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Background and aims: Increases in both the prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are closely related. Type 2 diabetes (T2DM) has been associated with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis and hepatocellular carcinoma. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of T2DM and has an important role in weight loss. Also, it may represent a new therapeutic option for the treatment of MASH in obese diabetic patients. The main outcomes were changes from baseline in liver steatosis and fibrosis at week 24. Material and methods: A total of one hundred eighty-seven patients with T2DM were eligible for this prospective study; ninety-five subjects were treated with oral semaglutide, and ninety-two patients were treated with dapagliflozin as an add-on to metformin. All the subjects were evaluated using Vibration Controlled Transient Elastography (VCTE) from June to December 2022. Results: From our cohort, 54% of the patients were females, with a mean age of 59.92 ± 11.89 years and a mean body mass index (BMI) of 29.53 ± 5.33 kg/m2. Following a six-month medication period, we observed a substantial reduction in anthropometric measurements, including the BMI, waist circumference (WC), and waist-to-hip ratio (WtHr), in both groups. Regarding HbA1c, a notable decrease was observed in the semaglutide group (p < 0.001) when compared to the dapagliflozin group (p = 0.011). In addition, the liver stiffness measurement (LSM) according to VCTE improved significantly in the semaglutide group participants from 8.07 ± 2.90 kPa at baseline to 6.51 ± 3.09 kPa after medication (p < 0.001). Conclusion: The superior metabolic effects of semaglutide, correlated to dapagliflozin, may contribute to a more efficient decrease in hepatic stress and injury, leading to a substantial enhancement of liver function in T2DM patients. Further investigations conducted over an ideal timeframe are necessary to confirm the evidence presented in this study. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol consumption (AC) represents a widespread cause of liver diseases affecting 10–20% of the population. The study aimed to evaluate the relationship between advanced liver fibrosis (ALF) measured by transient elastography (TE), laboratory parameters, and the amount of AC depending on non-modifiable risk factors such as age and gender. Methods: We examined 689 patients with an average age of 49.32 ± 14.31 years, 72.9% males, without liver pathology, who admitted a moderate/high consumption (female ≤ 7 versus > 7 drinks/week; male ≤ 14 versus > 14 drinks/week) for at least five years. The fibrosis level was adjusted according to transaminase levels. Predictive factors were established using univariate regression analysis. Results: ALF (≥F3) was detected in 19.30% of subjects, predominantly males (14.1%) and patients over 55 years (12.5%). Excessive consumption of distilled spirits is associated with ALF in females (OR = 4.5), males (OR = 6.43) and patients over 55 years (OR = 3.73). A particularity highlighted in both genders, regardless of the age group, was the negative correlation between the decrease in the number of platelets, the albumin concentration, and the appearance of AFL. Conclusions: Screening using TE represents an approach for early detection of ALF in asymptomatic populations and the development of a risk stratification scheme. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) represent a global phenomenon, with a continuously rising prevalence. The strategies concerning IBD management are progressing from clinical monitorization to a targeted approach, and current therapies strive to reduce microscopic mucosal inflammation and stimulate repair of the epithelial barrier function. Intestinal permeability has recently been receiving increased attention, as evidence suggests that it could be related to disease activity in IBD. However, most investigations do not successfully provide adequate information regarding the morphological integrity of the intestinal barrier. In this review, we discuss the advantages of confocal laser endomicroscopy (CLE), which allows in vivo visualization of histological abnormalities and targeted optical biopsies in the setting of IBD. Additionally, CLE has been used to assess vascular permeability and epithelial barrier function that could correlate with prolonged clinical remission, increased resection-free survival, and lower hospitalization rates. Moreover, the dynamic evaluation of the functional characteristics of the intestinal barrier presents an advantage over the endoscopic examination as it has the potential to select patients at risk of relapses. Along with mucosal healing, histological or transmural remission, the recovery of the intestinal barrier function emerges as a possible target that could be included in the future therapeutic strategies for IBD. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child–Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients. [ABSTRACT FROM AUTHOR]

Although high mortality is associated with liver cirrhosis, patients usually have a good quality of life in the compensated phase, and the disease may progress undiagnosed for many years. Vibration-controlled transient elastography with controlled attenuation parameter is a useful noninvasive tool used to estimate both the severity of fibrosis and steatosis. Hence, we aimed to establish the prevalence of significant liver fibrosis diagnosed by vibration-controlled transient elastography in an apparently healthy population. Between December 2021 and March 2022, we conducted a prospective screening of liver fibrosis in apparently healthy participants from different counties of Northeastern Romania. All subjects' medical history was recorded through a comprehensive questionnaire and underwent a liver stiffness measurement. Participants with abnormal liver stiffness measurement values were further evaluated by laboratory tests to identify the etiology of chronic liver disease. A total of 127 apparently healthy subjects were enrolled, mainly females (59.8%), with a mean age of 56 ± 11 years. Overall, 12.6% of participants were found to have significant to advanced fibrosis, and 5.4% had liver cirrhosis. Among 184 participants with clinically significant fibrosis (= 8.0 kPa), 26.1% had a history of heavy alcohol intake, 22.3% tested positive for hepatitis B and C infection, and 2.1% with other etiologies. The remaining 49.5% participants with clinically significant fibrosis were diagnosed with NAFLD, with a mean controlled attenuation parameter value of 282±34 dB/m. The high prevalence of significant liver fibrosis in the general population of Romania is alarming and should raise awareness among clinicians and public health systems. Vibration-controlled transient elastography has demonstrated its usefulness as a screening tool to identify advanced liver fibrosis in general population and should be used in liver disease prevention strategies. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C infection is a systemic disease that affects over 71 million patients all over the world and it is to be considered nowadays as a new cardiometabolic risk factor. This study aimed to evaluate the weight and metabolic changes after viral eradication in patients with hepatitis C virus (HCV) infection. We conducted a prospective study between October 2017 to December 2021, in a tertiary care center, in which we included 132 patients with HCV or cirrhosis. All patients received treatment with direct antivirals (DAAs) and achieved sustained viral response at 12 weeks (SVR12). During the study, clinical laboratory data and Fibroscan examinations were recorded in all patients. The study group was evaluated at the initiation of antiviral treatment, at SVR12, and within an average follow-up period of 6 months to 12 months after the previous evaluation. Evaluation at SVR12 and the data recorded in the post-SVR surveillance period show a further increase in BMI compared with baseline measurements with a statistically significant difference (27.11 ± 3.22 vs. 27.415 ± 3.03 vs. 28.04 ± 1.11 kg/m2, p = 0.012). The same observation was noticed for waist circumference (WC) at post-SVR evaluation (87.6 ± 13.1 vs. 88.4 ± 13.6 cm, p = 0.031). Moreover, the study population registered an increase in the average total cholesterol (TC) values at post-SVR evaluation (177.01 ± 42.2 mg/dL, p = 0.014) compared to baseline. In addition, the serum level of triglycerides had been modified after viral clearance, with a minimal decrease in the mean values of triglycerides (TGD) at SVR-12 assessment (133.48 ± 41.8 mg/dL, p = 0.78), followed by a significant increase to the mean value of 145.4 ± 47.2 mg/dL (p = 0.026) in the third evaluation. Our study highlights that HCV eradication does not improve the lipid profile in the short term, and these patients still have an additional cardiovascular risk factor due to high levels of TC, TGD, and weight gain. [ABSTRACT FROM AUTHOR]

Alcoholic liver cirrhosis (ALC) is a disease with multiple complications and is associated with poor prognosis and significant mortality. Identifying risk factors associated with a poor outcome is important to ensure effective treatment and increase life expectancy. We aimed to evaluate the predictive values of complications regarding mortality in ALC. We retrospectively analyzed 1429 patients with ALC hospitalized between January 2019 and April 2022 at the Institute of Gastroenterology and Hepatology Iasi. The electronic medical records were interrogated to obtain information about demographic data, complications, comorbidities, and prognostic scores: MELD-Na (model for end-stage liver disease-sodium) and CTP (Child–Turcotte–Pugh). Based on uni- and multivariate analysis, independent predictors of mortality were identified. The mean age at diagnosis was 56.15 ± 11.49 years with a ratio of 2:1 in favor of males. There were 296 deaths (20.8%), most of them during the first hospitalization (208/14.6%). It was observed during the univariate analysis that complications of the disease negatively affected the survival rate, significant values being related to infections (sepsis; OR = 21.98; p < 0.001; spontaneous bacterial peritonitis (SBP) (OR = 11.94; p < 0.001) and hepatorenal syndrome (HRS) (OR = 9.35; p < 0.001). The independent predictors, confirmed by multivariate analysis, were the association of variceal bleeding, infections, and hepatic encephalopathy or ascites, each combination being responsible for two out of 10 of the deaths during the first admission. The prognosis of the disease was negatively influenced by the worsening of liver dysfunction and the appearance of complications. The main predictors of mortality were infections, hepatic encephalopathy, variceal bleeding, and hepatorenal syndrome. Improving compliance and strict application of specific follow-up and treatment strategies could contribute to a better prognosis of patients with alcoholic liver cirrhosis. [ABSTRACT FROM AUTHOR]

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]

Background and Objectives: Bacterial infections represent one of the most frequent precipitating events of acute-on-chronic liver failure (ACLF) in a patient with liver cirrhosis (LC). Early diagnosis and treatment could influence the ACLF reversal rate and decrease the mortality rate in these patients. The study aimed to evaluate the role of presepsin, C-reactive protein (CRP), and procalcitonin (PCT) in the early diagnosis of bacterial infections in patients with LC and ACLF, defined according to the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. Material and Methods: We performed a prospective observational study including all consecutive cirrhotic patients with ACLF admitted to our tertiary university center. The patients were follow-up until discharge. All patients were screened for infection at admission, and we included patients with community-acquired or healthcare-associated bacterial infections. Results: In this study, we included 153 patients with a median age of 60 years, of whom 65.4% were male. Infections were diagnosed in 71 patients (46.4%). The presepsin, CRP, and PCT levels were higher in patients with infections than in those without infections (p < 0.001, p = 0.023, and p < 0.001, respectively). The ROC analysis results demonstrated that the best cut-offs values for infections diagnosis were for presepsin 2300 pg/mL (sensitivity of 81.7%, specificity of 92.7%, AUROC 0.959, p < 0.001), CRP 5.3 mg/dL (sensitivity of 54.9%, specificity of 69.6%, AUROC 0.648, p = 0.023), and PCT 0.9 ng/mL (sensitivity of 80.3%, specificity of 86.6%, AUROC 0.909, p < 0.001). Presepsin (OR 3.65, 95%CI 1.394–9.588, p = 0.008), PCT (OR 9.79, 95%CI 6.168–25.736, p < 0.001), and MELD score (OR 7.37, 95%CI 1.416–18.430, p = 0.018) were associated with bacterial infections in patients with ACLF. Conclusion: Presepsin level ≥2300 pg/mL and PCT level ≥0.9 ng/mL may be adequate non-invasive tools for the early diagnosis of infections in cirrhotics with ACLF. [ABSTRACT FROM AUTHOR]

Infections and sepsis represent severe liver cirrhosis (LC) complications and the precipitating factors of hepatic encephalopathy (HE). The early diagnosis and treatment of infections in patients with LC and HE can significantly increase their survival. Presepsin is a serum biomarker evaluated for the early diagnosis of infections and sepsis in the general and cirrhotic populations. This study aimed to evaluate the role of presepsin in the early diagnosis of infections in patients with LC and HE. This prospective observational study included all consecutive cirrhotic patients admitted to our tertiary university center with overt HE. The patients were follow-up until discharge. In this study, we included 365 patients with a median age of 59 years, of whom 61.9% were male. Infections were diagnosed in 134 patients (36.7%). The presepsin level was higher in patients with infections than those without infections (3167 vs. 500, p < 0.001). The ROC analysis results demonstrated that the best cut-off value for presepsin in infections detection was 980 pg/mL with a sensitivity of 80.17%, specificity of 82.5% (AUROC 0.869, CI 95%: 0.819–0.909, p < 0.001, Youden index J of 0.622), a positive predictive value of 40.63%, and a negative predictive value of 96.53%. In conclusion, in patients with LC and overt HE, presepsin levels >980 pg/mL could enhance the suspicion of bacterial infections. Presepsin may be an adequate non-invasive tool for the early diagnosis of infections in patients with LC and overt HE. [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]

Non-alcoholic fatty liver disease (NAFLD) has had, over the past few decades, a progressively growing prevalence among the general population all over the world, in parallel with metabolic conditions such as type 2 diabetes mellitus (T2DM), dyslipidemia, and obesity. However, NAFLD is also detected in 10–13% of subjects with a body mass index (BMI) ≤ 25 kg/m² (lean-NAFLD), whose major risk factors remain unknown. In this study, we aimed to characterize the clinical features and associated risk factors of lean-NAFLD in comparison with obese-NAFLD patients. Consecutive patients diagnosed with NAFLD by vibration-controlled transient elastography and controlled attenuation parameter were prospectively enrolled. Biological and clinical data obtained from the participants were stratified according to their BMI in two groups: lean-NAFLD and obese-NAFLD. In total, 331 patients (56.8% males) were included in the final analysis. Most of the subjects were obese-NAFLD (n = 258, 77.9%) and had a higher prevalence of T2DM, dyslipidemia, and components of the metabolic syndrome, together with abnormal biological parameters. Regarding liver stiffness measurements, the proportion of subjects with at least significant fibrosis (≥F2) was approximately twofold higher among obese-NAFLD (43.81%) in comparison with lean-NAFLD patients (23.29%). Moreover, obese individuals had a higher risk for liver fibrosis (OR = 2.6, 95%, CI 1.5–4.42, p < 0.001) than lean individuals. Although associated metabolic conditions and at least significant liver fibrosis were present in approximately one-quarter of the patients, these were more frequent among obese-NAFLD patients. Therefore, individualized screening strategies for NAFLD should be established according to BMI. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection induces hepatic steatosis due to viral and host factors. However, information regarding the effects of direct-acting antivirals (DAAs) therapy on liver steatosis and fibrosis is limited. Vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) represents a non-invasive method, which has been used in the last few years for the detection of hepatic steatosis and fibrosis before and at a sustained virological response at 12 weeks (SVR12). The aim of this study was to assess the modifications of liver steatosis and fibrosis in HCV-infected patients who achieved SVR12. Consecutive patients with chronic HCV infection that were treated with DAAs in a tertiary gastroenterology center from Romania were included. Demographics, laboratory data, and VCTE evaluation were recorded in all patients. Patients with previous hepatic decompensation and those who did not achieve SVR were excluded. Two hundred and eighty patients (67.1% females) who achieved SVR12 were included. Regarding the changes in biological parameters, including liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), reduced to normal levels at SVR12 compared to the baseline (28.72 ± 24.71 U/L vs. 40.72 ± 27.34 U/L for ALT, p < 0.013 and 27.21 ± 11.15 U/L vs. 33.35 ± 23.37 U/L for AST, p = 0.029). On the contrary, the levels of triglycerides increased significantly from the baseline to SVR12 (124.03 ± 113.49 mg/dL to 153.78 ± 94.53, p = 0.004). Regarding hepatic steatosis by CAP evaluation, at SVR12, 186 (66.4%) of the individuals had a CAP score of ≥248 dB/m, an increase of 4.6% from the baseline. After viral eradication with DAAs, we observed an increase in hepatic steatosis. Hence, a long-term follow-up is mandatory to identify HCV-infected patients with hepatic steatosis post-SVR and the risk factors for more severe outcomes. [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. Despite the high efficacy of direct acting antivirals (DAAs) in curing chronic HCV infection, there is a concern regarding a more aggressive phenotype of hepatocellular carcinoma (HCC) after DAA treatment. Although there are many clinical cohort studies that have evaluated the incidence and recurrence of HCC in these patients, data on the tumor characteristics of HCC after DAAs are not sufficient to establish a clear conclusion. A promising index was recently developed for the evaluation of HCC aggressiveness (AGI) which comprises 4 tumor-related parameters: maximum tumor diameter (MTD), number of tumor nodules, portal vein thrombosis (PVT) and serum AFP levels. Aim. We aimed to investigate the usefulness of AGI in assessing the pattern of HCV-related HCC after DAAs and the predictive value in survival. Material&methods. We carried out a retrospective comparative observational study in which we included patients treated with DAAs for HCV infection and diagnosed with HCC in the Institute of Gastroenterology and Hepatology from Iași, Romania, between January 1st, 2017 and December 31, 2019. Patients were matched based on age and sex with a historic cohort consisting of patients with HCV-related HCC without DAA therapy. Based on AGI, patients were divided into three aggressiveness classes: class A (low aggressiveness), B (intermediate aggressiveness) and C (high aggressiveness). Results. Among the 124 patients with chronic HCV infection diagnosed with HCC, 66 (53.2%) patients were males and 58 (46.8%) were female, with a mean age of 62.38 ± 9.88 years. According to DAAtreated and DAA-naive status, patients were divided into 2 groups: the DAA group included 30 treated patients and the non-DAA group included 94 DAAnaive patients. In the DAA group, the frequency of single HCC was much higher (73.3%) than in naïve patients (53.2%) (p = 0.052), as well as smaller tumor sizes (41.07 ± 18.116mm vs. 61.79 ± 34.477mm, p=0.001) and lower rates of malignant PVT (20% vs. 36%, p = 0.146). According to AGI, class B was the most frequently observed (42.6%) in DAA-naïve patients, followed by class A (31.9%) and class C (25.5%), whilst in DAA-treated patients the most frequent was class A (46.7%), closely followed by class B (40.0%), and class C in 13.3% of cases. The 3-year survival probability for AGI class A vs. B vs. C was 66.9% vs 40.2% vs 8.4%; p=0.001, from the time of diagnosis by Kaplan-Meier plot. There was a significantly higher survival rate in the DAA group compared to DAA-naïve patients (75.3% vs. 52.4%, p = 0.008). [ABSTRACT FROM AUTHOR]

Introduction. Hepatitis C virus may cause chronic liver infection which may progress to advanced fibrosis, liver cirrhosis and hepatocellular carcinoma (HCC). Eradication of HCV could reduce the risk of liver cirrhosis, HCC and liver-related deaths. Interferon-free (IFN-free) treatment can achieve high sustained virological response (SVR) rates, even in patients with one or more comorbidities. Objectives. We want to verify the influence of comorbidities and their treatment on the initiation and performing genotype-specific IFN-free therapy and also on obtaining SVR in these patients. Material and Methods. We made a retrospective study on 85 patients with chronic C infection - 63 female and 22 men (sex ratio 2.86/1), aged between 45 and 80 years old, with median age 62 ± 2.3 years old, hospitalized in "St Spiridon" Hospital Iasi - Gastroenterology between 2019 - 2021 in order to initiate IFN-free therapy. Distribution of the group according to comorbidities: cardiovascular disease - 46 patients (58,8%), diabetes - 8 patients (9,4%), 9 patients - endocrinological disorders (10,5%), 5 patients psychiatric diseases (5,8%), 2 patients respiratory diseases (2,35%), 4 patients hematological diseases (4,7%), 2 patients - neoplastic antecedents (cured gastric neoplasia) 2,3%, 4 patient neurological diseases (4,7%), 5 patients without associated disease (5,8%). The drug interactions were checked and the therapeutic schemes were modulated accordingly. 57 patients (67%) presented F1-F3 grade of fibrosis and 28 patients (32,9%) F4, of which 6 (7%) with decompensated cirrhosis. The associated treatment consisted of: antihypertensives, levothyroxine, insulin therapy, antidepressants, antiparkinsonian, antipsychotics, antidementia. Genotype-specific IFN-free therapy was: Viekirax-Exviera (ombitasvir, pari, ritonavir +dasabuvir) in 46 patients (55,42%), Harvoni (ledipasvir/sofosbuvir) in 26 patients ((31,32%) and Zepatier (Grazoprevir) - 11 patients (13,25%). Results. Out of the 85 patients, 2 with neurological pathology could not initiate the therapy (2,3%). 83 HCV patients (97,64%) started IFN-free treatment. One patient developed severe heart failure and needed to stop IFN-free treatment after six weeks administration (1,17% of total). 82 patients started and finished IFN-free treatment (96,4%). All of them achieved sustained SVR at 12 weeks after treatment (100%). Conclusion. Despite the presence in patients with HCV chronic infection of various comorbidities along with their treatments, IFN-free therapy could be initiated and followed in the vast majority of them. In our study, all patients which started and finished IFN-free regimens obtained SVR. Close monitoring and careful attention are needed to handle unexpected adverse events. [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]

Introduction. The overall burden of B / D and C viral hepatitis remains substantial, despite the major advances in the prevention and treatment of patients in recent years, due to comorbidities and complications associated with liver disease. In this context, the national screening program LIVE (RO) 2 aims to further assess all patients identified as positive for one of the hepatitis B / D / C viruses. Objectives. The study aimed to identify fortuitous pathologies discovered in patients with chronic viral B / D / C infection diagnosed in the LIVE (RO) screening program 2. Materials and Methods. We conducted a prospective study that included people from vulnerable groups (poor, uninsured, rural people, people in foster care, homeless, Roma population, people with disabilities, and suffering from alcohol or drug addiction) in different areas of North-Eastern Romania, between July 2021 - December 2022, during the national screening program LIVE (RO) 2-EAST. We also investigated the presence of newly discovered conditions in patients who tested positive and directed to the Institute of Gastroenterology and Hepatology in Iasi for the staging of liver disease and the establishment of antiviral treatment. Results. The study group included 1176 patients, of which 422 men (35.8%) and 754 women (64.1%), aged between 35 and 83 years, with a mean age of 56.32 years. The predominant source of origin was rural (73.1%). Of the patients with positive RDTs, 635 (53.9%) patients were detected with HBsAg, 521 (44.3%) patients with anti-HCV antibodies, and 20 (1.7%) patients with anti-HVD antibodies. Of these, 215 patients (18.2%) were diagnosed with a new pathology associated with B / D / C viral infection. The most common pathologies discovered incidentally were liver cirrhosis (94, 43.7%), liver cysts (35, 16.2%), liver hemangiomas (29, 13.4%), gallstones (24, 11.1%), type II diabetes mellitus (T2DM) (15, 6.9%), uterine fibroids (9, 4.1%), hepatocellular carcinoma (7, 3.2%), choledochal lithiasis (2, 0.9%). In addition, the presence of fortuitous pathologies was higher among patients with HBV infection than in those with HCV infection (65.3% vs. 42.1%, p = 0.012). Among the risk factors associated with hepatocellular carcinoma (HCC) are chronic alcohol consumption (43%, compared to 19% in the group of patients without HCC), and the association of T2DM in 3 patients (31%, compared to 10% in the group of patients with HCC). Conclusions. Patients with chronic B / D / C viral infection had a high prevalence of incidentally detected comorbidities, which necessitates the need for public health policies in vulnerable groups to promote access to existing health services to reduce the future burden of chronic diseases but also secondary complications of chronic liver disease. [ABSTRACT FROM AUTHOR]

Introduction. In recent decades, alcohol consumption, as part of an unhealthy lifestyle, which has been on the rise in many parts of the world, is a key factor that explains the constant upward trend of mortality associated with this etiology. This study aimed to investigate the prevalence of liver fibrosis in the asymptomatic alcohol-consuming population. Objectives. The purpose of the study was to evaluate the relationship between advanced liver fibrosis measured by transient elastography, laboratory parameters, and the amount of alcohol consumed depending on non-modifiable risk factors such as age and gender. Material and method. Between January 2022 and December 2022, we examined patients with day hospitalization in the Institute of Gastroenterology and Hepatology in Iasi, without liver history, who admitted a moderate or high consumption (women <7 versus >7 drinks/week; men <14 versus >14 drinks/week) for at least one year. The classification of the fibrosis stage by transient elastography was adjusted according to transaminase values. The results were analyzed by univariate analysis and logistic regression to establish models of prediction. Results: The study included 689 patients with an average age of 49.32±14.31 years, a proportion of 63.7% represented by men. Advanced fibrosis (F3) was detected in 19.30% of the examined patients, predominantly in men (14.1%) and patients over 55 years old (12.5%). Excessive alcohol consumption is associated 2 times more with advanced fibrosis in women (OR=5.08; CI 95%: 3.45-9.50) and the group under 40 years old (OR=6.29; CI 95%: 1.67-9.43) compared to men (OR=2.27; CI 95%: 1.76-3.81) respectively patients over 55 years old (OR=3.21; CI 95%: 2.28-4.45) (p<0.05). Using logistic regression, it was demonstrated that there was a strong correlation between advanced fibrosis, excessive alcohol consumption, low serum albumin level and the reduction of triglycerides in men (R2 Nagelkerke = 0.854; p<0.001) supplemented with the reduction of cholesterol in the age group 40-55 years (R2 Nagelkerke = 0.785; p<0.001), respectively of ferritin in those over 55 years old (R2 Nagelkerke = 0.804; p<0.001). The association of excessive alcohol consumption, age, low levels of albumin, LDL-cholesterol and C-reactive protein generated a significant predictive model (R2 Nagelkerke = 0.784; p<0.001) for female patients. Conclusion. Screening using transient elastography represents an approach that could provide early diagnosis of advanced liver fibrosis in an asymptomatic population, with the possibility to prevent the evolution of ALD and the development of complications of cirrhosis. [ABSTRACT FROM AUTHOR]

Introduction. Chronic viral hepatitis B/D and C can be complicated by comorbid conditions that may influence treatment eligibility and outcomes. The aim of this study was to evaluate the presence of the most common comorbidities in patients diagnosed with chronic viral B/D and C infection using rapid diagnostic tests (TDR). Materials and Methods. Between July 2021 and December 2022, we performed prospective screening for chronic viral B/D and C infection in people in vulnerable groups (poor, uninsured, rural people, people in foster care, people without shelter, Roma people, people with disabilities, people suffering from alcohol and drug addiction) from different areas of North-Eastern Romania, during the national program for the elimination of viral hepatitis LIVE(RO) 2-EST using TDRs for hepatitis B virus (Wama Immuno-Rapid HBV®) and hepatitis C virus (Wama Immuno-Rapid HCV®). We also investigated the presence of comorbid conditions in patients tested positive and presented at the Institute of Gastroenterology and Hepatology in Iasi for the staging of liver disease and the establishment of antiviral treatment. Results. Our study included 1176 patients who came to a tertiary center for the staging of liver disease, of which 422 men (35.8%) and 754 women (64.1%), aged 35 to 83 years, with an average age of 56.32 years. The predominant source of origin was rural (73.1%). Of the patients with positive TDR, 635 (53.9%) of patients were detected with HBsAg, 521 (44.3%) of patients with anti-HCV antibodies, and 20 (1.7%) of patients with anti-HVD antibodies. Of these, 646 patients (54.9%) had at least one comorbid condition. The most common comorbidities were cardiovascular disease (21.5%), psychiatric disorders (11.5%), type 2 diabetes (8.9%), metabolic disorders (6%), thyroid disorders (5%) and cancer (2%). In addition, the presence of comorbidities was higher among patients with HCV infection than in those with HBV infection (64.9% vs. 48.5%, p = 0.014), while psychiatric disorders were most common in patients with HBV/HVD coinfection (42.3%), most likely due to the Interferon regimen that has been administered in the past to 19 individuals. Conclusions. Patients with chronic viral hepatitis B/D and C had a high prevalence of multiple comorbidities. Effective strategies are needed to manage these comorbid conditions as well as interdisciplinary collaboration to allow greater access to antiviral treatment and to reduce the future burden of advanced liver disease and its manifestations. [ABSTRACT FROM AUTHOR]

Introduction. Over 71 million people worldwide suffer from chronic hepatitis C, a systemic disease that is currently being viewed as a new cardiometabolic risk factor. Aim. The objective of this study was to compare the lipid profiles of patients with hepatitis C virus (HCV) infection before and after viral elimination. Materials and Methods. We conducted a prospective study between October 2017 to January 2020, in a tertiary center, in which we included 132 patients with chronic HCV hepatitis or cirrhosis. All patients received treatment with direct antivirals. During the study we assesed biological data (blood count, TGP, TGO, serum albumin, urea, creatinine, total cholesterol (TC), LDL-cholesterol, HDLcholesterol, triglycerides). The study group was followed at the initiation of antiviral treatment, after 3 months after the completion of antiviral treatment and within an average follow-up period of 6 months to 12 months after the previous evaluation. Results. 128 of the 132 patients exhibit a persistent viral response (SVR). The average TC levels for patients who obtained SVR increased from baseline to 177.01 42.2 mg/dl. The discrepancies between the baseline values of the TC and those discovered during SVR and post-SVR surveillance were statistically significant (p 0.05 and p = 0.049, respectively). When compared to the baseline, the average LDL-cholesterol readings at SVR and post-SVR surveillance were higher on average (116.2 35.6 vs 124, 24 34.9 vs 136.72 22.5 mg/dL). The post-SVR examination reveals significant HDL value variability, with lower values discovered compared to the study's second surveillance moment. After viral clearance, the serum triglyceride level had also changed. The mean triglyceride concentrations are lower (128.441.8 mg/dL) at the time of the SVR assessment. In the third evaluations, the mean value is somewhat higher (135.445.2 mg/dL). The differences between the values acquired at the time of SVR and the beginning values were found to be statistically significant (p = 0.008, p 0.05). Conclusion. Our study highlights that HCV eradication does not improve the lipid profile on the short term, and these patients still have an additional cardiovascular risk factor due to high levels of TC, LDL-cholesterol and triglycerides. [ABSTRACT FROM AUTHOR]

Introduction. In order to meet the requirements of the WHO, namely - the eradication of viral hepatitis by 2030, UMF "Grigore T. Popa" from Iasi together with ARAS and the Hospital "St. Spiridon" from Iasi, carries out since 2020 the project "LIVE(RO) 2 - Integrated regional program for prevention, early detection (screening), diagnosis and targeting treatment of patients with chronic liver disease secondary to viral infections with liver viruses B/D and C in the North-East and South-East regions". This study aimed to assess the epidemiological characteristics of the vulnerable population in the eastern part of the country diagnosed with chronic B/D and C viral infection. Materials and Methods. Between July 2021 and December 2022, we performed a prospective screening of chronic viral hepatitis B/D and C in vulnerable people in the counties of North-East and South-East of Romania, within the national program LIVE(RO) 2 - EST. Rapid diagnostic tests were used to detect HBs antigen (HBsAg) and anti-HCV antibodies (HCVA): HBV (Wama Immuno-Rapid HBV®) and HCV (Wama Immuno-Rapid HCV®). Rapid test-positive patients were tested for HBV DNA and HCV RNA and those eligible under the national protocol were treated with antivirals. Results. The study included 55593 individuals tested rapidly, of which 2160 (3.8%) patients were tested positive (1120 women, 1040 men, mean age 55.86 ± 6.023 years, predominantly rural background - 76.19%). Of these, 1077 (49.8%) were HBsAg positive, 918 (42.5%) with HCV positive needle, 37 (1.7%) HBV/HCV coinfection and 128 (5.9%) HBV/VHD coinfection. HBV-DNA was performed in 724 (67.3%) individuals, of which 452 (62.5%) subjects > 2,000 children/ml. Also, 518 (54.3%) patients with HCV-positive Ac had detectable HCV RNA, of which 375 (72.3%) received antiviral treatment. Depending on the ethnicity, the prevalence of viral infection was 4.29% in Roma people and 3.23% in Romanian people. Among the vulnerable groups determined by work, inactive people (27.7%), uninsured people (11.2%), unskilled people (1.87%), unemployed people (0.6%) and people working in agriculture (0.59%) were predominantly tested. Among the special vulnerable groups, people with disabilities (3.99%), people addicted to alcohol (2.43%) and people with a minimum income (1.21%) were predominantly tested. Conclusions. The high prevalence of B/D and C viral infection in the vulnerable population tested in the North-East and South-East Region of Romania compared to the rest of the population, indicates the significant viral spread of the infection in these people, a condition that requires further testing and the need for policies public health in vulnerable groups to promote access to existing health services and early initiation of optimal antiviral treatment. [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]