Meta-analysis: Efficacy and safety of fibroblast growth factor 21 analogues for the treatment of non-alcoholic steatohepatitis and non-alcoholic steatohepatitis-related fibrosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) analogues have emerged as promising therapeutic targets for non-alcoholic steatohepatitis (NASH). However, the effects and safety of these analogues on NASH and NASH-related fibrosis remain unexplored. AIMS: To estimate the efficacy and safety of FGF21 analogues for treating NASH and NASH-related fibrosis. METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies up to 11 October 2023. Primary outcomes were defined as the fibrosis improvement ≥1 stage without worsening of NASH and NASH resolution without worsening fibrosis. Secondary outcomes included biomarkers of fibrosis, liver injury, and metabolism. Treatment-related adverse events were also analysed. RESULTS: Nine studies, including 1054 patients with biopsy-proven NASH and stage F1-F4 fibrosis, were identified. Seven studies reported histological outcomes. The relative risk (RR) for obtaining fibrosis improvement ≥1 stage efficacy was 1.79 (95% CI 1.29-2.48, I2 = 37%, p < 0.001) with FGF21 analogues relative to placebo. Although no statistically significant difference was observed between FGF21 analogues in NASH resolution, sensitivity analyses and fragility index suggest that this result is unstable. The drugs improved hepatic fat fraction (HFF), along with other biomarkers of fibrosis, liver injury, and metabolism (MRE, LSM, Pro-C3, ELF, ALT, AST, TG, HDL-C, and LDL-C). Additionally, no significant difference in serious adverse event incidence rate was observed (RR = 1.26, 95% CI 0.82-1.94, I2 = 24%, p = 0.3). CONCLUSIONS: FGF21 analogues appear as promising agents for the treatment of NASH and NASH-related fibrosis, and they generally seem to be safe and well tolerated.

Association between atherogenic index of plasma control level and incident cardiovascular disease in middle-aged and elderly Chinese individuals with abnormal glucose metabolism.

BACKGROUND: The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. METHODS: Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. RESULTS: 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90-1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99-1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01-2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03-2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. CONCLUSIONS: In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.

Global epidemiological features and impact of osteosarcopenia: A comprehensive meta-analysis and systematic review.

Osteosarcopenia is defined as the concurrent occurrence of osteopenia/osteoporosis and sarcopenia. The aim of the current study was to perform a systematic review with meta-analysis to determine the global prevalence, risk factors and clinical outcomes of osteosarcopenia. This review was registered in PROSPERO (CRD42022351229). PubMed, Cochrane, Medline and Embase were searched from inception to February 2023 to retrieve eligible observational population-based studies. Pooled osteosarcopenia prevalence was calculated with 95% confidence interval (CI), and subgroup analyses were performed. The risk factor of osteosarcopenia and its association with clinical outcomes were expressed as odds ratio (OR) and hazard ratio (HR), respectively. Heterogeneity was estimated using the I2 test. Study quality was assessed using validated instruments matched to study designs. The search identified 55 158 studies, and 66 studies (64 404 participants, mean age from 46.6 to 93 years) were analysed in the final analysis, including 48 cross-sectional studies, 17 cohort studies and 1 case-control study. Overall, the pooled prevalence of osteosarcopenia was 18.5% (95% CI: 16.7-20.3, I2  = 98.7%), including 15.3% (95% CI: 13.2-17.4, I2  = 97.6%) in men and 19.4% (95% CI: 16.9-21.9, I2  = 98.5%) in women. The prevalence of osteosarcopenia diagnosed using sarcopenia plus osteopenia/osteoporosis was 20.7% (95% CI: 17.1-24.4, I2  = 98.55%), and the prevalence of using sarcopenia plus osteoporosis was 16.1% (95% CI: 13.3-18.9, I2  = 98.0%). The global osteosarcopenia prevalence varied in different regions with 22.9% in Oceania, 21.6% in Asia, 20.8% in South America, 15.7% in North America and 10.9% in Europe. A statistically significant difference was found in the subgroups of the study population between the hospital (24.7%) and community (12.9%) (P = 0.001). Frailty (OR = 4.72, 95% CI: 2.71-8.23, I2  = 61.1%), malnutrition (OR = 2.35, 95% CI: 1.62-3.40, I2  = 50.0%), female sex (OR = 5.07, 95% CI: 2.96-8.69, I2  = 73.0%) and higher age (OR = 1.10, 95% CI: 1.06-1.15, I2 ==86.0%) were significantly associated with a higher risk for osteosarcopenia. Meta-analysis of cohort studies showed that osteosarcopenia significantly increased the risk of fall (HR = 1.54, 95% CI: 1.20-1.97; I2  = 1.0%, three studies), fracture (HR = 2.13, 95% CI: 1.61-2.81; I2  = 67.8%, seven studies) and mortality (HR = 1.75, 95% CI: 1.34-2.28; I2  = 0.0%, five studies). Despite the heterogeneity arising from varied definitions and criteria, our findings highlight a significant global prevalence of osteosarcopenia and its negative impact on clinical health. Standardizing diagnostic criteria for osteosarcopenia would be advantageous in the future, and early detection and management should be emphasized in this patient population.

Frailty in hypertensive population and its association with all-cause mortality: data from the National Health and Nutrition Examination Survey.

Objectives: This study aimed to investigate the relationship between frailty and all-cause mortality in hypertensive population. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 and mortality data from the National Death Index. Frailty was assessed using the revised version of the Fried frailty criteria (weakness, exhaustion, low physical activity, shrinking, and slowness). This study aimed to evaluate the association between frailty and all-cause mortality. Cox proportional hazard models were used to evaluate the association between frailty category and all-cause mortality, adjusted for age, sex, race, education, poverty-income ratio, smoking, alcohol, diabetes, arthritis, congestive heart failure, coronary heart disease, stroke, overweight, cancer or malignancy, chronic obstructive pulmonary disease, chronic kidney disease, and taking medicine for hypertension. Results: We gathered data of 2,117 participants with hypertension; 17.81%, 28.77%, and 53.42% were classified as frail, pre-frail, and robust, respectively. We found that frail [hazard ratio (HR) = 2.76, 95% confidence interval (CI) = 2.33-3.27] and pre-frail (HR = 1.38, 95% CI = 1.19-1.59] were significantly associated with all-cause mortality after controlling for variables. We found that frail (HR = 3.02, 95% CI = 2.50-3.65) and pre-frail (HR = 1.35, 95% CI = 1.15-1.58) were associated with all-cause mortality in the age group ≥65 years. For the frailty components, weakness (HR = 1.77, 95% CI = 1.55-2.03), exhaustion (HR = 2.25, 95% CI = 1.92-2.65), low physical activity (HR = 2.25, 95% CI = 1.95-2.61), shrinking (HR = 1.48, 95% CI = 1.13-1.92), and slowness (HR = 1.44, 95% CI = 1.22-1.69) were associated with all-cause mortality. Conclusion: This study demonstrated that frailty and pre-frailty were associated with an increased risk of all-cause mortality in patients with hypertension. More attention should be paid to frailty in hypertensive patients, and interventions to reduce the burden of frailty may improve outcomes in these patients.

Epidemiological Features of NAFLD From 1999 to 2018 in China.

With dramatic changes in lifestyles over the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disorder in China but has not received sufficient attention. NAFLD-related advanced liver disease and its mortality along with its overall disease burden are expected to increase substantially. There is thus an imperative need to clarify the epidemiological features of NAFLD to guide a holistic approach to management. We summarize eight epidemiological features of NAFLD in China over the past two decades using systematic review and meta-analysis methodology. Our data reveal a rapid growth in the NAFLD population, especially among younger individuals. Importantly, there is a strong ethnic difference in body mass index (BMI) and genetic risk of NAFLD compared with the US population. The etiology of advanced liver disease and its complications (e.g., hepatocellular carcinoma) has been altered because of a Westernized lifestyle and the implementation of effective vaccination strategies against viral hepatitis. Regional epidemiological patterns of NAFLD indicate that economics, environment, and lifestyle are critical factors in disease progression. The analysis also indicates that a large number of patients remain undiagnosed and untreated because of the inadequacy of diagnostic tools and the absence of effective pharmacologic therapies. Given the burden of NAFLD, future policy and research efforts need to address knowledge gaps to mitigate the risk burden.

Unexpected Rapid Increase in the Burden of NAFLD in China From 2008 to 2018: A Systematic Review and Meta-Analysis.

With rapid lifestyle transitions, the increasing burden of nonalcoholic fatty liver disease (NAFLD) in China has emerged as a major public health issue. To obtain a comprehensive overview of the status of NAFLD over the past decade, we evaluated the epidemiology, risk factors, complications, and management of NAFLD in China through a systematic review and meta-analysis. Five English literature databases and three Chinese databases were searched for relevant topics from 2008 to 2018. A total of 392 studies with a population of 2,054,554 were included. National prevalence of NAFLD was 29.2%, with a heavier disease burden among the middle-aged, males, those in northwest China and Taiwan, regions with a gross domestic product per capita greater than 100,000 yuan, and Uygur and Hui ethnic groups. Currently, original studies on natural history and complications of NAFLD in China are scarce. Several studies revealed that NAFLD is positively correlated with the incidence of extrahepatic tumors, diabetes, cardiovascular disease and metabolic syndrome. The Chinese population may have a higher hereditary risk of NAFLD due to more frequent nonsynonymous mutations in genes regulating lipid metabolism. Ultrasonography is the primary imaging tool in the detection of NAFLD in China. Serum tests and risk stratification algorithms for staging NAFLD remain under investigation. Specific pharmaceutical treatments for NAFLD are still undergoing clinical trials. It is noteworthy that the Chinese are underrepresented compared with their proportion of the NAFLD population in such trials. Conclusion: China experienced an unexpected rapid increase in the burden of NAFLD over a short period. Rising awareness and urgent actions need to be taken in order to control the NAFLD pandemic in China.

[Prevalence of Sarcopenia and Associated Factors in Community-dwelling Elderly Populations in Chengdu China].

OBJECTIVE: To determine the prevalence of sarcopenia in community-dwelling elderly populations in Chengdu and its associated risk factors. METHODS: A total of 947 community dwelling residents aged ≥60 yr. in Chengdu participated in this study. Their appendicular skeletal muscle mass was measured through bioelectrical impedance analyses. Sarcopenia was defined using the diagnostic algorithm recommended by the Asia Working Group (AWGS) for Sarcopenia. Data in relation to the demographic characteristics, chronic diseases and life style of the participants were obtained through a questionnaire survey, which included the 15-item geriatric depression scale (GDS-15) and the mini nutritional assessment (MNA). RESULTS: Overall, 10.5% of the elderly participants were identified with sarcopenia: 8.4% in men and 12.5% in women. The prevalence of sarcopenia increased with age: 2.3% in the 60-64 yr., 5.6% in the 65-74 yr., 19.7% in the ≥75 yr.. Age [odds ratio (OR)=1.109, 95% confldence interval (CI):1.054-1.168], smoking (OR=3.482, 95%CI:1.356-8.938) and Malnorishment (OR=5.598, 95%CI:2.677-11.709) are significant predictors of sarcopenia after adjustment for potential confounders. CONCLUSION: Approximately 10% community-dwelling elderly in Chengdu have sarcopenis. Age, smoking, malnutrition are risk factors of sarcopenia.

Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice.

With the increasing number of individuals with diabetes and obesity, nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent, affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden, and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD, including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice.

Comparison of procalcitonin, a potentially new inflammatory biomarker of frailty, to interleukin-6 and C-reactive protein among older Chinese hospitalized patients.

AIM: Procalcitonin (PCT) has predictive value for patients with infectious diseases, but has not been studied in frailty. The purpose of this study was to compare PCT to two other inflammatory biomarkers [interleukin-6 (IL-6)] and C-reactive protein (CRP) in their association with frailty among older hospitalized patients. METHODS: Retrospective study of inpatients (June-December, 2016), who had all three biomarkers measured within 24 h of admission. Frailty was defined according to the Chinese version of a validated frailty scale. Due to the association of biomarkers with infection, we divided patients into "non-infected" (no pneumonia or other infections) and "pneumonia" (using standard criteria) groups. RESULTS: Of 435 patients (mean age 81.6 ± 8.6 years), 181 (41.6%) were designated the non-infected group and 254 (58.4%) the pneumonia group. Prevalence of frailty in the non-infected group was 32.0% (58/181) and frailty (univariate analysis) was associated with higher PCT and IL-6 levels but not CRP. Prevalence of frailty in the pneumonia group was 40.2% (102/254) and frailty was associated with all three biomarkers. In multivariable analysis adjusting for age, gender, smoking, alcohol use, hemoglobin, albumin, neutrophils and creatinine, PCT (not IL-6 and CRP) was associated with frailty in the non-infected group (OR = 5.244; 95% CI, 1.622-16.947; P = 0.006) and none of the biomarkers were associated with frailty in the pneumonia group. CONCLUSIONS: Although the study is limited due to the retrospective methods, PCT but not IL-6 or CRP, was associated with frailty among older inpatients without infection. None of these biomarkers were associated with frailty among patients with pneumonia.

The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta-analysis.

BACKGROUND: Gastric cancer is a major health problem, and frailty and sarcopenia will affect the postoperative outcomes in older people. However, there is still no systematic review to determine the role of frailty and sarcopenia in predicting postoperative outcomes among older patients with gastric cancer who undergo gastrectomy surgery. METHODS: We searched Embase, Medline through the Ovid interface and PubMed websites to identify potential studies. All the search strategies were run on August 24, 2016. We searched the Google website for unpublished studies on June 1, 2017. The data related to the endpoints of gastrectomy surgery were extracted. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the association between sarcopenia and adverse postoperative outcomes by using Stata version 11.0. PRISMA guidelines for systematic reviews were followed. RESULTS: After screening 500 records, we identified eight studies, including three prospective cohort studies and five retrospective cohort studies. Only one study described frailty, and the remaining seven studies described sarcopenia. Frailty was statistically significant for predicting hospital mortality (OR 3.96; 95% CI: 1.12-14.09, P = 0.03). Sarcopenia was also associated with postoperative outcomes (pooled OR 3.12; 95% CI: 2.23-4.37). No significant heterogeneity was observed across these pooled studies (Chi2 = 3.10, I2 = 0%, P = 0.685). CONCLUSION: Sarcopenia and frailty seem to have significant adverse impacts on the occurrence of postoperative outcomes. Well-designed prospective cohort studies focusing on frailty and quality of life with a sufficient sample are needed.

Association between sarcopenia with lifestyle and family function among community-dwelling Chinese aged 60 years and older.

BACKGROUND: Sarcopenia is defined as the age-related decline in skeletal muscle mass and function. The risk factors and causes of sarcopenia must be identified to develop prevention and treatment strategies for this syndrome. Our aim was to examine the association between sarcopenia with lifestyle and family function among community-dwelling Chinese people aged 60 years and older. METHODS: We conducted this study to evaluate sarcopenia among 834 community-dwelling Chinese individuals aged ≥60 years using the Asian Working Group for Sarcopenia (AWGS) criteria. The sociodemographic characteristics, food consumption patterns, habits of smoking, and alcohol consumption of the participants were collected using a general questionnaire, whereas physical activity was assessed using the International Physical Activity Questionnaire (IPAQ; long-form version). Family function was assessed using the Family APGAR scale. In addition, the association of sarcopenia with lifestyle and family function was examined using univariate and multivariate analyses. RESULTS: The total prevalence rate of sarcopenia was 10.6%. Female participants with sarcopenia had a lower frequency per week of nut consumption than those without sarcopenia (p < 0.05), whereas, for male participants, the differences in food consumption patterns of those with sarcopenia versus those without sarcopenia were not significant. Among the participants, the mean Family APGAR score was 8 (standard deviation [SD] = 0.92). For both sexes, participants with sarcopenia had lower family function scores than those without sarcopenia. In the multivariate model, after adjustment for all covariates, frequency per week of nut consumption (adjusted OR 0.724, 95% CI 0.532-0.985, P < 0.05) and Family APGAR score (adjusted OR 0.683, 95% CI 0.496-0.940, P = 0.019) were statistically significantly associated with sarcopenia. The relationship between other lifestyle habits and sarcopenia was not significant. CONCLUSION: There was significant association between sarcopenia with intake of nuts and family function. Further studies should evaluate if adequate intake of nuts and a well-functioning family may be effective in lowering the risk of sarcopenia.

Association between sarcopenia and nutritional status and physical activity among community-dwelling Chinese adults aged 60 years and older.

AIM: The aim of the present study was to examine the association between sarcopenia and nutritional status and physical activity among community-dwelling Chinese people aged 60 years and older. METHODS: This study was carried out on 836 community-dwelling Chinese individuals aged ≥60 years to evaluate sarcopenia using the Asian Working Group for Sarcopenia criteria. Sociodemographic characteristics and lifestyle habits were collected using a general questionnaire. Nutritional status was assessed using the Mini Nutritional Assessment and biochemical parameters, whereas physical activity was assessed using the long form of the International Physical Activity Questionnaire. In addition, univariate and multivariate analysis was used to analyze the association between sarcopenia with nutritional status and physical activity. RESULTS: The total prevalence rate of sarcopenia was 10.5%, 47 (11.3%) men and 41 (9.7%) women who were classified as sarcopenia. The prevalence of sarcopenia was significantly lower among the participants of normal nutrition status. Compared with the participants with sarcopenia, those without sarcopenia had higher levels of prealbumin (P < 0.05) and hemoglobin (P < 0.05) for both sexes. In the multivariate model, after adjustment for all covariates, the Mini Nutritional Assessment score (adjusted OR 0.769, 95% CI 0.689-0.859, P < 0.05) was statistically significantly associated with sarcopenia, but the relationship between physical activity and sarcopenia was not significant. CONCLUSIONS: The prevalence of sarcopenia in the Chinese community-dwelling population aged 60 years and older was high. There was a significant association between sarcopenia and nutritional status, but not with physical activity, based on a questionnaire. Further studies should evaluate whether maintaining a good nutritional status might be effective in lowering the risk of sarcopenia. Geriatr Gerontol Int 2017; 17: 1959-1966.