Inequity in clinical research access for service users presenting comorbidity within alcohol treatment settings: findings from a focused ethnographic study (preprint)

Background While healthcare policy has fostered implementation strategies to improve inclusion and access of under-served groups to clinical care, systemic and structural factors still disproportionately prevent service users from accessing research opportunities embedded within clinical settings. This contributes to the widening of health inequalities, as the absence of representativeness prevents the applicability and effectiveness of evidence-based interventions in under-served clinical populations. The present study aims to identify the individual (micro), organisational (meso) and structural (macro) barriers to clinical research access in patients with comorbid alcohol use disorder and alcohol-related liver disease.Methods A focused ethnography approach was employed to explore the challenges experienced by patients in the access to and implementation of research processes within clinical settings. Data were collected through an iterative-inductive approach, using field notes and patient interview transcripts. The framework method was utilised for data analysis, and themes were identified at the micro, meso and macro levels.Results At the micro-level, alcohol-related barriers included encephalopathy and acute withdrawal symptoms. Alcohol-unrelated barriers also shaped the engagement of service users in research. At the meso-level, staff and resource pressures, as well as familiarity with clinical and research facilities were noted as influencing intervention delivery and study retention. At the wider, macro-level, circumstances including the ‘cost of living crisis’ and national industrial action within healthcare settings had an impact on research processes. The findings emphasise a ‘domino effect’ across all levels, demonstrating an interplay between individual, organisational and structural factors influencing access to clinical research.Conclusions A combination of individual, organisational and structural factors, exacerbated by the COVID-19 pandemic, and the socioeconomic landscape in which the study was conducted further contributed to the unequal access of under-served groups to clinical research participation. For patients with comorbid alcohol use disorder and alcohol-related liver disease, limited access to research further contributes towards a gap in effective evidence-based treatment, exacerbating health inequalities in this clinical population.

Use of immune-modulating agents to regulate hyperinflammation in severe COVID-19; the assessment of tocilizumab use in combination with steroids (preprint)

Introduction COVID-19 infection might lead to hyperinflammatory state in severe cases leading to devastating outcomes. Immune modulation using steroids or other immune modulators can regulate the intensity of inflammatory response; however, this theory has not been adequately assessed in practice. The current study aims to investigate the use of corticosteroids alone or in combination with tocilizumab for the treatment of patients with severe COVID-19. Methods The current retrospective cross-sectional study has been conducted on 168 patients with severe COVID-19 infection who were categorized into three treatment groups of A: primary treatment with high-dose methylprednisolone (> 1 mg/kg) continued with tocilizumab; B: primary treatment with low-dose methylprednisolone (< 1 mg/kg) continued with tocilizumab and C: treatment with high-dose methylprednisolone (> 1 mg/kg) only. The parameters including clinical outcome, laboratory parameters, length of hospitalization, intensive care unit (ICU) admission requirement and drug-related adverse events were compared between the groups. Results The outcomes were significantly better in group B considering the shorter length of ICU stay, lower CRP, LDH, and higher oxygen saturation and platelet count in group B than the other groups (P-value < 0.05). Logistic regression assessment in crude and adjusted models revealed increased risks of mortality, the incidence of nosocomial infection and the incidence of adverse effects, including hepatic dysfunction, renal dysfunction and GIB in both groups A and C compared with group B (P-value < 0.05). Conclusion Based on the findings of this study, low-dose steroid continued with tocilizumab was superior over high-dose steroid alone or in combination with tocilizumab in terms of all evaluated parameters.

Sentiment Analysis and Text Analysis of the Public Discourse on Twitter about COVID-19 and MPox (preprint)

Mining and analysis of the big data of Twitter conversations have been of significant interest to the scientific community in the fields of healthcare, epidemiology, big data, data science, computer science, and their related areas, as can be seen from several works in the last few years that focused on sentiment analysis and other forms of text analysis of tweets related to Ebola, E-Coli, Dengue, Human Papillomavirus, Middle East Respiratory Syndrome, Measles, Zika virus, H1N1, influenza like illness, swine flu, flu, Cholera, Listeriosis, cancer, Liver Disease, Inflammatory Bowel Disease, kidney disease, lupus, Parkinsons, Diphtheria, and West Nile virus. The recent outbreaks of COVID-19 and MPox have served as catalysts for Twitter usage related to seeking and sharing information, views, opinions, and sentiments involving both of these viruses. None of the prior works in this field analyzed tweets focusing on both COVID-19 and MPox simultaneously. To address this research gap, a total of 61,862 tweets that focused on MPox and COVID-19 simultaneously, posted between 7 May 2022 and 3 March 2023, were studied. The findings and contributions of this study are manifold. First, the results of sentiment analysis using the VADER approach show that nearly half the tweets had a negative sentiment. It was followed by tweets that had a positive sentiment and tweets that had a neutral sentiment, respectively. Second, this paper presents the top 50 hashtags used in these tweets. Third, it presents the top 100 most frequently used words in these tweets after performing tokenization, removal of stopwords, and word frequency analysis. Finally, a comprehensive comparative study that compares the contributions of this paper with 49 prior works in this field is presented to further uphold the relevance and novelty of this work.

Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform (preprint)

Biological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.

Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age (preprint)

ObjectiveBeginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. DesignWe conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. ResultsCompared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. ConclusionThese results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare ([~]1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver. What is already known on this topicClusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent. What this study addsSARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. How this study might affect research, practice or policyDespite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.

Safety and Efficacy of Nirmatrelvir/Ritonavir in Advanced Kidney Disease (preprint)

Background: Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ³ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ≥ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Methods: We performed a retrospective cohort study of hospitalized and non-hospitalized patients with a confirmed diagnosis of COVID-19 in Hong Kong, China, for an observation period from 1 January 2022 to 31 December 2022 (during the omicron BA.2 and BA.5 variant wave). Adult COVID-19 patients (age ≥ 18 years) were selected from medical records held by the Hospital Authority of Hong Kong. We included all patients with COVID-19 regardless of disease severity at baseline having chronic kidney disease (CKD) stage 4 or above (i.e with eGFR < 30 ml/min per 1.73m2) with or without dialysis who receive either nirmatrelvir/ritonavir or molnupiravir. Outcomes at day 90 post-treatment of each treatment arm (nirmatrelvir/ritonavir v.s. molnupiravir) were analyzed and compared. All-cause mortality, respiratory outcomes including mechanical ventilation and non-invasive ventilation, cardiovascular events including myocardial infarction and ischemic stroke, and hepatic complications including elevated liver enzymes were analyzed. Time-to-event analysis was performed for the designated outcomes using univariate and multivariate Cox proportional hazard model regression for unadjusted and adjusted hazard ratios (HR).Findings: We included 454 and 5,880 CKD stage 4 or above patients receiving nirmatrelvir/ritonavir and molnupiravir respectively from public clinics and hospitals managed by the Hospital Authority in Hong Kong during the period. At 90 days, 662 (10.4%) patients of the combined cohort experienced all-cause mortality. Nirmatrelvir/ritonavir group had significant lower all-cause mortality than molnupiravir group (6.82% vs 10.7%) with unadjusted HR of 0.67 (95% CI 0.472 - 0.97, p=0.0337*). After adjusting for sex, age, hypertension, diabetes mellitus, history of myocardial infarction and dialysis in multi-variate analysis, nirmatrelvir/ritonavir group was still associated with superior 90-day survival with adjusted HR of 0.60 (95% CI 0.48 - 0.992, p = 0.0452*). Composites of mechanical and non-invasive ventilation rate were similar in nirmatrelvir/ritonavir and molnupiravir groups (0.96% vs 1.10%, p=0.651). Nirmatrelvir/ritonavir group had higher proportion of patients who received non-invasive ventilation (1.10% vs 0.42%, p = 0.0383*) and trended towards fewer patients requiring mechanical ventilation although statistical significance was not reached (0% vs 0.59%, p = 0.996). There were no significant differences in rate of myocardial infarction (0.88% vs 2.14%, p = 0.0844) and ischemic stroke (0.22% vs 0.61%, p = 0.34) between nirmatrelvir/ritonavir and molnupiravir groups. Hepatic impairment, defined by elevated alanine aminotransferase concentration ≥ 2X upper limit of normal (ULN), was present in 1.45% and 0.94% of patients in nirmatrelvir/ritonavir and molnupiravir groups respectively (p=0.523).Interpretation: Nirmatrelvir/ritonavir is safe and efficacious when compared to molnupiravir in patients with advanced kidney disease.Funding: Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong Special Administrative Region, China and Mr. Lee Won Keung Donation Fund.Declaration of Interest: The authors report no conflict of interest.Ethical Approval: The study was approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster. Informed consent from individual patient was waived as the study involved analysis of anonymized data from hospital registry only. The study was performed in compliance with the Declaration of Helsinki.

Attitudes of vaccination workers toward COVID-19 vaccination in patients with chronic liver disease (preprint)

Objectives Vaccination workers play an important role in the acceptance of various vaccines in patients with chronic liver diseases. We mainly investigated the attitude of vaccination workers toward COVID-19 vaccination in patients with chronic liver disease.Methods An anonymous, population-based, cross-sectional online survey were completed by 721 out of 1008 (71.5%) vaccination workers from July 1st to July 14th, 2022, in patients with chronic liver disease in Taizhou, China. The data were uploaded to Wen-Juan-Xing, one of the largest online platforms for collecting survey data.Results We found that only 51.9% of vaccination workers recommended all chronic liver diseases vaccinations. 81% of vaccination workers fully recommended vaccination in patients with fatty liver and chronic hepatitis B, while 53.1% of them fully recommended in patients with cirrhosis and liver cancer. Logistic regression analysis showed that vaccination workers who had undergone systematic training were more likely to recommend that patients with four chronic liver diseases get vaccinated (OR: 1.59; 95% CI: 1.05–2.43, p = 0.030). Vaccination workers that believed it is safe to vaccinate against patients with four chronic liver diseases were likely to recommend (OR: 8.12; 95% CI: 1.84–35.88, p = 0.006).Conclusion Vaccination workers who hold a positive attitude towards recommending vaccination for patients with chronic liver disease needs to be improved. Strengthening the training of vaccination workers could improve vaccine immunization coverage.

A Systematic Review and Meta-Analysis on Chatgpt and its Utilization in Medical and Dental Research (preprint)

Background: Since its release, ChatGPT has taken the world by storm with its utilisation in various fields of life. This review's main goal was to offer a thorough and fact-based evaluation of ChatGPT's potential as a tool for medical and dental research, which could direct subsequent research and influence clinical practises. Methods: Different online databases were scoured for relevant articles that were in accordance with the study objectives. A team of reviewers was assembled to devise a proper methodological framework for inclusion of articles and meta-analysis. Results: 11 descriptive studies were considered for this review that evaluated the accuracy of ChatGPT in answering medical queries related to different domains such as systematic reviews, cancer, liver diseases, diagnostic imaging, education, and COVID-19 vaccination. The studies reported different accuracy ranges, from 18.3% to 100%, across various datasets and specialties. The meta-analysis showed an odds ratio (OR) of 2.25 and a relative risk (RR) of 1.47 with a 95% confidence interval (CI), indicating that the accuracy of ChatGPT in providing correct responses was significantly higher compared to the total responses for queries. However, significant heterogeneity was present among the studies, suggesting considerable variability in the effect sizes across the included studies. Conclusion: The observations indicate that ChatGPT has the ability to provide appropriate solutions to questions in the medical and dentistry areas, but researchers and doctors should cautiously assess its responses because they might not always be dependable. Overall, the importance of this study rests in shedding light on ChatGPT's accuracy in the medical and dentistry fields and emphasizing the need for additional investigation to enhance its performance.

Implications of COVID-19 for the busy gastroenterologist.

Coronavirus disease 2019 (COVID-19) is an infection caused by a novel coronavirus (SARS-CoV-2) originated in China in December 2020 and declared pandemic by WHO. This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2). The clinical symptoms of COVID-19 patients include fever, cough, and fatigue. Gastrointestinal symptoms (diarrhea, anorexia, and vomiting) may be present in 50% of patients and may be associated with worst prognosis. Other risk factors are older age, male gender, and underlying chronic diseases. Mitigation measures are essential to reduce the number of people infected. Hospitals are a place of increased SARS-CoV-2 exposure. This has implications in the organization of healthcare services and specifically endoscopy departments. Patients and healthcare workers safety must be optimized in this new reality. Comprehension of COVID-19 gastrointestinal manifestations and implications of SARS-CoV-2 in the management of patients with gastrointestinal diseases, under or not immunosuppressant therapies, is essential. In this review, we summarized the latest research progress and major societies recommendations regarding the implications of COVID-19 in gastroenterology, namely the adaptations that gastroenterology/endoscopy departments and professionals must do in order to optimize the provided assistance, as well as the implications that this infection will have, in particularly vulnerable patients such as those with chronic liver disease and inflammatory bowel disease under or not immunosuppressant therapies.

COVID-19 and the liver: overview.

On 12 March 2020, the WHO declared that the coronavirus disease 2019 (COVID-19) constitutes a pandemic. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19 related liver damage/dysfunction is due mainly to the viral infection by itself or other coexisting conditions, such as the use of potentially hepatotoxic medications and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Individuals at high risk for severe COVID-19 are typical of older age and/or present with comorbid conditions such as diabetes, cardiovascular disease, and hypertension. This is also the same profile for those at increased risk for unrecognized underlying liver disease, especially nonalcoholic fatty liver disease. This could make them more susceptible to liver injury from the virus, medications used in supportive management, or hypoxia. So the aim of this review was to illustrate the clinical implications of COVID-19 on the liver in healthy and diseased states as well as the implications of common liver disorders on the outcome of COVID-19.

Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases.

The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.

MINIMAL LIVER ENZYMES ABNORMALITIES AT ADMISSION ARE RELATED TO SEVERE COVID-19 CLINICAL COURSE IN A LARGE BRAZILIAN COHORT.

BACKGROUND: COVID-19 is a multisystemic disease, primarily affecting the respiratory system. Liver involvement is frequent, but the impact on the clinical course and outcomes are controversial. OBJECTIVE: The aim was to assess liver function at the admission and evaluate its effects on severity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective study of hospitalized patients in a tertiary hospital in Brazil, with a PCR-confirmed SARS-CoV-2 infection between April and October 2020. 1080 out of 1229 patients had liver enzymes on admission and were divided in two cohorts, based on the presence or absence of abnormal liver enzymes (ALE). Demographic, clinical, laboratory, imaging, clinical severity, and mortality were evaluated. Patients were followed until discharge, death or transfer to another institution. RESULTS: Median age was 60 years and 51.5% were male. The more frequent comorbidities were hypertension (51.2%), and diabetes (31.6%). Chronic liver disease and cirrhosis were present in 8.6% and 2.3%, respectively. ALE (aminotransferases higher than 40 IU/L) were present in 56.9% of patients [mild (1-2 times): 63.9%; moderate (2-5 times): 29.8%; severe (>5 times): 6.3%]. Male gender [RR 1.49, P=0.007], increased total bilirubin [RR 1.18, P<0.001] and chronic liver disease [RR 1.47, P=0.015] were predictors of abnormal aminotransferases on admission. Patients with ALE had a higher risk of disease severity [RR 1.19; P=0.004]. There was no association among ALE and mortality. CONCLUSION: ALE is common in COVID-19 hospitalized patients and were independently correlated with severe COVID-19. Even mild ALE at admission may be a severity prognostic marker.

Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease.

Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease. Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report. Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16-0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11-5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07-74.61, p = 0.043) were more likely to prolong the time from infection to recovery. Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.

The Beneficial Role of Phytochemicals and Vitamins in Viral-Induced Liver Failure: Evidence from Clinical Studies (preprint)

Probably one of the biggest global challenges is viral epidemics, nowadays. The COVID-19 crisis proved that the more foresight we have to find effective compounds in various aspects, the better we can deal with viral epidemics. Different types of viruses directly or indirectly affect liver function. Therefore, an important aspect of combating viral infections is protecting the liver as a vital human organ.Natural compounds as a rich source of potential hepatoprotective drugs have been interested. Several in vitro and in vivo researches have been conducted to investigate the effectiveness of phytochemicals and vitamins on liver failure caused by a viral infection, but few of these compounds have been studied in the clinical phase, and most of them have had acceptable effectiveness. In this review, we focused on the findings of clinical studies that have addressed the role of phytochemicals and vitamins in reversing liver dysfunction associated with viral infections.

Mechanisms of severe acute respiratory syndrome coronavirus-2 induced liver damage and alteration of some liver biomarkers: A review.

The most serious problem for people suffering from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is liver damage. The liver is a frequently affected organ due to the metabolizing and detoxifying functions of several endogenous and exogenous molecules. In COVID-19-affected individuals, even moderate loss of hepatic function could dramatically affect the therapeutic efficacy of antiviral drugs metabolized in the liver. The clear mechanism of hepatocellular damage from SARS-CoV-2 infection is not fully understood. The main objective of this review is to identify potential mechanisms of SARS-2 induced liver damage, treatment outcomes in SARS-CoV-2-infected patients, and future direction. Electronic databases including Web of Science, Google Scholar, MEDLINE, Scopus, and Cochrane library were used to systematically search without limitation of publication date and status. Observational, retrospective cohort, prospective case-control, cohort studies, cross-sectional studies, or clinical trials were included. Liver damage in coronavirus patients is characterized by histopathological changes and abnormal elevation of some liver function tests. These abnormalities include elevation of Alanine aminotransferase, Aspartate aminotransferase, Gamma-glutamyl transferase, Alkaline phosphatase, and Serum bilirubin levels. Histopathological changes of the liver might consist of complete or partial thrombosis of the portal and sinusoidal vessels, portal tract fibrosis, and focally markedly enlarged and fibrotic hepatocytes. Understanding the fundamental molecular and immunological processes of COVID-19-related liver injury is essential for the selection of appropriate drugs and the logical development of successful treatment.

SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups.

Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.

Alcohol-Associated Liver Disease Mortality Rates by Race Before and During the COVID-19 Pandemic in the US.

This cross-sectional study examines the national- and state-level age-adjusted mortality rates for alcohol-associated liver disease in 4 racial groups, with a focus on the American Indian or Alaska Native population.