Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease

Background: Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD.Methods: We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced.Results: In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosisConclusion: Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.     

Pharmacological Therapeutics: Current Trends for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term from nonalcoholic fatty liver disease (NAFLD) and is a positive diagnosis based on histopathology, imaging, or blood biomarkers. MAFLD is one of the common causes of liver dysfunction worldwide, likely due to the increase in metabolic syndrome as well as the high burden of disease and its relationship to other extrahepatic conditions. However, effective pharmacological therapeutic agents are still lacking; current management largely focuses on weight reduction and lifestyle modification. The purpose of this review was to summarize the updated evidence of novel therapies targeting different pathogenetic pathways in MAFLD.     

The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

Background/Aim:

To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT).

Patients and Methods:

Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy.

Results:

Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%).

Conclusion:

There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.     

Clinical and Histologic Features of Patients with Biopsy-Proven Metabolic Dysfunction-Associated Fatty Liver Disease

Background/AimsFatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis.MethodsFrom January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared.ResultsIn total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases.ConclusionsThe novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria. (Gut Liver 2021;15-458)     

Metabolic Dysfunction-Associated Fatty Liver Disease Predicts Long-term Mortality and Cardiovascular Disease

Background/AimsWe investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study.MethodsIndividuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions overweight/obesity (body mass index ≥23 kg/m²), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis.ResultsAmong 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85).ConclusionsMAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.     

Safety and Effectiveness of Essential Phospholipids Paste in Patients with Non-alcoholic Fatty Liver Disease or Viral Hepatitis

Background: Essential phospholipids (EPL) are used as adjuvant treatment in people with fatty liver disease and other chronic liver diseases. A new formulation of EPL paste was developed to improve patient compliance. The study was aimed to assess the safety, patient-reported outcomes, and impact on compliance of the new EPL paste formulation in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatitis.Methods: The study enrolled 147 patients (48.3% male; mean ± standard deviation (SD) age 44.8 ± 10.5 years) in the intention-to-treat population; 72.8% had NAFLD and 27.9% had viral hepatitis B (HBV) or hepatitis C (HCV). Patients received EPL paste (one 600 mg sachet 3 times daily) for 12 weeks, with 4-, 8-, and 12-week scheduled visits and a 13-week follow-up visit. Patient-reported outcomes were evaluated at 4, 8, and 12 weeks compared with baseline using dedicated Likert scales. Compliance was assessed by comparing actual versus prescribed dosing of the EPL.Results: After 12-week treatment with EPL paste, statistically significant improvements were observed in mean ± SD Global Overall Symptom scores (from 4.21 ± 1.09 to 1.87 ± 0.91; P < .01) and overall Gastrointestinal Symptom scores (from 19.91 ± 5.74 to 11.17 ± 3.57; P < .01), compared to baseline scores. Compliance with prescribed essential phospholipid treatment was 99% throughout the 12-week treatment period.Conclusion: Essential phospholipids paste had a favorable safety profile associated with improved gastrointestinal symptoms and with high levels of compliance in patients with NAFLD and viral hepatitis.     

Association Between Neutrophil-to-Lymphocyte Ratio with Inflammatory Activity and Fibrosis in Non-alcoholic Fatty Liver Disease

BackgroundInflammation plays an important role in the development and progression of non-alcoholic steatohepatitis (NASH), and NASH is a powerful driving force for the progression of fibrosis. The neutrophil-to-lymphocyte ratio (NLR) is a simple emerging indicator of inflammation. We aimed to assess the potential association between NLR and histological severity of non-alcoholic fatty liver disease (NAFLD).MethodsThis retrospective study consisted of 231 patients with biopsy-proven NAFLD in China from August 2017 to September 2019. The steatosis, activity, and fibrosis scoring system were used to evaluate liver biopsy tissue.ResultsOf the 231 patients with NAFLD, advanced inflammatory activity was present in 43.3% and significant fibrosis in 25.5% of patients. Multivariate logistic regression analysis showed NLR to be correlated with advanced inflammatory activity (Odds ratio (OR): 0.62, 95% CI: 0.42-0.94, P = .025) and significant fibrosis (OR: 0.57, 95% CI: 0.35-0.94, P = .028). The NLR was inversely associated with the degree of steatosis, lobular inflammation and fibrosis (r = −0.16, P = .014; r = −0.15, P = .019; r = −0.13, P = .046, respectively), but had no association with the severity of ballooning. The multivariate-adjusted models had good predictability for advanced inflammatory activity (area under curves (AUC) 0.790, 95% CI: 0.730-0.850) and for significant fibrosis (AUC 0.798, 95% CI: 0.728-0.868).ConclusionThis study showed negative correlations between elevated NLR levels with advanced inflammatory activity and significant fibrosis in patients with NAFLD. Our results also suggested that NLR could be considered as a simple and noninvasive mark to identify high-risk populations in NAFLD.     

Serum Resistin Levels in Adult Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Background and AimsPrevious studies reported that serum resistin levels were remarkably changed in patients with nonalcoholic fatty liver disease (NAFLD) but the conclusions were inconsistent. The aim of this study was to investigate accurate serum resistin levels in adult patients with NAFLD.MethodsA complete literature research was conducted in the PubMed, Embase, and Cochrane Library databases, and all the available studies up to 7 May 2020 were reviewed. The pooled standardized mean difference (SMD) values were calculated to investigate the serum resistin levels in patients with NAFLD and healthy controls.ResultsA total of 28 studies were included to investigate the serum resistin levels in patients with NAFLD. Patients with NAFLD had higher serum resistin levels than controls (SMD=0.522, 95% confidence interval [CI]: 0.004–1.040, I²=95.9%). Patients with nonalcoholic steatohepatitis (NASH) had lower serum resistin levels than the healthy controls (SMD=−0.44, 95% CI: −0.83–0.55, I²=74.5%). In addition, no significant difference of serum resistin levels was observed between patients with NAFL and healthy controls (SMD=−0.34, 95% CI: −0.91–0.23, I²=79.6%) and between patients with NAFL and NASH (SMD=0.15, 95% CI: −0.06–0.36, I²=0.00%). Furthermore, subgroup and sensitivity analyses suggested that heterogeneity did not affect the results of meta-analysis.ConclusionsThis meta-analysis investigated the serum resistin levels in adult patients with NAFLD comprehensively. Patients with NAFLD had higher serum resistin levels and patients with NASH had lower serum resistin levels than healthy controls. Serum resistin could serve as a potential biomarker to predict the development risk of NAFLD.     

Non-alcoholic fatty liver disease: further expression of the metabolic syndrome

Non-alcoholic fatty liver disease has been associated with metabolic disorders, including central obesity, dyslipidemia, hypertension and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease refers to a wide spectrum of liver damage, ranging from simple steatosis to non-alcoholic steatohepatitis, advanced fibrosis and cirrhosis.     

Drug-induced Fatty Liver Disease: Pathogenesis and Treatment

Metabolic dysfunction-associated fatty liver disease (commonly known as MAFLD) impacts global health in epidemic proportions, and the resulting morbidity, mortality and economic burden is enormous. While much attention has been given to metabolic syndrome and obesity as offending factors, a growing incidence of polypharmacy, especially in the elderly, has greatly increased the risk of drug-induced liver injury (DILI) in general, and drug-induced fatty liver disease (DIFLD) in particular. This review focuses on the contribution of DIFLD to DILI in terms of epidemiology, pathophysiology, the most common drugs associated with DIFLD, and treatment strategies.     

Histological Characteristics of Non-alcoholic Steatohepatitis in NAFLD Patients With Low Degree of Hepatocyte Apoptosis

Background: Caspase-cleaved K18 (cK18) may accurately reflect hepatocyte apoptosis in patients with non-alcoholic steatohepatitis (NASH). However, NASH can also exist within the normal range of cK18. The aim of this study was to investigate the risk factors and characteristics of NASH within the normal serum levels of cK18.Methods: In the study, 227 histopathologically confirmed non-alcoholic fatty liver disease (NAFLD) patients with normal cK18 levels (≤200 U/L), measured in serum using ELISA kits, were enrolled. The Rs738409 allele, coding patatin-like phospholipase domain-containing protein 3 (PNPLA3), was detected by MALDI-TOF mass spectrometry. Non-alcoholic steatohepatitis was defined as an NAFLD activity score (NAS) ≥5 with each part >0.Results: The prevalence of NASH was 31.7% among NAFLD patients with normal serum cK18 levels. Compared with non-NASH, NASH had a higher possibility of occurrence with central obesity, insulin resistance, and the G allele of PNPLA3. The mean serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were higher in NASH patients. Moreover, ALT, AST, TC, LDL-C, central obesity, and the PNPLA3 G allele were risk factors for NASH in NAFLD patients with normal serum cK18 levels, with odds ratios of 1.01 (95% CI: 1.00, 1.02), 1.03 (95% CI: 1.01, 1.05), 1.33 (95% CI: 1.04, 1.68), 1.41 (95% CI: 1.03, 1.92), 2.19 (95% CI: 1.15, 4.18), and 2.48 (95% CI: 1.15, 5.36), respectively; all P < .05.Conclusions: The major risk factors for NASH were central obesity, AST, and the PNPLA3 G allele, in NAFLD with low hepatocyte apoptosis.