farmacológico , Linfadenopatia/etiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
The transplant community has debated the necessity and merits of broader organ distribution for several years, but the debate has been fundamentally shaped by inaccurate assessments of donor supply and demand. The possible legal requirements of distribution must be balanced with (a) the moral and statutory imperatives to reduce inequities resulting from socioeconomic disparity, and (b) the shortcomings of MELD in predicting mortality risk in rural areas. In this viewpoint, we use the example of liver transplantation to discuss the drivers of geographic disparity as a direct consequence of donation rates, local organ use, wealth, and poverty. Seen in this light, strategies seeking to equalize MELD at transplant across the United States risk severely exacerbating existing inequalities in access to health care.
Assuntos
Necessidades e Demandas de Serviços de Saúde/organização & administração , Disparidades em Assistência à Saúde , Transplante de Fígado/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/organização & administração , Listas de Espera , Geografia , Humanos , Regionalização da Saúde , Estados UnidosRESUMO
BACKGROUND & AIMS: Variants at the ABCB4 or MDR2 locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin (IL) 17, yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells. METHODS: We performed studies with Mdr2-/- and littermate FVB/NJ (control) mice. IL17 was measured in serum samples by an enzyme-linked immunosorbent assay. Mice were injected with neutralizing antibodies against the γδ T-cell receptor (TCR; anti-γδ TCR) or mouse IL17A (anti-IL17A). Livers were collected and bacteria were identified in homogenates by culture procedures; TCRγδ+ cells were isolated by flow cytometry. Fecal samples were collected from mice and analyzed by 16S ribosomal DNA sequencing. Cells were stimulated with antibodies or bacteria, and cytokine production was measured. We obtained tissues from 10 patients undergoing liver transplantation for primary sclerosing cholangitis or chronic hepatitis C virus infection. Tissues were analyzed for cytokine production by γδ TCR+ cells. RESULTS: Mdr2-/- mice had collagen deposition around hepatic bile ducts and periportal-bridging fibrosis with influx of inflammatory cells and increased serum levels of IL17 compared with control mice. Administration of anti-IL17A reduced hepatic fibrosis. Livers from Mdr2-/- mice had increased numbers of IL17A+ γδTCR+ cells-particularly of IL17A+ Vγ6Jγ1 γδ TCR+ cells. Fecal samples from Mdr2-/- mice were enriched in Lactobacillus, and liver tissues were enriched in Lactobacillus gasseri compared with control mice. Mdr2-/- mice also had increased intestinal permeability. The γδ TCR+ cells isolated from Mdr2-/- livers produced IL17 in response to heat-killed L gasseri. Intraperitoneal injection of control mice with L gasseri led to increased serum levels of IL17 and liver infiltration by inflammatory cells; injection of these mice with anti-γδ TCR reduced serum level of IL17. Intravenous injections of Mdr2-/- mice with anti-γδ TCR reduced fibrosis; liver levels of IL17, and inflammatory cells; and serum levels of IL17. γδTCR+ cells isolated from livers of patients with primary sclerosing cholangitis, but not hepatitis C virus infection, produced IL17. CONCLUSIONS: In Mdr2-/- mice, we found development of liver fibrosis and inflammation to require hepatic activation of γδ TCR+ cells and production of IL17 mediated by exposure to L gasseri. This pathway appears to contribute to development of cholestatic liver disease in patients.
Assuntos
Colestase/patologia , Microbioma Gastrointestinal , Interleucina-17/metabolismo , Linfócitos Intraepiteliais/metabolismo , Cirrose Hepática/patologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Animais , Ductos Biliares/citologia , Ductos Biliares/imunologia , Ductos Biliares/microbiologia , Células Cultivadas , Colangite Esclerosante/microbiologia , Colangite Esclerosante/patologia , Colangite Esclerosante/cirurgia , Colestase/imunologia , Colestase/microbiologia , Colestase/cirurgia , Modelos Animais de Doenças , Doença Hepática Terminal/microbiologia , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Feminino , Hepatite C Crônica/patologia , Hepatite C Crônica/cirurgia , Hepatite C Crônica/virologia , Humanos , Interleucina-17/antagonistas & inibidores , Interleucina-17/sangue , Interleucina-17/imunologia , Lactobacillus gasseri/imunologia , Fígado/citologia , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/microbiologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Adulto Jovem , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATPRESUMO
Desmoplastic spindle cell tumors of liver are rare tumors of low malignant potential characterized by well-demarcated nests of spindle and epithelioid cells in a dense desmoplastic stroma. While surgery remains the definitive treatment, there have been reports of tumor recurrence locally and metastasis which respond poorly to chemotherapy. Hepatic transplant has been attempted in cases of recurrence or large size of primary tumor. Long-term follow-up and imaging surveillance are required as these tumors have shown a tendency for recurrence many years after initial therapy.
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Síndrome de Beckwith-Wiedemann/complicações , Síndrome de Cushing/etiologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neoplasias Epiteliais e Glandulares/cirurgia , Adolescente , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Epiteliais e Glandulares/complicaçõesRESUMO
Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to nonfunctional intrahepatic CD8+ T-cell responses. In light of dampened CD8+ T-cell responses, liver disease often manifests systemically as immunoglobulin (Ig)-related syndromes due to aberrant B-cell functions. These two opposing yet coexisting phenomena implicate the potential of altered CD4+ T-cell help. Elevated CD4+ forkhead box P3-positive (Foxp3+) T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells. While this population suppressed CD8+ T-cell responses, aberrant B-cell activities were maintained due to expression of CD40 ligand on a subset of CD4+ Foxp3+ T cells. In vivo blockade of CD40 ligand attenuated B-cell abnormalities in a mouse model of liver injury. A phenotypically similar population of CD4+ Foxp3+, CD40 ligand-positive T cells was found in diseased livers explanted from patients with chronic hepatitis C infection. This population was absent in nondiseased liver tissues and peripheral blood. CONCLUSION: Liver disease elicits alterations in the intrahepatic CD4+ T-cell compartment that suppress T-cell immunity while concomitantly promoting aberrant IgG mediated manifestations. (Hepatology 2017;65:661-677).
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Linfócitos T CD8-Positivos/imunologia , Fatores de Transcrição Forkhead/metabolismo , Imunoglobulina G/imunologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Análise de Variância , Animais , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , ELISPOT , Citometria de Fluxo , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Hepatócitos , Humanos , Imunoglobulina G/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Estatísticas não Paramétricas , Linfócitos T Reguladores/imunologiaRESUMO
UNLABELLED: Chronic liver disease is characterized by the liver enrichment of myeloid dendritic cells (DCs). To assess the role of disease on myelopoiesis, we utilized a systems biology approach to study development in liver-resident cells expressing stem cell marker CD34. In patients with endstage liver disease, liver CD34+ cells were comprised of two subsets, designated CD34+CD146+ and CD34+CD146-, and hematopoietic function was restricted to CD34+CD146- cells. Liver CD34 frequencies were reduced during nonalcoholic steatohepatitis (NASH) and chronic hepatitis C virus (HCV) compared to alcohol liver disease (ALD), and this reduction correlated with viral load in the HCV cohort. To better understand the relationship between liver CD34+CD146+ and CD34+CD146- subsets and any effects of disease on CD34 development, we used gene expression profiling and computational modeling to compare each subset during ALD and HCV. For CD34+CD146+ cells, increased expression of endothelial cell genes including von Willebrand factor, VE-cadherin, and eNOS were observed when compared to CD34+CD146- cells, and minimal effects of ALD and HCV diseases on gene expression were observed. Importantly for CD34+CD146- cells, chronic HCV was associated with a distinct "imprint" of programs related to cell cycle, DNA repair, chemotaxis, development, and activation, with an emphasis on myeloid and B lymphocyte lineages. This HCV signature was further translated in side-by-side analyses, where HCV CD34+CD146- cells demonstrated superior hematopoietic growth, colony formation, and diversification compared to ALD and NASH when cultured identically. Disease-associated effects on hematopoiesis were also evident by phenotypic alterations in the expression of CD14, HLA-DR, and CD16 by myeloid progeny cells. CONCLUSION: Etiology drives progenitor fate within diseased tissues. The liver may be a useful source of hematopoietic cells for therapy, or as therapeutic targets.
Assuntos
Células-Tronco Hematopoéticas/fisiologia , Hepacivirus/fisiologia , Fígado/citologia , Biologia de Sistemas , Antígenos CD34/análise , Antígeno CD146/análise , Linhagem da Célula , Hematopoese , Hepatite C Crônica/fisiopatologia , Humanos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Carga ViralRESUMO
BACKGROUND: Management of hepatocellular carcinoma (HCC) in the Model for End-Stage Liver Disease (MELD) exception era remains regionally variable. Outcomes were compared for patients undergoing transplant versus resection at a single institution in a UNOS region with short wait times for organ availability. METHODS: All patients who underwent resection of HCC from January 2000 to August 2012 and patients who underwent transplant post-January 2006, during the Milan Criteria (MC)-based MELD exception policy for HCC, were identified. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Two hundred fifty-seven patients were analyzed, of whom 131 underwent transplant and 126 underwent resection. All transplant patients met MC; 45 (36%) resection patients met MC. Median follow-up time was 30 months. Median wait time to transplant was 55 days; no patients dropped off the waitlist while awaiting an organ. Among patients meeting MC, transplant demonstrated significantly greater 5-year OS (65.7% vs. 43.8%; P = 0.005) and RFS (85.3% vs. 22.7%; P < 0.001) versus resection. For patients with hepatitis C, transplant (n = 87) demonstrated significantly improved 5-year outcomes compared to patients meeting MC who underwent resection (n = 21; OS: 63.5% vs. 23.3%; P = 0.001; RFS: 83.5% vs. 23.7%; P < 0.001). CONCLUSION: In a region with short waitlist times for organ availability, liver transplant is associated with improved survival compared to resection for HCC within MC and should be considered for all patients meeting MC, particularly those with hepatitis C.
Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Hepatite C Crônica/mortalidade , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/cirurgia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Listas de EsperaRESUMO
BACKGROUND: Combined resection of both the liver and pancreas for malignancy remains a controversial procedure. To many, the need for such an extended procedure implies an extent of disease that is usually not amenable to surgical control, and the extent of the procedure exposes the patients to substantial operative risks. The purpose of this study was to assess our results with combined resection of the liver and pancreas. STUDY DESIGN: Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included 26 pancreaticoduodenectomies (PD) and 14 distal pancreatic resections. Liver resections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections. RESULTS: There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy. Mean hospital stay was 14 days (range 7 to 42 days). Median follow-up was 30 months (range 3 to 76 months). Patients undergoing resection for neuroendocrine tumors had a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p = 0.01). CONCLUSIONS: Combined resection of the liver and pancreas can be performed safely. The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindication to resection in selected patients.
Assuntos
Hepatectomia , Neoplasias Hepáticas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Seleção de Pacientes , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Gallbladder duplication is a rare congenital biliary anomaly with different morphologies depending on events at embryogenesis. This case report describes a symptomatic duplicate gallbladder arising from the left intrahepatic duct 10 years after an open cholecystectomy: this is the rarest form of gallbladder duplication. The symptoms resolved following a second open cholecystectomy. This case illustrates the importance of preoperative imaging, intraoperative cholangiography, and a high index of suspicion of anomalous gallbladder anatomy in the diagnosis and management of this rare condition. We discuss the classification of anomalous gallbladder anatomy and review previous cases, to propose a modification of the common classification scheme.