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.

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).

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.

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.

Perspectives for 3D-Bioprinting in Modeling of Tumor Immune Evasion.

In a living organism, cancer cells function in a specific microenvironment, where they exchange numerous physical and biochemical cues with other cells and the surrounding extracellular matrix (ECM). Immune evasion is a clinically relevant phenomenon, in which cancer cells are able to direct this interchange of signals against the immune effector cells and to generate an immunosuppressive environment favoring their own survival. A proper understanding of this phenomenon is substantial for generating more successful anticancer therapies. However, classical cell culture systems are unable to sufficiently recapture the dynamic nature and complexity of the tumor microenvironment (TME) to be of satisfactory use for comprehensive studies on mechanisms of tumor immune evasion. In turn, 3D-bioprinting is a rapidly evolving manufacture technique, in which it is possible to generate finely detailed structures comprised of multiple cell types and biomaterials serving as ECM-analogues. In this review, we focus on currently used 3D-bioprinting techniques, their applications in the TME research, and potential uses of 3D-bioprinting in modeling of tumor immune evasion and response to immunotherapies.

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.

Diagnosing pleural effusions using mass spectrometry-based multiplexed targeted proteomics quantitating mid- to high-abundance markers of cancer, infection/inflammation and tuberculosis.

Pleural effusion (PE) is excess fluid in the pleural cavity that stems from lung cancer, other diseases like extra-pulmonary tuberculosis (TB) and pneumonia, or from a variety of benign conditions. Diagnosing its cause is often a clinical challenge and we have applied targeted proteomic methods with the aim of aiding the determination of PE etiology. We developed a mass spectrometry (MS)-based multiple reaction monitoring (MRM)-protein-panel assay to precisely quantitate 53 established cancer-markers, TB-markers, and infection/inflammation-markers currently assessed individually in the clinic, as well as potential biomarkers suggested in the literature for PE classification. Since MS-based proteomic assays are on the cusp of entering clinical use, we assessed the merits of such an approach and this marker panel based on a single-center 209 patient cohort with established etiology. We observed groups of infection/inflammation markers (ADA2, WARS, CXCL10, S100A9, VIM, APCS, LGALS1, CRP, MMP9, and LDHA) that specifically discriminate TB-PEs and other-infectious-PEs, and a number of cancer markers (CDH1, MUC1/CA-15-3, THBS4, MSLN, HPX, SVEP1, SPINT1, CK-18, and CK-8) that discriminate cancerous-PEs. Some previously suggested potential biomarkers did not show any significant difference. Using a Decision Tree/Multiclass classification method, we show a very good discrimination ability for classifying PEs into one of four types: cancerous-PEs (AUC: 0.863), tuberculous-PEs (AUC of 0.859), other-infectious-PEs (AUC of 0.863), and benign-PEs (AUC: 0.842). This type of approach and the indicated markers have the potential to assist in clinical diagnosis in the future, and help with the difficult decision on therapy guidance.

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.

Plateletcrit and Mean Platelet Volume in the Evaluation of Alcoholic Liver Cirrhosis and Nonalcoholic Fatty Liver Disease Patients.

Platelet (PLT) indices have been proposed as potential markers in the assessment of liver fibrosis and exacerbation of liver failure. The aim of our study was to verify mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in alcohol-related liver cirrhosis (ALC) and nonalcoholic fatty liver disease (NAFLD) patients. One hundred forty-two patients with ALC, 92 with NAFLD, and 68 in control group were enrolled in this study. Hematological indices (MPV, PCT, and PDW) and serological (indirect and direct) markers of liver fibrosis (AAR, APRI, FIB-4, GPR, PICP, PIIINP, TGF-α, PDGF-AB, laminin) were measured in each participant. MELD score in ALC patients and NAFLD fibrosis score (NFS) together with BARD score in the NAFLD group were also obtained. Results were compared between research and control groups. Then, a correlation between evaluated indices was performed in study groups. Receiver operating characteristic curves (ROCs) and area under the curve (AUC) values were applied to assess the diagnostic accuracy of measured indices. Significant increase in PDW and decrease in PCT in comparison to controls were noted in examined ALC (60.4% vs. 51.2% and 0.1% vs. 0.21%, respectively, p < 0.0001) and NAFLD (54.75% vs. 51.2% and 0.19 vs. 0.21%, respectively, p < 0.01) patients. Decreased level of MPV was observed in NAFLD group (7.85 fl vs. 8.90 fl, p < 0.0001). Additionally, PCT correlated with NFS (p < 0.0001). Evaluated PLT indices correlated with MELD score (MPV and PDW, p < 0.001; PCT, p < 0.05). They correlated with indirect and direct markers of liver fibrosis in the whole research group, too. PCT was the parameter with the greatest diagnostic accuracy in ALC patients (AUC = 0,839 for cutoff < 0.17%); in NAFLD group, it was MPV (AUC = 0,808 for cutoff < 7.9 fl). PCT in ALC and MPV in NAFLD can be perceived as potential diagnostic markers.

Gender-related disparities in the frequencies of PD-1 and PD-L1 positive peripheral blood T and B lymphocytes in patients with alcohol-related liver disease: a single center pilot study.

BACKGROUND: Exposure to excessive alcohol consumption dysregulates immune signaling. The programed cell death 1 (PD-1) receptor and its ligand PD-L1 play a critical role in the protection against immune-mediated tissue damage. The aim of our study was evaluation of the PD-1/PDL-1 expression on peripheral T and B lymphocytes, its correlation with markers of inflammation and the severity of liver dysfunction in the course of alcohol-related liver disease (ALD). MATERIAL AND METHODS: Fifty-six inpatients with ALD (38 males, 18 females, aged 49.23 ± 10.66) were prospectively enrolled and assigned to subgroups based on their: (1) gender, (2) severity of liver dysfunction (Child-Pugh, MELD scores, mDF), (3) presence of ALD complications, and followed for 30 days. Twenty-five age- and gender-matched healthy volunteers served as the control group. Flow cytometric analysis of the PD-1/PD-L1 expression on peripheral lymphocyte subsets were performed. RESULTS: General frequencies of PD-1/PD-L1 positive T and B subsets did not differ between the ALD and control group. When patients were analyzed based on their gender, significantly higher frequencies of PD1/PD-L1 positive B cells in ALD females compared to controls were observed. ALD females presented with significantly higher frequencies of PD-1+ and PD-L1+ B cells, as well as PD-L1+ all T cell subsets in comparison with ALD males. The same gender pattern of the PD-1/PDL1 expression was found in the subgroups with mDF > 32 and MELD > 20. No correlations of PD-1+ and PD-L1+ lymphocyte percentages with mDF, CTP and MELD scores, nor with complications of ALD were observed. Significant correlations of PD-L1 positive B cell frequencies with conventional markers of inflammation were found. CONCLUSIONS: Gender-related differences in the frequencies of PD-1/PD-L1 positive T and B cells were observed in patients with ALD. Upregulation of PD-1+/PD-L1+ lymphocytes paralleled both the severity of alcoholic hepatitis and liver dysfunction in ALD females.

Liver injury in the era of COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undoubtedly revolutionized the whole globe and given a new point of view on respiratory tract infections. Nevertheless, coronavirus disease 2019 (COVID-19) cannot be perceived as a disease limited only to pneumonia with diverse severity. More and more reports have demonstrated a wide range of possible systemic symptoms, including hepatic complications. Liver injury has been observed in a significant proportion of patients, especially in those with a severe or critical illness. COVID-19 might provoke a deterioration of liver function in patients with already diagnosed chronic liver diseases and without pre-existing liver disorders. The deterioration of liver function worsens the prognosis, increases the risk of a severe course of SARS-CoV-2 infection and prolongs the hospital stay. In general, patients who develop liver dysfunction in COVID-19 are mainly males, elderly people, and those with higher body mass index. The underlying mechanisms for hepatic failure in patients infected with SARS-CoV-2 are still unclear, nevertheless liver damage appears to be directly connected with virus-induced cytopathic effects. A liver injury observed during hospitalization might be simultaneously caused by the use of potentially hepatotoxic drugs, mainly antiviral agents. This minireview focuses on a possible relationship between COVID-19 and the liver, potential molecular mechanisms of liver damage, the characteristics of liver injury and suggested factors predisposing to hepatic manifestations in COVID-19 patients.

Towards an evaluation of alcoholic liver cirrhosis and nonalcoholic fatty liver disease patients with hematological scales.

BACKGROUND: Seeking potentially novel blood markers of liver fibrosis and steatosis is constantly of crucial importance. Despite a growing number of studies in this field of hepatology, a certain role of hematological indices in the course of liver disorders has not been fully elucidated, yet. AIM: To evaluate a diagnostic accuracy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and mean platelet volume-to-platelet-ratio (MPR) in the course of alcoholic liver cirrhosis (ALC) and nonalcoholic fatty liver disease (NAFLD). METHODS: One hundred forty-two patients with ALC, 92 with NAFLD and 68 persons in control group were enrolled in the study. Hematological indices (NLR, PLR and MPR), indirect and direct markers of liver fibrosis (aspartate transaminase to alkaline transaminase ratio, aspartate transaminase to platelet ratio index, fibrosis-4, gamma-glutamyl transpeptidase to platelet ratio, procollagen I carboxyterminal propeptide, procollagen III aminoterminal propeptide, transforming growth factor-α, platelet-derived growth factor AB, laminin) were measured in each person. Model for end-stage liver disease (MELD) score in ALC group and NAFLD fibrosis score together with BARD score were calculated in NAFLD patients. Receiver operating characteristic (ROC) curves and area under the curve (AUC) values were applied to assess the sensitivity and specificity of examined markers and to evaluate proposed cut-offs of measured indices in the course of ALC and NAFLD. RESULTS: MPR and NLR values in ALC patients were significantly higher in comparison to control group; PLR level was significantly lower. MPR and PLR correlated with assessed indirect and direct markers of liver fibrosis. MPR, NLR and PLR correlated with MELD score. NLR level in NAFLD patients was significantly higher in comparison to controls. MPR correlated with indirect markers of liver fibrosis and NAFLD fibrosis score. AUC values and proposed cut-offs for NLR, PLR and MPR in ALC patients were: 0.821 (> 2.227), 0.675 (< 70.445) and 0.929 (> 0.048), respectively. AUC values and proposed cut-offs for NLR, PLR and MPR in NAFLD group were: 0.725 (> 2.034), 0.528 (> 97.101) and 0.547 (> 0.038), respectively. CONCLUSION: Hematological markers are inseparably connected with serological indices of liver fibrosis in ALC and NAFLD patients. MPR and NLR turned out to be the most powerful parameters in ALC patients.

[The role of electrical bioimpedance in the evaluation of the hydration status of patients with liver cirrhosis]. / Rola bioimpedancji elektrycznej w ocenie stanu nawodnienia chorych na marskosc watroby.

Patients with liver cirrhosis are a group particularly exposed to the development of water and electrolyte disturbances, having a significant impact on the course of the disease and the quality of life. Precise and rapid assessment of the hydration status of patients often determines the further course of the disease, the success of treatment and the time of hospitalization. For this reason, it is important to maintain the water and electrolyte balance in a state of equilibrium. So far, no one optimized diagnostic tool has been found to assess the hydration status of the organism, which would become a gold standard. Despite some limitations, it should be noted that the electrical bioimpedance (BIA) method makes it possible to assess the total body water volume, extracellular space, intracellular space, as well as the content of sodium ions, which affects the flow of fluids between these spaces. It is an excellent non-invasive tool in diagnosing hydration status of patients with liver cirrhosis, kidney failure and cardiovascular diseases.

Deviations in Peripheral Blood Cell Populations are Associated with the Stage of Primary Biliary Cholangitis and Presence of Itching.

To evaluate the role of Th17, Treg cells, activated T CD3+ and B CD19+ lymphocytes in primary biliary cholangitis (PBC) patients. 40 female patients with PBC and 20 healthy donors were enrolled in this study. The percentages and absolute counts of Th17, Treg, activated T CD3+, B CD19+, NK, NKT-like lymphocytes were measured by flow cytometry. Our research revealed significantly lower frequencies and absolute counts of CD4+CD25+FOXP3+ Treg cells (p < 0.0001), higher percentages and absolute counts of Th17 cells (IL-17A+CD3+CD4+; p < 0.0001 and p = 0.009, respectively), CD3-/CD16+CD56+ NK cells (p < 0.0001 and p = 0.039, respectively), CD3+/CD16+CD56+ NKT-like cells (p < 0.0001 and p = 0.048, respectively). There were also higher percentages and numbers of B CD19+ lymphocytes (p = 0.002 and p = 0.001, respectively) and higher percentages and absolute counts of activated B CD19+CD25+ cells (p = 0.007 and p = 0.002, respectively). Moreover, we observed a statistically significant correlation between the presence of itching and particular peripheral blood subpopulations in PBC patients. Absolute counts of both CD4+CD3+ cells (p = 0.0119) and CD3+CD25+ cells (p = 0.0329) were lower in patients with pruritus. A similar dependency was noted in reference to percentages of NKT-like cells (CD3+/CD16+CD56+; p = 0.0359) and (CD3+) T lymphocytes (p = 0.0302). Th17 and Treg cells are involved in the course of PBC. There is also the association between the pruritus and peripheral blood subpopulations.

A rare case of skin blistering and esophageal stenosis in the course of epidermolysis bullosa - case report and literature review.

BACKGROUND: Epidermolysis bullosa (EB) constitutes a heterogenous group of rare multisystem genetically transmitted disorders comprising several blistering muco-cutaneous diseases with a monogenic basis and either autosomal dominant or autosomal recessive mode of inheritance. EB manifestation is not only limited to the skin. Systemic signs might involve the nose, ear, eye, genitourinary tract and upper gastrointestinal tract. The presence of particular symptoms is directly determined by a type of altered skin protein. Gastrointestinal manifestation of EB is most commonly reflected by esophageal stenosis due to recurrent esophageal blistering, followed by consequent scarring. CASE PRESENTATION: Here we present a case of a man with dystrophic EB and dysphagia, skin blistering, joints contractures and missing nails. To our knowledge, the presented man is the oldest one diagnosed with EB living in Poland. CONCLUSIONS: Management of an esophageal stricture in such circumstances is based on endoscopic dilatation. However, in most severe cases, placement of a gastrostomy tube is required. Despite great advances in medicine, a targeted therapy in the course of EB has not been established yet.

An MRM-Based Cytokeratin Marker Assay as a Tool for Cancer Studies: Application to Lung Cancer Pleural Effusions.

PURPOSE: The goal of this work was to develop an LC-MRM assay for the quantitative analysis of a set of established and diagnostically important cytokeratin (CK) markers used in cancer diagnosis, prognosis, and therapy monitoring. Second, the potential of this assay in lung cancer diagnosis through pleural effusion (PE) analysis was examined. EXPERIMENTAL DESIGN: A multiplexed MRM assay was developed for 17 CKs and their select caspase-cleaved fragments. Isotope-labeled standard peptides were used for high assay specificity and absolute peptide quantitation; with robust standard-flow LC coupled to a latest-generation triple-quadrupole instrument for high sensitivity. The potential clinical applicability was demonstrated by the analysis of 118 PE samples. RESULTS: The MRM assay was evaluated for endogenous detection, linearity, precision, upper and lower limits of quantification, selectivity, reproducibility and peptide stability, and is generally applicable to any epithelial cancer study. A set of 118 patients with known pathologies allowed us to define the range of CK levels in clinical PE samples. Specific CKs were able to differentiate cancer-related PEs from those caused by benign ailments. In addition, they allowed to differentiate between PEs from subjects with small cell lung cancer versus non-small cell lung carcinoma, and to further differentiate the latter into its two subtypes, adenocarcinoma and squamous cell carcinoma. CONCLUSION AND CLINICAL RELEVANCE: An MRM-based CK assay for carcinoma studies can differentiate between the three lung cancer histological types using less-invasive PE sampling providing potential therapy-guiding information on patients that are inoperable.