RESUMO
Previous studies have confirmed the affiliation between specific inflammatory cytokines and Hepatic fibrosis (HF); however, contradictions remain in the causality. The study implemented a bidirectional two-sample Mendelian randomization (MR) analysis with published statistics derived from Genome-wide Association Studies (GWAS) to investigate casualties between inflammatory cytokines and HF. Additionally, MR analysis was also introduced to consider if 1400 blood metabolites act as the key mediators in this process. Single nucleotide polymorphisms (SNPs) with strong correlations to inflammatory factors were selected for multiple MR analyses in this study. The inverse variance weighted method (IVW) was chosen as the principal analysis, and the others as the supportive. Besides, sensitivity tests were involved to identify potential heterogeneity and pleiotropic level. IVW methods revealed that a relatively high level of prediction-based monocyte chemoattractant protein-4 (MCP-4) (95% CI: 1.014-3.336, Pâ =â .045), along with neurturin (NRTN) (95% CI: 1.204-4.004, Pâ =â .010), may increase the risk of HF; while programmed cell death 1 ligand 1 (PD-L1) (95% CI: 0.223-0.928, Pâ =â .030), showed a protective effect on HF. No significant statistical differences were detected on any other inflammatory cytokines, nor did the impact of HF genetic predisposition on the 91 circulating inflammatory cytokines-related characteristics.
Assuntos
Antígeno B7-H1 , Estudo de Associação Genômica Ampla , Cirrose Hepática , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Cirrose Hepática/genética , Cirrose Hepática/sangue , Antígeno B7-H1/genética , Antígeno B7-H1/sangue , Predisposição Genética para DoençaRESUMO
Background: The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD. Results: Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters. Conclusion: A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.
Assuntos
Alanina Transaminase , Aspartato Aminotransferases , Biomarcadores , Hepatopatia Gordurosa não Alcoólica , Inquéritos Nutricionais , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/sangue , Masculino , Feminino , Estudos Transversais , Alanina Transaminase/sangue , Pessoa de Meia-Idade , Adulto , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Estados Unidos/epidemiologia , Índice de Gravidade de Doença , Fatores de Risco , Adulto Jovem , Cirrose Hepática/epidemiologia , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Prevalência , Idoso , AdolescenteRESUMO
BACKGROUND: The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) has emerged as a promising biomarker for assessing inflammation and lipid dysregulation. Increasing evidence indicates that these metabolic disturbances play a crucial role in the development of metabolic dysfunction-associated steatotic liver disease(MASLD). This study aims to investigate the association between NHR, MASLD, and liver fibrosis. METHODS: This cross-sectional study analyzed data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multivariate logistic regression models were used to investigate the association between NHR and both MASLD and liver fibrosis. Smoothed curve fitting and threshold effect analysis were performed to detect potential nonlinear relationships. Subgroup analyses were conducted to assess the consistency of these associations across different groups. RESULTS: The study involved 4,761 participants. We observed a significant positive association between NHR and MASLD (OR = 1.20, 95% CI: 1.09-1.31). However, there was no significant association between NHR and liver fibrosis (OR = 1.01; 95% CI: 0.94-1.09). The analysis of smoothed curve fitting and threshold effect revealed an inverted U-shaped relationship between NHR and MASLD, with a turning point at 5.63. CONCLUSION: Our findings indicate a positive correlation between elevated NHR levels and MASLD prevalence. However, we did not observe a significant association between NHR and liver fibrosis prevalence. Further prospective research is needed to validate these findings in a longitudinal setting.
Assuntos
HDL-Colesterol , Cirrose Hepática , Neutrófilos , Inquéritos Nutricionais , Humanos , Estudos Transversais , Masculino , Feminino , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Pessoa de Meia-Idade , HDL-Colesterol/sangue , Estados Unidos/epidemiologia , Adulto , Biomarcadores/sangue , Idoso , Fígado Gorduroso/sangue , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/patologiaRESUMO
Metabolic dysfunction-associated steatohepatitis (MASH) is a rising global disease signaling the urgent need for non-invasive tests (NITs). Recent work demonstrated that dynamic 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) imaging can identify MASH by measuring liver glucose transport rate, K1, and liver CT attenuation. By combining dynamic PET/CT with the serum-based fibrosis-4 (FIB-4) test, we were able to better distinguish clinical MASH from fibrotic subtypes, enabling determination of the core tenets of MASH: steatosis, inflammation, and fibrosis. Future studies using FDG-PET technology can further enable concomitant prediction of MASH severity and extrahepatic comorbidities such as cardiovascular disease.
Assuntos
Biomarcadores , Fluordesoxiglucose F18 , Cirrose Hepática , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Biomarcadores/sangue , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/sangue , Masculino , Feminino , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodosRESUMO
BACKGROUND: To date, there is an ongoing debate regarding the ability to predict PVT development using markers of FVIII or FVIII/PC ratio. This study presents evidence-based medical findings on the influence of FVIII activity levels and FVIII/PC values in the formation of PVT in cirrhosis. METHODS: The search for original studies on risk factors for portal vein thrombosis (PVT) associated with cirrhosis was conducted, which primarily focused on comparing circulating FVIII activity levels or FVIII/PC ratio in cirrhotic patients with and without PVT. The quality of evidence from each study was assessed using the Newcastle-Ottawa Scale. RESULTS: The meta-analysis included a total of 10 original studies. In total, 2250 cirrhotic patients were included, with 414 having PVT and 1836 without PVT. The pooled analysis using a random-effects model showed no significant difference in standardized mean difference (SMD) for FVIII activity levels in cirrhotic patients with or without PVT (SMD = 0.12, 95% CI=-0.46 to 0.70, P = 0.68), but there was significant heterogeneity (I2 = 95.52%, P = 0.00). Meta-regression analysis indicated that differences in mean FVIII activity levels in the PVT group, the number of cases in the non-PVT group, and the study design methods partially contributed to the heterogeneity (P < 0.05). However, compared to the non-PVT group, the PVT group had higher FVIII/PC ratio with a statistically significant difference (SMD = 0.39, 95% CI: 0.15 to 0.63, P = 0.00), and there was no significant heterogeneity (I2 = 28.62%). CONCLUSION: In conclusion, the FVIII/PC ratio not only reflects the severity of liver disease, but also can be used as one of the predictors of PVT development.
Assuntos
Fator VIII , Cirrose Hepática , Veia Porta , Trombose Venosa , Humanos , Fator VIII/análise , Fator VIII/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/sangue , Trombose Venosa/etiologia , Trombose Venosa/sangue , Fatores de Risco , Biomarcadores/sangueRESUMO
OBJECTIVE: The objective of this study was to thoroughly investigate the clinical value of triglyceride glucose-body mass index (TyG-BMI) in patients diagnosed with non-alcoholic fatty liver disease (NAFLD). Specifically, we aimed to determine its association with non-alcoholic steatohepatitis (NASH) and the progression of liver fibrosis. METHODS: The study included 393 patients diagnosed with NAFLD after liver biopsy. The patients were divided into two distinct cohorts: a training cohort (N = 320) and a validation cohort (N = 73). The training cohort was further divided into four groups based on TyG-BMI quartiles. The clinical characteristics of the patients in each group were compared in detail, and the association between TyG-BMI and NASH, NAFLD Activity Score (NAS) ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis was analyzed using multiple models. Additionally, we generated receiver operating characteristic (ROC) curves to evaluate the predictive ability of TyG-BMI for NASH and fibrosis staging in patients with NAFLD. RESULTS: Patients with higher TyG-BMI values had a significantly higher prevalence of NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis (all p < .05). TyG-BMI was an independent predictor of these diseases in both unadjusted and adjusted models (all p < .05). ROC curve analysis further revealed the excellent performance of TyG-BMI in predicting NASH, NAS ≥ 4, at-risk NASH, significant fibrosis, advanced fibrosis, and cirrhosis. The validation cohort yielded analogous results. Furthermore, we constructed three multivariate models of TyG-BMI in conjunction with elastography metrics, which demonstrated elevated diagnostic AUC values of 0.782, 0.792, 0.794, 0.785, 0.834, and 0.845, respectively. CONCLUSION: This study confirms a significant association between insulin resistance and NAFLD, including at-risk NASH and fibrosis staging, as assessed using the TyG-BMI index. TyG-BMI and its associated multivariate models can be valuable noninvasive indicators for NAFLD diagnosis, risk stratification, and disease course monitoring.
Assuntos
Índice de Massa Corporal , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Triglicerídeos , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Adulto , Glicemia/metabolismo , Glicemia/análise , Curva ROC , Índice de Gravidade de Doença , Fígado/patologia , Progressão da Doença , Biópsia , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: Emerging research suggests that hyperammonemia may enhance the probability of hepatic encephalopathy (HE), a condition associated with elevated levels of circulating ammonia in patients with cirrhosis. However, some studies indicate that blood ammonia levels may not consistently correlate with the severity of HE, highlighting the complex pathophysiology of this condition. METHODS: A systematic review and meta-analysis through PubMed, Scopus, Embase, Web of Science, and Virtual Health Library were conducted to address this complexity, analyzing and comparing published data on various laboratory parameters, including circulating ammonia, blood creatinine, albumin, sodium, and inflammation markers in cirrhotic patients, both with and without HE. RESULTS: This comprehensive review, which included 81 studies from five reputable databases until June 2024, revealed a significant increase in circulating ammonia levels in cirrhotic patients with HE, particularly those with overt HE. Notably, significant alterations were observed in the circulating creatinine, albumin, sodium, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα) in HE patients. CONCLUSIONS: These findings suggest an association between ammonia and HE and underscore the importance of considering other blood parameters such as creatinine, albumin, sodium, and pro-inflammatory cytokines when devising new treatment strategies for HE.
Assuntos
Amônia , Encefalopatia Hepática , Cirrose Hepática , Humanos , Amônia/sangue , Biomarcadores/sangue , Creatinina/sangue , Encefalopatia Hepática/sangue , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Hiperamonemia/sangue , Interleucina-6/sangue , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Albumina Sérica/análise , Sódio/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is related to an increased atherosclerotic cardiovascular disease (ASCVD) risk. This study investigated a potential relationship between liver fibrosis scores (LFS) reflecting NAFLD and ascending aortic dilatation (AAD). METHODS: This is an observational and cross-sectional study. Patients were consecutively enrolled from a cardiology clinic. The NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) index, aspartate aminotransferase (AST) to platelet ratio (APRI), and BARD scores of each patient were calculated. The ascending aortic diameters were evaluated by transthoracic echocardiography according to current clinical guidelines. The patients were allocated into two groups with and without AAD. RESULTS: A total of 272 patients were included in the study. In AAD group, age, patients with hypertension (HT), coronary artery disease (CAD), FIB-4 index, BARD score and the NFS were significantly higher. As compared to the AAD group, body mass index (BMI), hemoglobin, and diuretic use were significantly higher in patients without aortic dilatation. The NFS with AAD, and NFS and FIB-4 index with indexed aortic diameter (AI) showed significant positive correlation (R=0.546, R=0.332, R=0.314 with p<0.001, respectively). In multivariate logistic regression analysis hemoglobin levels (OR=0.728, 95%CI: 0.553-0.958; p=0.023), BMI (OR=0.762, 95%CI: 0.668-0.869, p<0.001), HT (OR=3.269, 95%CI: 1.045-10.220; p=0.042), BARD score (OR=1.248, 95%CIL 0.815-1.955; p=0.044), and FIB-4 index (OR=2.432, 95%CI: 1.395-4.246; p=0.002) were found to be independently related to AAD. CONCLUSIONS: Our study demonstrated a statistically significant relationship between NFS, FIB-4 index, BARD score and AAD. The presence of positive correlation among LFS and AAD in our study is remarkable. This may emphasize the increased risk of AAD in NAFLD.
Assuntos
Aorta , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Idoso , Dilatação Patológica , Aorta/patologia , Aorta/diagnóstico por imagem , Fatores de Risco , Índice de Gravidade de Doença , Ecocardiografia , Aspartato Aminotransferases/sangueRESUMO
Background and Objectives: Hepatic cirrhosis is a disease with an increasing frequency globally, but its mechanisms of disease development are not yet completely known. The aim of this study was to evaluate the relationship between thyroid hormone levels (T3, fT4, and TSH) and survival in patients with chronic liver disease. Materials and Methods: A total of 419 patients diagnosed with liver cirrhosis were included in the study. The MELD score was computed, and TSH, T3, and fT4 were collected from each patient using the ELISA procedure. Signs and symptoms of liver failure and portal hypertension confirmed the clinical diagnosis of liver cirrhosis, and biological tests and imaging methods confirmed the diagnosis. Results: The MELD score was positively associated with TSH on admission and TSH on discharge and negatively associated with T3 at discharge. TSH levels were higher in non-survivors than in survivors. The values of T3 and fT4 present no significant changes to be considered as prognostic factors. Conclusions: Although the differences between the median TSH values of the patients who died and those who survived are not very large, the statistical significance of the data obtained demonstrates that there are changes in metabolism of the thyroid hormones during the progression of liver cirrhosis. It is possible that TSH is the one which maintains the normal balance of thyroid activity for patients with liver cirrhosis, so it can be considered as an important marker of evolution of these patients.
Assuntos
Cirrose Hepática , Hormônios Tireóideos , Tireotropina , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Tireotropina/sangue , Idoso , Hormônios Tireóideos/sangue , Tri-Iodotironina/sangue , Adulto , Tiroxina/sangue , Índice de Gravidade de DoençaRESUMO
Background and Objectives: Sustained virologic responses (SVRs) lead to a decrease in portal hypertension, the regression of fibrosis, and the improvement in the hepatic synthesis of procoagulant and anticoagulant factors. We aimed to assess the influence of SVR on coagulation parameters in cirrhotic patients with HCV treated with DAAs. Methods: We performed a prospective study in the Institute of Gastroenterology and Hepatology Iasi, Romania, between January 2022 and February 2024. We included patients diagnosed with compensated and decompensated HCV-related liver cirrhosis, treated with direct antivirals (PrOD ± RBV or SOF/LED ± RBV) for 12/24 weeks. Blood samples for biochemical, immunological, and coagulation tests were collected at the baseline, end of treatment (EOT), and once sustained virological response had been achieved over a period of 12/24 weeks (SVR12/24). Results: We analyzed a group of 52 patients with HCV-related liver cirrhosis, predominantly female (68.0%), and the degree of severity of cirrhosis placed the patients mainly in Child-Pugh classes B (40%) and C (36%). All patients achieved SVRs. The MELD score decreased at EOT (13.48 ± 4.273; p = 0.001) and SVR (9.88 ± 2.774; p = 0.000), compared to the baseline (14.92 ± 4.707). The FibroScan values decreased at SVR (17.596 ± 3.7276; p = 0.000) compared to the baseline (26.068 ± 7.0954). For all common coagulation parameters (platelets, INR, PT, fibrinogen, aPTT), there was a trend towards improvement during treatment, including changes which were statistically significant for the majority of patients. Factor II was low at the baseline (75.40 ± 7.506) but increased at EOT (87.40 ± 9.587) and, later, at SVR (99.12 ± 11.695; p = 0.000). The FVIII values increased at the baseline (175.52 ± 16.414) and decreased at EOT (151.48 ± 13.703) and SVR (143.40 ± 13.937). The FvW values decreased during treatment (146.84 ± 9.428, at baseline; 141.32 ± 9.690, p = 0.000, at EOT; and 126.68 ± 17.960, at SVR). In regard to the anticoagulant factors (PC, PS, ATIII), a significant improvement was brought on by SVR. Advanced stages of liver disease showed the most diminished FII activity, while at the baseline and in Child-Pugh C patients we recorded the highest values of FVIII and FvW. Conclusions: Our study proved that the "reset" of coagulopathy might be due to the improvement in liver function due to viral eradication secondary to AAD therapy.
Assuntos
Antivirais , Cirrose Hepática , Resposta Viral Sustentada , Humanos , Feminino , Masculino , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Romênia , Idoso , Coagulação Sanguínea/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Hepatite C/complicações , Hepatite C/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/sangue , AdultoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent condition in the general population. Although recent studies have demonstrated a link between NAFLD and lipoprotein(a), a low-density lipoprotein-like particle synthesized in the liver, its precise physiological role and mechanism of action remain unclear. This study aimed to investigate the relationship between lipoprotein(a) levels and development of NAFLD and hepatic fibrosis in Korean adults. A total of 1501 subjects who underwent abdominal ultrasonography at least twice as part of a health checkup program were enrolled. Biochemical and ultrasonography results were analyzed longitudinally, and the degree of hepatic fibrosis was calculated in subjects with NAFLD using serum biomarkers, such as fibrosis-4 (FIB-4). During the 3.36-year follow-up period, 352 patients (23.5%) were diagnosed with NAFLD. The subjects were categorized into 4 groups based on their lipoprotein(a) levels. Remarkably, the incidence of NAFLD decreased as the lipoprotein(a) levels increased. Following logistic regression analysis and adjustment for various risk factors, the odds ratio for the development of NAFLD was 0.625 (95% CI 0.440-0.888; Pâ =â .032) when comparing the highest to the lowest tertile of lipoprotein(a). However, no significant association was observed between the occurrence of hepatic fibrosis and lipoprotein(a) levels in subjects with NAFLD. Lipoprotein(a) levels have been identified as a significant predictor of NAFLD development. Additional large-scale studies with extended follow-up periods are required to better understand the effect of lipoprotein(a) on NAFLD and hepatic fibrosis.
Assuntos
Biomarcadores , Lipoproteína(a) , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Masculino , Feminino , República da Coreia/epidemiologia , Lipoproteína(a)/sangue , Pessoa de Meia-Idade , Estudos Longitudinais , Estudos Retrospectivos , Adulto , Biomarcadores/sangue , Fatores de Risco , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Ultrassonografia , IncidênciaRESUMO
Chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC), continue to be a global health burden with a rise in incidence and mortality, necessitating a need for the discovery of novel biomarkers for HCC detection. This study aimed to identify novel non-invasive biomarkers for these different liver disease states. We performed untargeted metabolomics in plasma (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 34) and saliva samples (Healthy = 9, NAFLD = 14, Cirrhosis = 10, HCC = 22) to test for significant metabolite associations with each disease state. Additionally, we identified enriched biochemical pathways and analyzed correlations of metabolites between, and within, the two biofluids. We identified two salivary metabolites and 28 plasma metabolites significantly associated with at least one liver disease state. No metabolites were significantly correlated between biofluids, but we did identify numerous metabolites correlated within saliva and plasma, respectively. Pathway analysis revealed significant pathways enriched within plasma metabolites for several disease states. Our work provides a detailed analysis of the altered metabolome at various stages of liver disease while providing some context to altered pathways and relationships between metabolites.
Assuntos
Biomarcadores , Metaboloma , Metabolômica , Hepatopatia Gordurosa não Alcoólica , Saliva , Humanos , Saliva/metabolismo , Metabolômica/métodos , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Hepatopatias/metabolismo , Hepatopatias/sangue , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/metabolismo , Idoso , Cirrose Hepática/metabolismo , Cirrose Hepática/sangue , Cirrose Hepática/diagnósticoRESUMO
BACKGROUND/OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and insulin resistance (IR). Identifying characteristics that predict a higher risk of fibrosis using noninvasive methods is particularly important. METHODS: We performed a secondary analysis of data from an RCT of 48 patients after one anastomosis gastric bypass (OAGB) surgery, supplemented with specifically formulated probiotics and micronutrients or control treatment for 12 weeks. Patients were categorized using alanine aminotransferase (ALAT; >35 U/L for women, >50 U/L for men), higher NAFLD fibrosis score (NFS) > -1.455), and IR (HOMA-IR > 2.0). This trial was registered at Clinicaltrials.gov (ID: NCT03585413). RESULTS: Abnormal ALAT was associated with high triglycerides, blood pressure (BP), glucose, and fatty liver index (FLI). NFS > -1.455 was linked to higher age, body mass, waist circumference, and FLI, and lower albumin and platelet count. HOMA-IR > 2.0 was associated with higher BP and triglycerides, lower HDL-cholesterol, higher serum transaminases, and higher probabilities of steatosis and fibrosis. Twelve weeks postoperatively, patients with NFS > -1.455 showed greater reductions in body mass, systolic BP, serum insulin, and HbA1c, whereas those with NFS ≤ -1.455 showed improvements in FLI and lipid metabolism but had high glucose concentrations. Patients with HOMA-IR ≤ 2.0 also had high glucose concentrations. CONCLUSIONS: The evaluation of common biomarker scores for fibrosis and IR may help clinicians to recognize severe NAFLD and improve the outcomes of OAGB surgery.
Assuntos
Derivação Gástrica , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Masculino , Derivação Gástrica/métodos , Pessoa de Meia-Idade , Adulto , Hepatopatia Gordurosa não Alcoólica/cirurgia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/sangue , Prognóstico , Obesidade/complicações , Obesidade/cirurgia , Alanina Transaminase/sangue , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/sangue , Cirrose Hepática/cirurgia , Cirrose Hepática/complicações , Cirrose Hepática/sangue , Glicemia/metabolismoRESUMO
INTRODUCTION: A highly accurate diagnostic method is crucial to reduce mortality and increase hepatocellular carcinoma (HCC) survival. Current biomarkers have limited accuracy, and novel ones are needed. Fibroblast growth factor-19 (FGF-19) is overexpressed in HCC. This study aimed to assess FGF-19 as a potential novel diagnostic biomarker for HCC. METHODS: This case-control study involved 114 individuals divided into three equal groups: HCC (n=38), Cirrhosis (n=38), and Control (n=38). HCC biomarkers included alpha-fetoprotein (AFP), Des-γ-carboxy prothrombin (DCP), and FGF-19. RESULTS: The three markers, FGF-19, DCP, and AFP, were significantly different between the three groups, except that DCP was comparable between HCC and Cirrhosis groups (p=1.000). All individuals in the control group had FGF-19 levels below the minimum level in the HCC group. Thus, FGF-19 had 100% sensitivity and specificity in differentiating HCC from healthy controls. FGF-19 can discriminate between HCC and Cirrhosis groups at a 140.8 pg/mL cutoff with sensitivity and specificity of 81.8% and 87.9%, respectively. The sensitivity of FGF-19 was higher than AFP, trending toward statistical significance (p=0.095). Combining FGF-19 with AFP, DCP, or both improved sensitivity but decreased specificity. CONCLUSION: FGF-19 is a possible noninvasive serum biomarker for HCC. Its combination with AFP or DCP improves the sensitivity for detecting HCC.
Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Fatores de Crescimento de Fibroblastos , Cirrose Hepática , Neoplasias Hepáticas , Precursores de Proteínas , Protrombina , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Estudos de Casos e Controles , Biomarcadores Tumorais/sangue , Masculino , Fatores de Crescimento de Fibroblastos/sangue , Feminino , Pessoa de Meia-Idade , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análise , Precursores de Proteínas/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Prognóstico , Seguimentos , Adulto , Idoso , BiomarcadoresRESUMO
BACKGROUND: Endoscopic variceal ligation (EVL) is the primary treatment for esophageal variceal bleeding in patients with liver cirrhosis (LC). Postoperative rebleeding is a complication of EVL, contributing to over 20% of bleeding-related deaths. This study aims to examine the association between platelet-to-lymphocyte ratio (PLR) and rebleeding within 6 weeks after EVL in patients with LC. METHODS: The study included 145 eligible patients who underwent their first EVL procedure at Yijishan Hospital of Wannan Medical College between January 2016 and August 2022 (YJS cohort). An external validation cohort comprising 338 eligible patients from NO.2 People's Hospital of Fuyang City (FY cohort) between July 2018 and August 2022 was also utilized. RESULTS: In the YJS cohort, Multivariate logistic analysis indicated that high PLR is independently associated with early rebleeding after EVL. The restricted cubic spline analysis demonstrated that the risk of rebleeding increases with rising PLR, stabilizing at PLR values greater than 150. Similar findings were validated in the FY cohort. CONCLUSIONS: Our results have the potential to aid in the identification of high-risk patients for early rebleeding after EVL, thereby enabling improved clinical management and outcomes for these individuals.
This study is the first to report on the independent association between the platelet-to-lymphocyte ratio (PLR) and early rebleeding after endoscopic variceal ligation (EVL).The restricted cubic spline analysis showed a linear correlation between PLR and the risk of early rebleeding after EVL.An increase in PLR level is independently associated with a higher risk of early rebleeding after EVL.
Assuntos
Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Cirrose Hepática , Humanos , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Varizes Esofágicas e Gástricas/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Ligadura/efeitos adversos , Estudos Retrospectivos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hemorragia Gastrointestinal/sangue , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Contagem de Plaquetas , Recidiva , Idoso , Linfócitos , Contagem de Linfócitos , Plaquetas , AdultoRESUMO
OBJECTIVE: To assess the fibrinogen function in patients with hepatitis B-related cirrhosis and explore the relationship between dysfibrinogenemia and bleeding and thrombotic events. METHODS: Medical records and laboratory data of the patients with hepatitis B-related cirrhosis were collected. Patients were categorized into three groups based on the Child-Pugh score. Fibrinogen activity and antigen, fibrinogen-bound sialic acid (FSA), fibrinogen polymerization and fibrinolysis kinetic analysis, thrombin-antithrombin complex (TAT) and plasmin-α2-antiplasmin complex (PAP) were detected. RESULTS: Eighty patients with seventeen, thirty-eight and twenty-five in Child-Pugh A, B and C, respectively, were included. Seventeen patients experienced bleeding events and eight patients had thrombotic events. Fibrinogen activity and antigen levels were reduced with the severity of cirrhosis. Twenty-two patients exhibited dysfibrinogenemia. The FSA levels in patients with non-dysfibrinogenemia and those with dysfibrinogenemia were increased to 1.25 and 1.37 times of healthy controls, negatively correlated with fibrinogen activity (ρ = -0.393, p = 0.006). Compared to healthy controls, the amount of clot formation was reduced (p < 0.001), the polymerization was delayed (p < 0.001) and the rate of fibrinolysis was reduced (p < 0.001). The TAT levels were significantly increased in the Child-Pugh C patients compared to the Child-Pugh B patients (p = 0.032) while the PAP levels were comparable among 3 groups (p = 0.361). CONCLUSION: Sialylation of fibrinogen is one of the main causes of modifications of fibrinogen in patients with hepatitis B-related cirrhosis. The polymerization and fibrinolysis functions of fibrinogen are impaired. The degree of impaired fibrinolysis function is more severe than that of polymerization function, and may be partly related to the occurrence of thrombotic events.
Assuntos
Fibrinogênio , Fibrinólise , Hepatite B , Cirrose Hepática , Humanos , Masculino , Feminino , Fibrinogênio/metabolismo , Fibrinogênio/análise , Pessoa de Meia-Idade , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Cirrose Hepática/complicações , Hepatite B/complicações , Hepatite B/sangue , Hepatite B/metabolismo , Adulto , IdosoRESUMO
BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.
Assuntos
Cirrose Hepática , Microbiota , RNA Ribossômico 16S , Humanos , Masculino , Cirrose Hepática/sangue , Cirrose Hepática/microbiologia , Cirrose Hepática/virologia , Feminino , Pessoa de Meia-Idade , Estudos Transversais , RNA Ribossômico 16S/genética , Idoso , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Índice de Gravidade de Doença , Adulto , Hepatite C Crônica/complicações , Hepatite C Crônica/sangue , Hepatite C Crônica/microbiologia , Metaboloma , Metabolômica , Sangue/microbiologia , Sangue/virologiaRESUMO
BACKGROUND AND AIMS: The transition from compensated to decompensated cirrhosis is crucial, drastically reducing prognosis from a median survival of over 10 years to 2 years. There is currently an unmet need to accurately predict decompensation. We systematically reviewed and meta-analysed data regarding biomarker use to predict decompensation in individuals with compensated cirrhosis. METHODS: PubMed and EMBASE database searches were conducted for all studies from inception until February 2024. The study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality of Prognosis Studies framework was used to assess the risk of bias. The meta-analysis was conducted with a random effects model using STATA software. RESULTS: Of the 652 studies initially identified, 63 studies (n=31 438 patients) were included in the final review, examining 49 biomarkers. 25 studies (40%) were prospective with the majority of studies looking at all-cause decompensation (90%). The most well-studied biomarkers were platelets (n=17), Model for End-Stage Liver Disease (n=17) and albumin (n=16). A meta-analysis revealed elevated international normalised ratio was the strongest predictor of decompensation, followed by decreased albumin. However, high statistical heterogeneity was noted (l2 result of 96.3%). Furthermore, 21 studies were assessed as having a low risk of bias (34%), 26 (41%) moderate risk and 16 (25%) high risk. CONCLUSIONS: This review highlights key biomarkers that should potentially be incorporated into future scoring systems to predict decompensation. However, future biomarker studies should be conducted with rigorous and standardised methodology to ensure robust and comparable data.
Assuntos
Biomarcadores , Cirrose Hepática , Humanos , Biomarcadores/sangue , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Prognóstico , Progressão da Doença , Albumina Sérica/análise , Albumina Sérica/metabolismo , Coeficiente Internacional Normatizado , Valor Preditivo dos TestesRESUMO
BACKGROUND: Liver fibrosis is a critical public health concern, necessitating early detection to prevent progression. This study evaluates the recently developed LiverRisk score and steatosis-associated Fibrosis Estimator (SAFE) score against established indices for prognostication and/or fibrosis prediction in 4diverse cohorts, including participants with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We used data from the Mount Sinai Data Warehouse (32,828 participants without liver disease diagnoses), the Mount Sinai MASLD/MASH Longitudinal Registry (422 participants with MASLD), and National Health and Nutrition Examination Survey 2017-2020 (4133 participants representing the general population) to compare LiverRisk score, FIB-4 index, APRI, and SAFE score. Analyses included Cox proportional hazards regressions, Kaplan-Meier estimates, and classification metrics to evaluate performance in prognostication and fibrosis prediction. RESULTS: In Mount Sinai Data Warehouse, LiverRisk score was significantly associated with future liver-related outcomes but did not significantly outperform FIB-4 or APRI for predicting any of the outcomes. In the general population, LiverRisk score and SAFE score outperformed FIB-4 and APRI in identifying fibrosis, but LiverRisk score underperformed among participants who were non-White or had type 2 diabetes. Among participants with MASLD, SAFE score outperformed FIB-4 and APRI in 1 of 2 cohorts, but there were generally few significant performance differences between all 4 scores. CONCLUSIONS: LiverRisk score does not consistently outperform existing predictors in diverse populations, and further validation is needed before adoption in settings with significant differences from the original derivation cohorts. It remains necessary to replicate the ability of these scores to predict liver-specific mortality, as well as to develop diagnostic tools for liver fibrosis that are accessible and substantially better than current scores, especially among patients with MASLD and other chronic liver conditions.
Assuntos
Cirrose Hepática , Inquéritos Nutricionais , Sistema de Registros , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Prognóstico , Índice de Gravidade de Doença , Idoso , Estados Unidos/epidemiologia , Biomarcadores/sangue , Fígado Gorduroso/patologiaRESUMO
BACKGROUND: Liver cirrhosis is a chronic and progressive liver disease with significant global health implications. Recent evidence suggests an association between serum vitamin D levels and the severity of liver cirrhosis, potentially serving as a therapeutic target. This study aimed to investigate the relationship between serum vitamin D status and the severity of liver cirrhosis in a population of Nigerian patients. METHODS: This analytical, cross-sectional study involved 201 participants, including 103 with liver cirrhosis and 98 age- and sex-matched controls. Serum vitamin D was measured using ELISA, with deficiency defined as < 20 ng/ml. Cirrhosis severity was assessed using Child-Pugh and MELD scores. Spearman's correlation was used to assess the relationship between vitamin D and severity of liver cirrhosis while ordinal regression analysis assessed its performance as an indicator of the disease severity. RESULT: Among cirrhotic patients, 36.9% were deficient, 31.1% insufficient, and 32.0% had sufficient vitamin D levels. Serum vitamin D showed strong negative correlations with Child-Pugh and MELD scores (r = -0.696, p < 0.001; r = -0.734, p < 0.001, respectively). Ordinal regression showed that higher vitamin D levels were associated with lower severity scores (Child-Pugh: OR = 0.856, 95% CI: 0.815-0.900, p < 0.001; MELD: OR = 0.875, 95% CI: 0.837-0.915, p < 0.001). CONCLUSION: Lower serum vitamin D levels correlated with increased liver cirrhosis severity, suggesting its potential as both a prognostic marker and therapeutic target. Further studies should investigate the efficacy of vitamin D supplementation in improving cirrhosis outcomes.