Predictive Factors for the Prognosis of Alcoholic Liver Cirrhosis.

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.

New Insights on Using Oral Semaglutide versus Dapagliflozin in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.

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.

Changes in Components of Metabolic Syndrome after Antiviral Eradication in Hepatitis C Virus Infection.

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.

Impaired Intestinal Permeability Assessed by Confocal Laser Endomicroscopy-A New Potential Therapeutic Target in Inflammatory Bowel Disease.

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.

High prevalence of liver fibrosis among general population: a Romanian population-based study.

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.

The Impact of Alcohol Consumption Pattern on Liver Fibrosis in Asymptomatic Patients.

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.

Anticoagulation for Atrial Fibrillation in Patients with Decompensated Liver Cirrhosis: Bold and Brave?

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.

Clinical and Laboratory Characteristics of Normal Weight and Obese Individuals with Non-Alcoholic Fatty Liver Disease.

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.

Simultaneously Screening for Liver Steatosis and Fibrosis in Romanian Type 2 Diabetes Mellitus Patients Using Vibration-Controlled Transient Elastography with Controlled Attenuation Parameter.

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 (ß = 0.223, p = 0.022), total cholesterol (ß = 0.159, p = 0.031), and HDL-cholesterol (ß = −0.120, p = 0.006). In multivariate analyses, BMI (ß = 0.349, p < 0.001), fasting plasma glucose (ß = 0.211, p = 0.006), and triglycerides (ß = 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.

Changes in Liver Steatosis Using Controlled Attenuation Parameter among Patients with Chronic Hepatitis C Infection Treated with Direct-Acting Antivirals Therapy Who Achieved Sustained Virological Response.

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.

Screening for Liver Steatosis and Fibrosis in Patients with Inflammatory Bowel Disease Using Vibration Controlled Transient Elastography with Controlled Attenuation Parameter.

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 (ß = 0.357, p = 0.021), body mass index (BMI) (ß = 0.185, p = 0.048), disease duration (ß = 0.297, p = 0.041), C-reactive protein (ß = 0.321, p = 0.013), fasting plasma glucose (ß = 0.269, p = 0.038), and triglycerides (ß = 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.

The Role of Presepsin in Diagnosing Infections in Patients with Liver Cirrhosis and Overt Hepatic Encephalopathy.

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.

The Role of Presepsin and Procalcitonin in Early Diagnosis of Bacterial Infections in Cirrhotic Patients with Acute-on-Chronic Liver Failure.

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.