Usefulness of Cytokeratin-18M65 in Diagnosing Non-Alcoholic Steatohepatitis in Japanese Population

2015 ◽  
Vol 33 (6) ◽  
pp. 715-720 ◽  
Author(s):  
Yutaka Hasegawa ◽  
Soo Ryang Kim ◽  
Takashi Hatae ◽  
Mitsuhiro Ohta ◽  
Aya Fujinami ◽  
...  
Keyword(s):  
Japanese Population ◽  
Multivariate Logistic Regression Analysis ◽  
Fibrosis Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Multivariate Logistic Regression ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Significant Difference ◽  
Auc Value ◽  
Alcoholic Fatty Liver Disease

Objective: The aim of this study was to evaluate cytokeratin-18M65 (CK-18M65) for distinguishing between simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) against healthy individuals (HIs) in Japanese population. Methods: The serum from 24 HIs, 21 patients with SS and 20 patients with NASH were examined. Serum CK-18M65 was measured by enzyme-linked immunosorbent assay. Results: Aspartate aminotransferase was significantly different between NASH patients and HIs with p < 0.0001 (SS patients and HIs: p < 0.0001), as was alanine aminotransferase between NASH patients and HIs with p < 0.0001 (SS patients and HIs: p < 0.0001). Serum CK-18M65 increased in a stepwise fashion in HIs and also in SS and NASH patients. Multivariate logistic regression analysis revealed that NASH could be diagnosed with the use of CK-18M65 alone (p = 0.0285, OR 1.0038, 95% CI 1.0004-1.0073). At the optimal cut-off level of 548 U/l, CK-18M65 had an AUC value of 0.7369, 60.00% sensitivity and 85.70% specificity. In patients with NASH, no significant difference was observed between low fibrosis (Stage 0-1, 794.30 ± 454.41, n = 10) and high fibrosis (Stage 2-3, 809.70 ± 641.43, n = 10; p = 0.5967) and between slight steatosis (<33%, 512.89 ± 229.65, n = 9) and moderate steatosis (≥33%, 655.13 ± 480.78, n = 32) in patients with non-alcoholic fatty liver disease (NAFLD; p = 0.7647) with the use of CK-18M65. Conclusion: Serum CK-18M65 distinguished NASH from SS, but could not assess the severity of steatosis in NAFLD patients or the grade of fibrosis in NASH patients in Japanese population.

Thyroid Function and Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects

2018 ◽  
Vol 17 (5) ◽  
pp. 0-10
Author(s):  
Yiting Liu ◽  
Wei Wang ◽  
Xiaosong Yu ◽  
Xingshun Qi
Keyword(s):  
Logistic Regression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Thyroid Function ◽  
Fatty Liver Disease ◽  
Multivariate Logistic Regression Analysis ◽  
Elderly Subjects ◽  
Multivariate Logistic Regression ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Introduction and aims. The association between thyroid function and non-alcoholic fatty liver disease (NAFLD) remained controversial. A large cross-sectional study aimed to explore the relationship in euthyroid population. Material and methods. A total of 1773 euthyroid subjects who underwent health check-up during one-year period were enrolled. NAFLD was diagnosed by ultrasound and fatty liver index (FLI). Fibrosis was estimated by BARD score. Thyroid function parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were recorded. Multivariate logistic regression analyses were performed to identify the independent risk factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results. NAFLD was diagnosed by ultrasound in 638 (35.98%) subjects and by FLI ≥ 60 in 694 (39.14%) subjects. Regardless of ultrasound or FLI, the overall analysis demonstrated that TSH and FT3 levels were significantly higher in subjects with NAFLD than subjects without NAFLD, but FT4 level was not significantly different between them. This association remained in middle-age subjects, but not elderly subjects. In the multivariate logistic regression analysis, TSH (OR = 1.108, 95%CI = 1.056-1.398, P = 0.024) and FT3 (OR = 1.258, 95%CI = 1.123-1.409, P = 0.000) levels were independently associated with the risk of NAFLD diagnosed by ultrasound; and only FT3 level (OR = 1.252, 95%CI = 1.074 - 1.460, P = 0.004) was independently associated with the risk of NAFLD estimated by FLI ≥ 60. Additionally, FT3 level (OR = 1.178, 95%CI = 1.025 - 1.354, P = 0.021) was independently associated with the risk of fibrosis estimated by BARD score ≥ 2 in NAFLD subjects. Conclusion. Among the euthyroid population, FT3 and TSH levels were positively associated with the risk of NAFLD.

Prevalence, diagnosis and treatment with 3 different statins of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in military personnel. Do genetics play a role?

2020 ◽  
Vol 18 ◽  
Author(s):  
Georgios Sfikas ◽  
Michael Psallas ◽  
Charalambos Koumaras ◽  
Konstantinos Imprialos ◽  
Evangelos Perdikakis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Military Personnel ◽  
Fatty Liver Disease ◽  
Exercise Group ◽  
Severe Form ◽  
Laboratory Evaluation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. Aim: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. Methods: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomised to 4 groups (n=151 each): dietexercise, atorvastatin, rosuvastatin or pitavastatin for 1 year (i.e. until the next routine evaluation). Results: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001); 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs 5.62, p=0.07; FIB-4 3.42 vs 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). Conclusions : Atorvastatin, rosuvastatin and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

Donepezil Combined with DL-3-n-Butylphthalide Delays Cognitive Decline in Patients with Mild to Moderate Alzheimer’s Disease: A Multicenter, Prospective Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 673-681
Author(s):  
Jin Wang ◽  
Xiaojuan Guo ◽  
Wenhui Lu ◽  
Jie Liu ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Cohort Study ◽  
Prospective Cohort ◽  
Daily Living ◽  
Multivariate Logistic Regression Analysis ◽  
Multivariate Logistic Regression ◽  
Significant Difference

Background: Vascular factors and mitochondria dysfunction contribute to the pathogenesis of Alzheimer’s disease (AD). DL-3-n-butylphthalide (NBP) has an effect in protecting mitochondria and improving microcirculation. Objective: The aim was to investigate the effect of donepezil combined NBP therapy in patients with mild-moderate AD. Methods: It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n = 43) or the donepezil combined NBP group (n = 49) for 48 weeks. All patients were evaluated with Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using multivariate logistic regression analysis. Results: The multivariate logistic regression analysis showed that the changes of ADAS-cog score (OR = 2.778, 95% CI: [1.087, 7. 100], p = 0.033) and ADCS-ADL score (OR = 2.733, 95% CI: [1.002, 7.459], p = 0.049) had significant difference between donepezil alone group and donepezil combined NBP group, while the changes of NPI (OR = 1.145, 95% CI: [0.463, 2.829], p = 0.769), MMSE (OR = 1.563, 95% CI: [0.615, 3.971], p = 0.348) and CIBIC-plus (OR = 2.593, 95% CI: [0.696, 9.685], p = 0.156) had no significant difference. The occurrence of AEs was similar in the two groups. Conclusion: Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.

scholarly journals Clinical characteristics and longitudinal changes of patients with non-alcoholic fatty liver disease in 2 decades: the NAGALA study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takuro Okamura ◽  
Yoshitaka Hashimoto ◽  
Masahide Hamaguchi ◽  
Akihiro Obora ◽  
Takao Kojima ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Liver Disease ◽  
Fatty Liver ◽  
Body Mass ◽  
Fatty Liver Disease ◽  
Abdominal Ultrasonography ◽  
Alcoholic Fatty Liver ◽  
The Past ◽  
Significant Difference ◽  
Alcoholic Fatty Liver Disease

Abstract Background In this study, to clarify the evolving background of people with non-alcoholic fatty liver disease (NAFLD), we compared the current prevalence of NAFLD with that of 2 decades ago. Methods We included two cohorts. The past cohort was from 1994 to 1997 and included 4279 men and 2502 women. The current cohort was from 2014 to 2017 and included 8918 men and 7361 women. NAFLD was diagnosed by abdominal ultrasonography. Results The prevalence of NAFLD increased in both genders throughout these 2 decades (18.5% in the past cohort and 27.1% in the current cohort for men; and 8.0% in the past cohort and 9.4% in the current cohort for women). The prevalence of hyperglycemia increased, whereas the prevalence of low high-density lipoprotein cholesterol levels and hypertriglyceridemia significantly decreased. There was no significant difference in the mean body mass index. Multivariate analysis revealed that the prevalence of obesity and body mass index were significantly associated with the prevalence of NAFLD in both the past and current cohorts. Conclusions The incidence of NAFLD significantly increased throughout these 2 decades, and obesity is the most prevalent factor. Thus, body weight management is an essential treatment option for NAFLD.

scholarly journals Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 184
Author(s):  
Daryl Ramai ◽  
Waqqas Tai ◽  
Michelle Rivera ◽  
Antonio Facciorusso ◽  
Nicola Tartaglia ◽  
...  
Keyword(s):  
Public Health ◽  
Hepatocellular Carcinoma ◽  
Lipid Peroxidation ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Natural Progression ◽  
Public Health Threat ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a “multi-hit” or “multi-parallel hit” model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.

scholarly journals The Role of the Histone Methyltransferase EZH2 in Liver Inflammation and Fibrosis in STAM NASH Mice

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 93 ◽  
Author(s):  
Seul Lee ◽  
Dong-Cheol Woo ◽  
Jeeheon Kang ◽  
Moonjin Ra ◽  
Ki Hyun Kim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Epigenetic Modification ◽  
Treatment Options ◽  
Histone Methyltransferase ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Promising Therapeutic Target ◽  
Alcoholic Fatty Liver Disease ◽  
Potential Therapeutics

Non-alcoholic fatty liver disease (NAFLD) is a leading form of chronic liver disease, with few biomarkers and treatment options currently available. Non-alcoholic steatohepatitis (NASH), a progressive disease of NAFLD, may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Epigenetic modification can contribute to the progression of NAFLD causing non-alcoholic steatohepatitis (NASH), in which the exact role of epigenetics remains poorly understood. To identify potential therapeutics for NASH, we tested small-molecule inhibitors of the epigenetic target histone methyltransferase EZH2, Tazemetostat (EPZ-6438), and UNC1999 in STAM NASH mice. The results demonstrate that treatment with EZH2 inhibitors decreased serum TNF-alpha in NASH. In this study, we investigated that inhibition of EZH2 reduced mRNA expression of inflammatory cytokines and fibrosis markers in NASH mice. In conclusion, these results suggest that EZH2 may present a promising therapeutic target in the treatment of NASH.

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