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1.
Hepatol Res ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451566

RESUMO

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

2.
Dig Dis Sci ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824258

RESUMO

BACKGROUND: In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS: We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS: In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION: Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.

3.
Clin Transplant ; 36(3): e14555, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34874071

RESUMO

Acute liver failure is life-threatening and has to be treated by liver transplantation urgently. When deceased donors or ABO-compatible living donors are not available, ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) becomes the only choice. How to prepare ABO-I LDLT urgently is an unsolved issue. A quick preparation regimen was designed, which was consisted of bortezomib (3.5 mg) injection to deplete plasma cells and plasma exchange to achieve isoagglutinin titer ≤ 1: 64 just prior to liver transplantation and followed by rituximab (375 mg/m2 ) on post-operative day 1 to deplete B-cells. Eight patients received this quick preparation regimen to undergo ABO-I LDLT for acute liver failure from 2012 to 2019. They aged between 50 and 60 years. The median MELD score was 39 with a range from 35 to 48. It took 4.75 ± 1.58 days to prepare such an urgent ABO-I LDLT. All the patients had successful liver transplantations, but one patient died of antibody-mediated rejection at post-operative month 6. The 3-month, 6-month, and 1-year graft/patient survival were 100%, 87.5%, and 75%, respectively. In conclusion, this quick preparation regimen can reduce isoagglutinin titers quickly and make timely ABO-I LDLT feasible for acute liver failure.


Assuntos
Falência Hepática Aguda , Transplante de Fígado , Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Rejeição de Enxerto/etiologia , Humanos , Falência Hepática Aguda/cirurgia , Doadores Vivos , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Resultado do Tratamento
4.
World J Surg Oncol ; 19(1): 313, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702312

RESUMO

BACKGROUND: The outcomes and management of hepatocellular carcinoma (HCC) have undergone several evolutionary changes. This study aimed to analyze the outcomes of patients who had undergone liver resection for HCC with portal vein tumor thrombosis (PVTT) in terms of the evolving era of treatment. MATERIALS AND METHODS: A retrospective analysis of 157 patients who had undergone liver resection for HCC associated with PVTT was performed. The outcomes and prognostic factors related to different eras were further examined. RESULTS: Overall, 129 (82.1%) patients encountered HCC recurrence after liver resection, and the median time of recurrence was 4.1 months. Maximum tumor size ≥ 5 cm and PVTT in the main portal trunk were identified as the major prognostic factors influencing HCC recurrence after liver resection. Although the recurrence-free survival had no statistical difference between the two eras, the overall survival of patients in the second era was significantly better than that of the patients in the first era (p = 0.004). The 1-, 2-, and 3-year overall survival rates of patients in the second era were 60.0%, 45.7%, and 35.8%, respectively, with a median survival time of 19.6 months. CONCLUSION: The outcomes of HCC associated with PVTT remain unsatisfactory because of a high incidence of tumor recurrence even after curative resection. Although the management and outcomes of patients with HCC and PVTT have greatly improved over the years, surgical resection remains an option to achieve a potential cure of HCC in well-selected patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose Venosa , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Veia Porta/cirurgia , Prognóstico , Estudos Retrospectivos , Trombose Venosa/etiologia , Trombose Venosa/cirurgia
5.
J Surg Oncol ; 122(7): 1444-1452, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32875573

RESUMO

BACKGROUND AND OBJECTIVES: Precise prognostic prediction for an individual hepatocellular carcinoma (HCC) patient before and after liver resection is important. We aimed to establish simple prognostic models to predict disease-free survival (DFS) for these patients. METHODS: Six hundred and ninety-eight HCC patients with liver resections were reviewed. Preoperative (model 1) and postoperative (model 2) nomogram-based scoring systems were constructed by multivariate analyses, and DFS was estimated. RESULTS: Among 698 patients, 490 (70.2%) patients had tumor recurrence at a median follow-up of 84.4 months. Risk factors of tumor recurrence in model 1 included viral hepatitis, platelet count, albumin, indocyanine green retention rate, multiplicity of tumor, and radiologic total tumor volume (TTV). Prognostic variables identified in model 2 were viral hepatitis, platelet count, multiplicity of tumor, cirrhosis, microvascular invasion, and pathologic TTV. By nomogram in model 1, the patients were classified into three groups with 5-year DFS of 61.0%, 35.7%, and 21.1%, respectively (P < .0001). In model 2, the patients were divided into five groups with 5-year DFS of 58.0%, 43.7%, 24.0%, 15.4%, and 0.0%, respectively (P < .0001). CONCLUSION: Based on nomogram models, DFS for the patients who had liver resection for HCC can be predicted before liver resection and re-assessed after liver resection.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nomogramas , Prognóstico , Carga Tumoral
6.
Hepatol Res ; 50(12): 1386-1390, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32909341

RESUMO

The severe form of acute exacerbation of hepatitis B during pregnancy is a rare but life-threatening condition for both the mother and the fetus. A 32-year-old pregnant woman at 10 weeks of gestation was diagnosed with acute decompensated liver failure due to acute exacerbation of hepatitis B. The Model for End-stage Liver Disease score was up to 37. The patient was managed carefully with antiviral treatment, fluid resuscitation, correction of coagulopathy, close monitoring of hepatic function, and regular assessment of the fetus. She was transplanted with a deceased liver at 14 weeks and 1 day of gestation. With careful post-transplant care and avoidance of medication with risk of miscarriage and teratogenicity, a healthy baby was delivered at 39 weeks and 1 day of gestation. Herein, we report this critical condition of pregnancy that was complicated with liver failure due to acute exacerbation of hepatitis B, but had favorable outcomes for both the mother and the baby after liver transplantation.

7.
Transpl Infect Dis ; 21(6): e13190, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31587427

RESUMO

BACKGROUND: Combination of anti-hepatitis B immunoglobulin (HBIg) and antiviral nucleotide/nucleoside is the most common regimen for prophylaxis against hepatitis B virus (HBV) recurrence. However, what the optimal regimen is for HBIg administration remains subject to debate. METHODS: Two hundred and thirty-two HBV patients who had liver transplantation were included in this study. According to the decline rate of HBIg, the patients were divided into quick (group Q, n = 95) and slow decline groups (group S, n = 137). Quick HBIg decline was defined as anti-HBs titer <200 IU/mL at postoperative month (POM) 1, when 24 000 IU of HBIg was given perioperatively. HBV recurrence was defined as reappearance of hepatitis B surface antigen (HBsAg). RESULTS: After a mean (range) follow-up of 42.2 (24.1-76.8) months, the HBV recurrence rate was 12.1% for all 232 patients. The median (interquartile) HBIg titer was 96.2 (41.0-158.0) IU in group Q patients, compared to 418.0 (298.8-692.8) IU in group S patients at POM 1 (P < .001). For the patients in group Q, 18 patients (18.9%) had HBV recurrence; this was higher than the 10 (7.3%) patients in group S (P = .013). Multivariate analysis showed that quick HBIg decline and hepatocellular carcinoma recurrence were the risk factors for HBV recurrence. CONCLUSION: Perioperative low-dose HBIg and antiviral nucleotide/nucleoside can effectively prevent HBV recurrence in patients with slow HBIg decline. For patients with quick HBIg decline, the idealized HBIg and antiviral agent regimen should be adjusted to establish an effective regimen as prophylaxis against HBV recurrence.


Assuntos
Hepatite B Crônica/prevenção & controle , Imunização Passiva/métodos , Imunoglobulinas/administração & dosagem , Transplante de Fígado/efeitos adversos , Prevenção Secundária/métodos , Adulto , Idoso , Antivirais/administração & dosagem , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Anticorpos Anti-Hepatite B/sangue , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/virologia , Estudos Prospectivos , Recidiva , Resultado do Tratamento
8.
World J Surg Oncol ; 16(1): 24, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29415722

RESUMO

BACKGROUND: Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved. METHODS: A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed. RESULTS: Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07-2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99-1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors. CONCLUSION: The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.


Assuntos
Tomada de Decisão Clínica , Neoplasias Colorretais/patologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Proc Natl Acad Sci U S A ; 112(42): 13075-80, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26438846

RESUMO

The most deadly complication of Plasmodium falciparum infection is cerebral malaria (CM) with a case fatality rate of 15-25% in African children despite effective antimalarial chemotherapy. There are no adjunctive treatments for CM, so there is an urgent need to identify new targets for therapy. Here we show that the glutamine analog 6-diazo-5-oxo-L-norleucine (DON) rescues mice from CM when administered late in the infection a time at which mice already are suffering blood-brain barrier dysfunction, brain swelling, and hemorrhaging accompanied by accumulation of parasite-specific CD8(+) effector T cells and infected red blood cells in the brain. Remarkably, within hours of DON treatment mice showed blood-brain barrier integrity, reduced brain swelling, decreased function of activated effector CD8(+) T cells in the brain, and levels of brain metabolites that resembled those in uninfected mice. These results suggest DON as a strong candidate for an effective adjunctive therapy for CM in African children.


Assuntos
Antimaláricos/uso terapêutico , Diazo-Oxo-Norleucina/uso terapêutico , Glutamina/metabolismo , Malária Cerebral/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Animais , Antimaláricos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Diazo-Oxo-Norleucina/farmacologia , Malária Cerebral/metabolismo , Malária Falciparum/metabolismo , Camundongos
10.
Clin Proteomics ; 14: 29, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28785178

RESUMO

BACKGROUND: Hepatocellular carcinoma is an aggressive malignancy with poor prognosis and easy to recur even the tumor is totally removed by surgery. Portal vascular invasion is one of the major factors contributing to tumor recurrence and poor prognosis. However, why hepatocellular carcinoma is easy to grow into vessels is unclear. METHODS: Surgical specimens from seven hepatocellular carcinoma patients with portal vein thrombosis and seven patients without vascular invasion were utilized to analyze protein expression by proteomic technique. The proteins in the tumors were separated by 2-dimensional electrophoresis. Protein patterns in the gels were recorded as digitalized images. The differences of expression in hepatocellular carcinoma with or without portal vein thrombosis were identified by mass spectrometry. RESULTS: Clinically, the tumors with portal vein thrombosis were larger than those without portal vein thrombosis. The median survival time for the patients with portal vein thrombosis was much shorter [4 (ranged 2.5-47) vs. 53 (ranged 33-85) months, p = 0.002]. By analyzing the protein expression in cancer tissues with or without portal vein thrombosis, the differences of protein expression were mainly metabolic enzymes. Carbonic anhydrase I, betaine-homocysteine S-methyltransferase 1, fumarate hydratase, isovaleryl-CoA dehydrogenase, short-chain specific acyl-CoA dehydrogenase and arginase-1 were all down-regulated in the tumors with portal vein thrombosis. CONCLUSION: Metabolic enzymes and cytosol carbonic anhydrases were downregulated in hepatocellular carcinoma with portal vein thrombus. The deficiency of metabolic enzymes and cytosol carbonic anhydrases may alter cellular metabolisms and acid-base balance in hepatocellular carcinoma, which may facilitate to invade portal vein.

11.
Liver Int ; 37(3): 434-441, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27775209

RESUMO

BACKGROUND: Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. METHODS: All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2 years were included for analysis. RESULTS: Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (P<.0001) and overall survival (P<.0001) after liver resection. The hazard ratio of metformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (P<.05, 95% CI=0.60-0.72) for hepatocellular carcinoma recurrence and 0.79 (P<.05, 95% CI=0.72-0.88) for overall survival after liver resection. The risk reduction in hepatocellular carcinoma recurrence after liver resection was significantly associated with a dose/duration dependent of accumulated metformin usage. CONCLUSION: Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2 years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence.


Assuntos
Carcinoma Hepatocelular/cirurgia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Metformina/uso terapêutico , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Hepatectomia , Humanos , Hipoglicemiantes/uso terapêutico , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taiwan/epidemiologia
12.
Clin Transplant ; 31(2)2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27888549

RESUMO

BACKGROUND: Despite the technical and medical improvements in the recent years, hepatic artery thrombosis (HAT) remains a devastating complication after living donor liver transplantation (LDLT). We described our surgical techniques and monitoring protocols for hepatic artery reconstruction. We reported one of the lowest incidence rates of HAT in the literature. METHODS: Between 2008 and 2015, a total of 325 LDLTs performed at our institute were retrospectively analyzed. Under microscope assistance, all hepatic artery anastomosis were performed in a risk-free and back-wall first manner. We collected donors' and recipients' demographics, operative procedures, and outcome. RESULTS: A total of 325 adult LDLTs were enrolled in the study. Of these, 297(91.4%) were right liver graft. The mean diameter of the hepatic arteries of the graft was 1.9 ± 0.3 mm. A single HA anastomosis was performed in 310 patients (95.4%). The 1-, 3-, and 5-year overall patient survival rates were 84.8%, 76.8%, and 75.2%, respectively. Only one (0.3%) episode of HAT was encountered in our series. The patient was treated successfully with nonsurgical management. CONCLUSION: Our study showed that the occurrence of HAT is avoidable. Identifying risk factors associated with HAT, meticulous surgical techniques, and careful routine flow monitoring are mandatory to avoid disastrous complications.


Assuntos
Artéria Hepática/cirurgia , Transplante de Fígado , Doadores Vivos , Microscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Trombose/prevenção & controle , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Anastomose Cirúrgica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
13.
Clin Transplant ; 31(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28678384

RESUMO

We aimed to investigate the effect of body mass index (BMI) on the overall survival rates and to identify the risk factors associated with adverse outcomes. A total of 381 adult-to-adult living donor liver transplantations performed were retrospectively analyzed. These patients were classified according to the BMI categories established by the World Health Organization: The underweight group (BMI<18.5 kg/m2 ) and the non-underweight group (BMI≥18.5 kg/m2 ). The underweight group had significantly worse outcomes, compared with that of the non-underweight group (5-year overall survival: 45.6% vs 74.6%, P<.001). Underweight patients with CD4/CD8 ratio <1.4 had a significant worse prognosis, compared with those with CD4/CD8 ratio ≥1.4. (The 1-, 3-, and 5-year overall patient survival rates in both groups were 71.0% vs 20%, 58.9% vs 0%, and 53.6% vs 0%, respectively, P=.002.) In the multivariate analysis, only CD4/CD8 ratio <1.4 was an independent poor prognostic factor (hazard ratio=7.063, 95% confidence interval=1.329-37.547, P=.022). CONCLUSIONS: Pre-operative CD4/CD8 ratio <1.4 is an independent poor prognostic indicator for underweight patients undergoing liver transplantation. Early intervention in replenishing the nutrient deficit and cautious use of immunosuppressive regimens are essential to prepare this high-risk population for a more successful liver transplantation.


Assuntos
Índice de Massa Corporal , Transplante de Fígado/mortalidade , Magreza , Adulto , Relação CD4-CD8 , Feminino , Seguimentos , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Magreza/diagnóstico , Magreza/imunologia , Magreza/mortalidade
15.
Curr Opin Organ Transplant ; 19(4): 363-71, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24991977

RESUMO

PURPOSE OF REVIEW: In this review, we discuss the recent advances with regard to the mammalian target of rapamycin (mTOR) signaling pathway and focus on how this pathway modulates immune responses. Overall, these insights provide important clues in terms of strategically integrating mTOR and metabolic inhibitors into transplantation rejection protocols. RECENT FINDINGS: mTOR is regulated by environmental cues and activates diverse downstream pathways to guide cell growth and fate. What has emerged from recent studies is that mechanistically mTOR directs T cell differentiation and function in part by regulating metabolic programs. Such findings not only inform us with regard to the metabolic demands of effector and memory T cells but also elucidate metabolic pathways that might be targeted to selectively regulate immune responses. SUMMARY: Initial studies focused on the ability of the mTOR inhibitor rapamycin to suppress immune responses by inhibiting T cell proliferation. Since then, both pharmacologic and genetic studies have revealed a central role for mTOR in regulating T cell activation, differentiation, and function independent of proliferation. Specifically, it has become clear that mTOR plays an important role in regulating the metabolic machinery necessary for effector, regulatory, and memory T cell generation. As such, direct inhibition of metabolism may emerge as a potent and selective means of preventing graft rejection. This review will discuss new insights regarding the ability of downstream signaling pathways, including mTOR-dependent metabolic pathways in regulating T cell responses. Finally, we will discuss these new insights in the context of developing novel immunoregulatory regimens for transplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Linfócitos T/imunologia , Serina-Treonina Quinases TOR/imunologia , Animais , Diferenciação Celular/imunologia , Proliferação de Células , Rejeição de Enxerto/imunologia , Humanos , Ativação Linfocitária/imunologia , Transdução de Sinais , Linfócitos T/citologia
16.
Medicine (Baltimore) ; 103(14): e37632, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579088

RESUMO

Donor safety is crucial for living donor liver transplantation (LDLT), and sufficient liver regeneration significantly affects outcomes of living donors. This study aimed to investigate clinical factors associated with liver regeneration in living donors. The study retrospectively reviewed 380 living donors who underwent liver donation at Chang Gung Memorial Hospital in Linkou. The clinical characteristics and medical parameters of donors were analyzed and compared according to liver donation graft type. There were 355 donors (93.4%) with right hemi-liver donations and 25 donors (6.6%) with left hemi-liver donations. Left hemi-liver donors had a higher body mass index (BMI) and a larger ratio of remnant liver volume (RLV) to total liver volume (TLV). However, the 2 groups showed no significant difference in the liver regeneration ratio. The type of remnant liver (P < .001), RLV/body weight (P = .027), RLV/TLV (P < .001), serum albumin on postoperative day 7 and total bilirubin levels on postoperative day 30 were the most significant factors affecting liver regeneration in living donors. In conclusion, adequate liver regeneration is essential for donor outcome after liver donation. The remnant liver could eventually regenerate to an adequate volume similar to the initial TLV before liver donation. However, the remnant left hemi-liver had a faster growth rate than the remnant right hemi-liver in donors.


Assuntos
Regeneração Hepática , Transplante de Fígado , Humanos , Doadores Vivos , Hepatectomia , Estudos Retrospectivos , Fígado/cirurgia , Hepatomegalia
17.
Ann Surg ; 258(2): 306-11, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23108123

RESUMO

OBJECTIVE: To examine the results of split liver transplantation for 2 adults in the model of end-stage liver disease (MELD) era. BACKGROUND: In the MELD era, liver allografts are first allocated to recipients with the highest MELD scores. However, the application of split liver transplantation for 2 adults in urgent condition has doubled and has become a matter of concern. METHODS: Twenty-one deceased liver grafts were split into full right and full left lobes for 42 adult recipients. One of the hemiliver grafts was allocated to the recipient with the highest MELD score in the waiting list. The results of split liver transplantation were examined and compared with those of living donor liver transplantation. RESULTS: Among 42 recipients, 24 (57.1%) had MELD scores higher than 20. The median (interquartile) MELD score for the recipients with split liver transplantation was 22 (15-30), which was higher than that for the recipients with living donor liver transplantation (P < 0.001). The 1-, 3-, and 5-year survival rates for split liver transplantation were comparable with those of living donor transplantation (P = 0.489). Nevertheless, 10 of 42 split liver recipients died within 3 months after transplantation. By receiver operating characteristic curve analysis, the safe graft-recipient weight ratio was better more than 1% to avoid early patient death for split liver transplantation. CONCLUSIONS: Although most of the recipients with split liver transplantation had high MELD scores, the results were comparable with those of living donor liver transplantation. Split liver transplantation for 2 adults is still feasible in the MELD era.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Índice de Gravidade de Doença , Coleta de Tecidos e Órgãos/métodos , Adolescente , Adulto , Idoso , Seleção do Doador , Doença Hepática Terminal/mortalidade , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Doadores de Tecidos , Resultado do Tratamento , Adulto Jovem
18.
Ann Surg Oncol ; 20(11): 3582-90, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23760589

RESUMO

BACKGROUND: Hepatitis B virus (HBV) relapse and/or hepatocellular carcinoma (HCC) recurrence remains a major concern for patients who undergo liver transplantation (LT) because of HBV-related HCC. This study investigates the correlation between HBV relapse and HCC recurrence and it explores factors that affect patient outcomes after LT. METHODS: Between September 2002 and August 2009, 78 consecutive patients who underwent LT because of HBV-related HCC were enrolled in this study. Serum samples obtained before LT were assayed both for virological factors associated with HBV DNA and for genotypic characteristics of the virus. All patient clinicopathological features and virological factors were assessed further by univariate and multivariate analyses to determine prognostic factors. RESULTS: During a median follow-up period of 29.4 months, 13 (16.6 %) patients experienced HCC recurrence and 18 (23.1 %) patients experienced HBV relapse. HBV relapse exhibited a close association with HCC recurrence (p = 0.004) and led to unfavorable overall survival after LT. Multivariate analysis of prognostic factors showed that the basal core promoter (BCP) mutation independently predicted a shorter survival period free from HBV relapse (p = 0.036). Moreover, with the exception of unfavorable tumor characteristics, the BCP mutation was found to be an important prognostic factor that affected HCC recurrence after LT (p = 0.042). CONCLUSIONS: In this study, the HBV-BCP mutation was identified as an important predictor of post-LT clinical outcomes in patients with HBV-related HCC. Therefore, we recommend that aggressive antiviral treatment may be considered for patients associated with this risk factor.


Assuntos
Carcinoma Hepatocelular/mortalidade , Vírus da Hepatite B/genética , Hepatite B/complicações , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/mortalidade , Recidiva Local de Neoplasia/mortalidade , Prevenção Secundária , Adulto , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , DNA Viral/genética , Feminino , Seguimentos , Hepatite B/mortalidade , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Carga Viral
19.
Hepatogastroenterology ; 60(128): 2076-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24719950

RESUMO

BACKGROUND/AIMS: Untreated hepatocellular carcinoma (HCC) has a notoriously poor prognosis, with a median survival of 1-8 months and a 5-year survival of -3%. Potentially curative surgical therapeutic options include partial hepatic resection with adequate margins and liver transplantation (LT). By current guidelines, transarterial chemoembolization (TACE) is the standard of care for the intermediate stage HCC, namely unresectable, multifocal disease confined to the liver in the absence of portal vein thrombosis and is used as bridging therapy for LT wait-listed candidates with HCC to limit tumour progression and dropout rate. TACE is contraindicated in patients with poor liver reserve with hyperbilirubinemia (bilirubin > or = 2 mg/ dL). METHODOLOGY: In this study, 13 sequential HCC patients waitlisted for LT with total bilirubin level > or = 2 mg/dL, that underwent TACE prior to LT, were included. A mean of 4 TACE sessions were performed in each patient; 10 patients were either child A or B while 3 were in child C class. RESULTS: The 30-day mortality rate was nil with minimal adverse effects and none of the patients showed procedure related morbidity such as hepatic decompensation. Hyperbilirubinemia did not affect outcomes significantly and tumour response rate was 54.8%. Thus, with careful selection of patients TACE can still be performed even in presence of hyperbilirubinemia thus preventing disease progression while they are waitlisted for LT.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hiperbilirrubinemia/etiologia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Terapia Neoadjuvante , Listas de Espera , Adulto , Bilirrubina/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/complicações , Quimioembolização Terapêutica/efeitos adversos , Progressão da Doença , Feminino , Humanos , Hiperbilirrubinemia/sangue , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Metabolites ; 13(1)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677042

RESUMO

Liver transplantation can be performed with deceased or living donor allografts. Deceased liver grafts are donated from brain- or circulation-death patients, and they have usually suffered from a certain degree of damage. Post-transplant graft function and patient survival are closely related to liver allograft recovery. How to define the damage of liver grafts is unclear. A total of 47 liver donors, 23 deceased and 24 living, were enrolled in this study. All deceased donors had suffered from severe brain damage, and six of them had experienced cardio-pulmonary-cerebral resuscitation (CPR). The exploration of liver graft metabolomics was conducted by liquid chromatography coupled with mass spectrometry. Compared with living donor grafts, the deceased liver grafts expressed higher levels of various diacylglycerol, lysophosphatidylcholine, lysophosphatidylethanolamine, oleoylcarnitine and linoleylcarnitine; and lower levels of cardiolipin and phosphatidylcholine. The liver grafts from the donors with CPR had higher levels of cardiolipin, phosphatidic acid, phosphatidylcholine, phatidylethanolamine and amiodarone than the donors without CPR. When focusing on amino acids, the deceased livers had higher levels of histidine, taurine and tryptophan than the living donor livers. In conclusion, the deceased donors had suffered from cardio-circulation instability, and their lipid metabolites were increased. The elevation of lipid metabolites can be employed as an indicator of liver graft suffering.

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