RESUMO
The acute hepatic porphyrias (AHPs) are a group of rare, inherited disorders of the heme biosynthesis pathway, usually manifesting with attacks of acute abdominal pain and other neurovisceral symptoms, with or without cutaneous manifestations. AHPs are characterized by the accumulation of porphyrin precursors, porphobilinogen, and/or aminolevulinic acid, in the blood. The diagnosis is often missed or delayed due to both inadequate testing and the improper use of available laboratory tests. In this review, we describe the various clinical presentations of the 4 AHPs, elucidate the approach to diagnosis, and provide recommendations for immediate and long-term management. We also describe the different complications that can occur with long-standing AHP, including the development of HCC. The AHPs are very treatable conditions, with excellent outcomes if diagnosed and treated early. A high index of suspicion for the presence of these disorders, along with accurate testing and timely treatment, will help reduce the burden of disease and prevent irreversible complications in patients with AHP.
RESUMO
BACKGROUND: While hepatitis A and B are well-known causes of acute liver failure (ALF), few well-documented cases of hepatitis C virus (HCV) infection (absent preexisting liver disease or other liver insults) have been described that result in ALF. We reviewed the Acute Liver Failure Study Group registry for evidence of HCV as a primary or contributing cause to ALF. METHODS: From January 1998 to January 2017, 2,332 patients with ALF (INR ≥ 1.5, any degree of hepatic encephalopathy) and 667 with acute liver injury (ALI; INR ≥ 2.0, no hepatic encephalopathy) were enrolled. Anti-HCV testing was done routinely, with confirmatory RT-PCR testing for HCV RNA where necessary. RESULTS: A total of 136 patients were anti-HCV-antibody positive, as follows: 56 HCV RNA negative, 65 HCV RNA positive, and 8 with no result nor sera available for testing. Only three subjects with ALI/ALF were determined to represent acute HCV infection. Case 1: 47-year-old female with morbid obesity (BMI 52.4) developed ALF and recovered, experiencing anti-HCV seroconversion. Case 2: 37-year-old female using cocaine presented with ALI and fully recovered. Case 3: 54-year-old female developed ALF requiring transplantation and was anti-HCV negative but viremic prior to transplant experiencing anti-HCV seroconversion thereafter. Among 1636 APAP overdose patients, the 52 with concomitant chronic HCV had higher 3-week mortality than the 1584 without HCV (31% vs 17%, p = 0.01). CONCLUSIONS: ALI/ALF solely related to acute hepatitis C infection is very rare. Chronic HCV infection, found in at least 65 (2.2%) of ALI/ALF patients studied, contributed to more severe outcomes in APAP ALI/ALF; ClinicalTrials.gov number, NCT000518440. Trial Registration ClinicalTrials.gov number NCT000518440.
Assuntos
Encefalopatia Hepática , Hepatite C , Falência Hepática Aguda , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Hepatite C/complicações , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/etiologia , América do Norte , Encefalopatia Hepática/etiologia , Hepacivirus/genética , RNARESUMO
Importance: In January 2011, the US Food and Drug Administration (FDA) announced a mandate to limit acetaminophen (paracetamol) to 325 mg/tablet in combination acetaminophen and opioid medications, with manufacturer compliance required by March 2014. Objective: To assess the odds of hospitalization and the proportion of acute liver failure (ALF) cases with acetaminophen and opioid toxicity prior to and after the mandate. Design, Setting, and Participants: This interrupted time-series analysis used hospitalization data from 2007-2019 involving ICD-9/ICD-10 codes consistent with both acetaminophen and opioid toxicity from the National Inpatient Sample (NIS), a large US hospitalization database, and ALF cases from 1998-2019 involving acetaminophen and opioid products from the Acute Liver Failure Study Group (ALFSG), a cohort of 32 US medical centers. For comparison, hospitalizations and ALF cases consistent with acetaminophen toxicity alone were extracted from the NIS and ALFSG. Exposures: Time prior to and after the FDA mandate limiting acetaminophen to 325 mg in combination acetaminophen and opioid products. Main Outcomes and Measures: Odds of hospitalization involving acetaminophen and opioid toxicity and percentage of ALF cases from acetaminophen and opioid products prior to and after the mandate. Results: In the NIS, among 474â¯047â¯585 hospitalizations from Q1 2007 through Q4 2019, there were 39â¯606 hospitalizations involving acetaminophen and opioid toxicity; 66.8% of cases were among women; median age, 42.2 (IQR, 28.4-54.1). In the ALFSG, from Q1 1998 through Q3 2019, there were a total of 2631 ALF cases, of which 465 involved acetaminophen and opioid toxicity; 85.4% women; median age, 39.0 (IQR, 32.0-47.0). The predicted incidence of hospitalizations 1 day prior to the FDA announcement was 12.2 cases/100â¯000 hospitalizations (95% CI, 11.0-13.4); by Q4 2019, it was 4.4/100â¯000 hospitalizations (95% CI, 4.1-4.7) (absolute difference, 7.8/100â¯000 [95% CI, 6.6-9.0]; P < .001). The odds of hospitalizations with acetaminophen and opioid toxicity increased 11%/y prior to the announcement (odds ratio [OR], 1.11 [95% CI, 1.06-1.15]) and decreased 11%/y after the announcement (OR, 0.89 [95% CI, 0.88-0.90]). The predicted percentage of ALF cases involving acetaminophen and opioid toxicity 1 day prior to the FDA announcement was 27.4% (95% CI, 23.3%-31.9%); by Q3 2019, it was 5.3% (95% CI, 3.1%-8.8%) (absolute difference, 21.8% [95% CI, 15.5%-32.4%]; P < .001). The percentage of ALF cases involving acetaminophen and opioid toxicity increased 7% per year prior to the announcement (OR, 1.07 [95% CI, 1.03-1.1]; P < .001) and decreased 16% per year after the announcement (OR, 0.84 [95% CI, 0.77-0.92]; P < .001). Sensitivity analyses confirmed these findings. Conclusions and Relevance: The FDA mandate limiting acetaminophen dosage to 325 mg/tablet in prescription acetaminophen and opioid products was associated with a statistically significant decrease in the yearly rate of hospitalizations and proportion per year of ALF cases involving acetaminophen and opioid toxicity.
Assuntos
Acetaminofen , Analgésicos Opioides , Analgésicos , Hospitalização , Falência Hepática Aguda , Adulto , Feminino , Humanos , Masculino , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Hospitalização/estatística & dados numéricos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/epidemiologia , Falência Hepática Aguda/terapia , Prescrições/estatística & dados numéricos , Estados Unidos/epidemiologia , United States Food and Drug Administration , Combinação de Medicamentos , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Pessoa de Meia-IdadeRESUMO
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 JovemRESUMO
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 (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. 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 persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous 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. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT 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.
Assuntos
Vacinas contra COVID-19/normas , COVID-19/prevenção & controle , Hepatopatias , Transplante de Fígado , Adulto , Vacinas contra COVID-19/administração & dosagem , Consenso , Humanos , Guias de Prática Clínica como Assunto , SARS-CoV-2/imunologia , Estados UnidosRESUMO
PURPOSE: Erythropoietic protoporphyria (EPP), characterized by painful cutaneous photosensitivity, results from pathogenic variants in ferrochelatase (FECH). For 96% of patients, EPP results from coinheriting a rare pathogenic variant in trans of a common hypomorphic variant c.315-48T>C (minor allele frequency 0.05). The estimated prevalence of EPP derived from the number of diagnosed individuals in Europe is 0.00092%, but this may be conservative due to underdiagnosis. No study has estimated EPP prevalence using large genetic data sets. METHODS: Disease-associated FECH variants were identified in the UK Biobank, a data set of 500,953 individuals including 49,960 exome sequences. EPP prevalence was then estimated. The association of FECH variants with EPP-related traits was assessed. RESULTS: Analysis of pathogenic FECH variants in the UK Biobank provides evidence that EPP prevalence is 0.0059% (95% confidence interval [CI]: 0.0042-0.0076%), 1.7-3.0 times more common than previously thought in the UK. In homozygotes for the common c.315-48T>C FECH variant, there was a novel decrement in both erythrocyte mean corpuscular volume (MCV) and hemoglobin. CONCLUSION: The prevalence of EPP has been underestimated secondary to underdiagnosis. The common c.315-48T>C allele is associated with both MCV and hemoglobin, an association that could be important both for those with and without EPP.
Assuntos
Protoporfiria Eritropoética , Bancos de Espécimes Biológicos , Europa (Continente) , Ferroquelatase/genética , Humanos , Mutação , Protoporfiria Eritropoética/diagnóstico , Protoporfiria Eritropoética/epidemiologia , Protoporfiria Eritropoética/genética , Reino Unido/epidemiologiaRESUMO
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 , COVID-19 , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Interações Medicamentosas , Gastroenterologia/educação , Humanos , Terapia de Imunossupressão , Internato e Residência , Hepatopatias/epidemiologia , Transplante de Fígado/ética , Transplante de Fígado/métodos , Saúde Ocupacional , Pandemias , Segurança do Paciente , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , SARS-CoV-2 , Doadores de Tecidos , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND & AIMS: Non-medical factors which contribute to the severity of acute liver failure (ALF) remain poorly defined. The association of alcohol consumption on the severity of presentation and outcome were determined in patients with ALF and acute liver injury (ALI) in a large, multicentre registry. METHODS: Alcohol consumption during the 6 months prior to study entry was analysed in 1170 patients enrolled in the ALF Study Group Registry. Consumption was categorized as none/minimal (<3 alcoholic beverages/week) or at least moderate (≥3/week). Clinical characteristics, the severity of liver injury at presentation (ALI or ALF) and outcome were compared. RESULTS: In patients with acetaminophen (APAP) overdose, at least moderate alcohol consumption was associated with higher peak aminotransferases, bilirubin, creatinine and INR on admission, compared to no/minimal consumption. In patients with non-APAP ALI/ALF, at least moderate alcohol consumption was associated with higher peak aminotransferases and creatinine. In APAP, non-APAP or all aetiologies, at least moderate alcohol consumption was associated with a 75%, 89% and 82% higher odds, respectively, of presenting as ALF rather than ALI (all P < .005). At least moderate alcohol consumption increased the odds of death by 45% (P = .01) across all aetiologies. In multivariate analysis, older age, non-Caucasian race, peak INR, peak bilirubin and at least moderate alcohol consumption were significantly associated with death. Finally, in Kaplan-Meier analysis of patients with all aetiologies, at least moderate alcohol consumption was associated with decreased time-dependent survival (P = .002). CONCLUSION: Alcohol consumption adversely affects the presentation and outcome of both APAP- and non-APAP-induced ALI/ALF.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Falência Hepática Aguda , Acetaminofen , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Humanos , Falência Hepática Aguda/etiologia , Sistema de RegistrosRESUMO
Patients with primary sclerosing cholangitis (PSC) have frequent episodes of cholangitis with potential for high mortality while waiting for liver transplantation. However, data on wait-list mortality specific to liver disease etiology are limited. Using United Network for Organ Sharing (UNOS) database (2002-2013), of 81 592 listed patients, 11 284 (13.8%) died while waiting for transplant. Primary biliary cirrhosis (PBC) patients (N = 3491) compared to PSC (N = 4905) differed with age (56 vs. 47 years), female gender (88% vs. 33%), black race (6% vs. 13%), and BMI (25 vs. 27), P < 0.0001 for all. A total of 993 (11.8%) patients died while waiting for the transplant list. Using competing risk analysis controlling for baseline recipient factors and accounting for receipt of liver transplantation (LT), PBC compared to patients with PSC had higher overall and 3-month wait-list mortality (21.6% vs. 12.7% and 5.0% vs. 2.9%, respectively, Gray's test P < 0.001), [1.25 (1.07-1.47)]. Repeat analysis including all etiologies showed higher wait-list mortality for PBC compared to most etiologies, except for patients listed for diagnosis of alcoholic liver disease (ALD) + hepatitis C virus (HCV). Patients with PBC have high mortality while waiting for liver transplantation. These novel findings suggest that patients with PBC listed for LT may be considered for model for end-stage disease (MELD) exception points.
Assuntos
Colangite Esclerosante/cirurgia , Cirrose Hepática Biliar/cirurgia , Transplante de Fígado , Listas de Espera/mortalidade , Adulto , Idoso , Colangite Esclerosante/mortalidade , Feminino , Humanos , Cirrose Hepática Biliar/mortalidade , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologiaRESUMO
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 terapêuticoRESUMO
UNLABELLED: Porphyrias are a group of eight metabolic disorders, each resulting from a mutation that affects an enzyme of the heme biosynthetic pathway. Porphyrias are classified as hepatic or erythropoietic, depending upon the site where the gene defect is predominantly expressed. Clinical phenotypes are classified as follows: (1) acute porphyrias with neurovisceral symptoms: acute intermittent porphyria; delta amino-levulinic acid hydratase deficiency porphyria; hereditary coproporphyria; and variegate porphyria and (2) cutaneous porphyrias with skin blistering and photosensitivity: porphyria cutanea tarda; congenital erythropoietic porphyria; hepatoerythropoietic porphyria and both erythropoietic protoporphyrias: autosomal dominant and X-linked. Liver transplantation (LT) may be needed for recurrent and/or life-threatening acute attack in acute intermittent porphyria or acute liver failure or end-stage chronic liver disease in erythropoietic protoporphyria. LT in acute intermittent porphyria is curative. Erythropoietic protoporphyria patients needing LT should be considered for bone marrow transplantation to achieve cure. CONCLUSION: This article provides an overview of porphyria with diagnostic approaches and management strategies for specific porphyrias and recommendations for LT with indications, pretransplant evaluation, and posttransplant management.
Assuntos
Transplante de Fígado , Porfirias/cirurgia , Humanos , Porfirias/diagnósticoAssuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/virologia , Idoso , Antivirais/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Feminino , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
Acute right upper quadrant pain is one of the most common presenting symptoms in hospital emergency departments, as well as outpatient settings. Although gallstone-related acute cholecystitis is a leading consideration in diagnosis, a myriad of extrabiliary sources including hepatic, pancreatic, gastroduodenal, and musculoskeletal should also be considered. This document focuses on the diagnostic accuracy of imaging studies performed specifically to evaluate acute right upper quadrant pain, with biliary etiologies including acute cholecystitis and its complications being the most common. An additional consideration of extrabiliary sources such as acute pancreatitis, peptic ulcer disease, ascending cholangitis, liver abscess, hepatitis, and painful liver neoplasms remain a diagnostic consideration in the right clinical setting. The use of radiographs, ultrasound, nuclear medicine, CT, and MRI for these indications are discussed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Assuntos
Colecistite Aguda , Pancreatite , Humanos , Estados Unidos , Doença Aguda , Meios de Contraste , Pancreatite/diagnóstico por imagem , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Imageamento por Ressonância Magnética/métodos , Sociedades MédicasRESUMO
Liver function tests are commonly obtained in symptomatic and asymptomatic patients. Various overlapping lab patterns can be seen due to derangement of hepatocytes and bile ducts function. Imaging tests are pursued to identify underlying etiology and guide management based on the lab results. Liver function tests may reveal mild, moderate, or severe hepatocellular predominance and can be seen in alcoholic and nonalcoholic liver disease, acute hepatitis, and acute liver injury due to other causes. Cholestatic pattern with elevated alkaline phosphatase with or without elevated γ-glutamyl transpeptidase can be seen with various causes of obstructive biliopathy. Acute or subacute cholestasis with conjugated or unconjugated hyperbilirubinemia can be seen due to prehepatic, intrahepatic, or posthepatic causes. We discuss the initial and complementary imaging modalities to be used in clinical scenarios presenting with abnormal liver function tests. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Assuntos
Colestase , Hepatopatias , Humanos , Diagnóstico por Imagem/métodos , Medicina Baseada em Evidências , Hepatopatias/diagnóstico por imagem , Testes de Função Hepática , Sociedades Médicas , Estados UnidosRESUMO
Telaprevir and boceprevir have received US Food and Drug Administration approval for use as triple therapy with pegylated interferon and ribavirin in genotype 1 chronic hepatitis C virus (HCV) infection. Clinical trials of these agents included few African Americans, despite the overwhelming need for improved therapies in this racial group. Although African Americans are predicted to have improved response rates with this new treatment paradigm, clinical trials illustrate lower rates of sustained virologic response for this racial group versus whites. African Americans with genotype 1 HCV infection appear to require longer durations of therapy than do whites to achieve a sustained virologic response. Further investigation is required to adequately counsel African Americans with genotype 1 chronic HCV infection on the efficacy of telaprevir and boceprevir in their racial group. Increased participation of this racial group in HCV clinical trials is needed to improve therapies in this difficult-to-treat population.
Assuntos
Antivirais/farmacologia , Negro ou Afro-Americano , Farmacorresistência Viral/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/etnologia , Oligopeptídeos/farmacologia , Prolina/análogos & derivados , Inibidores de Serina Proteinase/farmacologia , Antivirais/administração & dosagem , Ensaios Clínicos como Assunto , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferons/administração & dosagem , Oligopeptídeos/administração & dosagem , Prolina/administração & dosagem , Prolina/farmacologia , Sujeitos da Pesquisa/provisão & distribuição , Ribavirina/administração & dosagem , Inibidores de Serina Proteinase/administração & dosagem , Fatores de Tempo , Falha de TratamentoRESUMO
UNLABELLED: Phenylbutyric acid (PBA), which is approved for treatment of urea cycle disorders (UCDs) as sodium phenylbutyrate (NaPBA), mediates waste nitrogen excretion via combination of PBA-derived phenylacetic acid with glutamine to form phenylactylglutamine (PAGN) that is excreted in urine. Glycerol phenylbutyrate (GPB), a liquid triglyceride pro-drug of PBA, containing no sodium and having favorable palatability, is being studied for treatment of hepatic encephalopathy (HE). In vitro and clinical studies have been performed to assess GPB digestion, safety, and pharmacology in healthy adults and individuals with cirrhosis. GPB hydrolysis was measured in vitro by way of pH titration. Twenty-four healthy adults underwent single-dose administration of GPB and NaPBA and eight healthy adults and 24 cirrhotic subjects underwent single-day and multiple-day dosing of GPB, with metabolites measured in blood and urine. Simulations were performed to assess GPB dosing at higher levels. GPB was hydrolyzed by human pancreatic triglyceride lipase, pancreatic lipase-related protein 2, and carboxyl-ester lipase. Clinical safety was satisfactory. Compared with NaPBA, peak metabolite blood levels with GPB occurred later and were lower; urinary PAGN excretion was similar but took longer. Steady state was achieved within 4 days for both NaPBA and GPB; intact GPB was not detected in blood or urine. Cirrhotic subjects converted GPB to PAGN similarly to healthy adults. Simulations suggest that GPB can be administered safely to cirrhotic subjects at levels equivalent to the highest approved NaPBA dose for UCDs. CONCLUSION: GPB exhibits delayed release characteristics, presumably reflecting gradual PBA release by pancreatic lipases, and is well tolerated in adults with cirrhosis, suggesting that further clinical testing for HE is warranted.
Assuntos
Fenilbutiratos/efeitos adversos , Adulto , Estudos Cross-Over , Feminino , Glutamina/análogos & derivados , Glutamina/urina , Humanos , Hidrólise , Lipase/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/metabolismo , Masculino , Método de Monte Carlo , Fenilbutiratos/metabolismo , Fenilbutiratos/farmacocinética , Distúrbios Congênitos do Ciclo da Ureia/complicações , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológicoRESUMO
OBJECTIVES: The study of noninvasive markers of fibrosis, such as aspartate aminotransferase (AST) to platelet ratio index (APRI), have been limited in African American populations. Given the disparate outcomes of chronic hepatitis C in African American populations, comparative analyses of the APRI score should be undertaken. Compare the diagnostic accuracy of the APRI score for significant fibrosis and cirrhosis in a sample of African American and white veterans with chronic hepatitis C in the southeastern United States. METHODS: We identified 268 veterans with chronic hepatitis C who had received a liver biopsy. The APRI score was calculated using laboratory values obtained within 180 days of liver biopsy and compared to the fibrosis stage (F0-F4). Performance characteristics of the APRI score for determining stages of fibrosis were compared in African American (n = 142) and white (n = 117) individuals. RESULTS: An APRI score of 0.99 had a comparably high negative predictive value for significant fibrosis (F3-F4) in African American 0.90 and white veterans (0.83). For cirrhosis (F4), an APRI score of 1.0 provided a negative predictive value of 0.96 in the African American subset and 0.94 in the white subset. We did not detect any difference in the performance of the APRI score for predicting stages of fibrosis between the two groups. CONCLUSION: The APRI score displayed similar performance in African Americans and whites. A threshold of 1.0 can reliably exclude cirrhosis in African American veterans with chronic HCV infection.
Assuntos
Aspartato Aminotransferases/sangue , Negro ou Afro-Americano/estatística & dados numéricos , Hepatite C/diagnóstico , Contagem de Plaquetas , População Branca/estatística & dados numéricos , Biópsia , Feminino , Hepatite C/sangue , Hepatite C/enzimologia , Hepatite C/patologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Veteranos/estatística & dados numéricosRESUMO
Wilson's disease (WD) is characterized by hepatic, neurological, and/or psychiatric disturbances. In some cases, liver transplantation is indicated. Because psychologists and other health care workers play an increasing role in the evaluation of individuals presenting for transplant, an understanding of the heterogeneous phenotype of WD is important for mental health professionals working in medical settings. This article reviews two cases of patients with WD (one probable, one confirmed) presenting for liver transplantation and a biopsychosocial assessment approach is demonstrated. Patients are presented in terms of medical, psychiatric, and psychosocial history, neuropsychological examination results, and the subsequent indications for liver transplantation. Both patients exhibited neurocognitive and psychiatric symptoms. One patient was determined to be a marginally suitable candidate for transplantation, whereas the other was considered at high risk for negative outcome post-transplant. This article demonstrates the importance of considering phenotypic presentation, neurocognitive function, psychiatric status, and psychosocial circumstances in assessing transplant readiness in patients with WD. A comprehensive and integrative biopsychosocial assessment approach is appropriate for evaluating patients with WD presenting for liver transplantation.
Assuntos
Degeneração Hepatolenticular/fisiopatologia , Transplante de Fígado/psicologia , Adulto , Transtornos Cognitivos , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Testes Neuropsicológicos , Seleção de Pacientes , FenótipoRESUMO
Chronic hepatitis C virus (HCV) infection continues to be transmitted to hemodialysis (HD) patients within HD facilities globally. The goal of the World Health Organization to micro-eliminate HCV infection from the HD population by the year 2030 is not on target to be achieved. Obstacles to eliminate HCV in HD settings remain daunting due to a complex system created by a confluence of guidelines, legislation, regulation, and economics. HCV prevalence remains high and seroconversion continues among the HD patient population globally as a result of the HD procedure. Preventive strategies that effectively prevent HCV transmission, treatment-as-prevention, and rapid referral to treatment balanced with kidney transplant candidacy should be added to the current universal precautions approach. A safer system must be designed before HCV transmission can be halted and eliminated from the HD population.