Gastroenterology Insights

Background: Development of cirrhosis and hepatocellular carcinoma (HCC) in patients with high alcohol intake is modulated by genetic predispositions. Genetic variation in angiotensin II type 1 receptor (AGTR1) has been described as a risk factor for non-alcoholic fatty liver disease in Asian patients. Methods: We analysed Caucasian patients with alcohol–associated cirrhosis without (n = 238) and with (n = 339) HCC, healthy controls (n = 200), and HCV–infected cirrhotic patients with and without HCC (n = 263) for association with the polymorphisms rs3772622 and rs2276736 in AGTR1. Results: Rs2276736 in AGTR1 was associated with both low–density lipoprotein (LDL) cholesterol levels and hepatic steatosis in patients with alcohol–associated liver disease. The distribution of genotypes for both rs3772622 and rs2276736 in AGTR1 were comparable between controls, cirrhosis patients, and those with HCC. Minor allele frequencies were 32% (44%) in healthy controls, 35%/34% (46%/45%) in alcohol–associated liver disease without/with HCC and 31%/38% (43%/39%) in HCV cirrhosis and HCV HCC, respectively. The genotype of the most important genetic risk factor for fatty liver disease, PNPLA3 I148M, did not interact with the AGTR1 polymorphisms. Conclusion: Genetic variation in AGTR1, although associated with blood lipid levels and hepatic steatosis, is not a risk factor for alcohol–associated cirrhosis or HCC in Caucasians. Full article

The quality of upper gastrointestinal endoscopy (EGD) is crucial and carries significant consequences for patient outcomes, the employment of healthcare resources, and the future course of gastroenterology as a medical specialty. In this review, we navigate through the terrain of the Quality Indicators (QIs) for EGD, shedding light on their indispensable function in ensuring and augmenting the quality of patient care throughout the pre-procedural, intra-procedural, post-procedural, and outcome-oriented facets of the practice. We delve into the comprehensive scope of the QIs and the challenges impeding the delivery of high-quality EGD, from variability in practitioner training and patient compliance to the systemic limitations of current QIs and the barriers hindering the adoption of advanced techniques. Future directions for bolstering the quality of EGD are highlighted, encapsulating the integration of emergent endoscopic technologies, the evolution of patient-centered metrics, the refinement of endoscopist training and credentialing processes, and the promise held by Artificial Intelligence (AI). Particular emphasis is placed on the role of advanced endoscopic techniques and equipment in enhancing EGD quality. This article presents a cogent narrative, promoting the pursuit of excellence in EGD as an ever-evolving endeavor that necessitates the collective dedication of clinicians, researchers, educators, and policymakers. Full article

Gastrointestinal bleeding (GIB) is a common cause of urgent hospitalization in patients with cirrhosis. However, limited studies have examined the prevalence and risk of these complications based on etiology. This study aims to compare the occurrence and risk of cirrhosis complications on inpatient mortality between alcoholic cirrhosis (ALC) and other etiology-induced cirrhosis (NALC). This retrospective analysis included 7,159,694 patients. ALC was diagnosed based on ICD-10, while NALC included primary and secondary biliary cirrhosis, nonalcoholic steatohepatitis (NASH), and unspecified cirrhosis of the liver. GIB included bleeding from esophageal and gastric varices. Bivariate analyses using appropriate statistical tests were performed to compare the two groups. ALC patients had a significantly higher incidence of GIB compared with NALC patients (10.8% vs. 6.4%, p < 0.01), with an associated 60% higher risk of GIB than NALC patients (p < 0.01). ALC was associated with a higher prevalence of ascites (45.6% vs. 27.9%, p < 0.01) and hepatic encephalopathy (HE) (45.5% vs. 27.2%, p < 0.01) compared with NALC patients. The risk of ascites and HE was 2.2 times and 2.3 times higher, respectively, in ALC patients compared with NALC patients (p < 0.01). Furthermore, ALC patients had higher hospital mortality rates compared with NALC patients, with a 47% higher risk of hospital mortality after adjustment (p < 0.01). ALC patients also had prolonged hospital stays, higher charges, more emergency room (ER) visits, and more frequent esophagogastroduodenoscopy (EGD) requirements compared with those of NALC patients (p < 0.01). ALC patients have a significantly higher risk of developing GIB, ascites, and HE compared with NALC patients, leading to increased mortality and greater medical burden on hospitals. Full article

Left ventricular diastolic dysfunction (LVDD) is a hallmark of cirrhotic cardiomyopathy and has been linked to a poorer quality of life and worse outcomes in patients with end-stage liver disease. Its impact on survival after a liver transplant (LT) is not known, especially when using current diagnostic criteria to define LVDD. We conducted a systematic review and meta-analysis of the current published literature on mortality after a LT in patients with LVDD. We searched for articles in PubMed, Scopus, EMBASE, Web of Science, and the COCHRANE Central database. We included cohort studies that compared post-transplant outcomes between cirrhotic patients with and without LVDD. Our primary outcome of interest was all-cause mortality after a LT in relation to the presence of LVDD per the 2016 American Society of Echocardiography criteria. A total of 1029 articles were screened during the selection process. Two studies included in the meta-analysis showed no significant difference in mortality, but there was high heterogeneity. A narrative review of other studies that classified diastolic function (DD) using different criteria was also performed, revealing an association with worse outcomes in these patients. High-quality prospective studies using current criteria are needed to confirm these findings. Full article

Mast cells have vital functions in allergic responses and parasite ejection, while the underlying mechanisms remain unclear. Meanwhile, MCs are essential for the maintenance of GI barrier function, and their interactions with neurons, immune cells, and epithelial cells have been related to various gastrointestinal (GI) disorders. An increasing number of investigations are being disclosed, with a lack of inner connections among them. This review aims to highlight their properties and categorization and further delve into their participation in GI diseases via interplay with neurons and immune cells. We also discuss their roles in diseases like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Based on the evidence, we advocated for their potential application in clinical practices and advocated future research prospects. Full article

The pathogenesis of inflammatory bowel disease (IBD) implicates several interconnecting factors. Immunity and external factors interact, and most aspects are still under investigation. Autophagy and apoptosis are two critical pathways that decide the fate of the individual cells of the intestinal mucosa. Experimental and clinical data indicate that the two are closely interconnected and usually mutually exclusive. However, despite the abundant information on their role, very limited translation into therapeutic application has been seen during recent years. In this review, research on these two pathways is presented. After a general overview of autophagy and apoptosis, their association with IBD, including the important mitophagy and ferroptosis, is discussed. The influence of autophagy- and apoptosis-related genes is also discussed. Finally, the interplay of autophagy and apoptosis in IBD is presented and the implications for treatment applications are examined. It is shown that dysregulated autophagy leads to increased apoptosis of enterocytes and impairs the tight junction proteins of the protective intestinal barrier. Dysregulated autophagy also induces the downregulation of lysozyme and the other antimicrobial proteins’ production. Mucus production by the goblet cells is also reduced due to defective autophagy and increased apoptosis. Full article

Our genetic background has not changed over the past century, but chronic diseases are on the rise globally. In addition to the genetic component, among the critical factors for many diseases are inhabitants of our intestines (gut microbiota) as a crucial environmental factor. Dysbiosis has been described in liver diseases with different etiologies like non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), viral hepatitis, autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), cirrhosis, hepatocellular carcinoma (HCC). On the other hand, new technologies have increased our understanding of liver disease genetics and treatment options. Genome-wide association studies (GWAS) identify unknown genetic risk factors, positional cloning of unknown genes associated with different diseases, gene tests for single nucleotide variations (SNVs), and next-generation sequencing (NGS) of selected genes or the complete genome. NGS also allowed studying the microbiome and its role in various liver diseases has begun. These genes have proven their effect on microbiome composition in host genome–microbiome association studies. We focus on altering the intestinal microbiota, and supplementing some bacterial metabolites could be considered a potential therapeutic strategy. The literature data promote probiotics/synbiotics role in reducing proinflammatory cytokines such as TNF-α and the interleukins (IL-1, IL-6, IL-8), therefore improving transaminase levels, hepatic steatosis, and NAFLD activity score. However, even though microbial therapy appears to be risk-free, evaluating side effects related to probiotics or synbiotics is imperative. In addition, safety profiles for long-term usage should be researched. Thus, this review focuses on the human microbiome and liver diseases, recent GWASs on liver disease, the gut-liver axis, and the associations with the microbiome and microbiome during/after liver disease therapy. Full article

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disease associated with the deregulation of lipid metabolism, leading to atherosclerosis, dyslipidemia, and hepatic steatosis, with potential progression to cirrhosis. Our study aims to assess the role of LAL-D in the setting of cryptogenic liver disease. Methods: A large multicenter cross-sectional study was conducted, which included 135 patients with cryptogenic liver disease from four liver centers in Brazil. All patients were submitted to the investigation of LAL enzyme activity on dried blood spots. Results: Three patients (two female) presented levels of LAL below the reference limit, compatible with LAL-D (2.2%). They had a mean age of 43.9 ± 10.1 years and a mean body-mass index (BMI) of 23.1 ± 1.7 kg/m². The mean serum levels of glucose, HDL-cholesterol, and triglycerides were 89.7 ± 3.2, 21.7 ± 3.2, and 206.7 ± 25.5 mg/dL, respectively. All patients had duodenal polyposis with xanthomatous macrophages. LAL-D investigation should be considered for individuals with chronic liver disease of an unknown etiology, especially with a normal BMI, high triglycerides, and low-HDL-cholesterol levels. The identification of LAL-D patients is extremely important since enzyme replacement therapy with Sebelipase Alfa significantly increases their survival. Full article

Background and aim: Over the last few years, SARS-CoV-2 has been reported as a possible cause of acute pancreatitis (AP), but whether it is a relevant clinical–epidemiological entity is still a matter of debate. We aim to evaluate the epidemiological characteristics of AP during the first year of the COVID pandemic (2020) and compare them with the pre-COVID period (2008–2019) to identify any differences and clarify a potential causative role of SARS-CoV-2. Methods: We used a monocentric retrospective study of 132 AP patients during 2020 and 1987 AP patients during 2008–2019. Diagnosis and severity were classified according to the revised Atlanta criteria. Propensity score matching was performed according to clinical–epidemiological features, and outcome analysis was performed on two subgroups of 109 patients. Results: The total number of AP cases in 2020 is one of the lowest in the last 13 years (132 cases, median 161, IQR 146-183). No major epidemiological differences were noted. During 2020, we observed a significant modification of the distribution of etiologies (p < 0.001), mainly based on a decrease in biliary forms (59.6% vs. 43.2%) and an increase in alcoholic forms (6.9% vs. 12.9%). Idiopathic forms remain unchanged (20.5% vs. 21.9%). The proportion of AP of idiopathic etiology and SARS-CoV-2 infection was 0.008%. There were no differences in terms of severity distribution (p = 0.127), length of stay (p = 0.916), need for ICU (p = 0.139), or mortality (p = 0.462). Even among statistically matched groups, there were no differences between the length of stay (9 vs. 10 days, p = 0.890), need for ICU admission (1.8% vs. 3.7%, p = 0.683), or in-hospital mortality (0 vs. 1.8%, p = 0.342). Conclusions: The lower AP diagnoses indicate delayed and likely missed diagnoses, probably because of both hesitancy and organizational problems during the pandemic. The unchanged proportion of idiopathic forms supports the hypothesis that SARS-CoV-2 is not an AP trigger. Full article

Background: The literature discussed colorectal surgery using a robotic platform, which is mainly the previous da Vinci Si system. The role of the da Vinci Xi surgical system remains unclear. This study aims to evaluate the benefits and feasibility of using the robot-assisted method in colorectal surgery. Methods: We retrospectively collected 418 patients undergoing minimally invasive colorectal surgery between March 2020 and December 2021, in a single center. Patients were divided into robotic and laparoscopic groups. Primary outcomes were conversion rates to open surgery, complications, and length of stay (LOS). Secondary outcomes were post-operation functional outcomes. Results: A total of 218 patients received colectomy, while 200 patients received rectum resection. No differences were found in the conversion rate in both groups. A lower complication rate (colectomy: 7.5% vs. 23.2%, p = 0.01, rectum resection: 14.1% vs. 28.7%, p = 0.038) and shorter LOS (5 vs. 8 days, p < 0.001) was found in the robotic group. The robotic approach was associated with good functional outcomes in tolerated solid food and the termination of urinary drainage. Conclusions: The new da Vinci Xi system is safe and feasible both for colonic and rectal surgery, with reduced complications. Shorter LOS and reliable short-term outcomes may reflect both better functional recovery and surgical quality when compared to laparoscopic surgery. Full article

Globally, gastric cancer is a major cause of cancer mortality, with a 5-year survival rate of 32% for locally advanced and metastatic gastric cancer (A/MCG). This systematic literature review summarized the clinical, safety, and humanistic outcomes associated with systemic regimens administered as a first-line therapy for A/MGC. The search included articles published in English in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and the American Society of Clinical Oncology meeting library, from inception to April 2022. Phase II and III randomized controlled trials (RCTs) conducted among western populations diagnosed with stage III and IV A/MGC were included. Two investigators independently reviewed the studies, conducted data extraction, and assessed risk of bias in accordance with PRISMA guidelines. Twenty-four randomized controlled trials totaling 8705 patients were included. Median overall survival ranged from 5.0 to 13.1 months, median progression-free survival ranged from 2.0 to 7.7 months, and objective response ranged from 13.0 to 64.1%. Two studies reported high quality-of-life outcomes. Grade 3 and 4 adverse events were reported in most studies. This review provides a comprehensive overview of first-line systemic therapy outcomes in western populations with A/MGC. With the evolving treatment landscape of A/MGC, an improvement in clinical outcomes can be seen in recently published RCTs with immunotherapies. The potential of new targeted treatments and immunotherapies may present more favorable forthcoming options for treating A/MGC. Full article

Numerous clinical studies published in the Chinese language support the use of Medilac-S (Bacillus subtilis R0179 and Enterococcus faecium R0026; non-commercial name IBacilluS+) as an adjuvant in various indications, including ulcerative colitis, irritable bowel syndrome, acute gastritis, and Helicobacter pylori therapy. This systematic review with a meta-analysis was conducted to summarize clinical studies evaluating the efficacy of this probiotic formulation as an adjuvant to conventional IBS medications. The systematic literature searches in six international and Chinese databases identified 37 eligible studies, of which 33 reported the efficacy of Medilac-S adjunctive therapy using a standardized categorical scale. These 33 studies were included in the meta-analysis using a random-effect model with a stratification by IBS subtype. Overall, Medilac-S significantly improved the efficacy of conventional IBS treatment (RR = 1.21; 95% CI: 1.17–1.25; and p < 0.0001) with an average probability of treatment effectiveness being 21% higher with the probiotic adjuvant, regardless of the subtype. Adverse events, reported in 78% of the trials, were described as mild-to-moderate and self-resolving, with a similar incidence in the probiotic adjuvant (6.2%; n = 1347) and control (5.9%; n = 1331) groups. The results of this meta-analysis strengthen the conclusions that Medilac-S is a safe and effective adjuvant to a variety of conventional treatments in IBS patients. Full article

Biomechanics are gaining ground in gastroenterology in the creation of educational models and to describe the necessary forces to perforate hallow organs during endoscopy. We thus investigated the breaking forces of porcine intestinal segments and whether they could be predicted based on body weight or crown–rump length. Based on a priori power-analyses, 10 pigs were included. The breaking forces were determined with a motorized test stand. We found that the breaking forces of intestinal segments were different (H(6) = 33.7, p < 0.0001): Ileal breaking force ($\overline{\mathrm{x}}$ = 24.14 N) was higher than jejunal ($\overline{\mathrm{x}}$ = 14.24 N, p = 0.0082) and colonic ($\overline{\mathrm{x}}$ = 11.33 N, p < 0.0001) breaking force. The latter was also smaller than cecal breaking force ($\overline{\mathrm{x}}$ = 24.6 N, p = 0.0044). Likewise, rectal ($\overline{\mathrm{x}}$ = 23.57 N) breaking force was higher than jejunal (p = 0.0455) and colonic (p = 0.0006) breaking force. Breaking forces were not correlated to body weight or crown–rump length (R < 0.49, p > 0.148). Intestinal segments differ in their breaking forces. The colon had the least resistance to traction forces. It remains to be determined if similar relationships exist in humans in order to validate porcine models for endoscopy and surgery. Full article

Introduction: Despite being one of the most frequent chronic digestive diseases worldwide, with a prevalence of 1%, celiac disease (CD) remains severely underdiagnosed. Among the instruments used to improve its diagnostic rate, hematologic parameters have been proposed as screening tests to select patients with an increased probability of having CD. Assessment of coagulation is included in routine check-ups, and CD has been reported to be associated with coagulopathy. We aimed to assess if subtle changes in coagulation tests could be used in clinical practice to prompt testing for CD. Methods: We retrospectively recruited all patients with clinical suspicion for CD during a study period of 7 years (between 2015 and 2022), who were tested using IgA tissue transglutaminase (tTG) serology and serum total IgA (IgG tTG in case of IgA deficiency) and who underwent upper gastrointestinal endoscopy with multiple biopsy sampling of the duodenal bulb and distal duodenum. We stratified patients into three groups: newly diagnosed CD, gluten-free diet-treated CD, and non-CD controls. Results: Altogether, there were 133 CD patients (71 newly diagnosed, 62 GFD-treated) and 57 non-CD controls. Mean age and gender distribution were similar among the three groups: 43.3 years for newly diagnosed CD, 41.6 years for non-CD controls, and 44 years for GFD-treated CD patients, with a male gender distribution of 21.1%, 28%, and 24.1%, respectively. Among the included newly diagnosed CD patients, 14% had a prolonged INR. The mean INR was slightly higher in newly diagnosed CD patients, compared to GFD-treated CD patients and non-CD controls: 1.12 ± 0.30, 1.02 ± 0.83, and 1.00 ± 0.08, respectively (p = 0.009). Consequently, prothrombin activity was slightly lower in newly diagnosed CD patients, compared to GFD-treated CD and non-CD controls: 94.9 ± 19.3%, 102.3 ± 12.8%, and 101.9 ± 15.15, respectively. Interestingly, after GFD, the mean INR and prothrombin activity of CD individuals reached a value similar to that of non-CD controls. Conclusions: Subtle changes in INR, defined as a value within the normal range, but closer to the upper limit, could be an indicator of probability for CD. Full article

The overall prevalence of hyponatremia in cirrhotics is around 50%. Hypovolemic hyponatremia is a result of excessive fluid loss caused mostly by diuretic treatment or diarrhea. More common is hypervolemic hyponatremia, which results from excessive activation of water and sodium-retaining mechanisms caused by effective arterial hypovolemia. This review focuses on the associations of hyponatremia with clinical outcomes and reviews the available data on its management. Hyponatremia is a strong predictor of mortality and is also associated with an increased probability of hepatorenal syndrome, disturbance of consciousness, infections, and unfavorable post-transplant outcomes. In the management of hyponatremia, it is crucial to distinguish between hypovolemic and hypervolemic hyponatremia. The treatment of hypervolemic hyponatremia should be started only in symptomatic patients. The cessation of the treatment with traditional diuretics and fluid restriction may prevent further decrease in natremia. Pharmacological treatment is directed towards cirrhosis itself, precipitating factor, or hyponatremia directly. Currently, only albumin infusions can be recommended routinely. Other possibilities, such as vaptans, splanchnic vasoconstrictors, niravoline, or osmotic diuretics, are restricted to specific use cases (e.g., imminent liver transplantation) or need more research to determine their efficacy. We tried to summarize the management of hyponatremia into a concise flowchart. Full article

The gastrointestinal (GI) tract may be a significant entrance or interaction site for SARS-CoV-2; therefore, the gut mucosal immune system participates in virus interaction as a first-line physical and immunological defense, leading to GI involvement and symptoms. This review focuses on the GI symptoms associated with SARS-CoV-2 infection while providing specific results on variant-specific signs and syndromes related to coronavirus disease 2019 (COVID-19). The pattern of symptoms changed during the virus evolution, since the data provided a current and thorough picture of the symptoms experienced by SARS-CoV-2 infected people, and variations in symptom patterns occurred as the Alpha, Delta, and Omicron variants have spread. Since the beginning of the pandemic, GI symptoms have been linked to SARS-CoV-2 infections, even though most infected people do not report them. For example, diarrhea (28.2%) was the most frequently reported GI symptom in the early phase of the pandemic. The most observed GI tract symptoms during COVID-19 were anorexia (loss of appetite), nausea, vomiting, diarrhea, and abdominal pain, usually in at least one-third of the patients. Mesenteric ischemia and GI bleeding were less observed but more severe. While GI symptoms are not associated with increased mortality, they complicate the disease, increase the duration of the illness, and result in worse outcomes. Nevertheless, it is accepted that symptoms between variants differ significantly, i.e., the Omicron variant causes milder COVID-19 than the Delta. Still, the rate of GI symptoms has declined in the following variant-dominated phases of the pandemic (Alpha: 19.4%, Delta: 17.9%, Omicron: 13.8%), which was also demonstrated for other GI signs associated with COVID-19. Full article

Hepatorenal syndrome stands as one of several potential triggers of acute kidney injury in individuals grappling with either acute or persistent liver ailments. The nature of the decline in kidney function has led to the identification of two variants of hepatorenal syndrome. In cases where terlipressin therapy is accessible, the initial approach involves administering terlipressin alongside albumin. Terlipressin, a synthetic analog of vasopressin, boasts double the preference for vasopressin V1 receptors compared to V2 receptors. The FDA granted approval to terlipressin in September 2022, demonstrating its intrinsic activity, although a significant portion of its function arises from its transformation into lysine vasopressin. This article provides a comprehensive examination of terlipressin’s various pharmacodynamic and pharmacokinetic facets, as well as its clinical utility, aiming to keep the scientific community well informed about its safe and efficient utilization. Full article

Intrahepatic cholangiocarcinoma (iCCA) represents the second most frequent type of primary liver neoplasm. The diagnosis and treatment of patients with iCCA involves many challenges. To date, surgical resection with negative margins is the main curative option, achieving an acceptable long-term survival. Despite enabling a considerable improvement in the outcome, iCCA recurrence after surgery is still common. Tumor extension and the histological subtype, as well as vascular and lymph node involvements, are key factors used to define the prognosis. In this narrative review, we aimed to discuss the potential benefits of using different surgical strategies in the field of iCCA, including vascular resection, the mini-invasive approach, liver transplantation, the mechanism used to enable future liver remnant augmentation, and lymph node dissection. We also discussed the new protocols developed in the field of systemic treatment, including immunotherapy and molecular targeted therapy. Recent advancements in the diagnosis, surgical treatment, and understanding of tumor biology have changed the landscape in terms of treatment options. Creating a multidisciplinary tumor board is essential to achieving the best patient outcomes. Further investigational trials are required with the intent of tailoring the treatments and establishing the right patient population who would benefit from the use of new therapeutics algorithms. Full article

The association between H. pylori and small intestinal permeability (IP) on serum testosterone levels in men as mediated by metabolic endotoxemia remains unclear. We sought to explore relationships using correlational analysis between H. pylori IgG class antibody levels and small IP via dual sugar probe analysis on T levels in 50 male participants of reproductive age. Sleep quality, physical activity levels, and Irritable Bowel Syndrome (IBS) symptom severity were measured as potential confounders. Measures for H. pylori (antibodies) increased small IP (lactulose/rhamnose ratio), and hypogonadism (testosterone) did not exceed diagnostic cut-off values for respective pathologies. There was no correlation between lactulose/rhamnose e ratio and GI function markers, zonulin, H. pylori, and IBS questionnaire scores; inflammatory markers, high-sensitivity C-reactive Protein (hsCRP) and Lipopolysaccharide-Binding Protein (LBP); nor endocrine markers, testosterone, Luteinizing hormone (LH), and Follicle-stimulating hormone (FSH). There was a moderate inverse relationship revealed between IBS symptom severity and LBP (r = −0.457, p = 0.004); and hsCRP and testosterone (r = −0.398, p = 0.004). This was independent of physical activity level and sleep quality, but not BMI, which supports the existing link between adiposity, inflammation, and hypogonadism currently present in the literature. Full article