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Background:: Since its declaration as a global pandemic on March11th 2020, COVID-19 has had a significant effect on solid-organ transplantation. The aim of this study was to analyze the impact of COVID-19 on Liver transplantation (LT) in United States. Method(s):: We retrospectively analyzed the United Network for Organ Sharing database regarding characteristics of donors, adult-LT recipients, and transplant outcomes during early-COVID period (March 11- September 11, 2020) and compared them to pre-COVID period (March 11 - September 11, 2019). Result(s):: Overall, 4% fewer LTs were performed during early-COVID period (4107 vs 4277). Compared to pre-COVID period, transplants performed in early-COVID period were associated with: increase in alcoholic liver disease as most common primary diagnosis (1315 vs 1187, P< 0.01), higher MELD score in the recipients (25 vs 23, P<0.01), lower time on wait-list (52 vs 84 days, P<0.01), higher need for hemodialysis at transplant (9.4 vs 11.1%, P=0.012), longer distance from recipient hospital (131 vs 64 miles, P<0.01) and higher donor risk index (1.65 vs 1.55, P<0.01). Early-COVID period saw increase in rejection episodes before discharge (4.6 vs 3.4%, P=0.023) and lower 90-day graft/patient survival (90.2 vs 95.1 %, P<0.01;92.2 vs 96.5 %, P<0.01). In multivariable cox-regression analysis, early-COVID period was the independent risk factor for graft failure at 90-days post-transplant (Hazard Ratio 1.77, P<0.01). Conclusion(s):: During early-COVID period in United States, overall LT decreased, alcoholic liver disease was primary diagnosis for LT, rate of rejection episodes before discharge was higher and 90-days post-transplant graft survival was lower.Copyright © 2022 The Author(s)
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Liver enzyme abnormalities occur frequently in patients diagnosed with Coronavirus disease 2019 (COVID-19). It has been suggested that patients with severe acute liver injury are more likely to be admitted to intensive care, require intubation or renal replacement therapy and their mortality rate is higher than patients without severe acute liver injury. This review article explores the possible aetiologies of liver dysfunction seen in patients with COVID-19 and also the effect of COVID-19 on patients with pre-existing liver disease. Finally, we suggest clinical approaches to treating a patient with liver enzyme disturbance and COVID-19 and also caring for patients who require liver transplantation in the COVID-19 era.Copyright © 2022 Bentham Science Publishers.
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Purpose: COVID-19 pandemic has had a significant impact on access to routine healthcare in both hospitalized and out-patient settings. This impact was also noted in various aspects of pre and post-transplant care of liver transplant (LT) recipients. The aim of our study was to analyze the direct and indirect impact of COVID-19 on mortality in patients with recent LT. Method(s): We retrospectively analyzed 30-day, 6-month and 1-year mortality data from the UNOS database in adult LT recipients from 3 distinct groups;Pre-COVID (March 11- September 10, 2019: LT and immediate follow-up care before pandemic), Para-COVID (September 11- March10, 2020: LT before pandemic and follow-up care during pandemic), and COVID (March 11- September 10, 2020: LT and follow-up care during pandemic). Result(s): 12,598 LTs were performed during the study period. During COVID period, there was increase in LT for alcoholic liver disease, average MELD score was higher, LT for hepatitis C decreased, use of thymoglobulin induction decreased and waiting time was shorter. During the 30-day period, overall mortality between 3 groups remained same. In the COVID group, mortality from graft failure was higher (7.4 vs 17.9%, p=0.07), rate of infection was lower (14% vs 4.2%, p=0.039), and incidence of graft rejection prior to discharge was higher. During the 6-month follow-up, overall mortality, mortality from malignancy and COVID, and graft failure increased significantly in the COVID group. During the 1-year follow-up period, mortality was highest in COVID group over para-COVID group and lowest in the pre-COVID group. In the COVID group, increased mortality was from graft failure and COVID. Overall mortality in the study cohort directly from COVID was 7.8%, which was highest in the COVID group. Multivariable cox regression for one year mortality showed that risk factors for mortality were COVID period [Hazard Ratio (95%CI) 1.22 (1.02-1.46), p=0.027], older age of recipient, diabetes, portal vein thrombosis, ventilation at the time of transplant, hemodialysis at the time of transplant, re-transplant, and prolonged cold ischemic time. Conclusion(s): COVID-19 significantly impacted LT short term outcomes with increased mortality seen from COVID directly as well as indirectly. During COVID, cautious and lower use of immuno-suppression was likely associated with higher rates of rejection and lower rates of infection. Disruptions in routine post-transplant follow-up likely contributed to increased death from graft failure, malignancy, and poor control of chronic medical conditions like diabetes. (Figure Presented).
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Objectives: Coronavirus disease 2019 (COVID-19) has had a global impact and is spreading quickly. ChuanKeZhi injection (CKZI) is widely used in asthma patients. In this paper, we aimed to explore active compounds of CKZ and determine potential mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology, molecular docking and dynamic simulation studies. Materials and Methods: We used the Systematic Pharmacology Database and Analysis Platform of Traditional Chinese Medicine (TCMSP) to screen active compounds and potential target proteins of CKZ. COVID-19 target genes were screened via the American National Center for Biotechnology Information (NCBI) gene database and human gene database (GeenCards). The protein interaction network was constructed by the Protein Interaction Network Database (Search Tool for the Retrieval of Interacting Genes/Proteins (STRING)) platform. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by the Metascape database. The main active compounds of CKZ were docked with angiotensin-converting enzyme 2 (ACE2), spike protein S1, and SARS-CoV-2-3CL pro and also docked with hub targets. We performed molecular dynamics (MD) simulation studies for validation. Results: We finally obtained 207 CKZ potential targets and 4681 potential COVID-19 targets. Key targets included mainly AKT1, TNF, IL6, VEGFA, IL1B, TP53, JUN, CASP3, etc. There were 217 Gene Ontology (GO) items in the GO enrichment analysis (p < 0.05). The main KEGG pathways included the advanced glycation end products (AGE)- receptor for AGE (RAGE) signalling pathway in diabetic complications, rheumatoid arthritis, chemical carcinogenesis-receptor activation, alcoholic liver disease, etc. Molecular docking and dynamics simulation studies both exhibited great binding capacity. Conclusions: Network pharmacology, molecular docking and dynamics simulation studies were used to identify the potential and key targets, pharmacological functions, and therapeutic mechanisms of CKZI in the treatment of COVID-19. CKZI may be an effective and safe drug in COVID-19 treatment. However, further work is needed for validation.
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Background & Aims: Prior studies have indicated the presence of hepatic inflammation (as signified by elevated liver function test (LFT) values), as conferring an escalated risk toward adverse outcomes in patients admitted with COVID-19. In line with this hypothesis, we study the various thresholds of LFTs and its associated prognostic risks toward COVID- 19 related hospital deaths Method: This was a single-center retrospective study involving patients admitted with COVID-19. Univariate Cox regression analysis identified the LFT variables significantly associated with our primary endpoint, in-hospital death. Subsequently, 500 iterations of thresholds were generated for each biomarker to estimate the prognostic relationship between biomarker and endpoint. Multivariate Cox regression and event-analyses were performed for each threshold to identify the minimal cutoffs at which the prognostic relationship was significant. Event curves were drawn for each significant relationship. Results: A total of 858 patients with COVID-19 were included with a median follow-up time of 5 days from admission. From the total, 90 patients passed away during admission (10.5%). The deceased cases were more likely to be older (66.2 vs 55.3y p<0.001);however, there was no difference in gender (male: 66 vs 56.2% p=0.11). Between the cases and controls (no-death), deceased cases had higher incidence of nonalcoholic fatty liver disease (7.78 vs 2.99% p=0.042), COPD (18.9 vs 7.80% p=0.001), lung cancer (4.44 vs 0.65% p= 0.009), ICU admissions (81.1 vs 26% p<0.001), and intubation events (84.4 vs 19.5% p<0.001), however there was no difference in alcohol use (21.1 vs 30.6% p=0.083) and alcoholic liver disease (5.56 vs 2.08% p=0.097). Upon univariate Cox analysis, the following LFT parameters were associated with in-hospital death: Bilirubin (p<0.001), AST (p<0.001), ALT (p<0.001). However, alkaline phosphatase (p=0.449) was not associated with the primary endpoint. The iterations of event regression analyses using 500 sequences of LFT thresholds showed the following cutoffs to be significantly associated with in-hospital death (minimally significant values): ALT (281.71 IU/L), AST (120.94 IU/L), bilirubin (2.615 mg/ dL). On the multivariate analysis, while controlling for demographics and cardiopulmonary/ medical comorbidities, the following adjusted hazard ratios were derived for each cutoff: ALT (aHR: 6.43 95%CI 1.85-22.40), AST (aHR: 3.35 95%CI 1.84-6.11), and bilirubin (aHR: 2.77 95%CI 1.15-6.65). Conclusion: The delineated cutoffs for AST, ALT, and bilirubin levels can serve as clinical benchmarks to help determine when a COVID-19 infection poses significant risk. Given this finding, the cutoffs can be used as part of a risk assessment for patients to support early preventative therapies and medical management. (Table Presented)
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stress. We studied admissions, readmission (RAD) rates, and demographics of ALD patients before and after the onset of the COVID-19 pandemic. Methods: We reviewed the number of hospitalizations before and after the onset of the COVID-19 pandemic for ALD at four teaching hospitals in the Northwell Health System, two bordering New York City to the east (region A) and two in NYC (region B). Coding data of hospital discharges for ALD (alcoholic hepatitis, alcohol-associated cirrhosis, nonspecific alcohol liver disease) during the 14 months between January 2019 and February 2020 (period 1) were compared to those between June 2020 and July 2021 (period 2) for admissions, RAD, and demographics. Data from March to May 2020 were excluded due to New York City lockdown, limited and delayed access to health care due to COVID-19 pandemic. The Fisher's exact test and Mann- Whitney test are used for statistic comparisons. Results: The number of hospitalizations for ALD increased by 32% during the COVID-19 pandemic. However, the increase was only observed in region A, but not in region B (55% vs -1%). With the onset of the pandemic, the median age for ALD admissions decreased by 4.5 years overall, significantly in region B (7.5 years), but not in region A (2 years). In both regions, the percentage of the white race admissions also decreased. No significant difference was observed in the gender distribution, Medicaid insurance status and overall rate of RAD (Table 1). However, the white population had decreased RAD rates from 32% to 17% in region B, the non-white population RAD rates increased from 17% to 31% in region A, and in regions A and B combined (Table 2). Conclusion: Our study shows that admission for ALD increased during the COVID-19 pandemic in areas bordering NYC but not in NYC. These rates differed by race, accompanied with a slight shift to younger age. Our results suggest that observations based on certain communities or regions may not be universally applicable. Future research for the impact of COVID-19 on ALD and other social-economic adaptation should take demographic and geographic variations into consideration. (Table Presented)
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BACKGROUND Alcohol misuse is a major public health concern in the United States. Centers for Disease Control reported 261 deaths per day due to excess alcohol consumption. National Institute of Alcohol Abuse and Alcoholism reports a significant increase in alcohol sale during the current Covid-19 pandemic. We aim to study the impact of alcohol misuse during the current pandemic in inpatient admissions. METHODS We retrospectively reviewed all the hospitalizations at BronxCare Health System, a safety-net community hospital in New York City, between March and September during the years of 2017 to 2020. All adult inpatient encounters with an admitting diagnosis of decompensated alcoholic liver cirrhosis (DALC) and alcoholic hepatitis (AH) were included in our study. RESULTS We compared two groups based on time periods: pre-pandemic and pandemic. There was a significant increase in admissions in the pandemic group. We ed a total of 64 admissions for DALC and 51 for AH in the pre-pandemic group and 90 hospitalizations for DALC and 69 hospitalizations for AH in the pandemic group. The mean age of patients admitted for DALC 57 years (SD ±11) and 54 years (SD ±9) respectively, p=0.036. We observed a decrease in the number of female hospitalizations (26.3% vs 18.8%, p=0.1829) and an increase in-hospital mortality (8.7% vs 12.0%, p=0.394) related to DALC. However, these findings did not reach statistical significance. The mean age of patients admitted for AH was 48 years (SD ±10) in both the groups, p=0.34. There were no statistically significant differences in gender (24.8% vs 23.2%, p=0.8666) or in-hospital mortality (1.9% vs 4.3%, p= 0.3779). Figures 1 and 2 illustrate an increase in the number of hospitalizations related to DALC and AH during the COVID-19 pandemic. CONCLUSION There was a significant increase in admissions for DALC and AH during the Covid 19 pandemic at our safety net hospital serving a community where alcohol misuses was high. There has been disproportionate impact of Covid 19 in terms of higher mortality in safety net populations. Our study highlights the broader impact of Covid 19 on other major public health concerns including stress, anxiety further exacerbating alcoholism and alcohol abuse which may explain some of the disparities in Covid 19 related mortalities. (Figure Presented)
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Introduction: The COVID-19 pandemic created massive disruptions in established healthcare utilization patterns. The impact of these interruptions in patients with liver diseases including cirrhosis is underreported at a population level. As such, we used a large, state-wide dataset to report inpatient liver disease outcomes during the 2020 Coronavirus pandemic using 2018 and 2019 as comparator years. Methods: Using the all-payer California State Inpatient Dataset for 2018-2020, we explored year-to-year trends, and 2020 month-to-month variations in liver-related (alcoholic liver disease, hepatocellular cancer, cirrhosis and attendant complications including hepatic encephalopathy, variceal bleeding, ascites, spontaneous bacterial peritonitis [SBP], and hepatorenal syndrome) hospitalizations, length of stay, and inpatient mortality (all-cause & viral pneumonia-specific) using joinpoin, linear, and logistic regression models. We also investigated trends in endoscopy utilization for esophageal variceal bleeding and variations in liver transplantation during the pandemic. Results: There was an increase in decompensated cirrhosis hospitalizations (264,008 in 2019 to 272,092 in 2020, p<0.001) and all-cause mortality (11.6% in 2019 to 13.8% in 2020, p<0.001). Alcoholic hepatitis and alcohol-related liver disease hospitalizations also increased in this period (ptrend<0.001) [Fig 1]. The 2020 month-to-month trend analyses showed the lowest hospitalization rates in April, coinciding with the early stages of the pandemic. This was associated with significant trend in mortality for patients with cirrhosis (ptrend<0.001) and alcoholic liver disease (ptrend=0.004) where mortality was highest in December 2020. Viral pneumonia admissions increased from 0.3% (n=940) in 2019 to 6% (n=18,544) of all hospitalizations (p<0.001) and this was associated with a significant increase in respiratory failure and death, 0% in 2019 to 1.8% in 2020 (p<0.001). Sensitivity analysis showed that decompensated cirrhosis accounted for >95% of viral pneumonia deaths in 2020 among all liver disease patients. There was no significant change in rates of liver transplant surgery during the 2020 pandemic (ptrend=0.36). In addition, endoscopic treatment for esophageal variceal bleeding within the first 24 hours of admission was not significantly different between 2019 and 2020 (44% vs 41%, p=0.65), and rates of paracentesis for SBP were also comparable (30% in 2019 vs 30.6% in 2020, p=0.07). Conclusions: The Covid-19 pandemic resulted in significant increases in hospitalization for decompensated cirrhosis and alcohol-related liver disease in California. Patients with decompensated cirrhosis accounted for the majority of viral pneumonia cases and deaths among all liver-related admissions. However, liver transplantation and endoscopy utilization rates were comparable with prepandemic numbers. (Figure Presented) Figure 1: Trends in hospitalization, length of stay, and mortality rates of liver diseases in California from 2018 to 2020(Figure Presented) Figure 2: 2020 month-to-month trends in liver-related hospitalizations and mortality in California State
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Background: The COVID-19 pandemic is alleged to have provoked more significant financial and emotional hardships on women compared to men. During the pandemic, liquor stores in the US were considered essential businesses and alcohol sales increased by > 34%. Although women have lower and less active alcohol dehydrogenase in the GI tract and liver, compared to men, alcoholic liver disease (ALD) has traditionally been a disease primarily of middle-aged and older men. The current study was designed to evaluate whether increased alcohol consumption during the COVID-19 pandemic resulted in an increase in ALD admissions, particularly in women. Methods: Admissions to a multi-hospital health system for ALD were compared for two periods (April 2019 – March 2020 (Pre-COVID, “PC”) and April 2020 – March 2021 (During-COVID, “COV”)). Admissions for ALD were identified by querying an electronic database (EPIC) using ICD-10 codes. Statistical data were analyzed using a Poisson Regression Model. Admission rates were compared using the annual quarterly average for the two time periods, and stratified by age and gender. Results: Comparing PC and COV admissions for ALD, an average quarterly increase of 33% (p=0.031) was detected in women <50 (75 PC;104 COV). During the same two periods, ALD admissions for males <50 increased 24% (p=0.043) (131 PC;166 COV). In women >50 there was an average quarterly increase of 22% (p=0.063) (131 PC;163 COV) in admissions for ALD, while a 24% (p=0.003) decrease was observed in males >50 (341 PC;267 COV). Males >50 remained the highest total admission group, but did have a significant proportional decline compared to the other groups. Total female admissions increased from 206 to 267, demonstrating an increase of 29% (p=0.005). Total male admissions decreased from 472 to 433;a 9% decrease (p=0.195). Total admissions for ALD showed a mild increase from 678 PC to 709 COV. Conclusions: The current study, comparing the PC and COV periods, demonstrates a significant increase in the number of ALD hospital admissions for both men and women <50. Importantly, a significant increase in the number of younger women requiring admission was identified. In women >50 a similar trend was observed, while a decrease in the number of admissions for ALD was detected in males >50. This study underestimates the prevalence of ALD during the COVID era, as only patients with significant ALD would have been admitted. Patient hesitancy to present to hospitals during the pandemic, as well as cessation of elective admissions may have also contributed. This large multi-hospital analysis demonstrates a concerning gender disparity with women, especially young women, being significantly more likely to be admitted with ALD during the COVID period compared to the twelve months prior to the pandemic. (Figure Presented)
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Natural Killer (NK) cells are the key lymphocyte subset of the natural immune system that arbitrates antiviral and anticancer responses. In the human body NK cells inhabit in the bone marrow, lymph nodes, tonsils, skin, liver, gut, and lungs. This bibliographic study covers the origins and evolution of these cells. This review of NK cells includes synopsis of their well-known and evolving themes including their development, functions of cytokine production, anticancer cytotoxicity, clearing of viral infections and exhaustion. Within the liver, NK cells are enhanced in lymphocytes and possess distinctive phenotypic characters and useful properties, which contain tumour cytotoxicity and explicit cytokine profiles. NK cells, while providing innate immunity in the liver, play important roles in providing protection versus pathogens and tumours utilising their cytotoxicity and cytokine production. Accruing substantiation from the last few decades proposes that NK cells perform a vital role in regulating viral hepatitis and liver tumours. In addition, they contribute to the pathogenesis of liver damage including its inflammation. Understanding the description of hepatic NK cell functions has aided us in better understanding the pathogenesis of diseases of the liver and consequently divulging novel therapeutic goals for treating these illnesses.
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Introduction: Acute pulmonary thromboembolism is a pulmonary pathology that is becoming more frequent nowadays, the use of new mechanical and thrombolytic therapies has a significant impact on the cardiopulmonary prognosis. Case: A 41-year-old male, a retired military man, smoking, overweight, dyslipidemia, alcoholic liver disease, who attended the emergency department due to abrupt dyspnea, with tachycardia, chest pain, and syncope;the patient had tachycardia of 120 bpm, BP 90/60 mmHg and SO2 of 82%, with a history of COVID-19 infection, suspected of massive pulmonary embolism, it was decided to carry out computed tomography where a bilateral submassive pulmonary embolism was documented (Fig. 1A), it was proposed to perform systemic thrombolysis, however due to the risk of bleeding, it was decided to perform EKOS ultrasound directed thrombolysis. Baseline pulmonary angiography was performed with a large number of thrombi (Fig. 1B), distributed in both main right and left branches and deficient pulmonary filling of distal vessels, due to the large amount of thrombus, it was decided to perform manual thrombus aspiration, obtaining a large amount of thrombus (Fig. 1C), as well as thrombolysis in situ with Alteplase a dose of 1 mg/catheter/hour for 12 hours, with a total dose of 24 mg;Ultrasound probe was placed in both pulmonary arteries with the EKOS system (Fig. 1D). Results: Pulmonary angiography was performed 24 hours after the procedure, where no bleeding occurred and almost complete resolution of the thrombus was observed. The patient later with 92% SO2, without oxygen requirements, with HR 90 bpm, with no evidence of ventricular dysfunction, was discharged home with anticoagulation. Conclusion: Low dose fibrinolysis and thromboaspiration are considered, as well as the use of EKOS endovascular ultrasound, a safe and effective procedure, in the context of a patient with high-risk of bleeding, with favorable results that condition clinical and prognostic improvement.
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Background Chronic liver disease (CLD) patients, including those with ALD, are particularly susceptible to infections. Thus, respiratory infections such as seasonal flue or COVID 19 may be speculated to be a major threat to these patients. However, despite general recommendations for seasonal flu vaccinations systematic evaluations of the efficacy of such vaccinations are widely lacking. In the current pandemic, substantial evidence on the efficacy on vaccination against upper airway respiratory infection is essential to improve the outcome of patients with Alcoholic liver disease. Methods Evaluating a large cohort of patients with alcoholic liver disease form the USA with a total of 4667 patients, we investigated the efficacy of vaccination of patients with ALD. As quality of hepatological treatment may have significantly changed and improved over the past several decades the analysis was limited to the years 2000 to 2020. Results During the last decade vaccinations against several seasonal influenza A variants (H1N1 (p = 0.000), H3N2 (p = 0.000)), influenza B virus (p = 0.000), Massachusetts-2-2010-liver variant (p = 0.000), and B-Wisconsin-1-2010 (p = 0.006) variant all demonstrated a highly significant survival benefit for these patients. Discussion and Conclusion Vaccination against ongoing or seasonal viral upper airway infections improves survival of patients with ALD and should therefore be recommended and carried out consistently.
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Hepatic disease is common in severe COVID-19. This study compared the histologic/molecular findings in the liver in fatal COVID-19 (n = 9) and age-matched normal controls (n = 9); three of the fatal COVID-19 livers had pre-existing alcohol use disorder (AUD). Controls showed a high resident population of sinusoidal macrophages that had variable ACE2 expression. Histologic findings in the cases included periportal/lobular inflammation. SARS-CoV2 RNA and nucleocapsid protein were detected in situ in 2/9 COVID-19 livers in low amounts. In 9/9 cases, there was ample in situ SARS-CoV-2 spike protein that co-localized with viral matrix and envelope proteins. The number of cells positive for spike/100× field was significantly greater in the AUD/COVID-19 cases (mean 5.9) versus the non-AUD/COVID-19 cases (mean 0.4, p < 0.001) which was corroborated by Western blots. ACE2+ cells were 10× greater in AUD/COVID-19 livers versus the other COVID-19/control liver samples (p < 0.001). Co-expression experiments showed that the spike protein localized to the ACE2 positive macrophages and, in the AUD cases, hepatic stellate cells that were activated as evidenced by IL6 and TNFα expression. Injection of the S1, but not S2, subunit of spike in mice induced hepatic lobular inflammation in activated macrophages. It is concluded that endocytosed viral spike protein can induce hepatitis in fatal COVID-19. This spike induced hepatitis is more robust in the livers with pre-existing AUD which may relate to why patients with alcohol abuse are at higher risk of severe liver disease with SARS-CoV2 infection.