1.Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients
Fuxi LI ; Junzhao YE ; Yanhong SUN ; Yansong LIN ; Tingfeng WU ; Congxiang SHAO ; Qianqian MA ; Xianhua LIAO ; Shiting FENG ; Bihui ZHONG
Diabetes & Metabolism Journal 2021;45(3):417-429
Background:
Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear.
Methods:
Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.
Results:
There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals.
Conclusion
A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
2.Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients
Fuxi LI ; Junzhao YE ; Yanhong SUN ; Yansong LIN ; Tingfeng WU ; Congxiang SHAO ; Qianqian MA ; Xianhua LIAO ; Shiting FENG ; Bihui ZHONG
Diabetes & Metabolism Journal 2021;45(3):417-429
Background:
Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear.
Methods:
Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.
Results:
There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals.
Conclusion
A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
3.Research advances in dietary intervention in the treatment of metabolic associated fatty liver disease
Junzhao YE ; Yansong LIN ; Bihui ZHONG
Journal of Clinical Hepatology 2021;37(3):709-713
Poor dietary habit is an important cause of the global prevalence of metabolic associated fatty liver disease (MAFLD), and the adjustment of dietary pattern is the cornerstone of MAFLD management. In recent years, a large number of new dietary intervention methods have been proposed and applied in the treatment of MAFLD, including calorie restrict diet, low-carbohydrate diet, low-glycemic index diet, low free sugar diet, intermittent fasting pattern, high protein diet, and Mediterranean diet, and these new methods have different effects in clinical practice. This article introduces the treatment concepts and practical methods of these new dietary treatment strategies and the evidence of their benefits in the treatment of MAFLD in China and globally, so as to provide a new perspective for clinicians to guide patients to achieve individualized nutritional therapy.
4.Pathogenesis of hepatorenal syndrome
Xianhua LIAO ; Junzhao YE ; Bihui ZHONG
Journal of Clinical Hepatology 2020;36(11):2406-2410
Hepatorenal syndrome (HRS) is one of the common serious complications in patients with end-stage liver disease and has poor prognosis and high mortality, and in-depth studies on its pathogenesis will help to achieve precise prevention and treatment. Although the exact pathogenesis of HRS has not yet been fully elucidated, achievements have been made in the pathogenesis of HRS. The classic mechanism of the hypothesis of visceral vasodilation continues to be enriched and perfected, and new understandings have been gained for the role of systemic inflammation and intestinal bacterial translocation in pathogenesis. In addition, a new concept of cardiorenal syndrome is put forward for the involvement of cardiac dysfunction in HRS, and renal pathology has been questioned and challenged. This article reviews the research advances in the pathogenesis of HRS in recent years and related implications for clinical work.
5.Epidemiology of nonalcoholic fatty liver disease in some regions of China
Tingfeng WU ; Xianhua LIAO ; Bihui ZHONG
Journal of Clinical Hepatology 2020;36(6):1370-1373
Nonalcoholic fatty liver disease (NAFLD) has replaced viral hepatitis and become the most important chronic liver disease in the world. Abdominal ultrasound remains the main method for the diagnosis of NAFLD in China. The studies in China showed that in the last two decades, the prevalence rate of NAFLD was 13%-43% and tended to increase year by year, and the new cases accounted for about 4% each year, with a certain proportion of patients with non-obese NAFLD. There is a significant difference in prevalence rate between the populations from different regions, with a higher prevalence rate of NAFLD in the well-developed southeast coastal regions where people have a similar lifestyle to those in Western countries. Metabolic disorders, such as type 2 diabetes, obesity, hyperlipidemia, hyperuricemia, and hypertension, are risk factors for NAFLD. National-wide large-sample epidemiological investigation is still needed in China to help support the diagnosis, treatment, and prevention of NAFLD.
6.Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China:A multicenter prospective observational study
Jie YUSHENG ; Lin CHAOSHUANG ; Yuan JING ; Zhao ZHIXIN ; Guan YUJUAN ; Zhou YUANPING ; Zhou XIAOHUI ; Zhong BIHUI ; Ye YINONG ; Zhang LIHUA ; Tao LING ; Li JIANPING ; Zhang XIAOHONG ; Chong YUTIAN
Liver Research 2020;4(3):153-158
Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diag-nosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.
7.Factors influencing accuracy of fibrosis diagnosis using shear wave elastrography in patients with chronic hepatitis B
Junzhao YE ; Wei WANG ; Bing LIAO ; Yang WANG ; Yanqin WU ; Xianhua LIAO ; Bihui ZHONG
The Journal of Practical Medicine 2016;32(15):2454-2458
Aims The purpose of this study is to investigate thediagnostic value of SWEfor fibrosis in patients with CHBand the factorsinfluencing the accuracy. Methods From July 2013 to October 2015, 261 patients with CHB were recruited from the First Affiliated Hospital of Sun Yat-sen University.All patients received SWE, anthropometry measurement, blood cell count, liver function test and virological indicators measurement. Liver fibrosis was staged from F0 to F4 by METAVIR scorebased onliver biopsy results of 133 CHB patients , while 128 patients were diagnosed as decompensated cirrhosis. Diagnostic accuracyof SWE were evaluated by Receiver Operating Characteristic Curve (ROC) using liver hepatic pathology and decompensated cirrhosis as gold standards. Logistic model was used to find out confounding factors that influence the accuracy of SWE. Results The Area Under ROC (AUC) for liver stiffness measurement with SWE were 0.891, 0.932 and 0.910 for the diagnosis of significant fibrosis (≥ F2), advanced fibrosis (≥F3) and cirrhosis (F4), respectively. A multifactor logistic regression combined modelwas built and showed that hepatic steatosis will decrease the accuracy of SWE. Conclusion SWE could be a valuable method for the noninvasive liver fibrosis assessment. The accuracy of SWE may be influenced by hepatic steatosis.
8.Research advances in radiological examination for nonalcoholic fatty liver disease
Journal of Clinical Hepatology 2016;32(8):1477-1482
There is a high prevalence of nonalcoholic fatty liver disease (NAFLD) around the world, and early diagnosis and evaluation of liver fatty degeneration and fibrosis degree play important roles in the early treatment and prognostic evaluation of patients with NAFLD. This article reviews the principles, diagnostic accuracy, influencing factors, and practicability of various imaging techniques applied in liver fat quantification and fibrosis prediction. Studies have shown that radiological fat quantitative diagnosis based on ultrasound and magnetic resonance and liver fibrosis evaluation based on elastography have a high level of accuracy and promising prospects; however, such techniques lack standard cut-off values and operating procedures which may provide a reference for clinical application.
9.Expression and significance of IL-21 in patients infected with hepatitis B virus at different stages
Jiayan YAO ; Kang CHAO ; Minrui LI ; Yanqin WU ; Junzhao YE ; Bihui ZHONG
The Journal of Practical Medicine 2015;(7):1061-1064
Objective To determine the expression of interleukin-21 (IL-21) in patients infected with hepatitis B virus (HBV) and its association with HBV-DNA and ALT. Methods Clinical dates and blood specimen were collected from 25 unrelated healthy controls (HC) and 101 independent chronic HBV infected patients, including 25 patients in immune tolerant phase (IT), 25 in immune clearance phase (IC), 26 patients in inactive HBV carrier state (IA) and 25 patients in immune reactive phase (IR). Serum IL-21 levels were measured by Cytometric Bead Array (CBA). IL-21 mRNA and IL-21 receptor mRNA were measured by real-time PCR. Results Chronic HBV-infected patients had higher levels of serum IL-21 and IL-21 mRNA , with P <0.001 for both. In subgroup analysis, both serum IL-21 and IL-21 mRNA levels in IC, IR were higher than those in IT, IA and HC (all P < 0.001). Serum IL-21 level in IA was higher than that in HC and IT (P <0.001, P = 0.036). IL-21R mRNA levels were different between groups. Serum IL-21 level was associated with HBV-DNA (r = -0.472, P < 0.001), but not with ALT. Conclusion IL-21, up-regulated in chronic HBV infection, is associated with immune activity and may play a key role in HBV control.
10.Relation between apolipoproteinC3 (-482C>T) polymorphism and nonalcoholic fatty liver disease in the Han Chinese population
Minrui LI ; Shenghong ZHANG ; Xianhua LIAO ; Bihui ZHONG
The Journal of Practical Medicine 2014;(16):2566-2569
Objective To investigate the relation between apolipoproteinC3 (-482C>T ) polymorphism and nonalcoholic fatty liver disease (NAFLD) and its clinical characteristics in the Han Chinese population. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis(PAGE)were used to analyse the genotype of the apolipoproteinC3 (-482C>T) variants. Results No relation between the apolipopreoteinC3 (-482C>T) polymorphism and NAFLD was found. However, NAFLD patients carrying T allele were more susceptible to insulin resistant (IR), hypertension, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol (HDL) than homozygote CC genotype. Conclusion There was no relation between the apolipopreoteinC3 (-482C>T)polymorphism and NAFLD in Han Chinese population, but T-carriers were more susceptible to metabolic disorder.

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