Nonalcoholic fatty liver disease: one entity, multiple impacts on liver health.

Nonalcoholic fatty liver disease (NAFLD) is very prevalent and now considered the most common cause of chronic liver disease. Staging the severity of liver damage is very important because the prognosis of NAFLD is highly variable. The long-term prognosis of patients with NAFLD remains incompletely elucidated. Even though the annual fibrosis progression rate is significantly higher in patients with nonalcoholic hepatitis (NASH), both types of NAFLD (nonalcoholic fatty liver and nonalcoholic steatohepatitis) can lead to fibrosis. The risk for progressive liver damage and poor outcomes is assessed by staging the severity of liver injury and liver fibrosis. Algorithms (scores) that incorporate various standard clinical and laboratory parameters alongside imaging-based approaches that assess liver stiffness are helpful in predicting advanced fibrosis.

Model of disease severity in alcoholic hepatitis and novel prognostic insights.

INTRODUCTION: Harmful alcohol consumption is one of the leading risk factors for global disease burden and injury condition, causing death and disability early in life, with over 3 million deaths worldwide every year. Alcoholic hepatitis (AH) is a clinical syndrome characterized by hepatic failure with recent onset of jaundice, consequence of a heavy chronic alcohol drinking. The disease severity ranges from mild to severe cases, with high short-term mortality. Individual variety regarding disease outcome and therapeutic response complicates the prognosis stratification. Thus, novel parameters and continuously sought for a better disease outcome assessment. AIMS AND OBJECTIVES: To highlight new parameters that accurately assess 30-day mortality (short-term) in patients with AH and to develop a new severity score that uses readily available parameters accessible to any clinician. MATERIALS AND METHODS: This is a prospective study on patients diagnosed with AH between 2022-2023. We identified 70 patients with AH who met the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for diagnosis after exclusion of patients with severe comorbidities that could influence disease outcome. Clinical and paraclinical parameters were assessed at least on admission and day 7. Mortality at 30-day was considered the endpoint. The database was composed using Microsoft Excel (Microsoft Corporation) and the data was analyzed using SPSS Statistics version 26 (IBM Corporation). RESULTS: A total of 70 patients were included in the study with a mortality at 30-days of 22.9% (n=16). The independent variables associated with increased short-term mortality identified using the univariate analysis were: fever, infection, esophageal varices, prothrombin time PT, INR, total bilirubin, CRP, LDH and CHI (creatinine height index). Using multivariate regression we determined a novel prognostic score, with criterion for retaining variable being p<0.05. Total bilirubin day 7, CRP, PT, fever and CHI resulted after the analysis and were included into a new mortality score. Our Prognostic Model Score obtained an area under the ROC of 0.950 (95% CI: 0.890-0.980, p<0.001), with a cut-off value of 13.75 (Sn=87.5%, Sp=91%). Regarding the consecrated prognostic scores, MDF and Lille score obtained good AUROCs=0.839 and 0.881, respectively (p<0.000), with cut-off values comparable with literature (MDF=34.35 vs 32) and (Lille=0.475 vs 0.450). The discriminatory power for ABIC (p=0.58), GAHS (p=0.16), MELD-Na (p=0.61) was not significant. CONCLUSION: We obtained a new prognostic score for the assessment of 30-day mortality in AH that includes markers of inflammation (CRP, fever) and markers of sarcopenia (CHI) along parameters of hepatic disfunction (total bilirubin and PT). Amongst consecrated prognostic models, MDF and Lille scores were representative for our study, while ABIC, GAHS and MELD-Na did not attain statistical significance. Our score is unique by the addition of CRP and this could prove to be a useful tool in AH severity stratification.

A Comparison of 13C-Methacetin and 13C-Octanoate Breath Test for the Evaluation of Nonalcoholic Steatohepatitis.

BACKGROUND: While non-alcoholic fatty liver disease (NAFLD) is a wide-spread liver disease, only some patients progress towards steatohepatitis and cirrhosis. AIM: We comparatively analyzed the methacetin breath test (MBT) for the microsomal function of the liver and the octanoate breath test (OBT) for mitochondrial activity, in detecting patients with steatohepatitis and estimating fibrosis. METHODS: 81 patients with histologically proven NAFLD (SAF score) were evaluated. The parameters used for both breath tests were the dose/h and the cumulative dose recovery at multiple timepoints. The statistical association between histological diagnosis and breath test results used Independent Samples t Test. The accuracy for diagnosis was evaluated using area under the receiver operator characteristic (AUROC) and the sensitivity and specificity were assessed using the Youden J method. RESULTS: Both MBT and OBT were able to differentiate patients with simple steatosis from NASH and to stratify patients with significant fibrosis and cirrhosis (p-values < 0.001 for most analyzed timepoints). The best parameter for NASH diagnosis was OBT dose at 30 min. In the case of significant fibrosis, the most accurate test was MBT cumulative dose at 30 min. CONCLUSIONS: Both MBR and OBT tests are potentially useful tools in assessing patients with NAFLD.

The correlation between Body Mass Index and histological features of Nonalcoholic Fatty Liver Disease.

Introduction: NAFLD is strongly associated with metabolic syndrome, and for many years, fatty liver was an exclusive feature of obese patients. The study tries to assess whether the body mass index (BMI) and body circumference is correlated to steatosis, fibrosis, or inflammatory activity of the liver. Methods: 81 patients with recent hepatic biopsy were included in the study and were weighed and measured. The biopsy results were compared to the measurements. Results: The average BMI overall for the whole lot was 30.16. There was a significant difference in BMI across the inflammatory activity categories (p = 0.009): groups with higher necro inflammatory activity tended to have higher BMI values (average values per grade: 0-28, 1-29, 2-33, 3-32, 4-29). There was no significant difference for grades of steatosis (p = 0.871). With regards to waist circumference, the overall average was 90.70cm/35.70in. There was a significant difference across the steatosis categories (p < 0.001): groups with higher steatosis scores had higher waist circumferences (average values per grade: 1-77cm / 30 in, 2-95 cm / 37 in, 3-94 cm / 37 in). There was no significant difference for grades of activity (p = 0.058). Conclusion: BMI and waist circumference are easy to measure, non-invasive parameters, which could be useful in screening patients at higher risk for necro inflammatory activity or severe steatosis.

A Primer into the Current State of Artificial Intelligence in Gastroenterology.

Artificial intelligence (AI) is not a new idea or field of research. However, recent advancements in computing technology as well as increasing worldwide experience in applying AI to various fields have enabled us to hope that applying it to the medical practice could improve outcomes. The aim of the article was to evaluate potential applications of artificial intelligence (AI) in the clinical practice of gastroenterology. AI algorithms can offer many benefits over the traditional diagnostic, prognostic, therapeutic scores, or non-AI enhanced procedures that we perform today. It can very easily process complex mathematical data, which would allow to account for many parameters and with highly sophisticated formulas to determine a conclusion, to a degree that would be impractical or impossible for a human to do alone in the clinical practice. This could allow for significantly more individualized treatments for each patient. As more data becomes available, it can be fed into the algorithm, which allows it to change based on the new data. However, we must be aware that most studies performed today are still early retrospective studies, and their utility still needs to be evaluated in future large scale prospective studies. Apart from the medical challenges, it must be noted that the impact of large-scale implementation of artificial intelligence will have challenges related to ethical and financial aspects as well.

The Role of Noninvasive 13C-Octanoate Breath Test in Assessing the Diagnosis of Nonalcoholic Steatohepatitis.

BACKGROUND: The diagnosis of NASH needs a liver biopsy, an invasive procedure that is not frequently accepted by patients. The aim of our study was to evaluate the efficacy of the 13C-Octanoate breath test (OBT) as a non-invasive surrogate marker to differentiate patients with NASH from patients with simple steatosis (NAFL). METHODS: We performed a prospective study on patients with histologically established non-alcoholic steatohepatitis and no other hepatic disease. Each patient underwent a testing protocol, which included a clinical exam, laboratory blood tests, standard abdominal ultrasound, and a 13C-Octanoate breath test. RESULTS: The study group included: 82 patients with steatohepatitis, 64 patients with simple steatosis, and 21 healthy volunteers. The univariate and bivariate analysis identified that significant values were the percent dose recovery (PDR) at 15 min-r = 0.65 (AUROC = 0.902) and cumulative percent dose recovery (cPDR) at 120 min-r = 0.69 (AUROC = 0.899). DISCUSSION: Our study showed that 13C-OBT had good efficacy for identifying patients with NASH from those with NAFL (steatosis alone) but not those with NAFL from healthy subjects. Considering all these pathogenic steps in NASH we considered that OBT could have the clinical utility to identify patients at risk for NASH, especially "fast progressors".

Non-invasive Ultrasonographic Score for Assessment of the Severity of Inflammatory Bowel Disease.

Intestinal ultrasound and shear wave elastography have gained increasing interest because of their promising results in the assessment of inflammatory bowel disease. The aim of this study was to find an ultrasonographic score to replace invasive endoscopic procedures for the management of these patients. The score includes ultrasound parameters that correlate well with clinical severity scales and inflammatory markers: bowel wall thickness, the Limberg score, disease extension and acoustic radiation force impulse measurements. The score proved to be well correlated with the Harvey Bradshaw Index, the Mayo score, C-reactive protein and fecal calprotectin. For Crohn's disease, a cutoff value of 8 points could identify active disease with 81.81% sensitivity and 83% specificity, while for ulcerative colitis, a cutoff value of 7 points could discriminate between remission and relapse with 86.85% sensitivity and 94% specificity. In conclusion, our ultrasonographic score can differentiate relapse from remission in inflammatory bowel disease.

Non-invasive laboratory, imaging and elastography markers in predicting varices with high risk of bleeding in cirrhotic patients.

Introduction. Upper digestive tract endoscopy remains the gold-standard for detecting esophageal or gastric varices and assessment of bleeding risk, but this method is invasive. The aim of the study was to identify non-invasive factors that could be incorporated into an algorithm for estimating the risk of variceal bleeding.Methods. A prospective study was performed on 130 cirrhotic patients. Tests were performed on all patients which included liver enzymes, complete blood count and coagulation parameters, abdominal ultrasound, elastography of both the liver and the spleen. Upper gastrointestinal endoscopy was performed in all patients included in the study and the results were classified, in accordance with Baveno VI into 2 outcome groups: Group 1 - patients with low bleeding risk and Group 2 - patients with varices needing treatment.Results. The study lot (130 patients) was divided into: Group I (low bleeding risk - 102 patients), and Group II (high bleeding risk - 28 patients). Parameters found to have significant differences in univariate analysis were transaminases, platelet count, spleen size, INR, portal vein diameter and both liver and spleen elastography. Calculating AUROC for each parameter identifies spleen elastography as having the best result, followed by INR, AST and platelet count. Liver elastography had the worst AUROC. Independent variables identified by logistic regression included spleen elastography, INR, platelet count, spleen diameter, ALT, age, and gender.Conclusions. Spleen stiffness is the best single parameter predicting the presence of high-risk esophageal varices.

The role of spleen stiffness using ARFI in predicting esophageal varices in patients with Hepatitis B and C virus-related cirrhosis.

INTRODUCTION: Current guidelines recommend that all patients with cirrhosis undergo upper gastrointestinal endoscopy (UGE) screening for esophageal varices (EV). Unfortunately, UGE has a lot of disadvantages, consequently various non-invasive methods of diagnosing EV have been proposed. We evaluated if spleen stiffness (SS) measured by Acoustic Radiation Force Impulse (ARFI) is a viable technique in diagnosing EV. METHODS: We recruited 178 patients with cirrhosis caused by Hepatitis B and C who underwent biochemical tests, abdominal ultrasound, UGE, LS and SS measurements using ARFI elastography. Based on the endoscopic results the patients were divided in 3 groups: without EV, with small EV (<5 mm) and with large EV (>5 mm). RESULTS: ARFI SS was the only non-invasive parameter associated with the presence of EV (2.7±0.30 vs. 3.4±0.52, p<0.001) and large EV (2.91±0.36 vs. 3.86±0.37, p=0.001) after multivariate logistic regression (p<0.001). ARFI SS for predicting EV showed an AUROC of 0.872 (CI 95%: 0.799-0.944), for a cut-off value of 2.89 m/s: Sensitivity (Se) 91.4% (CI 95%: 81-97%), Specificity (Sp) 67.7% (CI 95%: 51-85%). ARFI SS for diagnosing large EV (>5mm) had better results with an AUROC 0.969 (CI 95%:0.935-0.99), and for a cut-off of 3.30 m/s: Se 96.4% (CI 95%: 82-99.9%), Sp 88.5% (CI 95%: 78-95%). CONCLUSIONS: SS measured using ARFI is a good method of detecting EV and is an excellent method of diagnosing large EV in patients with virus-related cirrhosis.

Spleen Stiffness as Predictor of Esophageal Varices in Cirrhosis of Different Etiologies.

The purpose of this study is to determine whether esophageal varices (EV) can be identified through the evaluation of spleen stiffness (SSM) via acoustic radiation force impulse (ARFI). A total of 135 patients suffering from cirrhosis underwent a clinical exam, laboratory tests, abdominal ultrasound, liver stiffness (LSM) measurement, SSM evaluation and upper gastrointestinal endoscopy. Based on the endoscopy results, the patients were classified into three groups: those with no evident EV, those with small EV and those with varices needing treatment (VNT). Patients with EV of any grade had significantly higher average SSM values over those with no EV (3.37 m/s versus 2.79 m/s, p-value < 0.001), while patients with VNT showed an even greater difference (3.96 m/s versus 2.93 m/s, p-value < 0.001). SSM proved to be an excellent method of predicting patients with VNT.