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BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.
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Gastroenterologistas , Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Transversais , Comorbidade , Obesidade/metabolismo , Doenças Metabólicas/complicaçõesRESUMO
There is ongoing recognition of the burden of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), with fibrosis being the most important histological feature that is associated with progression to cirrhosis and the occurrence of major adverse liver outcomes. Liver biopsy is the gold standard applied to detect NASH and determine the stage of fibrosis, but its use is limited. There is a need for non-invasive testing (NIT) techniques to identify patients considered at-risk NASH (NASH with NAFLD activity score > 4 and ≥ F2 fibrosis). For NAFLD-associated fibrosis, several wet (serological) and dry (imaging) NITs are available and demonstrate a high negative predictive value (NPV) for excluding those with advanced hepatic fibrosis. However, identifying at-risk NASH is more challenging; there is little guidance on how to use available NITs for these purposes, and these NITs are not specifically designed to identify at-risk NASH patients. This review discusses the need for NITs in NAFLD and NASH and provides data to support the use of NITs, focusing on newer methods to non-invasively identify at-risk NASH patients. This review concludes with an algorithm that serves as an example of how NITs can be integrated into care pathways of patients with suspected NAFLD and potential NASH. This algorithm can be used for staging, risk stratification and the effective transition of patients who may benefit from specialty care.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fígado/patologia , Cirrose Hepática/epidemiologia , Fibrose , Valor Preditivo dos Testes , BiópsiaRESUMO
GOALS: To analyze our experience with adenoma detection rates in patients with liver cirrhosis in a community setting. BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and leading cause of cancer death in men and women in the USA. The majority of CRCs arise from premalignant polyps (adenomas), which are typically detected and removed during colonoscopy. Data are limited on the risk of CRC in patients with various chronic liver diseases and the association between CRC and demographics, liver disease etiology and colonoscopy findings. STUDY RESULTS: A total of 351 colonoscopies were performed (2006 to 2019) in patients with liver cirrhosis. Mean age was 62.3 ± 9.4 years, there were 158 females and 193 males. Adenomas were found in 159 procedures (49.07%) and were more likely found in the right colon (76.73%) vs the left colon (18.87%). Left-sided adenoma occurrence was significantly lower in women (61% lower than men, p = 0.05). Neither indication for the procedure (p = 0.08) nor advancing age (p = 0.94) affected adenoma detection rates. No significant differences were observed in the findings of adenomas between different chronic liver diseases. CONCLUSIONS: Adenoma detection rates in patients with cirrhosis (49%) undergoing elective colonoscopy were higher than rates reported in the literature for LT candidates (22-42%) undergoing standardized screenings. Colonoscopy screenings should be expanded to all patients with cirrhosis, regardless of etiology.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Hepatopatias , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Pólipos do Colo/patologia , Colonoscopia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adenoma/patologia , Hepatopatias/complicaçõesRESUMO
BACKGROUND & AIMS: Globally, nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We assessed the clinical presentation and patient-reported outcomes (PROs) among NAFLD patients from different countries. METHODS: Clinical, laboratory, and PRO data (Chronic Liver Disease Questionnaire-nonalcoholic steatohepatitis [NASH], Functional Assessment of Chronic Illness Therapy-Fatigue, and the Work Productivity and Activity Index) were collected from NAFLD patients seen in real-world practices and enrolled in the Global NAFLD/NASH Registry encompassing 18 countries in 6 global burden of disease super-regions. RESULTS: Across the global burden of disease super-regions, NAFLD patients (n = 5691) were oldest in Latin America and Eastern Europe and youngest in South Asia. Most men were enrolled at the Southeast and South Asia sites. Latin America and South Asia had the highest employment rates (>60%). Rates of cirrhosis varied (12%-21%), and were highest in North Africa/Middle East and Eastern Europe. Rates of metabolic syndrome components varied: 20% to 25% in South Asia and 60% to 80% in Eastern Europe. Chronic Liver Disease Questionnaire-NASH and Functional Assessment of Chronic Illness Therapy-Fatigue PRO scores were lower in NAFLD patients than general population norms (all P < .001). Across the super-regions, the lowest PRO scores were seen in Eastern Europe and North Africa/Middle East. In multivariate analysis adjusted for enrollment region, independent predictors of lower PRO scores included younger age, women, and nonhepatic comorbidities including fatigue (P < .01). Patients whose fatigue scores improved over time experienced a substantial PRO improvement. Nearly 8% of Global NAFLD/NASH Registry patients had a lean body mass index, with fewer metabolic syndrome components, fewer comorbidities, less cirrhosis, and significantly better PRO scores (P < .01). CONCLUSIONS: NAFLD patients seen in real-world practices in different countries experience a high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients.
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Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Doença Crônica , Fadiga , Feminino , Fibrose , Humanos , Cirrose Hepática , Masculino , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Prevalência , Qualidade de Vida , Sistema de RegistrosRESUMO
BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. METHODS: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). RESULTS: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60-300) vs 100 (interquartile range, 35-200) for GEs, 100 (interquartile range, 30-200) for ENDOs, and 10 (interquartile range, 4-50) for PCPs (all P < .0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs 8%-26%) and practice guidelines for others (39%-44%). The Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: epidemiology, 62% vs 53%; diagnostics, 80% vs 73%; and treatment, 61% vs 58% (P < .0001), and ENDOs scores were higher than PCPs: epidemiology, 70% vs 60%; diagnostics, 71% vs 64%; and treatment, 79% vs 68% (P < .0001). Being a hepatologist or ENDO was associated with higher knowledge scores than a GE or PCP, respectively (P < .05). Higher NAFLD knowledge scores were associated independently with a greater number of NAFLD patients seen (P < .05). CONCLUSIONS: Despite the growing burden of NAFLD, a significant knowledge gap remains for the identification, diagnosis, and management of NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Médicos , Humanos , América Latina/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Prevalência , Inquéritos e QuestionáriosRESUMO
Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) is a severe and often fatal complication of end-stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off-label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short-term prognosis in patients with HRS-AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS-AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS-AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS-AKI and supported by recommendations for first-line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS-AKI and the potential benefits if terlipressin was approved in the United States.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Transplante de Fígado , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/tratamento farmacológico , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Terlipressina , Estados Unidos/epidemiologia , Vasoconstritores/uso terapêuticoRESUMO
Several governmental agencies and private organizations monitor data on relative value units (RVUs) and salary earned by various medical specialists. There are currently no data that define the RVU production and salary earned by hepatologists. A web-based survey that queried the number of patients that a hepatologist cares for, RVU production, and salary support was sent to 2,587 members of the American Association for the Study of Liver Diseases. A total of 391 members completed the survey, 229 of whom reported spending more than 75% of their time in clinical practice/direct patient care and served as the basis for this analysis. The mean age of the cohort was 48 years, 77% were male, and all regions of country were represented. Their mean duration in clinical practice was 11.4 years. Hepatologists worked in four practice settings: university hospital with a liver transplant (LT) program (UHLT, n = 148), non-university hospital with LT (nonUHLT, n = 35), university hospital with no LT (UHnoLT, n = 29), and community practice (CP, n = 17). The average number of patients seen monthly was lowest for hepatologists at a UHLT (154) and highest for those in CP (293). Hepatologists at LT programs saw the highest percentage of patients with liver disease (91% of encounters), performed the fewest endoscopic procedures (12%-17%), but received the highest compensation/RVU ($68-$85) compared with hepatologists at UHnoLT and CP ($44-$63/RVU). The mean base salary for all hepatologists with fewer than 5 years of experience was $273,507, and this increased to $347,656 for those with more than 5 years of experience. We concluded that hepatologists at LT centers are compensated at much higher rates per encounter than in other practice settings. This may be due to salary subsidies provided by the UHLT and nonUHLT to their hepatologists.
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Gastroenterologistas/economia , Padrões de Prática Médica/economia , Área de Atuação Profissional/economia , Inquéritos e Questionários , Adulto , Fatores Etários , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/normas , Medição de Risco , Salários e Benefícios , Fatores Sexuais , Estados UnidosRESUMO
Thrombocytopenia is a consequence of portal hypertension and is the most common hematological manifestation of chronic liver disease (CLD) (ie, cirrhosis). Data indicates the rates of CLD are increasing and, as a result, so will the incidence of this complication. Although bleeding risks are only relevant when elective procedures are performed, this is a frequent concern as these procedures are commonly part of the spectrum of care for patients with cirrhosis. As such, thrombocytopenia remains a pertinent issue. Fortunately, we now have effective and accurate treatment modalities to raise platelet counts before scheduled procedures, known as thrombopoietin receptor agonists. Two drugs in this therapeutic class (avatrombopag and lusutrombopag) are now approved for the treatment of thrombocytopenia in adults with CLD undergoing a procedure and have revolutionized how this is managed. Although there is progress in the field, peer-reviewed literature and expert guidance are lacking. Recognizing these unmet needs, a group of expert hepatologists comprised this review, which summarizes the most current and relevant peer-reviewed literature on thrombocytopenia in CLD and provides clinical expertise on this timely topic.
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Hepatopatias , Trombocitopenia , Adulto , Doença Crônica , Humanos , Incidência , Cirrose Hepática/complicações , Hepatopatias/complicações , Contagem de Plaquetas , Trombocitopenia/terapiaRESUMO
BACKGROUND: Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA. Key eligibility criteria included a non-alcoholic fatty liver disease activity score of 4 or higher, stage 1-3 fibrosis, and at least 8% liver fat content. Patients were randomly assigned (1:1:1) via a web-based system and stratified by diabetic status to receive either 3 mg or 6 mg subcutaneous NGM282 or placebo. The primary endpoint was the absolute change from baseline to week 12 in liver fat content. Responders were patients who achieved a 5% or larger reduction in absolute liver fat content as measured by MRI-proton density fat fraction. Efficacy analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02443116. FINDINGS: Between July 14, 2015, and Aug 30, 2016, 166 patients were screened across 18 sites in Australia and the USA. 82 patients were randomly assigned to receive 3 mg NGM282 (n=27), 6 mg NGM282 (n=28), or placebo (n=27). At 12 weeks, 20 (74%) patients in the 3 mg dose group and 22 (79%) in the 6 mg dose group achieved at least a 5% reduction in absolute liver fat content from baseline (relative risk 10·0 [95% CI 2·6-38·7] vs 11·4 [3·0-43·8], respectively; p<0·0001 for both comparisons) versus two (7%) in the placebo group. Overall, 76 (93%) of 82 patients experienced at least one adverse event, most of which were grade 1 (55 [67%]), and only five (6%) were grade 3 or worse. The most commonly (≥10%) reported adverse events were injection site reactions (28 [34%]), diarrhoea (27 [33%]), abdominal pain (15 [18%]), and nausea (14 [17%]). These adverse events were reported more frequently in the NGM282 groups compared with the placebo group. No life-threatening events or patient deaths occurred during the study. INTERPRETATION: NGM282 produced rapid and significant reductions in liver fat content with an acceptable safety profile in patients with non-alcoholic steatohepatitis. Further study of NGM282 is warranted in this patient population. FUNDING: NGM Biopharmaceuticals.
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Fatores de Crescimento de Fibroblastos/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Fatores de Crescimento de Fibroblastos/uso terapêutico , Humanos , Testes de Função Hepática , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Resultado do TratamentoRESUMO
UNLABELLED: Hepatitis C virus (HCV)-infected patients with cirrhosis are historically a difficult-to-treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1-infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open-label, single-arm study (OPTIMIST-2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1-infected treatment-naive or treatment-experienced patients with cirrhosis. Patients (aged 18-70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient-reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%-91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment-naive and treatment-experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient-reported outcomes improved from baseline to follow-up week 12. CONCLUSION: Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment-naive and treatment-experienced HCV GT1-infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360-369).
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Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Both hepatitis C virus (HCV) mono-infected and HIV/HCV co-infected patients are in need of safe, effective, all-oral HCV regimens. In a phase 2 study we aimed to assess the efficacy and safety of grazoprevir (MK-5172; HCV NS3/4A protease inhibitor) and two doses of elbasvir (MK-8742; HCV NS5A inhibitor) in patients with HCV mono-infection and HIV/HCV co-infection. METHODS: The C-WORTHY study is a phase 2, multicentre, randomised controlled trial of grazoprevir plus elbasvir with or without ribavirin in patients with HCV; here, we report findings for previously untreated (genotype 1) patients without cirrhosis who were HCV mono-infected or HIV/HCV co-infected. Eligible patients were previously untreated adults aged 18 years or older with chronic HCV genoype 1 infection and HCV RNA at least 10â000 IU/mL in peripheral blood without evidence of cirrhosis, hepatocellular carcinoma, or decompensated liver disease. In part A of the study we randomly assigned HCV-mono-infected patients to receive 12 weeks of grazoprevir (100 mg) plus elbasvir (20 mg or 50 mg) with or without ribavirin (arms A1-3); in part B we assigned HCV-mono-infected patients to 8 or 12 weeks of grazoprevir (100 mg) plus elbasvir (50 mg) with or without ribavirin (arms B1-3) and HIV/HCV co-infected patients to 12 weeks of therapy with or without ribavirin. The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL 12 weeks after end of treatment (SVR12). Randomisation was by presence or absence of ribavirin, 8 or 12 weeks of treatment, and dosage of elbasvir. Patients were stratified by gentoype 1a versus 1b. The patients, investigators, and study site personnel were masked to treatment group assignements but the funder was not. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT01717326. FINDINGS: 218 patients with HCV mono-infection (n=159) and HIV/HCV co-infection (n=59) were enrolled. SVR12 for patients treated for 12 weeks with or without ribavirin ranged from 93-98% in mono-infected and 87-97% in co-infected patients. SVR12 rates in mono-infected and co-infected patients treated for 12 weeks without ribavirin were 98% (95% CI 88-100; 43/44) and 87% (95% CI 69-96; 26/30), respectively, and with ribavirin were 93% (95% CI 85-97; 79/85) and 97% (95% CI 82-100; 28/29), respectively. Among mono-infected patients with genotype 1a infection treated for 8 weeks, SVR12 was 80% (95% CI 61-92; 24/30). Five of six patients who discontinued early for reasons other than virological failure had HCV RNA less than 25 IU/mL at their last study visit. Virological failure among patients treated for 12 weeks occurred in seven patients (7/188, 4%) and was associated with emergence of resistance-associated variants to one or both drugs. The safety profile of grazoprevir plus elbasvir with or without ribavirin was similar in mono-infected and co-infected patients. No patient discontinued due to an adverse event or laboratory abnormality. The most common adverse events were fatigue (51 patients, 23%), headache (44, 20%), nausea (32, 15%), and diarrhoea (21, 10%). INTERPRETATION: Once-daily grazoprevir plus elbasvir with or without ribavirin for 12 weeks in previously untreated HCV-mono-infected and HIV/HCV-co-infected patients without cirrhosis achieved SVR12 rates of 87-98%. These results support the ongoing phase 3 development of grazoprevir plus elbasvir. FUNDING: Merck & Co, Inc.
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Antivirais/administração & dosagem , Benzofuranos/administração & dosagem , Infecções por HIV/complicações , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , RNA Viral/sangue , Ribavirina/administração & dosagem , Adulto , Idoso , Amidas , Carbamatos , Coinfecção , Ciclopropanos , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sulfonamidas , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
BACKGROUND & AIMS: Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon alfa-2a and ribavirin in this patient population. METHODS: This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60 mg once-daily plus asunaprevir 100mg twice-daily, with weekly peginterferon alfa-2a and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients. RESULTS: Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93-100); one patient had a missing post-treatment week-12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each). CONCLUSIONS: Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens.
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DNA Viral/genética , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Interferon-alfa/administração & dosagem , Isoquinolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Antivirais/administração & dosagem , Carbamatos , Esquema de Medicação , Portadores de Fármacos , Quimioterapia Combinada , Feminino , Seguimentos , Genótipo , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Proteínas Recombinantes/administração & dosagem , Resultado do Tratamento , Valina/análogos & derivados , Carga Viral/genética , Adulto JovemRESUMO
Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.
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PURPOSE: Albumin, the most abundant and arguably most important protein in the human body, plays a unique role in decompensated cirrhosis because its structure and function are quantitatively and qualitatively affected. A literature review was performed to provide insights into albumin use. The manuscript was developed using a multidisciplinary approach; 2 hepatologists, a nephrologist, a hospitalist, and a pharmacist, who are all members of or work closely with the Chronic Liver Disease Foundation, collaborated to write this expert perspective review. SUMMARY: Cirrhosis represents the potential end in the spectrum of all chronic liver diseases. Decompensated cirrhosis, defined by the overt manifestation of liver failure (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased mortality. Human serum albumin (HSA) infusion serves an important role in the treatment of advanced liver disease. The benefits of HSA administration in patients with cirrhosis are widely accepted, and its use has been advocated by several professional societies. However, inappropriate HSA use can lead to significant adverse patient events. This paper discusses the rationale for the administration of HSA in the treatment of complications of cirrhosis, analyzes the data on the use of HSA in cirrhosis, and streamlines practical recommendations set forth in published guidance. CONCLUSION: Use of HSA in clinical practice needs to be improved. The objective of this paper is to empower pharmacists to facilitate and improve the use of HSA in patients with cirrhosis at their practice sites.
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Varizes Esofágicas e Gástricas , Síndrome Hepatorrenal , Humanos , Farmacêuticos , Varizes Esofágicas e Gástricas/complicações , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/terapia , Hemorragia Gastrointestinal/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações , Albuminas/uso terapêuticoRESUMO
Decompensated cirrhosis, defined by the overt manifestations of liver failure and portal hypertension (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased morbidity and mortality in chronic liver disease. Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication. The goals of treatment of HRS-AKI are to reverse renal failure and prolong survival in these critically ill patients or perhaps to allow the transplant team to complete the pretransplant evaluation and bridge the patient to transplant. Historically, in the United States, standard-of-care treatments for HRS-AKI were chosen by default despite lack of data, off-label use, and suboptimal results. Terlipressin represents the first drug in the United States indicated for the treatment of HRS-AKI. This review provides an up-to-date overview of HRS-AKI, discusses terlipressin and how to incorporate this new treatment into patient care and streamline society guidelines on HRS diagnosis and treatment in a practical way for clinical use, and concludes with a sample order set that highlights the recommendations discussed throughout the supplement.
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BACKGROUND: Hepatitis C virus (HCV) is the most common cause of chronic liver disease in the United States. African Americans are known to have a higher prevalence of HCV and lower response to anti-HCV therapy. GOAL: The aim of this study is to assess the differences in the prevalence of chronic HCV infection in according to patients' ethnic background. STUDY: We used the recent National Health and Nutrition Examination Survey with extensive clinical and laboratory data. Active HCV infection was defined as having HCV-positive antibody with detectable HCV RNA by polymerase chain reaction. HCV clearance was defined as HCV-positive antibody with negative HCV RNA. Clinico-demographic data were compared between anti-HCV positive individuals with or without HCV clearance. The stratum-specific χ test for independence was used. Logistic regression was used to identify independent predictors of HCV clearance. P-values ≤0.05 were considered statistically significant. All analyses were run using SAS 9.1 and SUDAAN 10.0. RESULTS: The cohort included 14,750 adults (age 47.6 ± 0.75 y, 64% white, 21% African American, 10% Hispanics, and 63% male). Of these, 1.32 ± 0.11% were anti-HCV positive with 75.94 ± 4.72% having active HCV viremia. The only parameter significantly different between those who did or did not clear HCV was the proportion of African Americans: 8.0 ± 3.7% versus 24.9 ± 5.0%, P=0.0163. Indeed, the rate of HCV clearance was lowest among African Americans (9.3 ± 3.5%) as compared with both whites (27.2 ± 6.5%) and Hispanics 31.2 ± 9.1% (P<0.05). In multivariate analysis, the only independent predictor of active HCV infection was African American race: odds ratio (95% confidence interval)=3.80 (1.31-11.06), P=0.0151. CONCLUSIONS: African Americans not only have lower response to anti-HCV therapy but also are less likely to naturally clear HCV, potentially contributing to higher prevalence of HCV.
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Negro ou Afro-Americano/estatística & dados numéricos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/imunologia , RNA Viral/sangue , Viremia/epidemiologia , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/etnologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Estados Unidos/epidemiologia , Estados Unidos/etnologia , Viremia/etnologia , Viremia/virologiaRESUMO
Gastroenterology, hepatology and liver transplant exchanges between the USA and Cuba have mainly consisted of scientific events and short visits. This has facilitated Cuba's inclusion in recognized scientific organizations, familiarity with Cuba's biotech products for treatment of liver disease, and access by Cuban professionals to the highest level of scientific information for clinical practice. It has also given health professionals in the US a more accurate picture of Cuba's health sector. The results of the Global Alcoholic Liver Disease Survey, which included Cuba and was designed and coordinated in the USA, opened doors to joint research and scientific publications. Until now, there have been no protocols for ongoing cooperation to enable bilateral clinical trials or continuing professional development in diagnostic, therapeutic and surgical techniques for hepatology and liver transplantation. There are many mutually beneficial research prospects in these areas. What has been accomplished to date, described in this article, is encouraging and sets the stage for future collaboration. KEYWORDS Hepatology, liver transplant, health, medicine, science, Cuba, USA.
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Gastroenterologia , Cooperação Internacional , Transplante de Fígado , Cuba , Humanos , Estados UnidosRESUMO
Background and Aims: Approximately half of adults with hepatitis C in the United States do not know their infection status, and the majority of persons who know they are positive for hepatitis C virus (HCV) antibodies fail to receive care. We conducted a screening program in retail pharmacies and calculated the percentages of anti-HCV-positive individuals and how many subsequently entered a pathway to care. Methods: At 45 Walgreens retail pharmacies in 9 US cities, direct store advertising was used to recruit individuals for HCV antibody testing. Participants were at least 18 years old with at least 1 HCV risk factor, such as being born between 1945 and 1965. One day per week at each site, a phlebotomist obtained consent from interested participants and performed the testing. Within 3 business days, an HCV management specialist contacted anti-HCV-positive individuals and provided test results and a pathway for obtaining HCV RNA testing. During the following 21 to 28 days, the same HCV management specialist telephoned individuals to determine whether they underwent an HCV RNA test. Results: Between September 2015 and February 2016, 1298 individuals consented. Two patients withdrew consent after testing. In all, 8% (103/1296) were HCV antibody-positive; of them, 91 (88%) were contacted by an HCV management specialist. During the 21- to 28-day follow-up, 56 individuals (62%; 56/91) were reached by an HCV management specialist, and 29 (52%; 29/56) confirmed that an HCV RNA test was ordered. Conclusions: These results provide evidence in support of point-of-care HCV screening in retail pharmacies for at-risk individuals in the United States.
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OBJECTIVES: Although effective, direct acting antiviral (DAA) therapies for genotype 1 (GT 1) hepatitis C virus (HCV) have been associated with compliance challenges. Additionally, treatment at predominantly community-based centers has been associated with low retention of patients on treatment and higher dropout rates. The OPTIMAL Phase IV interventional trial (ClinicalTrials.gov Identifier: NCT01405027) was designed to evaluate the impact of an education program for community investigator (CI) sites participating in a Chronic Liver Disease Foundation study treating chronic GT 1 HCV patients. METHODS: This physician educational program was administered by 22 Hepatology Centers of Educational Expertise (HCEE) academic sites to 33 CI sites asked to participate from December 2011 to July 2012. The HCEE mentors from DAA-experienced academic sites educated those at CI sites on therapeutic management, practice, and patient outcomes through a series of four standardized educational sequence visits regarding the use of first generation HCV protease inhibitors and the overall treatment of HCV. RESULTS: Treatment duration compliance rates for patients treated at CI sites versus those treated at HCEE academic sites were evaluable in 77 of 84 HCEE academic site patients, 102 of 113 patients treated at CI sites, and 179 of 197 overall patients. The treatment duration compliance rates for patients treated at HCEE academic sites, CI sites and overall were 85.4 ± 25.39%, 83.8 ± 27.37%, and 84.5 ± 26.48%, respectively, and did not differ statistically between the groups (p = 0.49). Almost half (47%) of the patients in the study achieved a sustained virological response for 24 weeks (SVR24) regardless of the type of site (p = 0.64). Safety profiles were similar at both HCEE and CI sites. CONCLUSIONS: These results demonstrated that education of CI sites unfamiliar with DAAs resulted in patient outcomes consistent with those observed at DAA-experienced academic sites.
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We report a case of P. aeruginosa cholangitis in an adult with cystic fibrosis (CF). The patient had a past history of cholecystectomy and a new finding of intrahepatic biliary duct stricture. Evaluation and treatment with endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous biliary tract drainage was complicated by post-procedure pain and fever. The only organism recovered from biliary drainage was P. aeruginosa. Southern blot analysis of respiratory and biliary cultures confirmed that the isolates were identical. Despite aggressive antibiotic therapy and drainage, persistent cholangitis and infection have not been eradicated after 6 months. The most likely mechanism of infection of the biliary tract was direct introduction of the upper respiratory tract pathogen during the diagnostic procedure.