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.

Eosinophilic enteritis: the great mimic.

Eosinophilic enteritis (EoN), a subtype of eosinophilic gastrointestinal disease, is a rare and complicated inflammatory condition affecting the small intestine. This case report discusses a 42-year-old patient who presented with acute gastrointestinal symptoms including diarrhea, nausea, and vomiting. Initial laboratory investigations revealed leukocytosis, peripheral eosinophilia, and distinctive imaging findings, prompting further evaluation. Endoscopic evaluation revealed extensive mucosal lesions in the small intestine, with subsequent biopsies confirming eosinophilic infiltration, ultimately leading to the diagnosis of chronic enteritis, probably of an eosinophilic nature. The case highlights the complex differential diagnostic process involved in identifying EoN, which requires a comprehensive understanding of all the clinical and histopathological features of the disease. The efficacy of budesonide therapy is also discussed in the management of EoN and it was evidenced by our patient's positive response to treatment. This case report contributes significant insights into the understanding and management of EoN, providing essential information for the medical community to facilitate accurate diagnosis and tailored therapeutic interventions for individuals experiencing this complex disorder.

Reclassification of Inflammatory Bowel Disease Type Unclassified by Small Bowel Capsule Endoscopy.

Background and Objectives: Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory bowel diseases (IBDs) without a unique, gold standard diagnostic test. UC and Crohn's colitis are impossible to distinguish in approximately 10% of cases. The term IBD type unclassified (IBD-U) is recommended for cases of chronic colitis showing overlapping endoscopic, radiological, and biopsy histological features between UC and CD, while indetermined colitis is reserved for colectomy specimens. Our aim was to assess the role of small-bowel capsule endoscopy (SBCE) in the diagnostic work-up of IBD-U. Materials and Methods: We retrospectively studied the cases of IBD-U explored by SBCE in a tertiary referral gastroenterology center. Patients were investigated using SBCE after contraindications were excluded. Diagnostic criteria for small bowel CD consisted in more than three ulcerations, irregular ulcers, or stenosis, and the Lewis score was used for the quantification of inflammation. The immediate impact of reclassification and outcome data was recorded over a follow-up period of more than one year. Results: Twenty-eight patients with IBD-U were examined using SBCE. Nine patients had small bowel lesions that met the diagnostic criteria for CD, resulting in a reclassification rate of 32.1%. In five of these cases, the treatment was subsequently changed. In the remaining nineteen examinations, no significant findings were observed. There were no complications associated with SBCE. Median follow-up time was 32.5 months (range 12-60). During follow-up, twelve patients were classified as having UC, and seven remained as having an unclassified type; one case of colectomy, for medically refractory UC, was recorded. Conclusions: SBCE is a useful safe tool in the work-up of IBD-U, allowing reclassification in about one third of cases, with subsequent treatment modifications. SBCE may provide a definite diagnosis, enhance the comprehension of the disease's progression, and optimize the short- and long-term management strategy.

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease-Oxidative Stress and Inflammation Relevance.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease.

Aim: The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). Background: Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. Methods: The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. Results: A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. Conclusion: Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Severe Intentional Corrosive (Nitric Acid) Acute Poisoning: A Case Report and Literature Review.

Despite being one of the most debilitating conditions encountered in the field of toxicology, there is a lack of neutralization measures for the toxins involved in acute corrosive poisoning, and this promotes progressive contact injury of deep tissues after poisoning has occurred. Multiple controversies still surround management strategies during the acute phase of poisoning and the long-term follow-up of the patient. Here, we report a severe case of intentional poisoning with nitric acid complicated by extensive injury of the upper digestive tract, multiple stricture formation, and complete dysphagia. Serial endoscopic dilation and insertion of a jejunostomy feeding tube were necessary, and underlying psychiatric illness negatively affected the outcome of the patient. We conclude that an interdisciplinary approach is necessary to properly reduce the extent of lesions and sequelae induced by corrosion. Early endoscopic mapping of injuries is of major importance to better predict the evolution and possible complications of poisoning. Interventional and reconstructive surgical procedures may significantly improve the life expectancy and quality of life of patients following intoxication with corrosive substances.

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.

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.

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.

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease.

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.

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.

Improvement of carotid atherosclerosis and peripheral artery disease after hepatitis C virus eradication by direct-acting antivirals.

INTRODUCTION: Recent research points to a link between chronic hepatitis C virus (HCV) infection and cardiovascular disease, especially carotid atherosclerosis, and suggests that HCV clearance may impact cardiovascular outcomes. AIM: To determine if viral eradication by the new oral direct-acting antiviral (DAA) agents has benefit regarding carotid atherosclerosis, peripheral artery disease (PAD), steatosis, and liver fibrosis. PATIENTS, MATERIALS AND METHODS: We conducted a prospective study on 168 patients diagnosed with chronic HCV infection or HCV-related cirrhosis. They were all treated with DAAs, with sustained virological response (SVR). Laboratory data, vibration-controlled transient elastography (VCTE), carotid intima-media thickness (IMT) measurement, and ankle-brachial index (ABI) were recorded in all patients. RESULTS: We found an average IMT of 1.22±0.2 mm, with a variance range from 1.14±0.19 mm in the mild and moderate fibrosis (≤F2) group to 1.29±0.25 mm in the severe fibrosis (≥F3) group. Also, patients with severe fibrosis (≥F3) present a more critical decrease of IMT values, with the carotid thickness affecting only 18.2% of individuals in the follow-up period. At the baseline, the best values of ABI were recorded in patients having F1-F2 fibrosis stage (mean value 1.02±0.19). Instead, in the group with severe fibrosis, the average value of ABI was lower (0.91±0.16) at the baseline, with a significant increase at SVR evaluation (p<0.001). CONCLUSIONS: Our research highlights the beneficial effect of viral eradication on both carotid atherosclerosis and PAD, especially in those with advanced fibrosis and cirrhosis.

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.

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.

Ischemic Heart Disease and Liver Cirrhosis: Adding Insult to Injury.

The link between heart and liver cirrhosis was recognized decades ago, although much data regarding atherosclerosis and ischemic heart disease are still missing. Ischemic heart disease or coronary artery disease (CAD) and liver cirrhosis could be associated with characteristic epidemiological and pathophysiological features. This connection determines increased rates of morbidity and all-cause mortality in patients with liver cirrhosis. In the era of a metabolic syndrome and non-alcoholic fatty liver disease pandemic, primary prevention and early diagnosis of coronary artery disease could improve the prognosis of liver cirrhosis patients. This review outlines a summary of the literature regarding prevalence, risk assessment and medical and interventional treatment options in this particular population. A collaborative heart-liver team-based approach is imperative for critical management decisions for patients with CAD and liver cirrhosis.

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.

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.