Hepatitis E Virus: What More Do We Need to Know?

Hepatitis E virus (HEV) infection is typically a self-limiting, acute illness that spreads through the gastrointestinal tract but replicates in the liver. However, chronic infections are possible in immunocompromised individuals. The HEV virion has two shapes: exosome-like membrane-associated quasi-enveloped virions (eHEV) found in circulating blood or in the supernatant of infected cell cultures and non-enveloped virions ("naked") found in infected hosts' feces and bile to mediate inter-host transmission. Although HEV is mainly spread via enteric routes, it is unclear how it penetrates the gut wall to reach the portal bloodstream. Both virion types are infectious, but they infect cells in different ways. To develop personalized treatment/prevention strategies and reduce HEV impact on public health, it is necessary to decipher the entry mechanism for both virion types using robust cell culture and animal models. The contemporary knowledge of the cell entry mechanism for these two HEV virions as possible therapeutic target candidates is summarized in this narrative review.

Determinants of COVID-19 Disease Severity-Lessons from Primary and Secondary Immune Disorders including Cancer.

At the beginning of the COVID-19 pandemic, patients with primary and secondary immune disorders-including patients suffering from cancer-were generally regarded as a high-risk population in terms of COVID-19 disease severity and mortality. By now, scientific evidence indicates that there is substantial heterogeneity regarding the vulnerability towards COVID-19 in patients with immune disorders. In this review, we aimed to summarize the current knowledge about the effect of coexistent immune disorders on COVID-19 disease severity and vaccination response. In this context, we also regarded cancer as a secondary immune disorder. While patients with hematological malignancies displayed lower seroconversion rates after vaccination in some studies, a majority of cancer patients' risk factors for severe COVID-19 disease were either inherent (such as metastatic or progressive disease) or comparable to the general population (age, male gender and comorbidities such as kidney or liver disease). A deeper understanding is needed to better define patient subgroups at a higher risk for severe COVID-19 disease courses. At the same time, immune disorders as functional disease models offer further insights into the role of specific immune cells and cytokines when orchestrating the immune response towards SARS-CoV-2 infection. Longitudinal serological studies are urgently needed to determine the extent and the duration of SARS-CoV-2 immunity in the general population, as well as immune-compromised and oncological patients.

Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review.

The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10-20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients' survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients.

Galad Score as a Prognostic Marker for Patients with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for more than 75% of primary liver cancers, which are the second leading cause of cancer-related deaths. The GALAD (gender, age, AFP-L3, AFP, and des-carboxy-prothrombin) score is a diagnostic tool developed based on gender, age, alpha-fetoprotein, alpha-fetoprotein L3, and des-gamma-carboxy prothrombin, originally designed as a diagnostic tool for HCC in high-risk patients. METHODS: We analyzed 212 patients with and without cirrhosis. The population study was divided into patients with liver cirrhosis without evidence of HCC at the time of serum sample collection for GALAD score determination and patients with liver cirrhosis and a confirmed diagnosis of HCC at the time of serum sample collection for GALAD score determination. Patients were followed up until death or liver transplantation. The association between variables and HCC mortality risk was performed, and the results were presented as hazard ratio (HR). The receiver operating characteristic (ROC) curve was used to assess the performance of the GALAD HCC diagnosis. The survival probability was explored using the non-parametric test, and the equality of survival amongst categories was assessed with the log-rank test. RESULTS: Biomarkers were higher in the HCC group compared to cirrhosis. Kaplan-Meier survival probability analysis for individual GALAD categories revealed that a high GALAD level was associated with decreased survival during follow-up, and the difference between the curves was statistically significant (p = 0.01). CONCLUSIONS: Our findings suggest that the GALAD score has promise as a prognostic tool, with implications for improving patient management and treatment strategies for HCC.

A systematic review and meta-analysis of endoscopic mucosal resection vs endoscopic submucosal dissection for colorectal sessile/non-polypoid lesions.

BACKGROUND: Current international guidelines strongly advise endoscopic submucosal dissection (ESD) instead of endoscopic mucosal resection (EMR) for the endoscopic resection of sessile colorectal tumours >20 mm. AIMS: To compare the safety and efficacy of EMR and ESD for treating large non-invasive colorectal lesions. MATERIAL AND METHODS: We performed a systematic review using electronic databases (MEDLINE/PubMed, EMBASE, and Cochrane Library) on February 21st, 2021 and a meta-analysis to assess en-bloc and R0 rates, and related adverse events. RESULTS: Twenty-four studies were included, comparing 3,424 ESD and 5,122 EMR procedures. The en-bloc resection rate was 90.8% in the ESD and 33.0% in the EMR group (p < .001). The R0 resection rate was 85.0% in the ESD and 64.6% in the EMR group (p = .005). The rate of perforation was 5.1% in the ESD and 1.67% in the EMR group (p < .001). The bleeding rate was 4.3% in the ESD and 3.6% in the EMR group (p = .008). The overall need for surgery, including oncologic reasons and complications, was 5.9% in the ESD and 3.1% in the EMR group (p < .001). CONCLUSIONS: ESD for large non-pedunculated colorectal lesions allows a higher rate of R0 resections than EMR, at the cost of a higher perforation rate and the need for additional surgery.

Real-Life Effectiveness and Safety of Golimumab and Its Predictors of Response in Patients with Ulcerative Colitis.

BACKGROUND: Golimumab is a new anti-TNF-alpha monoclonal antibody for patients with ulcerative colitis. AIMS: To assess the short- and long-term effectiveness and safety of golimumab in daily clinical practice and to identify predictors of response. METHODS: Consecutive patients treated with golimumab in 22 Italian centers were enrolled. Clinical, laboratory, and endoscopic data were prospectively collected before and during treatment. A subgroup of patients completed a questionnaire to assess personal satisfaction with a golimumab autoinjector system. RESULTS: A total of 196 patients were included. After 3 months, 130 patients were responders (66.3%) and showed significant reductions in mean partial, total, and endoscopic Mayo scores and in mean ESR, C-reactive protein, and fecal calprotectin levels (p < 0.001). Multivariate analysis revealed that a higher total Mayo score (p < 0.001, OR 1.5, 95% CI 1.2-1.8) and naïve status to anti-TNF-alpha (p = 0.015, OR 3.0, 95% CI 1.2-7.5) were predictive of a favorable response. Seventy-seven (39.3%) of the 130 responders maintained a response at month 12 of therapy. There were 17 adverse events, 28 patients needed hospitalization, and 15 patients underwent surgery. Self-administration of the drug was appreciated by most patients. CONCLUSIONS: The efficacy and safety of golimumab in daily clinical practice were confirmed for the short- and long-term treatment of patients with active ulcerative colitis. Patients naïve to the anti-TNF-alpha monoclonal antibody and those with a higher total Mayo score were more likely to respond to golimumab.

Current Approaches for Monitoring of Patients with Inflammatory Bowel Diseases: A Narrative Review.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) require proactive monitoring both during the active phase to evaluate therapeutic response and during the remission phase to evaluate relapse or colorectal cancer surveillance. However, monitoring may vary between patients with ulcerative colitis (UC) and Crohn's disease (CD), with distinct tools and intervals. METHODS: This narrative review aims to focus on modern approaches to IBD monitoring, considering international guidelines and expert consensus. RESULTS: The most recent European diagnostic guidelines advocate a combination of clinical, laboratory, endoscopic, and radiological parameters to evaluate the disease course of patients with IBD. Unfortunately, the conventional symptom-based therapeutic approach does not improve long-term outcomes and there is no single ideal biomarker available. Endoscopy plays a key role in evaluating response to therapy as well as monitoring disease activity. Recently, bedside intestinal ultrasound (IUS) has gained increasing interest and diffusion as it appears to offer several advantages including the monitoring of therapeutic response. CONCLUSION: In light of growing clinical advances, we present a schematic evidence-based monitoring algorithm that can be easily applied in clinical practice which combines all major monitoring modalities, including noninvasive tools such as IUS and video-capsule endoscopy.

Gender Differences in Liver Steatosis and Fibrosis in Overweight and Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease before and after 8 Weeks of Very Low-Calorie Ketogenic Diet.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

Higher-Level Steatosis Is Associated with a Greater Decrease in Metabolic Dysfunction-Associated Steatoic Liver Disease after Eight Weeks of a Very Low-Calorie Ketogenic Diet (VLCKD) in Subjects Affected by Overweight and Obesity.

The most common form of chronic liver disease, recently defined as MASLD, is strongly linked to obesity and metabolic syndrome. Lifestyle changes are part of MASLD prevention. The very low-calorie ketogenic diet (VLCKD) is a useful option for treating MASLD and reducing liver steatosis in patients with obesity. We assessed whether a greater degree of steatosis could have a positive or negative impact on how well 8 weeks of using the VLCKD improve steatosis and fibrosis in a patient population of overweight and obese individuals. Anthropometric parameters, along with changes in hormone and metabolic biomarkers, were also assessed both before and after the dietary change. The study population included 111 overweight (14.41%) or obese subjects (85.59%) aged between 18 and 64 years; the 75 women and 36 men involved were not taking any medicine. In both the raw (0.37 95% CI 0.21; 0.52) and the multivariate models (model a: 0.439 95% CI 0.26; 0.62; model b: 0.437 95% CI 0.25; 0.63), there was a positive and statistically significant correlation between the CAP delta value and the CAP before using the VLCKD. Additionally, the liver stiffness delta was found to be positively and statistically significantly correlated with liver stiffness before the use of the VLCKD in both models: the multivariate model (model a: 0.560 95% CI 0.40; 0.71; model b: 0.498 95% CI 0.34; 0.65) and the raw model (0.52 95% CI 0.39; 0.65). Systolic and diastolic blood pressure, insulin resistance (measured by HOMA-IR), insulin, HbA1c, fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, BMI, waist circumference, and fat mass, were all decreased (p < 0.001) following the use of the VLCKD. However, following the use of the VLCKD, there was an increase in vitamin D levels. (p < 0.001). We found that using the VLCKD for 8 weeks has a greater effect on improving steatosis and fibrosis in subjects who initially have more severe forms of these conditions.

Corrigendum: Can vitamin D status influence seroconversion to SARS-COV2 vaccines?

[This corrects the article DOI: 10.3389/fimmu.2022.1038316.].

Prevention of influenza complications in patients with liver disease: a retrospective cohort study.

Introduction: Patients with chronic liver disease are highly prone to acquiring influenza infection diseases and experiencing associated complications. National and international guidelines recommend the influenza vaccine for patients with liver disorders to reduce the risk of influenza complications. Our study aims to evaluate the risk of flu complications faced by patients with liver disease and assess influenza vaccination coverage. Methods: The archive of hospital discharge forms was used to define the list of Apulian patients with liver disease, considering data from 2017 through 2022. The vaccination status of these patients was assessed via data collected from the Regional Immunization Database. We focused on influenza vaccine shots administered during the 2020/21, 2021/22, and 2022/23 flu seasons. Results: A declining trend across the flu seasons was observed, with a VC of 49.5% in the 2020/21 flu season, 48.1% in the 2021/22 season, and 45.0% in the 2022/23 season. Subjects with multiple comorbidities have higher vaccination rates. Additionally, the multivariate models demonstrate that vaccination compliance increases with age and is strongly associated with having received a previous influenza vaccine shot. Conclusion: The VC rates reported in our study are unsatisfactory and did not reach the minimum achievable goal (75%) the Italian Ministry of Health set. A multifactorial approach is required to raise the immunization rates and therefore protect the patients from the influenza-associated risk of collateral liver damage; the role of gastroenterologists and hepatologists is crucial, as their responsibilities should extend beyond patient care to the prevention of complications after infectious diseases.

Effectiveness and application of artificial intelligence for endoscopic screening of colorectal cancer: the future is now.

INTRODUCTION: Artificial intelligence (AI) in gastrointestinal endoscopy includes systems designed to interpret medical images and increase sensitivity during examination. This may be a promising solution to human biases and may provide support during diagnostic endoscopy. AREAS COVERED: This review aims to summarize and evaluate data supporting AI technologies in lower endoscopy, addressing their effectiveness, limitations, and future perspectives. EXPERT OPINION: Computer-aided detection (CADe) systems have been studied with promising results, allowing for an increase in adenoma detection rate (ADR), adenoma per colonoscopy (APC), and a reduction in adenoma miss rate (AMR). This may lead to an increase in the sensitivity of endoscopic examinations and a reduction in the risk of interval-colorectal cancer. In addition, computer-aided characterization (CADx) has also been implemented, aiming to distinguish adenomatous and non-adenomatous lesions through real-time assessment using advanced endoscopic imaging techniques. Moreover, computer-aided quality (CADq) systems have been developed with the aim of standardizing quality measures in colonoscopy (e.g. withdrawal time and adequacy of bowel cleansing) both to improve the quality of examinations and set a reference standard for randomized controlled trials.

Factors affecting the quality of bowel preparation for colonoscopy in hard-to-prepare patients: Evidence from the literature.

Adequate bowel cleansing is critical for a high-quality colonoscopy because it affects diagnostic accuracy and adenoma detection. Nevertheless, almost a quarter of procedures are still carried out with suboptimal preparation, resulting in longer procedure times, higher risk of complications, and higher likelihood of missing lesions. Current guidelines recommend high-volume or low-volume polyethylene glycol (PEG)/non-PEG-based split-dose regimens. In patients who have had insufficient bowel cleansing, the colonoscopy should be repeated the same day or the next day with additional bowel cleansing as a salvage option. A strategy that includes a prolonged low-fiber diet, a split preparation regimen, and a colonoscopy within 5 h of the end of preparation may increase cleansing success rates in the elderly. Furthermore, even though no specific product is specifically recommended in the other cases for difficult-to-prepare patients, clinical evidence suggests that 1-L PEG plus ascorbic acid preparation are associated with higher cleansing success in hospitalized and inflammatory bowel disease patients. Patients with severe renal insufficiency (creatinine clearance < 30 mL/min) should be prepared with isotonic high volume PEG solutions. Few data on cirrhotic patients are currently available, and no trials have been conducted in this population. An accurate characterization of procedural and patient variables may lead to a more personalized approach to bowel preparation, especially in patients undergoing resection of left colon lesions, where intestinal preparation has a poor outcome. The purpose of this review was to summarize the evidence on the risk factors influencing the quality of bowel cleansing in difficult-to-prepare patients, as well as strategies to improve colonoscopy preparation in these patients.

Endoscopic Ultrasound Advanced Techniques for Diagnosis of Gastrointestinal Stromal Tumours.

Gastrointestinal Stromal Tumors (GISTs) are subepithelial lesions (SELs) that commonly develop in the gastrointestinal tract. GISTs, unlike other SELs, can exhibit malignant behavior, so differential diagnosis is critical to the decision-making process. Endoscopic ultrasound (EUS) is considered the most accurate imaging method for diagnosing and differentiating SELs in the gastrointestinal tract by assessing the lesions precisely and evaluating their malignant risk. Due to their overlapping imaging characteristics, endosonographers may have difficulty distinguishing GISTs from other SELs using conventional EUS alone, and the collection of tissue samples from these lesions may be technically challenging. Even though it appears to be less effective in the case of smaller lesions, histology is now the gold standard for achieving a final diagnosis and avoiding unnecessary and invasive treatment for benign SELs. The use of enhanced EUS modalities and elastography has improved the diagnostic ability of EUS. Furthermore, recent advancements in artificial intelligence systems that use EUS images have allowed them to distinguish GISTs from other SELs, thereby improving their diagnostic accuracy.

Breaking through Multiple Myeloma: A Paradigm for a Comprehensive Tumor Ecosystem Targeting.

Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival. These advancements include thalidomide and its derivatives, lenalidomide and pomalidomide, which exhibit diverse mechanisms of action against the plasma cell clone. Additionally, proteasome inhibitors such as bortezomib, ixazomib, and carfilzomib disrupt protein degradation, proving specifically toxic to cancerous plasma cells. Recent advancements also involve monoclonal antibodies targeting surface antigens, such as elotuzumab (anti-CS1) and daratumumab (anti-CD38), bispecific t-cell engagers such as teclistamab (anti-BCMA/CD3) and Chimeric antigen receptor T (CAR-T)-based strategies, with a growing focus on drugs that exhibit increasingly targeted action against neoplastic plasma cells and relevant effects on the tumor microenvironment.

Diagnosis and Management of Esophagogastric Varices.

Acute variceal bleeding (AVB) is a potentially fatal complication of clinically significant portal hypertension and is one of the most common causes of acute upper gastrointestinal bleeding. Thus, esophagogastric varices represent a major economic and population health issue. Patients with advanced chronic liver disease typically undergo an upper endoscopy to screen for esophagogastric varices. However, upper endoscopy is not recommended for patients with liver stiffness < 20 KPa and platelet count > 150 × 109/L as there is a low probability of high-risk varices. Patients with high-risk varices should receive primary prophylaxis with either nonselective beta-blockers or endoscopic band ligation. In cases of AVB, patients should receive upper endoscopy within 12 h after resuscitation and hemodynamic stability, whereas endoscopy should be performed as soon as possible if patients are unstable. In cases of suspected variceal bleeding, starting vasoactive therapy as soon as possible in combination with endoscopic treatment is recommended. On the other hand, in cases of uncontrolled bleeding, balloon tamponade or self-expandable metal stents can be used as a bridge to more definitive therapy such as transjugular intrahepatic portosystemic shunt. This article aims to offer a comprehensive review of recommendations from international guidelines as well as recent updates on the management of esophagogastric varices.

The Effects of Eight Weeks' Very Low-Calorie Ketogenic Diet (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity.

Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not take any drugs. This prospective, real-life study included thirty-three participants who followed a VLCKD for 8 weeks. NAFLD was diagnosed using transient elastography (FibroScan). Data on anthropometric measurements, bioimpedance analysis, and biochemical assays were gathered both before and after the dietary intervention. BMI (kg/m2) (from 33.84 ± 6.55 to 30.89 ± 6.38, p < 0.01), waist circumference (cm) (from 106.67 ± 15.51 to 98.64 ± 16.21, p < 0.01), and fat mass (Kg) (from 38.47 ± 12.59 to 30.98 ± 12.39, p < 0.01) were significantly lower after VLCKD. CAP (db/m), the FibroScan parameter quantifying fatty liver accumulation, showed a significant reduction after VLCKD (from 266.61 ± 67.96 to 223 ± 64.19, p < 0.01). After VLCKD, the fatty liver index (FLI), a benchmark of steatosis, also revealed a significant decline (from 62.82 ± 27.46 to 44.09 ± 31.24, p < 0.01). Moreover, fasting blood glucose, insulin, triglycerides, total cholesterol, LDL-cholesterol, ALT, γGT, and FT3 blood concentrations, as well as insulin resistance (quantified by HOMAIR) and systolic and diastolic blood pressure levels, were significantly lower after VLCKD (p < 0.01 for all the parameters). By contrast, HDL-cholesterol, 25 (OH) vitamin D, and FT4 blood concentrations were higher after VLCKD (p < 0.01 for all parameters). The variation (δ) of CAP after VLCKD did not show a correlation with the δ of any other parameter investigated in this study. We conclude that VLCKD is a helpful approach for NAFLD independent of changes in factors commonly associated with NAFLD (obesity, fat mass, insulin resistance, lipids, and blood pressure) as well as vitamin D and thyroid hormone levels.

GALAD outperforms aMAP and ALBI for predicting HCC in patients with compensated advanced chronic liver disease: A 12-year prospective study.

BACKGROUND AND AIMS: Surveillance programs are strongly recommended in patients with liver cirrhosis for early detection of HCC development. Six-monthly ultrasound sonography is the most reliable and commonly used technique, especially when associated with serum determination of α-fetoprotein, but different score systems have been proposed to overcome the unsatisfactory diagnostic accuracy of α-fetoprotein. The aim of this 12-year prospective study is to compare the gender, age, AFP-L3, AFP, des-gamma-carboxy prothrombin (GALAD) versus age, gender, bilirubin, albumin, and platelets and albumin-bilirubin scores in predicting HCC onset. APPROACH AND RESULTS: A cohort of 545 consecutive patients with compensated advanced chronic liver disease without suspected focal lesions was followed up every 6 months by liver imaging and α-fetoprotein to detect HCC occurrence. Harrell's C-index for censored data was employed to evaluate the performance of any parameters or scores helping to predict HCC development. ROC curve analysis showed that the GALAD score was more accurate in evaluating HCC development than albumin-bilirubin and age, gender, bilirubin, albumin, and platelets. The AUC ranged from 0.7268 to 0.6851 at 5 and 10 years, both in the total cohort and in the sub-cohorts (viral hepatitis, NASH, and alcohol). The HCC Risk model was constructed using univariate and multivariate Cox proportional hazard regression analysis, showing a strong association of GALAD with HR > 1, p < 0.05, in the total and sub-cohorts, and a better risk prediction in the alcohol cohort, both alone and standardized with other blood parameters. CONCLUSIONS: GALAD is the most reliable and accurate score system to detect HCC risk of development in patients with compensated advanced chronic liver disease.

The Replacement of Only One Portion of Starchy Carbohydrates with Green Leafy Vegetables Regresses Mid and Advanced Stages of NAFLD: Results from a Prospective Pilot Study.

The gold standard treatment for NAFLD is weight loss and lifestyle interventions, which require a diet enriched in fiber and reduced in sugars and saturated fats. Fibres may be advantageous for NAFLD patients since they reduce and slow the absorption of carbohydrates, lipids, and proteins, lowering the energy density of the meal and increasing their sense of satiety. Furthermore, the polyphenol content and other bioactive compounds of vegetables have antioxidant and anti-inflammatory properties preventing disease progression. The aim of this study is to ascertain the effects of a diet enriched by green leafy vegetables and with a moderate restriction of carbohydrate intake in patients with NAFLD over a three month period. Among the forty patients screened, twenty four patients completed the clinical trial consisting of swapping one portion of carbohydrate-rich food for one portion of green leafy vegetables, and liver and metabolic markers of NAFLD were evaluated. All patients underwent routine blood tests, anthropometric measurements, bioelectrical impedance analysis, fibroscan, and fatty liver index (FLI) evaluation before and at the end of the study. The population under study (n = 24) had a median age of 47.5 (41.5-52.5) years and included mainly women (70.8%). We found that FLI, which is used to predict fatty liver (73 (33-89) vs. 85 (54-95), p < 0.0001) and the FAST score, which is a fibroscan-derived parameter identifying patients at risk of progressive NASH (0.03 (0.02-0.09) vs. 0.05 (0.02-0.15), p = 0.007), were both improved after changes in diet. The BMI (33.3 (28.6-37.3) vs. 35.3 (31.2-39.0), p < 0.0001), WC (106.5 (95.0-112.5) vs. 110.0 (103.0-124.0), p < 0.0001), neck circumference (38.0 (35.0-41.5) vs. 39.5 (38.0-42.5), p < 0.0001), fat mass (32.3 (23.4-40.7) vs. 37.9 (27.7-43.5), p < 0.0001), and extracellular water (17.3 (15.2-20.8) vs. 18.3 (15.9-22.7), p = 0.03) were also all significantly lower after three months of diet. Metabolic parameters linked to NAFLD decreased: HbA1c (36.0 (33.5-39.0) vs. 38.0 (34.0-40.5), p = 0.01), triglycerides (72 (62-90) vs. 90 (64-132), p = 0.03), and the liver markers AST (17 (14-19) vs. 18 (15-27), p = 0.01) and γGT (16 (13-20) vs. 16 (14-27), p = 0.02). In conclusion, replacing only one portion of starchy carbohydrates with one portion of vegetables for a three month period is sufficient to regress, at least in part, both mid and advanced stages of NAFLD. This moderate adjustment of lifestyle habits is easily achievable.