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INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. MATERIALS AND METHODS: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. RESULTS: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). CONCLUSIONS: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Cirrose Hepática , Inquéritos Nutricionais , Valor Preditivo dos Testes , Curva ROC , Índice de Gravidade de Doença , Humanos , Masculino , Estudos Transversais , Cirrose Hepática/diagnóstico , Cirrose Hepática/complicações , Feminino , Pessoa de Meia-Idade , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Idoso , Estados Unidos/epidemiologia , Fatores de Risco , Adulto , Área Sob a Curva , Distribuição de Qui-Quadrado , PrevalênciaRESUMO
INTRODUCTION AND OBJECTIVES: Autoimmune hepatitis (AIH) is a prevalent noninfectious liver disease. However, there is currently a lack of noninvasive tests appropriate for evaluating liver fibrosis in AIH patients. The objective of this study was to develop and validate a predictive model for noninvasive assessment of significant liver fibrosis (S ≥ 2) in patients to provide a reliable method for evaluating liver fibrosis in individuals with AIH. MATERIALS AND METHODS: The clinical data of 374 AIH patients were analyzed. A prediction model was established through logistic regression in the training set, and bootstrap method was used to validate the models internally. In addition, the clinical data of 109 AIH patients were collected for external verification of the model.The model was expressed as a nomogram, and area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and decision curve analysis were used to evaluate the accuracy of the prediction model. RESULTS: Logistic regression analysis revealed that age, platelet count (PLT), and the A/G ratio were identified as independent risk factors for liver fibrosis in AIH patients (P < 0.05). The diagnostic model that was composed of age, PLT and A/G was superior to APRI and FIB-4 in both the internal validation (0.872, 95%CI: 0.819-0.924) and external validation (0.829, 95%CI: 0.753-0.904). CONCLUSIONS: Our predictive model can predict significant liver fibrosis in AIH patients more accurately, simply, and noninvasively.
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Hepatite Autoimune , Cirrose Hepática , Nomogramas , Valor Preditivo dos Testes , Curva ROC , Humanos , Hepatite Autoimune/complicações , Hepatite Autoimune/sangue , Hepatite Autoimune/diagnóstico , Cirrose Hepática/diagnóstico , Cirrose Hepática/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Contagem de Plaquetas , Modelos Logísticos , Fatores de Risco , Reprodutibilidade dos Testes , China/epidemiologia , Técnicas de Apoio para a Decisão , Área Sob a Curva , Fatores Etários , Biomarcadores/sangue , Estudos Retrospectivos , Adulto Jovem , Povo Asiático , Idoso , População do Leste AsiáticoRESUMO
BACKGROUND & AIMS: In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis. METHODS: This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs. RESULTS: 161 T2D offspring and 78 controls, 10-46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034). CONCLUSIONS: The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Adolescente , Adulto , Criança , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Fibrose , Predisposição Genética para Doença , Genótipo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.
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Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.
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Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Masculino , Adulto , Obesidade/complicações , Obesidade/cirurgia , Fígado/patologia , Colesterol , Biópsia , Alanina TransaminaseRESUMO
BACKGROUND: Ataxia-telangiectasia (A-T) is a DNA repair disorder characterized by changes in several organs and systems. Advances in clinical protocols have resulted in increased survival of A-T patients, however disease progression is evident, mainly through metabolic and liver changes. OBJECTIVE: To identify the frequency of significant hepatic fibrosis in A-T patients and to verify the association with metabolic alterations and degree of ataxia. METHODS: This is a cross-sectional study that included 25 A-T patients aged 5 to 31 years. Anthropometric data, liver, inflammatory, lipid metabolism and glucose biomarkers (oral glucose tolerance test with insulin curve-OGTT) were collected. The Cooperative Ataxia Rating Scale was applied to assess the degree of ataxia. The following were calculated: Homeostasis Model Assessment-Insulin Resistance, Homeostasis Model Assessment-Adiponectin (HOMA-AD), Matsuda index, aspartate aminotransferase (AST): platelet ratio index, nonalcoholic fatty liver disease fibrosis score and BARD score. Liver ultrasonography and transient liver elastography by FibroScan® were performed. RESULTS: Significant hepatic fibrosis was observed in 5/25 (20%). Patients in the group with significant hepatic fibrosis were older (p < 0.001), had lower platelet count values (p = 0.027), serum albumin (p = 0.019), HDL-c (p = 0.013) and Matsuda index (p = 0.044); and high values of LDL-c (p = 0.049), AST (p = 0.001), alanine aminotransferase (p = 0.002), gamma-glutamyl transferase (p = 0.001), ferritin (p = 0.001), 120-min glycemia by OGTT (p = 0.049), HOMA-AD (p = 0.016) and degree of ataxia (p = 0.009). CONCLUSIONS: A non-invasive diagnosis of significant hepatic fibrosis was observed in 20% of A-T patients associated with changes in liver enzymes, ferritin, increased HOMA-AD, and the severity of ataxia in comparison with patients without hepatic fibrosis.
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Ataxia Telangiectasia , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Estudos Transversais , Cirrose Hepática , FígadoRESUMO
INTRODUCTION AND OBJECTIVES: The association between type 2 diabetes, non-alcoholic fatty liver disease, and liver fibrosis is well established, but it is unknown whether complications of type 2 diabetes influence fibrosis levels. We defined the complications of type 2 diabetes by the presence of diabetic nephropathy, retinopathy, or neuropathy and aimed to evaluate their association with the degree of liver fibrosis measured by the fibrosis-4 (FIB-4) index. MATERIALS AND METHODS: This is a cross-sectional study evaluating the association of type 2 diabetes complications with liver fibrosis. A total of 2389 participants were evaluated from a primary care practice. FIB-4 was evaluated as a continuous and categorical measure using linear and ordinal logistic regression. RESULTS: Patients with complications were older, had higher hemoglobin A1c, and a higher median FIB-4 score (1.34 vs. 1.12, P<0.001). On adjusted analysis, type 2 diabetes complications were associated with higher fibrosis by continuous FIB-4 score (Beta-coefficient: 0.23, 95% confidence interval [CI]: 0.004-1.65) and demonstrated increased odds of fibrosis by categorical FIB-4 score (odds ratio [OR]: 4.48, 95% CI: 1.7-11.8, P=0.003), independent of hemoglobin A1c level. CONCLUSIONS: The presence of type 2 diabetes complications is associated with the degree of liver fibrosis, independent of hemoglobin A1c level.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas , Estudos Transversais , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Fibrose , Complicações do Diabetes/complicaçõesRESUMO
BACKGROUND: MicroRNAs are involved in gene regulation in several common liver diseases and may play an essential role in activating hepatic stellate cells. The role of these post-transcriptional regulators in schistosomiasis needs to be further studied in populations from endemic areas for a better understanding of the disease, the development of new therapeutic approaches, and the use of biomarkers for the prognosis of schistosomiasis. AREAS COVERED: We performed a systematic review to describe the main human microRNAs identified in non-experimental studies associated with aggravation of the disease in people infected with Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum). Structured searches were carried out in PubMed, Medline, Science Direct, Directory of Open Access Journals, Scielo, Medcarib, and Global Index Medicus databases without time and language restrictions. This is a systematic review following the guidelines of the PRISMA platform. EXPERT OPINION: The miR-146a-5p, miR-150-5p, let-7a-5p, let-7d-5p, miR-92a- 3p, and miR-532-5p are associated with liver fibrosis in schistosomiasis caused by S. japonicum, revealing that these miRNAs that have been shown to be associated with liver fibrosis are good targets for new studies that evaluate their potential as a biomarker or even treating liver fibrosis in schistosomiasis.
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MicroRNAs , Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Animais , Humanos , MicroRNAs/genética , Esquistossomose Japônica/complicações , Esquistossomose Japônica/genética , Esquistossomose/complicações , Esquistossomose/genética , Cirrose Hepática/genética , Schistosoma japonicum/genética , BiomarcadoresRESUMO
We aimed to determine the biomarker performance of the proteolytic enzymes cathepsin B (Cat B) and plasma kallikrein (PKa) and transforming growth factor (TGF)-ß to detect hepatic fibrosis (HF) in chronic hepatitis C (CHC) patients. We studied 53 CHC patients and 71 healthy controls (HCs). Hepatic-disease stage was determined by liver biopsies, aminotransferase:platelet ratio index (APRI) and Fibrosis (FIB)4. Hepatic inflammation and HF in CHC patients were stratified using the METAVIR scoring system. Cat-B and PKa activities were monitored fluorometrically. Serum levels of TGF-ß (total and its active form) were determined using ELISA-like fluorometric methods. Increased serum levels of Cat B and PKa were found (p < 0.0001) in CHC patients with clinically significant HF and hepatic inflammation compared with HCs. Levels of total TGF-ß (p < 0.0001) and active TGF-ß (p < 0.001) were increased in CHC patients compared with HCs. Cat-B levels correlated strongly with PKa levels (r = 0.903, p < 0.0001) in CHC patients but did not correlate in HCs. Levels of Cat B, PKa and active TGF-ß increased with the METAVIR stage of HF. Based on analyses of receiver operating characteristic (ROC) curves, Cat B and PKa showed high diagnostic accuracy (area under ROC = 0.99 ± 0.02 and 0.991 ± 0.007, respectively) for distinguishing HF in CHC patients from HCs. Taken together, Cat B and PKa could be used as circulating biomarkers to detect HF in HCV-infected patients.
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Resumen Introducción: La enfermedad del hígado graso no alcohólico (EHGNA) o hígado graso se caracteriza por una excesiva acumulación de grasa en el hígado, es un desorden metabólico con una prevalencia mundial cercana al 25 %, con un espectro de daño hepático que abarca la esteatosis sin fibrosis, esteatohepatitis con fibrosis variable y la cirrosis o grado máximo de fibrosis, dicha fibrosis determina el pronóstico y los desenlaces de la enfermedad. Objetivo: evaluar la asociación entre el índice de masa corporal (IMC) y el grado de fibrosis hepática en pacientes con diagnóstico de hígado graso en un centro de hepatología en la ciudad de Bogotá, Colombia. Pacientes y métodos: se realiza un estudio de casos y controles de pacientes con diagnóstico de hígado graso, a quienes se les haya realizado elastografía en tiempo real (Supersonic). Se tomó la información de pacientes con diagnóstico de hígado graso que cumplieron criterios de inclusión. Las variables continuas se describieron utilizando medidas de tendencia central y desviación estándar. Las variables categóricas se describieron con números y porcentajes. Se consideró un intervalo de confianza (IC) del 95 % como estadísticamente significativo. Resultados: se incluyeron 361 pacientes, de los cuales el 95,2 % (n = 344 pacientes) presentó algún grado de alteración (12 % fibrosis mínima, 33 % fibrosis moderada, 34 % fibrosis grave y 16 % cirrosis) y solo el 5 % mostró un hígado normal. No tener un adecuado peso se relaciona con fibrosis grave F3, odds ratio (OR): 3,24 (IC: 1,03-10) y cirrosis F4, OR: 2,33 (IC: 2,33-42,99). No se encontraron diferencias estadísticamente significativas entre la alteración del IMC y cualquier grado de fibrosis (OR: 2,74; IC: 0,90-8,40). La presencia de diabetes mellitus (DM) presenta una probabilidad de riesgo de 10 veces de terminar en cirrosis F4, en especial, con mal control de la enfermedad (OR: 5,16; IC: 1,23-30,33). Conclusión: existe una asociación entre el IMC, el perfil glicémico anormal y el desarrollo de fibrosis grave y avanzada. En la práctica clínica, son necesarias una mayor vigilancia y evaluación de los pacientes con hígado graso, con el fin de evitar la progresión de la fibrosis.
Abstract Introduction: Non-alcoholic fatty liver disease (NAFLD) or fatty liver, is characterized by an excessive accumulation of fat in the liver, is a metabolic disorder with a worldwide prevalence close to 25%, with a spectrum of liver damage that covers the steatosis without fibrosis, steatohepatitis with variable fibrosis and cirrhosis or maximum degree of fibrosis, this fibrosis determines prognosis and outcomes in the disease. Objective: To evaluate the association between body mass index and the degree of liver fibrosis in patients diagnosed with fatty liver in a hepatology center in the city of Bogotá, Colombia. Patients and methods: A case-control study is carried out with patients diagnosed with fatty liver, who have undergone real-time elastography (Supersonic). Information was taken from patients diagnosed with fatty liver who met the inclusion criteria. Continuous variables were described using measures of central tendency and standard deviation. Categorical variables were described with numbers and percentages. A 95% confidence interval was considered statistically significant. Results: 361 patients were included, of which 95.2% (n=344) presented some degree of alteration (12% minimal fibrosis, 33% moderate fibrosis, 34% severe fibrosis and 16% cirrhosis) and only 5% showed a liver normal. Not having an adequate weight is related to severe fibrosis F3 OR 3.24 (1.03-10) and cirrhosis F4 OR 2.33 (2.33-42.99). No statistically significant differences were found between altered body mass index and any degree of fibrosis OR 2.74 (0.90-8.40). The presence of DM presents a 10-fold risk probability of ending in F4 cirrhosis, especially with poor disease control OR 5.16 (1.23-30.33). Conclusion: There is an association between abnormal body mass index and glycemic profile and the development of severe and advanced fibrosis. It is necessary in clinical practice, greater surveillance and evaluation of patients with fatty liver, in order to prevent the progression of fibrosis.