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Human diseases have been a critical threat from the beginning of human history. Knowing the origin, course of action and treatment of any disease state is essential. A microscopic approach to the molecular field is a more coherent and accurate way to explore the mechanism, progression, and therapy with the introduction and evolution of technology than a macroscopic approach. Non-coding RNAs (ncRNAs) play increasingly important roles in detecting, developing, and treating all abnormalities related to physiology, pathology, genetics, epigenetics, cancer, and developmental diseases. Noncoding RNAs are becoming increasingly crucial as powerful, multipurpose regulators of all biological processes. Parallel to this, a rising amount of scientific information has revealed links between abnormal noncoding RNA expression and human disorders. Numerous non-coding transcripts with unknown functions have been found in addition to advancements in RNA-sequencing methods. Non-coding linear RNAs come in a variety of forms, including circular RNAs with a continuous closed loop (circRNA), long non-coding RNAs (lncRNA), and microRNAs (miRNA). This comprises specific information on their biogenesis, mode of action, physiological function, and significance concerning disease (such as cancer or cardiovascular diseases and others). This study review focuses on non-coding RNA as specific biomarkers and novel therapeutic targets. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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Ulcerative colitis (UC) is one of the main forms of inflammatory bowel disease (IBD). Despite the widening range of drug treatment options, primary nonresponse, secondary loss of response as well as adverse events call for additional treatment alternatives. Tofacitinib is an oral small-molecule drug of the class of Janus kinase inhibitors which, in the European Union, was approved for the treatment of moderate to severe active UC in August 2018. This position paper, drawn up by the IBD Working Group of the Austrian Society of Gastroenterology and Hepatology, summarizes the mechanism of action, clinical development, marketing authorization status, efficacy and safety of tofacitinib. Also, by providing a synopsis of available data from both pivotal and post-marketing studies, clinical aspects of specific interest are highlighted and discussed. The available body of evidence indicates that tofacitinib is an additional effective medication for the treatment of UC that exhibits a good safety profile. This position paper aims at optimizing the safe and effective use of tofacitinib in daily clinical practice. © 2022, The Author(s).
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INTRODUCTION:This study aimed to evaluate the role of prophylactic norfloxacin in preventing bacterial infections and its effect on transplant-free survival (TFS) in patients with acute-on-chronic liver failure (ACLF) identified by the Asian Pacific Association for the Study of the Liver criteria.METHODS:Patients with ACLF included in the study were randomly assigned to receive oral norfloxacin 400 mg or matched placebo once daily for 30 days. The incidence of bacterial infections at days 30 and 90 was the primary outcome, whereas TFS at days 30 and 90 was the secondary outcome.RESULTS:A total of 143 patients were included (72 in the norfloxacin and 71 in the placebo groups). Baseline demographics, biochemical variables, and severity scores were similar between the 2 groups. On Kaplan-Meier analysis, the incidence of bacterial infections at day 30 was 18.1% (95% confidence interval [CI], 10-28.9) and 33.8% (95% CI, 23-46) (P = 0.03);and the incidence of bacterial infections at day 90 was 46% (95% CI, 34-58) and 62% (95% CI, 49.67-73.23) in the norfloxacin and placebo groups, respectively (P = 0.02). On Kaplan-Meier analysis, TFS at day 30 was 77.8% (95% CI, 66.43-86.73) and 64.8% (95% CI, 52.54-75.75) in the norfloxacin and placebo groups, respectively (P = 0.084). Similarly, TFS at day 90 was 58.3% (95% CI, 46.11-69.84) and 43.7% (95% CI, 31.91-55.95), respectively (P = 0.058). Thirty percent of infections were caused by multidrug-resistant organisms. More patients developed concomitant candiduria in the norfloxacin group (25%) than in the placebo group (2.63%).DISCUSSION:Primary norfloxacin prophylaxis effectively prevents bacterial infections in patients with ACLF.
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The aim of the study. To analyze formation features of the epidemic situation for tuberculosis (TB) in the context of the COVID-19 pandemic in order to predict the further actions of medical organizations. Materials and methods. The data for the region for the last 5 years (2017-2021) were analyzed, including 1,762 newly diagnosed cases of patients with TB and comorbidities (according to the data of the Regional Public Health Organization «Regional Clinical Anti-Tuberculosis Dispensary»). All cases were verified using standard diagnostic methods, including molecular genetic methods, to determine the resistance of pathogens to antibacterial drugs. Results. It was revealed that the epidemiological situation in the region was multidirectional: thus, during the COVID-19 epidemic, the most pronounced incidence decrease was observed among cases of chronic course hepatitis (by 16.4 times), while among patients with tuberculosis the incidence decreased by 2.75 times, and among patients with acute hepatitis - only by 1.5 times (P<0.05). Among the cases of comorbid infection, the most severe course was observed in patients with combined (TB + HIV) infection: there was both a more severe general condition, and the development of adverse (undesirable) reactions to anti-TB drugs, which required an extension of maintenance therapy. Conclusions. The results of the study showed that against the background of the COVID-19 pandemic in the region, there was no tendency towards a worsening of the epidemic situation, primarily for the more socially significant infection - tuberculosis. At the same time, there was an increase in the number of cases of comorbid pathology, including HIV + TB. In the treatment of patients with comorbid forms of infection, it is necessary to take into account the possibility of developing hepatotoxic reactions and, as a result, the appointment of accompanying drugs with hepatoprotective and detoxification effects in therapy.
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While rare, there is now a documented cohort of patients presenting with autoimmune hepatitis secondary to vaccination against COVID-19. With this case report, we aim to compare the published cases in order to discern any unifying characteristics among those affected, and share the story of a seventy-two-year old patient presenting with autoimmune hepatitis less than two weeks after receiving his first dose of the Pfizer COVID-19 vaccine.
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The design and construction of a visible light–driven photoelectrochemical (PEC) device is described based on a CdSe-Co3O4@TiO2 nanoflower (NF). Moreover, an application to the ultrasensitive detection of viruses, such as hepatitis E virus (HEV), HEV-like particles (HEV-LPs), and SARS-CoV-2 spike protein in complicated lysate solution, is demonstrated. The photocurrent response output of a PEC device based on CdSe-Co3O4@TiO2 is enhanced compared with the individual components, TiO2 and CdSe-Co3O4. This can be attributed to the CdSe quantum dot (QD) sensitization effect and strong visible light absorption to improve overall system stability. A robust oxygen-evolving catalyst (Co3O4) coupled at the hole-trapping site (CdSe) extends the interfacial carrier lifetime, and the energy conversion efficiency was improved. The effective hybridization between the antibody and virus resulted in a linear relationship between the change in photocurrent density and the HEV-LP concentration ranging from 10 fg mL–1 to 10 ng mL–1, with a detection limit of 3.5 fg mL–1. This CdSe-Co3O4@TiO2-based PEC device achieved considerable sensitivity, good specificity, and acceptable stability and demonstrated a significant ability to develop an upgraded device with affordable and portable biosensing capabilities. Graphical : [Figure not available: see fulltext.]. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
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Emerging evidence indicates that gut virome plays a role in human health and disease, however, much less is known about the viral communities in blood. Here we conducted a direct metatranscriptomic sequencing of virus-like-particles in blood from 1200 healthy individuals, without prior amplification to avoid potential amplification bias and with a strictly bioinformatic and manual check for candidate viral reads to reduce false-positive matches. We identified 55 different viruses from 36 viral families, including 24 human DNA, RNA and retroviruses in 70% of the studied pools. The study showed that anelloviruses are widely distributed and dominate the blood virome in healthy individuals. Human herpesviruses and pegivirus-1 are commonly prevalent in asymptomatic humans. We identified the prevalence of RNA viruses often causing acute infection, like HEV, HPIV, RSV and HCoV-HKU1, revealing of a transmissible risk of asymptomatic infection. Several viruses possible related to transfusion safety were identified, including human Merkel cell polyomavirus, papillomavirus, parvovirus B19 and herpesvirus 8 in addition to HBV. In addition, phages in Caudovirales and Microviridae, were commonly found in pools of samples with a very low abundance;a few sequences for invertebrate, plant and giant viruses were found in some of individuals;however, the remaining 31 viruses mostly reflect extensive contamination from commercial reagents and the work environments. In conclusion, this study is the first comprehensive investigation of blood virome in healthy individuals by metatranscriptomic sequencing of VLP in China. Further investigation of potential false positives representing a major challenge for the identification of novel viruses in mNGS, will offer a systemic idea and means to reveal true viral infections of human. © 2022
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Introduction and objectives: Liver injury in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant- and Omicron subvariant-infected patients is unknown at present, and the aim of this study is to summarize liver injury in these patients. Materials and Methods: In this study, 460 SARS-CoV-2-infected patients were enrolled. Five severe or critical patients were excluded, and 34 patients were also excluded because liver injury was not considered to be related to SARS-CoV-2 infection. Liver injury was compared between Omicron and non-Omicron variants- and between Omicron subvariant-infected patients;additionally, the clinical data related to liver injury were also analyzed. Results: Among the 421 patients enrolled for analysis, liver injury was detected in 76 (18.1%) patients, including 46 Omicron and 30 non-Omicron variant-infected patients. The ratios did not differ between Omicron and non-Omicron variant-, Omicron BA.1, BA.2 and BA.5 subvariant-infected patients (P>0.05). The majority of abnormal parameters of liver function tests were mildly elevated (1-3 × ULN), the most frequently elevated parameter of liver function test was γ-glutamyl transpeptidase (GGT, 9.5%, 40/421), and patients with cholangiocyte or biliary duct injury markers were higher than with hepatocellular injury markers. Multivariate analysis showed that age (>40 years old, OR=1.898, 95% CI=1.058–3.402, P=0.032), sex (male gender, OR=2.031, 95% CI=1.211–3.408, P=0.007), serum amyloid A (SAA) level (>10 mg/ml, OR=3.595, 95% CI=1.840–7.026, P<0.001) and vaccination status (No, OR=2.131, 95% CI=1.089–4.173, P=0.027) were independent factors related to liver injury. Conclusions: Liver injury does not differ between Omicron and non-Omicron variants or between Omicron subvariant-infected patients. The elevations of cholangiocyte or biliary duct injury biomarkers are dominant in SARS-CoV-2-infected patients. © 2022 Fundación Clínica Médica Sur, A.C.
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Fomepizole is a promising new treatment for preventing liver injury following paracetamol (acetaminophen) overdose. However, we need robust clinical trials to be performed to demonstrate its effect on clinical outcomes that are important to our patients and important to healthcare providers. Until such trials are performed, the toxicology community should learn the lessons from the COVID pandemic—potential novel therapeutic options may be theoretically appealing, but their effectiveness needs to be assessed in robust clinical trials before they are used in clinical practice. © 2022 The Author. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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Objectives: One consequence of social distancing during the coronavirus disease 2019 (COVID-19) pandemic was an increase in alcohol use disorders. We postulated that this would be associated with a rise in alcohol-related gastrointestinal and liver disease. Methods: Using Explorys Inc., an aggregate of electronic health records from US health care systems from 1999 to June 2021, we identified patients with "alcoholic hepatitis," "inflammation of pancreas caused by alcohol," and "alcoholic gastritis," based on Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT). We compared patients utilizing health care during the pandemic to those before it. Results: We identified 8,445,720 patients treated from June 21, 2020 to June 20, 2021 ("COVID cohort") and 65,587,860 patients treated before this ("pre-COVID cohort"). African American patients were more likely to be treated for all causes during COVID-19 [odds ratio (OR): 1.65;P<0.0001]. Alcoholic hepatitis (OR: 2.77), alcoholic pancreatitis (OR: 3.67), and alcoholic gastritis (OR: 1.70) (for each, P<0.0001) were more likely in all patients in the COVID cohort. African Americans in the COVID cohort were more likely to be diagnosed with alcoholic hepatitis (OR: 2.63), alcoholic pancreatitis (OR: 2.17), and alcoholic gastritis (OR: 3.09) [for each, P<0.0001]. Conclusions: The prevalence of alcohol-related liver and gastrointestinal disease increased during COVID-19. We suspect these increases are associated with increased alcohol use disorder resulting from the stress of social isolation. These data suggest COVID-19 disproportionately affected African Americans in overall health care utilization and increased burden of alcoholic gastrointestinal and liver disease. © 2023 Lippincott Williams and Wilkins. All rights reserved.
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Introduction: Hepatitis B virus (HBV) and its satellite virus hepatitis D (HDV) are common worldwide hepatotrophic infections responsible for cirrhosis and hepatocellular carcinoma. EASL practice guidelines recommend HDV screening in all Hep B patients. Novel therapies for Hep D are promising. Aim: To determine screening rates for HDV in HBV patients referred to our Laboratory of Hub Hospital Pordenone (Friuli Venezia Giulia). Methods: We retrospectively considered HBsAg positive results from 01.01.2018 to 31.12.2021. Using an extended database to 30.11.2022, we considered, among those were HBsAg positive, anti-HDV results and if we detected positivity for anti-HDV, we checked if HDV-RNA was performed. Results: 931 patients (55% non-Italian native) positive for hepatitis B surface antigen were studied with a majority male patients (65%). Of 931, 470 (50%) Hep B patients were screened for Hep D and 13 (1.4%) (9 non-Italian native) were positive for anti-HDV. Of 13, 6 were positive for serum HDV-RNA;3 subjects were negative for HDV-RNA while 4 patients did not perform HDV-RNA. 10 Hep-B patients (1%) negative for anti-HDV at first time were re-tested for anti-HDV more than once. Comparing 2018-2019 vs 2020-2021, screening rate for Hep D decreased from 56% to 40%. Conclusions: Despite current HDV guidelines, in our Hospital HDV screening is suboptimal and it is actually declining. In fact COVID-19 has caused the slowing down of hepatitis testing program. Therefore we suggest: 1) anti-HDV simplified and automated reflex testing algorithms in Hep B patients for an early diagnosis and linkage to care of HDV infection;2) enhancement of molecular biology for HDV-RNA assay in our Italian Labs;3) repeating more than once anti-HDV especially in high-risk HBV patients. Furthermore, we need to be careful for Hep B vaccine to reduce Hep D screening and disease burden.
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Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)
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Hemorrhagic cholecystitis is a rare disorder associated with considerable morbidity and mortality. The clinical presentation of hemorrhagic cholecystitis is non-specific and imaging findings can be difficult to accurately interpret without a high level of suspicion. Most recent reports of hemorrhagic cholecystitis have been associated with concurrent therapeutic anticoagulation. Here, we report imaging findings of a case of acute, spontaneous hemorrhagic cholecystitis in a 67-year-old male patient admitted for hypoxic respiratory failure secondary to COVID-19 pneumonia. © 2022
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The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.