RESUMO
One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.
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Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Grécia/epidemiologia , Incidência , Hepatite C/epidemiologia , Masculino , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Prevalência , AdolescenteRESUMO
BACKGROUND AND AIMS: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. APPROACH AND RESULTS: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). CONCLUSIONS: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.
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Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Fígado/patologia , Fibrose , Algoritmos , Biomarcadores , Aprendizado de Máquina , Biópsia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologiaRESUMO
BACKGROUND AND AIMS: Thyroid axis is currently under investigation as a therapeutic target in metabolic dysfunction-associated steatotic liver disease (MASLD). Thyroid function was examined herein in the full spectrum of disease. METHODS: Subjects were recruited and had liver biopsies in two Gastroenterology-Hepatology Clinics (Greece and Australia) and one Bariatric-Metabolic Surgery Clinic (Italy). The main working sample was n = 677 subjects with MASLD after excluding subjects with abnormal free thyroxine levels. Participants were classified according to thyroid-stimulating hormone (TSH) standard criteria: Subclinical hyperthyroidism (<0.4 uIU/mL); Euthyroidism with relatively low (0.4 to <2.5 uIU/mL); euthyroidism with relatively high (2.5-4.0 uIU/mL); subclinical hypothyroidism (>4 uIU/mL). RESULTS: TSH as a continuous variable was positively associated with significant fibrosis (F ≥ 2), metabolic dysfunction-associated steatohepatitis (MASH) and at-risk MASH. Subclinical hypothyroidism was associated with fibrosis F ≥ 2 (odds ratio [OR] = 3.47, 95% confident interval [CI] [1.50, 8.05], p = .02), MASH (OR = 3.44, 95% CI [1.48, 7.98] p = .001) and at-risk MASH (OR = 3.88, 95% CI [1.76, 8.55], p = .001), before and after controlling for adiposity, central obesity, and insulin resistance. When leptin, adiponectin, or growth differentiation factor-15 were examined as moderators, significance was lost. Sex-specific analysis revealed a strong association between TSH and the presence of significant fibrosis among women, eliminated only when adipokines/mitokines were adjusted for. Restricted cubic spline analysis revealed associations between TSH and liver outcomes (p-values < .01) with inflection points for fibrosis F ≥ 2 being 2.49, for MASH being 2.67 and for at-risk MASH being 6.96. CONCLUSIONS: These observations provide support for studies on the administration of thyroid hormone in MASLD therapeutics for subclinical hypothyroidism and liver-specific thyroid receptor agonists for subjects across the TSH continuum.
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Fígado Gorduroso , Hipotireoidismo , Masculino , Humanos , Feminino , Adipocinas , Hipotireoidismo/complicações , Tireotropina , Obesidade/complicações , Fígado Gorduroso/complicações , FibroseRESUMO
Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.
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Hepatite B Crônica , Hepatite B , Viroses , Humanos , Masculino , Feminino , Antivirais/uso terapêutico , Sofosbuvir/uso terapêutico , Vírus da Hepatite B , Inquéritos e Questionários , Quimioterapia Combinada , Medidas de Resultados Relatados pelo Paciente , Cirrose Hepática/tratamento farmacológico , Hepatite B/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológicoRESUMO
Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.
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Diabetes Mellitus Tipo 2 , Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Quimioterapia Combinada , Fadiga , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Sistema de Registros , Sofosbuvir/uso terapêuticoRESUMO
INTRODUCTION: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment. METHODS: Data were pooled from 10 phase 3 clinical trials of treatment-naive patients with HCV genotype 1-6 without cirrhosis/with compensated cirrhosis (treatment adherence analysis) and 13 phase 3 clinical trials of all patients with HCV (interruption analysis). RESULTS: Among 2,149 patients included, overall mean adherence was 99.4%. Over the treatment duration, adherence decreased (weeks 0-4: 100%; weeks 5-8: 98.3%; and weeks 9-12: 97.1%) and the percentage of patients with ≥80% or ≥90% adherence declined. SVR12 rate in the intention-to-treat (ITT) population was 97.7% (modified ITT SVR12 99.3%) and remained high in nonadherent patients in the modified ITT population (<90%: 94.4%-100%; <80%: 83.3%-100%). Psychiatric disorders were associated with <80% adherence, and shorter treatment duration was associated with ≥80% adherence. Among 2,902 patients in the interruption analysis, 33 (1.1%) had a G/P treatment interruption of ≥1 day, with an SVR12 rate of 93.9% (31/33). No virologic failures occurred. DISCUSSION: These findings support the impact of treatment duration on adherence rates and further reinforce the concept of "treatment forgiveness" with direct-acting antivirals.
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Ácidos Aminoisobutíricos/uso terapêutico , Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Ciclopropanos/uso terapêutico , Hepatite C/tratamento farmacológico , Lactamas Macrocíclicas/uso terapêutico , Leucina/análogos & derivados , Adesão à Medicação , Prolina/análogos & derivados , Pirrolidinas/uso terapêutico , Quinoxalinas/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Feminino , Humanos , Leucina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prolina/uso terapêutico , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
BACKGROUND: Chronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options. METHODS: We conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both. Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of these medications. The primary end point was a sustained virologic response 12 weeks after the end of treatment. RESULTS: Among the 104 patients enrolled in the trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6 infection. The sustained virologic response rate was 98% (102 of 104 patients; 95% confidence interval, 95 to 100). No patients had virologic failure during treatment, and no patients had a virologic relapse after the end of treatment. Adverse events that were reported in at least 10% of the patients were pruritus, fatigue, and nausea. Serious adverse events were reported in 24% of the patients. Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response. CONCLUSIONS: Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection. (Funded by AbbVie; ClinicalTrials.gov number, NCT02651194 .).
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Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Quinoxalinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Ciclopropanos , Combinação de Medicamentos , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Pirrolidinas , Quinoxalinas/efeitos adversos , RNA Viral/sangue , Sulfonamidas/efeitos adversos , Carga ViralRESUMO
BACKGROUND & AIMS: Non-alcoholic and alcohol-related fatty liver disease are overlapping diseases in which metabolic syndrome and alcohol consumption each contribute to progressive liver disease. We aimed to assess the effects of alcohol consumption and metabolic syndrome on mortality in individuals with fatty liver. METHODS: We searched the National Health and Nutrition and Examination Survey III for adults (20-74 years old) with hepatic steatosis, detected by ultrasound, for whom mortality and follow-up data were available. We collected data from the alcohol use questionnaire (self-reported number of days a participant drank alcohol; the number of drinks [10 g alcohol] per day on a drinking day; the number of days the participant had 5 or more drinks) and calculated the average amount of alcohol consumption in drinks/day for each participant during the year preceding enrollment. Excessive alcohol consumption for men was >3 drinks/day and for women was >1.5 drinks/day. We also collected clinical data, and mortality data were obtained from the National Death Index. Demographic and clinical parameters were compared among consumption groups using the χ2 test for independence or survey regression models. We used Cox proportional hazard models to identify independent predictors of all-cause and cause-specific mortality. RESULTS: The study cohort included 4264 individuals with hepatic steatosis (mean age, 45.9 years; 51% male; 76% white; 46% with metabolic syndrome; 6.2% with excessive alcohol use). There was no significant difference in mean age between individuals with vs without excessive alcohol consumption (P=.65). However, overall mortality was significantly higher among participants with excessive alcohol consumption (32.2%) vs participants with non-excessive alcohol use (22.2%) after mean 20 years of follow up (P=.003), as well as after 5 years of follow up. In multivariate analysis, the presence of metabolic syndrome (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.12-1.83) and excessive alcohol consumption (aHR, 1.79; 95% CI, 1.21-2.66) were independently associated with an increased risk of death in individuals with hepatic steatosis; any lower average amount of alcohol consumption was not associated with mortality (all P>.60). In a subgroup analysis, the association of excessive alcohol use with mortality was significant in individuals with metabolic syndrome (aHR, 2.46; 95% CI, 1.40-4.32) but not without it (P=.74). CONCLUSION: In review of data from the National Health and Nutrition and Examination Survey III, we associated alcohol consumption with increased mortality in participants with fatty liver and metabolic syndrome. These findings indicate an overlap between non-alcoholic and alcohol-related fatty liver disease.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Cirrose Hepática Alcoólica/etiologia , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Cirrose Hepática Alcoólica/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Malnutrition risk screening in cirrhotic patients is crucial, as poor nutritional status negatively affects disease prognosis and survival. Given that a variety of malnutrition screening tools is usually used in routine clinical practice, the effectiveness of eight screening tools in detecting malnutrition risk in cirrhotic patients was sought. A total of 170 patients (57·1 % male, 59·4 (sd 10·5) years, 50·6 % decompensated ones) with cirrhosis of various aetiologies were enrolled. Nutritional screening was performed using the Malnutrition Universal Screening Tool, Nutritional Risk Index, Malnutrition Screening Tool, Nutritional Risk Screening (NRS-2002), Birmingham Nutritional Risk Score, Short Nutritional Assessment Questionnaire, Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Malnutrition diagnosis was defined using the Subjective Global Assessment (SGA). Data on 1-year survival were available for 145 patients. The prevalence of malnutrition risk varied according to the screening tools used, with a range of 13·5-54·1 %. RFH-NPT and LDUST were the most accurate in detecting malnutrition (AUC = 0·885 and 0·892, respectively) with a high sensitivity (97·4 and 94·9 %, respectively) and fair specificity (73·3 and 58 %, respectively). Malnutrition according to SGA was an independent prognostic factor of within 1-year mortality (relative risk was 2·17 (95 % CI 1·0, 4·7), P = 0·049) after adjustment for sex, age, disease aetiology and Model for End-stage Liver Disease score, whereas nutrition risk according to RFH-NPT, LDUST and NRS-2002 showed no association. RFH-NPT and LDUST were the only screening tools that proved to be accurate in detecting malnutrition in cirrhotic patients.
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Cirrose Hepática/complicações , Desnutrição/diagnóstico , Avaliação Nutricional , Adulto , Idoso , Antropometria , Área Sob a Curva , Estudos Transversais , Feminino , Humanos , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Estado Nutricional , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Curva ROC , Medição de Risco , Inquéritos e QuestionáriosRESUMO
Treatment of hepatitis C virus (HCV) infection has been revolutionized with the introduction of pangenotypic, interferon- and ribavirin-free regimens associated with high cure rates and a low side effect profile. Additionally, there is evidence that HCV cure reduces HCV complications, improves patient-reported outcomes and is cost-saving in most western countries in the long term. This is a review of the comprehensive burden of HCV and the value of eliminating HCV infection. With the introduction of the interferon-free all-oral, once a day pill treatment regimen for the cure of HCV, the potential to eliminate HCV by 2030 has become a possibility for some regions of the world. Nevertheless, there are barriers to screening, linkage to care, and treatment in many countries that must be overcome in order to reach this goal. In conclusion, globally, work must continue to ensure national policies are in place to support screening, linkage to care and affordable treatment in order to eliminate HCV.
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Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Administração Oral , Antivirais/economia , Erradicação de Doenças , Saúde Global , Custos de Cuidados de Saúde , Política de Saúde , Hepatite C Crônica/diagnóstico , Humanos , Programas de Rastreamento/organização & administração , Resultado do TratamentoRESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) exhibit an increased risk for acquiring hepatitis B virus (HBV), thus they should be vaccinated preferably, if not already infected or immunized. We assessed the efficacy of HBV vaccination in IBD patients and impact of different factors on the immune response. We also evaluated the success rate of 2 different revaccination strategies in the nonresponders. METHODS: This was a retrospective observational cohort study carried out in 5 tertiary centers. All patients were tested for hepatitis B surface antigen, antibodies against hepatitis B surface antigen (anti-HBs), and antibodies against hepatitis B core antigen. Patients tested negative and underwent the standard schedule with 20 µg at 0, 1, and 6 months. Nonresponders (anti-HBs <10 IU/L) were offered a revaccination scheme with either 3 doses of 40 µg at 0, 1, and 6 months or an accelerated scheme with 20 µg at 0, 1, and 2 months. RESULTS: A total of 409 patients were included, and 273 (66.7%) of those (females: 49.5%; Crohn's disease [CD]: 56.7%) responded to baseline vaccination. A total of 189 (69.2%) of 273 (females: 48.1%; CD: 60.3%) developed anti-HBs >100 IU/L. Body mass index <30 kg/m2 (Pâ =â .017) was positively associated, while diagnosis of CD (Pâ =â .013), extensive UC (P <.0001), extraintestinal manifestations (Pâ =â .001), and treatment with immunomodulators/anti-tumor necrosis factor (Pâ <â .00) negatively affected the response. Revaccination was offered to 103 patients, and 58.3% of them achieved anti-HBs >10 IU/L. Both revaccination strategies were equally effective. CONCLUSIONS: IBD patients demonstrate lower response to HBV vaccination compared with the general population. Age, body mass index, type, disease activity, and immunosuppression negatively affect the response. Half of nonresponders may benefit from an enhanced revaccination attempt.
In this retrospective study, we addressed the impact of several factors on the immune response postvaccination against hepatitis B virus in a large cohort of >400 inflammatory bowel disease patients and compared the effectiveness of 2 different revaccination strategies on nonresponders.
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AIMS: Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints. METHODS: Using the LITMUS Metacohort derived from the European NAFLD Registry, the largest MASLD dataset in Europe, we create three combinations of features which vary in degree of procurement including a 19-variable feature set that are attained through a routine clinical appointment or blood test. This data was used to train predictive models using supervised machine learning (ML) algorithm XGBoost, alongside missing imputation technique MICE and class balancing algorithm SMOTE. Shapley Additive exPlanations (SHAP) were added to determine relative importance for each clinical variable. RESULTS: Analysing nine biopsy-derived MASLD outcomes of cohort size ranging between 5385 and 6673 subjects, we were able to predict individuals at training set AUCs ranging from 0.719-0.994, including classifying individuals who are At-Risk MASH at an AUC = 0.899. Using two further feature combinations of 26-variables and 35-variables, which included composite scores known to be good indicators for MASLD endpoints and advanced specialist tests, we found predictive performance did not sufficiently improve. We are also able to present local and global explanations for each ML model, offering clinicians interpretability without the expense of worsening predictive performance. CONCLUSIONS: This study developed a series of ML models of accuracy ranging from 71.9-99.4% using only easily extractable and readily available information in predicting MASLD outcomes which are usually determined through highly invasive means.
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Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Humanos , Aprendizado de Máquina , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Pacientes , Aprendizado de Máquina SupervisionadoRESUMO
BACKGROUND: Mortality among people who inject drugs (PWID) is high, with overdose and HIV infection being the main causes of death. In Greece, there have been no data on mortality, and two HIV outbreaks have been recorded in this population in the past decade. In this study, we aim to estimate the all-cause crude mortality rate and the standardised mortality ratio in this population during 2018-2022. METHODS: PWID recruited from two community-based programs in Athens and Thessaloniki during 2018-2021 were interviewed and tested for HIV/HCV. Data on vital status (deceased/alive) and date of death were obtained from death registries through December 31, 2022. All-cause crude mortality rates (CMR) and standardised mortality ratios (SMR) were estimated. Determinants of mortality were assessed using Cox proportional-hazards model. RESULTS: Of 2,530 participants, 301 died over 8,543 person-years (PYs) of follow-up. The CMR (95 % CI) was 3.52 (3.15-3.94) deaths per 100 PYs; 3.10 per 100 PYs (2.68-3.58) in Athens and 4.48 per 100 PYs (3.74-5.37) in Thessaloniki. An increasing trend in CMR was identified over 2018-2022 in Athens (from 2.90 to 4.11 per 100 PYs, 41.5 % increase, p = 0.018). The pooled SMR (95 % CI) was 15.86 (14.17-17.76) for both cities and was particularly increased in younger individuals, females, those injecting daily, not enrolled to opioid agonist treatment and HIV-infected individuals. Older age, living in Thessaloniki, Greek origin, homelessness, history of injection in the past 12 months, and HIV infection were independently associated with higher risk of death. CONCLUSION: Mortality among PWID in the two largest cities (Athens and Thessaloniki) in Greece in 2018-2022 was high, with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens may reflect the long-term impact of the COVID-19 pandemic. Preventive programs such as take-home naloxone, screening and treatment for HIV, are urgently needed.
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Overdose de Drogas , Infecções por HIV , Abuso de Substâncias por Via Intravenosa , Humanos , Abuso de Substâncias por Via Intravenosa/mortalidade , Abuso de Substâncias por Via Intravenosa/epidemiologia , Feminino , Masculino , Adulto , Grécia/epidemiologia , Pessoa de Meia-Idade , Infecções por HIV/mortalidade , Overdose de Drogas/mortalidade , Causas de Morte , Adulto Jovem , Fatores de RiscoRESUMO
BACKGROUND: The role of metabolic/inflammatory hormonal systems in metabolic dysfunction associated steatotic liver disease (MASLD) remains to be fully elucidated. PURPOSE: To report the levels of the novel total and H-specific growth differentiation factor-15 (GDF-15) and other established hormonal systems and to describe hormonal patterns in controls and patients with MASLD and its stages. METHODS: This is a multicenter study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven MASLD (n = 374) and Controls (n = 81) were recruited. RESULTS: We report for the first time that total and H-specific GDF-15 levels are higher in MASLD, at-risk metabolic dysfunction associated steatohepatitis (MASH), and severe fibrosis than in Controls. In addition, follistatin-like-3 (FSTL-3), free insulin-like growth factor-1 (IGF-1), leptin, and insulin levels were higher in MASLD patients than in Controls, while adiponectin levels were lower in MASLD subjects than in Controls. Activin-A, follistatin (FST), FSTL-3, and insulin levels significantly increased in severe fibrosis compared to no/mild fibrosis, while free IGF-1 decreased. In addition, adiponectin levels were lower in subjects without fibrosis vs. any fibrosis. Moreover, GDF-15 presented a strong positive association for the likelihood of having MASLD and at-risk MASH, while in adjusted analyses, FST and adiponectin showed inverse associations. Two different patterns of at-risk MASH were revealed through unsupervised analysis (total variation explained=54%). The most frequent pattern met in our sample (34.3%) was characterized by higher levels of total and H-specific GDF-15, follistatins, and activins, as well as low adiponectin levels. The second pattern revealed was characterized by high levels of free IGF-1, insulin, and leptin, with low levels of activin-A and adiponectin. Similar patterns were also generated in the case of overall MASLD. CONCLUSIONS: Total and H-specific GDF-15 levels increase as MASLD severity progresses. FSTL-3, free IGF-1, leptin, and insulin are also higher, whereas adiponectin and activin-A levels are lower in the MASLD group than in Controls. Hormonal systems, including GDF-15, may not only be involved in the pathophysiology but could also prove useful for the diagnostic workup of MASLD and its stages and may potentially be of therapeutic value.
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Leptina , Hepatopatia Gordurosa não Alcoólica , Humanos , Fator de Crescimento Insulin-Like I/análise , Hepatopatia Gordurosa não Alcoólica/complicações , Folistatina , Fator 15 de Diferenciação de Crescimento , Adiponectina , Insulina , Ativinas , Fibrose , BiópsiaRESUMO
AIMS: A new non-invasive tool (NIT) for non-alcoholic fatty liver disease (NAFLD) proposed in 2022 by the multi-ethnic Dallas Heart Study, i.e. the Dallas Steatosis Index (DSI), was validated herein using for the first time the gold standard i.e. liver biopsy-proven NAFLD. METHODS: This is a multicenter study based on samples and data from two Gastroenterology-Hepatology Clinics (Greece and Australia) and one Bariatric-Metabolic Surgery Clinic (Italy). Overall, n = 455 patients with biopsy-proven NAFLD (n = 374) and biopsy-proven controls (n = 81) were recruited. RESULTS: The ability of DSI to correctly classify participants as NAFLD or controls was very good, reaching an Area Under the Curve (AUC) = 0.887. The cut-off point that could best differentiate the presence vs. absence of NAFLD corresponded to DSI = 0.0 (risk threshold: 50% | Sensitivity: 0.88; Positive Predictive Value (PPV): 93.0%; F1-score = 0.91). DSI demonstrated significantly better performance characteristics than other liver steatosis indexes. Decision curve analysis revealed that the benefit of DSI as a marker to indicate the need for invasive liver assessment was confirmed only when higher DSI values, i.e. ≥ 1.4, were used as risk thresholds. DSI performance to differentiate disease progression was inadequate (all AUCs < 0.700). CONCLUSIONS: DSI is more useful for disease screening (NAFLD vs. controls) than to differentiate diseases stages or progression. The value of any inclusion of DSI to guidelines needs to be further studied.
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BACKGROUND: Non-invasive tools (NIT) for metabolic-dysfunction associated liver disease (MASLD) screening or diagnosis need to be thoroughly validated using liver biopsies. PURPOSE: To externally validate NITs designed to differentiate the presence or absence of liver steatosis as well as more advanced disease stages, to confirm fully validated indexes (n = 7 NITs), to fully validate partially validated indexes (n = 5 NITs), and to validate for the first time one new index (n = 1 NIT). METHODS: This is a multi-center study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven MASLD (n = 374, including 237 patients with metabolic-dysfunction associated steatohepatitis (MASH)) and Controls (n = 81) were recruited. A complete validation analysis was performed to differentiate the presence of MASLD vs. Controls, MASH vs. metabolic-dysfunction associated steatotic liver (MASL), histological features of MASH, and fibrosis stages. RESULTS: The index of NASH (ION) demonstrated the highest differentiation ability for the presence of MASLD vs. Controls, with the area under the curve (AUC) being 0.894. For specific histological characterization of MASH, no NIT demonstrated adequate performance, while in the case of specific features of MASH, such as hepatocellular ballooning and lobular inflammation, ION demonstrated the best performance with AUC being close to or above 0.850. For fibrosis (F) classification, the highest AUC was reached by the aspartate aminotransferase to platelet ratio index (APRI) being ~0.850 yet only with the potential to differentiate the severe fibrosis stages (F3, F4) vs. mild or moderate fibrosis (F0-2) with an AUC > 0.900 in patients without T2DM. When we excluded patients with morbid obesity, the differentiation ability of APRI was improved, reaching AUC = 0.802 for differentiating the presence of fibrosis F2-4 vs. F0-1. The recommended by current guidelines index FIB-4 seemed to differentiate adequately between severe (i.e., F3-4) and mild or moderate fibrosis (F0-2) with an AUC = 0.820, yet this was not the case when FIB-4 was used to classify patients with fibrosis F2-4 vs. F0-1. Trying to improve the predictive value of all NITs, using Youden's methodology, to optimize the suggested cut-off points did not materially improve the results. CONCLUSIONS: The validation of currently available NITs using biopsy-proven samples provides new evidence for their ability to differentiate between specific disease stages, histological features, and, most importantly, fibrosis grading. The overall performance of the examined NITs needs to be further improved for applications in the clinic.
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Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Testes de Função Hepática , Biópsia , Fígado/patologia , Aspartato AminotransferasesRESUMO
BACKGROUND: The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis-liver biopsy-is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. METHODS: This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. FINDINGS: Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54-0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75-0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86-0·94]), ADAPT (0·85 [0·81-0·89]), and FibroScan liver stiffness measurement (0·83 [0·80-0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4-5]), then ADAPT (six [5-7]), MACK-3 (seven [6-8]), and PRO-C3 (nine [7-11]). INTERPRETATION: None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort. FUNDING: The Innovative Medicines Initiative 2 Joint Undertaking.
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Hepatopatia Gordurosa não Alcoólica , Adolescente , Adulto , Feminino , Humanos , Masculino , Biomarcadores , Fibrose , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos ProspectivosRESUMO
BACKGROUND: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. METHODS: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. RESULTS: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. CONCLUSIONS: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.
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BACKGROUND/AIM: Previous randomized clinical trials have shown that moderate hypofractionation has a non-inferior or even superior efficacy to conventionally fractionated external beam radiation therapy (EBRT) in low and intermediate-risk prostate cancer. We herein aimed to evaluate the acute and late gastrointestinal (GI) toxicity of hypofractionated radiotherapy (HRT) in a real-world setting. PATIENTS AND METHODS: Patients with intermediate-risk prostate adenocarcinoma eligible to receive HRT were prospectively enrolled. All patients were submitted to rectoscopy after completion of HRT, every three months after radiotherapy for the first year and every six months for the second year. Toxicity events were classified as acute, when presenting during radiotherapy or within the first three months following its completion, and as late when appearing three months to three years post-HRT. RESULTS: Twenty prostate cancer patients participated in this study and received 22 sessions of HRT (5 sessions a week; 2.75 Gy per session) and an overall dose of 60.5 Gy. None of our patients developed acute GI toxicity; late GI toxicity (RTOG/EORTC grade 3 rectal bleeding) was observed in 1 patient only (1/20, 5%), at 6- and 12-months post-HRT. No rectal mucosa damage was observed on follow-up rectoscopy in the acute phase in any of our patients; five patients (5/20, 25%) developed late telangiectasias. Vienna retroscopy score (VRS) was 1 in 4/5 patients (80%) and 2 in 1/5 (20%). CONCLUSION: Minimal radiation-induced rectal mucosal damage was observed in our patient population, and only as a late event, further attesting to the safety of HRT in this setting.
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Gastroenteropatias , Neoplasias da Próstata , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Reto/patologiaRESUMO
BACKGROUND & AIMS: Undernutrition is widely prevalent in patients with cirrhosis and affects prognosis. Given the lack of data regarding the dietary intake (DI) and habits of patients with cirrhosis, the aim of the present study was to evaluate them by assessing diet's adequacy compared to the new guidelines, and the association of DI with nutritional status indicators. METHODS: One hundred and eighty-seven patients (57.8% male, 59.9 ± 10.9 years old, 44.9% decompensated ones) with cirrhosis of various etiologies were enrolled. The patients' DI was assessed using three 24 h recalls, which were analyzed regarding macronutrients' intake, food groups consumption, adherence to the Mediterranean diet and meal patterns. The Goldberg cut-off limits for the ratio of energy intake to resting energy expenditure were used to evaluate dietary underreporting and patients were accordingly classified as low or adequate energy reporters (LERs and AERs). RESULTS: Among the AERs (n = 91, 48.7%) only 29.7% and 31.9% met current recommendations regarding energy and protein intake, accordingly. Patients reported low intake of several healthy food groups and low adherence to the Mediterranean diet. They reported a median of 4.3 eating episodes per day and they frequently omitted late evening snack. Nevertheless, no statistically significant associations were found between parameters of DI and annual and two-year survival. CONCLUSIONS: Low energy reporting was very frequent in this sample of patients with liver cirrhosis. Diet quality was rather poor, whereas energy and protein intakes were lower than those recommended.