Association of Metabolic Dysfunction-Associated Fatty Liver Disease with Cognitive Impairment and All-Cause Dementia: A Comprehensive Review.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant public health concern, affecting one-third of the global population and posing a risk for progressive liver disease. MAFLD is characterized by hepatic steatosis and impaired metabolic status, which not only impact the liver but also other systems of the human body, making it a multisystemic disorder. Emerging evidence suggests that MAFLD and its associated pathological pathways may contribute to cognitive impairment, potentially through neuroinflammation and neurodegeneration. Studies have detected cognitive impairment in patients with MAFLD using magnetic resonance imaging, which revealed decreased brain volume and cerebral perfusion, in addition to self-reported cognitive tests. While numerous studies have demonstrated an association between MAFLD and cognitive impairment, the relationship between MAFLD and all-cause dementia remains controversial. However, the shared pathological pathways between MAFLD and dementia, such as systemic inflammation, insulin resistance, gut dysbiosis, hyperammonemia, and vascular dysfunction, indicate the possibility of a common prevention strategy for both diseases. In this review, we provide a summary of the current evidence regarding the association between cognitive impairment, all-cause dementia, and MAFLD.

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease Cross Talk.

Nonalcoholic fatty liver disease is a multisystem condition with effects beyond the liver. The identification of chronic kidney disease as an independent mediator of nonalcoholic fatty liver disease or associated entity with shared cardiometabolic risk factors remains controversial and continues to draw scientific interest. With increasing prevalence of nonalcoholic fatty liver disease and lack of Food and Drug Administration approved therapies, these shared cardiometabolic risk factors have drawn significant attention. In this article, we review shared pathophysiological mechanisms between nonalcoholic fatty liver disease and chronic kidney disease along with current treatment strategies that might be useful for both disease processes.

Prevalence of metabolic dysfunction-associated fatty liver disease in kidney transplant recipients: A cross-sectional study using FibroScan.

Background and Aim: Metabolic dysfunction-associated fatty liver disease (MAFLD) is expected to be prevalent among kidney transplant recipients (KTRs). In this study, we evaluated the prevalence of MAFLD among KTRs, data that have not been investigated by any clinical study to date. Materials and Methods: We included a total of 52 KTRs and 53 age-, sex-, and BMI-matched individuals as the control group through prospective consecutive recruitment. We detected the presence of hepatic steatosis and liver fibrosis using the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) defined by FibroScan. Results: Among the KTRs, 18 (34.6%) had metabolic syndrome. The prevalence of MAFLD among the KTRs and controls was 42.3% and 51.9%, respectively (p=0.375). The CAP and LSM values did not differ significantly between the KTRs and controls (p=0.222 and p=0.119). Among the KTRs, patients with MAFLD had significantly higher age, BMI, waist circumference, LDL, and total cholesterol levels (p<0.001, p=0.011, p=0.033, p=0.022, and p=0.029, respectively). In multivariable analysis, age was the only independent factor for MAFLD among the KTRs (OR: 1.120, 95% confidence interval (CI): 1.039-1.208). Conclusion: MAFLD among KTRs did not show a significantly higher prevalence compared to the normal population. Further clinical studies with larger populations are needed.

Changes in the etiology of chronic liver disease by referral to a FibroScan center: Increasing prevalence of the nonalcoholic fatty liver disease.

Background and Aim: Chronic liver disease (CLD) is a leading cause of morbidity and mortality worldwide with a wide etiological spectrum. FibroScan® is used for follow-up of fibrosis and steatosis. This single-center study aims to review the distribution of indications by referral to FibroScan®. Materials and Methods: Demographic characteristics, CLD etiologies, and FibroScan® parameters of the patients who were referred to our tertiary care center between 2013 and 2021 were retrospectively evaluated. Results: Out of 9345 patients, 4946 (52.93%) were males, and the median age was 48 [18-88] years. Nonalcoholic fatty liver disease (NAFLD) was the most common indication (N=4768, 51.02%), followed by hepatitis B (N=3194, 34.18%) and hepatitis C (N=707, 7.57%). Adjusting for age, sex, and CLD etiology, the results revealed that patients with older age (Odds ratio (OR)=2.908; confidence interval (CI)=2.597-3.256; p<0.001) and patients with hepatitis C (OR=2.582; CI=2.168-3.075; p<0.001), alcoholic liver disease (OR=2.019; CI=1.524-2.674, p<0.001), and autoimmune hepatitis (OR=2.138; CI=1.360-3.660, p<0.001) had increased odds of advanced liver fibrosis compared to NAFLD. Conclusion: NAFLD was the most common indication for referral to FibroScan®.

Epidemiology, natural history, and diagnosis of metabolic dysfunction-associated fatty liver disease: a comparative review with nonalcoholic fatty liver disease.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide - with an estimated global prevalence of 37%. Different from nonalcoholic fatty liver disease (NAFLD), which is an exclusion diagnosis, MAFLD is defined by a set of positive criteria. This recent change in terminology is challenging because MAFLD and NAFLD denote two similar, albeit not identical, clinical populations. When the diagnostic criteria for MAFLD are applied, liver histology appears more severe and clinical outcomes are less favorable. However, the clinical management of MAFLD and NAFLD remains similar. While liver biopsy is still the reference standard for achieving a final diagnosis, noninvasive imaging- or biomarker-based diagnostic modalities are currently gaining momentum. However, liver biopsy should be recommended when diagnostic challenges exist. In this review, we compared the epidemiology, natural history, and diagnosis of MAFLD with respect to the traditional NAFLD definition.

Prevention of hepatocellular carcinoma and monitoring of high-risk patients.

Hepatocellular carcinoma (HCC) accounts for some 80% of primary liver tumors. According to recent data, HCC is the sixth most common type of cancer and the third leading cause of cancer-related mortality worldwide. Risk factors for HCC include the presence of the hepatitis B virus, hepatitis C virus, non-alcoholic fatty liver disease, and exposure to noxious agents, such as alcohol, or toxins, such as aflatoxin, which are considered preventable etiologies of HCC. Monitoring strategies are needed for patients at risk of developing HCC. There is a consensus on routine monitoring of cirrhotic patients due to definitive evidence of a significantly high rate of progression to HCC; however, the appropriate surveillance of patients with advanced fibrosis remains a topic of discussion. Nevertheless, adherence to a strict observation protocol is the cornerstone of early detection and treatment with curative options for patients with a high risk of developing HCC. This review examines prevention strategies, risk factors, and surveillance based on current guidelines.

Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver.

Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, awareness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.

The Effect of Plant Metabolites on Coronaviruses: A Comprehensive Review Focusing on their IC50 Values and Molecular Docking Scores.

Coronaviruses have caused worldwide outbreaks in different periods. SARS (severe acute respiratory syndrome) was the first emerged virus from this family, followed by MERS (Middle East respiratory syndrome) and SARS-CoV-2 (2019-nCoV or COVID 19), which is newly emerged. Many studies have been conducted on the application of chemical and natural drugs for treating these coronaviruses and they are mostly focused on inhibiting the proteases of viruses or blocking their protein receptors through binding to amino acid residues. Among many substances which are introduced to have an inhibitory effect against coronaviruses through the mentioned pathways, natural components are of specific interest. Secondary and primary metabolites from plants, are considered as potential drugs to have an inhibitory effect on coronaviruses. IC50 value (the concentration in which there is 50% loss in enzyme activity), molecular docking score and binding energy are parameters to understand the ability of metabolites to inhibit the specific virus. In this study we reviewed 154 papers on the effect of plant metabolites on different coronaviruses and data of their IC50 values, molecular docking scores and inhibition percentages are collected in tables. Secondary plant metabolites such as polyphenol, alkaloids, terpenoids, organosulfur compounds, saponins and saikosaponins, lectins, essential oil, and nicotianamine, and primary metabolites such as vitamins are included in this study.

Accuracy of Fibrosis-4 index and non-alcoholic fatty liver disease fibrosis scores in metabolic (dysfunction) associated fatty liver disease according to body mass index: failure in the prediction of advanced fibrosis in lean and morbidly obese individuals.

BACKGROUND AND AIM: While non-invasive scores are increasingly being used to screen for advanced fibrosis in metabolic (dysfunction) associated fatty liver disease (MAFLD), the effect of BMI on their clinical utility remains uncertain. This study assessed the usefulness of the Fibrosis-4 index (FIB-4) and the non-alcoholic fatty liver disease fibrosis score (NFS) in lean, overweight, obese, severely obese, and morbidly obese patients with biopsy-proven MAFLD. METHODS: A total of 560 patients (28 lean, 174 overweight, 229 obese, 89 severely obese, 40 morbidly obese) were included. Diagnostic performances and optimal cut-off values for FIB-4 and NFS were calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: In both lean and morbidly obese patients with MAFLD, both FIB-4 and NFS failed to discriminate advanced fibrosis. Conversely, both scores showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients. FIB-4 was able to exclude advanced fibrosis with the highest diagnostic accuracy in the subgroup of overweight patients (area under the ROC curve: 0.829, 95% confidence interval: 0.738-0.919). CONCLUSION: FIB-4 and NFS can confidently be used to exclude advanced fibrosis in overweight, obese, and severely obese patients. However, they do not appear clinically useful in lean and morbidly obese patients.

A Review of the Epidemiology, Pathophysiology, and Efficacy of Anti-diabetic Drugs Used in the Treatment of Nonalcoholic Fatty Liver Disease.

In recent years, epidemiological studies have consistently demonstrated that the coexistence of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is strongly associated with increased mortality and morbidity related to hepatic- and extrahepatic causes. Indeed, compared with the general population, patients with T2DM are more likely to be diagnosed with more severe forms of NAFLD (i.e., nonalcoholic steatohepatitis (NASH) with liver fibrosis). There is an ongoing debate whether NALFD is a consequence of diabetes or whether NAFLD is simply a component and manifestation of the metabolic syndrome, since liver fat (steatosis) and even more advanced stages of liver fibrosis can occur in the absence of diabetes. Nevertheless, insulin resistance is a key component of the mechanism of NAFLD development; furthermore, therapies that lower blood glucose concentrations also appear to be effective in the treatment of NAFLD. Here, we will discuss the pathophysiological and epidemiological associations between NAFLD and T2DM. We will also review currently available anti-diabetic agents with their regard to their efficacy of NAFLD/NASH treatment.

Feasibility of Fibroscan in Assessment of Hepatic Steatosis and Fibrosis in Obese Patients: Report From a General Internal Medicine Clinic.

BACKGROUND: In metabolic associated fatty liver disease (MAFLD) vibration controlled transient elastography (VCTE) by Fibroscan has emerged as a non-invasive diagnostic tool for the measurement of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are surrogate markers for hepatic steatosis and fibrosis, respectively. However, obesity constitutes a limitation in terms of creating unreliable examinations due to increased skin to liver capsule distance. Here, we aimed to investigate the feasibility of VCTE in the evaluation of hepatic steatosis and fibrosis in obese individuals. METHODS: A total of 126 consecutive obese patients (body mass index ≥30 kg/m2) without a known history of MAFLD enrolled in the study. We performed CAP and LSM measurements and calculated Fibrosis-4 Index for each patient and included data of those patients to the analysis, from whom valid measurements were able to be taken. RESULTS: Reliable VCTE measurements were able to be obtained in 122 patients (97%), from those in 34 patients with M and 88 patients in XL probe (median age: 50 [18-75], 45 males and 77 females). In 1 patient VCTE failed to take any measurements and in 3 the measurements were classified as unreliable. The mean CAP value was 323 ± 48 dB/m and the median LSM value 5.3 [1.8-34.3] kPa. CONCLUSION: CAP and LSM assessments by Fibroscan are reliable diagnostic tools for the early diagnosis of hepatic steatosis and fibrosis in obese individuals.

Macro- and micronutrients in metabolic (dysfunction) associated fatty liver disease: association between advanced fibrosis and high dietary intake of cholesterol/saturated fatty acids.

BACKGROUND AND AIM: There is still no approved pharmacotherapy for metabolic (dysfunction) associated fatty liver disease (MAFLD). Although dietary and lifestyle modifications for weight loss remain the mainstay for disease management, the association between macro- and micronutrients and fibrosis stage in patients with MAFLD remains unclear. This study was undertaken to address this issue. METHODS: This is a retrospective analysis of prospectively collected data from patients in whom MAFLD was diagnosed with vibration controlled transient elastography. Steatosis was defined by a controlled attenuation parameter ≥238 dB/m, whereas a liver stiffness measurement ≥11 kPa was considered to indicate advanced fibrosis. RESULTS: The study sample consisted of 106 patients with MAFLD (mean age 49 ± 10 years, 52 men and 54 women). Among the different micro- and macronutrients tested, only the dietary intake of cholesterol and saturated fatty acid (SFA) was independently associated with the presence of advanced fibrosis. CONCLUSION: Our findings suggest that cholesterol/SFA-restricted dietary regimens - as exemplified by the traditional Mediterranean diet - may reduce the risk of advanced fibrosis in patients with MAFLD.

The prevalence of metabolic-associated fatty liver disease in the Turkish population: A multicenter study.

Background and Aim: The objective of the present study was to investigate the prevalence of metabolic-associated fatty liver disease (MAFLD) in patients with dyspepsia. Materials and Methods: A total of 909 consecutive patients who presented with dyspepsia at 8 tertiary care centers in Turkey between March 2019 and December 2019 were included. Results: The median age was 47 years. Among them, 30.3% of the patients were obese, 18.8% had type 2 diabetes mellitus (T2DM), 35.1% had metabolic syndrome, 84.8% had dyslipidemia, and 23.9% had hypertension. The prevalence of MAFLD was 45.5%. Among the patients with MAFLD, the prevalence of obesity, T2DM, metabolic syndrome, dyslipidemia, and hypertension was 43.3%, 24.9%, 52.5%, 92.3%, and 31.9%, respectively. MAFLD was significantly associated with all of the metabolic comorbidities (p<0.001). The median Fibrosis-4 Index score of the MAFLD patients was 0.88 (range: 0.1-9.5). Of note, 53 patients with hepatic steatosis did not meet the MAFLD criteria. Conclusion: The results of the present study indicated that there was a significantly high prevalence of MAFLD observed in daily clinical practice in Turkey. Early diagnosis and prevention efforts should be implemented to reduce disease progression, and a region-based strategy is recommended.

Sustainability of diet-based moderate calorie restriction among obese patients with metabolic-associated fatty liver disease.

Background and Aim: The long-term sustainability of weight loss continues to be a subject of investigation. This study was designed to examine the effects of weight loss and the long-term sustainability of lifestyle modifications among obese patients with metabolic-associated fatty liver disease (MAFLD). Materials and Methods: A total of 40 patients who were prescribed a hypocaloric diet (~500 calories reduction for each patient), and who were followed up for 12 weeks in 4 face-to-face interviews were enrolled in the study. The patients were contacted at the 36th month, and their current weight was recorded. Results: The mean weight at baseline of 87±13 kg decreased to 79±11 kg after 12 weeks of intervention (p<0.001). The mean weight at the 36th month did not significantly differ from that measured at the baseline (p=0.563). The mean controlled attenuation parameter decreased from 320±13 dB/m to 273±37 dB/m (p<0.001), while the median liver stiffness measurement decreased from 8.7 kPa (3.6-45.7 kPa) to 5.7 kPa (2.2-29.9 kPa) (p<0.001). Conclusion: Strict follow-up through nutritional consultation can help achieve weight loss in obese patients with MAFLD. However, for long-term results, the collaboration of nutritionists and gastroenterologists is essential to prevent weight regain.