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1.
Hepatology ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33660316

RESUMO

The 13 C-Methacetin breath test (MBT) is a non-invasive, 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). METHODS: The 13 C-MBT Breath ID device (Exalenz Biosciences, Ltd.) provided the percent dose recovery (PDR) throughout 60 minutes after administration of 13 C methacetin solution as the change in exhaled 13 CO2 / 12 CO2 compared to 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. RESULTS: 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 and 76% had ALF with the remaining 24% having ALI. The mean PDR peak on Day 1 or 2 was significantly lower in non-survivors compared to transplant-free survivors (2.3 %/hr vs 9.1 %/hr, p < 0.0001). In addition, serial PDR peaks were consistently lower in non-survivors vs survivors (p < 0.0001). The 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 MELD scores (AUROC=0.83). The 13 C-MBT was well tolerated with only 2 gastrointestinal adverse events reported. CONCLUSIONS: The 13 C-MBT is a promising tool to estimate the likelihood of hepatic recovery in ALF and ALI patients. 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 ALF and ALI patients.

2.
Hepatology ; 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33577086

RESUMO

BACKGROUND AND RATIONALE: The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease and liver transplant recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and liver transplantation about vaccine prioritization and administration. MAIN RESULTS: The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger individuals. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly seen in women and individuals with a history of prior drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups CONCLUSIONS: Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with chronic liver disease and liver transplant recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

3.
JAMA ; 324(9): 899-900, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870294
4.
Artigo em Inglês | MEDLINE | ID: mdl-32652308

RESUMO

The Coronavirus disease 2019 (COVID-19) pandemic is expected to have a long-lasting impact on the approach to care for patients at risk for and with hepatocellular carcinoma (HCC) due to the risks from potential exposure and resource reallocation. The goal of this document is to provide recommendations on HCC surveillance and monitoring, including strategies to limit unnecessary exposure while continuing to provide high-quality care for patients. Publications and guidelines pertaining to the management of HCC during COVID-19 were reviewed for recommendations related to surveillance and monitoring practices, and any available guidance was referenced to support the authors' recommendations when applicable. Existing HCC risk stratification models should be utilized to prioritize imaging resources to those patients at highest risk of incident HCC and recurrence following therapy though surveillance can likely continue as before in settings where COVID-19 prevalence is low and adequate protections are in place. Waitlisted patients who will benefit from urgent LT should be prioritized for surveillance whereas it would be reasonable to extend surveillance interval by a short period in HCC patients with lower risk tumor features and those more than 2 years since their last treatment. For patients eligible for systemic therapy, the treatment regimen should be dictated by the risk of COVID-19 associated with route of administration, monitoring and treatment of adverse events, within the context of relative treatment efficacy.

5.
Hepatology ; 72(1): 287-304, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32298473

RESUMO

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19), the illness caused by the SARS-CoV-2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID-19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID-19 pandemic on liver patients and healthcare providers. APPROACH AND RESULTS: This article discusses what is known about COVID-19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID-19 pandemic on their patients' care. CONCLUSIONS: The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID-19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.


Assuntos
Betacoronavirus , Consenso , Infecções por Coronavirus/epidemiologia , Hepatopatias/terapia , Transplante de Fígado , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Interações Medicamentosas , Gastroenterologia/educação , Humanos , Imunossupressão , Internato e Residência , Hepatopatias/epidemiologia , Transplante de Fígado/ética , Transplante de Fígado/métodos , Saúde do Trabalhador , Pandemias , Segurança do Paciente , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Doadores de Tecidos
6.
JAMA ; 323(12): 1175-1183, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207804

RESUMO

Importance: Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) and is associated with disease progression, development of cirrhosis, and need for liver transplant. Despite its importance, NASH is underrecognized in clinical practice. Observations: NASH affects an estimated 3% to 6% of the US population and the prevalence is increasing. NASH is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome. Although a number of noninvasive tests and scoring systems exist to characterize NAFLD and NASH, liver biopsy is the only accepted method for diagnosis of NASH. Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. Lifestyle modification is the mainstay of treatment, including dietary changes and exercise, with the primary goal being weight loss. Substantial improvement in histologic outcomes, including fibrosis, is directly correlated with increasing weight loss. In some cases, bariatric surgery may be indicated to achieve and maintain the necessary degree of weight loss required for therapeutic effect. An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the US. The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD, with annual all-cause mortality rate of 25.56 per 1000 person-years and a liver-specific mortality rate of 11.77 per 1000 person-years. Conclusions and Relevance: Nonalcoholic steatohepatitis affects 3% to 6% of the US population, is more prevalent in patients with metabolic disease and obesity, progresses to cirrhosis in approximately 20% of cases, and is associated with increased rates of liver-specific and overall mortality. Early identification and targeted treatment of patients with nonalcoholic steatohepatitis are needed to improve patient outcomes, including directing patients toward intensive lifestyle modification to promote weight loss and referral for bariatric surgery as indicated for management of obesity and metabolic disease.


Assuntos
Fígado/patologia , Hepatopatia Gordurosa não Alcoólica , Cirurgia Bariátrica , Diagnóstico Diferencial , Progressão da Doença , Humanos , Estilo de Vida , Cirrose Hepática/etiologia , Cirrose Hepática/mortalidade , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/complicações , Prevalência , Estados Unidos/epidemiologia
7.
Int J Infect Dis ; 92: 184-188, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978574

RESUMO

BACKGROUND: There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. METHODS: All HCV infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. Logistic regression model was used to determine factors associated with SVR. RESULTS: Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pre-treatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). CONCLUSION: HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. Though not statistically significant, the virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Feminino , Hepacivirus/genética , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade
8.
Histopathology ; 76(6): 822-831, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31894595

RESUMO

AIMS: The aim of this study was to perform a comprehensive retrospective analysis of liver transplant biopsies with parenchymal rejection (PR) at our institution, including histological features, laboratory values and follow-up biopsies, and to compare PR with portal-based acute cellular rejection (ACR). METHODS AND RESULTS: Biopsies from 173 patients were evaluated (retrospective database search 1990-2017), including 49 isolated PR, 35 PR with portal ACR (PR/ACR), 34 mild ACR and 52 moderate ACR cases. The rise and fall of serum liver enzymes was calculated as a measure of acute liver injury and response to immunotherapy, respectively. Isolated PR was associated with delayed-onset acute rejection (P < 0.001), as well as younger age (P = 0.004), and showed a similar rise in liver enzymes to mild ACR. PR/ACR and moderate ACR showed the highest elevations in transaminases (P < 0.05). Isolated PR on an initial biopsy was associated with recurrent episodes of PR (P = 0.01), chronic ductopaenic rejection (P = 0.002) and chronic vascular rejection (P = 0.017). Immunohistochemistry for C4d was performed, and strong C4d staining of venules was only detected in one severe isolated PR case (one of three, 33%) and one moderate ACR case (one of 20, 5%). CONCLUSIONS: Isolated PR represents a form of late acute rejection with distinct clinical and histological features. There is value in reporting PR in liver transplant biopsies to identify patients at higher risk of developing recurrent PR and chronic rejection. Standardisation of terminology and histological criteria of PR can help in uniform reporting and ensure appropriate management.

9.
Am J Gastroenterol ; 114(10): 1626-1635, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31517638

RESUMO

OBJECTIVES: Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS: We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS: The prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum triglycerides, and hypertension. The best AIC model for cirrhosis consisted of lower platelet count, lower AST/ALT ratio, higher body mass index, and female sex. The area under the receiver operator curves of the prediction models were 0.70 (95% confidence interval: 0.65-0.76) for detecting NASH-F2-3 and 0.85 (95% confidence interval: 0.77-0.92) for detecting cirrhosis. When models were fixed at maximum Youden's index, their positive and negative predictive values were 35% and 88% for NASH F2-F3 and 30% and 98% for cirrhosis, respectively. DISCUSSION: Clinically significant histological phenotypes are observed in patients with NAFLD and normal aminotransferase levels. Our models can assist the clinicians in excluding advanced liver histology in NAFLD patients with normal aminotransferase levels.


Assuntos
Cirrose Hepática/epidemiologia , Fígado/patologia , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/patologia , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biópsia , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
10.
Liver Int ; 39(9): 1661-1671, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31081997

RESUMO

BACKGROUND & AIMS: Current estimates of the population-based disease burden of liver failure or end-stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in-hospital mortality among patients with ESLD in the United States (US). METHODS: A retrospective analysis was performed utilizing the National Inpatient Sample from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in-hospital mortality were analysed from 2005 to 2014. RESULTS: Hospitalization rates for decompensated cirrhosis during this period increased from 105.3/100 000 persons to 159.9/100 000 persons. In terms of HCC, hospitalization rates increased from 13.6/100 000 to 22.1/100 000. In patients with non-alcoholic fatty liver disease (NAFLD)-related decompensated cirrhosis, the hospitalization rate increased from 13.4/100 000 to 32.1/100 000 with an annual incremental increase of 10.6%, a magnitude twofold higher than other aetiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (from 29.3% to 27.6% for HCV; from 39.0% to 37.4% for ALD). Although the overall in-hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD-related decompensated cirrhosis showed no significant change. CONCLUSIONS: Among aetiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non-HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD-related hospitalizations and its impact on resource utilization.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Doença Hepática Terminal/mortalidade , Hospitalização/tendências , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Idoso , Doença Hepática Terminal/etiologia , Feminino , Hepatite C Crônica/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Modelos Lineares , Hepatopatias Alcoólicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Estados Unidos
11.
Clin Gastroenterol Hepatol ; 17(10): 2110-2116, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30731196

RESUMO

BACKGROUND & AIMS: Evaluation of patients with acute liver injury (ALI) or acute liver failure (ALF) often includes measurement of plasma levels of acetaminophen, to determine exposure and/or toxicity. However, once liver injury has developed, acetaminophen might be undetectable in plasma. We investigated the association between level of acetaminophen measured and outcomes of patients designated as having ALF or ALI due to acetaminophen toxicity. METHODS: We performed a retrospective analysis of data from 434 subjects in the Acute Liver Failure Study Group who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) or ALI (severe liver injury with coagulopathy but no encephalopathy) due to acetaminophen toxicity from January 1, 2010 through December 31, 2014. We collected data on patient demographics, biochemical features, reported acetaminophen use, N-acetylcysteine therapy, liver transplant, and outcomes. Descriptive statistics were used to assess patient demographics, clinical characteristics, and outcomes whereas differences in continuous variables between patients with vs without acetaminophen detection on admission were analyzed using the Wilcoxon rank-sum test. The primary aim was to determine the proportion of patients with detectable plasma levels of acetaminophen. RESULTS: Acetaminophen was undetectable in serum samples from 227 patients (52%). There were no significant differences between groups of patients with detectable vs undetectable levels in demographic features, alcohol use, median levels of alanine aspartate, or use of N-acetylcysteine (given to 94.7% of patients with detectable acetaminophen vs 95.9% of those with undetectable acetaminophen; P=.63). We observed a significant difference in median dose taken between patients with detectable (29,500 mg; interquartile range, 15,000 mg-50,007 mg) vs no detectable parent compound (14,950 mg; interquartile range, 3960 mg-25,000) (P=.003). A lower proportion of patients with detectable plasma levels of acetaminophen (72.3%) survived without a liver transplant than of patients with undetectable levels (86.3%) in univariate analysis (P=.0006), although this was not significant in multivariable analysis (P=.12). Although most patients had unintentional overdoses, a higher proportion of patients with suicidal overdoses (43%) had detectable levels of acetaminophen than patients with accidental overdoses (29.3%; P=.01). CONCLUSION: More than half of patients who present at the hospital with acetaminophen-induced ALI or ALF have undetectable levels of acetaminophen. Clinicians should not exclude acetaminophen toxicity because of undetectable levels or withhold N-acetylcysteine for patients with ALI or ALF when acetaminophen toxicity is suspected.


Assuntos
Acetaminofen/envenenamento , Analgésicos não Entorpecentes/envenenamento , Falência Hepática Aguda/induzido quimicamente , Acetaminofen/sangue , Adulto , Analgésicos não Entorpecentes/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Overdose de Drogas/sangue , Feminino , Humanos , Falência Hepática Aguda/sangue , Falência Hepática Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Plasma/química , Estudos Retrospectivos
12.
Hepatology ; 70(3): 788-801, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30661255

RESUMO

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) > 1.67 × upper limit of normal and total bilirubin ≤ 2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 [7α-hydroxy-4-cholesten-3-one] and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with inflammatory bowel disease, 46% on ursodeoxycholic acid). Baseline median serum ALP and bilirubin were 348 U/L (interquartile range 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; P = 0.029 versus placebo), gamma-glutamyl transferase (-30%; P < 0.001), alanine aminotransferase (ALT) (-49%; P = 0.009), and aspartate aminotransferase (-42%; P = 0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between ursodeoxycholic acid-treated and untreated patients. At week 12, cilofexor-treated patients with a 25% or more relative reduction in ALP had greater reductions in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, tissue inhibitor of metalloproteinase 1, C-reactive protein, and bile acids than nonresponders. Adverse events were similar between cilofexor and placebo-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.


Assuntos
Colangite Esclerosante/tratamento farmacológico , Colestase/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/administração & dosagem , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Administração Oral , Adulto , Fosfatase Alcalina/sangue , Análise de Variância , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Colangite Esclerosante/sangue , Colangite Esclerosante/patologia , Colestase/sangue , Colestase/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Clin Gastroenterol Hepatol ; 17(11): 2379-2381, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30458247

RESUMO

The pathogenetic pathways leading to increasing prevalence of advanced fibrosis in the setting of nonalcoholic fatty liver disease (NAFLD) and resulting in higher rates of liver-related and cardiovascular morbidity and mortality in the United States are multifactorial.1 The negative health impact of "low-normal" thyroid function, which is defined as a higher level of thyroid-stimulating hormone (TSH) within the euthyroid reference range, may be comparable with overt and subclinical hypothyroidism.2-4 We reported a strong association between biopsy-proven advanced fibrosis in NAFLD with increasing TSH levels in a dose-dependent manner even within the euthyroid reference range.5 To generalize our findings across all ethnicities, we examined the association of both low-normal thyroid function and subclinical hypothyroidism with advanced fibrosis in the US general population.


Assuntos
Hipotireoidismo/complicações , Cirrose Hepática/epidemiologia , Adulto , Feminino , Humanos , Hipotireoidismo/diagnóstico , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Tireotropina/sangue , Estados Unidos/epidemiologia
14.
Hepatol Commun ; 2(4): 349-353, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29619414

RESUMO

Immunoglobulin G4 (IgG4)-related disease is a fibroinflammatory systemic disorder with multiorgan involvement. Proximal bile duct involvement results in IgG4-related sclerosing cholangitis, which is characterized by a lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells and fibrosis. Differentiating between cholangiocarcinoma and IgG4-sclerosing cholangitis can present a diagnostic dilemma. We describe an unusual presentation of a hepatic mass meeting multiple criteria for IgG4-sclerosing cholangitis but was ultimately found to be cholangiocarcinoma. Several published case reports describe patients with suspected cholangiocarcinoma who are later found to have IgG4-sclerosing cholangitis, but few reports have demonstrated the reverse. Distinguishing between cholangiocarcinoma and IgG4-sclerosing cholangitis is challenging, and a high clinical suspicion for cholangiocarcinoma must always be maintained. (Hepatology Communications 2018;2:349-353).

15.
Transplantation ; 102(5): 794-802, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29319619

RESUMO

BACKGROUND: Data are limited on marijuana use and its impact on liver transplant (LT) waitlist outcomes. We aimed to assess the risk of waitlist mortality/delisting and likelihood of LT among prior marijuana users and to determine the prevalence and factors associated with marijuana use. METHODS: Retrospective cohort of adults evaluated for LT over 2 years at a large LT center. Marijuana use was defined by self-report in psychosocial assessment and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT listing during study period. RESULTS: Eight hundred eighty-four adults were evaluated, and 585 (66%) were listed for LT (median follow-up, 1.4 years; interquartile range, 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being recent users and 41% prior users. Marijuana use had statistically significant association with alcoholic cirrhosis (incidence rate ratio [IRR], 1.9) and hepatitis C (IRR, 2.1) versus hepatitis B, tobacco use (prior IRR, 1.4; recent IRR, 1.3 vs never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs social), and illicit drug use (prior IRR, 2.3; recent, 1.9 vs never). In adjusted competing risk regression, marijuana use was not associated with the probability of LT (prior hazard ratio [HR], 0.9; recent HR, 0.9 vs never) or waitlist mortality/delisting (prior HR, 1.0; recent HR, 1.0 vs never). However, recent illicit drug use was associated with higher risk of death or delisting (HR, 1.8; P = 0.004 vs never). CONCLUSIONS: Unlike illicit drug use, marijuana use was not associated with worse outcomes on the LT waitlist. Prospective studies are needed to assess ongoing marijuana use on the LT waitlist and post-LT outcomes.


Assuntos
Transplante de Fígado/métodos , Abuso de Maconha/epidemiologia , Fumar Maconha/epidemiologia , Transplantados , Listas de Espera , Adolescente , Adulto , Tomada de Decisão Clínica , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Abuso de Maconha/diagnóstico , Abuso de Maconha/mortalidade , Fumar Maconha/efeitos adversos , Fumar Maconha/mortalidade , Pessoa de Meia-Idade , Seleção de Pacientes , Prevalência , Estudos Retrospectivos , Fatores de Risco , São Francisco/epidemiologia , Listas de Espera/mortalidade , Adulto Jovem
16.
Hepatology ; 67(3): 1003-1013, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29080224

RESUMO

Cerebral edema remains a significant cause of morbidity and mortality in patients with acute liver failure (ALF) and has been linked to elevated blood ammonia levels. l-ornithine phenylacetate (OPA) may decrease ammonia by promoting its renal excretion as phenylacetylglutamine (PAGN), decreasing the risk of cerebral edema. We evaluated the safety, tolerability, and pharmacokinetics of OPA in patients with ALF and acute liver injury (ALI), including those with renal failure. Forty-seven patients with ALI/ALF and ammonia ≥60 µM were enrolled. Patients received OPA in a dose escalation scheme from 3.3 g every 24 hours to 10 g every 24 hours; 15 patients received 20 g every 24 hours throughout the infusion for up to 120 hours. Plasma phenylacetate (PA) concentrations were uniformly below target (<75 µg/mL) in those receiving 3.3 g every 24 hours (median [interquartile range] 5.0 [5.0] µg/mL), and increased to target levels in all but one who received 20 g every 24 hours (150 [100] µg/mL). Plasma [PAGN] increased, and conversion of PA to PAGN became saturated, with increasing OPA dose. Urinary PAGN clearance and creatinine clearance were linearly related (r = 0.831, P < 0.0001). Mean ammonia concentrations based on the area under the curve decreased to a greater extent in patients who received 20 g of OPA every 24 hours compared with those who received the maximal dose of 3.3 or 6.7 g every 24 hours (P = 0.046 and 0.022, respectively). Of the reported serious adverse events (AEs), which included 11 deaths, none was attributable to study medication. The only nonserious AEs possibly related to study drug were headache and nausea/vomiting. CONCLUSION: OPA was well-tolerated in patients with ALI/ALF, and no safety signals were identified. Target [PA] was achieved at infusion rates of 20 g every 24 hours, leading to ammonia excretion in urine as PAGN in proportion to renal function. Randomized, controlled studies of high-dose OPA are needed to determine its use as an ammonia-scavenging agent in patients with ALF. (Hepatology 2018;67:1003-1013).


Assuntos
Hiperamonemia/tratamento farmacológico , Falência Hepática Aguda/tratamento farmacológico , Ornitina/análogos & derivados , Acetatos/sangue , Adolescente , Adulto , Idoso , Amônia/sangue , Feminino , Glutamina/análogos & derivados , Glutamina/metabolismo , Humanos , Hiperamonemia/complicações , Testes de Função Renal , Fígado/patologia , Falência Hepática Aguda/complicações , Masculino , Pessoa de Meia-Idade , Ornitina/administração & dosagem , Ornitina/efeitos adversos , Ornitina/farmacocinética , Fenóis/sangue , Sistema de Registros , Resultado do Tratamento , Adulto Jovem
17.
Clin Gastroenterol Hepatol ; 16(6): 936-946, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29199145

RESUMO

BACKGROUND & AIMS: Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described. METHODS: We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n = 250) or acetaminophen-induced ALF (n = 912) from January 2000 through September 2016. We analyzed data on patient presentation, disease course, demographics, medical and psychiatric history, medication use, substance use, and details of acetaminophen ingestion. Sex differences in continuous and categorical variables were evaluated by Wilcoxon rank-sum and χ2 analysis or the Fisher exact test. Our primary aim was to evaluate sex differences in the presentation and clinical course of acetaminophen-induced acute liver injury or liver failure, and our secondary goal was to compare overall and transplant-free survival between sexes. RESULTS: Most patients with acetaminophen-induced ALI (68%) or ALF (76%) were women. Higher proportions of women than men had psychiatric disease (60% of women vs 48% of men, P < .01) and had co-ingestion with sedating agents (70% of women vs 52% of men, P < .01)-more than half of which were opioids. Higher proportions of women had severe hepatic encephalopathy (HE) (68% of women vs 58% of men), and required intubation (67% of women vs 59% of men, P values <.03). Higher proportions of women used vasopressors (26% of women vs 19% of men, P = .04) or mannitol (13% of women vs 6% of men, P < .01); proportions of male vs female patients with transplant-free survival were similar (68%). On adjusted analysis, women had higher risk of severe HE (adjusted odds ratio [AOR], 1.66; 95% CI, 1.17-2.35). We found a significant interaction between sex and co-ingestion of sedating agents (P < .01); co-ingestion increased odds of severe HE in women 2-fold (AOR, 1.86; 95% CI, 1.28-2.69; P < .01) but not in men (AOR; 0.62; 95% CI, 0.34-1.13; P = .12). CONCLUSIONS: In an analysis of the Acute Liver Failure Study Group cohort, we found acetaminophen-induced ALI and ALF to be more common among women. Women have greater critical care needs than men, and increased risk for severe HE, which could be due in part to increased use of sedatives. Future studies should investigate sex differences in acetaminophen metabolism and hepatotoxicity, particularly among users of opioids.


Assuntos
Acetaminofen/efeitos adversos , Analgésicos não Entorpecentes/efeitos adversos , Antipiréticos/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/epidemiologia , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Fatores Sexuais , Análise de Sobrevida
18.
Clin Liver Dis ; 20(2): 365-85, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27063275

RESUMO

Nonalcoholic fatty liver disease is the most common cause of liver disease in the United States. There are no drug therapies approved for the treatment of nonalcoholic steatohepatitis (NASH). Multiple different pathways are involved in the pathogenesis and each can be the target of the therapy. It is possible that more than 1 target is involved in disease development and progression. Multiple clinical trials with promising agents are underway. Because NASH is a slowly progressive disease and treatment likely to be of prolonged duration, acceptance and approval of any agent will require information on long-term clinical benefits and safety.


Assuntos
Ácido Quenodesoxicólico/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/agonistas , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antioxidantes/uso terapêutico , Inibidores de Caspase/uso terapêutico , Ácido Quenodesoxicólico/uso terapêutico , Ácidos Cólicos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Incretinas/uso terapêutico , Resistência à Insulina , Liraglutida/uso terapêutico , Receptores X do Fígado/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/metabolismo , Pectinas/uso terapêutico , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose
19.
Ann Intern Med ; 164(11): 724-32, 2016 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-27043883

RESUMO

BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. DESIGN: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440). SETTING: 31 liver disease and transplant centers in the United States. PATIENTS: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. LIMITATIONS: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. CONCLUSION: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.


Assuntos
Falência Hepática Aguda/terapia , Adulto , Causas de Morte , Cuidados Críticos , Feminino , Humanos , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Estados Unidos
20.
Liver Int ; 36(7): 1043-50, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26837055

RESUMO

BACKGROUND & AIMS: Published estimates of survival associated with mushroom (amatoxin)-induced acute liver failure (ALF) and injury (ALI) with and without liver transplant (LT) are highly variable. We aimed to determine the 21-day survival associated with amatoxin-induced ALI (A-ALI) and ALF (A-ALF) and review use of targeted therapies. METHODS: Cohort study of all A-ALI/A-ALF patients enrolled in the US ALFSG registry between 01/1998 and 12/2014. RESULTS: Of the 2224 subjects in the registry, 18 (0.8%) had A-ALF (n = 13) or A-ALI (n = 5). At admission, ALF patients had higher lactate levels (5.2 vs. 2.2 mm, P = 0.06) compared to ALI patients, but INR (2.8 vs. 2.2), bilirubin (87 vs. 26 µm) and MELD scores (28 vs. 24) were similar (P > 0.2 for all). Of the 13 patients with ALF, six survived without LT (46%), five survived with LT (39%) and two died without LT (15%). Of the five patients with ALI, four (80%) recovered and one (20%) survived post-LT. Comparing those who died/received LT (non-spontaneous survivors [NSS]) with spontaneous survivors (SS), N-acetylcysteine was used in nearly all patients (NSS 88% vs. SS 80%); whereas, silibinin (25% vs. 50%), penicillin (50% vs. 25%) and nasobiliary drainage (0 vs. 10%) were used less frequently (P > 0.15 for all therapies). CONCLUSION: Patients with mushroom poisoning with ALI have favourable survival, while around half of those presenting with ALF may eventually require LT. Further study is needed to define optimal management (including the use of targeted therapies) to improve survival, particularly in the absence of LT.


Assuntos
Amanitinas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Falência Hepática Aguda/etiologia , Intoxicação Alimentar por Cogumelos/epidemiologia , Acetilcisteína/uso terapêutico , Adulto , Doença Hepática Induzida por Substâncias e Drogas/terapia , Estudos de Coortes , Feminino , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Intoxicação Alimentar por Cogumelos/terapia , América do Norte/epidemiologia , Penicilinas/uso terapêutico , Sistema de Registros , Silibina , Silimarina/uso terapêutico
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