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OBJECTIVE: The role of Non-Alcoholic Fatty Liver Disease (NAFLD) on antiviral response in Chronic Hepatitis B (CHB) remains unclear. Previous studies mainly focus on the impact of the Non-Alcoholic Fatty Liver (NAFL) on antiviral efficacy, whereas the role of Non-Alcoholic Steatohepatitis (NASH) has not been highlighted. The authors aimed to investigate the association of NAFLD (NAFL and NASH), viral and histological characteristics with antiviral response. METHODS: The authors collected data of treatment-naïve CHB patients who underwent liver biopsy. All these patients received antiviral monotherapy and 48-week follow-up. The antiviral response was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the variables associated with antiviral response. RESULTS: Overall, 120 treatment-naïve CHB patients were enrolled, with 49.2 % (59/120) of them were complicated by NAFLD. Male (Odd Ratio [OR = 4.222], 95 % Confidence Interval [95 % CI 1.620-11.003]) and overweight (OR = 8.709, 95 % CI 3.355-22.606) were independent predictors for concurrent NAFLD. After 48-week follow-up, the authors found that the overall antiviral response did not differ between CHB patients with and without concomitant NAFL/NASH (p > 0.05). High viral load (Hazard Ratio [HR = 0.522], 95 % CI 0.286-0.952), advanced fibrosis (HR = 2.426, 95 % CI 1.256-4.686), and moderate-to-severe interface hepatitis (HR = 2.541, 95 % CI 1.406-4.592) were significantly correlated with antiviral response after 8-week follow-up. CONCLUSION: Neither NAFL nor NASH had an impact on antiviral therapy for CHB. It was low hepatitis B load, advanced fibrosis, and moderate-to-severe interface hepatitis that contributed to the virological response.
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Antivirales , Hepatitis B Crónica , Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/patología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/patología , Femenino , Antivirales/uso terapéutico , Adulto , Biopsia , Persona de Mediana Edad , Hígado/patología , Resultado del Tratamiento , Carga Viral , Estimación de Kaplan-Meier , Estudios RetrospectivosRESUMEN
Several models of mice-fed high-fat diets have been used to trigger non-alcoholic steatohepatitis and some chemical substances, such as carbon tetrachloride. The present study aimed to evaluate the joint action of a high-fat diet and CCl4 in developing a short-term non-alcoholic steatohepatitis model. C57BL6/J mice were divided into two groups: standard diet-fed (SD), the high-fat diet-fed (HFD) and HFD + fructose-fed and carbon tetrachloride (HFD+CCl4). The animals fed with HFD+CCl4 presented increased lipid deposition compared with both SD and HFD mice. Plasma cholesterol was increased in animals from the HFD+CCl4 group compared with the SD and HFD groups, without significant differences between the SD and HFD groups. Plasma triglycerides showed no significant difference between the groups. The HFD+CCl4 animals had increased collagen deposition in the liver compared with both SD and HFD groups. Hydroxyproline was also increased in the HFD+CCl4 group. Liver enzymes, alanine aminotransferase and aspartate aminotransferase, were increased in the HFD+CCl4 group, compared with SD and HFD groups. Also, CCl4 was able to trigger an inflammatory process in the liver of HFD-fed animals by promoting an increase of â¼2 times in macrophage activity, â¼6 times in F4/80 gene expression, and pro-inflammatory cytokines (IL-1b and TNFa), in addition to an increase in inflammatory pathway protein phosphorylation (IKKbp). HFD e HFD+CCl4 animals increased glucose intolerance compared with SD mice, associated with reduced insulin-stimulated AKT activity in the liver. Therefore, our study has shown that short-term HFD feeding associated with fructose and CCl4 can trigger non-alcoholic steatohepatitis and cause damage to glucose metabolism.
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Tetracloruro de Carbono , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Hígado , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Animales , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Triglicéridos/sangre , Triglicéridos/metabolismo , Fructosa/efectos adversosRESUMEN
Unmet needs exist in metabolic dysfunction-associated steatotic liver disease (MASLD) risk stratification. Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited. Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors. With this aim, omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades. While the research in this field is thriving, much of the publication has been haphazard, often using single-omics data and specimen sets of convenience, with many identified candidate biomarkers but lacking clinical validation and utility. If we incorporate these biomarkers to direct patients' management, it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual, analytically valid test useful in MASLD clinical practice is rigorous and, therefore, not easily accomplished. This article presents an overview of this area's current state, the conceivable opportunities and challenges of omics-based laboratory diagnostics, and a roadmap for improving MASLD biomarker research.
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Biomarcadores , Metabolómica , Humanos , Biomarcadores/análisis , Biomarcadores/metabolismo , Metabolómica/métodos , Proteómica/métodos , Genómica/métodos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Medición de Riesgo/métodos , Hígado/patología , Hígado/metabolismo , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/sangre , Cirrosis Hepática/patologíaRESUMEN
INTRODUCTION AND OBJECTIVES: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups. MATERIALS AND METHODS: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death. RESULTS: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25). CONCLUSIONS: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes.
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Costo de Enfermedad , Costos de la Atención en Salud , Enfermedad del Hígado Graso no Alcohólico , Sistema de Registros , Humanos , Enfermedad del Hígado Graso no Alcohólico/economía , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Dinamarca/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Biopsia/economía , Cirrosis Hepática/economía , Cirrosis Hepática/mortalidad , Cirrosis Hepática/epidemiología , Anciano , Seguro por Discapacidad/economía , Seguro por Discapacidad/estadística & datos numéricosRESUMEN
ABSTRACT BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.
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INTRODUCTION: Metabolic-associated fatty liver disease (MAFLD) previously known but still debatable, as nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease and subsequent cirrhosis worldwide, accounting for around 30% of liver diseases. The change in its nomenclature has been brought about by the novel discoveries regarding its pathogenesis, in which metabolic dysfunction plays the most important role. It is widely known that for every disease, the treatment should always be targeted toward the underlying etiology and pathogenesis. AREAS COVERED: MAFLD/NAFLD pathogenesis is heterogeneous, and includes multiple gene polymorphisms, presence of insulin resistance, as well as concomitant diseases that contribute to the disease onset and progression. As a result of this, even though lifestyle modification (owing to metabolic abnormalities) is the first line of treatment, multiple drugs have been tested to target each of the known pathways leading to MAFLD/NAFLD and progression of steatohepatitis. We aim to review the most relevant information regarding previous and ongoing research and recommendations regarding treatment of MAFLD/NAFLD. EXPERT OPINION: Combination therapies associated to weight loss and exercise will be the optimal approach for these patients. It is important to evaluate each patient to select the specific combination according to patient characteristics.
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Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Cirrosis Hepática/patología , Estilo de VidaRESUMEN
Metabolic-associated fatty liver disease (MAFLD) is the main condition of altered liver enzymes worldwide. With a constant increase in liver hospitalizations, MAFLD is the second cause of cirrhosis and soon will be the first cause of liver transplantation. Early recognition of MAFLD and a personalized approach are essential to its treatment. This case study presents personalized management of a patient with MAFLD with advanced fibrosis and severe steatosis. The impact of silymarin use, concomitant treatment with diet, exercise, insulin sensitizers and antifibrotic agents, was evaluated. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.
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Cirrhosis is an emerging major cause of the development of hepatocellular carcinoma (HCC), but in non-alcoholic fatty liver disease (NAFLD), up to 50% of patients with HCC had no clinical or histological evidence of cirrhosis. It is currently challenging to propose general recommendations for screening patients with NAFLD without cirrhosis, and each patient should be evaluated on a case-by-case basis based on the profile of specific risk factors identified. For HCC screening in NAFLD, a valid precision-based screening is needed. Currently, when evaluating this population of patients, the use of non-invasive methods can guide the selection of those who should undergo a screening and surveillance program. Hence, the objective of the present study is to review the epidemiology, the pathophysiology, the histopathological aspects, the current recommendations, and novel perspectives in the surveillance of non-cirrhotic NAFLD-related HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Factores de Riesgo , FibrosisRESUMEN
INTRODUCTION AND OBJECTIVES: Recent translational research indicated a bidirectional relationship between NASH (non-alcoholic steatohepatitis) and periodontitis; however, few clinical cohorts have studied this in detail. Thus we investigated this assumed association in a well-defined cohort. MATERIALS AND METHODS: Data were generated prospectively for 132 patients (32 patients with NASH and 100 unselected, consecutively collected, anonymized controls from a local dental practice): detailed periodontal parameters, i.e., pocket-probing-depths (PPD), bleeding-on-probing (BOP), plaque-index, and utilization of dental care were assessed and correlated with relevant hepatic parameters (liver stiffness via fibroscan, AST, ALT, bilirubin, and MELD-score). Gingiva samples were tested for Porphyromonas gingvalis (P.g.) and Actinobacillus actinomyctemcomitans (A.a.) by PCR. RESULTS: 87.5% of NASH patients and 47% of controls suffered from moderate to severe periodontitis (p=0.01). Liver stiffness was significantly correlated with elevated PPD (p=0.02) and BOP (p=0.03). 34 % of the NASH patients did not make use of regular dental health care. In these patients, AST (p=0.04), MELD score (p<0.01), and liver stiffness (p=0.01) were significantly elevated compared to those who see a dentist regularly. The severity of NASH was not associated with the intraoral detection of P.g. and A.a. CONCLUSIONS: The present study suggests that NASH might be associated with periodontitis, irrespective of the intraoral presence of P.g. and A.a. Moreover, regular dental care utilization might mitigate the course of NASH, and patients should be reminded by their hepatologists of the importance of regular dental visits. Future studies should investigate the role of regular dental care and additional anti-inflammatory treatments of the oral cavity.
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Enfermedad del Hígado Graso no Alcohólico , Enfermedades Periodontales , Periodontitis , Humanos , Prevalencia , Porphyromonas gingivalis , Enfermedades Periodontales/diagnóstico , Enfermedades Periodontales/epidemiología , Enfermedades Periodontales/complicaciones , Periodontitis/diagnóstico , Periodontitis/epidemiología , Periodontitis/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now considered the most common chronic liver disease worldwide. NAFLD is related to changes in lipid metabolism and is characterized by the increase or accumulation of fat in hepatocytes that may progress to nonalcoholic steatohepatitis (NASH), which leads to the appearance of inflammatory processes. Treatment consists of changes in diet, physical activity, and weight control; however, these disorders represent a health problem and require the development of novel alternatives to treatment and prevention. NAFLD/NASH are strongly associated with other disorders, such as metabolic syndrome (MetS); in fact, NAFLD is considered the hepatic manifestation of MetS. These disorders are related to other components of MetS, including dyslipidemia, which is characterized by an imbalance in blood cholesterol and triglyceride levels. Prebiotics and probiotics benefit from treating and preventing several ailments, including liver diseases. Specifically, in dyslipidemia, NAFLD, and NASH, probiotics play a fundamental role in conducting the biotransformation of primary bile acids into secondary bile acids, which generally have important activity as immunomodulators and metabolism regulators. The mechanisms of action of pre and probiotics involve the activity of bile acid receptors, such as FXR and TGR-5, and the events resulting from their activation. Therefore, prebiotics and probiotics may be reasonable options to prevent and treat metabolic- related liver diseases.
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Dislipidemias , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Humanos , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Prebióticos , Hígado/metabolismo , Probióticos/uso terapéutico , Síndrome Metabólico/metabolismo , Dislipidemias/tratamiento farmacológico , Dislipidemias/metabolismo , Ácidos y Sales Biliares/metabolismoRESUMEN
ABSTRACT Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.
RESUMO A doença metabólica e doença hepática gordurosa metabólica estão aumentando a prevalência mundial e, portanto, espera-se um número maior de carcinoma hepatocelular (CHC) relacionado à doença hepática gordurosa não alcóolica (DHGNA) nos próximos anos. Esta revisão descreve os fatores de risco associados ao CHC em pacientes com DHGNA. A presença de cirrose hepática é a preponderante. Sexo masculino, variantes do gene PNPLA3, diabetes e obesidade também parecem predispor ao desenvolvimento de CHC, mesmo em indivíduos não cirróticos. Até agora, modificações significativas no estilo de vida, incluindo controle glicêmico e tratamento da obesidade, são terapias eficazes para DHGNA/ Esteatohepatite não-alcoolica e, portanto, provavelmente, também para CHC. Alguns medicamentos que propunham-se diminuir a atividade inflamatória e fibrose, bem como a obesidade, foram estudados. Outros dados sugeriram a possibilidade de quimioprevenção do CHC. Até o momento, no entanto, não há evidências definitivas para o uso rotineiro desses medicamentos. Esperamos, no futuro, poder traçar o perfil de pacientes com maior risco de DHGNA-CHC e traçar estratégias para diagnóstico precoce e prevenção.
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Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.
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Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg/kg, i.p.) of CCl4. Caffeine was administered at 50 mg/kg p.o. The effects of HFSCD+CCl4 and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl4-treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4/MAPK/NF-κB signaling pathway.
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FN-kappa B , Enfermedad del Hígado Graso no Alcohólico , Animales , Cafeína/farmacología , Cafeína/uso terapéutico , Inflamasomas/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratas , Transducción de Señal , Receptor Toll-Like 4/metabolismoRESUMEN
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of ß-hydroxyphosphocarnitine (ß-HPC) on NASH induced in rats. METHODS: NASH was produced via the ad libitum daily chronic administration of a fructose solution (400 kcal) for 9 weeks, an oral dose of fat solution (16 kcal) for 7 weeks and a subcutaneous injection of CCl4 (30%) two times a week for 2 weeks to Wistar rats. To evaluate the effect of ß-HPC, a dose of 100 mg/kg was administered perorally for 4 weeks and its biochemical and hepatic effects on rats with NASH were analyzed. Serum levels of glucose, triglycerides, cholesterol, and liver enzymes were quantified. Histological changes were evaluated on slices stained with H&E, trichromic and PAS. Glycogen content was measured in liver samples. α-SMA and SREBP-1 immunopositive cells were identified in liver tissue. RESULTS: NASH was characterized by elevated triglycerides, elevated liver damage enzymes, and the presence of necrosis, inflammation, steatosis, and fibrosis. Significant amounts of glycogen were found, along with α-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with ß-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in α-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. ß-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with ß-HPC did not show any alterations in liver enzyme function. CONCLUSIONS: Our research shows that ß-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting ß-HPC could be potentially used in the treatment of NASH.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Carnitina/análogos & derivados , Colesterol , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Fructosa/metabolismo , Fructosa/farmacología , Fructosa/uso terapéutico , Glucosa/metabolismo , Glucógeno/metabolismo , Glucógeno/farmacología , Glucógeno/uso terapéutico , Inflamación/tratamiento farmacológico , Hígado , Cirrosis Hepática/metabolismo , Necrosis , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Organofosfatos , Ratas , Ratas Wistar , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/farmacología , TriglicéridosRESUMEN
ABSTRACT Background Insulin resistance (IR), assessed by different criteria, is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). More recently with the characterization of this metabolic dysfunction-associated fatty liver disease (MAFLD), one of the proposed criteria for this diagnosis has been the determination of the homeostasis model assessment-insulin resistance (HOMA-IR). Objective: The purpose of this study was to evaluate the relationship of HOMA-IR>2.5 with clinical, metabolic, biochemical and histological data obtained in non-diabetic patients diagnosed with NAFLD by liver biopsy. Methods: Cross-sectional, retrospective study was carried out with data from 174 adult individuals of both genders with non-diabetics NAFLD, without obvious signs of portal hypertension. The body mass index (BMI) was classified according to the World Health Organization (1998), and the metabolic syndrome by the criteria of NCEP-ATP-III. Biochemical tests were evaluated using an automated method and insulinemia through immunofluorometric assay. Histological findings were classified according to Kleiner et al. (2005). Results: The mean age of the studied population was 53.6±11.2 years, with 60.3% being female. The average BMI was 30.3 kg/m2 and 75.9% of the patients had increased waist circumference. Among evaluated metabolic parameters, there was a higher prevalence of metabolic syndrome (MS) in patients with HOMA-IR>2.5, with no statistical difference in relation to BMI between studied groups. Values of liver enzymes and serum ferritin were significantly higher in patients with this marker of IR, who had a higher prevalence of non-alcoholic steatohepatitis (NASH) and advanced liver fibrosis. In the multivariate analysis, the clinical diagnosis of MS, hyperferritinemia and the presence of NASH in the liver biopsy were the factors independently associated with the presence of altered HOMA-IR. Conclusion: HOMA-IR values >2.5 identify patients with NAFLD with distinct clinical and metabolic characteristics and with a greater potential for disease progression, which validates this parameter in the identification of patients with MAFLD.
RESUMO Contexto A resistência à insulina (RI), avaliada por diferentes critérios, é um fator importante na patogênese da doença hepática gordurosa não alcoólica (DHGNA). Mas, recentemente, com a caracterização desta disfunção metabólica associada com a doença hepática gordurosa (DGH), um dos critérios propostos para este diagnóstico tem sido a determinação do modelo de avaliação da homeostase-resistência à insulina (HOMA-IR). Objetivo: O objetivo deste estudo foi avaliar a relação do HOMA-IR> 2,5 com dados clínicos, metabólicos, bioquímicos e histológicos obtidos em pacientes não diabéticos diagnosticados com DHGNA por biópsia hepática. Métodos Estudo transversal, retrospectivo, com dados de 174 indivíduos adultos de ambos os sexos com DHGNA não-diabética, sem sinais evidentes de hipertensão portal. O índice de massa corporal (IMC) foi classificado de acordo com a Organização Mundial da Saúde (1998) e a síndrome metabólica pelos critérios do NCEP-ATP-III. Os exames bioquímicos foram avaliados pelo método automatizado e a insulinemia por imunofluorometria. Os achados histológicos foram classificados de acordo com Kleiner et al. (2005). Resultados: A média de idade da população estudada foi de 53,6±11,2 anos, sendo 60,3% do sexo feminino. O IMC médio foi de 30,3 kg/m2 e 75,9% dos pacientes apresentaram circunferência da cintura aumentada. Entre os parâmetros metabólicos avaliados, houve maior prevalência de síndrome metabólica (SM) em pacientes com HOMA-IR >2,5, sem diferença estatística em relação ao IMC entre os grupos estudados. Os valores das enzimas hepáticas e da ferritina sérica foram significativamente maiores nos pacientes com este marcador de RI, que apresentaram maior prevalência de esteato-hepatite não alcoólica (EHNA) e fibrose hepática avançada. Na análise multivariada, o diagnóstico clínico de SM, hiperferritinemia e a presença de EHNA na biópsia hepática foram os fatores independentemente associados à presença de HOMA-IR alterado. Conclusão: Valores de HOMA-IR >2,5 identificam pacientes com DHGNA com características clínicas e metabólicas distintas e com maior potencial de progressão da doença, o que valida esse parâmetro na identificação de pacientes com DHG.
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Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host's metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Simbióticos , Humanos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Prebióticos , Probióticos/uso terapéuticoRESUMEN
ABSTRACT BACKGROUND: In Latin America, liver cancer is one of the top causes of cancer mortality. It is the fifth most common cause of death among malignant tumors in Mexico and is the leading cause in Hidalgo State (43.8% of the population living in poverty). OBJECTIVE: To conduct a correlational analysis on the main risk factors for liver cancer in Hidalgo State, Mexico, including municipal disaggregation and comparison with the national level. DESIGN AND SETTING: Cross-sectional, correlational, descriptive and comparative epidemiological study using Mexican governmental databases covering 1990-2019. METHODS: A comprehensive review of the databases of the General Directorate of Health Information (DGIS) was performed to analyze official death figures, hospital discharges and national and municipal population projections, using specific search criteria defined in the Global Burden of Disease classification, based on the risk factors for liver cancer. RESULTS: Liver cancer rates showed an evident rise in Hidalgo (183%), moving from 21st place in Mexico in 1990 to 9th place in 2019. This increase was correlated with alcoholism. An increasing trend for liver cancer deaths, of 133.89%, is projected for 2030. Females and the population over 60 years of age are more affected. There are some critical regions with liver cancer death rates twice the national rate or more. CONCLUSION: Targeted effective public health strategies should be structured by identifying, characterizing and regionalizing critical marginalized municipalities that are vulnerable to alcoholism and other risk factors for liver cancer. This approach may be helpful for other states in Mexico or similar countries.
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INTRODUCTION AND OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that can progress to liver cirrhosis, liver failure and hepatocellular carcinoma. It is the second leading cause of liver transplant in the US. We aim to investigate the prevalence, demographics and risk factors NASH patients in the US. PATIENTS AND METHODS: We used a large database (Explorys IBM) that aggregates electronic health records from 26 nationwide healthcare systems. We identified adults with NASH between 2010-2020. Demographics including age, gender and race were collected. NASH risk factors including Diabetes Millets (DM), Hyperlipidemia (HLD), Hypertension (HTN) and Obesity were also collected. Cochran-Armitage test was used to assess the statistical significance of year-by-year trend. Univariable and multivariable logistic regression were used to estimate the odds ratio (OR) of risk factors. RESULTS: NASH annual prevalence rate increased from 1.51% in 2010 to 2.79% in 2020 (p < 0.0001). The proportion of patients with NASH by gender was 54.1% female vs 45.9% male (OR 1.04 [0.91-1.11]). Caucasian had higher odds of NASH than non-Caucasian (OR 1.42 [1.31-1.54]). NASH is strongly associated with DM and obesity (OR 18.61 [17.35-19.94]) and (OR 20.97 [17.87-23.21]), respectively. Other components of metabolic syndrome were associated with NASH to a lesser degree; HTN (OR 3.24 [3.20-3.28]) and HLD (OR 4.93 [4.85-4.01]). CONCLUSION: The prevalence of NASH has significantly increased in the US in the last decade. This is likely related to the increased prevalence of risk factors as well as increased awareness of the disease.
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Diabetes Mellitus , Hipertensión , Neoplasias Hepáticas , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Adulto , Diabetes Mellitus/epidemiología , Femenino , Humanos , Hipertensión/epidemiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Neoplasias Hepáticas/complicaciones , Masculino , Síndrome Metabólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become a challenge in public health, as the prevalence of obesity and overweight has been increasing. It has been observed that serum ferritin (SF) levels are commonly elevated in NAFLD patients. PURPOSE: To assess the relationship between SF levels and NAFLD, exploring the role of SF as a non-invasive marker of NAFLD. METHODS: Clinical, anthropometric, laboratory, and histological data of patients with obesity who underwent bariatric surgery in a reference center in Brazil were retrospectively evaluated. Data were collected in the preoperative period up to the first year postoperatively. RESULTS: A total of 431 patients were analyzed. The prevalence of hyperferritinemia was 18% in the preoperative period and 14% 1 year after the surgery. After multiple regression analysis, elevated SF was not an independent predictor of steatosis, non-alcoholic steatohepatitis (NASH), or liver fibrosis. CONCLUSIONS: Increased SF levels are common in patients with NAFLD; however, SF was not considered an independent predictor of steatosis, NASH, or fibrosis.