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.

Nutritional Approaches in Children with Overweight or Obesity and Hepatic Steatosis.

Childhood obesity is a global public health problem. Worldwide, 41 million children under 5 years and 340 million children and adolescents between 5 and 19 years are overweight. In addition, the recent COVID-19 epidemic has further amplified this social phenomenon. Obesity is a condition associated with various comorbidities, such as nonalcoholic fatty liver disease (NAFLD). The pathophysiology of NAFLD in obesity is intricate and involves the interaction and dysregulation of several mechanisms, such as insulin resistance, cytokine signaling, and alteration of the gut microbiota. NAFLD is defined as the presence of hepatic steatosis in more than 5% of hepatocytes, evaluated by histological analysis. It can evolve from hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Body weight reduction through lifestyle modification remains the first-line intervention for the management of pediatric NAFLD. Indeed, studies suggest that diets low in fat and sugar and conversely rich in dietary fibers promote the improvement of metabolic parameters. This review aims to evaluate the existing relationship between obesity and NAFLD in the pediatric population and to assess the dietary patterns and nutritional supplementations that can be recommended to prevent and manage obesity and its comorbidities.

Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France.

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.

Why Did Downstaging in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) Not Result in a Mortality Benefit: Exploratory Analysis of a Randomised Controlled Trial (preprint)

Background: To address the disparity in UKCTOCS between decrease in advanced stage disease and lack of mortality reduction in tubo-ovarian cancer (OC) in the multimodal screening (MMS) compared to no screening (C) group, we undertook exploratory analyses by histotype. Methods: In UKCTOCS, 202562(50625 MMS;50623 USS;101314C) eligible women were randomised (2001-5) and followed up till 30June2020. Screening group participants underwent annual screening till 31Dec2011. An outcomes committee adjudicated on OC diagnosis, histotype, stage and cause of death. Treatment details were extracted from hospital records. In women diagnosed with cancer (high-grade serous, HGSC; non-high-grade serous, non-HGSC) at censorship (31Dec2014), we compared descriptive statistics(p-values) and survival from randomisation (Versatile test) in MMS and USS group separately to the C group.Findings: In both the MMS(259/50625) and C(520/101314) groups, 0.51% developed HGSC. In HGSC, on an intention-to-screen analysis, there was a reduction in advanced(III/IV/unable to stage) stage disease(MMS75%195/259; C86%,446/520;p=0·0003), higher rates of primary surgery(MMS61%,158/259; C42%,219/520;p<0·0001), zero residual disease(MMS 46%,119/259; C30%,157/520;p<0·0001) and treatment including surgery and chemotherapy(MMS74%,192/259; C64%,331/520;p=0·003) in the MMS compared to C group. There was no difference in those receiving first line combination chemotherapy(MMS55%, 142/259; C56%, 293/520;p=0·687). There was evidence of improvement in survival from randomisation in HGSC in MMS(MMS21%,54/259; C14%,74/520;p=0·042) in the case only analysis. No differences were observed in the comparisons in USS or non-HGSC in the MMS versus C group.Interpretation: Our findings provide robust evidence for the first time that screening can detect HGSC earlier and result in improved treatment outcomes. The lack of overall mortality benefit is likely related to the magnitude of early detection and treatment improvement as well as tumour biology. The findings do not support use of surrogate end points in place of disease-specific mortality.Funding National Institute for Health Research, MRC, Cancer Research UK, The Eve Appeal.Trial Registration: This trial is registered with ISRCTN number 22488978; ClinicalTrials.gov number NCT00058032.Funding: The Long Term Follow Up (LFTU) UKCTOCS is supported by National Institute for Health Research (NIHR HTA grant 16/46/01), Cancer Research UK (CRUK) and The Eve Appeal. UKCTOCS was funded by Medical Research Council (G9901012 and G0801228), CRUK (C1479/A2884), and the Department of Health, with additional support from The Eve Appeal. Researchers at UCL are supported by the NIHR University College London Hospitals (UCLH) Biomedical Research Centre and MRC CTU at UCL core funding (MR_UU_12023).Declaration of Interest: UM has stock ownership awarded by University College London (UCL) in Abcodia, which holds the licence for ROCA (between 1 April 2011 and 30 October 2021). She has received grants from the Medical Research Council (MRC), Cancer Research UK, the National Institute for Health Research (NIHR), and The Eve Appeal. She holds patent number EP10178345.4 for Breast Cancer Diagnostics. MP has received grants and AG-M, MB, and AR, have been funded by grants from MRC, CRUK, NIHR, and The Eve Appeal. UM, SA and AG-M received research funding from iLOF (intelligent Lab on Fiber), Micronoma, Imperial College London, QIMR Berghofer Medical Research Institute, Innovate UK, Mercy Bioanalytics, University of Innsbruck, NHMRC and MRC Proximity to Discovery Industrial Connectivity Award. UM has received an honorarium from NY Obstetrical Society and reimbursements for invited talks from NY Obstetrical Society (USA), National Cancer Policy Forum (USA), and Robinson College, Cambridge. She is a member of ACED (International Alliance for Cancer Early Detection) Gynaecological Cancers Working Group, and a member of Advisory Boards or Committees for Tina’s Wish, Mixed COVID Vaccines study, India, Yorkshire Cancer Research, GEM3, NOVEL, and PROTECTOR. UM and SA received research funding from RNA Guardian and Dana Faber. MP was a member of the EME funding committee while the project was active. MB reports funding from NIHR UCL Hospitals Biomedical Research Centre. SA received funding from Abcodia. AG-M is a member of ACED (International Alliance for Cancer Early Detection) Gynaecological Cancers Working Group, and Co-Director Research Domain Trials for ACED. RM has received grants from The Eve Appeal, Rosetrees Charity, and Barts Charity, Yorkshire Cancer Research, Ovacure, BGCS, GSK, personal fees from AstraZeneca and consulting fees from Everything Genetics Limited. AMcG was a member of NIHR HTA and EME Editorial Board from 1 April 2012 to 31 March 2022. LJF received a grant form MRC for the psycho-social arm of the UKCTOCS study 2001-2013. SJS holds the (expired) patent for ROCA, patented and owned by Massachusetts General Hospital and Queen Mary University of London, licenced to Abcodia. He reports personal fees from Abcodia, Guardant Health, and Freenome, outside the submitted work, funding from NIHR, NCI and Mercy Bioanalytics and consulting fees from Guardant Health. He participates on Board of SISCAPA Assay Technologies and has stock ownership for this. IJJ reports grants from Eve Appeal Charity, Medical Research Council, Cancer Research UK, and NIHR during the conduct of the study. He co-invented the ROCA in 1995, it was patented by Massachusetts General Hospital and Queen Mary University of London and is owned by these universities. Massachusetts General Hospital and Queen Mary University of London granted a licence to ROCA to Abcodia in 2014. IJJ is a board member, shareholder, and consultant to Abcodia and has rights to royalties from sales of the ROCA. He founded (1985), was a trustee of (2012–14), and is now an Emeritus trustee (2015–present) of The Eve Appeal, one of the funding agencies for UKCTOCS. NS received an honorarium from Astra-Zeneca-MSD and GlaxoSmithKline for participation in Advisory board. All other authors declare no competing interests.Ethical Approval: Approved by the UK North West MREC (00/8/34) on June 23, 2000.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Effect of Pre-Transplant Covid-19 Exposure on Post-Liver Transplant Clinical Outcomes.

BACKGROUND: COVID-19 has led to an unprecedented global health crisis. This situation caused an immediate reduction in solid organ transplantation activity. This study aimed to present the follow-up results of patients with chronic liver disease who underwent liver transplantation (LT) after a history of COVID-19 infection. METHODS: Sociodemographic characteristics and clinicopathological data of 474 patients who underwent LT at Inonu University Liver Transplant Institute between March 11, 2020 and March 17, 2022 were prospectively recorded and analyzed retrospectively. Among these, the data of 35 patients with chronic liver disease who were found to be exposed to COVID-19 infection in the pre-LT period were analyzed for this study. RESULTS: The median body mass index, Child score, and Model for end-stage liver disease/ Pediatric end-stage liver disease scores of the 35 patients were calculated as 25.1 kg/m2 (IQR: 7.4), 9 points (IQR: 4), and 16 points (IQR: 10), respectively. Graft rejection occurred in 4 patients at a median of 25 days post-transplant. Five patients underwent retransplantation at a median of 25 days post-transplant. The most common cause of retransplantation is early hepatic artery thrombosis. There were 5 deaths during postoperative follow-up. Mortality developed in 5 (14.3%) patients exposed to COVID-19 infection in the pretransplant period, whereas mortality occurred in 56 (12.8%) patients not exposed to COVID-19 infection. There was no statistically significant difference in mortality between the groups (P = .79). CONCLUSIONS: The results of this study showed that exposure to COVID-19 before LT does not affect post-transplant patients and graft survival.

MANAGEMENT OF RISK FACTORS FOR HEALTH CARE WORKERS AFTER INITIAL CONTACT WITH PATIENTS INFECTED WITH SARS-CoV-2 IN NIAMEY, THE CENTER OF THE EPIDEMIC IN NIGER (preprint)

Background: The covid-19 pandemic is caused by a new corona virus called SARS Cov-2. Health care workers are particularly exposed target. Aim: this study aims to analyze the risk factors of SARS-Cov-2 infection in health workers who have been in contact with positive patient. Methods: This is a prospective cohort conducted among health workers from March 2022 to January 2021 in health care facilities in Niamey. A questionnaire was administrated at inclusion. rRT-PCR was performed if clinical signs were present. ELISA testing was performed at baseline, day15 and day 30. The chi-square or Fisher test, Kaplan-Meir survival model, Cow regression and logistic regression were used as statistical test. Results: 259 health workers were included. More than half of the respondents were female. 45.95% of the participants were nurses and 36.68% were physicians. The prevalence of Covid-19 was 28.8%. 56.4% of the participants had positive serology at day 30. The risk factors associated with Covid-19 were professional category (p=0.024). Membership structure (p<0.001) and the chronic liver disease (p=0.034). Hand hygiene (p=0.019) and alcohol-based hand cleaning (p<0.001) protects against the occurrence of SARS-Cov-2 infection. According to the characterization of the preventive measures those who practiced them rarely were associated with a positive rRT-PCR and those who practice them occasionally or most of the time were associated with negative serology and rRT-PCR. Conclusion: Comorbidities, function and affiliation are the main risk factors for Covid-19 and hand hygiene is a protective factor.

Does COVID-19 infection significantly affect liver transplantation? Results of liver transplantation in the COVID-19 era at a single, high-volume centre.

BACKGROUND: Liver transplantation is a proven management method for end-stage cirrhosis and is estimated to have increased life expectancy by 15 years. The COVID-19 pandemic posed a challenge to patients who were candid for a solid-organ transplant. It has been suggested that the outcomes of liver transplants could be adversely affected by the infection, as immunosuppression makes liver transplant candidates more susceptible to adverse effects while predisposing them to higher thrombotic events. MATERIAL AND METHODS: In this retrospective study, the cases who received liver transplants from January 2018 to March 2022 were assessed regarding early postoperative mortality rate and hepatic artery thrombosis (HAT) with COVID-19 infection. This study included 614 cases, of which 48 patients were infected. RESULTS: This study shows that the early COVID-19-related early postoperative mortality rates substantially increased in the elective setting (OR: 2.697), but the results for the acute liver failure were insignificant. The average model for end-stage liver disease score increased significantly during the pandemic due to new regulations. Although mortality rates increased during the pandemic, the data for the vaccination period show that mortality rates have equalised with the prepandemic era. Meanwhile, COVID-19 infection is assumed to have increased HAT by 1.6 times in the elective setting. CONCLUSION: This study shows that COVID-19 infection in an acute liver failure poses comparatively little risk; hence transplantation should be considered in such cases. Meanwhile, the hypercoagulative state induced by the infection predisposes this group of patients to higher HAT rates.

The road to pandemic recovery: Tracking COVID-19's impact on cirrhosis care and outcomes among 111,558 Veterans.

BACKGROUND AIMS: This study aimed to evaluate quarterly trends in process and health outcomes among Veterans with cirrhosis and assess the factors associated with cirrhosis outcomes before and during the COVID-19 pandemic. APPROACH RESULTS: US Veterans with cirrhosis were identified using the Veterans Health Administration Corporate Data Warehouse. Quarterly measures were evaluated from September 30, 2018, through March 31, 2022, including twice yearly screening for hepatocellular carcinoma (HCC-6), new HCC, surveillance for or treatment of esophageal varices, variceal bleeding, all-cause hospitalization, and mortality. Joinpoint analyses were used to assess the changes in trends over time. Logistic regression models were used to identify the demographic and medical factors associated with each outcome over time. Among 111,558 Veterans with cirrhosis with a mean Model for End-stage Liver Disease-Sodium of 11±5, rates of HCC-6 sharply declined from a prepandemic peak of 41%, to a nadir of 28%, and rebounded to 36% by March 2022. All-cause mortality did not significantly change over the pandemic, but new HCC diagnosis, EVST, variceal bleeding, and all-cause hospitalization significantly declined over follow-up. Quarterly HCC diagnosis declined from 0.49% to 0.38%, EVST from 50% to 41%, variceal bleeding from 0.15% to 0.11%, and hospitalization from 9% to 5%. Rurality became newly, significantly associated with nonscreening over the pandemic (aOR for HCC-6=0.80, 95% CI 0.74 to 0.86; aOR for EVST=0.95, 95% CI 0.90 to 0.997). CONCLUSIONS: The pandemic continues to impact cirrhosis care. Identifying populations at the highest risk of care disruptions may help to address ongoing areas of need.

Negative impact of the pandemic on hospital admissions, morbidity and early mortality for acute cirrhosis decompensation.

INTRODUCTION: The global pandemic has diverted resources away from management of chronic diseases, including cirrhosis. While there is increasing knowledge on COVID-19 infection in liver cirrhosis, little is described on the impact of the pandemic on decompensated cirrhosis admissions and outcomes, which was the aim of this study. METHODS: A single-centre, retrospective study, evaluated decompensated cirrhosis admissions to a tertiary London hepatology and transplantation centre, from October 2018 to February 2021. Patients were included if they had an admission with cirrhosis decompensation defined as new-onset jaundice or ascites, infection, encephalopathy, portal hypertensive bleeding or renal dysfunction. RESULTS: The average number of admissions stayed constant between the pre-COVID-19 (October 2018-February 2020) and COVID-19 periods (March 2020-February 2021). Patients transferred in from secondary centres had consistently higher severity scores during the COVID-19 period (UK Model for End-Stage Liver Disease 58 vs 54; p=0.007, Model for End-Stage Liver Disease-Sodium 22 vs 18; p=0.006, EF-CLIF Acute Decompensation (AD) score 55.0 vs 51.0; p=0.055). Of those admitted to the intensive care without acute-on-chronic liver failure, there was a significant increase in AD scores during the COVID-19 period (58 vs 48, p=0.009). In addition, there was a trend towards increased hospital readmission rates during the COVID-19 period (29.5% vs 21.5%, p=0.067). When censored at 30 days, early mortality postdischarge was significantly higher during the COVID-19 period (p<0.001) with a median time to death of 35 days compared with 62 days pre-COVID-19. DISCUSSION: This study provides a unique perspective on the impact that the global pandemic had on decompensated cirrhosis admissions. The findings of increased early mortality and readmissions, and higher AD scores on ICU admission, highlight the need to maintain resourcing for high-level hepatology care and follow-up, in spite of other disease pressures.

Exploration of the Link Between COVID-19 and Alcoholic Hepatitis from the Perspective of Bioinformatics and Systems Biology (preprint)

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been suggested to purpose threats to health of mankind. Alcoholic hepatitis (AH) is a life-threatening acute and chronic liver failure that takes place in sufferers who drink excessively. During the epidemic, AH has an increasing incidence of severe illness and mortality. However, for these two diseases, the intrinsic relationship of molecular pathogenesis, as well as common therapeutic strategies are still poorly understood. Methods: The transcriptome of the COVID-19 and AH has been compared to obtain the altered genes and hub genes were screened out through protein-protein interaction (PPI) network analysis. Via gene ontology (GO), pathway enrichment and transcription regulator analysis, a deeper appreciation of the interplay mechanism between hub genes were established. Results: With 181 common differentially expressed genes (DEGs) of AH and COVID-19 were obtained, 10 hub genes were captured. Follow-up studies located that these 10 genes typically mediated the diseases occurrence by regulating the activities of the immune system. Other results suggest that the common pathways of the two ailments are enriched in regulating the function of immune cells and the release of immune molecules. Conclusion: This study reveals the common pathogenesis of COVID-19 and AH and assist to discover necessary therapeutic targets to combat the ongoing pandemic induced via SARS-CoV-2 infection and acquire promising remedy strategies for the two diseases.

Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis (preprint)

Understanding the biological basis of clinical risk factors for severe COVID–19 is required to ensure at–risk patient populations receive appropriate clinical care. Patients with decompensated liver cirrhosis, in particular those classified as Childs–Pugh class B and C, are at increased risk of severe COVID–19 upon infection with SARS–CoV–2. The biological mechanisms underlying this are unknown. We hypothesised this may be due to changes in expression levels of intrinsic antiviral proteins within the serum as well as alterations in the innate immune response to SARS–CoV–2 infection. We identified significant alterations in the serum proteome of patients with more severe liver disease and an increased frequency of auto–antibodies capable of neutralising type I interferons. No difference in SARS–CoV–2 pseudoparticle infection or live SARS–CoV–2 virus infection was observed with serum from decompensated cirrhotic patients. Principal component analysis of the serum proteome identified two main clinical parameters associated with serum proteome changes – aetiology and MELD–Na score. Among patients with MELD-Na scores >20 we detected significant inhibition of IFN–α2b and IFN-α8 signalling but not IFN–β1a, mediated by auto–antibodies. Our results suggest pre–existing neutralising auto–antibodies targeting type I IFN may increase the likelihood of severe COVID–19 in chronic liver disease patients upon SARS–CoV–2 infection and may also be of relevance to other viral infections in this patient population.

Musculoskeletal Manifestations, Post-COVID Syndrome, Relationship with Laboratory Parameters in Hospitalized Patients Infected with COVID-19 (preprint)

Background: This study aims to characterize the prevalence of musculoskeletal manifestations in hospitalized COVID-19 patients and the relationship between C-Reactive protein (CRP) and interleukin levels.Methods: A medical records review study was performed on patients at Baskent University between March 7 and December 31, 2020. The study included hospitalized patients above 18 years diagnosed with COVID-19 by polymerase chain reaction. Pregnant individuals, those with end-stage disease or missing documentation were excluded. Patient demographics and laboratory results were obtained from electronic health records and previous study performed in the same hospital. The relationship between musculoskeletal manifestations, CRP, and interleukin levels were determined. A Pvalue of less than .05 was consideredstatistically significant.Results: Totally, 109 patients were analyzed; 34.86% (n = 38) of the patients had arthralgia, 1.83% (n = 2) had arthritis, 41.28% (n = 45) underwentfatigue, and 32.11% (n = 35) experiencedpost-COVID syndrome. There was no correlation between musculoskeletal manifestations, CRP, and interleukin levels (P > .05). There was positive correlation between post-COVID syndrome, fatigue, duration of O2 support, duration of hospitalization (P < .05), and the patients were elderly. CRP levels were positively correlated with duration of hospitalization, duration of O2 support, history of intensive care, and duration of intensive care (P < .05). Interleukin 6 levels were positively correlated with CRP levels, duration of hospitalization, and O2 support duration (P < .05), but there was no correlation with interleukin 10 levels (P > .05).Conclusion: There was no correlation between musculoskeletal manifestations, CRP, and interleukin levels. Patients who are hospitalized, elderly, abnormally fatigued, or O2 supported should be followed for post-COVID syndrome.

Mortality due to SARS COV-2 And its Associated Factors in East Shewa Zone Treatment Centers, Ethiopia, 2022: A retrospective cross-sectional study (preprint)

Background: Coronavirus disease (COVID-19) is an infectious disease that is caused by the SARS-CoV-2virus. The objective of this study was to determine SARS COV-2 Mortality and its associated factors in East Shewa Zone Treatment centers, Oromia, Ethiopia, 2022. The study of these types of viral infection will add new insight into the most common causes of mortality in SARS-CoV-2infection and the most common co-morbidities associated with the disease in the East Shewa Zone. Methods: The study was conducted on patients who were admitted to Adama Hospital medical college and Modjo Primary Hospital for SARS-COV 2 treatment. The study period was from March 2020- Dec 2022 GC. The study population was SARS-COV 2 patients who come to Adama Hospital and Medical College and Modjo Primary Hospital for treatment. All eligible SARS-CoV-2 patients' data were collected from Both Adama and Modjo treatment center SARS-CoV-2 accession registration book and medical record card. Result: A total of 409 patient data were collected from which 199 were from Adama Hospital and Medical College and 210 samples were collected from Modjo Primary Hospital Treatment center. The study design was a retrospective Cross-sectional study. The most affected age group in terms of mortality was the age group between 60-69 years old which suffers a 45.28% death rate. The major sign symptoms identified include cough (80.4%), Shortness of breath (66.7%) followed by fever (43.2%). SARS-CoV-2 Comorbidity was detected in 152 (37.2%) patients. Pneumonia was identified as the major comorbid disease to be recorded with 89(21.8%) cases. Other major comorbidities include Hypertension (16.9%) and Diabetes Mellites (13.9%). The least identified comorbidities were anemia (0.2%), Rectal cancer (0.2%), breast cancer (0.5%), and Chronic liver disease. Conclusion: Nearly one in four (22.7%) SARS-COV 2 patients admitted for treatment to Adama Hospital and Medical College and Modjo Primary Hospital did not make their way out of treatment Hospitals alive. Pneumonia was identified as the major comorbid disease to be recorded with 89(21.8%) cases.

Immune response of primary and booster immunity of SARS-CoV-2 vaccination among patients with chronic liver disease: a real-world study (preprint)

Aim: The present study discussed the humoral immune response and antibody dynamics after primary and booster immunity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic liver disease (CLD) in the real world. Thus, it provided data to develop SARS-CoV-2 vaccination strategy. Methods: Patients with confirmed CLD and completed primary or booster immunity of SARS-CoV-2 vaccines were enrolled. Serological specimens were collected after primary or booster immunity of SARS-CoV-2 vaccines to detect novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD). Thus, we could evaluate the humoral immune response and antibody dynamics after primary and booster immunity of SARS-CoV-2 vaccines among patients with CLD. Simultaneously, baseline demographics, liver disease-related situations, comorbidity-related situations, SARS-CoV-2 vaccination information, and laboratory examination-related indicators of patients were collected. Results: A total of 315 patients received SARS-CoV-2 vaccines, including 223 patients who completed the primary immunity of SARS-CoV-2 vaccines, 114 patients who completed booster immunity of SARS-CoV-2 vaccines, and 22 patients who underwent the antibody detection of SARS-CoV-2 vaccines after both primary and booster immunities. The positive rate of nCoV NTAb was 59.64% in Primary and 87.72% in Booster (P<0.001). The median level of nCoV NTAb was 11.53 AU/mL in Primary and 31.98 AU/mL in Booster (P<0.001). The positive rate of nCoV S-RBD was 69.06% in Primary and 91.23% in Booster (P<0.001). The median level of nCoV S-RBD was 21.60AU/mL in Primary and 112.65 AU/mL in Booster (P<0.001). After booster immunity of SARS-CoV-2 vaccines in 22 patients, the positive rate of nCoV NTAb increased from 59.09% to 86.36%, and that of nCoV S-RBD increased from 68.18% to 90.91%. The median level of nCoV NTAb increased from 11.24 AU /mL to 59.14 AU /mL after booster immunity. The median level of nCoV S-RBD increased from 27.28 AU/mL to 219.10 AU/mL. Compared to the antibody level of primary immunity, the median level of nCoV NTAb and nCoV S-RBD in 22 patients was increased by 5.26 and 8.03 times, respectively. Among 22 patients, 9 were negative for nCoV NTAb after primary immunity, while 6 were transformed positive after booster immunity, and the positive conversion rate of nCoV NTAb was 66.7%. On the other hand, 7 patients were negative for nCoV S-RBD after primary immunity, while 5 were transformed positive after booster immunity, and the positive conversion rate of nCoV S-RBD was 71.4%. Conclusion: Patients with CLD show improved humoral immune response after completing primary and booster immunity of SARS-CoV-2 vaccines, while booster immunity further improves the positive rate and antibody level of patients with CLD. Finally, the positive conversion rate among patients with primary immunity failure also can be improved after booster immunity. Keywords: immune response; primary and booster immunity; SARS-CoV-2 vaccination; chronic liver disease

A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity (preprint)

Host genetic susceptibility is a key risk factor for severe illness associated with COVID-19. Despite numerous studies of COVID-19 host genetics, our knowledge of COVID-19-associated variants is still limited, and there is no resource comprising all the published variants and categorizing them based on their confidence level. Also, there are currently no computational tools available to predict novel COVID-19 severity variants. Therefore, we collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. We further evaluated the classifier's predictions using feature importance analyses to investigate the biological properties of COVID-19 susceptibility variants, which identified conservation scores as the most impactful predictive features. The results of enrichment analyses revealed that genes carrying high-confidence COVID-19 susceptibility variants shared pathways, networks, diseases and biological functions, with the immune system and infectious disease being the most significant categories. Additionally, we investigated the pleiotropic effects of COVID-19-associated variants using phenome-wide association studies (PheWAS) in ~40,000 BioMe BioBank genotyped individuals, revealing pre-existing conditions that could serve to increase the risk of severe COVID-19 such as chronic liver disease and thromboembolism. Lastly, we generated a web-based interface for exploring, downloading and submitting genetic variants associated with COVID-19 susceptibility for use in both research and clinical settings (https://itanlab.shinyapps.io/COVID19webpage/). Taken together, our work provides the most comprehensive COVID-19 host genetics knowledgebase to date for the known and predicted genetic determinants of severe COVID-19, a resource that should further contribute to our understanding of the biology underlying COVID-19 susceptibility and facilitate the identification of individuals at high risk for severe COVID-19.

Safety and Immunogenicity of a Booster SARS-Cov-2 Vaccination in Patients with Chronic Liver Disease (preprint)

This article is aim to investigate the safety and immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine booster in patients with chronic liver disease(CLD). A total of 114 patients with CLD who received a SARS-CoV-2 vaccine booster were enrolled in this study. Serum samples were collected from enrolled patients at least 14 days after the booster dose and tested for SARS-CoV-2 neutralizing antibody (novel coronavirus neutralizing antibody, nCoV NTAb) and IgG antibody against SARS-CoV-2 spike binding domain(novel coronavirus spike receptor-binding domain antibodynCoV S-RBD antibody)levels. The positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD were 87.72% and 91.23%, respectively, after the booster injection of coronavirus disease 2019 (COVID-19) vaccine. The booster injection resulted in the production of nCov NTAb in 66.7% of patients and nCov-SRBD antibody in 71.43% of patients with CLD who failed basic immunization. After basic SARS-CoV-2 immunization, the booster SARS-CoV2 vaccine increased the serum conversion rate and the level of nCov NTAb and nCov-SRBD antibodies in patients with CLD (including patients with cirrhosis). The severity of the liver disease is related to the immune response to COVID-19 vaccine.

Concordance of ICD-10 Codes and the Clinical Diagnosis of Alcoholic Hepatitis.

INTRODUCTION: Many studies on alcoholic hepatitis (AH) use the International Classification of Disease (ICD) coding to identify patients. Data regarding the diagnostic accuracy of ICD codes for AH are limited. METHODS: A total of 151 patients with ICD-10 codes for AH were reviewed for the presence or absence of AH using standardized diagnostic criteria. RESULTS: Sixty-eight of the 151 patients met AH criteria, corresponding to a positive predictive value of 45%. Patients with AH experienced higher model for end-stage liver disease and mortality than those who did not ( P < 0.05). DISCUSSION: Our results suggest ICD-10 codes are not reliable for identifying AH. Studies using the ICD codes should be interpreted cautiously.

Liver transplantation in the Intensive Care Unit: twenty years experience in a center medium income on Peru.

Liver transplantation is the major treatment for end-stage liver disease. Postoperative care is a great challenge to reduce morbidity and mortality in patients. In this sense, management in the liver ICU allows hemodynamic management, coagulation monitoring, renal support, electrolyte disturbances, respiratory support and early weaning from mechanical ventilation and evaluation of the liver graft. OBJECTIVE: The present study shows the results of the management of liver transplant patients in 20 years of experience in a transplant center in a low- to middle-income country. MATERIALS AND METHODS: The medical records of 273 adult patients in the ICU in the immediate postoperative liver transplant were reviewed, from March 20, 2000 to November 30, 2020, including the effect of the pandemic caused by COVID-19. Liver-kidney, retransplanted, SPLIT, and domino transplant patients were excluded. RESULTS: The most frequent etiology for LTx was NASH (35%), the mean age was 49 years, MELD Score ranged 15 - 20 (47.5%), 21 - 30 (46%) > 30 (6.2%). ICU pre transplant stay 7%, average ICU stay: 7.8 days. APACHE average admission: 14.9 points. Weaning extubation of 91.8% patients in ICU and Fast Track in 8.2%. The most frequent respiratory complication was atelectasis 56.3%, pneumonia (31.3%); AKI 1 (60.9%), and 11.1% with hemodyalisis support (AKI3). Immunosuppression: Tacrolimus (8.9%). Post-operative ICU mortality was 6.2%. CONCLUSIONS: The management of liver transplantation in the ICU is essential to achieve optimal results in patients who present advanced liver disease and require advanced life support in the immediate postoperative period and thus optimize graft survival.

The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.

Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (-45%) and NAFLD (-35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.