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OBJECTIVE: To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. BACKGROUND: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). METHODS: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. RESULTS: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. CONCLUSIONS: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/métodos , Doadores Vivos , Recidiva Local de Neoplasia/etiologia , Seleção de Pacientes , América do Norte , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: In 2015, the United Network for Organ Sharing implemented a policy introducing a 6-mo waiting period before granting model for end-stage liver disease exception points to liver transplant (LT) candidates with hepatocellular carcinoma (HCC). This study analyzes the policy impact on post-LT HCC recurrence. METHODS: This was a United Network for Organ Sharing retrospective cohort study of patients with HCC who underwent LT from January 1, 2010, to May 31, 2019. HCC-specific data included alpha-fetoprotein, tumor characteristics, locoregional therapy (LRT), and explant data used to calculate the Risk Estimation of Tumor Recurrence After Transplant score. The primary exposure was pre-/post-policy era, divided on October 8, 2015. Survival analysis techniques were used to evaluate the unadjusted and sequentially adjusted association between policy era and HCC recurrence, accounting for competing risks. RESULTS: A total of 7940 patients were included, 5879 (74.0%) pre-policy era and 2061 (26.0%) post-policy era. Post-policy patients were older, received more LRT, and had lower alpha-fetoprotein levels and smaller tumor sizes at transplant. Incidence rates of HCC recurrence were 19.8 and 13.7 events per 1000 person-years for pre- and post-policy eras, respectively. Post-policy era was associated with an unadjusted 35% reduction in the risk of HCC recurrence (Pâ <â 0.001). After adjusting for recipient, donor, and tumor characteristics at listing this association remained (subhazard ratio 0.69; 95% confidence interval, 0.55-0.86; P = 0.001); however, after additionally adjusting for LRT episodes and Risk Estimation of Tumor Recurrence After Transplant score, there was no longer a statistically significant association (subhazard ratio 0.77; 95% confidence interval, 0.59-1.00; P = 0.054). CONCLUSIONS: We observed a significant reduction in post-LT HCC recurrence after policy implementation. This may be due to waitlist selection of healthier patients, increased LRT utilization, and potential selection of favorable tumor biology.
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NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Fatores de RiscoRESUMO
BACKGROUND: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC. METHODS: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts. RESULTS: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12). CONCLUSIONS: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Adulto , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/tratamento farmacológico , Estudos RetrospectivosAssuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Hepatocellular carcinoma (HCC) has well-defined environmental risk factors. In addition, epidemiologic studies have suggested hereditary risk factors. The goals of this study were to determine the rate of pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes in patients with HCC, possible enrichment of P/LP variants in particular genes, and potential impact on clinical management. MATERIALS AND METHODS: A prospective study at a tertiary medical center enrolled 217 patients with a personal history of HCC. Multigene panel testing was performed for 134 cancer predisposition genes in all patients. The rate of P/LP variants was compared with population rates. A separate retrospective cohort included 219 patients with HCC who underwent testing at a commercial laboratory. RESULTS: In the prospective cohort, P/LP germline variants were identified in 25 of 217 patients with HCC (11.5%). Four patients (1.8%) had P/LP variants in the highly penetrant cancer genes BRCA2 (n = 2), MSH6 (n = 1), and PMS2 (n = 1). In addition, multiple patients had P/LP variants in FANCA (n = 5) and BRIP1 (n = 4), which were significantly enriched in HCC compared with the general population. Detection of P/LP variants led to changes in clinical management in regard to therapy selection, screening recommendations, and cascade testing of relatives. In a separate retrospective analysis of 219 patients with HCC, 30 (13.7%) were positive for P/LP variants including 13 (5.9%) with highly penetrant genes APC (n = 2), BRCA1 (n = 1), BRCA2 (n = 6), MSH2 (n = 2), or TP53 (n = 2). CONCLUSION: P/LP germline variants in cancer predisposition genes were detected in 11%-14% of patients with HCC. Inherited genetics should not be overlooked in HCC as there are important implications for precision treatment, future risk of cancers, and familial cancer risk.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Testes Genéticos/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Variação Genética , Células Germinativas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos RetrospectivosRESUMO
The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT. METHODS: Patients with recurrent HCC after LT between January 1996 and December 2017 were retrospectively reviewed. RESULTS: Of 711 patients, 96 (13.5%) patients had post-LT HCC recurrence. The median time to recurrence was 17.1 months, and the median survival was 10.1 months. Initial recurrence was more often in the graft (34.4%), and most (60.4%) had multiple recurrent lesions, and 26% were in multiple sites. In multivariate analysis, factors associated with shorter survival were poorly differentiated histology in explant (Hazard ratio [HR] = 1.96; p = 0.027), bilirubin ≥1.2 mg/dL (HR = 2.47; p = 0.025), and albumin <3.5 mg/dL (HR = 2.13; p = 0.014) at recurrence, alpha-fetoprotein at recurrence ≥ 1000 ng/mL (HR = 2.96; p = 0.005), and peritoneal disease (HR = 3.20; p = 0.022). There was an increased survival in patients exposed to sirolimus (HR = 0.32; p < 0.0001). CONCLUSIONS: Recurrent HCC after LT is often in extrahepatic sites with a decreased survival in those with poorly differentiated explant pathology, high bilirubin, low albumin, marked elevation of alpha-fetoprotein at recurrence, and peritoneal recurrence. Sirolimus-based immunosuppression may provide benefit.
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Liver transplantation (LT) is curative for most patients with hepatocellular carcinoma (HCC). However, 10%-15% of patients experience HCC recurrence. Patients who are reported as within Milan criteria by imaging are frequently found to be outside the criteria on explant. This under-staging of HCC worsens post-LT outcomes. However, risk factors for under-staging have not been elucidated. Furthermore, it is not known if there is regional or center-level variation in under-staging. We conducted a retrospective analysis of adult patients transplanted for HCC in the United Network for Organ Sharing (UNOS) database between 2012 and 2016. Under-staging was determined on the basis of comparing pre-LT imaging to explant findings. Kaplan-Meier methods and Cox regression were used to evaluate the impact of under-staging on HCC recurrence and post-LT survival. Mixed effects logistic regression was used to identify risk factors for under-staging and to study regional and center-level variation in adjusted analyses. A total of 5424 patients were included in the cohort, of whom 24.9% (n = 1353) were under-staged. Post-LT HCC recurrence and death were significantly associated with under-staging (each P < 0.001). In adjusted analyses, independent predictors of under-staging included age (odds ratio [OR], 1.13 per 10 years; 95% confidence interval [CI], 1.03-1.25), male sex (OR, 1.61; 95% CI, 1.36-1.89), down-staging (OR, 4.03; 95% CI, 2.65-6.11), and pre-LT alpha-fetoprotein (P < 0.001). There was also significant variation in under-staging between UNOS regions and among transplant centers, ranging from 14.8% to 38.1%. We report novel risk factors for HCC under-staging, which worsens post-LT outcomes. Significant center-level and regional variation in under-staging highlights the need for standards that achieve greater uniformity in staging.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Criança , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). RESULTS: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3-12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3-12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. CONCLUSIONS: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Atitude , Carcinoma Hepatocelular/terapia , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/terapia , Recidiva Local de NeoplasiaRESUMO
PURPOSE: To identify and characterize the delayed effects of transarterial radioembolization (TARE) on the liver. MATERIALS AND METHODS: A single-institution retrospective analysis was undertaken of all patients who received TARE between 2005 and 2014 and survived at least 1 year from the initial TARE (n = 106). Patients were evaluated for the presence or absence of radioembolization-induced chronic hepatotoxicity (RECHT) occurring at least 6 months after TARE. The mean age of patients was 63 years of age, and the malignancy most commonly treated was neuroendocrine tumor (54%). Adjudication of hepatic decompensation to RECHT versus alternative causes was performed by a multidisciplinary panel of specialists from hepatology, radiation oncology, and interventional radiology. RESULTS: Eight patients were excluded from analysis because of liver transplantation (2) or incomplete data (6). RECHT occurred in 13 of 98 patients (13%), and 5 deaths (5%) occurred from hepatic decompensation. There were a total of 69 toxicity events in patients developing RECHT. The most common events were elevation of alkaline phosphatase (10), decrease in serum albumin (10), and development of ascites (9). RECHT patients had a higher intrahepatic tumor volume (P = .021) and a higher number of hepatic comorbidities leading to cirrhosis (P = .015). CONCLUSIONS: Delayed radiation-induced hepatic toxicity occurred in 13% of patients following radioembolization, with 5 fatalities adjudicated to be a result of the treatment. Tumor involvement of greater than 50% of the liver and cirrhosis were predisposing factors for RECHT.
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Embolização Terapêutica/efeitos adversos , Hepatopatias/etiologia , Neoplasias Hepáticas/radioterapia , Exposição à Radiação/efeitos adversos , Lesões por Radiação/etiologia , Compostos Radiofarmacêuticos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Embolização Terapêutica/mortalidade , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Lesões por Radiação/diagnóstico , Lesões por Radiação/mortalidade , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga TumoralAssuntos
Antineoplásicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Falência Hepática Aguda/induzido quimicamente , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/terapia , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/terapia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/imunologia , Recuperação de Função Fisiológica , Talidomida/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria on explant pathology are at increased risk of recurrence and death. Discordance between contemporary magnetic resonance imaging (MRI) and explant pathology, and preoperative characteristics predictive of discordance are not well understood. METHODS: Patients who underwent orthotopic liver transplantation for HCC after preoperative MRI were identified in a prospectively collected institutional database (January 2003 to December 2013). Patients were dichotomized to "within" or "outside" Milan criteria by both imaging and explant pathologic evaluation. Binary logistic regression and Kaplan-Meier methodology were used to identify independent predictors of imaging/pathologic discordance and its impact on posttransplant survival. RESULTS: Of 318 patients with HCC meeting Milan criteria by MRI at the time of orthotopic liver transplantation, 248 (78.0%) remained within a pathological correlate of Milan criteria on explant examination. Understaging was associated with worse median recurrence-free survival (64.0 months vs 140.0 months, P = 0.002) and overall survival (96.0 months vs 143.0 months, P = 0.005), and did not vary between patients exceeding criteria due to tumor explant greater than 5 cm, more than 3 tumor foci, or a tumor greater than 3 cm in the setting of multifocality. Discordance was independently associated with an increasing serum alpha fetal protein level (odds ratio, 2.82; 95% confidence interval, 1.37-5.79; P = 0.005). CONCLUSIONS: Underestimating HCC burden before liver transplant remains frequent despite contemporary imaging technologies. Patients with an increasing alpha fetal protein before transplantation may benefit from more frequent testing or novel neoadjuvant therapies.
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Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Transplante de Fígado , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias/métodos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Tomada de Decisão Clínica , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
BACKGROUND & AIMS: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. METHODS: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. RESULTS: Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P < .0001), therapy with PEGα-2a (odds ratio = 4.7; P = .03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P = .005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P < .0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P = .002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P = .005), and lack of a sustained virologic response (HR = 3.3; P = .04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P = .04) and lack of a sustained virologic response (HR = 2.1; P = .04). CONCLUSIONS: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.
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Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Transplante de Fígado/efeitos adversos , Polietilenoglicóis/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Adulto , Estudos de Casos e Controles , Feminino , Hepatite C/virologia , Humanos , Transplante de Fígado/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Disfunção Primária do Enxerto/patologia , Proteínas Recombinantes/efeitos adversos , Recidiva , Fatores de RiscoAssuntos
Amiodarona/toxicidade , Fígado Gorduroso/diagnóstico , Cirrose Hepática/diagnóstico , Fígado/diagnóstico por imagem , Fígado/patologia , Idoso , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Complicações do Diabetes , Feminino , Insuficiência Cardíaca/complicações , Humanos , Testes de Função Hepática , Contagem de Plaquetas , Radiografia , Albumina Sérica/análise , Tomografia Computadorizada de EmissãoRESUMO
AIM: To determine factors affecting the outcome of patients with cirrhosis undergoing surgery and to compare the capacities of the Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) score to predict that outcome. METHODS: We reviewed the charts of 195 patients with cirrhosis who underwent surgery at two teaching hospitals over a five-year period. The combined endpoint of death or hepatic decompensation was considered to be the primary endpoint. RESULTS: Patients who reached the endpoint had a higher MELD score, a higher CTP score and were more likely to have undergone an urgent procedure. Among patients undergoing elective surgical procedures, no statistically significant difference was noted in the mean MELD (12.8 +/- 3.9 vs 12.6 +/- 4.7, P = 0.9) or in the mean CTP (7.6 +/- 1.2 vs 7.7 +/- 1.7, P = 0.8) between patients who reached the endpoint and those who did not. Both mean scores were higher in the patients reaching the endpoint in the case of urgent procedures (MELD: 22.4 +/- 8.7 vs 15.2 +/- 6.4, P = 0.0007; CTP: 9.9 +/- 1.8 vs 8.5 +/- 1.8, P = 0.008). The performances of the MELD and CTP scores in predicting the outcome of urgent surgery were only fair, without a significant difference between them (AUC = 0.755 +/- 0.066 for MELD vs AUC = 0.696 +/- 0.070 for CTP, P = 0.3). CONCLUSION: The CTP and MELD scores performed equally, but only fairly in predicting the outcome of urgent surgical procedures. Larger studies are needed to better define the factors capable of predicting the outcome of elective surgical procedures in patients with cirrhosis.
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Anestesia Geral/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Tratamento de Emergência/efeitos adversos , Indicadores Básicos de Saúde , Cirrose Hepática/diagnóstico , Cirrose Hepática/cirurgia , Falência Hepática/etiologia , Modelos Biológicos , Idoso , Anestesia Geral/mortalidade , Procedimentos Cirúrgicos Eletivos/mortalidade , Tratamento de Emergência/mortalidade , Feminino , Georgia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Falência Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Nonalcoholic steatohepatitis (NASH) is one of the most common liver disorders in North America. The mechanism of liver injury in NASH involves insulin resistance and oxidative stress as well as cytokine release. Therapeutic interventions aimed at enhancing insulin sensitivity or reducing oxidative stress have been studied. The role of peptide hormones secreted by adipose tissue--adipocytokines--in the potential pathogenesis of NASH is an area of intense research. As the function of adipokines in modulating hepatic inflammation and fibrosis is elucidated, the potential for novel treatment strategies in patients with NASH is likely to be realized.