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1.
Hepatol Commun ; 6(8): 2079-2089, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1958741

ABSTRACT

Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics are unknown. We assessed the safety and efficacy of FMT in patients with prior overt HE, comparing five FMT donors. We performed an open-label study of FMT capsules, administered 5 times over 3 weeks. Primary outcomes were change in psychometric HE score (PHES) and serious adverse events (SAEs). Serial stool samples underwent shallow shotgun metagenomic sequencing. Ten patients completed FMT administration and 6-month follow-up. Model for End-Stage Liver Disease (MELD) score did not change after FMT (14 versus 14, p = 0.51). Thirteen minor adverse events and three serious adverse events (two unrelated to FMT) were reported. One SAE was extended-spectrum beta-lactamase Escherichia coli bacteremia. The PHES improved after three doses of FMT (+2.1, p < 0.05), after five doses of FMT (+2.9, p = 0.007), and 4 weeks after the fifth dose of FMT (+3.1, p = 0.02). Mean change in the PHES ranged from -1 to +6 by donor. Two taxa were identified by random forest analysis and confirmed by linear regression to predict the PHES- Bifidobacterium adolescentis (adjusted R2 = 0.27) and B. angulatum (adjusted R2 = 0.25)-both short-chain fatty acid (SCFA) producers. Patients who responded to FMT had higher levels of Bifidobacterium as well as other known beneficial taxa at baseline and throughout the study. The FMT donor with poorest cognitive outcomes in recipients had the lowest fecal SCFA levels. Conclusion: FMT capsules improved cognition in HE, with an effect varying by donor and recipient factors (NCT03420482).


Subject(s)
Cognition , Fecal Microbiota Transplantation , Hepatic Encephalopathy , Capsules , Cognition/physiology , Hepatic Encephalopathy/therapy , Humans
2.
Arch Pathol Lab Med ; 2022 Jun 03.
Article in English | MEDLINE | ID: covidwho-1879615

ABSTRACT

CONTEXT.­: Coronavirus disease 2019 (COVID-19) has been associated with liver injury, and a small subset of patients recovering from severe disease have shown persistent markedly elevated liver biochemistries for months after infection. OBJECTIVE.­: To characterize persistent biliary injury after COVID-19. DESIGN.­: A search of the pathology archives identified 7 post-COVID-19 patients with persistent biliary injury, and the clinical, radiologic, and pathologic features were assessed. RESULTS.­: All patients in this cohort presented with respiratory symptoms and had a complicated clinical course with acute elevation of liver biochemistries. Alkaline phosphatase (ALP) was markedly and persistently elevated after discharge (median peak ALP: 1498 IU/L, at a median of 84 days from diagnosis). Magnetic resonance cholangiopancreatography (MRCP) showed 3 patients with irregularity, stricturing, and dilatation of intrahepatic ducts; no radiographic abnormalities were identified in the remaining 4 patients. Liver biopsies showed mild portal changes with features of cholestatic injury in 4 patients (bile duct injury and canalicular cholestasis) and marked biliary obstruction in 2 patients (profound cholestasis, ductular reaction, and bile infarcts), but no SARS-CoV-2 ribonucleic acid (RNA) was identified on in-situ hybridization. On follow-up, most patients had minimal intervention and showed marked improvement of liver biochemistries but with mild persistent elevation of ALP. CONCLUSIONS.­: A subset of critically ill COVID-19 patients demonstrates marked and persistent cholestatic injury, with radiographic and histologic evidence of secondary sclerosing cholangitis, suggesting that cholestatic liver disease and secondary sclerosing cholangitis may be long-term sequelae of COVID-19 acute illness as a longstanding manifestation of critical illness.

3.
J Infect Dis ; 225(1): 19-29, 2022 01 05.
Article in English | MEDLINE | ID: covidwho-1606548

ABSTRACT

BACKGROUND: Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated). METHODS: In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission. RESULTS: Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old. CONCLUSION: Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.


Subject(s)
COVID-19/diagnosis , Dyslipidemias/drug therapy , Hospital Mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Cohort Studies , Dyslipidemias/complications , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , SARS-CoV-2
4.
J Infect Dis ; 224(5): 777-782, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1381012

ABSTRACT

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.


Subject(s)
COVID-19/immunology , Interferon Type I/immunology , Interferon-gamma/immunology , Interferons/immunology , COVID-19/blood , Chemokines/blood , Cytokines/blood , Humans , Interferon Type I/blood , Interferon Type I/genetics , Interferon-gamma/blood , Interferon-gamma/genetics , Interferons/blood , Leukocytes, Mononuclear/immunology , SARS-CoV-2/isolation & purification
5.
Hepatology ; 74(2): 1049-1064, 2021 08.
Article in English | MEDLINE | ID: covidwho-1372725

ABSTRACT

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.


Subject(s)
COVID-19 Vaccines/standards , COVID-19/prevention & control , Liver Diseases , Liver Transplantation , Adult , COVID-19 Vaccines/administration & dosage , Consensus , Humans , Practice Guidelines as Topic , SARS-CoV-2/immunology , United States
6.
J Infect Dis ; 224(5): 777-782, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1243489

ABSTRACT

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.


Subject(s)
COVID-19/immunology , Interferon Type I/immunology , Interferon-gamma/immunology , Interferons/immunology , COVID-19/blood , Chemokines/blood , Cytokines/blood , Humans , Interferon Type I/blood , Interferon Type I/genetics , Interferon-gamma/blood , Interferon-gamma/genetics , Interferons/blood , Leukocytes, Mononuclear/immunology , SARS-CoV-2/isolation & purification
7.
Hepatol Commun ; 2020 Jul 11.
Article in English | MEDLINE | ID: covidwho-1204736

ABSTRACT

A newly identified coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the infectious coronavirus disease 2019 (COVID-19), emerged in December 2019 in Wuhan, Hubei Province, China, and now poses a major threat to global public health. Previous studies have observed highly variable alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with COVID-19. However, circulating levels of the cholangiocyte injury biomarker γ-glutamyltransferase (GGT) have yet to be reported in the existing COVID-19 case studies. Herein, we describe the relationship between GGT levels and clinical and biochemical characteristics of patients with COVID-19. Our study is a retrospective case series of 98 consecutive hospitalized patients with confirmed COVID-19 at Wenzhou Central Hospital in Wenzhou, China, from January 17 to February 5, 2020. Clinical data were collected using a standardized case report form. Diagnosis of COVID-19 was assessed by symptomatology, reverse transcriptase-polymerase chain reaction (RT-PCR), and computed tomography (CT) scan. The medical records of patients were analyzed by the research team. Of the 98 patients evaluated, elevated GGT levels were observed in 32.7%; increased C-reactive protein (CRP) and elevated ALT and AST levels were observed in 22.5%, 13.3%, and 20.4%, respectively; and elevated alkaline phosphatase (ALP) and triglycerides (TGs) were found in 2% and 21.4%, respectively. Initially, in the 82 patients without chronic liver disease and alcohol history; age older than 40 years (P = 0.027); male gender (P = 0.0145); elevated CRP (P = 0.0366), ALT (P < 0.0001), and ALP (P = 0.0003); and increased TGs (P = 0.0002) were found to be associated with elevated GGT levels. Elevated GGT (P = 0.0086) and CRP (P = 0.0162) levels have a longer length of hospital stay. Conclusion: A sizable number of patients with COVID-19 infection had elevated serum GGT levels. This elevation supports involvement of the liver in persons with COVID-19.

8.
Hepatology ; 73(2): 875-876, 2021 02.
Article in English | MEDLINE | ID: covidwho-1126369
9.
ACS Nano ; 15(1): 665-673, 2021 01 26.
Article in English | MEDLINE | ID: covidwho-940874

ABSTRACT

Deep-learning (DL)-based image processing has potential to revolutionize the use of smartphones in mobile health (mHealth) diagnostics of infectious diseases. However, the high variability in cellphone image data acquisition and the common need for large amounts of specialist-annotated images for traditional DL model training may preclude generalizability of smartphone-based diagnostics. Here, we employed adversarial neural networks with conditioning to develop an easily reconfigurable virus diagnostic platform that leverages a dataset of smartphone-taken microfluidic chip photos to rapidly generate image classifiers for different target pathogens on-demand. Adversarial learning was also used to augment this real image dataset by generating 16,000 realistic synthetic microchip images, through style generative adversarial networks (StyleGAN). We used this platform, termed smartphone-based pathogen detection resource multiplier using adversarial networks (SPyDERMAN), to accurately detect different intact viruses in clinical samples and to detect viral nucleic acids through integration with CRISPR diagnostics. We evaluated the performance of the system in detecting five different virus targets using 179 patient samples. The generalizability of the system was confirmed by rapid reconfiguration to detect SARS-CoV-2 antigens in nasal swab samples (n = 62) with 100% accuracy. Overall, the SPyDERMAN system may contribute to epidemic preparedness strategies by providing a platform for smartphone-based diagnostics that can be adapted to a given emerging viral agent within days of work.


Subject(s)
COVID-19 Testing/instrumentation , COVID-19 Testing/methods , COVID-19/diagnosis , Deep Learning , Signal Processing, Computer-Assisted , Telemedicine/methods , Antigens, Viral/isolation & purification , CRISPR-Cas Systems , Communicable Disease Control , Disaster Planning , Humans , Image Processing, Computer-Assisted/methods , Metal Nanoparticles/chemistry , Neural Networks, Computer , Platinum , Point-of-Care Testing , Public Health , Reproducibility of Results , Smartphone
12.
Hepatology ; 72(5): 1819-1837, 2020 11.
Article in English | MEDLINE | ID: covidwho-691225

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 pandemic has drastically altered all facets of clinical care and research. Clinical research in hepatology has had a rich tradition in several domains, including the discovery and therapeutic development for diseases such as hepatitis B and C and studying the natural history of many forms of chronic liver disease. National Institutes of Health, foundation, and industry funding have provided important opportunities to advance the academic careers of young investigators while they strived to make contributions to the field. Instantaneously, however, all nonessential research activities were halted when the pandemic started, forcing those involved in clinical research to rethink their research strategy, including a shift to coronavirus disease 2019 research while endeavoring to maintain their preexisting agenda. Strategies to maintain the integrity of ongoing studies, including patient follow-up, safety assessments, and continuation of investigational products, have included a shift to telemedicine, remote safety laboratory monitoring, and shipping of investigational products to study subjects. As a revamp of research is being planned, unique issues that face the research community include maintenance of infrastructure, funding, completion of studies in the predetermined time frame, and the need to reprogram career path timelines. Real-world databases, biomarker and long-term follow up studies, and research involving special groups (children, the homeless, and other marginalized populations) are likely to face unique challenges. The implementation of telemedicine has been dramatically accelerated and will serve as a backbone for the future of clinical research. As we move forward, innovation in clinical trial design will be essential for conducting optimized clinical research.


Subject(s)
Biomedical Research/organization & administration , Coronavirus Infections/prevention & control , Gastroenterology/methods , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Telemedicine/organization & administration , COVID-19 , Coronavirus Infections/epidemiology , Delivery of Health Care , Female , Forecasting , Humans , Male , Needs Assessment , Pandemics/statistics & numerical data , Pneumonia, Viral/epidemiology , Program Development , Program Evaluation , Research Design , United States
13.
Clin Liver Dis (Hoboken) ; 15(5): 175-180, 2020 May.
Article in English | MEDLINE | ID: covidwho-326970
14.
Hepatology ; 73(3): 890-900, 2021 03.
Article in English | MEDLINE | ID: covidwho-273691

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) leads to elevated liver biochemistries in approximately half of patients on presentation. To date, data are limited regarding the trend of liver biochemistries over the course of illness. We aimed to evaluate the trend, etiology, and outcomes associated with liver biochemistries in COVID-19. APPROACH AND RESULTS: A total of 60 patients with COVID-19 were admitted between March 21 and March 28, 2020. The mean age was 57 years, 65% were male, and 28% were Hispanic. At the study conclusion, 6 patients were deceased, 28 were discharged, and 26 remained admitted. Patients who remained admitted were followed for a median of 12 days. Of 60 patients, 41 (69%) had at least one abnormal liver biochemistry on admission. Median aspartate aminotransferase (AST) was higher than alanine aminotransferase (ALT) at admission (46 vs. 30 U/L) and during the hospital course. Aminotransferases rose above normal in 54 (93%) patients, whereas alkaline phosphatase and total bilirubin elevations were rare. Ten (17%) patients developed aminotransferases more than 5 times the upper limit of normal. AST highly correlated with ALT throughout the illness course (r = 0.97; P < 0.0001), whereas correlations with markers of muscle injury and inflammation were weak. Statin use was common before (40%) and during admission (80%) at our center, with no difference in peak liver biochemistries between users and nonusers. No demographic or comorbid illness was associated with liver injury. Admission AST (69 vs. 49; P < 0.05), peak AST (364 vs. 77; P = 0.003), and peak ALT (220 vs. 52; P = 0.002) were higher in intubated patients. CONCLUSIONS: AST-dominant aminotransferase elevation is common in COVID-19, mirrors disease severity, and appears to reflect true hepatic injury.


Subject(s)
Aspartate Aminotransferases/blood , COVID-19/complications , Liver Diseases/virology , SARS-CoV-2 , Adult , Aged , Alanine Transaminase/blood , Biomarkers/blood , COVID-19/blood , Cohort Studies , Female , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/blood , Intensive Care Units , Length of Stay , Liver/enzymology , Liver/virology , Liver Diseases/blood , Liver Diseases/enzymology , Liver Function Tests , Male , Middle Aged , Severity of Illness Index
15.
Hepatology ; 72(1): 287-304, 2020 07.
Article in English | MEDLINE | ID: covidwho-66361

ABSTRACT

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19), the illness caused by the SARS-CoV-2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID-19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID-19 pandemic on liver patients and healthcare providers. APPROACH AND RESULTS: This article discusses what is known about COVID-19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID-19 pandemic on their patients' care. CONCLUSIONS: The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID-19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.


Subject(s)
Betacoronavirus , Consensus , Coronavirus Infections/epidemiology , Liver Diseases/therapy , Liver Transplantation , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Drug Interactions , Gastroenterology/education , Humans , Internship and Residency , Liver Diseases/epidemiology , Liver Transplantation/ethics , Liver Transplantation/methods , Occupational Health , Pandemics , Patient Safety , Pneumonia, Viral/drug therapy , Pneumonia, Viral/transmission , SARS-CoV-2 , Tissue Donors
16.
J Vasc Interv Radiol ; 31(6): 869-875, 2020 06.
Article in English | MEDLINE | ID: covidwho-42072

ABSTRACT

This paper describes country-wide special measures undertaken for interventional radiology staff during the current coronavirus disease 2019 (COVID-19) pandemic. Although each interventional radiology service around the world faces unique challenges, the principles outlined in this article will be useful when designing or strengthening individual practices and integrating them within wider hospital and national measures. Moving beyond the current outbreak, these measures will be useful for any future infectious diseases which are likely to arise.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/complications , Pneumonia, Viral/prevention & control , Radiology, Interventional/methods , COVID-19 , Humans , Singapore
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