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Purpose: Alcohol consumption is a strong risk factor for both cirrhosis and esophageal squamous cell carcinoma (ESCC). Few studies have been conducted on the treatment of ESCC in patients with cirrhosis. This study aimed to analyze the clinical outcomes of ESCC in patients with cirrhosis. Materials and methods: Medical records of patients with esophageal cancer between January 2009 and December 2023 were retrospectively reviewed. A total of 479 patients with ESCC were included and divided into cirrhotic (n = 69) and non-cirrhotic (n = 410) groups. Clinical outcomes and survival according to treatment were compared between these groups. Results: The cirrhotic group was younger (median age 64 years vs. 69 years, p = 0.022) and had a higher proportion of male (97.1 % vs. 88.3 %, p = 0.042) than the non-cirrhotic group. Patients with cirrhosis were less likely to undergo surgery (31.9 % vs. 47.8 %, p = 0.015) and were more likely to receive no active cancer treatment (26.1 % vs. 13.7 %, p = 0.010). Overall survival was lower in the cirrhotic group (hazard ratio [HR], 1.41; 95 % confidence interval [CI], 1.01-1.99; p = 0.045), however, no difference was found between Child-Pugh class A patients and those in the non-cirrhotic group (HR, 1.04 [95 % CI, 0.69-1.56]; p = 0.864). Postoperative mortality was significantly higher in cirrhotic group (27.3 % vs. 8.7 %, p = 0.011). Upon performing concurrent chemoradiotherapy (CRT), the clinical complete response rate (84.2 % vs. 43.3 %, p = 0.004) was better in the cirrhotic group. CRT yielded better overall survival for patients with cancer in the resectable stages in the cirrhotic group compared to surgery (HR, 0.19 [95 % CI, 0.42-0.84]; p = 0.029]. Conclusions: In patient with ESCC and cirrhosis, chemoradiotherapy may be a better treatment option than surgery.
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Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.
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Cardiomiopatias , Cirrose Hepática , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cardiomiopatias/terapia , Cardiomiopatias/etiologia , Animais , Antagonistas Adrenérgicos beta/uso terapêutico , Antioxidantes/uso terapêuticoRESUMO
Background: Immune checkpoint inhibitor (ICI)-based therapy such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab became mainstream first-line systemic treatment in advanced hepatocellular carcinoma (HCC) patients since remarkably superior efficacy of ICI-based therapy compared to tyrosine kinase inhibitors (TKIs) was reported in two recent randomized controlled trials (RCTs) (IMbrave150, HIMALAYA). However, the optimal second-line therapy after treatment failure of first-line ICI-based therapy remains unknown as no RCT has examined this issue. Summary: Therefore, at present, most clinicians are empirically treating patients with TKIs or retrial of ICI or locoregional treatment (LRT) modality such as transarterial therapy, radiofrequency ablation, and radiation therapy in this clinical setting without solid evidence. In this review, we will discuss current optimal strategies for second-line treatment after the failure of first-line ICI-based therapy by reviewing published studies and ongoing prospective trials. Key Messages: Clinicians should consider carefully whether to treat the patients with TKI, other ICI-based therapy, or LRT in this situation by considering several factors including liver function reserve, performance status, adverse events of previous therapy, and presence of lesion that can consider LRT such as oligoprogression and vascular invasion. In the meantime, we await the results of ongoing prospective trials to elucidate the best management options.
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Inflamação , Trombofilia , Trombose , Humanos , Trombofilia/sangue , Inflamação/sangue , Trombose/sangue , Endotélio Vascular/fisiopatologia , FemininoRESUMO
Cirrhotic cardiomyopathy (CCM) is defined as systolic or diastolic dysfunction in the absence of prior heart disease or another identifiable cause in patients with cirrhosis, in whom it is an important determinant of outcome. Its underlying pathogenic/pathophysiological mechanisms are rooted in two distinct pathways: 1) factors associated with portal hypertension, hyperdynamic circulation, gut bacterial/endotoxin translocation and the resultant inflammatory phenotype; 2) hepatocellular insufficiency with altered synthesis or metabolism of substances such as proteins, lipids, carbohydrates, bile acids and hormones. Different criteria have been proposed to diagnose CCM; the first in 2005 by the World Congress of Gastroenterology, and more recently in 2019 by the Cirrhotic Cardiomyopathy Consortium. These criteria mainly utilised echocardiographic evaluation, with the latter refining the evaluation of diastolic function and integrating global longitudinal strain into the evaluation of systolic function, an important addition since the haemodynamic changes that occur in advanced cirrhosis may lead to overestimation of systolic function by left ventricular ejection fraction. Advances in cardiac imaging, such as cardiac magnetic resonance imaging and the incorporation of an exercise challenge, may help further refine the diagnosis of CCM. Over recent years, CCM has been shown to contribute to increased mortality and morbidity after major interventions, such as liver transplantation and transjugular intrahepatic portosystemic shunt insertion, and to play a pathophysiologic role in the genesis of hepatorenal syndrome. In this review, we discuss the pathogenesis/pathophysiology of CCM, its clinical implications, and the role of cardiac imaging modalities including MRI. We also compare diagnostic criteria and review the potential diagnostic role of electrocardiographic QT prolongation. At present, no definitive medical therapy exists, but some promising potential treatment strategies for CCM are reviewed.
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In patients with portal hypertension, there are many complications including cardiovascular abnormalities, hepatorenal syndrome, ascites, variceal bleeding, and hepatic encephalopathy. The underlying mechanisms are not yet completely clarified. It is well known that portal hypertension causes mesenteric congestion which produces reactive oxygen species (ROS). ROS has been associated with intestinal mucosal injury, increased intestinal permeability, enhanced gut bacterial overgrowth, and translocation; all these changes result in increased endotoxin and inflammation. Portal hypertension also results in the development of collateral circulation and reduces liver mass resulting in an overall increase in endotoxin/bacteria bypassing detoxication and immune clearance in the liver. Endotoxemia can in turn aggravate oxidative stress and inflammation, leading to a cycle of gut barrier dysfunction â endotoxemia â organ injury. The phenotype of cardiovascular abnormalities includes hyperdynamic circulation and cirrhotic cardiomyopathy. Oxidative stress is often accompanied by inflammation; thus, blocking oxidative stress can minimize the systemic inflammatory response and alleviate the severity of cardiovascular diseases. The present review aims to elucidate the role of oxidative stress in cirrhosis-associated cardiovascular abnormalities and discusses possible therapeutic effects of antioxidants on cardiovascular complications of cirrhosis including hyperdynamic circulation, cirrhotic cardiomyopathy, and hepatorenal syndrome.
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Cardiomiopatias , Anormalidades Cardiovasculares , Endotoxemia , Varizes Esofágicas e Gástricas , Síndrome Hepatorrenal , Hipertensão Portal , Humanos , Varizes Esofágicas e Gástricas/complicações , Síndrome Hepatorrenal/complicações , Espécies Reativas de Oxigênio/farmacologia , Endotoxemia/complicações , Hemorragia Gastrointestinal , Cirrose Hepática/terapia , Hipertensão Portal/complicações , Estresse Oxidativo , Inflamação/complicações , Cardiomiopatias/complicações , Anormalidades Cardiovasculares/complicações , Endotoxinas/farmacologiaRESUMO
Background: The estimated prevalence of hepatitis C virus (HCV) in Canada is approximately 1.0%. However, the number of individuals living with HCV but unaware of it is estimated to be 30%-44%. Increased screening programs that are accessible, effective, and feasible are important to ensure treatment and meet WHO elimination goals. We implemented an HCV point of care test (POCT) program in community pharmacies to examine the effectiveness and feasibility in screening. Methods: Twenty two London Drugs pharmacies in British Columbia and Alberta implemented an HCV POC screening program using OraQuick rapid antibody tests. Consenting patients filled out a 10-question screening questionnaire to examine risk factors. The participants then were tested using the POCT. While waiting for the test (20 minutes), patients were educated on HCV and treatment options. Results: Three hundred seventy-one participants underwent HCV screening. The most common HCV risk factor was being born between 1945 and 1975 (baby boomer) (93% of cohort), while the second most common was having a tattoo or body piercing (22%). Seven people (2%) tested positive; four were HCV-RNA PCR-positive and were treated, whereas the PCR status of three was unknown as they were lost to follow-up or not tested. Conclusions: Pharmacy-based POCT was shown to be effective and feasible in the western Canadian context, especially for baby boomers. Sustainable funding for pharmacy screening programs may be considered nationwide to identify HCV-infected persons and help meet elimination goals.
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Background: Pegylated interferon (Peg-IFN) is recommended as first-line therapy for chronic hepatitis B (CHB) but has significant side effects and is rarely used compared to oral nucleos(t)ide analogues (NA). There are limited recent clinical efficacy or economic analysis data comparing approved CHB therapy in North America. Methods: This retrospective study examined clinical outcomes, off-treatment durability, and cost-effectiveness of Peg-IFN versus NA for CHB. Demographic (age, sex, ethnicity), clinical data (i.e., liver tests, hepatitis B virus DNA, serology, transient elastography) and documented side effects were collected by retrospective chart review of patients followed in the University of Calgary Liver Unit who received Peg-IFN therapy from January 2007 to December 2020. The cost-effectiveness of Peg-IFN versus NA therapy was modelled over a 10-year time horizon. Results: Sixty-eight CHB patients were treated with Peg-IFN (median age 45.65, 74% male, 84% Asian); 50/68 (74%) completed 48 weeks of treatment with a median follow-up of 6.54 years (interquartile range 5.07). At the last known follow-up, 23/68 (34%) have not required NA treatment and one had HBsAg loss; 27 have been started on NA. Predictors of obtaining a sustained virological response included being hepatitis B e antigen-negative at treatment end and a quantitative hepatitis B surface antigen <1000 IU/mL. Economic modelling showed that finite Peg-IFN was not cost-effective versus NA at a 10-year time horizon. Conclusions: PEG-IFN remains a potential treatment for CHB although there is a significant intolerance/failure rate. Using PEG-IFN based on patient preference is reasonable and optimal patient selection may improve treatment cost-effectiveness.
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OBJECTIVES: Long-term treatment with nucleoside analog (NA) reduces the risks for decompensation and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with compensated cirrhosis (CC). However, whether antiviral therapy has differential efficacy on the risks for decompensation and HCC is insufficiently elucidated. Therefore, we investigated the disease state transition, focusing on decompensation event-specific HCC risk in NA-treated CHB patients with CC. METHODS: We prospectively followed up on 1163 NA-treated CHB patients with CC every six months for up to seven years. The cumulative incidence and risk of HCC were analyzed by the Kaplan-Meier method and competing risk model. The multistate model was used to estimate the transition probabilities to HCC from different disease states. RESULTS: HCC predominated the first liver-related events, with a 5-year cumulative incidence of 9.0%, followed by decompensation (8.3%, including 7.9% nonbleeding decompensation and 2.4% variceal bleeding) and 0.2% death. The decompensation stage had a significantly higher 5-year cumulative HCC incidence than the CC stage (27.6% vs. 9.1%; HR = 2.42, 95% CI: 1.24, 4.71). Furthermore, nonbleeding decompensation events had a higher 5-year transition probability to HCC than bleeding (27.6% vs. 15.8%; HR = 2.69, 95% CI: 1.41, 4.17). Viral suppression modified the on-treatment transition risk to HCC (1-year: HR = 0.45, 95% CI: 0.28, 0.73; 3-year: HR = 0.23, 95% CI: 0.14, 0.38). An online calculator was developed to facilitate HCC risk stratification. CONCLUSIONS: In NA-treated CHB patients with compensated cirrhosis, the risk was higher for HCC than for decompensation; more importantly, different decompensation events conferred distinct HCC risks.
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Carcinoma Hepatocelular , Varizes Esofágicas e Gástricas , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Vírus da Hepatite B , Varizes Esofágicas e Gástricas/complicações , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Antivirais/uso terapêutico , Hemorragia Gastrointestinal/complicações , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologiaRESUMO
Abnormal cardiac function in the setting of cirrhosis and in the absence of a primary cardiac disease is known as cirrhotic cardiomyopathy. The pathogenesis of cirrhotic cardiomyopathy is multifactorial but broadly is comprised of two pathways. The first is due to cirrhosis and synthetic liver failure with abnormal structure and function of many substances, including proteins, lipids, hormones, and carbohydrates such as lectins. The second is due to portal hypertension which invariably accompanies cirrhosis. Portal hypertension leads to a leaky, congested gut with resultant endotoxemia and systemic inflammation. This inflammatory phenotype comprises oxidative stress, cellular apoptosis, and inflammatory cell infiltration. Galectins exert all these pro-inflammatory mechanisms across many different tissues and organs, including the heart. Effective therapies for improving cardiac function in patients with cirrhosis are not available. Conventional strategies for other noncirrhotic heart diseases, including vasodilators, are not feasible because of the significant baseline vasodilation in cirrhotic patients. Therefore, exploring new treatment modalities for cirrhotic cardiomyopathy is of great importance. Galectin-3 inhibitors such as modified citrus pectin, N-acetyllactosamine, TD139 and GB0139 exert anti-apoptotic, anti-oxidative and anti-inflammatory effects and thus have potential therapeutic interest. This review briefly summarizes the physiological and pathophysiological role of galectin and specifically examines its role in cardiac disease processes. We present a more detailed discussion of galectin in cardiovascular complications of cirrhosis, particularly cirrhotic cardiomyopathy. Finally, therapeutic studies of galectin-3 inhibitors in cirrhotic cardiomyopathy are reviewed.
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Cirrhotic cardiomyopathy is a syndrome of blunted cardiac systolic and diastolic function in patients with cirrhosis. However, the mechanisms remain incompletely known. Since contractility and relaxation depend on cardiomyocyte calcium transients, any factors that impact cardiac contractile and relaxation functions act eventually through calcium transients. In addition, calcium transients play an important role in cardiac arrhythmias. The present review summarizes the calcium handling system and its role in cardiac function in cirrhotic cardiomyopathy and its mechanisms. The calcium handling system includes calcium channels on the sarcolemmal plasma membrane of cardiomyocytes, the intracellular calcium-regulatory apparatus, and pertinent proteins in the cytosol. L-type calcium channels, the main calcium channel in the plasma membrane of cardiomyocytes, are decreased in the cirrhotic heart, and the calcium current is decreased during the action potential both at baseline and under stimulation of beta-adrenergic receptors, which reduces the signal to calcium-induced calcium release. The study of sarcomere length fluctuations and calcium transients demonstrated that calcium leakage exists in cirrhotic cardiomyocytes, which decreases the amount of calcium storage in the sarcoplasmic reticulum (SR). The decreased storage of calcium in the SR underlies the reduced calcium released from the SR, which results in decreased cardiac contractility. Based on studies of heart failure with non-cirrhotic cardiomyopathy, it is believed that the calcium leakage is due to the destabilization of interdomain interactions (dispersion) of ryanodine receptors (RyRs). A similar dispersion of RyRs may also play an important role in reduced contractility. Multiple defects in calcium handling thus contribute to the pathogenesis of cirrhotic cardiomyopathy.
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BACKGROUND & AIMS: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. METHODS: We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. RESULTS: Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). CONCLUSION: This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS. GOV NUMBER: NCT04695769. IMPACT AND IMPLICATIONS: HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy.
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Hepatite C Crônica , Hepatite C , Masculino , Humanos , Feminino , Sofosbuvir/efeitos adversos , Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Ribavirina/efeitos adversos , Resultado do Tratamento , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Retratamento , GenótipoRESUMO
Currently, the demand for more reliable drug screening devices has made scientists and researchers develop novel potential approaches to offer an alternative to animal studies. Organ-on-chips are newly emerged platforms for drug screening and disease metabolism investigation. These microfluidic devices attempt to recapitulate the physiological and biological properties of different organs and tissues using human-derived cells. Recently, the synergistic combination of additive manufacturing and microfluidics has shown a promising impact on improving a wide array of biological models. In this review, different methods are classified using bioprinting to achieve the relevant biomimetic models in organ-on-chips, boosting the efficiency of these devices to produce more reliable data for drug investigations. In addition to the tissue models, the influence of additive manufacturing on microfluidic chip fabrication is discussed, and their biomedical applications are reviewed.
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Bioimpressão , Animais , Humanos , Bioimpressão/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Microfluídica/métodos , Dispositivos Lab-On-A-Chip , BiomiméticaRESUMO
Dust accumulation is detrimental to optical elements, electronic devices, and mechanical systems and is a significant problem in space missions and renewable energy deployment. In this paper, we report the demonstration of antidust nanostructured surfaces that can remove close to 98% of lunar particles solely via gravity. The dust mitigation is driven by a novel mechanism, whereby particle removal is facilitated by the formation of particle aggregates due to interparticle forces, allowing the particles to be removed in the presence of other particles. The structures are fabricated using a highly scalable nanocoining and nanoimprint process, where nanostructures with precise geometry and surface properties are patterned on polycarbonate substrates. The dust mitigation properties of the nanostructures have been characterized using optical metrology, electron microscopy, and image processing algorithms to demonstrate that the surfaces can be engineered to remove nearly all of the particles above 2 µm in size in the presence of Earth's gravity. Compared to the 35.0% area coverage on a smooth polycarbonate surface, the particle coverage on nanostructures with 500 nm period is significantly reduced to 2.4%, an improvement of 93%. This work enhances the understanding of the particulate adhesion on textured surfaces and demonstrates a scalable, effective solution to antidust surfaces that can be broadly applied to windows, solar panels, and electronics.
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BACKGROUND: Hyperdynamic circulation in portal hypertension (PHT) depends on central neural activation. However, the initiating mechanism that signals PHT to the central neural cardiovascular-regulatory centers remains unclear. We aimed to test the hypothesis that oxidative stress in the gut initiates the signal that activates central cardiovascular nuclei in portal hypertensive rats. METHODS: Two groups of rats were used. One had portal hypertension produced by partial portal vein ligation, while controls underwent sham operation. Hemodynamics including portal pressure, cardiac output, mean arterial pressure (MAP) and peripheral vascular resistance were measured. Activation of central cardiovascular nuclei was determined by immunohistochemical Fos expression in the paraventricular nucleus (PVN) of the hypothalamus. Myeloperoxidase activity, an oxidative stress marker, was measured in the jejunum. Hydrogen peroxide, the antioxidant N-acetyl-cysteine (NAC) or saline controls were administered for 12-14 days by gavage or osmotic minipumps placed in the peritoneal cavity. RESULTS: Compared with controls, PHT rats showed increased cardiac output (54.2 ± 9.5 vs 33.6 ± 2.4 ml/min/100 g BW, p < 0.01), decreased MAP (96.2 ± 6.4 mmHg vs 103.2 ± 7.8, p < 0.01) and systemic vascular resistance (1.84 ± 0.28 vs 3.14 ± 0.19 mmHg/min/ml/100 g BW, p < 0.01). PHT rats had increased jejunal myeloperoxidase and PVN Fos expression. NAC treatment eliminated the hyperdynamic circulation, decreased jejunal myeloperoxidase and PVN Fos expression in PHT rats, but had no effect on sham controls. H2O2 significantly increased PVN Fos expression and decreased MAP. CONCLUSION: These results indicate that in PHT, mesenteric oxidative stress is the initial signal that activates chemoreceptors and triggers hyperdynamic circulation by central neural cardiovascular-regulatory centers.
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Hipertensão Portal , Peroxidase , Ratos , Animais , Peroxidase/metabolismo , Peroxidase/farmacologia , Ratos Sprague-Dawley , Peróxido de Hidrogênio/farmacologia , Hemodinâmica , Veia Porta , Estresse OxidativoRESUMO
BACKGROUND: Direct-acting antiviral agents (DAAs) have transformed chronic hepatitis C (CHC) treatment. Continued affordable access to DAAs requires updated cost-effectiveness analyses (CEA). Utility is a preference-based measure of health-related quality of life (HRQoL) used in CEA. This study evaluated the impact of DAAs on utilities for patients with CHC in two clinical settings. METHODS: This prospective longitudinal study included patients aged ≥18 years, diagnosed with CHC and scheduled to begin DAA treatment, from two tertiary care hospital clinics and four community clinics in Toronto, Calgary, and Montreal. Patients completed two utility instruments (EQ-5D-5L and Health Utilities Index 2/3 (HUI2/3)) before treatment, 6 weeks after treatment initiation, and 12 weeks and 1 year after treatment completion. We measured utilities for all patients, and for hospital-based and community-based groups. RESULTS: Between 2017 and 2020, 209 patients (126 hospital-based, 83 community-based; average age 53 years; 65% male) were recruited, and 143 completed the 1-year post-treatment assessment. Pre-treatment, utilities were (mean ± standard deviation) 0.77 ± 0.21 (EQ-5D-5L), 0.69 ± 0.24 (HUI2) and 0.58 ± 0.34 (HUI3). The mean changes at 1-year post-treatment were 0.035, 0.038 and 0.071, respectively. While utilities for hospital-based patients steadily improved, utilities for the community-based cohort improved between baseline and 12-weeks post-treatment, but decreased thereafter. DISCUSSION: This study suggests that utilities improve after DAA treatment in patients with CHC in a variety of settings. However, community-based patients may face challenges related to comorbid health and social conditions that are not meaningfully addressed by treatment. Our study is essential for valuing health outcomes in CHC-related CEA.
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Antivirais , Hepatite C Crônica , Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Feminino , Antivirais/uso terapêutico , Qualidade de Vida , Hepatite C Crônica/tratamento farmacológico , Estudos Prospectivos , Estudos Longitudinais , Inquéritos e Questionários , HospitaisRESUMO
BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and its management in cirrhosis can be challenging due to the altered hepatic metabolism of medications and increased risk of bleeding. AIMS: To provide a comprehensive overview of the diagnosis, pathophysiology and management of AF in patients with cirrhosis from both a cardiology and a hepatology perspective. METHODS: An extensive literature search was performed using the terms 'atrial fibrillation' and 'cirrhosis'. Guideline documents and consensus statements were explored. RESULTS: The prevalence of AF in patients with cirrhosis ranges between 6.6% and 14.2%, while the incidence of new-onset AF in the post-operative period after liver transplant ranged between 6.8% and 10.2%. AF in patients with cirrhosis is associated with adverse outcomes in both pre-transplant and post-transplant settings, including an increased risk of stroke when compared to the general population. We review the pathogenesis of AF in general and in cirrhosis. This review also provides guidance on the management of AF, including the use of anticoagulation and rate versus rhythm control. In the absence of strict contraindications, all patients with cirrhosis and AF should be anticoagulated. The use of DOACs is preferred over vitamin K antagonists. In patients with a high bleeding risk, a DOAC with an approved antidote may be preferred. CONCLUSIONS: Atrial fibrillation is increased in patients with cirrhosis. AF management requires careful consideration of treatment options. Since patients with cirrhosis were excluded from all major randomised clinical trials, dedicated research on the pathophysiology and management of AF in cirrhosis is needed.