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Dr. Davide Giuseppe Ribaldone

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Department of Medical Sciences, University of Turin, 10124 Turin, Italy

Dr. Gian Paolo Caviglia

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Department of Medical Sciences, University of Turin, 10126 Turin, Italy

Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice

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20 April 2024

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20 June 2024

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Dear Colleagues,

Management of gastrointestinal and hepatic diseases is constantly evolving. The progressive understanding of pathogenic mechanisms has improved daily management. This is real translational medicine.

For example, understanding the mechanisms underlying HCV virus infection has allowed the development of Direct-Acting Antivirals (DAA), with a cure of 98% of patients. However, patients with advanced liver disease, albeit cured from HCV infection, are still at risk of hepatocellular carcinoma (HCC) development. Therefore, these patients will be a medical issue for the years to come.

New antiviral agents are currently under development for the treatment of chronic delta hepatitis (CHD). Hopefully, in the next future we will be able at least to control liver disease progression in patients with CHD, the most severe form of chronic viral hepatitis.

In the coming decades, NAFLD/NASH will supplant viral hepatitis as the leading cause of chronic liver damage. Relevant efforts are ongoing for the identification of novel biomarkers and tools for the detection of liver fibrosis and for the stratification of the risk of liver disease progression. Moreover, novel molecules targeting several pathways involved in NAFLD onset and progression are under investigation.

The decrease in the prevalence of Helicobacter pylori (H. pylori) infection, the widespread use of proton pump inhibitors, and the relative ease of access to gastroscopies have reduced the incidence of peptic disease and stomach cancer, once the main gastrointestinal pathology. In many areas of the world, however, H. pylori infection is still widespread and there is still room for improvement in eradication strategies.

Understanding the inflammatory pathways involved in inflammatory bowel disease has allowed the development of target therapies (anti-TNF, anti-IL12/23, anti-JAK, S1P1 modulators).

Growing understanding of the microbiome will lead to applications that will go beyond the confines of the gut, though the COVID-19 pandemic will still affect the management of all diseases.

The objective of this Topic is to present the most up-to-date data on the pathogenesis and management of gastrointestinal and hepatological diseases, with a view to an increasingly personalized management of the patient.

Dr. Davide Giuseppe Ribaldone
Dr. Gian Paolo Caviglia
Topic Editors

Keywords

inflammatory bowel diseases
chronic viral hepatitis
hepatocellular carcinoma
digestive endoscopy
microbiota
celiac disease
NALFD
COVID-19
Helicobacter pylori

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	14.7 Days	CHF 2600	Submit
Current Oncology curroncol	2.6	2.6	1994	18.4 Days	CHF 2200	Submit
Diagnostics diagnostics	3.6	3.6	2011	18.8 Days	CHF 2600	Submit
Gastrointestinal Disorders gastrointestdisord	0.7	1.8	2019	29.3 Days	CHF 1200	Submit
Journal of Clinical Medicine jcm	3.9	5.4	2012	19.7 Days	CHF 2600	Submit

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Open AccessArticle

Comparison of Surgical Risk Scores in a European Cohort of Patients with Advanced Chronic Liver Disease

Lidia Canillas

Amalia Pelegrina

Elena Colominas-González

Aina Salis

César J. Enríquez-Rodríguez

and

J. Clin. Med. 2023, 12(18), 6100; https://doi.org/10.3390/jcm12186100 - 21 Sep 2023

Viewed by 239

Abstract

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. This is a retrospective, observational study to evaluate the predictive capacity of surgical risk scores in European patients with ACLD. Cirrhosis was defined by the presence of thrombocytopenia with <150,000/uL and splenomegaly, and AST-to-Platelet Ratio Index >2, a nodular liver edge seen via ultrasound, transient elastography of >15 kPa, and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n = 512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between the H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, and platelet count were not associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic_90D = 0.876) and overall predictive capacity (Brier_90D = 0.054), but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic_30D = 0.770), without signs of portal hypertension (C-statistic_30D = 0.555), or with abdominal wall (C-statistic_30D = 0.608) or urgent (C-statistic_180D = 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn’s discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessArticle

Prevalence of Multiple Sclerosis in Patients with Inflammatory Bowel Disease

Nuria Perez-Diaz-del-Campo

and

Davide Giuseppe Ribaldone

Gastrointest. Disord. 2023, 5(3), 287-295; https://doi.org/10.3390/gidisord5030023 - 30 Jun 2023

Viewed by 704

Abstract

Being two immune-mediated diseases (IMIDs), the association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) is plausible, but data in the literature are conflicting. The aim of our study was to evaluate the possible association between IBD and MS in a cohort of patients with IBD. In a retrospective study, we examined the medical records of 5739 patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2022. Among these patients, we identified 14 with MS, with a prevalence of 0.24%. The reported prevalence of MS in the general population in Northern Italy in 2021 was 0.18% (p = 0.24). For each of the patients with MS identified, more than ten patients without MS were analyzed. The 14 MS cases were then compared with 342 controls. From the 14 patients with MS, 12 (85.7%) were female and 2 (14.3%) were male, while in the control group, 158 (46.2%) were female and 184 (53.8%) were male (p = 0.004). As for therapy, significant differences were found in mesalazine (5 (41.7%) cases vs. 317 (92.7%) controls, p < 0.0001) and anti-TNF treatment (0% cases vs. 26.6% controls, p = 0.03, respectively) at the time of MS diagnosis. Moreover, a Kaplan–Meier curve analysis showed that the 20-year survival probability was 98.4% for patients with IBD, while for patients diagnosed with MS and IBD it was 82.1% (p = 0.02). In conclusion, patients with IBD have a similar risk of developing MS compared to the general population, but female sex appears to increase the risk. Indeed, life expectancy at 20 years for patients with IBD and MS is lower than for patients with IBD alone. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessArticle

Associations between Liver Enzymes, Lifestyle Risk Factors and Pre-Existing Medical Conditions in a Population-Based Cross-Sectional Sample

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J. Clin. Med. 2023, 12(13), 4276; https://doi.org/10.3390/jcm12134276 - 26 Jun 2023

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Abstract

While alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) enzymes are commonly used indicators of liver dysfunction recent studies have suggested that these may also serve as predictive biomarkers in the assessment of extrahepatic morbidity. In order to shed further light on the interactions between serum liver enzyme abnormalities, factors of lifestyle and health status we examined ALT and GGT activities in a population-based sample of 8743 adult individuals (4048 men, 4695 women from the National FINRISK 2002 Study, mean age 48.1 ± 13.1 years) with different levels of alcohol drinking, smoking, physical activity, body weight and the presence or absence of various pre-existing medical conditions. The assessments also included laboratory tests for inflammation, lipid status and fatty liver index (FLI), a proxy for fatty liver. The prevalence of ALT and GGT abnormalities were significantly influenced by alcohol use (ALT: p < 0.0005 for men; GGT: p < 0.0005 for both genders), smoking (GGT: p < 0.0005 for men, p = 0.002 for women), adiposity (p < 0.0005 for all comparisons), physical inactivity (GGT: p < 0.0005; ALT: p < 0.0005 for men, p < 0.05 for women) and coffee consumption (p < 0.0005 for GGT in both genders; p < 0.001 for ALT in men). The total sum of lifestyle risk factor scores (LRFS) influenced the occurrence of liver enzyme abnormalities in a rather linear manner. Significantly higher LRFS were observed in the subgroups of individuals with pre-existing medical conditions when compared with those having no morbidities (p < 0.0005). In logistic regression analyses adjusted for the lifestyle factors, both ALT and GGT associated significantly with fatty liver, diabetes and hypertension. GGT levels also associated with coronary heart disease, angina pectoris, cardiac insufficiency, cerebrovascular disease, asthma and depression. Combinations of abnormal ALT and GGT activities significantly increased the odds for hypertension coinciding with abnormalities in biomarkers of inflammation, lipid status and FLI. The data indicates that ALT and GGT activities readily respond to unfavorable factors of lifestyle associating also with a wide array of pre-existing medical conditions. The data supports close links between both hepatic and extrahepatic morbidities and lifestyle risk factors and may open new insights on a more comprehensive use of liver enzymes in predictive algorithms for assessing mechanistically anchored disease conditions. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

Open AccessReview

Fecal and Circulating Biomarkers for the Non-Invasive Assessment of Intestinal Permeability

Nuria Perez-Diaz-del-Campo

Gabriele Castelnuovo

Davide Giuseppe Ribaldone

and

Gian Paolo Caviglia

Diagnostics 2023, 13(11), 1976; https://doi.org/10.3390/diagnostics13111976 - 05 Jun 2023

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Abstract

The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessArticle

Controlled Attenuation Parameter Is Associated with a Distinct Systemic Inflammatory Milieu after Clearance of HCV Infection

Yanqin Du

Tanvi Khera

Zhaoli Liu

Magdalena Tudrujek-Zdunek

Anna Dworzanska

Markus Cornberg

Cheng-Jian Xu

Krzysztof Tomasiewicz

and

Heiner Wedemeyer

Biomedicines 2023, 11(6), 1529; https://doi.org/10.3390/biomedicines11061529 - 25 May 2023

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Abstract

Hepatitis C virus (HCV) infection is closely associated with lipid metabolism defects along with a high prevalence of hepatic steatosis. After HCV clearance, steatosis persists in many patients. However, the reasons behind this phenomenon are not completely clear. To investigate the association between 92 soluble inflammatory mediators (SIMs) and the steatosis grade, we made use of a cohort of 94 patients with chronic HCV infection who cleared HCV after direct-acting antiviral agent (DAA) treatment. Patients were classified into three groups according to their controlled attenuation parameter (CAP). CAP is associated with ALT, γ-GT and liver stiffness after HCV clearance. While stem cell factor (SCF) and tumor necrosis factor ligand superfamily member 12 (TWEAK) levels were significantly reduced in patients with CAP > 299 dB/m, the levels of fibroblast growth factor (FGF)-21 and interleukin-18 receptor 1 (IL-18R1) were higher in those patients at week 96 after virus clearance. These four markers also showed a linear correlation with CAP values. FGF-21 levels correlated with CAP only after HCV clearance. Taken together, these four biomarkers, namely SCF, TWEAK, FGF-21 and IL-18R1, are associated with CAP status after virus clearance. A potential role of these proteins in the pathogenesis of post-sustained viral response (SVR) nonalcoholic steatohepatitis requires further investigation. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessArticle

Serum Cardiotrophin-1 Concentration Is Negatively Associated with Controlled Attenuation Parameters in Subjects with Non-Alcoholic Fatty Liver Disease

and

J. Clin. Med. 2023, 12(7), 2741; https://doi.org/10.3390/jcm12072741 - 06 Apr 2023

Viewed by 803

Abstract

Background: Since non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity, cardiovascular disease, and diabetes, biomarkers for the diagnosis of NAFLD have become an important issue. Although cardiotrophin-1 (CT-1) has a protective effect on the liver in NAFLD animal models, the serum levels of CT-1 in human subjects with NAFLD were still unknown. Objective: The present study aimed to investigate the relationship between the circulating concentration of CT-1 and the severity of hepatic steatosis graded by the value of the controlled attenuation parameter (CAP) in humans. Design and Methods: The study was designed as a cross-sectional study, and a total of 182 subjects were enrolled. Hepatic steatosis measurement was carried out with a Firoscan^® device and recorded by CAP. The enrolled study subjects were categorized into CAP < 238 dB/m, 238 ≤ CAP ≤ 259 dB/m, 260 ≤ CAP ≤ 290 dB/m, and CAP > 290 dB/m. Serum CT-1 concentrations were determined by enzyme-linked immunosorbent assay. The association between the serum CT-1 concentration and NAFLD was examined by multivariate linear regression analysis. Results: Body mass index, percentage of body fat, systolic and diastolic blood pressure, alanine aminotransferase (ALT), cholesterol, triglyceride, hemoglobin A1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly increased in groups with higher CAP value, whereas high-density lipoprotein cholesterol was significantly decreased. In addition, serum CT-1 concentrations were significantly decreased in subjects with higher CAP values. In multivariate linear regression models, including age, sex, body fat percentage, CAP, high sensitivity- C reactive protein, uric acid, creatinine, ALT, total cholesterol, and HOMA-IR, only age, CAP and uric acid independently associated with CT-1 levels. Moreover, having NAFLD was independently associated with CT-1 after adjustment for sex, obesity and type 2 diabetes. Conclusions: Serum CT-1 concentrations are decreased in subjects with NAFLD and negatively associated with CAP. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessArticle

The Impact of Partial Splenic Embolization on Portal Hypertensive Gastropathy in Cirrhotic Patients with Portal Hypertension

and

J. Clin. Med. 2023, 12(7), 2662; https://doi.org/10.3390/jcm12072662 - 03 Apr 2023

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Abstract

This study investigated the impact of partial splenic embolization (PSE) on portal hypertensive gastropathy (PHG). We retrospectively analyzed endoscopic findings and the portal venous system of 31 cirrhotic patients with PHG. The improved group was defined as the amelioration of PHG findings using the McCormack classification. Child–Pugh scores of the improved group (18 of 31 patients) were significantly lower compared with those of the non-improved group (p = 0.018). The changes in the diameters of the portal trunk and those of the spleno-portal junction and spleen hilum in the splenic vein of the improved group were significantly larger than those of the non-improved group (p = 0.007, p = 0.025, and p = 0.003, respectively). The changes in the diameters of the portal vein and splenic hilum of the splenic vein showed significant correlations with Child–Pugh score (r = 0.386, p = 0.039; r = 0.510, p = 0.004). In a multivariate analysis of baseline factors related to the improved group, Child–Pugh grade A was significantly associated with the improvement of PHG (odds ratio 6.875, p = 0.033). PSE could be useful for PHG, especially in patients with Child–Pugh grade A, at least in the short term. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessArticle

The Choice of the Most Appropriate Suture Threads for Pancreatic Anastomoses on the Basis of Their Mechanical Characteristics

Maria Laura Costantino

and

Alessandro Zerbi

Biomedicines 2023, 11(4), 1055; https://doi.org/10.3390/biomedicines11041055 - 30 Mar 2023

Viewed by 754

Abstract

The choice of the most appropriate suture threads for pancreatic anastomoses may play an important role in reducing the incidence of post-operative pancreatic fistula (POPF). The literature on this topic is still not conclusive. The aim of this study was to analyze the mechanical characteristics of suture materials to find the best suture threads for pancreatic anastomoses. A single-axial electromagnetic actuation machine was used to obtain the stress–deformation relationship curves and to measure both the ultimate tensile strength (UTS) and the Young’s modulus at the 0–3% deformation range (E_0–3) of four different suture materials (Poliglecaprone 25, Polydioxanone, Polyglactin 910, and Polypropylene) at baseline and after incubation in saline solution, bile, and pancreatic juice for 1, 3, and 7 days. Polydioxanone and Polypropylene showed stable values of UTS and E_0–3 in all conditions. Polyglactin 910 presented significant UTS and E_0–3 variations between different time intervals in all types of liquids analyzed. Poliglecaprone 25 lost half of its strength in all biological liquids analyzed but maintained low E_0–3 values, which could reduce the risk of lacerations of soft tissues. These results suggest that Polydioxanone and Poliglecaprone 25 could be the best suture materials to use for pancreatic anastomoses. In vivo experiments will be organized to obtain further confirmations of this in vitro evidence. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Open AccessReview

Cognitive Impairment in Celiac Disease Patients: Scoping Review Exploring Psychological Triggers in a Chronic Condition

Alberto Caruso

and

Dina Di Giacomo

Gastrointest. Disord. 2023, 5(1), 87-101; https://doi.org/10.3390/gidisord5010009 - 01 Mar 2023

Viewed by 1647

Abstract

Celiac disease (CD), also known as gluten-sensitive enteropathy, is an inflammatory autoimmune reaction triggered by ingestion of gluten in genetically predisposed subjects. Celiac disease is often associated with a wide range of disorders, caused by immune responses and by malabsorption with subsequent nutritional deficiencies. Prevalent neurologic manifestations are ataxia, epilepsy, cerebral calcification, cerebral white matter lesions, peripheral neuropathy and myopathy, but also cognitive impairment. The study aimed to identify emerging and urgent research domains in order to establish a CD-specific patient-tailored protocol that includes both psychological and neuropsychological evaluations. We performed a systematic search of MEDLINE, PubMed, SCOPUS, Web of Science and Cochrane library in November 2022. We conducted a descriptive analysis of the characteristics of the included literature. Based on the exclusion/inclusion criteria, a total of seven articles were included in the scoping review process. This review demonstrated the lack of research on CD-related cognitive impairment key features and tries to focus on both cognitive and psychological manifestations as well as their two-way interaction. We tried to establish the specific areas involved, in order to have a comprehensive view of this condition and trying to determine a correct way of assessing CD cognitive impairment and its correlations with psychological distress and personal coping skills to a chronic condition. Nevertheless, research on this topic is progressively increasing and future studies should address specific key points. Full article

(This article belongs to the Topic Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	14.7 Days	CHF 2600	Submit
Current Oncology curroncol	2.6	2.6	1994	18.4 Days	CHF 2200	Submit
Diagnostics diagnostics	3.6	3.6	2011	18.8 Days	CHF 2600	Submit
Gastrointestinal Disorders gastrointestdisord	0.7	1.8	2019	29.3 Days	CHF 1200	Submit
Journal of Clinical Medicine jcm	3.9	5.4	2012	19.7 Days	CHF 2600	Submit

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Advances in Gastrointestinal and Liver Disease: From Physiological Mechanisms to Clinical Practice

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