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Background: Cirrhosis can be present undected for years prior to a symptomatic presentation. Early detection may result in improved outcomes. Data are lacking, however, regarding the yield of screening in many populations. We aimed to determined prevalence of significant liver fibrosis diagnosed by vibration-controlled transient elastography (VCTE) in apparently healthy Romanians., Methods: Between December 2021 and March 2022, we prospectively screened 1,027 subjects from different counties of Northeastern Romania using VCTE and B-mode ultrasonagraphy after a comprehensive medical history questionnaire. Participants with abnormal liver stiffness measurement values were further evaluated by laboratory tests to identify the severity and etiology of chronic liver disease., Results: Overall, 17.9% of subjects had liver stiffness measurments (LSM) ≥8 kpa, including 55 with LSM ≥13.0 kpa. Among these subjects, 26.1% had a history of heavy alcohol intake, 22.3% tested positive for hepatitis B and/or C infection, and 49.5% were diagnosed with NAFLD. The prevalence of elevated LSM was highest among older subjects (>60 y old) and those with diabetes. Among those with LSM ≥13 kPa and ≥9.6 kpa, FIB-4 was <2.67 in 46.9% and 87.5% respectively., Conclusion: There is high prevalence of significant liver fibrosis in the Romanian general population. VCTE is a usefool tool for early detection of liver disease and appears more sensitive than FIB-4., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end-stage liver disease. Cardiovascular disease (CVD) has been associated with NAFLD and CVD-related events represent the main cause of death in patients with NAFLD, surpassing liver-related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Stefan Chiriac et al.)

Nonalcoholic fatty liver disease (NAFLD) has a rising prevalence worldwide. Its potential for evolution towards liver cirrhosis and hepatocellular carcinoma, as well as associations with extrahepatic manifestations, represents a double burden for patients and physicians alike. Recently, there has been increasing evidence of the association between NAFLD and a number of endocrinopathies, such as hypothyroidism, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism, and hypercortisolism. Definite correlations are supported by clear evidence so far, but further studies are needed in order to completely clarify the pathogenic mechanisms and, especially, to identify therapeutic implications. In this review, we present the main relationships between NAFLD and endocrinopathies, emphasizing the reciprocal causality, evolutive interconnections, and current clinical scenarios of presentations of which the clinicians should be aware., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ana-Maria Singeap et al.)

Nonalcoholic fatty liver disease has become the main concern of hepatologists around the world and the main research topic for identifying effective and safe therapy. Advances in the treatment of chronic viral hepatitis in recent years have opened the way towards reducing mortality in patients with chronic liver disease. This goal has not yet been reached, as the burden of chronic liver disease remains a future major health problem as the incidence of the nonalcoholic fatty liver disease continues to rise. The proportion of patients with liver cirrhosis and those with hepatocellular carcinoma due to nonalcoholic liver disease on the liver transplant waiting list has increased in the last years. The upward trend in the incidence and prevalence of the disease in recent decades raises concern over a possible global epidemic, especially as the disease is still underestimated and underdiagnosed. Chronic kidney disease presented an increase in incidence and prevalence during the last years, and it has been associated not only with increased morbidity and mortality but also with high costs for the health system. During the last decade, several studies have shown the association between nonalcoholic fatty disease and chronic kidney disease, two major worldwide health problems., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Camelia Cojocariu et al.)

Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25-30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications., Competing Interests: The authors declare no conflicts of interest in this work., (Copyright © 2020 Cristina M. Muzica et al.)

Background and Aims: Inflammatory bowel diseases (IBD) are frequently associated with extraintestinal manifestations, hepatic injury being of concern in these patients. Current literature reports an increased prevalence of liver steatosis and fibrosis in subjects with IBD and the pathophysiology is yet to be completely understood. The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with IBD, as well as to determine the factors that connect these two disorders. Methods: From September 2021 to June 2022, 82 consecutive IBD patients were enrolled from a tertiary care center hospital in Iasi. Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter (CAP) was used to assess the presence of NAFLD, with a cut-off score for CAP of 248 dB/m. Significant liver fibrosis was considered at a cut-off for liver stiffness measurements (LSM) of 7.2 kPa. Results: In total, 82 IBD patients (54.8% men, mean age of 49 ± 13 years) were included, 38 (46.3%) of them being diagnosed with NAFLD, with a mean CAP score of 286 ± 35.4 vs. 203 ± 29.7 in patients with IBD only. Age (β = 0.357, p = 0.021), body mass index (BMI) (β = 0.185, p = 0.048), disease duration (β = 0.297, p = 0.041), C—reactive protein (β = 0.321, p = 0.013), fasting plasma glucose (β = 0.269, p = 0.038), and triglycerides (β = 0.273, p = 0.023) were strongly associated with the presence of liver steatosis. The multivariate analysis showed that older age, BMI, and disease duration were strongly associated with significant liver fibrosis in our group. Conclusions: NAFLD is a multifaced pathology with growing prevalence among IBD patients. Additional studies are needed to completely understand this problem and to create a solid evidence-based framework for more effective preventative and intervention strategies. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a common finding among patients with type 2 diabetes mellitus (T2DM). Between NAFLD and T2DM exist a bidirectional relationship. Patients with T2DM are at high risk for NAFLD, and evidence suggests that T2DM is linked to progressive NAFLD and poor liver outcomes. NAFLD promotes the development of T2DM and leads to a substantial increase in the risk of T2DM complications. This study aimed to assess the prevalence of liver steatosis and fibrosis in patients with T2DM from north-eastern Romania by using Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP), which is a non-invasive method and can assess simultaneously liver steatosis and fibrosis. In total, 424 consecutive patients with T2DM were enrolled and evaluated using VCTE with CAP from January 2020 to January 2022. Clinical and laboratory data were recorded in all patients. For the CAP score, we used the following cut-offs: mild steatosis (S1)—274 dB/m, moderate steatosis (S2)—290 dB/m, and severe steatosis (S3)—302 dB/m. For liver fibrosis, to differentiate between fibrosis stages, the cut-off values were F ≥ 8.2 kPa for significant fibrosis (F2), F ≥ 9.7 kPa for advanced fibrosis (F3), and F ≥ 13.6 kPa for cirrhosis (F4). In total, 380 diabetic patients (72.6%) had liver steatosis (51.3% females, the mean age of 55.22 ± 10.88 years, mean body mass index (BMI) 29.12 ± 5.64 kg/m2). Among them, 26 (8.4%) patients had moderate liver steatosis (S2) and 242 (78.5%) patients had severe hepatic steatosis (S3). According to VCTE measurements, 176 (57.14%) patients had liver fibrosis, 36 (11.7%) of them had advanced fibrosis (F3), and 42 (13.6%) diabetic patients had cirrhosis (F4). Univariate analyses showed that severe steatosis was significantly associated with ferritin (β = 0.223, p = 0.022), total cholesterol (β = 0.159, p = 0.031), and HDL-cholesterol (β = −0.120, p = 0.006). In multivariate analyses, BMI (β = 0.349, p < 0.001), fasting plasma glucose (β = 0.211, p = 0.006), and triglycerides (β = 0.132, p = 0.044) were predictors of S3. Patients with T2DM have a high prevalence of severe steatosis and advanced fibrosis which can lead to the development and progression of complications with high morbidity and mortality rates. Hence, it is necessary to implement screening strategies to prevent advanced liver disease in patients with T2DM. [ABSTRACT FROM AUTHOR]

Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) is a widely used non-invasive technique for concomitant assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the level both of hepatic steatosis and fibrosis as well as the associated risk factors in patients referred to our unit with clinically suspected NAFLD or diagnosed by abdominal ultrasonography. Two hundred four patients were prospectively included in this study and assessed by VCTE with CAP. The final analysis included 181 patients with reliable liver stiffness measurements (LSMs) (53% female, mean age 57.62 ± 11.8 years and BMI 29.48 ± 4.85 kg/m2). According to the cut-off values for steatosis grading, there were 10 (5.5%) patients without steatosis (S0), 30 (16.6%) with mild (S1), 45 (24.9%) moderate (S2), and 96 (53%) severe (S3) steatosis. Based on LSM, there were 73 (40.3%) patients without fibrosis (F0), 42 (23.2%) with mild (F1), 32 (17.7%) significant (F2), 19 (10.5%) advanced (F3) fibrosis, and 15 (8.3%) with cirrhosis (F4). In addition, we found an association between several metabolic components and hepatic steatosis and fibrosis. Thus, in the multivariate analysis, higher BMI, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and serum uric were associated with increased CAP. Furthermore, higher serum uric acid and alpha-fetoprotein together with lower platelets count and albumin levels were associated with increased LSM. The assessment of steatosis and fibrosis using VCTE and CAP should be performed in all patients with suspected or previously diagnosed NAFLD in units with available facilities. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is currently the most severe form of liver disease consisting of malignant processes following fibrotic and cirrhotic damage. Despite there are several validated scores for assessing the overall risk to develop HCC in patients diagnosed with chronic liver diseases, most of these are designed for patients with viral hepatitis B and C and subsequently rely on specific measurements, such as viral load or viral profiling. PAGE-B is commonly used to predict HCC risk in patients with viral hepatitis B. In this context, this study aimed to evaluate the applicability of PAGE-B in different liver diseases predisposing to HCC. On a series of 104 consecutive patients, PAGE-B was calculated according to standard guidelines. Based on the collected data, the applicability of PAGE-B was evaluated in several liver pathologies predisposing to HCC, such as alcoholic liver disease, chronic viral hepatitis C, and non-alcoholic fatty liver disease. The mean age of the patients was 67,65 ± 1,15 years, while the sex distribution was 57,28 % males to 42,72 % females. The selected cohort consisted of 11 patients with alcoholic liver disease (10,57 %), 54 patients with chronic viral hepatitis C (51,92 %), and 39 patients with non-alcoholic fatty liver disease (37,5 %). We found that the patients with alcoholic liver disease patients scored highest for PAGE-B (20,09 ± 0,45), while non-alcoholic fatty liver disease patients score lowest (17,89 ± 0,47), significantly different from one another (p = 0,021). In conclusion, our results suggested that PAGE-B could be useful in evaluating HCC risk in chronic liver diseases, but further studies are needed to find a suitable scoring system to predict the overall risk to develop HCC in patients that are diagnosed with nonalcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Introduction. Non-alcoholic fatty liver disease (NAFLD) is usually associated with type 2 diabetes mellitus (T2DM). The limited number of NAFLD treatment options is well known. Semaglutide, a GLP-1 receptor agonist approved to treat T2DM, is crucial for obtaining a healthy weight. Additionally, may constitute a cutting-edge therapy option for T2DM patients with NAFLD. In this study, liver steatosis and fibrosis in T2DM patients are measured using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). Material and Methods. Fifty-seven consecutive patients with T2DM and NAFLD receiving oral semaglutide were enrolled from September 2022 to February 2023 and evaluated by VCTE with CAP. Clinical and analytical data for every subject were recorded. Oral semaglutide was initiated at a dose of 3 mg once daily and subsequently increased to 7 mg at 4 weeks, and 14 mg at 8 weeks in accordance with the diabetologist's recommendations. Results. VCTE analysis showed that 40 diabetic people (70.2%) had significantly lower CAP levels after 24 weeks compared to baseline. Only 14 (24.5%) diabetic patients experienced a significant decrease in liver fibrosis. Regarding body mass index (BMI), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), have improved significantly compared to the baseline (mean BMI 28.72±5.43 kg/m2 to 25.67 ±6.11 kg/m2, mean AST 58.17 ± 16.33 IU/L to 34.54 ± 13.8 IU/L, mean ALT 63.31 ± 12.66 IU/L to 39.17 ± 14.3 IU/L). The mean hemoglobin A1c (HbA1c) value reduced significantly from baseline to 24 weeks (from 8.9% to 7.4%). A significant correlation existed between changes in CAP values and fasting plasma glucose (p=0.31, p=0.52), as well as AST (p=0.188, p=0.48), and BMI (p=0.274, p=0.44). Nausea and diarrhea were the most often reported side effects. Conclusion. In individuals with T2DM with NAFLD, oral semaglutide therapy has improved glycemic control, liver enzymes, body weight, and liver steatosis. These findings suggest that semaglutide may be useful in the treatment of NAFLD patients, therefore more studies concerning liver fibrosis are necessary. [ABSTRACT FROM AUTHOR]

Background and Aims. Inflammatory bowel diseases (IBD) are caused by a dysregulated immune response in the hosts, favored by genetic susceptibility. In addition to symptoms related to the digestive tract, about 40% of patients with IBD also experience extraintestinal manifestations. Although, non-alcoholic fatty liver disease (NAFLD) has been frequently associated with IBDs, the relationship between these two pathologies remains unclear. The aim of this study was to investigate the prevalence of NAFLD among IBD patients, as well as the factors that connect these two conditions. Material and methods. From January 2022 to November 2022, consecutive IBD patients were enrolled from a tertiary care center hospital in Iasi. Patients' demographic information, clinical characteristics including blood pressure, biological parameters, and anthropometric measurements were collected. Following informed consent, participants underwent a fibroscan evaluation for liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Results. 93 patients with IBD were enrolled (65,3% men, 55,6% with ulcerative colitis). 45 (48,3%) of them were diagnosed with NAFLD, with a mean CAP score of 283 ± 33.4 vs. 215 ± 23.7 in patients with IBD only. Regarding liver fibrosis, mean LSM value in the NAFLD group was 6.8 ± 1.9 kPa vs. 5.7 ± 2.3 kPa in the non-NALFD group. Subjects with NAFLD exhibited higher body mass indexes than those with IBD only (26.2 vs. 33.1, p<0.05). In addition, the prevalence of diabetes was much greater among this group (27.5% vs. 0%; p=0.0001), as was the prevalence of elevated HbA1c levels in the absence of a diabetes diagnosis (14% vs. 7.35%; p=0.23). They also had a non-significantly higher mean systolic blood pressure and greater incidences of hypertension. Compared to those without NAFLD, the NAFLD cohort had higher rates of diagnosed hypercholesterolaemia, were older with a higher mean disease duration and had a higher nonsignificant level of triglycerides. The 10-year risk of myocardial infarction or death estimated by the Framingham risk scores for hard coronary heart disease was higher in the NAFLD group (2.32% vs. 4.27%, p=0.0024). Conclusions. NAFLD is a multifaceted condition that is becoming more common in IBD patients. Although the present evidences in the literature suggest a small risk for the advance of liver fibrosis, the cardiovascular risk seems to be of a greater interest. Considering the above data, patients with IBD should be evaluated with a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Background and Aims. Non-alcoholic fatty liver disease (NAFLD) and obesity are independently related to an increased risk for atherosclerotic cardiovascular disease (ASCVD), the primary cause of mortality in NAFLD patients. Even though many subjects with NAFLD are normal weight, it still remains uncertain whether their ASCVD risk is of major importance. The aim of this study is to assess and compare the ASCVD risk between lean and obese patients with NAFLD. Methods. Normal weight and obese patients were evaluated between January 2020 and February 2023 and their data was analyzed. NAFLD was diagnosed by vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP) and the American College of Cardiology/American Heart Association guidelines was used to evaluate the ASCVD risk. Results. In the obese group, 104 (63.8%) patients were diagnosed with NAFLD, compared to 32 (12.3%) in the lean population. In comparison to those with obese NAFLD, subjects with lean NAFLD had significantly higher ASCVD scores (mean 15.3% vs 22.7%, p<0.001). Moreover, subjects with lean NAFLD and significant liver fibrosis had a higher risk of ASCVD events, compared to their obese counterparts (OR, 2.51 vs 1.95, p=0.034). Regarding the presence of the components of the metabolic syndrome, the prevalence of type 2 diabetes mellitus was higher the obese group, while changes in the lipid profile and higher systolic blood pressure were more frequently found in lean subjects. Conclusions: Subjects with lean NAFLD had an ASCVD score that were significantly higher than those with obese NAFLD. In both study groups, the presence of significant liver fibrosis was an essential risk factor associated with an ASCVD event, but the effects were more pronounced in lean individuals. [ABSTRACT FROM AUTHOR]

Introduction. Metabolic syndrome (MS) patients are at increased risk for severe liver fibrosis and nonalcoholic fatty liver disease. However, there aren't any recommendations until this moment for screening MS patients. This study aimed to evaluate the diagnostic precision of non-invasive tests in identifying advanced liver fibrosis (F3) and cirrhosis (F4) in MS patients using vibration-controlled transient elastography (VCTE) as a standard quantification method. Materials and Methods. Between September 2022 to March 2023, we prospectively enrolled MS patients at the Gastroenterology and Hepatology Institute Iasi who had undergone evaluation using noninvasive tests like the aspartate aminotransferase to platelet ratio index (APRI) score, fibrosis-4 (FIB-4) index, and NAFLD fibrosis score (NFS). When compared to liver stiffness measures (LSM), we assessed the specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) for each of these indicators in the identification of at least advanced liver fibrosis (=F3). Results. Of the 116 MS patients included in this study, who had a mean BMI of 27.82±4.62 kg/m2 and at least three metabolic conditions, 69 individuals (59.5%) were females. Using a cut-off of 9.7 kPa, 35 (30.2%) patients had at least advanced fibrosis (=F3) according to LSM measurements. VCTE examinations present a higher correlation with the FIB-4 index (r=0.566), NFS (r=0.585), and APRI score (r=0.624) (p< 0.001). The NPV for the FIB-4 index was the highest (90.38%), followed by the NPV for the NFS score (87.84%). The main result of our research showed that all the biomarkers had reasonably high NPV (>85%) and accuracy (>83%) for predicting advanced liver fibrosis, with moderate specificity (80%) and PPV (75%). Conclusion. To prevent progressive fibrosis in MS patients, the FIB-4 index and NFS score seem to be the most suitable surrogate VCTE biomarkers. It may be necessary to take action and further evaluation of liver fibrosis in a tertiary care center for populations at risk after these non-invasive and affordable screening tests are used in primary care settings. [ABSTRACT FROM AUTHOR]