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1.
Dig Liver Dis ; 2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-2049106

ABSTRACT

BACKGROUND: Global pandemic of COVID-19 represents an unprecedented challenge. COVID-19 has predominantly targeted vulnerable populations with pre-existing chronic medical diseases, such as diabetes and chronic liver disease. AIMS: We estimated chronic liver disease-related mortality trends among individuals with diabetes before and during the COVID-19 pandemic. METHODS: Utilizing the US national mortality database and Census, we determined the quarterly age-standardized chronic liver disease-related mortality and quarterly percentage change (QPC) among individuals with diabetes. RESULTS: The quarterly age-standardized mortality for chronic liver disease and/or cirrhosis among individuals with diabetes remained stable before the COVID-19 pandemic and sharply increased during the COIVD-19 pandemic at a QPC of 8.5%. The quarterly mortality from nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) increased markedly during the COVID-19 pandemic. Mortality for hepatitis C virus (HCV) infection declined with a quarterly rate of -3.3% before the COVID-19 pandemic and remained stable during the COVID-19 pandemic. While ALD- and HCV-related mortality was higher in men than in women, NAFLD-related mortality in women was higher than in men. CONCLUSIONS: The sharp increase in mortality for chronic liver disease and/or cirrhosis among individuals with diabetes during the COVID-19 pandemic was associated with increased mortality from NAFLD and ALD.

2.
Clin Gastroenterol Hepatol ; 20(10): 2307-2316.e3, 2022 10.
Article in English | MEDLINE | ID: covidwho-1982710

ABSTRACT

BACKGROUND & AIMS: During the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic. METHODS: Population-based analyses were performed on United States national mortality records (2017-2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC). RESULTS: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD. CONCLUSION: All-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.


Subject(s)
COVID-19 , Hepatitis, Viral, Human , Liver Diseases, Alcoholic , Non-alcoholic Fatty Liver Disease , Hepatitis, Viral, Human/complications , Hepatitis, Viral, Human/epidemiology , Humans , Liver Cirrhosis/epidemiology , Liver Diseases, Alcoholic/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Pandemics , United States/epidemiology
6.
Hepatology ; 74(6): 3316-3329, 2021 12.
Article in English | MEDLINE | ID: covidwho-1458999

ABSTRACT

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.


Subject(s)
Alcohol Drinking/adverse effects , COVID-19/complications , Liver Diseases, Alcoholic/etiology , Liver Transplantation/statistics & numerical data , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Cost of Illness , End Stage Liver Disease/epidemiology , End Stage Liver Disease/etiology , Female , Health Care Rationing/statistics & numerical data , Health Care Rationing/trends , Hepatitis, Alcoholic/epidemiology , Hepatitis, Alcoholic/etiology , Humans , Interrupted Time Series Analysis/methods , Liver Diseases, Alcoholic/epidemiology , Liver Diseases, Alcoholic/surgery , Liver Transplantation/trends , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/etiology , Retrospective Studies , SARS-CoV-2/genetics , Severity of Illness Index , Time Factors , United States/epidemiology , Waiting Lists
7.
Curr Opin Infect Dis ; 34(5): 471-476, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1408783

ABSTRACT

PURPOSE OF REVIEW: The ubiquitous expression of angiotensin-converting enzyme-2 receptors and its significance as the origin of viral entry have assisted in comprehending the pathophysiology of extrapulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we focus on the clinical significance of gastrointestinal manifestations. RECENT FINDINGS: The global pandemic, a result of the widespread implications of SARS-CoV-2, remains a significant burden to current healthcare systems. Fever, dyspnea, and tussive symptoms have primarily been recognized as the most common presenting signs/symptoms. During the past one year our scope of practice has transcended beyond the management of the respiratory system to incorporate other varying systemic manifestations such as anorexia, nausea, vomiting, diarrhea, and abdominal pain. The outcomes reported by recent studies suggest an association between the presence of gastrointestinal symptoms and important clinical factors such as delay in presentation, disease severity, and mortality. SUMMARY: We provide a summarization of the most recent in-depth investigations of coronavirus disease 2019 with gastrointestinal manifestations and their conclusions. Although the pathophysiology remains an area of evolving interest, a better understanding of this disease process may allow for early recognition, efficient triage, and improved prognostication for those presenting with gastrointestinal manifestations of SARS-CoV-2.


Subject(s)
COVID-19/complications , COVID-19/pathology , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/pathology , Gastrointestinal Tract/pathology , Gastrointestinal Diseases/virology , Gastrointestinal Tract/virology , Humans , Pandemics/prevention & control , SARS-CoV-2/pathogenicity
8.
Clin Gastroenterol Hepatol ; 19(12): 2664-2666.e2, 2021 12.
Article in English | MEDLINE | ID: covidwho-1306898

ABSTRACT

Chronic liver disease (CLD) and cirrhosis accounts for approximately 2 million deaths annually worldwide. CLD and cirrhosis-related mortality has increased steadily in the United States.1,2 With the global pandemic of coronavirus disease 2019 (COVID-19), patients with CLD and cirrhosis represent a vulnerable population at higher risk for complications and mortality.3,4 Although high mortality from COVID-19 among patients with CLD and cirrhosis have been reported,5 national trends in mortality related to CLD and cirrhosis before and during the COVID-19 pandemic have not been assessed. This study estimated the temporal quarterly trends in CLD and cirrhosis-related mortality in the United States from 2017 Q1 to 2020 Q3 using provisional data releases from the National Vital Statistics System.6,7.


Subject(s)
COVID-19 , Liver Diseases , Humans , Liver Cirrhosis/epidemiology , Liver Diseases/epidemiology , Pandemics , SARS-CoV-2 , United States/epidemiology
10.
Transplantation ; 104(11): 2221-2224, 2020 11.
Article in English | MEDLINE | ID: covidwho-1005670

ABSTRACT

BACKGROUND: The regional impact of coronavirus disease 2019 on solid organ transplantation in the United States has not been fully evaluated. METHODS: A retrospective analysis of month-to-month trends on waitlist additions, waitlist deaths, and transplant surgeries between all United Network for Organ Sharing (UNOS) regions was performed. A linear regression model trained on historical data was used to estimate anticipated transplantation volume. RESULTS: All UNOS regions reported a decrease in total waitlist additions and transplant surgeries. The largest decreases in total transplants were identified in regions 1, 2, 6, and 9, with regions 2, 7, 8, and 9 noting the largest decrease in waitlist additions. Six of the 11 regions noted increases in waitlist deaths, with UNOS regions 9, 1, and 2, all located within the Northeast, noting the highest percent increase in waitlist deaths at 170%, 89%, and 54%, respectively. The largest reductions in solid organ transplantation and waitlist deaths were seen in kidney and lung transplantation. Current transplantation volume is significantly lower than the low range of the 95% confidence interval derived from the linear regression model (2182 versus 3110; P < 0.05). CONCLUSIONS: Significant decreases in total waitlist additions and transplant surgeries with increases in waitlist deaths were noted in the majority of US transplant domains. The impact was especially prevalent in areas with high burden of coronavirus disease 2019 infection. National and regional strategies aimed at minimizing disruptions in transplantation are needed.


Subject(s)
Coronavirus Infections/epidemiology , Organ Transplantation/trends , Pneumonia, Viral/epidemiology , Waiting Lists , Betacoronavirus , COVID-19 , Humans , Organ Transplantation/statistics & numerical data , Pandemics , Retrospective Studies , SARS-CoV-2 , United States/epidemiology
12.
Eur J Gastroenterol Hepatol ; 33(7): 990-995, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-636414

ABSTRACT

BACKGROUND/AIMS: The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury. METHODS: A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies. RESULTS: Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19. CONCLUSION: A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19.


Subject(s)
COVID-19/complications , Liver Diseases , Alanine Transaminase/analysis , Alkaline Phosphatase/analysis , Aspartate Aminotransferases/analysis , Bilirubin/analysis , Humans , Liver , Liver Diseases/diagnosis , Liver Diseases/epidemiology , Liver Diseases/virology , Pandemics , gamma-Glutamyltransferase/analysis
13.
mBio ; 11(3)2020 06 23.
Article in English | MEDLINE | ID: covidwho-612678

ABSTRACT

It is well understood that the adaptive immune response to infectious agents includes a modulating suppressive component as well as an activating component. We now show that the very early innate response also has an immunosuppressive component. Infected cells upregulate the CD47 "don't eat me" signal, which slows the phagocytic uptake of dying and viable cells as well as downstream antigen-presenting cell (APC) functions. A CD47 mimic that acts as an essential virulence factor is encoded by all poxviruses, but CD47 expression on infected cells was found to be upregulated even by pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that encode no mimic. CD47 upregulation was revealed to be a host response induced by the stimulation of both endosomal and cytosolic pathogen recognition receptors (PRRs). Furthermore, proinflammatory cytokines, including those found in the plasma of hepatitis C patients, upregulated CD47 on uninfected dendritic cells, thereby linking innate modulation with downstream adaptive immune responses. Indeed, results from antibody-mediated CD47 blockade experiments as well as CD47 knockout mice revealed an immunosuppressive role for CD47 during infections with lymphocytic choriomeningitis virus and Mycobacterium tuberculosis Since CD47 blockade operates at the level of pattern recognition receptors rather than at a pathogen or antigen-specific level, these findings identify CD47 as a novel potential immunotherapeutic target for the enhancement of immune responses to a broad range of infectious agents.IMPORTANCE Immune responses to infectious agents are initiated when a pathogen or its components bind to pattern recognition receptors (PRRs). PRR binding sets off a cascade of events that activates immune responses. We now show that, in addition to activating immune responses, PRR signaling also initiates an immunosuppressive response, probably to limit inflammation. The importance of the current findings is that blockade of immunomodulatory signaling, which is mediated by the upregulation of the CD47 molecule, can lead to enhanced immune responses to any pathogen that triggers PRR signaling. Since most or all pathogens trigger PRRs, CD47 blockade could be used to speed up and strengthen both innate and adaptive immune responses when medically indicated. Such immunotherapy could be done without a requirement for knowing the HLA type of the individual, the specific antigens of the pathogen, or, in the case of bacterial infections, the antimicrobial resistance profile.


Subject(s)
Betacoronavirus/immunology , CD47 Antigen/metabolism , Immunomodulation/immunology , Receptors, Pattern Recognition/immunology , A549 Cells , Adaptive Immunity/immunology , Animals , CD47 Antigen/genetics , Cell Line, Tumor , Cytokines/immunology , Female , Humans , Immunity, Innate/immunology , Lymphocytic choriomeningitis virus/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mycobacterium tuberculosis/immunology , SARS-CoV-2 , Up-Regulation/immunology
14.
Am J Gastroenterol ; 115(7): 1129-1132, 2020 07.
Article in English | MEDLINE | ID: covidwho-618936

ABSTRACT

INTRODUCTION: High rates of concurrent gastrointestinal manifestations have been noted in patients with corona virus disease 2019 (COVID-19); however, the association between these digestive manifestations and need for hospitalization has not been established. METHODS: This is a retrospective review of consecutive patients diagnosed with COVID-19. A total of 207 patients were identified; 34.5% of patients noted concurrent gastrointestinal symptoms, with 90% of gastrointestinal symptoms being mild. RESULTS: In a multivariate regression model controlled for demographics and disease severity, an increased risk of hospitalization was noted in patients with any digestive symptom (adjusted odds ratio 4.84, 95% confidence interval: 1.68-13.94). DISCUSSION: The presence of digestive symptoms in COVID-19 is associated with a need for hospitalization.


Subject(s)
Coronavirus Infections/complications , Gastrointestinal Diseases/etiology , Pneumonia, Viral/complications , Adult , Aged , Betacoronavirus , COVID-19 , Digestive System Diseases/etiology , Digestive System Diseases/virology , Female , Gastrointestinal Diseases/virology , Hospitalization , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2
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