Human Neutrophil Alpha-Defensins Promote NETosis and Liver Injury in Alcohol-Related Liver Cirrhosis: Potential Therapeutic Agents.

Background: Neutrophils are thought to play a pivotal role in the pathogenesis of many inflammatory diseases, such as hepatitis, liver cirrhosis, etc. Activated human neutrophils release human neutrophil peptides (HNP1-3) or alpha-defensins that are antimicrobial peptides in azurophil granules. Furthermore, HNP1-3 build a scaffold of neutrophil extracellular traps (NETs) and promote the process of programmed cell death called NETosis. Our study aimed to investigate the role of alpha-defensins in the pathogenesis of alcohol-related liver cirrhosis (ALC). Methods: The concentrations of alpha-defensins in the plasma of 62 patients with ALC and 24 healthy subjects were measured by ELISA. The patients with ALC were prospectively recruited based on the severity of liver dysfunction according to the Child-Pugh and Model of End-Stage Liver Disease-Natrium (MELD-Na) scores, modified Maddrey's Discriminant Function (mDF), and the presence of ALC complications. Results: The concentrations of alpha-defensins in plasma were significantly higher in the ALC patients than in the controls. The plasma levels of HNP1-3 correlated with the MELD and mDF scores. ALC subgroups with MELD > 20 and mDF > 32 displayed significantly higher HNP1-3 concentrations. The plasma levels of HNP1-3 revealed a good predictive AUC for hepatic encephalopathy and ascites development (0.81 and 0.74, respectively) and for patient survival (0.87) in those over 40 years of age. Conclusion: These findings suggest that alpha-defensins play an important role in the assessment of ALC.

COVID-19, Possible Hepatic Pathways and Alcohol Abuse-What Do We Know up to 2023?

The pandemic period due to coronavirus disease 2019 (COVID-19) revolutionized all possible areas of global health. Significant consequences were also related to diverse extrapulmonary manifestations of this pathology. The liver was found to be a relatively common organ, beyond the respiratory tract, affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple studies revealed the essential role of chronic liver disease (CLD) in the general outcome of coronavirus infection. Present concerns in this field are related to the direct hepatic consequences caused by COVID-19 and pre-existing liver disorders as risk factors for the severe course of the infection. Which mechanism has a key role in this phenomenon-previously existing hepatic disorder or acute liver failure due to SARS-CoV-2-is still not fully clarified. Alcoholic liver disease (ALD) constitutes another not fully elucidated context of coronavirus infection. Should the toxic effects of ethanol or already developed liver cirrhosis and its consequences be perceived as a causative or triggering factor of hepatic impairment in COVID-19 patients? In the face of these discrepancies, we decided to summarize the role of the liver in the whole picture of coronavirus infection, paying special attention to ALD and focusing on the pathological pathways related to COVID-19, ethanol toxicity and liver cirrhosis.

Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study.

BACKGROUND: Vedolizumab is recommended as a first-line biological treatment, along with other biological drugs, in ulcerative colitis (UC) patients in whom conventional therapy failed and as a second-line biological treatment following a failure of a tumor necrosis factor alpha (TNF-α) antagonist. OBJECTIVES: We aimed to assess the real-world effectiveness and safety of vedolizumab induction therapy in UC patients treated in the scope of the National Drug Program (NDP) in Poland. MATERIAL AND METHODS: The endpoints were the proportions of patients who reached clinical response, clinical remission and mucosal healing at week 14. Partial Mayo scores, Mayo subscores and C-reactive protein (CRP) levels were also evaluated. RESULTS: Our study population consisted of 100 patients (55 biologic-naïve and 45 biologic-exposed). The median total Mayo score at baseline was 10 (interquartile range (IQR): 9-11), and 52 patients (52%) had extensive colitis. The clinical response at week 14 was achieved in 83 (83%) and clinical remission in 24 (24%) cases. Mucosal healing was observed in 56 (62%) patients at week 14. In patients with prior failure of biologic treatment (n = 25), 17 (68%) responded to vedolizumab treatment. A decrease in the median CRP level (from 3.7 mg/L to 2.6 mg/L) and the median total Mayo score (from 10 to 4) was observed. No new safety concerns were recorded and no patients discontinued the treatment due to adverse events (AEs). CONCLUSIONS: Vedolizumab was effective and safe as induction therapy for UC in a Polish real-world population including patients with severely active UC and a low number of patients with prior biological treatment failures.

Chronic intestinal schistosomiasis caused by co-infection with Schistosoma intercalatum and Schistosoma mansoni.

The Grand Round concerns a 24-year-old man from Zimbabwe who was studying and living in Poland. The patient had been complaining of abdominal pain, fatigue, alternating diarrhoea and constipation, and presence of blood in his stool for 3 years. The patient had the following diagnostic tests: colonoscopy, CT scan, histopathology, and parasitological and molecular tests. Results of the examinations showed that the cause of the patient's complaints was chronic intestinal schistosomiasis due to the co-infection with Schistosoma intercalatum and Schistosoma mansoni. The patient had two cycles of praziquantel therapy (Biltricide) and responded well to the treatment. In the Grand Round, we describe full diagnostics as well as clinical and therapeutic management in the patient with S intercalatum and S mansoni co-infection. This case allows us to draw attention to cases of forgotten chronic tropical diseases (including rare ones) in patients from regions with a high endemic index staying in non-endemic regions of the world for a long time. Co-infection with S intercalatum and S mansoni should be considered as a very rare clinical case.

The Efficacy and Safety of Single-Strain Probiotic Formulations Containing Bifidobacterium lactis or Bacillus coagulans in Adult Patients with Irritable Bowel Syndrome-A Randomized Double-Blind Placebo-Controlled Three-Arm Interventional Trial.

Probiotics offer a potential new therapeutic approach for irritable bowel syndrome (IBS), but current results are still controversial. The aim of this study was to assess the efficacy and safety of single-strain probiotic formulations in adult IBS patients and to compare the effects of Bifidobacterium lactis NORDBIOTIC™ BI040 (DSM 33812/34614) and Bacillus coagulans NORDBIOTIC™ BC300 (DSM 33836) in a prospective three-arm interventional randomized double-blind placebo-controlled clinical trial. The study included 123 IBS subjects diagnosed according to the Rome IV criteria. The primary outcomes were changes in symptom severity and symptom improvement as assessed using the IBS Severity Scoring System (IBS-SSS) after 4, 8, and 12 weeks of intervention and after 4 weeks of follow-up. Secondary outcomes included the assessment of individual IBS symptoms and the occurrence of adverse events. During the 12-week intervention, IBS-SSS scores significantly decreased (p-values < 0.001) in the study groups but differences between the interventional and placebo groups did not reach statistical significance. However, at the 16th week of follow-up, a significant improvement in the total IBS-SSS score in comparison to the placebo group (20.5%) was found in 43.8% and 52.9% of the Bifidobacterium lactis (p = 0.038, OR 3.0, [95% CI 1.1-8.6]) and the Bacillus coagulans (p = 0.005, OR 4.6 [95% CI 1.5-12.2]) groups, respectively. Bifidobacterium lactis had a beneficial effect on the intensity and frequency of pain, whereas Bacillus coagulans decreased the bowel dissatisfaction. Both strains increased the percentage of patients with normal stool consistency, but only Bifidobacterium lactis induced a decrease in the number of patients with constipation after 6 weeks of supplementation. Both probiotic strains were well tolerated, without differences in the occurrence of adverse events between groups. In conclusion, single-strain supplementation was safe and efficient in IBS patients but showed a different range of effects. Bifidobacterium lactis BI040 primarily reduced the frequency and intensity of pain, while Bacillus coagulans BC300 increased bowel satisfaction [ClinicalTrials.gov NCT05064930].

The Occurrence of Gluten-Related Antibodies, Sensitization to Selected Food Allergens, and Antibodies against Intrinsic Factor in Adult Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Due to the possible overlap of IBS clinical symptoms with gluten-related diseases, food allergies, and autoimmune gastritis (AIG), the aim of this study was to present the frequency of anti-tissue transglutaminase 2 (TTG2) autoantibodies, anti-deamidated gluten peptide (DGP) antibodies, specific immunoglobulin E antibodies (sIgE) to selected food allergens, and anti-intrinsic factor (IF) autoantibodies in adult patients with diarrhea-predominant IBS (IBS-D). The study involved 244 patients (170 women) aged 18-75 years. The antibodies were measured with the use of multiparametric immunoassays. Elevated antibody concentrations, irrespective of the class of tested antibody, occurred in 44 patients (17.6%), including 11 patients (4.5%) with positive DGP antibodies, four patients (1.6%) with TTG2 autoantibodies, six patients (2.5%) with IF autoantibodies, and 31 patients (12.7%) with sIgE to food allergens. Sensitization to gluten, proteins from cow's milk, and bovine serum albumin was found in 2.1%, 5.3%, and 9.0% of patients, respectively. Our study showed a high percentage of positive results for the tested antibodies in the IBD-D patients, which indicates the need to perform serological tests for CD, food allergies, and AIG in this group of patients.

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease. Objectives: We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland. Design: This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019. Methods: The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment. Results: In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years. Conclusion: Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high. Registration: ENCePP (EUPAS34119).

Selected Aspects of the Intricate Background of Immune-Related Cholangiopathies-A Critical Overview.

Primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are rare immune-related cholangiopathies with still poorly explained pathogenesis. Although triggers of chronic inflammation with subsequent fibrosis that affect cholangiocytes leading to obliteration of bile ducts and conversion to liver cirrhosis are unclear, both disorders are regarded to be multifactorial. Different factors can contribute to the development of hepatocellular injury in the course of progressive cholestasis, including (1) body accumulation of bile acids and their toxicity, (2) decreased food intake and nutrient absorption, (3) gut microbiota transformation, and (4) reorganized host metabolism. Growing evidence suggests that intestinal microbiome composition not only can be altered by liver dysfunction, but in turn, it actively impacts hepatic conditions. In this review, we highlight the role of key factors such as the gut-liver axis, intestinal barrier integrity, bile acid synthesis and circulation, and microbiome composition, which seem to be strongly related to PBC and PSC outcome. Emerging treatments and future therapeutic strategies are also presented.

Blood concentrations of mediators released from activated neutrophils are related to the severity of alcohol-induced liver damage.

BACKGROUND: Immune dysregulation and neutrophil infiltration are hallmarks of alcohol-related liver disease (ALD). Our objective was to evaluate the blood profile of neutrophil-derived mediators [neutrophil elastase (NE), myeloperoxidase (MPO), alpha1-antitrypsin (A1AT)], and their potential relevance in ALD. METHODS: 62 patients with ALD /47 males, and 15 females, aged 49,2 ± 9,9/ were prospectively recruited and distributed according to their 1/ gender, 2/ severity of liver dysfunction (by Child-Turcotte-Pugh, MELD scores, and mDF) 3/ presence of complications of ALD complications, and followed for 90 days. 24 age- and sex-matched healthy volunteers served as the control group. Neutrophil-derived biomarkers were quantified using enzyme-linked immunosorbent assays (ELISAs). RESULTS: Blood concentrations of MPO and NE were significantly higher in ALD patients in comparison with controls. A1AT levels were not different. There were no gender-related differences in the studied biomarker levels. Both NE and MPO correlated with routine markers of inflammation, while NE with MELD and mDF scores. Patients with a severe ALD course i.e. MELD>20 or mDF>32, presented with significantly higher NE blood concentrations. CONCLUSIONS: Our results point out the critical role of neutrophils in the pathogenesis of ALD. NE and MPO correlated with the intensity of inflammation, and NE was related to the severity of liver dysfunction.

Red blood cell distribution width derivatives in alcohol-related liver cirrhosis and metabolic-associated fatty liver disease.

BACKGROUND: Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring. There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function. AIM: To study red blood cell distribution width (RDW), RDW-to-platelet ratio (RPR) and RDW-to-lymphocyte ratio (RLR) in alcohol-related liver cirrhosis (ALC) and metabolic-associated fatty liver disease (MAFLD). METHODS: The study group was composed of 302 people: 142 patients with ALC and 92 with MAFLD; 68 persons were included as controls. RDW, RPR and RLR were measured in each person. Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio (GPR), procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin]. MELD score in ALC patients and non-alcoholic fatty liver disease (NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group. The achieved results were compared to controls. Then a correlation between assessed markers was done. Diagnostic value of each investigated parameter and its suggested cut-off in the research group were evaluated with area under the curve (AUC). RESULTS: RDW, RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls (ALC: P < 0.0001; NAFLD: P < 0.05, P < 0.0001 and P < 0.0001, respectively). RPR correlated positively with MELD score (P < 0.01) and indirect indices of liver fibrosis (FIB-4 and GPR; P < 0.0001) in ALC patients; negative correlations were found between PDGF-AB and both: RDW and RPR (P < 0.01 and P < 0.0001, respectively). RPR correlated positively with NAFLD fibrosis score and APRI (P < 0.0001) in the MAFLD group; a positive relationship was observed between RDW and FIB-4, too (P < 0.05). AUC values and suggested cut-offs for RDW, RPR and RLR in ALC patients were: 0.912 (> 14.2%), 0.965 (> 0.075) and 0.914 (> 8.684), respectively. AUC values and suggested cut-offs for RDW, RPR and RLR in MAFLD patients were: 0.606 (> 12.8%), 0.724 (> 0.047) and 0.691 (> 6.25), respectively. CONCLUSION: RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC. They can also be associated with a deterioration of liver function in this group.

Impact of Obesity on the Course of Management of Inflammatory Bowel Disease-A Review.

It is already well-known that visceral adipose tissue is inseparably related to the pathogenesis, activity, and general outcome of inflammatory bowel disease (IBD). We are getting closer and closer to the molecular background of this loop, finding certain relationships between activated mesenteric tissue and inflammation within the lumen of the gastrointestinal tract. Recently, relatively new data have been uncovered, indicating a direct impact of body fat on the pattern of pharmacological treatment in the course of IBD. On the other hand, ileal and colonic types of Crohn's disease and ulcerative colitis appear to be more diversified than it was thought in the past. However, the question arises whether at this stage we are able to translate this knowledge into the practical management of IBD patients or we are still exploring the scientific background of this pathology, having no specific tools to be used directly in patients. Our review explores IBD in the context of obesity and associated disorders, focusing on adipokines, creeping fat, and possible relationships between these disorders and the treatment of IBD patients.

A rare case of a juvenile polyp of patient with Peutz-Jeghers syndrome, complicated with intussusception of the small intestine.

We report a rare case of Peutz-Jeghers syndrome (PJS) in a 35-year-old female. The patient was diagnosed with PJS when she was 11 years old. She has remained under observation since then. We strongly believe that PJS is a very rare diagnosis. However, it can have serious complications such as the intussusception we observed in our patient. Her condition (recurrent abdominal pain and vomiting) in childhood required further diagnostic procedures. Although the diagnosis of PJS was made, among many resected polyps, one of them appeared to be a juvenile polyp. The diagnosis was confirmed in the histopathology report, which was incredibly unique. Genetic testing revealed LKB1/STK11 gene mutation. Clinicians should be aware of the malignant potential in the course of PJS. Hence, these patients require tailor-made management, long-term follow-up, and our particular attention.

The Usefulness of Extended Inflammation Parameters and Systemic Inflammatory Response Markers in the Diagnostics of Autoimmune Hepatitis.

(1) Introduction: Autoimmune hepatitis (AIH) is a chronic disease. A persistent autoimmune reaction in the liver is significantly related to the systemic inflammatory response. Extended Inflammation Parameters (EIP) can be used to assess the activation of immune cells such as activated neutrophils (NEUT-RI and NEUT-GI) and activated lymphocytes (RE-LYMP and AS-LYMP) in the phase of active inflammation. The role of the systemic inflammatory response markers should also be emphasised, especially: NLR, PLR, and RLR, which have recently been widely studied as markers in autoimmune skin diseases or liver diseases. (2) Materials and Methods: The study included 30 patients with AIH and 30 healthy volunteers. The parameters of the EIP group (RE-LYMP, AS-LYMP, NEUT-RI, NEUT-GI), calculated haematological indices Red Blood Cell Distribution Width-to-Platelet Ratio (RPR), Mean Platelet Volume-to-Platelet Ratio (MPR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Red Blood Cell Distribution Width-to-Lymphocyte Ratio (RLR), and selected blood morphological and biochemical indices were analysed. The aim of the study was to assess the usefulness of the EIP and systemic inflammatory response markers in the diagnostics of AIH. (3) Results: Compared to the controls, the patients with AIH showed significantly higher EIP values: NEUT-RI (48.05 vs. 43.30), NEUT-GI (152.65 vs. 147.40), RE-LYMP (0.07 vs. 0.03), and the inflammatory response markers: MPR (0.05 vs. 0.04), RPR (0.07 vs. 0.05), and NLR (2.81 vs. 1.42. Among the examined markers, EIP has significant diagnostic potential: NEUT-RI (AUC = 0.86), NEUT-GI (AUC = 0.80), and RE-LYMP (AUC = 0.78), and so do calculated haematological indices, i.e., MPR (AUC = 0.75), PLR (AUC = 1.00), and RLR (AUC = 1.00) Moreover, the importance of NEUT-GI (AUC = 0.89), MPR (AUC = 0.93), PLR (AUC = 0.86), RPR (AUC = 0.91), and FIB-4 (AUC = 0.83) in the detection of liver fibrosis in the course of AIH has also been proven. (4) Conclusions: EIP and systemic inflammatory response markers may turn out to be useful in detecting AIH and in looking for features of already developed liver cirrhosis in its course.

Indicator of Inflammation and NETosis-Low-Density Granulocytes as a Biomarker of Autoimmune Hepatitis.

Introduction. Interest in the potential role of low-density granulocytes (LDGs) in the development of autoimmune diseases has been renewed recently. Due to their pro-inflammatory action, more and more attention is paid to the role of LDGs, including those expressing the enzyme myeloperoxidase (MPO), in the development of autoimmune hepatitis (AIH). LDGs are actively involved in the formation of neutrophil extracellular traps (NETs). This phenomenon may favour the externalization of the autoantigen and lead to damage to internal organs, including the liver. Aim. The main aim of the study was to assess the diagnostic usefulness of the LDG percentage, including the fraction showing MPO expression as markers of systemic inflammation in AIH. Materials and methods. The study included a group of 25 patients with AIH and 20 healthy volunteers. Mononuclear cells, isolated from peripheral blood, were labelled with monoclonal antibodies conjugated to the appropriate fluorochromes (CD15-FITC, CD14-PE, CD10-PE-Cy5, MPO+) and then analyzed on a Navios Flow Cytometer (Beckman Coulter). Results. Patients with AIH had a higher median percentage of LDG (1.2 vs. 0.1; p = 0.0001) and LDG expressing MPO (0.8 vs. 0.3; p = 0.0017) when compared to healthy volunteers. Moreover, the percentage of LDG was characterised by 100% of sensitivity and 55% of specificity (AUC = 0.84; p < 0.0001), while the percentage of LDG expressing MPO was 92% of sensitivity and 55% of specificity (AUC = 0.78; p = 0.0001) in the detection of AIH. Conclusions. Assessment of inflammatory markers, such as the percentage of LDG and the percentage of LDG expressing MPO, may be helpful in assessing the phenomenon of an increased systemic inflammatory response and in assessing liver fibrosis (LC, Liver cirrhosis), which is inherent in liver decompensation. Taking into account the above arguments, the assessment of the percentage of LDG, including LDG expressing MPO, may turn out to be a useful marker in the diagnosis of AIH.

A Rare Case of Upper Gastrointestinal Bleeding: Osler-Weber-Rendu Syndrome.

Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia (HHT), is a rare, autosomal dominant condition that affects approximately 1 in 5000 patients causing abnormal blood vessel formation. HHT patients have mucocutaneous telangiectasias and arteriovenous malformations in various organs. The most prominent symptom of HHT is epistaxis, which, together with gastrointestinal bleeding, may cause iron deficiency anemia. This study is a case report of a 62-year-old patient who was admitted to the Department of Gastroenterology due to acute upper gastrointestinal bleeding and a history of recurrent epistaxis and melena for 4 days, which was confirmed in digital rectal examination. Urgent upper gastrointestinal endoscopy revealed active bleeding from multiple angioectatic spots with bright-looking salmon-colored patches in the antrum and the body suggestive of HHT. The bleeding from two angioectatic spots was stopped by argon plasma coagulation, and four clips were placed to provide good hemostasis. The patient was treated with a proton pomp inhibitor infusion and iron infusion. She was discharged with no signs of GI bleeding, normalized iron levels and a diagnosis of HHT. She was referred to further genetic testing, including evaluation of first-degree relatives. She also had performed unenhanced thin-cut computed tomography (CT) with angiography to exclude the presence of pulmonary arteriovenous malformations (PAVMs). Due to the fact that the patient did not manifest any other HHT-related symptoms and that the instrumental screening discloses no silent AVMs in other organs, the "watch-and-wait strategy" was applied. Although, Osler-Weber-Rendu syndrome is widely described in the medical literature, effective treatment of gastrointestinal telangiectasias is not always available and still lacks standardization to date, which makes the management of gastroenterological involvement still a challenging issue.

Wilson's Disease: An Update on the Diagnostic Workup and Management.

Wilson's disease (WD) is a rare autosomal recessive disorder of hepatocellular copper deposition. The diagnostic approach to patients with WD may be challenging and is based on a complex set of clinical findings that derive from patient history, physical examination, as well as laboratory and imaging testing. No single examination can unequivocally confirm or exclude the disease. Timely identification of signs and symptoms using novel biomarkers and modern diagnostic tools may help to reduce treatment delays and improve patient prognosis. The proper way of approaching WD management includes, firstly, early diagnosis and prompt treatment introduction; secondly, careful and lifelong monitoring of patient compliance and strict adherence to the treatment; and, last but not least, screening for adverse effects and evaluation of treatment efficacy. Liver transplantation is performed in about 5% of WD patients who present with acute liver failure at first disease presentation or with signs of decompensation in the course of liver cirrhosis. Increasing awareness of this rare inherited disease among health professionals, emphasizing their training to consider early signs and symptoms of the illness, and strict monitoring are vital strategies for the patient safety and efficacy of WD therapy.

Gullo's syndrome - what do we know?

Benign pancreatic hyperenzymemia (Gullo's syndrome) is characterized by a more than threefold increase of the serum pancreatic enzymes lipase and amylase activity in the absence of any pancreatic disease. Recently, there is an increase in describing cases of Gullo's syndrome in medical literature. Gullo's syndrome is a diagnosis of exclusion, and clinicians should be aware of various other conditions which can cause elevation of pancreatic enzymes. However, the diagnostic pathway should be done with the right accuracy to avoid unnecessary examinations.

Characteristics of patients with moderate-to-severe ulcerative colitis treated with vedolizumab: results from a Polish multicenter, prospective, observational real-life study (the POLONEZ study).

BACKGROUND: Vedolizumab, a humanized antibody targeting the α4ß7 integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients. METHODS: This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score. RESULTS: A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups. CONCLUSIONS: Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119). LAY SUMMARY: Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.

Etiopathogenesis and Diagnostic Strategies in Autoimmune Hepatitis.

Autoimmune hepatitis (AIH) is a chronic liver disease with the incidence of 10 to 17 per 100,000 people in Europe. It affects people of any age, but most often occurs in the 40-60 age group. The clinical picture is varied, from asymptomatic to severe acute hepatitis or liver failure. The disease onset is probably associated with the impaired function of T lymphocytes, the development of molecular mimicry, intestinal dysbiosis, or infiltration with low density neutrophils, which, alongside autoantibodies (i.e., ANA, ASMA), implicate the formation of neutrophil extracellular traps (NETs), as a component of the disease process, and mediate the inappropriate immune response. AIH is characterized with an increased activity of aminotransferases, elevated concentration of serum immunoglobulin G, the presence of circulating autoantibodies and liver inflammation. The result of the histological examination of the liver and the presence of autoantibodies, although not pathognomonic, still remain a distinguishing feature. The diagnosis of AIH determines lifelong treatment in most patients. The treatment is implemented to prevent the development of cirrhosis and end-stage liver failure. This work focuses mainly on the etiopathogenesis and diagnosis of AIH.

Oxidative Stress-A Key Player in the Course of Alcohol-Related Liver Disease.

Oxidative stress is known to be an inseparable factor involved in the presentation of liver disorders. Free radicals interfere with DNA, proteins, and lipids, which are crucial in liver metabolism, changing their expression and biological functions. Additionally, oxidative stress modifies the function of micro-RNAs, impairing the metabolism of hepatocytes. Free radicals have also been proven to influence the function of certain transcriptional factors and to alter the cell cycle. The pathological appearance of alcohol-related liver disease (ALD) constitutes an ideal example of harmful effects due to the redox state. Finally, ethanol-induced toxicity and overproduction of free radicals provoke irreversible changes within liver parenchyma. Understanding the underlying mechanisms associated with the redox state in the course of ALD creates new possibilities of treatment for patients. The future of hepatology may become directly dependent on the effective action against reactive oxygen species. This review summarizes current data on the redox state in the natural history of ALD, highlighting the newest reports on this topic.