ASSOCIATION ANALYSIS OF PIOGLITAZONE EFFECTIVENESS IN TREATMENT OF NAFLD PATIENTS WITH OBESITY AND PPARG RS1801282 (PRO12ALA) GENOTYPE

2021 ◽  
Vol 74 (7) ◽  
pp. 1617-1621
Author(s):  
Vadym P. Shypulin ◽  
Oleksandr A. Martynchuk ◽  
Nikolai N. Rudenko ◽  
Aleksandr K. Koliada ◽  
Viktoriia V. Tishchenko ◽  
...  

The aim: To study the association between the effectiveness of treatment with pioglitazone non-alcoholic fatty liver disease (NAFLD) in patients with obesity and PPARG rs1801282 (Pro12Ala)-polymorphism in Ukrainians. Materials and methods: 123 patients with NAFLD in combination with obesity 1, 2, 3 classes were included in comprehensive weight loss program (5 visits, 12-weeks). The case group was treated with pioglitazone 15 mg / day, while the control group received only program. Ultrasound (US) steatometry and genetic testing rs1801282 polymorphism in PPARG gene were performed. Results: Pioglitazone, PPARG rs1801282 genotype, CAP before treatment, previous weight loss attempts, and duration of obesity were associated with the change in controlled attenuation parameter (CAP) during treatment. There was a significant association between the target CAP reduction achievement and pioglitazone treatment (adjusted odds ratio 0.23, 95% CI 0.07–0.73; p = 0.01) with the CC genotype of PPARG gene (adjusted odds ratio 92.9, 95% CI 7.4–1159; p < 0.001) compared to patients with the CG genotype. Conclusions: Pioglitazone and PPARG rs1801282 polymorphism could influence on dynamics of CAP reduction during treatment.

Author(s):  
Mahshid Akbari ◽  
Sima Zohari-Anboohi

Introduction: A high prevalence of non-alcoholic fatty liver disease is associated with obesity and lifestyle disorders. The present study was conducted to compare the nutritional pattern of patients with and without non-alcoholic fatty liver disease referred to the hospitals affiliated to Tehran University of Medical Sciences in 2017.Materials and Methods: The present case-control study was performed on a total of 300 outpatients and inpatients, aged 18–65 years. These patients were referred to the ultrasonography section of the hospitals, and those recruited in the study were selected by the convenience method of sampling. According to the results of ultrasonography, these subjects were divided into two groups: case (100 patients) and control (200 subjects for increasing the statistical power of study). The data were analyzed using the Statistical Package for the Social Sciences (version 19), descriptive statistics, and the Mann–Whitney test. P<0.05 was considered significant.Results: A significant difference was detected between the mean consumption of unhealthy foods in the case group as compared to the control group (P=0.001), while those with fatty liver reported a low average intake of fruits and vegetables with a significant difference (P=0.001).Conclusion: The results showed that patients with fatty liver complied with poor dietary habits as compared to individuals without the disease. 


2020 ◽  
Vol 6 ◽  
pp. 15-23
Author(s):  
Vadym Shypulin ◽  
Nikolai Rudenko ◽  
Oleksandr Martynchuk ◽  
Aleksandr Koliada ◽  
Vitaly Guryanov ◽  
...  

The aim: to investigate the metabolic effects of different treatment options in patients with obesity and concomitant non-alcoholic fatty liver disease (NAFLD) based on the presence of CG and GG genotypes PPARG rs1801282 (Pro12Ala) polymorphism in Ukrainians. Materials and methods: 123 patients with NAFLD in combination with obesity 1, 2, 3 classes were included in the motivational weight loss program (5 visits, 3 months). The case group was treated with pioglitazone 15 mg / day, while the control group received only a program. Ultrasound steatometry, anthropometric and laboratory tests before and after treatment, genetic testing rs1801282 polymorphism in PPARG gene were performed. Results: the carriers of CG and GG genotypes PPARG rs1801282 polymorphism had less high stimulated insulin levels compared with groups of different genotypes (p<0.001). It was found pioglitazone effectiveness with significant difference in dynamics of CAP reduction (p<0.001) regardless of polymorphism. Dynamics of BMI decrease was the lowest in control group CC carries – –2.81 (–3.23; –2.39) kg (p<0.001) compared among other groups. Subjects from pioglitazone group with rs1801282 polymorphism carrying of CG and GG genotypes had significant differences in dynamics of fasting С-peptide decrease, serum uric acid reduction – –1.31 (–1.50; –1.13) µg/L and -165.3 (–182.80; –147.80) µmol/L (p<0.001) respectively compared among other groups. Conclusions: Better reduction of metabolic parameters during pioglitazone treatment of patients with obesity and concomitant NAFLD appears to be associated with carrying of CG and GG genotypes PPARG rs1801282 polymorphism.


2021 ◽  
Vol 11 (11) ◽  
pp. 1063
Author(s):  
Chia-Jung Kuo ◽  
Cheng-Yu Lin ◽  
Chun-Wei Chen ◽  
Chiu-Yi Hsu ◽  
Sen-Yung Hsieh ◽  
...  

Long-term use of gastric-acid-suppressive drugs is known to be associated with several adverse effects. However, the association between enteric infection and acid suppression therapy is still uncertain. This study aimed to evaluate the association between gastric acid suppression and the risk of enteric infection. Materials and Methods: We conducted a population-based case-control study using the data from Chang Gung Research Database (CGRD) in Taiwan. Between January 2008 and December 2017, a total of 154,590 adult inpatients (age > 18) were identified. A pool of potential eligible controls according to four propensity scores matching by sex, age, and index year were extracted (n = 89,925). Subjects with missing data or who received less than 7 days of proton pump inhibitors (PPIs) and/or H2-receptor antagonists (H2RAs) were excluded. Finally, 17,186 cases and 69,708 corresponding controls were selected for analysis. The use of PPIs and H2RAs, the result of microbiological samples, and co-morbidity conditions have been analyzed. Confounders were controlled by conditional logistic regression. Results: 32.84% of patients in the case group used PPIs, compared with 7.48% in the control group. Of patients in the case group, 9.9% used H2RAs, compared with 6.9% in the control group. Of patients in the case group, 8.3% used a combination of PPIs and H2RAs, compared with 2.7% in the control group. The most common etiological pathogens were Enterococcus (44.8%), Clostridioides difficile (34.5%), and Salmonella spp. (10.2%). The adjusted odds ratio (OR) for PPI use with enteric infection was 5.526 (95% confidence interval [CI], 5.274–5.791). For H2RAs, the adjusted odds ratio was 1.339 (95% confidence interval [CI], 1.261–1.424). Compared to the control group, persons with enteric infection had more frequent acid-suppressive agent usage. Conclusions: This study demonstrates that gastric-acid-suppressive drug use is associated with an increased risk of enteric infection after adjusting for potential biases and confounders.


2020 ◽  
Vol 7 (1) ◽  
pp. e07-e07
Author(s):  
Maryam Riahinezhad ◽  
Hossein Saneian ◽  
Maryam Farghadani ◽  
Shafigheh Parsai Arshad

Introduction: Non-alcoholic fatty liver disease (NAFLD) as a multi-factorial disorder is the most common cause of abnormal liver function tests in adolescents. Objectives: The present study aimed to assess Doppler perfusion index (DPI) in adolescents with NAFLD as compared with healthy subjects. Patients and Methods: Thirty-seven adolescents with NAFLD and 25 healthy individuals were enrolled in the study. Hemodynamic indices were measured using a color Doppler ultrasound machine. Severity of fatty liver disease and steatosis grade were assessed using FibroScan. The measured indices were peak systolic velocity (PSV), resistive index (RI), end-diastolic velocity (EDV), time-averaged mean velocity (TAMV), time-averaged peak velocity (TAPV), portal venous blood flow (PVBF) volume, hepatic arterial blood flow (HABF) volume, and DPI. Results: The mean of DPI in the case and control groups was 0.31±0.11 and 0.31±0.09, respectively (P=0.972). HABF volume was significantly lower in the case group as compared with the control group (103.8 versus 153.3 respectively, P=0.015). PSV, TAMV, mean velocity, and PVBF volume were significantly lower in the case group as compared with the control group (P<0.05). Patients with a higher steatosis grade indicated a significantly lower mean of PSV and TAMV portal than controls (P<0.05). Conclusion: DPI was similar in adolescents with NAFLD and healthy subjects and was not associated with severity of fatty liver disease and steatosis grade. In addition, the percentage of steatosis would be increased with increased liver span.


2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.


2019 ◽  
Vol 17 (1) ◽  
pp. 1328-1338
Author(s):  
Yufeng Xing ◽  
Chuantao Zhang ◽  
Fenfen Zhai ◽  
Tianran Zhou ◽  
Xiang Cui ◽  
...  

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takuya Kawamura ◽  
Hiroaki Tanaka ◽  
Ryota Tachibana ◽  
Kento Yoshikawa ◽  
Shintaro Maki ◽  
...  

AbstractWe aimed to investigate the effects of maternal tadalafil therapy on fetal programming of metabolic function in a mouse model of fetal growth restriction (FGR). Pregnant C57BL6 mice were divided into the control, L-NG-nitroarginine methyl ester (L-NAME), and tadalafil + L-NAME groups. Six weeks after birth, the male pups in each group were given a high-fat diet. A glucose tolerance test (GTT) was performed at 15 weeks and the pups were euthanized at 20 weeks. We then assessed the histological changes in the liver and adipose tissue, and the adipocytokine production. We found that the non-alcoholic fatty liver disease activity score was higher in the L-NAME group than in the control group (p < 0.05). Although the M1 macrophage numbers were significantly higher in the L-NAME/high-fat diet group (p < 0.001), maternal tadalafil administration prevented this change. Moreover, the epididymal adipocyte size was significantly larger in the L-NAME group than in the control group. This was also improved by maternal tadalafil administration (p < 0.05). Further, we found that resistin levels were significantly lower in the L-NAME group compared to the control group (p < 0.05). The combination of exposure to maternal L-NAME and a high-fat diet induced glucose impairment and non-alcoholic fatty liver disease. However, maternal tadalafil administration prevented these complications. Thus, deleterious fetal programming caused by FGR might be modified by in utero intervention with tadalafil.


2021 ◽  
Vol 8 (1) ◽  
pp. e000634
Author(s):  
Monica A Tincopa ◽  
Jane Wong ◽  
Michael Fetters ◽  
Anna S Lok

ObjectiveDespite clear evidence that weight loss via nutritional and physical activity changes improves histological outcomes in non-alcoholic fatty liver disease (NAFLD), many patients struggle to implement and maintain these health behaviour changes. The aim of this study was to characterise disease knowledge, attitudes and behaviours among persons with NAFLD and to identify the factors driving these health behaviours and perceptions.DesignWe conducted semistructured interviews among patients with NAFLD. We used purposeful sampling to enroll equivalent percentages based on age and sex, and enrolled approximately one-third of patients with cirrhosis to capture those perspectives. Interviews were conducted until thematic saturation was achieved. Transcripts were coded using NVivo software to identify themes and subthemes.ResultsA total of 29 patient interviews were completed. Ambiguity about the diagnosis and aetiology of their liver disease was a key theme, though the vast majority of patients were aware that weight loss via nutrition and exercise was the primary therapy. Most patients were asymptomatic, diagnosed incidentally, and reported low level of concern regarding their diagnosis. The primary barriers and facilitators to health behaviour change were the presence of social support, competing medical comorbidities and low motivation to change behaviours.ConclusionsAlthough patients are aware that lifestyle interventions are the primary therapy for NAFLD, there is a gap in knowledge about the condition. The presence of social support and competing medical comorbidities were the most consistent facilitators and barriers to lifestyle change. Tailoring treatment recommendations to provide relevant disease education, specific nutrition and exercise regimens, and personalised approaches based on specific individual barriers and facilitators will likely aid in uptake and maintenance of first-line therapy for NAFLD.


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