Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.

Autoimmune dermatological diseases (AIDD) encompass a diverse group of disorders characterized by aberrant immune responses targeting the skin and its associated structures. In recent years, emerging evidence suggests a potential involvement of the renin–angiotensin system (RAS) in the pathogenesis and progression of these conditions. RAS is a multicomponent cascade, primarily known for its role in regulating blood pressure and fluid balance. All of the RAS components play an important role in controlling inflammation and other immune responses. Angiotensin II, the main effector, acts on two essential receptors: Angiotensin Receptor 1 and 2 (AT1R and AT2R). A disturbance in the axis can lead to many pathological processes, including autoimmune (AI) diseases. AT1R activation triggers diverse signaling cascades involved in inflammation, fibrosis and tissue remodeling. Experimental studies have demonstrated the presence of AT1R in various cutaneous cells and immune cells, further emphasizing its potential contribution to the AI processes in the skin. Furthermore, recent investigations have highlighted the role of other RAS components, beyond angiotensin-converting enzyme (ACE) and Ang II, that may contribute to the pathophysiology of AIDD. Alternative pathways involving ACE2, Ang receptors and Ang-(1-7) have been implicated in regulating immune responses and tissue homeostasis within the skin microenvironment. Understanding the intricate involvement of the RAS in AIDD may provide novel therapeutic opportunities. Targeting specific components of the RAS, such as angiotensin receptor blockers (ARBs), ACE inhibitors (ACEIs) or alternative RAS pathway modulators, could potentially ameliorate inflammatory responses, reduce tissue damage and lessen disease manifestations. Further research is warranted to outline the exact mechanisms underlying RAS-mediated immune dysregulation in AIDD. This abstract aims to provide a concise overview of the intricate interplay between the RAS and AIDD. Therefore, we elaborate a systematic review of the potential challenge of RAS in the AIDD, including psoriasis, systemic sclerosis, vitiligo, lupus erythematosus and many more.

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis. Antibiotic prophylaxis is effective but can lead to an increased incidence of Clostridioides difficile infection (CDI). The aim of this study was to evaluate the incidence of CDI and the risk factors in cirrhotic patients with a previous episode of SBP receiving norfloxacin as secondary prophylaxis. Materials and Methods: We performed a prospective, cohort study including patients with liver cirrhosis and SBP, successfully treated over a 2-year period in a tertiary university hospital. All the patients received secondary prophylaxis for SBP with norfloxacin 400 mg/day. Results: There were 122 patients with liver cirrhosis and SBP included (mean age 57.5 ± 10.8 years, 65.5% males). Alcoholic cirrhosis was the major etiology accounting for 63.1% of cases. The mean MELD score was 19.7 ± 6.1. Twenty-three (18.8%) of all patients developed CDI during follow-up, corresponding to an incidence of 24.8 cases per 10,000 person-years. The multivariate Cox regression analysis demonstrated that alcoholic LC etiology (HR 1.40, 95% CI 1.104–2.441, p = 0.029) and Child-Pugh C class (HR 2.50, 95% CI 1.257–3.850, p = 0.034) were independent risk factors for CDI development during norfloxacin secondary prophylaxis. The development of CDI did not influence the mortality rates in cirrhotic patients with SBP receiving norfloxacin. Conclusions: Cirrhotic patients with SBP and Child-Pugh C class and alcoholic liver cirrhosis had a higher risk of developing Clostridioides difficile infection during norfloxacin secondary prophylaxis. In patients with alcoholic Child-Pugh C class liver cirrhosis, alternative prophylaxis should be evaluated as SBP secondary prophylaxis.

Treponema pallidum infection has emerged in recent years as an important community threat and burden to the health care system. Here, we report the case of a patient with cholestatic liver disease secondary to late latent syphilis. A 41 year-old male patient was referred to the clinic for assessment of an abnormal liver function panel. Ultrasound of the abdomen demonstrated an intense liver echogenicity, normal bile ducts, and no ascites. Virologic study revealed negative results for antibodies against common viral hepatitis and metabolic and autoimmune disease. The patient was tested for syphilis and a positive result was reported. The patient was diagnosed with late latent syphilis and syphilitic hepatitis and initiated benzathine penicillin at G 7.2 million units total, delivered as three doses of 2.4 million units intramuscular each at one-week intervals. He was assessed monthly and by the end of the sixth month, he had nonreactive VDRL (seroconversion), which confirmed recovery. Syphilitic hepatitis is an overlooked type of hepatitis and should be kept in mind as a differential diagnosis in an abnormal liver panel of uncertain etiology. Health care providers should be advised that higher levels of ALP may be the single landmark in cases of syphilitic hepatitis.

Novel direct oral anticoagulants (DOACs) are prescribed worldwide in the treatment of non-valvular atrial fibrillation. Adverse reactions have been reported following the use of DOACs. One notable trend in the literature is the growing number of reported cases of esophagitis dissecans superficialis (EDS) generated by DOAC use. We hereby report the case of a 73-year-old woman who presented to the hospital with asthenia, dysphagia, and melena two days prior to admission. The patient had taken apixaban due to non-valvular paroxysmal atrial fibrillation for a few weeks. The biological panel showed moderate anemia with a hemoglobin level of 7.7 g/dL Apixaban-induced EDS was diagnosed by the characteristic endoscopic findings. The patient received treatment with a proton pump inhibitor (pantoprazole) in a double dose. Also, an iron treatment was recommended for a period of six months. The follow-up endoscopy at one month confirmed the healing of the esophageal lesions. The case was discussed with the cardiologist. The first anticoagulant treatment proposed after discharge was a vitamin K antagonist (acenocumarol) but the patient refused this medication and thus it was decided to initiate rivaroxaban. Although DOACs have demonstrated their efficacy in the prevention and treatment of stroke and thromboembolism among the aging demographic, cases of DOAC-induced EDS will continue to pose numerous challenges for physicians worldwide.