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1.
Clin Transl Gastroenterol ; 13(7): e00502, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35905417

RESUMO

INTRODUCTION: Indeterminate acute liver failure (IND-ALF) is a rare clinical syndrome with a high mortality rate. Lacking a known etiology makes rapid evaluation and treatment difficult, with liver transplantation often considered as the only therapeutic option. Our aim was to identify genetic variants from whole exome sequencing data that might be associated with IND-ALF clinical outcomes. METHODS: Bioinformatics analysis was performed on whole exome sequencing data for 22 patients with IND-ALF. A 2-tier approach was used to identify significant single-nucleotide polymorphisms (SNPs) associated with IND-ALF clinical outcomes. Tier 1 identified the SNPs with a higher relative risk in the IND-ALF population compared with those identified in control populations. Tier 2 determined the SNPs connected to transplant-free survival and associated with model for end-stage liver disease serum sodium and Acute Liver Failure Study Group prognostic scores. RESULTS: Thirty-one SNPs were found associated with a higher relative risk in the IND-ALF population compared with those in controls, of which 11 belong to the human leukocyte antigen (HLA) class II genes but none for the class I. Further analysis showed that 5 SNPs: rs796202376, rs139189937, and rs113473719 of HLA-DRB5; rs9272712 of HLA-DQA1; and rs747397929 of IDO1 were associated with a higher probability of IND-ALF transplant-free survival. Using 3 selected SNPs, a model for the polygenic risk score was developed to predict IND-ALF prognoses, which are comparable with those by model for end-stage liver disease serum sodium and Acute Liver Failure Study Group prognostic scores. DISCUSSION: Certain gene variants in HLA-DRB5, HLA-DQA1, and IDO1 were found associated with IND-ALF transplant-free survival. Once validated, these identified SNPs may help elucidate the mechanism of IND-ALF and assist in its diagnosis and management.


Assuntos
Doença Hepática Terminal , Falência Hepática Aguda , Genes MHC da Classe II , Cadeias HLA-DRB5/genética , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/genética , Falência Hepática Aguda/cirurgia , Índice de Gravidade de Doença , Sódio , Sequenciamento Completo do Exoma
2.
Ann Hepatol ; 27(5): 100718, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35460882

RESUMO

BACKGROUND: Loneliness, "a subjective feeling of being isolated", is a strong predictor of adverse health. We characterized loneliness in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). METHODS: We surveyed loneliness in ambulatory ESLD adults awaiting LT at 7 U.S. sites using the validated UCLA Three-Item Loneliness Scale, May2020-Jan2021; "lonely"=total ≥5. Liver Frailty Index (LFI) assessed frailty; "frail"=LFI≥4.4. Logistic regression associated loneliness and co-variables. RESULTS: Of 454 participants, median MELDNa was 14 (IQR 10-19) and 26% met criteria for "lonely". Compared to those not lonely, those lonely were younger (57 v. 61y), more likely to be female (48% v. 31%) or frail (21 v. 11%), and less likely to be working (15% v. 26%) or in a committed partnership (52% v. 71%). After multivariable adjustment, frailty (OR=2.24, 95%CI=1.23-4.08), younger age (OR=1.19, 95%CI=1.07-1.34), female sex (OR=1.83, 95%CI=1.14-2.92), not working (OR=2.16, 95%CI=1.16-4.03), and not in a committed partnership (OR=2.07, 95%CI=1.29-3.32) remained significantly associated with higher odds of loneliness. CONCLUSION: Loneliness is prevalent in adults awaiting LT, and independently associated with younger age, female sex and physical frailty. These data lay the foundation to investigate the extent to which loneliness impacts health outcomes in LT, as in the general population.

3.
Am J Gastroenterol ; 117(4): 617-626, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35081550

RESUMO

INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) is the second leading cause of acute liver failure (ALF) in the United States. Our study aims were to characterize secular trends in the implicated agents, clinical features, and outcomes of adults with DILI ALF over a 20-year period. METHODS: Among 2,332 patients with ALF enrolled in the ALF Study Group registry, 277 (11.9%) were adjudicated as idiosyncratic DILI ALF (INR ≥ 1.5 and hepatic encephalopathy) through expert opinion. The 155 cases in era 1 (January 20, 1998-January 20, 2008) were compared with the 122 cases in era 2 (January 21, 2008-January 20, 2018). RESULTS: Among 277 cases of DILI ALF, 97 different agents, alone or in combination, were implicated: antimicrobials, n = 118 (43%); herbal/dietary supplements (HDS), n = 42 (15%); central nervous system agents/illicit substances, n = 37 (13%); oncologic/biologic agents, n = 29 (10%); and other, n = 51 (18%). Significant trends over time included (i) an increase in HDS DILI ALF (9.7% vs 22%, P < 0.01) and decrease in antimicrobial-induced DILI ALF (45.8% vs. 38.5%, P = 0.03) and (ii) improved overall transplant-free survival (23.5%-38.7%, P < 0.01) while the number of patients transplanted declined (46.4% vs 33.6%, P < 0.03). DISCUSSION: DILI ALF in North America is evolving, with HDS cases rising and other categories of suspect drugs declining. The reasons for a significant increase in transplant-free survival and reduced need for liver transplantation over time remain unclear but may be due to improvements in critical care, increased NAC utilization, and improved patient prognostication.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Falência Hepática Aguda , Transplante de Fígado , Adulto , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Humanos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/epidemiologia , Transplante de Fígado/estatística & dados numéricos , América do Norte/epidemiologia , Sistema de Registros , Estados Unidos/epidemiologia
4.
Hepatol Commun ; 6(1): 237-246, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34558844

RESUMO

Physical frailty and impaired cognition are common in patients with cirrhosis. Physical frailty can be assessed using performance-based tests, but the extent to which impaired cognition may impact performance is not well characterized. We assessed the relationship between impaired cognition and physical frailty in patients with cirrhosis. We enrolled 1,623 ambulatory adult patients with cirrhosis waiting for liver transplantation at 10 sites. Frailty was assessed with the liver frailty index (LFI; "frail," LFI ≥ 4.4). Cognition was assessed at the same visit with the number connection test (NCT); continuous "impaired cognition" was examined in primary analysis, with longer NCT (more seconds) indicating worse impaired cognition. For descriptive statistics, "impaired cognition" was NCT ≥ 45 seconds. Linear regression associated frailty and impaired cognition; competing risk regression estimated subhazard ratios (sHRs) of wait-list mortality (i.e., death/delisting for sickness). Median NCT was 41 seconds, and 42% had impaired cognition. Median LFI (4.2 vs. 3.8) and rates of frailty (38% vs. 20%) differed between those with and without impaired cognition. In adjusted analysis, every 10-second NCT increase associated with a 0.08-LFI increase (95% confidence interval [CI], 0.07-0.10). In univariable analysis, both frailty (sHR, 1.63; 95% CI, 1.43-1.87) and impaired cognition (sHR, 1.07; 95% CI, 1.04-1.10) associated with wait-list mortality. After adjustment, frailty but not impaired cognition remained significantly associated with wait-list mortality (sHR, 1.55; 95% CI, 1.33-1.79). Impaired cognition mediated 7.4% (95% CI, 2.0%-16.4%) of the total effect of frailty on 1-year wait-list mortality. Conclusion: Patients with cirrhosis with higher impaired cognition displayed higher rates of physical frailty, yet frailty independently associated with wait-list mortality while impaired cognition did not. Our data provide evidence for using the LFI to understand mortality risk in patients with cirrhosis, even when concurrent impaired cognition varies.


Assuntos
Disfunção Cognitiva/etiologia , Fragilidade/etiologia , Cirrose Hepática/complicações , Idoso , Feminino , Humanos , Cirrose Hepática/psicologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Listas de Espera/mortalidade
5.
Hepatol Commun ; 6(4): 910-919, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34676697

RESUMO

Acute kidney injury (AKI) and frailty are major drivers of outcomes among patients with cirrhosis. What is unknown is the impact of physical frailty on the development of AKI. We included adults with cirrhosis without hepatocellular carcinoma listed for liver transplantation at nine US centers (n = 1,033). Frailty was assessed using the Liver Frailty Index (LFI); "frail" was defined by LFI ≥ 4.2. Chronic kidney disease as a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2 . Our primary outcome, AKI, was defined as an increase in serum creatinine ≥0.3 mg/dL or a serum creatinine ≥1.5-fold increase. Wait-list mortality was defined as either a death on the wait list or removal for being too sick. We performed Cox regression analyses to estimate the hazard ratios (HRs) for AKI and wait-list mortality. Of 1,033 participants, 41% were frail and 23% had CKD. Twenty-one percent had an episode of AKI during follow-up. Frail versus nonfrail patients were more likely to develop AKI (25% vs. 19%) and wait-list mortality (21% vs. 13%) (P < 0.01 for each). In multivariable Cox regression, each of the following groups was associated with a higher risk of AKI as compared with not frail/no CKD: frail/no CKD (adjusted HR [aHR] = 1.87, 95% confidence interval [CI] = 1.29-2.72); not frail/CKD (aHR = 4.30, CI = 2.88-6.42); and frail/CKD (aHR = 4.85, CI = 3.33-7.07). We use a readily available metric, LFI, to identify those patients with cirrhosis most at risk for AKI. We highlight that serum creatinine and creatinine-based estimations of glomerular filtration rate may not fully capture a patient's vulnerability to AKI among the frail phenotype. Conclusion: Our work lays the foundation for implementing physical frailty in clinical practice to identify AKI earlier, implement reno-protective strategies, and expedite liver transplantation.


Assuntos
Injúria Renal Aguda , Fragilidade , Injúria Renal Aguda/diagnóstico , Fragilidade/complicações , Humanos , Cirrose Hepática/complicações , Estudos Prospectivos , Listas de Espera
6.
Hepatology ; 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862808

RESUMO

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

7.
Liver Int ; 41(10): 2467-2473, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34219362

RESUMO

BACKGROUND & AIMS: Cirrhosis leads to malnutrition and muscle wasting that manifests as frailty, which may be influenced by cirrhosis aetiology. We aimed to characterize the relationship between frailty and cirrhosis aetiology. METHODS: Included were adults with cirrhosis listed for liver transplantation (LT) at 10 US centrer who underwent ambulatory testing with the Liver Frailty Index (LFI; 'frail' = LFI ≥ 4.4). We used logistic regression to associate aetiologies and frailty, and competing risk regression (LT as the competing risk) to determine associations with waitlist mortality (death/delisting for sickness). RESULTS: Of 1,623 patients, rates of frailty differed by aetiology: 22% in chronic hepatitis C, 31% in alcohol-associated liver disease (ALD), 32% in non-alcoholic fatty liver disease (NAFLD), 21% in autoimmune/cholestatic and 31% in 'other' (P < .001). In univariable logistic regression, ALD (OR 1.53, 95% CI 1.12-2.09), NAFLD (OR 1.64, 95% CI 1.18-2.29) and 'other' (OR 1.58, 95% CI 1.06-2.36) were associated with frailty. In multivariable logistic regression, only ALD (OR 1.40; 95% 1.01-1.94) and 'other' (OR 1.59; 95% 1.05-2.40) remained associated with frailty. A total of 281 (17%) patients died/were delisted for sickness. In multivariable competing risk regression, LFI was associated with waitlist mortality (sHR 1.05, 95% CI 1.03-1.06), but aetiology was not (P > .05 for each). No interaction between frailty and aetiology on the association with waitlist mortality was found (P > .05 for each interaction term). CONCLUSIONS: Frailty is more common in patients with ALD, NAFLD and 'other' aetiologies. However, frailty was associated with waitlist mortality independent of cirrhosis aetiology, supporting the applicability of frailty across all cirrhosis aetiologies.


Assuntos
Doença Hepática Terminal , Fragilidade , Transplante de Fígado , Adulto , Fragilidade/diagnóstico , Humanos , Cirrose Hepática , Listas de Espera
8.
Hepatology ; 74(5): 2735-2744, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34021505

RESUMO

BACKGROUND AND AIMS: Extrahepatic portal vein occlusion (EHPVO) from portal vein thrombosis is a rare condition associated with substantial morbidity and mortality. The purpose of this study is to investigate the efficacy of transjugular intrahepatic portosystemic shunts (TIPS) for the treatment of chronic EHPVO, cavernomatosis, and mesenteric venous thrombosis in adults without cirrhosis who are refractory to standard-of-care therapy. APPROACH AND RESULTS: Thirty-nine patients with chronic EHPVO received TIPS. Laboratory parameters and follow-up were assessed at 1, 3, 6, 12, and 24 months, and every 6 months thereafter. Two hepatologists adjudicated symptom improvement attributable to mesenteric thrombosis and EHPVO before/after TIPS. Kaplan-Meier was used to assess primary and overall TIPS patency, assessing procedural success. Adverse events, radiation exposure, hospital length-of-stay and patency were recorded. Cavernoma was present in 100%, with TIPS being successful in all cases using splenic, mesenteric, and transhepatic approaches. Symptom improvement was noted in 26 of 30 (87%) at 6-month follow-up. Twelve patients (31%) experienced TIPS thrombosis. There were no significant long-term laboratory adverse events or deaths. At 36 months, freedom from primary TIPS thrombosis was 63%; following secondary interventions, overall patency was increased to 81%. CONCLUSIONS: TIPS in chronic, noncirrhotic EHPVO with cavernomas and mesenteric venous thrombosis is technically feasible and does not adversely affect liver function. Most patients demonstrate subjective and objective benefit from TIPS. Improvement in patency rates are needed with proper timing of adjuvant anticoagulation.


Assuntos
Anticoagulantes/administração & dosagem , Isquemia Mesentérica/terapia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Trombose Venosa/terapia , Adulto , Idoso , Doença Crônica/terapia , Terapia Combinada/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular
9.
Cardiovasc Intervent Radiol ; 44(7): 1070-1080, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33825060

RESUMO

PURPOSE: To evaluate hepatocellular carcinoma (HCC) treatment allocation, deviation from BCLC first-treatment recommendation, and outcomes following multidisciplinary, individualized approach. METHODS: Treatment-naïve HCC discussed at multidisciplinary tumor board (MDT) between 2010 and 2013 were included to allow minimum 5 years of follow-up. MDT first-treatment recommendation (resection, transplant, ablation, transarterial radioembolization (Y90), transarterial chemoembolization, sorafenib, palliation) was documented, as were subsequent treatments. Overall survival (OS) analyses were performed on an intention-to-treat (ITT) basis, stratified by BCLC stage. RESULTS: Three hundred and twenty-one patients were treated in the 4-year period. Median age was 62 years, predominantly male (73%), hepatitis C (41%), and Y90 initial treatment (52%). There was a 76% rate of BCLC-discordant first-treatment. Median OS was not reached (57% alive at 10 years), 51.0 months, 25.4 months and 13.4 months for BCLC stages A, B, C and D, respectively. CONCLUSION: Deviation from BCLC guidelines was very common when individualized, MDT treatment recommendations were made. This approach yielded expected OS in BCLC A, and exceeded general guideline expectations for BCLC B, C and D. These results suggest that while guidelines are helpful, implementing a more personalized approach that incorporates center expertise, patient-specific characteristics, and the known multi-directional treatment allocation process, improves patient outcomes.


Assuntos
Algoritmos , Antineoplásicos/uso terapêutico , Braquiterapia/métodos , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
10.
Hepatology ; 74(2): 961-972, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33660316

RESUMO

BACKGROUND AND AIMS: The 13 C-methacetin breath test (MBT) is a noninvasive, quantitative hepatic metabolic function test. The aim of this prospective, multicenter study was to determine the utility of initial and serial 13 C-MBT in predicting 21-day outcomes in adults with acute liver failure (ALF) and non-acetaminophen acute liver injury (ALI). APPROACH AND RESULTS: The 13 C-MBT BreathID device (Exalenz Biosciences, Ltd.) provided the percent dose recovery (PDR) for a duration of 60 minutes after administration of 13 C-methacetin solution as the change in exhaled 13 CO2 /12 CO2 compared with pre-ingestion ratio on study days 1, 2, 3, 5, and 7. Results were correlated with 21-day transplant-free survival and other prognostic indices. A total of 280 subjects were screened for enrollment between May 2016 and August 2019. Median age of the 62 enrolled patients with adequate data was 43 years, 79% were Caucasian, 76% had ALF with the remaining 24% having ALI. The mean PDR peak on day 1 or day 2 was significantly lower in nonsurvivors compared with transplant-free survivors (2.3%/hour vs. 9.1%/hour; P < 0.0001). In addition, serial PDR peaks were consistently lower in nonsurvivors versus survivors (P < 0.0001). The area under the receiver operating characteristic curve (AUROC) of the 13 C-MBT in the combined cohort was 0.88 (95% CI: 0.79-0.97) and higher than that provided by King's College (AUROC = 0.70) and Model for End-Stage Liver Disease scores (AUROC = 0.83). The 13 C-MBT was well tolerated with only two gastrointestinal adverse events reported. CONCLUSIONS: The 13 C-MBT is a promising tool to estimate the likelihood of hepatic recovery in patients with ALF and ALI. Use of the PDR peak data from the 13 C-MBT point-of-care test may assist with medical decision making and help avoid unnecessary transplantation in critically ill patients with ALF and ALI.


Assuntos
Acetamidas/análise , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Terminal/epidemiologia , Falência Hepática Aguda/diagnóstico , Testes Imediatos , Acetamidas/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Testes Respiratórios/métodos , Isótopos de Carbono , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Doença Hepática Induzida por Substâncias e Drogas/cirurgia , Tomada de Decisão Clínica/métodos , Progressão da Doença , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/patologia , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto Jovem
11.
Hepatology ; 74(2): 937-949, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33636020

RESUMO

BACKGROUND AND AIMS: Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. APPROACH AND RESULTS: A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. CONCLUSIONS: In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.


Assuntos
Transtornos da Coagulação Sanguínea/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Hemorragia/epidemiologia , Falência Hepática Aguda/sangue , Acetaminofen/efeitos adversos , Adolescente , Adulto , Idoso , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Feminino , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Falência Hepática Aguda/complicações , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Tromboelastografia/estatística & dados numéricos , Adulto Jovem
12.
Clin Gastroenterol Hepatol ; 19(12): 2615-2625.e3, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920216

RESUMO

BACKGROUND & AIMS: Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry. METHODS: A retrospective review of this prospective, multicenter cohort study of all APAP-ALF patients enrolled during the study period (1998-2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998-2007; recent, 2008-2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT). RESULTS: Of 1190 APAP-ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P < .001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P < .001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P < .001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86). CONCLUSIONS: TFS in APAP-ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.


Assuntos
Acetaminofen , Falência Hepática Aguda , Acetaminofen/efeitos adversos , Estudos de Coortes , Humanos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/terapia , Estudos Prospectivos , Estudos Retrospectivos
13.
Sleep ; 44(6)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33367862

RESUMO

Cognitive impairment and disturbed sleep-wake rhythms are disabling complications of liver cirrhosis, yet there is limited understanding of how they are related. We tested the hypothesis that alterations of sleep, rest-activity, and light exposure patterns are associated with worse cognition in cirrhosis. A total of 54 ambulatory adult patients with cirrhosis and 41 age-/gender-matched healthy controls wore wrist actigraphy for rest-activity and light measurements and completed Patient-Reported Outcomes Measurement Information System sleep instruments for self-reported sleep quality. We used standard nonparametric descriptors to characterize rest-activity and light patterns, and wake after sleep onset and sleep efficiency to assess objective sleep quality. The NIH Toolbox cognition battery was used for objective cognitive evaluation using T-scores from a demographically adjusted population reference. Spearman's correlation and multivariable models were used to explore associations between measures of cognition, sleep, rest-activity, and light. Cognition was significantly impaired in cirrhosis patients. Sleep quality was worse in cirrhosis patients by subjective and objective measures compared with controls. Cirrhosis patients exhibited fragmented and dampened rest-activity rhythms, lower daytime and higher nighttime light exposure compared with controls. Worse working memory and processing speed was associated with lower daytime activity level, higher rest-activity fragmentation, lower day-to-day stability, and greater nocturnal light exposure. No association was found between cognition and sleep quality. Rest-activity fragmentation and abnormal light exposure patterns are common in patients with liver disease and are associated with the severity of cognitive impairment. Further research is needed to investigate the effects of timed bright light and exercise intervention on cognitive function in patients with liver disease.


Assuntos
Disfunção Cognitiva , Transtornos do Sono-Vigília , Actigrafia , Adulto , Ritmo Circadiano , Disfunção Cognitiva/complicações , Humanos , Cirrose Hepática/complicações , Descanso , Sono
14.
J Vasc Interv Radiol ; 32(2): 211-219, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33349507

RESUMO

PURPOSE: To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile. MATERIALS AND METHODS: This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49-81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4-19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method. RESULTS: The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9-11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively. CONCLUSIONS: Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.


Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Derivação Portossistêmica Transjugular Intra-Hepática , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Bases de Dados Factuais , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/mortalidade , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos
15.
Hepatology ; 73(3): 998-1010, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32416631

RESUMO

BACKGROUND AND AIMS: Radioembolization (yttrium-90 [Y90]) is used in hepatocellular carcinoma (HCC) as a bridging as well as downstaging liver-directed therapy to curative liver transplantation (LT). In this study, we report long-term outcomes of LT for patients with HCC who were bridged/downstaged by Y90. APPROACH AND RESULTS: Patients undergoing LT following Y90 between 2004 and 2018 were included, with staging by United Network for Organ Sharing (UNOS) tumor-node-metastasis criteria at baseline pre-Y90 and pre-LT. Post-Y90 toxicities were recorded. Histopathological data of HCC at explant were recorded. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS), disease-specific mortality (DSM), and time-to-recurrence, were reported. Time-to-endpoint analyses were estimated using Kaplan-Meier. Univariate and multivariate analyses were performed using a log-rank test and Cox proportional-hazards model, respectively. During the 15-year period, 207 patients underwent LT after Y90. OS from LT was 12.5 years, with a median time to LT of 7.5 months [interquartile range, 4.4-10.3]. A total of 169 patients were bridged, whereas 38 were downstaged to LT. Respectively, 94 (45%), 60 (29%), and 53 (26%) patients showed complete, extensive, and partial tumor necrosis on histopathology. Three-year, 5-year, and 10-year OS rates were 84%, 77%, and 60%, respectively. Twenty-four patients developed recurrence, with a median RFS of 120 (95% confidence interval, 69-150) months. DSM at 3, 5, and 10 years was 6%, 11%, and 16%, respectively. There were no differences in OS/RFS for patients who were bridged or downstaged. RFS was higher in patients with complete/extensive versus partial tumor necrosis (P < 0.0001). For patients with UNOS T2 treated during the study period, 5.2% dropped out because of disease progression. CONCLUSIONS: Y90 is an effective treatment for HCC in the setting of bridging/downstaging to LT. Patients who achieved extensive or complete necrosis had better RFS, supporting the practice of neoadjuvant treatment before LT.


Assuntos
Braquiterapia/métodos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Transplante de Fígado , Terapia Neoadjuvante/métodos , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Sobrevida , Radioisótopos de Ítrio
16.
Hepatology ; 73(3): 1132-1139, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32491208

RESUMO

BACKGROUND AND AIMS: Frailty, as measured by the Liver Frailty Index (LFI), is associated with liver transplant (LT) waitlist mortality. We sought to identify an optimal LFI cutoff that predicts waitlist mortality. APPROACH AND RESULTS: Adults with cirrhosis awaiting LT without hepatocellular carcinoma at nine LT centers in the United States with LFI assessments were included. Multivariable competing risk analysis assessed the relationship between LFI and waitlist mortality. We identified a single LFI cutoff by evaluating the fit of the competing risk models, searching for the cutoff that gave the best model fit (as judged by the pseudo-log-likelihood). We ascertained the area under the curve (AUC) in an analysis of waitlist mortality to find optimal cutoffs at 3, 6, or 12 months. We used the AUC to compare the discriminative ability of LFI+Model for End Stage Liver Disease-sodium (MELDNa) versus MELDNa alone in 3-month waitlist mortality prediction. Of 1,405 patients, 37 (3%), 82 (6%), and 135 (10%) experienced waitlist mortality at 3, 6, and 12 months, respectively. LFI was predictive of waitlist mortality across a broad LFI range: 3.7-5.2. We identified an optimal LFI cutoff of 4.4 (95% confidence interval [CI], 4.0-4.8) for 3-month mortality, 4.2 (95% CI, 4.1-4.4) for 6-month mortality, and 4.2 (95% CI, 4.1-4.4) for 12-month mortality. The AUC for prediction of 3-month mortality for MELDNa was 0.73; the addition of LFI to MELDNa improved the AUC to 0.79. CONCLUSIONS: LFI is predictive of waitlist mortality across a wide spectrum of LFI values. The optimal LFI cutoff for waitlist mortality was 4.4 at 3 months and 4.2 at 6 and 12 months. The discriminative performance of LFI+MELDNa was greater than MELDNa alone. Our data suggest that incorporating LFI with MELDNa can more accurately represent waitlist mortality in LT candidates.


Assuntos
Fragilidade/patologia , Transplante de Fígado/estatística & dados numéricos , Fígado/patologia , Listas de Espera/mortalidade , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Feminino , Fragilidade/diagnóstico , Fragilidade/mortalidade , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
17.
JAMA Surg ; 156(3): 256-262, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33377947

RESUMO

Importance: Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown. Objective: To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation. Design, Setting, and Participants: This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020. Exposures: At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance). Main Outcomes and Measures: The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men. Results: Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty. Conclusions and Relevance: These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.


Assuntos
Fragilidade/complicações , Fragilidade/mortalidade , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Transplante de Fígado , Listas de Espera/mortalidade , Estudos de Coortes , Feminino , Fragilidade/diagnóstico , Força da Mão , Humanos , Cirrose Hepática/terapia , Masculino , Pessoa de Meia-Idade , Atividade Motora , Equilíbrio Postural , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais
18.
J Vasc Interv Radiol ; 31(12): 2113-2120.e1, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32948389

RESUMO

PURPOSE: The purpose of this study was to present the institutional experience of performing endoscopy, cholangiography, and biliary interventions through the modified Hutson loop by interventional radiology. MATERIALS AND METHODS: A total of 61 of 64 modified Hutson loop access procedures were successful. This single-center retrospective study included 61 successful procedures of biliary interventions using existing modified Hutson loops (surgically affixed subcutaneous jejunal limb adjacent to biliary anastomosis or anastomoses) for diagnostic or therapeutic purposes in 21 patients. Seventeen of 21 patients (81%) had undergone liver transplantation. Indications included biliary strictures (n = 18) and biliary leaks (n = 3). The clinical success and complications were evaluated. RESULTS: There were 3 of 26 modified Hutson loop retrograde biliary intervention failures (12%) before introduction of endoscopy and no failures (0 of 38 [0%]) subsequently (P = .06). Endoscopy or cholangioscopy was performed in 19 procedures by interventional radiologists. Retrograde biliary interventions included diagnostic cholangiography (n = 26), cholangioplasty (n = 25), stent placement (n = 29), stent retrieval (n = 25), and biliary drainage catheter placement (n = 5). No procedure-related mortality occurred. There was 1 major complication (duodenal perforation) (1.6%) and 12 minor complications (19%). In the 9 patients undergoing therapeutic interventions for biliary strictures, there was a significant decrease in median alkaline phosphatase (288.5 to 174.5 U/L; P = .03). There was a trend toward decrease in median bilirubin levels (1.7 to 1 mg/dL; P = .06) at 1 month post-intervention. CONCLUSIONS: The modified Hutson loop provided interventional radiologists a safe and effective alternative access to manage biliary complications in patients with biliary-enteric anastomoses. Introduction of the endoscope in interventional radiology has improved the success rate of these procedures.


Assuntos
Fístula Anastomótica/terapia , Colangiopancreatografia Retrógrada Endoscópica , Colestase/terapia , Drenagem , Radiografia Intervencionista , Adulto , Idoso , Fístula Anastomótica/diagnóstico por imagem , Fístula Anastomótica/etiologia , Cateteres , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Colestase/diagnóstico por imagem , Colestase/etiologia , Constrição Patológica , Drenagem/efeitos adversos , Drenagem/instrumentação , Feminino , Hepatectomia/efeitos adversos , Humanos , Jejunostomia/efeitos adversos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Stents , Resultado do Tratamento , Adulto Jovem
19.
Liver Transpl ; 26(10): 1328-1336, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32574418

RESUMO

Hepatorenal syndrome (HRS) is one of the most ominous complications of portal hypertension in patients with decompensated cirrhosis and ascites. It is associated with very high mortality on the wait list. Liver transplantation (LT) is the most successful therapeutic option for patients with HRS. However, not all the LT candidates with HRS are able to receive a deceased donor allograft in a timely manner because it is a scarce resource and patients may need alternative best supportive treatment with systemic splanchnic vasoconstrictors and albumin as a bridge to transplant. The combination of terlipressin and albumin is efficacious in the reversal of HRS and is used worldwide. More recently, the multicenter, randomized, placebo-controlled double-blind study to confirm efficacy and safety of terlipressin in subjects with hepatorenal syndrome type 1 (the CONFIRM study) trial demonstrated the efficacy of terlipressin and albumin in the reversal of HRS in a North American cohort. The aim of this article is to review the role of terlipressin and albumin in LT candidates with HRS in the United States.


Assuntos
Síndrome Hepatorrenal , Transplante de Fígado , Albuminas , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/tratamento farmacológico , Síndrome Hepatorrenal/etiologia , Humanos , Transplante de Fígado/efeitos adversos , Lipressina/uso terapêutico , Terlipressina , Vasoconstritores/efeitos adversos
20.
J Hepatol ; 73(3): 575-581, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32240717

RESUMO

BACKGROUND & AIMS: To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation. METHODS: Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk. RESULTS: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09). CONCLUSION: Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty. LAY SUMMARY: Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.


Assuntos
Fragilidade/epidemiologia , Fragilidade/mortalidade , Cirrose Hepática/epidemiologia , Índice de Gravidade de Doença , Listas de Espera/mortalidade , Comorbidade , Feminino , Seguimentos , Humanos , Cirrose Hepática/patologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Estados Unidos/epidemiologia
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