RESUMO

BACKGROUND: This study aimed to assess the frequency and intensity of anxious and depressive symptoms in patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a descriptive and cross-sectional study, resulting from 106 patients from the Hepatology outpatient clinic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil without a history of alcohol abuse, verified by the alcohol use disorders identification test (AUDIT). These were assessed using the sociodemographic data sheet, Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Scale (HAM-D). RESULTS: A total of 69.8% were women and 30.2% were men, with a mean age of 61 years. The majority (71.7%) discovered MASLD through routine exams, presenting as comorbidities: Type 2 diabetes mellitus (59.4%), Dyslipidemia (49.1%), Arterial hypertension (68.9%), Obesity (61.3%) and Metabolic syndrome [MetS (63.2%)]. The HADS scale indicates 34% probability of anxiety and 33% depressive symptoms. The Hamilton's scales of intensity indicates 63.9% severe anxiety and 54.3% severe depression. There is also a relationship between anxiety, depression and the female gender, as well as between depression and MetS. CONCLUSION: The findings point to the presence of anxiety and depression in more than one third of MASLD patients, most with severe symptoms. The group is concentrated in the elderly, with many comorbidities, including MetS. There was a positive correlation between anxiety, depression and being female; also, being significant between MetS and depression.

Assuntos

Ansiedade , Depressão , Síndrome Metabólica , Humanos , Feminino , Masculino , Estudos Transversais , Pessoa de Meia-Idade , Depressão/etiologia , Ansiedade/etiologia , Ansiedade/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/psicologia , Idoso , Adulto , Fígado Gorduroso/complicações , Fígado Gorduroso/psicologia , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Brasil/epidemiologia , Fatores Socioeconômicos

RESUMO

OBJECTIVES: The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. METHODS: A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. RESULTS: At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. CONCLUSION: Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

Assuntos

Antivirais , Carcinoma Hepatocelular , Técnicas de Imagem por Elasticidade , Hepatite C Crônica , Cirrose Hepática , Neoplasias Hepáticas , Resposta Viral Sustentada , Humanos , Técnicas de Imagem por Elasticidade/métodos , Masculino , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/virologia , Feminino , Pessoa de Meia-Idade , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico por imagem , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/virologia , Seguimentos , Fatores de Tempo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/virologia , Resultado do Tratamento , Adulto , Idoso , Valor Preditivo dos Testes

RESUMO

BACKGROUND & AIM: Patatin-like phospholipase domain-containing 3 gene (PNPLA3) polymorphism has been implicated in susceptibility to non-alcoholic fatty liver disease (NAFLD), with evidence for potential interaction with nutrition. However, the combination of meat consumption with genetic polymorphism has not been tested. Therefore, this study aims to test the association between the joint presence of PNPLA3 rs738409 G-allele with high meat consumption and NAFLD in populations with diverse meat consumption. METHODS: A cross-sectional study among Israeli screening and Brazilian primary healthcare populations. Food consumption was assessed by a food-frequency questionnaire. PNPLA3 polymorphism was defined as homozygous (GG) or heterozygous (GC). Inconclusive/probable NAFLD was defined as a fatty liver index (FLI) ≥ 30 and probable NAFLD as FLI ≥ 60. RESULTS: The sample included 511 subjects from the screening and primary healthcare populations (n = 213 and n = 298, respectively). Genetic polymorphism (homozygous GG or heterozygous GC) combined with high consumption of total meat, red and/or processed meat, unprocessed red meat, and processed meat was associated with the highest odds for inconclusive/probable NAFLD (OR = 2.75, 95%CI 1.27-5.97, p = 0.011; OR = 3.24, 1.43-7.34, p = 0.005; OR = 2.92, 1.32-6.47, p = 0.008; OR = 3.16, 1.46-6.83, p = 0.003, respectively), adjusting for age, gender, BMI, alcohol consumption, carbohydrate, and saturated fat intake. In addition, genetic polymorphism combined with high processed meat consumption was associated with the highest odds for probable NAFLD (OR = 2.40, 95%CI 1.04-5.56, p = 0.040). CONCLUSIONS: High red meat intake may confer a greater risk for NAFLD among PNPLA3 polymorphism carriers. Prospective studies are needed to confirm these findings and consider minimizing red and processed meat consumption among PNPLA3 polymorphism carriers.

Assuntos

Lipase , Proteínas de Membrana , Hepatopatia Gordurosa não Alcoólica , Carne Vermelha , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos Transversais , Masculino , Feminino , Lipase/genética , Pessoa de Meia-Idade , Carne Vermelha/efeitos adversos , Brasil/epidemiologia , Proteínas de Membrana/genética , Adulto , Israel/epidemiologia , Predisposição Genética para Doença , Dieta/efeitos adversos , Polimorfismo de Nucleotídeo Único , Alelos , Polimorfismo Genético , Aciltransferases , Fosfolipases A2 Independentes de Cálcio

RESUMO

BACKGROUND: Prevalence of hepatocellular carcinoma (HCC) is increasing, especially in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). AIM: To investigate rifaximin (RIF) effects on epigenetic/autophagy markers in animals. METHODS: Adult Sprague-Dawley rats were randomly assigned (n = 8, each) and treated from 5-16 wk: Control [standard diet, water plus gavage with vehicle (Veh)], HCC [high-fat choline deficient diet (HFCD), diethylnitrosamine (DEN) in drinking water and Veh gavage], and RIF [HFCD, DEN and RIF (50 mg/kg/d) gavage]. Gene expression of epigenetic/autophagy markers and circulating miRNAs were obtained. RESULTS: All HCC and RIF animals developed metabolic-dysfunction associated steatohepatitis fibrosis, and cirrhosis, but three RIF-group did not develop HCC. Comparing animals who developed HCC with those who did not, miR-122, miR-34a, tubulin alpha-1c (Tuba-1c), metalloproteinases-2 (Mmp2), and metalloproteinases-9 (Mmp9) were significantly higher in the HCC-group. The opposite occurred with Becn1, coactivator associated arginine methyltransferase-1 (Carm1), enhancer of zeste homolog-2 (Ezh2), autophagy-related factor LC3A/B (Map1 Lc3b), and p62/sequestosome-1 (p62/SQSTM1)-protein. Comparing with controls, Map1 Lc3b, Becn1 and Ezh2 were lower in HCC and RIF-groups (P < 0.05). Carm1 was lower in HCC compared to RIF (P < 0.05). Hepatic expression of Mmp9 was higher in HCC in relation to the control; the opposite was observed for p62/Sqstm1 (P < 0.05). Expression of p62/SQSTM1 protein was lower in the RIF-group compared to the control (P = 0.024). There was no difference among groups for Tuba-1c, Aldolase-B, alpha-fetoprotein, and Mmp2 (P > 0.05). miR-122 was higher in HCC, and miR-34a in RIF compared to controls (P < 0.05). miR-26b was lower in HCC compared to RIF, and the inverse was observed for miR-224 (P < 0.05). There was no difference among groups regarding miR-33a, miR-143, miR-155, miR-375 and miR-21 (P > 0.05). CONCLUSION: RIF might have a possible beneficial effect on preventing/delaying liver carcinogenesis through epigenetic modulation in a rat model of MASLD-HCC.

RESUMO

ABSTRACT Background: This study aimed to assess the frequency and intensity of anxious and depressive symptoms in patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This is a descriptive and cross-sectional study, resulting from 106 patients from the Hepatology outpatient clinic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil without a history of alcohol abuse, verified by the alcohol use disorders identification test (AUDIT). These were assessed using the sociodemographic data sheet, Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Scale (HAM-D). Results: A total of 69.8% were women and 30.2% were men, with a mean age of 61 years. The majority (71.7%) discovered MASLD through routine exams, presenting as comorbidities: Type 2 diabetes mellitus (59.4%), Dyslipidemia (49.1%), Arterial hypertension (68.9%), Obesity (61.3%) and Metabolic syndrome [MetS (63.2%)]. The HADS scale indicates 34% probability of anxiety and 33% depressive symptoms. The Hamilton's scales of intensity indicates 63.9% severe anxiety and 54.3% severe depression. There is also a relationship between anxiety, depression and the female gender, as well as between depression and MetS. Conclusion: The findings point to the presence of anxiety and depression in more than one third of MASLD patients, most with severe symptoms. The group is concentrated in the elderly, with many comorbidities, including MetS. There was a positive correlation between anxiety, depression and being female; also, being significant between MetS and depression.

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RESUMO Contexto: Este estudo teve como objetivo avaliar a frequência e a intensidade dos sintomas ansiosos e depressivos em pacientes com diagnóstico de doença hepática esteatótica associada à disfunção metabólica [do inglês: Metabolic dysfunction-associated steatotic liver disease (MASLD)]. Métodos: Trata-se de um estudo descritivo e transversal, resultante do acompanhamento de 106 pacientes do Ambulatório de Doença Hepática Esteatótica Associada à Disfunção Metabólica (A2MG700) da Disciplina de Gastroenterologia Clínica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brasil, sem história de abuso de álcool, verificada pelo Alcohol Use Disorders Identification Test (AUDIT). Foram avaliados os dados sociodemográficos, Escala hospitalar de ansiedade e depressão [do inglês: Hospital Anxiety and Depression Scale (HADS)], Escala de avaliação de ansiedade de Hamilton [do inglês: Hamilton Anxiety Rating Scale (HAM-A)] e Escala de depressão de Hamilton [do inglês: Hamilton Depression Scale (HAM-D)]. Resultados: Um total 69,8% dos indivíduos eram do sexo feminino com idade média de 61 anos. A maioria dos indivíduos avaliados (71,7%) descobriu a doença por meio de exames de rotina e apresentavam diabetes mellitus tipo 2 (59,4%), dislipidemia (49,1%), hipertensão arterial (68,9%), obesidade (61,3%) e síndrome metabólica [SM (63,2%)]. A análise da escala HADS demonstrou probabilidade de ansiedade em 34% dos participantes e 33% de sintomas depressivos. A escala de intensidade de Hamilton demonstrou que 63,9% dos indivíduos apresentavam ansiedade severa e 54,3% depressão severa. Observamos também relação entre ansiedade, depressão e o sexo feminino, assim como, entre depressão e SM. Conclusão: Nossos achados demonstram a presença de ansiedade e depressão em mais de 1/3 dos indivíduos com MASLD avaliados e a maioria apresenta sintomas graves. O grupo era composto por pacientes idosos e com comorbidades, incluindo SM. Observamos correlação positiva entre ansiedade, depressão e sexo feminino, sendo significativa entre SM e depressão.

RESUMO

Abstract Objectives The primary objective was to evaluate Liver-Related Events (LREs), including hepatic decompensation (ascites, hemorrhagic varices and encephalopathy) and Hepatocellular Carcinoma (HCC), as well as changes in liver stiffness during the follow-up period among patients who achieved a Sustained Virological Response (SVR) after treatment for chronic Hepatitis C Virus (HCV) infection. Methods A total of 218 patients with HCV were treated, and those who achieved an SVR were followed up for 3-years. Transient Elastography (TE) using FibroScan® was performed at various time points: before treatment, at the end of treatment, at 6-months post-treatment, at 1-year post-treatment, at 2-years post-treatment, and at 3-years post-treatment. Results At 6-months post-treatment, a Liver Stiffness Measurement (LSM) cutoff of > 19 KPa was identified, leading to a 14.5-fold increase in the hazard of negative outcomes, including decompensation and/or HCC. The analysis of relative changes in liver stiffness between pre-treatment and 6-months posttreatment revealed that a reduction in LSM of -10 % was associated with a -12 % decrease in the hazard of decompensation and/or HCC, with this trend continuing as the LSM reduction reached -40 %, resulting in a -41 % hazard of decompensation and/or HCC. Conversely, an increase in the relative change during this period, such as an LSM increase of +10 %, led to a + 14 % increase in the hazard of decompensation. In cases where this relative change in LSM was +50 %, the hazard of decompensation increased to +92. Conclusion Transient elastography using FibroScan® can be a good tool for monitoring HCV patients with SVR after treatment to predict LREs in the long term.

RESUMO

Healthcare systems in Latin America are broadly heterogeneous, but all of them are burdened by a dramatic rise in liver disease. Some challenges that these countries face include an increase in patients requiring a transplant, insufficient rates of organ donation, delayed referral, and inequitable or suboptimal access to liver transplant programs and post-transplant care. This could be improved by expanding the donor pool through the implementation of education programs for citizens and referring physicians, as well as the inclusion of extended criteria donors, living donors and split liver transplantation. Addressing these shortcomings will require national shifts aimed at improving infrastructure, increasing awareness of organ donation, training medical personnel, and providing equitable access to care for all patients.

RESUMO

•In this review, we described different murine models of carcinogenesis: classic models, new transgenic and combined models, that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic physiopathological, and environmental abnormalities. •Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches. •Cholangiocarcinoma has been highlighted, with an increase in prevalence. This review has an important role in understanding the pathophysiology and the development of new drugs. Background - This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective - A review through MEDLINE and EMBASE was performed to assess articles until August 2022.Methods - Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results - In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion - Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

Assuntos

Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Animais , Camundongos , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Carcinogênese , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/induzido quimicamente , Modelos Animais de Doenças , Neoplasias Hepáticas/patologia

RESUMO

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

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RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

RESUMO

The efficacy of systemic therapy for hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is poorly understood. In this study we evaluated the effects of sorafenib based on the expression of molecular markers related to major hepatocarcinogenesis pathways and angiogenesis in a NASH-related HCC model. Forty male rats were submitted to NASH-HCC induction through the combination of a high-fat and choline deficient diet and diethylnitrosamine (100 mg/L) administration in the drinking water for 13 and 16 weeks. After the induction period, the rats received daily gavage administration of saline solution (control) or Sorafenib (5 mg/kg/day) for 3 weeks. Thereafter, the animals were euthanized and samples from liver nodules were collected for histopathological analysis and immunohistochemical assessment of HEP-PAR-1, glutamine-synthetase, VEGF, survivin, ß-catenin and p53. A semi-quantitative score was used for VEGF, survivin and ß-catenin analysis. For p53, the percentage of positive cells was determined. Results were processed by Wilcoxon's test or Student's t-test. Both protocols efficiently induced HCC, most of them being moderately to poorly differentiated. Sorafenib-treated animals showed a decreased expression of VEGF and p53 in HCCs generated at 13 weeks when compared to control animals (p = 0.03; p = 0.04, respectively). No significant difference in ß-catenin and survivin were observed. There was a significant decrease in VEGF and p53 expression when comparing the two control groups (13 vs. 16 weeks, p < 0.01). p53 and VEGF are promising biomarkers for assessment of efficacy of Sorafenib, whereas survivin and ß-catenin were not found useful. Decreased immunohistochemical expression of p53 and VEGF in the 16 week control group may indicate a different metabolic status of HCC.