Automated office blood pressure measurements in primary care are misleading in more than one third of treated hypertensives: The VALENTINE-Greece Home Blood Pressure Monitoring study

Abstract Background This study assessed the diagnostic reliability of automated office blood pressure (OBP) measurements in treated hypertensive patients in primary care by evaluating the prevalence of white coat hypertension (WCH) and masked uncontrolled hypertension (MUCH) phenomena. Methods Primary care physicians, nationwide in Greece, assessed consecutive hypertensive patients on stable treatment using OBP (1 visit, triplicate measurements) and home blood pressure (HBP) measurements (7 days, duplicate morning and evening measurements). All measurements were performed using validated automated devices with bluetooth capacity (Omron M7 Intelli-IT). Uncontrolled OBP was defined as ≥140/90 mmHg, and uncontrolled HBP was defined as ≥135/85 mmHg. Results A total of 790 patients recruited by 135 doctors were analyzed (age: 64.5 ± 14.4 years, diabetics: 21.4%, smokers: 20.6%, and average number of antihypertensive drugs: 1.6 ± 0.8). OBP (137.5 ± 9.4/84.3 ± 7.7 mmHg, systolic/diastolic) was higher than HBP (130.6 ± 11.2/79.9 ± 8 mmHg; difference 6.9 ± 11.6/4.4 ± 7.6 mmHg, p Conclusions In primary care, automated OBP measurements are misleading in approximately 40% of treated hypertensive patients. HBP monitoring is mandatory to avoid overtreatment of subjects with WCH phenomenon and prevent undertreatment and subsequent excess cardiovascular disease in MUCH

A case report of successful treatment of pyoderma gangrenosum in a patient with autoimmune hepatitis, and review of the literature

Background: Pyoderma Gangrenosum (PG) is a cutaneous condition, its diagnosis suggested by the presence of a painful cutaneous ulcer showing rapid progression. Pyoderma gangrenosum is associated with a concomitant systemic disease in 50 to 70% of cases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and lymphoproliferative disorders. Although PG has also been reported with viral hepatitis, it is rarely associated with autoimmune hepatitis. Case presentation: A 19-year-old Caucasian female, with a prior diagnosis of autoimmune hepatitis (AIH) in remission, presented with bilateral lower limb ulcers 4years after the diagnosis of AIH. She was diagnosed with PG and treated with high-dose prednisolone, methotrexate and cyclosporine. One year later she was well, the ulcers completely healed, and with the autoimmune hepatitis still in remission. Conclusion: We report a case of autoimmune hepatitis and the subsequent, rarely occurring, extra-hepatic onset of pyoderma gangrenosum, with the AIH in remission, strengthening the association between the two conditions. Since both the AIH and the PG can present serious diagnostic challenges, thus delaying vital therapy, it is important that the development of either prompts us to consider the possibility of the other developing in the future or if already present facilitate its diagnosis, such considerations making the case for a systematic follow up. © 2015 Androutsakos et al

Liver fibrosis assessment in a cohort of Greek HIV mono-infected patients by non-invasive biomarkers

Background: Non-alcoholic Fatty Liver Disease (NAFLD) is common in HIV-infected individuals. Liver biopsy remains the gold-standard procedure for the diagnosis of liver fibrosis, but both Transient Elastography (TE) and Non-invasive Biomarkers (NIBMs) have emerged as alternatives. Objectives: Our study’s aim was to validate commonly used NIBMs for the assessment of liver fibrosis in a cohort of Greek HIV-mono-infected patients Methods: Inclusion criteria were confirmed HIV-infection and age>18 years and exclusion criteria HBV or HCV seropositivity, liver disease other than NAFLD, alcohol abuse, ascites, transaminases levels>4xULN(upper limit of normal) and Body-Mass index(BMI)>40. Liver stiffness (LS) measurement with TE and thorough laboratory work up and medical history were acquired at study entry. FIB-4, APRI, NFS, BARD, Forns and Lok scores were calculated for each patient. Results: A total of 157 patients were eligible for this study. Significant liver fibrosis, compatible with Metavir score of F3-F4, was found in only 11(7%) patients. These findings were in accordance with those of the NIBMs; the BARD score constituting the only exception, allocating 102(65%) patients as having significant liver fibrosis. In order to obtain a balance between sensitivity and specificity new cut-offs for each NIBM were calculated; FIB-4 score yielded the best results, since by changing the cut-off to 1.49 a sensitivity and specificity balanced for both close to 85% was achieved. Conclusion: Our findings suggest that NIBMs can be used for the evaluation of liver fibrosis in HIV mono-infected patients. New cut-offs for NIBMs should probably be calculated, to help distinguishing patients with significant from those with mild/no fibrosis. © 2019 Bentham Science Publishers

Causative factors of liver fibrosis in HIV-infected patients. A single center study

Background: Liver disease is a leading cause of morbidity and mortality among Human Immunodeficiency virus (HIV) infected patients; however no consensus exists on HIV-related risk factors for it. The aim of this study was to identify risk factors for liver fibrosis/cirrhosis in a cohort of Greek HIV-infected patients. Methods: Patients attending the HIV outpatient clinic of Pathophysiology Department at «Laiko» General Hospital in Athens, Greece, between December 2014 and December 2017 were eligible for inclusion. Inclusion criteria were confirmed HIV infection and age > 18 years. Exclusion criteria were Body-Mass index (BMI) > 40, liver metastases of malignant diseases and concurrent or previous chemotherapy. Liver stiffness (LS) was measured using Vibration Controlled Transient Elastography (TE) and laboratory tests were acquired in all patients. Patients were classified in 2 groups: those with mild or no fibrosis (equivalent to Metavir score F0-F2) and those with significant fibrosis (equivalent to Metavir score F3-F4). Results: A total of 187 consecutive patients were included in this study. Median TE value was 5.1 kilopascals (KPa) (range 2.8-26.3), with 92.5% (173/187) of the patients having no/mild fibrosis and 7.4% (14/187) significant fibrosis. On multivariate logistic regression analysis older patient's age, abnormal serum aspartate aminotransferase (AST) value, Hepatitis C virus (HCV) infection, alcohol abuse, CD4/CD8 ratio and an increased number of liver related events (LREs) were significantly correlated with liver fibrosis/cirrhosis. Conclusions: In our cohort of HIV-infected individuals HCV/HIV co-infection, older age, alcohol abuse and CD4/CD8 ratio seem to correlate with fibrogenesis in the liver. © 2020 The Author(s)

Methotrexate-Related Liver Cirrhosis in Psoriatic Arthritis: A Case Report and Review of the Literature

Methotrexate is an anchor-drug for the treatment of inflammatory arthritides affecting peripheral joints, such as rheumatoid and psoriatic arthritis (PsA), but also for other immune-mediated diseases like psoriasis. Although it is generally a well-tolerated drug, adverse effects often occur. Reversible derangement of liver function test is the most common laboratory adverse event. However, in some cases, liver cirrhosis and/or fibrosis can occur. Besides, many of these diseases like PsA and psoriasis are closely linked with clinical conditions and risk factors that also contribute to liver damage/cirrhosis, such as increased body mass index, dyslipidaemia and diabetes mellitus (DM). It has been hypothesised that the aforementioned risk factors along with methotrexate usage can act synergistically, causing liver damage in these patients. Herein, we describe a PsA patient with DM who developed fatal liver cirrhosis after 10 years of treatment with MTX. We also review the literature about the liver toxicity of MTX in the context of PsA and psoriasis, describing concurring risk factors and histopathological findings. PubMed and Scopus were searched, without date limits. The keywords “methotrexate” AND “psoriatic arthritis” OR “psoriasis” AND “Liver damage” OR “liver fibrosis” OR “cirrhosis” were used. We found that although fibrosis/cirrhosis is present in about 10-25% of the patients, MTX can rarely cause liver damage itself. However, it can exert its effect when other factors, like increased alcohol consumption and obesity coexist. Prospective studies are needed, specifically examining the hepatotoxicity of MTX in individuals with immune-mediated diseases. © 202

Decreased serum DNase1-activity in patients with autoimmune liver diseases

Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC). Sera from 146 patients with chronic hepatitis B or C, 140 with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and 114 healthy individuals served as disease and healthy controls. Available serum samples during remission from 50 AIH and 39 PBC patients were also investigated by paired analyzes. DNase1-activity was significantly lower in AIH, PBC and PSC compared to viral hepatitis (p 1400 mg/dl; p < 0.05); in PBC, with AST (p < 0.01), alanine aminotransferase (ALT) (p < 0.03) and anti-mitochondrial antibodies (AMA) (p = 0.008). In PSC, DNase1-activity was inversely associated with alkaline phosphatase (ALP) (p < 0.05). In AIH, complete responders were characterized by increased baseline DNase1-activity compared to partial responders, relapsers and non-responders (p < 0.02), whereas it was significantly increased after achievement of remission (p < 0.001). Serum DNase1-activity is significantly decreased in ALD patients, indicating its potential implication in their pathogenesis. Furthermore, DNase1-activity could be used as a new surrogate biomarker for predicting response to AIH treatment. © 2017 Informa UK Limited, trading as Taylor & Francis Group

Regulatory T cell counts and development of malignancy in patients with HIV infection

Background: T-regulatory cells (Tregs) play an important role in maintaining homeostasis by attenuating the cytokine response to T-cell receptor (TCR) stimulation and by suppressing the functioning of neighboring immune cells. In Human Immunodeficiency Virus (HIV) infection, Tregs can be either beneficial, by suppressing generalized T-cell activation, or detrimental, by suppressing protective anti-HIV cell-mediated immunity. An imbalance of Tregs and effector T-cells can blunt immune responses to malignant cells or facilitate inflammation-mediated pathologies. Objective: The purpose of our study was to explore the possible correlation between Tregs’ concentration and HIV infection’s parameters as well as the development of hematological and solid malignancies. Methods: In a longitudinal prospective study, ex vivo phenotyping of fresh peripheral blood mononuclear cells from patients with primary HIV infection was performed at baseline. All patients were then followed up every 3 months and the development of solid or hematological malignancies was noted. Results: A total of 155 patients were included in the study and the median follow-up period was 64 months. Treg counts were significantly higher among males, patients with high viral load (&lt;350 copies/ml) and patients with virological failure to antiretroviral treatment (ART). Linear regression analysis showed a significant negative correlation between Treg levels and CD4 (+) T-cell counts. Patients with neoplasia had lower levels of Tregs while increasing levels showed a negative correlation with the development of neoplasia. Conclusion: In our population of HIV-infected patients, high levels of Tregs were associated with disease progression, and low baseline levels were associated with a higher probability of developing neoplasia. © 2020 Bentham Science Publishers

Decreased serum DNase1-activity in patients with autoimmune liver diseases

Deoxyribonuclease1 (DNase1) is involved in chromatin degradation of apoptotic cells. Its deficiency results in accumulation of self-DNA, which in turn may induce inflammation and autoimmunity. We assessed for the first time serum DNase1-activity in a large consecutive cohort of treatment-naïve patients with autoimmune liver diseases (ALD). DNase1-activity was determined by single radial enzyme-diffusion (SRED) at diagnosis of 224 patients with autoimmune hepatitis (AIH), 249 with primary biliary cirrhosis (PBC) and 36 with primary sclerosing cholangitis (PSC). Sera from 146 patients with chronic hepatitis B or C, 140 with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) and 114 healthy individuals served as disease and healthy controls. Available serum samples during remission from 50 AIH and 39 PBC patients were also investigated by paired analyzes. DNase1-activity was significantly lower in AIH, PBC and PSC compared to viral hepatitis (p &lt; 0.02, p &lt; 0.001, p = 0.03), NAFLD/NASH (p &lt; 0.001) and healthy (p &lt; 0.001). No significant difference was found in between each specific ALD. In AIH, DNAse1-activity was positively correlated with aspartate aminotransferase (AST) (p &lt; 0.02), bilirubin (p &lt; 0.01) and increased IgG (&gt;1400 mg/dl; p &lt; 0.05); in PBC, with AST (p &lt; 0.01), alanine aminotransferase (ALT) (p &lt; 0.03) and anti-mitochondrial antibodies (AMA) (p = 0.008). In PSC, DNase1-activity was inversely associated with alkaline phosphatase (ALP) (p &lt; 0.05). In AIH, complete responders were characterized by increased baseline DNase1-activity compared to partial responders, relapsers and non-responders (p &lt; 0.02), whereas it was significantly increased after achievement of remission (p &lt; 0.001). Serum DNase1-activity is significantly decreased in ALD patients, indicating its potential implication in their pathogenesis. Furthermore, DNase1-activity could be used as a new surrogate biomarker for predicting response to AIH treatment. © 2017 Informa UK Limited, trading as Taylor &amp; Francis Group

Antibody Responses after SARS-CoV-2 Vaccination in Patients with Liver Diseases

The novel mRNA-based vaccines against SARS-CoV-2 display encouraging safety and efficacy profiles. However, there is a paucity of data regarding their immunogenicity and safety in patients with liver diseases (PWLD), especially in those with cirrhosis. We prospectively as-sessed anti-SARS-CoV-2 S-spike IgG antibodies and neutralizing activity in fully vaccinated PWLD (n = 87) and controls (n = 40). Seroconversion rates were 97.4% (37/38) in cirrhotic PWLD, 87.8% (43/49) in non-cirrhotic PWLD and 100% (40/40) in controls. Adequate neutralizing activity was detected in 92.1% (35/38), 87.8% (43/49) and 100% (40/40) of cirrhotics, non-cirrhotics and controls, respectively. On multivariable analysis, immunosuppressive treatment was negatively correlated with anti-SARS-CoV-2 antibody titers (coefficient (SE): −2.716 (0.634), p &lt; 0.001) and neutralizing activity (coefficient (SE): −24.379 (4.582), p &lt; 0.001), while age was negatively correlated only with neutralizing activity (coefficient (SE): −0.31(0.14), p = 0.028). A total of 52 responder PWLD were reassessed approximately 3 months post-vaccination and no differences were detected in humoral responses between cirrhotic and non-cirrhotic PWLD. No significant side effects were noted post vaccination, while no symptomatic breakthrough infections were reported during a 6-month follow up. Overall, our study shows that m-RNA-based SARS-CoV-2 vaccines are safe and efficacious in PWLD. However, PWLD under immunosuppressive treatment and those of advanced age should probably be more closely monitored after vaccination. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection?

Non-alcoholic fatty liver disease (NAFLD) is an ‘umbrella’ term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment. © 2022 by the authors. Licensee MDPI, Basel, Switzerland