Non-alcoholic Fatty Liver Disease Liver Fat Score Research Articles

Long-term effects of the changes in hepatic steatosis status on the risk of incident type 2 diabetes mellitus: A 15-year community-based prospective cohort study

AimsWe investigated the long-term effect of changes in hepatic steatosis on the risk of developing T2DM. MethodsWe evaluated 3510 participants from the 2001–2016 Korean Genome and Epidemiology Study. Those with significant alcohol consumption or T2DM during 2001–2004 were excluded. Steatosis was defined as non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS) of over −0.64, and baseline values were assessed between 2001 and 2002. Differences in NAFLD-LFS (ΔLFS) and changes in steatosis status (no, intermittent [resolved or incident], and persistent steatosis) were assessed between 2003 and 2004. Changes in the risk of diabetes status were observed until 2016. ResultsOver 52,650 person-years of follow-up, T2DM developed in 296 participants (8.4%). The incidence of diabetes in those with no steatosis, intermittent steatosis, and persistent steatosis during follow-up increased by 5.1%, 14.1%, and 27.1% respectively. Multivariate-adjusted analysis revealed that the risk was higher in those with persistent steatosis than those with no steatosis and intermittent steatosis. Baseline NAFLD-LFS and ΔLFS was associated with increased risk of incident T2DM. ConclusionsInitial severity as well as aggravation of steatosis is an independent predictor of incident T2DM. Strategies aimed at reducing liver fat may prevent future development of diabetes among patients with NAFLD.

Liver fibrosis indices are related to diabetic peripheral neuropathy in individuals with type 2 diabetes

The association between nonalcoholic fatty liver (NAFL) or liver fibrosis and diabetic peripheral neuropathy (DPN) has not been well studied. We aimed to investigate the association of NAFL or liver fibrosis indices and DPN in individuals with type 2 diabetes. In this observational study, we included 264 individuals with type 2 diabetes, and calculated non-alcoholic fatty liver disease (NAFLD) liver fat score, NAFLD fibrosis score, and Fibrosis-4 (FIB-4) index to evaluate the status of NAFLD or liver fibrosis. DPN was diagnosed when the Michigan Neuropathy Screening Instrument—Physical Examination score was ≥ 2.5. The NAFLD fibrosis score and FIB-4 index were significantly higher in individuals with DPN than in those without DPN. Logistic analyses showed that the NAFLD fibrosis score and FIB-4 index were associated with DPN after adjustment for covariates (adjusted odds ratio 1.474 and 1.961, respectively). In the subgroup analysis, this association was only significant in the group with a high NAFLD liver fat score (> − 0.640). Serum levels of fetuin-A, a hepatokine, were decreased in individuals with abnormal vibration perception or 10-g monofilament tests compared with their counterparts. The present study suggests that liver fibrosis might be associated with DPN in individuals with type 2 diabetes.

Dairy protein intake is inversely related to development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is closely related to metabolic dysfunction, including insulin resistance, obesity, and metabolic syndrome. Dairy protein, rich in casein and whey protein, could help to reduce metabolic diseases. Therefore, we investigated the relationship between dairy protein intake and incident NAFLD. We analyzed data for 5171 adults aged 40-69 years from the Korean Genome and Epidemiology Study.(KoGES) Participants were separated as men, women aged ≥50 years, and women aged <50 years and then divided into tertiles based on dairy protein intake. NAFLD was defined as NAFLD liver fat score >-0.640. Scores were calculated as 1.18 × metabolic syndrome (Yes: 1, No: 0)+0.45 × diabetes mellitus (Yes: 2, No: 0)+0.15 × serum insulin+0.04 × AST-0.94 × (AST/ALT)-2.89. Cox proportional hazards spline curves were drawn to visualize dose-response relationships between dairy protein intake and incident NAFLD. Multiple Cox hazard regression analysis was conducted to examine associations between dairy protein intake and incident NAFLD. The Cox proportional hazards spline curves revealed a negative linear relationship between dairy protein intake and incident NAFLD. The cumulative incidence of NAFLD significantly decreased with increasing tertiles of dairy protein intake in men and women aged ≥50 years. After adjusting for confounding factors, the hazard ratios and 95% confidence intervals for NAFLD in the middle and highest tertiles, compared to the lowest tertile, were 0.80 (0.67-0.96) and 0.71 (0.57-0.88) in men, 0.89 (0.72-1.09) and 0.72 (0.56-0.92) in women aged ≥50 years, and 1.01 (0.80-1.27) and 0.91 (0.67-1.24) in women aged <50 years, respectively. We found that higher dairy protein intake was significantly and inversely associated with the risk of incident NAFLD in men and women aged ≥50 years. Consumption of milk and other dairy products could help prevent the development of NAFLD.

Differences among Three Skeletal Muscle Mass Indices in Predicting Non-Alcoholic Fatty Liver Disease: Korean Nationwide Population-Based Study.

Recent studies have investigated the relationship between sarcopenia and non-alcoholic fatty liver disease (NAFLD); however, there is no unified definition of sarcopenia. Thus, we aimed to investigate the differences among three skeletal muscle mass indices (SMI) in predicting NAFLD. This study included 8133 adults from the 2008–2010 Korea National Health and Nutrition Survey. SMI was calculated as appendicular skeletal muscle mass divided by height-square (hSMI), weight (wSMI), or body mass index (bSMI). The presence of NAFLD was defined by using the NAFLD-liver fat score. On the receiver operating characteristic curve analysis, the predictive power of wSMI for NAFLD was significantly higher than those of hSMI and bSMI in men (wSMI vs. hSMI, p = 0.003; wSMI vs. bSMI, p < 0.001). In women, the predictive power of hSMI was only significantly higher than that of bSMI (p = 0.023), and other predictive powers were not significantly different. In addition, hSMI was correlated with insulin resistance and NAFLD-liver fat score in the opposite direction to wSMI and bSMI in both men and women. Among the three definitions of SMI, wSMI showed the highest diagnostic performance for predicting NAFLD in men, suggesting the importance of defining sarcopenia for its association with specific diseases.

Acupuncture for type 2 diabetes mellitus with nonalcoholic fatty liver disease: A protocol for systematic review and meta-analysis.

Background:T2DM with NAFLD is a common disorder of glucose and lipid metabolism affecting the quality of life of patients. Due to the limitations and adverse reactions of drug treatment, acupuncture has been proved to be an effective method for the treatment of T2DM with NAFLD. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of NAFLD in T2DM class, and to provide high-quality evidence for acupuncture in the treatment of this disease.Methods:From establishment of the database to 31 July 2021, We will search the Cochrane Central Register of controlled trials, PubMed, MEDLINE, EMBASE, Web of science. Five Chinese databases, including China National Knowledge Infrastructure (CNKI), WanFang database, VIP, Chinese Biomedical Literature Database (CBM) and the Chinese clinical trial registry. There are no restrictions on language or publication, and they are independently screened and collected by two reviewers. Review Manager 5.3 software will be used for meta analysis. If necessary, heterogeneity testing, data synthesis, and subgroup analysis will be performed.Results:The effectiveness and safety of acupuncture in the treatment of T2DM with NAFLD will be assessed by the outcomes of test's, including: imaging indicators, biomarkers of hepatic steatosis, serological indicators of hepatic fibrosis, improvement of serum NAFLD liver fat score, BMI, blood glucose indexes, blood lipid indexes, insulin level and safety indicators.Conclusion:This meta-analysis will further determine the beneficial efficacy and safety of acupuncture for T2DM combined with NAFLD.

Liver fat scores do not reflect interventional changes in liver fat content induced by high-protein diets

Non-alcoholic fatty liver disease (NAFLD) is common in Metabolic Syndrome and type 2 diabetes (T2DM), driven by energy imbalance, saturated fats and simple carbohydrates. NAFLD requires screening and monitoring for late complications. Liver fat indices may predict NAFLD avoiding expensive or invasive gold-standard methods, but they are poorly validated for use in interventional settings. Recent data indicate a particular insensitivity to weight-independent liver fat reduction. We evaluated 31 T2DM patients, completing a randomized intervention study on isocaloric high-protein diets. We assessed anthropometric measures, intrahepatic lipid (IHL) content and serum liver enzymes, allowing AUROC calculations as well as cross-sectional and longitudinal Spearman correlations between the fatty liver index, the NAFLD-liver fat score, the Hepatosteatosis Index, and IHL. At baseline, all indices predicted NAFLD with moderate accuracy (AUROC 0.731–0.770), supported by correlation analyses. Diet-induced IHL changes weakly correlated with changes of waist circumference, but no other index component or the indices themselves. Liver fat indices may help to easily detect NAFLD, allowing cost-effective allocation of further diagnostics to patients at high risk. IHL reduction by weight-independent diets is not reflected by a proportional change in liver fat scores. Further research on the development of treatment-sensitive indices is required.Trial registration: The trial was registered at clinicaltrials.gov: NCT02402985.

Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases.

Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.

Diagnostic accuracy assessment of molecular prediction model for the risk of NAFLD based on MRI-PDFF diagnosed Chinese Han population

BackgroundSeveral molecular prediction models based on the clinical parameters had been constructed to predict and diagnosis the risk of NAFLD, but the accuracy of these molecular prediction models remains need to be verified based on the most accurate NAFLD diagnostic method. The aim of this study was to verify the accuracy of three molecular prediction models Fatty liver index (FLI), NAFLD liver fat score system (NAFLD LFS), and Liver fat (%) in the prediction and diagnosis of NAFLD in MRI-PDFF diagnosed Chinese Han population.Patients and methodsMRI-PDFF was used to diagnose the hepatic steatosis of all the subjects. Information such as name, age, lifestyle, and major medical histories were collected and the clinical parameters were measured by the standard clinical laboratory techniques. The cut-off values of each model for the risk of NAFLD were calculated based on the MRI-PDFF results. All data were analyzed using the statistical analysis software SPSS 23.0.ResultsA total of 169 subjects were recruited with the matched sex and age. The ROC curves of FLI, NAFLD LFS, and Liver fat (%) models were plotted based on the results of MRI-PDFF. We founded that the accuracy of FLI, NAFLD LFS, and Liver fat (%) models for the prediction and diagnosis of NAFLD were comparative available in Chinese Han population as well as the validity of them in other ethnics and regions.ConclusionsThe molecular prediction models FLI, NAFLD LFS, and Liver fat (%) were comparative available for the prediction and diagnosis of NAFLD in Chinese Han population. MRI-PDFF could be used as the golden standard to develop the new molecular prediction models for the prediction and diagnosis of NAFLD.

Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV-HIV Co-infected Adults.

There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation. Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV-HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated. HBV-HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV-HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV-HIV. Negative predictive values were higher than positive predictive values for all scores in both groups. The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.

Relationship between Muscle Mass and Non-Alcoholic Fatty Liver Disease.

Simple SummarySarcopenia and non-alcoholic fatty liver disease share common pathological and physiological mechanisms that can co-occur with aging. Low skeletal muscle mass index and non-alcoholic fatty liver disease were related, regardless of abdominal obesity. Maintenance of muscle mass should be emphasized for prevention of non-alcoholic fatty liver disease. Management of fatty liver also could be an important strategy to preserve muscle mass.Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs = 1.21, 95% CIs = 1.05–1.40). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs = 1.56, 95% CIs = 1.38–1.78). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

Diagnostic value of serological biomarkers for detection of non-alcoholic fatty liver disease (NAFLD) and/or advanced liver fibrosis in people living with HIV.

We aimed to evaluate the accuracy of serological biomarkers for non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis (METAVIR-F3F4) in HIV mono-infected individuals. In all, 674 participants from the PROSPEC-HIV study (NCT02542020), who had blood sample tests and transient elastography (TE) performed on the same day, were eligible. Exclusion criteria were viral hepatitis co-infection (n=90), abusive alcohol intake (n=61), missing data (n=47) or unreliable TE (n=39). NAFLD was defined by controlled attenuation parameter≥248dB/m and advanced fibrosis by liver stiffness measurement≥8.7kPa with M probe or ≥7.2kPa with XL probe. Biomarkers for NAFLD [Steato-ELSA, Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), NAFLD-Liver Fat Score (NAFLD-LFS)] and fibrosis [Fibrosis-4 score (FIB-4), Aspartate-to-Platelet Ratio Index (APRI) and NAFLD Fibrosis Score (NFS)] were calculated. A total of 437 patients [57% female, age=44 (interquartile range: 35-52)years, body mass index (BMI)=26.1 (23.4-29.3)kg/m2 , CD4=660 (427-901)cells/μL] were included. The prevalence [95% confidence interval (CI)] of NAFLD and advanced fibrosis were 38.2% (33.8-42.9) and 10.5% (8.0-13.8), respectively. The areas (95% CI) under the receiver operator curve (AUROCs) for diagnosis of NAFLD were 0.854 (0.818-0.889), 0.840 (0.804-0.877), 0.805 (0.762-0.847) and 0.793 (0.750-0.836) for Steato-ELSA, FLI, HSI and NAFLD-LFS (P<0.001), respectively. All tests yielded satisfactory sensitivities, specificities and negative predictive values (NPVs). The AUROCs (95% CI) for diagnosis of advanced fibrosis were 0.736 (0.659-0.814), 0.700 (0.614-0.7851) and 0.795 (0.726-0.864) for FIB-4, APRI and NFS (P=0.077), respectively. These tests yielded high specificities and negative predictive values (NPVs)>90%. Biomarkers for NAFLD had a good accuracy and those for fibrosis had high specificities and NPVs. These tests should be integrated to HIV care to detect NAFLD and to exclude advanced liver fibrosis.

Development of a simple nonalcoholic fatty liver disease scoring system indicative of metabolic risks and insulin resistance.

BackgroundNonalcoholic fatty liver disease (NAFLD) is estimated to affect approximately 30% population worldwide. However, there is yet a basic and generally implementable approach to define individuals at risk for NAFLD estimative of metabolic risk.MethodsTotal of 3,634 general participants without history of liver disease and alcohol consumption who received the Korean National Health and Nutrition Examination Survey between 2008 and 2010 were studied. Logistic regression was used to identify significant covariates indicative of NAFLD. Multivariable-adjusted logistic regression was carried out for evaluation on estimative impact of the derived score on metabolic risks.ResultsSex [female; odd ratio (OR), 2.492; 95% confidence interval (CI), 1.921–3.233; P<0.001], waist circumference (WC) (OR, 1.093; 95% CI, 1.077–1.110, P<0.001) systolic blood pressure (OR, 1.033; 95% CI, 1.025–1.040; P<0.001), fasting serum glucose (FSG) (OR, 1.032; 95% CI, 1.026–1.038; P<0.001), triglyceride (OR, 1.007; 95% CI, 1.006–1.009; P<0.001), and alanine aminotransferase (OR, 1.110; 95% CI, 1.097–1.124; P<0.001) were independently indicative of NAFLD, which constituted the derived scoring system. The system revealed a significant correlation with the NAFLD liver fat score, fatty liver index (FLI), body mass index, age, alanine aminotransferase, and triglycerides (BAAT) score, lipid accumulation product, and hepatic steatosis index. In addition, the derived score was significantly estimative of insulin resistance.ConclusionsThe developed score may be supportive of stratification of individuals at high risk of NAFLD, non-invasive fast diagnosis of NAFLD, and estimation of metabolic risk. Future studies that compare the derived score with standard diagnostic tests-validated data, such as ultrasonography of the liver, are needed.

Comparative Assessment and External Validation of Hepatic Steatosis Formulae in a Community-Based Setting.

Several hepatic steatosis formulae have been validated in various cohorts using ultrasonography. However, none of these studies has been validated in a community-based setting using the gold standard method. Thus, the aim of this study was to externally validate hepatic steatosis formulae in community-based settings using magnetic resonance imaging (MRI). A total of 1301 community-based health checkup subjects who underwent liver fat quantification with MRI were enrolled in this study. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC). Non-alcoholic fatty liver disease (NAFLD) liver fat score showed the highest diagnostic performance with an AUROC of 0.72, followed by Framingham steatosis index (0.70), hepatic steatosis index (HSI, 0.69), ZJU index (0.69), and fatty liver index (FLI, 0.68). There were considerable gray zones in three fatty liver prediction models using two cutoffs (FLI, 28.9%; HSI, 48.9%; and ZJU index, 53.6%). The diagnostic performance of NAFLD liver fat score for detecting steatosis was comparable to that of ultrasonography. The diagnostic agreement was 72.7% between NAFLD liver fat score and 70.9% between ultrasound and MRI. In conclusion, the NAFLD liver fat score showed the best diagnostic performance for detecting hepatic steatosis. Its diagnostic performance was comparable to that of ultrasonography in a community-based setting.

Hepatic fibrosis is associated with total proteinuria in Korean patients with type 2 diabetes.

The association between non-alcoholic fatty liver disease (NAFLD) and diabetic kidney disease assessed using either albuminuria or proteinuria remains controversial. This study aimed to investigate the association between hepatic steatosis or fibrosis and albuminuria or proteinuria in Korean patients with type 2 diabetes mellitus (T2D).We enrolled 1108 patients with T2D and categorized as 3 groups; non-proteinuria (NP), isolated non-albumin proteinuria (iNAP), and albuminuria. Urinary albumin and protein levels were assessed as urinary albumin-to-creatinine ratio (uACR) and urinary protein-to-creatinine ratio (uPCR), respectively. Hepatic steatosis and fibrotic burden were assessed using the NAFLD liver fat score, Fibrosis-4 calculator (FIB-4) index, and NAFLD fibrosis score (NFS).The prevalence of significant steatosis was similar among groups (NP: 74.6% vs iNAP: 70.3% vs albuminuria: 79.9%, P = .085). The prevalence of significant fibrosis was significantly higher in the iNAP (18.7%) and albuminuria (16.5%) groups than in the NP group (9.5%, P = .001). Both uPCR and uACR showed a correlation with NFS (uPCR: r = 0.123, P < .001; uACR: r = 0.064, P = .033). In multivariate logistic regression analysis, uPCR ≥150 mg/g was found to have a stronger association with hepatic fibrosis than uACR ≥30 mg/g (adjusted odds ratio 1.55 [95% CI 1.03–2.33] vs adjusted odds ratio 1.16 [95% CI, 0.72–1.87]).In conclusion, patients with iNAP and albuminuria had a higher prevalence of hepatic fibrosis than those without proteinuria. Total proteinuria was associated with advanced liver fibrosis, whereas albuminuria was related to hepatic steatosis.

Thrombospondin1 as a potential therapeutic target for human nonalcoholic fatty liver disease.

Thrombospondin1 as a potential therapeutic target for human nonalcoholic fatty liver disease.

560-P: The Liver Fibrosis Score Is Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) is interrelated with nonalcoholic fatty liver disease (NAFLD) and liver fibrosis. However, the association between NAFLD and diabetic peripheral neuropathy (DPN) has not been well studied. Methods: We prospectively enrolled subjects with T2DM to evaluate risk factors of DPN and to develop a screening tool of DPN. In this study, we analyzed the data of 127 subjects in whom we could calculate NAFLD and liver fibrosis scores. DPN was diagnosed using the Michigan Neuropathy Screening Instrument. Non-invasive markers of NAFLD (hepatic steatosis index, and NAFLD liver fat score) and liver fibrosis (NAFLD fibrosis score, and fibrosis-4 score) were calculated using equations containing several combinations of age, the presence of obesity or metabolic syndrome, liver function test, fasting insulin level, and platelet count. Body composition was measured by bio-impedance analysis. Clinical parameters and various markers were compared according to the presence of DPN. Results: The prevalence of DPN in our study was 39.3%. There was no significant difference in body mass index, diabetes duration, and liver function test between subjects with DPN and those without DPN. Subjects with DPN showed older age, and higher fasting blood glucose level. Hepatic steatosis index and NAFLD liver fat score were comparable between subjects with or without DPN. In contrast, subjects with DPN showed significantly higher NAFLD fibrosis score (-0.7 vs. -1.3, P = 0.004) and fibrosis-4 score (1.6 vs. 1.2, P = 0.014) compared to those without DPN. These two scores were negatively associated with lean body mass. After adjusting lean body mass, the association between liver fibrosis scores and DPN was still significant. Conclusion: The liver fibrosis scores but not NAFLD scores were higher in subjects with DPN compared to those without DPN. Liver fibrosis and DPN might share common pathophysiology. Disclosure K. Kim: None. T. Oh: None. Y. Shin: None. S. Choi: None. H. Jang: Speaker’s Bureau; Self; Daiichi Sankyo, Handok, Pfizer Inc., Takeda Pharmaceutical Company Limited.

1072-P: Activation of Heat Shock Response Ameliorates Nonalcoholic Fatty Liver Disease Biomarkers

Background: Nonalcoholic fatty liver disease (NAFLD) often accompanies with metabolic disorders, such as metabolic syndrome (Mets) and type 2 diabetes (T2D). Effective treatment strategy to control NAFLD is not fully established yet. Cellular stress adaptation is one of the most important homeostatic ability, but this response can be deteriorated by metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates stress adaptive heat shock response and improves metabolic abnormalities such as insulin resistance, hyperglycemia and inflammation in Mets and T2D. Methods: Retrospective analysis of the effects of MES+HS treatment on NAFLD biomarkers was performed in the subject with healthy men (n=10), Mets (n=40) and the patient with T2D (n=100). Results: In healthy males, there were no alterations in NAFLD steatosis or fibrosis biomarkers. In subjects with Mets, many of the NAFLD steatosis markers, such as AST/ALT ratio (from 0.80 to 0.94. p&amp;lt;0.01), fatty liver index (FLI: from 62.3 to 57.3. p&amp;lt;0.01), NAFLD-liver fat score (NAFLD-LFS: from 0.002 to - 0.276. p&amp;lt;0.01), liver/spleen (L/S) ratio (from 0.994 to 1.098. p&amp;lt;0.01) and hepatic steatosis index (HSI: from 37.2 to 36.0. p&amp;lt;0.01) were ameliorated upon MES+HS treatment, but NAFLD fibrosis markers were not. In patients with T2D, all those investigated NAFLD steatosis markers including AST/ALT ratio (from 0.94 to 1.08. p&amp;lt;0.05), FLI (from 64.0 to 59.6. p&amp;lt;0.01), LFS (from 1.40 to 0.90. p&amp;lt;0.05), L/S ratio (from 0.987 to 1.096. p&amp;lt;0.01) and HSI (from 40.2 to 39.4. p&amp;lt;0.01), visceral adiposity index (VAI: from 219.4 to 197.2. p&amp;lt;0.01) and triglyceride × fasting glucose index (TyG: from 4.05 to 3.95. p&amp;lt;0.01) were improved and NAFLD fibrosis markers such as Fib4 index (from 1.72 to 1.62. p&amp;lt;0.05) and NAFLD-fibrosis score (from - 0.23 to - 0.18. p&amp;lt;0.05) were ameliorated upon MES+HS treatment. Conclusions: Thus MES+HS, a physical interventional medicine may become a novel treatment strategy for NAFLD as well as metabolic disorders. Disclosure T. Kondo: None. S. Kitano: None. N. Miyakawa: None. T. Watanabe: None. R. Goto: None. M. Sakaguchi: None. M. Igata: None. J. Kawashima: None. H. Motoshima: None. T. Matsumura: None. E. Araki: Advisory Panel; Self; Abbott. Speaker’s Bureau; Self; ARKRAY, Astellas Pharma Inc., AstraZeneca, Eli Lilly Japan K.K., Merck &amp; Co., Inc., Novo Nordisk Inc., WebMD LLC. Other Relationship; Self; Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Japan Ministry of Economy, Trade and Industry (24-065)

Prevalence of NAFLD in Guatemala Following Exposure to a Protein-Energy Nutrition Intervention in Early Life

Abstract Objectives The global prevalence of non-alcoholic fatty liver disease (NAFLD) has risen to 25%, with Hispanic populations among those at greatest risk. We describe the prevalence of NAFLD in a cohort of Guatemalan adults and examine whether exposure to a protein-energy supplement from conception to age two years is associated with lower prevalence of NAFLD. Methods From 1969 to 1977, four villages in Guatemala were cluster-randomized to receive a protein-energy supplement (Atole) or a no-protein, low-energy beverage (Fresco). We conducted a follow-up of participants in the original study from 2015 to 2017. We assessed blood samples (n = 1093; 61.1% women; aged 37 to 53 years) for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and estimated NAFLD prevalence using the liver fat score (calculated using fasting insulin, fasting AST, the AST/ALT ratio, and presence of metabolic syndrome and type 2 diabetes). We used generalized linear and logistic models, pooled and stratified by sex, to estimate the difference-in-difference effect of Atole from conception to age two years on NAFLD. Results Median ALT and AST were 19.7 U/L (interquartile range, IQR: 14.1, 27.4) and 26.0 U/L (IQR: 21.4, 32.8), respectively. The median NAFLD liver fat score was 0.2 (IQR: −1.2, 1.6) in women and −1.2 (IQR: −2.2, 0.5) in men (P &amp;lt; 0.0001). The prevalence of NAFLD was 67.4% among women and 39.5% among men (P &amp;lt; 0.0001). The association between Atole exposure from conception to age 2 y and NAFLD prevalence was not significant (OR: 0.90, 95% CI: 0.50 to 1.63). Conclusions These findings suggest that the prevalence of NAFLD among Guatemalan adults far exceeds the global average. We did not find a significant association between protein-energy supplementation in early life and later NAFLD. There is a need for further studies on the causes and onset of NAFLD throughout the life course. Funding Sources Funding for this study was provided by the National Institutes of Health.

Prevalence of NAFLD in Guatemala following exposure to a protein-energy nutrition intervention in early life

Introduction and objectivesThe global prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 25%, with Hispanic populations at greatest risk. We describe the prevalence of NAFLD in a cohort of Guatemalan adults and examine whether exposure to a protein-energy supplement from conception to two years is associated with lower prevalence of NAFLD. Materials and methodsFrom 1969 to 1977, four villages in Guatemala were cluster-randomized to receive a protein-energy supplement (Atole) or a no-protein, low-energy beverage (Fresco). We conducted a follow-up of participants from 2015 to 2017. We assessed blood samples (n=1093; 61.1% women; aged 37–53 years) for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and estimated NAFLD prevalence using the liver fat score. We used generalized linear and logistic models to estimate the difference-in-difference effect of Atole from conception to two years on NAFLD. ResultsMedian ALT and AST were 19.7U/L (interquartile range, IQR: 14.1, 27.4) and 26.0U/L (IQR: 21.4, 32.8), respectively. The median NAFLD liver fat score was 0.2 (IQR: −1.2, 1.6) in women and −1.2 (IQR: −2.2, 0.5) in men (p<0.0001). The prevalence of NAFLD was 67.4% among women and 39.5% among men (p<0.0001). The association between Atole exposure from conception to two years and NAFLD was not significant (OR: 0.90, 95% CI: 0.50–1.63). ConclusionsNAFLD prevalence among Guatemalan adults exceeds the global average. Protein-energy supplementation in early life was not associated with later NAFLD. There is a need for further studies on the causes and onset of NAFLD throughout the life course.