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Winyupakorn J, Sangketchon C, Devakul Na Ayutthaya W, Sethasine S. Liver injury in non-severe COVID-19 with various pandemic phases: A real-world study. J Formos Med Assoc 2025:S0929-6646(25)00144-5. [PMID: 40169313 DOI: 10.1016/j.jfma.2025.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 10/15/2024] [Accepted: 03/26/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND COVID-19 severity affects liver damage. The utilization of various anti-COVID-19 drugs in non-severe cases related to liver impairment in the short term seemed intriguing. OBJECTIVES To assess the dynamic course of liver injury in mild to moderate COVID-19 patients within 10 days of admission and identify risk variables, including medication linkage. METHODS This prospective cohort study of 300 newly diagnosed mild to moderate COVID-19 cases between September 2021 and October 2022. Tertiary center hospitel, field hospital, or cohort ward admissions were made. Patient demographics and treatment were recorded. The drug, liver injury (LI) dynamics, and clinical course were evaluated. RESULTS Hospitel/field hospital (188) and cohort wards (112) had 300 individuals. One hundred fifteen participants had liver damage. Favipiravir (45 %), remdesivir (17.4 %), molnupiravir (11.3 %), Andrographis paniculata (ADG) (8.7 %), and favipiravir plus ivermectin (7.7 %) were given to most LI group (n = 104). The baseline AST/ALT levels of 68 (65.4 %) treated patients were abnormal. Favipiravir, remdesivir, and favipiravir + ivermectin increased mean AST/ALT in participants with normal baseline AST/ALT (p = 0.001, 0.003, and 0.016, respectively), but not molnupiravir or Andrographis paniculata. Transaminase levels climbed in untreated patients independent of baseline. The ground-glass imaging pattern was linked to mild LI. Most subjects had transaminase declines after 10 days. Preexisting liver disease did not increase the likelihood of in-hospital LI. CONCLUSION In the real world, a less-than-critical level of liver damage was reported in mild to moderate COVID-19 that allows clinicians to administer a variety of standard medications during short periods of hospital stay.
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Affiliation(s)
- Jirayuth Winyupakorn
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok, 10300, Thailand
| | - Chunlanee Sangketchon
- Division of Disaster and Emergency, Medical Operation Department, Faculty of Science and Health Technology, Vajira Hospital, Navamindradhiraj University, Dusit, 10300, Bangkok, Thailand
| | - Watcharaporn Devakul Na Ayutthaya
- Division of Pharmacology, Department of Basic Medical Science, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok, 10300, Thailand
| | - Supatsri Sethasine
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok, 10300, Thailand.
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2
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Lam E, Gomez-Paz S, Gonzalez-Mosquera LF, Mirabella S, Cardenas-Maldonado D, Fogel J, Rubinstein S. Multi-Organ Systems Involvement in COVID-19 is Associated With a Worse Prognosis. J Acute Med 2024; 14:61-73. [PMID: 38855050 PMCID: PMC11153311 DOI: 10.6705/j.jacme.202406_14(2).0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 09/11/2016] [Accepted: 09/19/2016] [Indexed: 06/11/2024]
Abstract
Background Coronavirus disease 2019 (COVID-19) has multiple organ system involvement but the association of organ system involvement with disease prognosis has not been reported. We study the association of organ systems involved with in-hospital mortality and hospital length of stay (LOS) in COVID-19. Methods Retrospective study of 808 consecutive patients with confirmed-laboratory diagnosis of COVID-19 in a New York hospital from March 1-May 15, 2020. Results Increased number of organs systems involved was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.11-1.66, p < 0.01) and increased LOS (B = 0.02, SE = 0.01, p < 0.05). Increased platelet count was associated with decreased odds for mortality (OR: 0.996, 95% CI: 0.994-0.998, p < 0.001). Increased white blood cell count was associated with increased odds for mortality (OR: 14.00, 95% CI: 3.41-57.38, p < 0.001). Increased creatinine and glucose were each associated with increased LOS (B = 0.11, SE = 0.04, p < 0.01, and B = 0.12, SE = 0.05, p < 0.05, respectively). Increased odds for mortality were also found in high FiO2 oxygen requirement (OR: 11.63, 95% CI: 3.90-34.75, p < 0.001) and invasive mechanical ventilation (OR: 109.93, 95% CI: 29.44-410.45, p < 0.001). Conclusion Multiple organ systems involvement in COVID-19 is associated with worse prognosis. Clinical/laboratory values corresponding to each organ system may be used as prognostic tools in clinical settings to tailor treatments for COVID-19 patients.
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Affiliation(s)
- Eric Lam
- Nassau University Medical Center Department of Medicine East Meadow, NY USA
| | - Sandra Gomez-Paz
- Department of Medicine Division of Nephrology & Hypertension East Meadow, NY USA
| | | | - Steven Mirabella
- Nassau University Medical Center Department of Medicine East Meadow, NY USA
| | | | - Joshua Fogel
- Brooklyn College Department of Business Management Brooklyn, NY USA
| | - Sofia Rubinstein
- Department of Medicine Division of Nephrology & Hypertension East Meadow, NY USA
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3
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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4
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Clinical Predictors for Abnormal ALT in Patients Infected with COVID-19—A Retrospective Single Centre Study. Pathogens 2023; 12:pathogens12030473. [PMID: 36986395 PMCID: PMC10057561 DOI: 10.3390/pathogens12030473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/09/2023] [Accepted: 03/09/2023] [Indexed: 03/19/2023] Open
Abstract
Objective: Abnormal liver tests have been associated with worse clinical outcomes in patients infected with COVID-19. This retrospective observational study from Singapore aims to elucidate simple clinical predictors of abnormal alanine aminotransferase (ALT) in COVID-19 infections. Design: 717 patients hospitalised with COVID-19 at the National Centre for Infectious Diseases (NCID), Singapore, from 23 January–15 April 2020 were screened, of which 163 patients with baseline normal alanine transferase (ALT) and at least two subsequent ALTs performed were included in the final analysis. Information on baseline demographics, clinical characteristics and biochemical laboratory tests were collected. Results: 30.7% of patients developed abnormal ALT. They were more likely to be older (60 vs. 55, p = 0.022) and have comorbidities of hyperlipidaemia and hypertension. The multivariate logistic regression showed that R-factor ≥1 on admission (adjusted odds ratio (aOR) 3.13, 95% Confidence Interval (CI) 1.41–6.95) and hypoxia (aOR 3.54, 95% CI 1.29–9.69) were independent risk factors for developing abnormal ALT. The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58% vs. 18.6%, p < 0.0005), admission to the Intensive Care Unit (ICU)/High Dependency Unit (HDU) (32% vs. 11.5%, p = 0.003) and intubation (20% vs. 2.7%, p < 0.0005). There was no difference in death rate between the two groups. Conclusions: Liver injury is associated with poor clinical outcomes in patients with COVID-19. R-factor ≥1 on admission and hypoxia are independent simple clinical predictors for developing abnormal ALT in COVID-19.
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Ekpanyapong S, Reddy KR. Liver and Biliary Tract Disease in Patients with Coronavirus disease-2019 Infection. Gastroenterol Clin North Am 2023; 52:13-36. [PMID: 36813421 PMCID: PMC9531659 DOI: 10.1016/j.gtc.2022.09.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Coronavirus disease-2019 (COVID-19) had become a global pandemic since March 2020. Although, the most common presentation is of pulmonary involvement, hepatic abnormalities can be encountered in up to 50% of infected individuals, which may be associated with disease severity, and the mechanism of liver injury is thought to be multifactorial. Guidelines for management in patients with chronic liver disease during COVID-19 era are being regularly updated. Patients with chronic liver disease and cirrhosis, including liver transplant candidates and liver transplant recipients are strongly recommended to receive SARS-CoV-2 vaccination because it can reduce rate of COVID-19 infection, COVID-19-related hospitalization, and mortality.
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Affiliation(s)
- Sirina Ekpanyapong
- Division of Gastroenterology and Hepatology, Department of Medicine, Huachiew General Hospital, 665 Bumroongmueang Road, Khlong Mahanak, Bangkok 10100, Thailand; Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, Liver Transplant Office, HUP3400 Spruce Street, Philadelphia, PA 19104, USA
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, Liver Transplant Office, HUP3400 Spruce Street, Philadelphia, PA 19104, USA.
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6
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Clinical predictors of recovery of COVID-19 associated-abnormal liver function test 2 months after hospital discharge. Sci Rep 2022; 12:17972. [PMID: 36289394 PMCID: PMC9606373 DOI: 10.1038/s41598-022-22741-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 10/19/2022] [Indexed: 01/24/2023] Open
Abstract
This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020-06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5-5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7-82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.
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7
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Boyuk B, Akin S, Aladag N, Isik A, Erman H, Ozgur Y, Topal M, Karademir N, Tomar Uysal B, Ozbilgehan B, Kabaca D, Kalmaz C, Arslan S, Keskin O. COVID-19 pneumonia in patients with impaired fasting glucose, newly diagnosed diabetes and pre-existing diabetes: a tertiary center experience. J Investig Med 2022; 70:1481-1487. [PMID: 35654475 PMCID: PMC9195151 DOI: 10.1136/jim-2022-002363] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2022] [Indexed: 01/08/2023]
Abstract
COVID-19 infection is known to increase mortality in patients with diabetes. We aim to demonstrate the differences in disease course and clinical outcomes of patients with COVID-19 regarding the presence of impaired fasting glucose, pre-existing diabetes mellitus (DM) or new-onset DM. 236 patients with positive reverse transcription-PCR tests for SARS-CoV-2 were included in this single-center, retrospective observational study between March 2020 and May 2021. Laboratory results, comorbidities, medications and imaging findings were noted. Logistic regression was used to estimate associated factors for admission to the intensive care unit (ICU). 43 patients with normal glucose, 53 with impaired fasting glucose, 60 with newly diagnosed DM, and 80 with pre-existing DM were classified. Patients with pre-existing DM had higher fasting glucose and glycated hemoglobin than the other groups (p<0.001 for all). Patients with newly diagnosed DM were more likely to need dexamethasone 6 mg (p=0.001). In both newly diagnosed diabetes and impaired fasting glucose groups, 250 mg methylprednisolone was needed at higher rates (p=0.002). Newly diagnosed DM had higher rates of intubation (21.6%) and more mortality (20.0%) (p=0.045 and p=0.028, respectively). Mortality and hospitalization in the ICU were lower in the group receiving antidiabetic treatment. The risk of ICU attendance was higher in patients with impaired fasting glucose (HR=1.71, 95% CI: 0.48 to 6.08) and newly diagnosed DM (HR=1.88, 95% CI: 0.57 to 6.17), compared with pre-existing DM and non-diabetics. Newly diagnosed DM and impaired fasting glucose are associated with increased mortality and intubation in inpatients with COVID-19.
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Affiliation(s)
- Banu Boyuk
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Seydahmet Akin
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Nazire Aladag
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Arzu Isik
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Hande Erman
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Yasemin Ozgur
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Meryem Topal
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Nevra Karademir
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Busra Tomar Uysal
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Bahar Ozbilgehan
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Dilan Kabaca
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Canan Kalmaz
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
| | - Seyma Arslan
- Public Health, Istanbul Universitesi Istanbul Tip Fakultesi, Istanbul, Turkey
| | - Ozcan Keskin
- Internal Medicine, Istanbul Kartal Dr Lufti Kirdar City Hospital, Istanbul, Turkey
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8
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Chin YF, Tang WF, Chang YH, Chang TY, Lin WC, Lin CY, Yang CM, Wu HL, Liu PC, Sun JR, Hsu SC, Lee CY, Lu HY, Chang JY, Jheng JR, Chen CC, Kau JH, Huang CH, Chiu CH, Hung YJ, Tsai HP, Horng JT. Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a Syrian hamster model. J Food Drug Anal 2022; 30:252-270. [PMID: 39666306 PMCID: PMC9635900 DOI: 10.38212/2224-6614.3412] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/10/2022] [Accepted: 04/28/2022] [Indexed: 05/28/2024] Open
Abstract
On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3-4 post-infection days). As expected, SARS-CoV-2 induced lung inflammation and hemorrhagic effusions in the alveoli and perivascular areas; additionally, it increased the expression of several immune markers of lung injury - including lung Ki67-positive cells, Iba-1-positive macrophages, and myeloperoxidase-positive neutrophils. Virus-induced lung alterations were significantly attenuated by orally administered PLE. In addition, pretreatment of hamsters with PLE significantly reduced viral loads and immune marker expression. A purified active fraction of PLE was found to confer higher antiviral protection. Notably, PLE prevented SARS-CoV-2-induced increase in serum markers of liver and kidney function as well as the decrease in serum high-density lipoprotein and total cholesterol levels in a dose-dependent fashion. Differently from lung pathology, monitoring of serum biomarkers in Syrian hamsters may allow a more humane assessment of the novel drugs with potential anti-SARS-CoV-2 activity. Our results expand prior research by confirming that PLE may exert an in vivo therapeutic activity against SARS-CoV-2 by attenuating viral loads and lung tissue inflammation, which may pave the way for future clinical applications.
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Affiliation(s)
- Yuan-Fan Chin
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Wen-Fan Tang
- Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan,
Taiwan
| | - Yu-Hsiu Chang
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Tein-Yao Chang
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
- Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114,
Taiwan
| | - Wen-Chin Lin
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
- Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114,
Taiwan
| | - Chia-Yi Lin
- Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan,
Taiwan
| | - Chuen-Mi Yang
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Hsueh-Ling Wu
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Ping-Cheng Liu
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Jun-Ren Sun
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
- Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114,
Taiwan
- Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei,
Taiwan
| | - Shu-Chen Hsu
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Chia-Ying Lee
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Hsuan-Ying Lu
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Jia-Yu Chang
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Jia-Rong Jheng
- Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University School of Medicine, Indianapolis, IN,
USA
| | - Cheng Cheung Chen
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei,
Taiwan
| | - Jyh-Hwa Kau
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei,
Taiwan
- Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei,
Taiwan
| | - Chih-Heng Huang
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
- Graduate Institute of Medical Science, National Defense Medical Center, Taipei,
Taiwan
- Department of Microbiology and Immunology, National Defense Medical Center, Taipei,
Taiwan
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan,
Taiwan
| | - Yi-Jen Hung
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Hui-Ping Tsai
- Institute of Preventive Medicine, National Defense Medical Center, Taipei,
Taiwan
| | - Jim-Tong Horng
- Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan,
Taiwan
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan,
Taiwan
- Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Kweishan, Taoyuan,
Taiwan
- Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan,
Taiwan
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9
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Araya S, Tsegay YG, Atlaw A, Aragaw M, Tadlo G, Tsegaye N, Kahase D, Gebreyohanes Z, Bitew M, Berhane N. Organ function biomarker abnormalities, associated factors and disease outcome among hospitalized patients with COVID-19. Biomark Med 2022; 16:417-426. [PMID: 35234521 PMCID: PMC8890361 DOI: 10.2217/bmm-2021-0681] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: The aim of this study was to determine the magnitude of abnormal organ function tests and biomarkers in hospitalized patients with confirmed COVID-19 and to define the association among markers of organ failure, disease severity and its outcome in hospitalized COVID-19 patients in Ethiopia. Methods: A prospective cohort study was conducted among COVID-19 patients admitted to Millennium COVID-19 Treatment Center from December 2020 to June 2021. Results: The median age of the 440 study participants was 60.3 ± 1.3 years, and from these 71.3% of patients were male. Disease severity: p-value: 0.032; adjusted odds ratio (AOR) (95% CI): 4.4 (0.022-0.085); and the presence of any co-morbidity; p-value: 0.012; AOR (95% CI): 0.80 (0.47-0.83) was significantly associated with mortality. Aspartate transaminase, alanine transaminase and alkaline phosphatase parameter values of patients overall, were elevated - mainly among critical patients (56.9 ± 57.7, 58.5 ± 63 and 114.6 ± 60, respectively).
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Affiliation(s)
- Shambel Araya
- Addis Ababa University College of Health Science, Department of Medical Laboratory Science, Addis Ababa, Ethiopia
| | - Yakob G Tsegay
- Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia.,Department of Research & Development Center, College of Health Sciences, Defense University, Addis Ababa, Ethiopia
| | - Assegdew Atlaw
- Addis Ababa University, College of Health Science, Department of Medical Microbiology, Immunology & Parasitology, Addis Ababa, Ethiopia
| | - Mintsnot Aragaw
- Addis Ababa University College of Health Science, Department of Medical Laboratory Science, Addis Ababa, Ethiopia.,Department of Medical Laboratory Science, St. Paul Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia
| | - Getachew Tadlo
- Department of Medical Laboratory Science, St. Paul Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia
| | - Nebiyu Tsegaye
- Addis Ababa University College of Health Science, Department of Medical Laboratory Science, Addis Ababa, Ethiopia.,Department of Medical Laboratory Science, St. Paul Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia
| | - Daniel Kahase
- Department of Medical Laboratory Sciences, College of Medicine & Health Sciences, Wolkite University, South Nation Nationality & Peoples, Ethiopia
| | - Zenebe Gebreyohanes
- Department of Medical Laboratory Science, St. Paul Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia
| | | | - Nega Berhane
- Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia
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10
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Krishnan A, Prichett L, Tao X, Alqahtani SA, Hamilton JP, Mezey E, Strauss AT, Kim A, Potter JJ, Chen PH, Woreta TA. Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients. World J Gastroenterol 2022; 28:570-587. [PMID: 35316959 PMCID: PMC8905016 DOI: 10.3748/wjg.v28.i5.570] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/21/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood. AIM We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality. METHODS This retrospective, observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System (Baltimore, MD, United States). Demographic data, clinical characteristics, laboratory findings, treatment measures, and outcome data were collected. Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis. RESULTS A total of 2698 (70.4%) had abnormal alanine aminotransferase (ALT) at the time of admission. Other more prevalent abnormal liver chemistries were aspartate aminotransferase (AST) (44.4%), alkaline phosphatase (ALP) (16.1%), and total bilirubin (T-Bil) (5.9%). Factors associated with liver injury were older age, Asian ethnicity, other race, being overweight, and obesity. Higher ALT, AST, T-Bil, and ALP levels were more commonly associated with disease severity. Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization. Abnormal AST, T-Bil, and ALP were associated with a need for vasopressor drugs, whereas higher levels of AST, T-Bil, and a decreased albumin levels were associated with mechanical ventilation. CONCLUSION Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient's severity and prognosis. Elevated liver chemistries, specifically ALT, AST, ALP, and T-Bil levels, can be used to stratify risk and predict the need for advanced therapies in these patients.
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Affiliation(s)
- Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Laura Prichett
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Xueting Tao
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
- Liver Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh 12713, Saudi Arabia
| | - James P Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Esteban Mezey
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Alexandra T Strauss
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Ahyoung Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - James J Potter
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
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11
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Ekpanyapong S, Bunchorntavakul C, Reddy KR. COVID-19 and the Liver: Lessons Learnt from the EAST and the WEST, A Year Later. J Viral Hepat 2022; 29:4-20. [PMID: 34352133 PMCID: PMC8446947 DOI: 10.1111/jvh.13590] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023]
Abstract
Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus) has been a major cause for significant morbidity and mortality. Since the start of the pandemic, several hepato-biliary manifestations in coronavirus disease 2019 (COVID-19) have been described and unique considerations raised. The review aims to summarize the pathogenesis and hepato-biliary manifestations in COVID-19 and discuss the similarities, contrasting features and disease-specific management across a range of hepato-biliary diseases from the EAST and the WEST. Published studies and regional society guidelines from the EAST and the WEST were comprehensively reviewed and summarized. A wide range of hepato-biliary manifestations, including the infrequent and chronic manifestation of cholangiopathy, has been observed in COVID-19. The pathogenesis of liver injury is multifactorial and with scant evidence for a direct SARS-CoV-2 infection of the liver. Patients with non-alcoholic fatty liver disease, cirrhosis, and liver cancer are potentially at increased risk for severe COVID-19, and there are unique considerations in chronic hepatitis B or C, hepatocellular carcinoma, and in those immunosuppressed such as autoimmune hepatitis or liver transplant recipients. With the surges in SARS-CoV-2 infection, liver transplant activity has variably been impacted. Preliminarily, SARS-CoV-2 vaccines appear to be safe in those with chronic liver disease and in transplant recipients, while emerging data suggest the need for a third dose in immunosuppressed patients. In conclusion, patients with chronic liver disease, particularly cirrhosis, and liver transplant recipients, are vulnerable to severe COVID-19. Over the past year, several unique considerations have been highlighted across a spectrum of hepato-biliary diseases. Vaccination is strongly recommended for those with chronic liver disease and liver transplant recipients.
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Affiliation(s)
- Sirina Ekpanyapong
- Division of Gastroenterology and HepatologyDepartment of MedicineRajavithi HospitalBangkokThailand
| | | | - K. Rajender Reddy
- Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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12
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Przekop D, Gruszewska E, Chrostek L. Liver function in COVID-19 infection. World J Hepatol 2021; 13:1909-1918. [PMID: 35069997 PMCID: PMC8727219 DOI: 10.4254/wjh.v13.i12.1909] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/07/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) disease affects multiple organs, including anomalies in liver function. In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease. Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients, severity of liver injury, presence of comorbidity and pre-treatment. The method of antiviral treatment can also impact on liver function, which manifests as increasing values in liver function tests. Therefore, analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.
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Affiliation(s)
- Dagmara Przekop
- Diagnostics-Experimental Center of Sexually Transmissible Diseases, Bialystok 15-879, Poland
| | - Ewa Gruszewska
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok 15-269, Poland
| | - Lech Chrostek
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok 15-269, Poland
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13
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Kukla M, Menżyk T, Dembiński M, Winiarski M, Garlicki A, Bociąga-Jasik M, Skonieczna M, Hudy D, Maziarz B, Kusnierz-Cabala B, Skladany L, Grgurevic I, Wójcik-Bugajska M, Grodzicki T, Stygar D, Rogula T. Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes. Sci Rep 2021; 11:21514. [PMID: 34728695 PMCID: PMC8563971 DOI: 10.1038/s41598-021-00928-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 10/11/2021] [Indexed: 12/15/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.
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Affiliation(s)
- Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland.,Department of Endoscopy, University Hospital in Kraków, Cracow, Poland
| | - Tomasz Menżyk
- Department of Internal Medicine, Gastroenterology and Acute Intoxication, Regional Hospital, Tarnów, Poland
| | - Marcin Dembiński
- Department of Endoscopy, University Hospital in Kraków, Cracow, Poland.,2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Marek Winiarski
- Department of Endoscopy, University Hospital in Kraków, Cracow, Poland.,2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Aleksander Garlicki
- Chair of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Monika Bociąga-Jasik
- Chair of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Magdalena Skonieczna
- Department of Systems Biology and Engineering, Silesian University of Technology, 44-100, Gliwice, Poland.,Biotechnology Centre, Silesian University of Technology, 44-100, Gliwice, Poland
| | - Dorota Hudy
- Department of Systems Biology and Engineering, Silesian University of Technology, 44-100, Gliwice, Poland.,Biotechnology Centre, Silesian University of Technology, 44-100, Gliwice, Poland
| | - Barbara Maziarz
- Chair of Clinical BioChemistry, Department of Diagnostics, Faculty of Medicine, Jagiellonian University Medical College, 31-501, Cracow, Poland
| | - Beata Kusnierz-Cabala
- Chair of Clinical BioChemistry, Department of Diagnostics, Faculty of Medicine, Jagiellonian University Medical College, 31-501, Cracow, Poland
| | - Lubomir Skladany
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Banska Bystrica, Slovakia
| | - Ivica Grgurevic
- Zagreb University School of Medicine, Šalata ul. 2, 10000, Zagreb, Croatia.,Division for Liver Diseases, Department of Gastroenterology, Dubrava University Hospital, Zagreb, Croatia
| | - Małgorzata Wójcik-Bugajska
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Tomasz Grodzicki
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Dominika Stygar
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, 40-055, Katowice, Poland.
| | - Tomasz Rogula
- Case Western Reserve University School of Medicine, Cleveland, OH, USA.,1st Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Cracow, Poland
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14
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Miele L, Napodano C, Cesario A, De Magistris A, Pocino K, Basile U, Rapaccini GL, Gasbarrini A, Grieco A. COVID-19, adaptative immune response and metabolic-associated liver disease. Liver Int 2021; 41:2560-2577. [PMID: 34555255 PMCID: PMC8661993 DOI: 10.1111/liv.15061] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 08/13/2021] [Accepted: 08/17/2021] [Indexed: 01/08/2023]
Abstract
Metabolic diseases are associated with a higher risk of a severer coronavirus disease 2019 (COVID-19) course, since fatty liver is commonly associated with metabolic disorders, fatty liver itself is considered as a major contributor to low-grade inflammation in obesity and diabetes. Recently a comprehensive term, metabolic (dysfunction) associated fatty liver disease (MAFLD), has been proposed. The hepatic inflammatory status observed in MAFLD patients is amplified in presence of severe acute respiratory syndrome coronavirus 2 infection. Intestinal dysbiosis is a powerful activator of inflammatory mediator production of liver macrophages. The intestinal microbiome plays a key role in MAFLD progression, which results in non-alcoholic steatohepatitis and liver fibrosis. Therefore, patients with metabolic disorders and COVID-19 can have a worse outcome of COVID-19. This literature review attempts to disentangle the mechanistic link of MAFLD from COVID-19 complexity and to improve knowledge on its pathophysiology.
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Affiliation(s)
- Luca Miele
- Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly
- Dipartimento di Medicina e Chirurgia TraslazionaleScuola di Medicina e ChirurgiaUniversità Cattolica del Sacro CuoreRomeItaly
| | - Cecilia Napodano
- Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly
- Dipartimento di Medicina e Chirurgia TraslazionaleScuola di Medicina e ChirurgiaUniversità Cattolica del Sacro CuoreRomeItaly
| | - Alfredo Cesario
- Open Innovation ManagerScientific DirectorateFondazione Policlinico Universitario A.Gemelli IRCCSUniversità Cattolica del Sacro CuoreRomeItaly
| | - Antonio De Magistris
- Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly
| | - Krizia Pocino
- Dipartimento di Medicina e Chirurgia TraslazionaleScuola di Medicina e ChirurgiaUniversità Cattolica del Sacro CuoreRomeItaly
| | - Umberto Basile
- Dipartimento di Scienze di laboratorio e infettivologicheFondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
| | - Gian L. Rapaccini
- Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly
- Dipartimento di Medicina e Chirurgia TraslazionaleScuola di Medicina e ChirurgiaUniversità Cattolica del Sacro CuoreRomeItaly
| | - Antonio Gasbarrini
- Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly
- Dipartimento di Medicina e Chirurgia TraslazionaleScuola di Medicina e ChirurgiaUniversità Cattolica del Sacro CuoreRomeItaly
| | - Antonio Grieco
- Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly
- Dipartimento di Medicina e Chirurgia TraslazionaleScuola di Medicina e ChirurgiaUniversità Cattolica del Sacro CuoreRomeItaly
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15
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Sirinawasatien A, Chantarojanasiri T, Ekpanyapong S, Tivatunsakul N, Luvira V. Coronavirus disease 2019 gastrointestinal and liver manifestations in adults: A review. JGH Open 2021; 5:1257-1265. [PMID: 34816011 PMCID: PMC8593773 DOI: 10.1002/jgh3.12671] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 10/09/2021] [Accepted: 10/12/2021] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is an important health problem that has a serious adverse impact on the global economy and healthcare systems. The virus is not only involved in the respiratory system, but also causes other systemic effects as well as several gastrointestinal and liver issues. Evidence has shown direct viral invasion into the gastrointestinal tissue and supporting vascular network, causing various manifestations such as diarrhea, nausea, gastrointestinal bleeding, and abnormal liver function tests. The degree of gastrointestinal injury, especially in terms of liver involvement, is correlated with disease severity. There is no specific treatment for gastrointestinal involvement, and the symptoms can be managed with supportive therapy. Moreover, increased liver decompensation and mortality can be found in COVID-19-infected patients with coexisting liver disease. As the virus can be identified in gastrointestinal contents, endoscopic procedures during the pandemic should be carefully selected and proper protection strategies should be encouraged to prevent viral transmission.
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Affiliation(s)
- Apichet Sirinawasatien
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of MedicineRungsit UniversityBangkokThailand
| | - Tanyaporn Chantarojanasiri
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of MedicineRungsit UniversityBangkokThailand
| | - Sirina Ekpanyapong
- Division of Gastroenterology, Department of Medicine, Rajavithi Hospital, College of MedicineRungsit UniversityBangkokThailand
| | - Naris Tivatunsakul
- Division of Gastroenterology, Department of MedicineBanpong HospitalRatchaburiThailand
| | - Viravarn Luvira
- Department of Clinical Tropical Medicine, Faulty of Tropical MedicineMahidol UniversityBangkokThailand
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16
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Weber S, Hellmuth JC, Scherer C, Muenchhoff M, Mayerle J, Gerbes AL. Liver function test abnormalities at hospital admission are associated with severe course of SARS-CoV-2 infection: a prospective cohort study. Gut 2021; 70:1925-1932. [PMID: 33514597 PMCID: PMC7852072 DOI: 10.1136/gutjnl-2020-323800] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/11/2021] [Accepted: 01/17/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Liver injury has frequently been reported in COVID-19 patients. The clinical relevance of liver injury related to SARS-CoV-2 infection remains unclear with a need for prospective studies on the impact of liver function test (LFT) abnormalities at baseline. DESIGN Data of 217 patients without pre-existing liver disease prospectively included in the COVID-19 registry of the LMU university hospital were analysed in order to assess the association of abnormal LFT at admission and course of the disease. Severe course was defined as admission to the intensive care unit (ICU) or as COVID-19-related death. RESULTS Abnormal LFT at baseline was present in 58% of patients, with a predominant elevation of aspartate aminotransferase (AST) (42%), gamma-glutamyltransferase (GGT) (37%) and alanine aminotransferase (ALT) (27%), hypoalbuminaemia was observed in 33%. Elevation of ALT and GGT, as well as hypoalbuminaemia, was associated with higher proportions of patients requiring ICU treatment and mechanical ventilation. After adjusting for age, gender and comorbidities, hypoalbuminaemia combined with abnormal AST or GGT at hospital admission was a highly significant independent risk factor for ICU admission (OR 46.22 and 38.8, respectively) and for a composite endpoint of ICU admission and/or COVID-19-related death (OR 42.0 and 26.9, respectively). CONCLUSION Abnormal LFTs at hospital admission, in particular GGT and albumin, are associated with a severe course of SARS-CoV-2 infection.
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Affiliation(s)
- Sabine Weber
- Department of Medicine II, University Hospital Munich, Munich, Bavaria, Germany
| | - Johannes C Hellmuth
- Department of Medicine III, University Hospital Munich, Munich, Bavaria, Germany
| | - Clemens Scherer
- Department of Medicine I, University Hospital Munich, Munich, Bavaria, Germany
| | - Maximilian Muenchhoff
- Virology, Ludwig Maximilians University of Munich, Munich, Bavaria, Germany
- German Centre for Infection Research (DZIF), partner site Munich, Munich, Bavaria, Germany
| | - Julia Mayerle
- Department of Medicine II, University Hospital Munich, Munich, Bavaria, Germany
| | - Alexander L Gerbes
- Department of Medicine II, University Hospital Munich, Munich, Bavaria, Germany
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17
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Kukla M, Menżyk T, Dembiński M, Winiarski M, Garlicki A, Bociąga-Jasik M, Skonieczna M, Hudy D, Maziarz B, Kuśnierz-Cabala B, Kapusta M, Skladany L, Grgurevic I, Mikolasevic I, Filipec-Kanizaj T, Wójcik-Bugajska M, Grodzicki T, Rogula T, Stygar D. Fetuin-A Deficiency but Not Pentraxin 3, FGF-21, or Irisin, Predisposes to More Serious COVID-19 Course. Biomolecules 2021; 11:1422. [PMID: 34680053 PMCID: PMC8533535 DOI: 10.3390/biom11101422] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/19/2021] [Accepted: 09/22/2021] [Indexed: 02/07/2023] Open
Abstract
Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.
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Affiliation(s)
- Michał Kukla
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (M.K.); (M.W.-B.); (T.G.)
- Department of Endoscopy, University Hospital in Kraków, Jakubowskiego 2, 30-688 Kraków, Poland; (M.D.); (M.W.)
| | - Tomasz Menżyk
- Department of Internal Medicine, Gastroenterology and Acute Intoxication, Regional Hospital, Lwowska 178A, 33-100 Tarnów, Poland;
| | - Marcin Dembiński
- Department of Endoscopy, University Hospital in Kraków, Jakubowskiego 2, 30-688 Kraków, Poland; (M.D.); (M.W.)
- 2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland
| | - Marek Winiarski
- Department of Endoscopy, University Hospital in Kraków, Jakubowskiego 2, 30-688 Kraków, Poland; (M.D.); (M.W.)
- 2nd Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland
| | - Aleksander Garlicki
- Chair of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (A.G.); (M.B.-J.)
| | - Monika Bociąga-Jasik
- Chair of Gastroenterology, Hepatology and Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (A.G.); (M.B.-J.)
| | - Magdalena Skonieczna
- Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland; (M.S.); (D.H.)
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland
| | - Dorota Hudy
- Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland; (M.S.); (D.H.)
- Biotechnology Centre, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland
| | - Barbara Maziarz
- Department of Diagnostics, Chair of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (B.M.); (B.K.-C.); (M.K.)
| | - Beata Kuśnierz-Cabala
- Department of Diagnostics, Chair of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (B.M.); (B.K.-C.); (M.K.)
| | - Maria Kapusta
- Department of Diagnostics, Chair of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (B.M.); (B.K.-C.); (M.K.)
| | - Lubomir Skladany
- Department of Internal Medicine and HEGITO (Hepatology, Gastroenterology and Liver Transplantation), F.D. Roosevelt University Hospital, Nam. l. Svobodu 1, 975 17 Banska Bystrica, Slovakia;
| | - Ivica Grgurevic
- School of Medicine, Zagreb University, Šalata ul. 2, 10000 Zagreb, Croatia; (I.G.); (T.F.-K.)
- Division for Liver Diseases, Department of Gastroenterology, Dubrava University Hospital, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia
| | - Ivana Mikolasevic
- Department of Gastroenterology, Clinical Hospital Center Rijeka, Krešimirova ul. 42, 51000 Rijeka, Croatia;
| | - Tajana Filipec-Kanizaj
- School of Medicine, Zagreb University, Šalata ul. 2, 10000 Zagreb, Croatia; (I.G.); (T.F.-K.)
| | - Małgorzata Wójcik-Bugajska
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (M.K.); (M.W.-B.); (T.G.)
| | - Tomasz Grodzicki
- Department of Internal Medicine and Geriatrics, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland; (M.K.); (M.W.-B.); (T.G.)
| | - Tomasz Rogula
- 1st Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Kraków, Poland;
- Health Education Campus, Case Western Reserve University School of Medicine, 9501 Euclid Ave, Cleveland, OH 44106, USA
| | - Dominika Stygar
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland
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18
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Wang T, Smith DA, Campbell C, Harris S, Salih H, Várnai KA, Woods K, Noble T, Freeman O, Moysova Z, Marjot T, Webb GJ, Davies J, Barnes E, Matthews PC. Longitudinal Analysis of the Utility of Liver Biochemistry as Prognostic Markers in Hospitalized Patients With Corona Virus Disease 2019. Hepatol Commun 2021; 5:1586-1604. [PMID: 34510830 PMCID: PMC8239606 DOI: 10.1002/hep4.1739] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 03/22/2021] [Accepted: 04/11/2021] [Indexed: 02/04/2023] Open
Abstract
The association of liver biochemistry with clinical outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently unclear, and the utility of longitudinally measured liver biochemistry as prognostic markers for mortality is unknown. We aimed to determine whether abnormal liver biochemistry, assessed at baseline and at repeat measures over time, was associated with death in hospitalized patients with COVID-19 compared to those without COVID-19, in a United Kingdom population. We extracted routinely collected clinical data from a large teaching hospital in the United Kingdom, matching 585 hospitalized patients who were SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) positive to 1,165 hospitalized patients who were RT-PCR negative for age, sex, ethnicity, and preexisting comorbidities. A total of 26.8% (157/585) of patients with COVID-19 died compared to 11.9% (139/1,165) in the group without COVID-19 (P < 0.001). At presentation, a significantly higher proportion of the group with COVID-19 had elevated alanine aminotransferase (20.7% vs. 14.6%, P = 0.004) and hypoalbuminemia (58.7% vs. 35.0%, P < 0.001) compared to the group without COVID-19. Within the group with COVID-19, those with hypoalbuminemia at presentation had 1.83-fold increased hazards of death compared to those with normal albumin (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.25-2.67), while the hazard of death was ~4-fold higher in those aged ≥75 years (adjusted HR, 3.96; 95% CI, 2.59-6.04) and ~3-fold higher in those with preexisting liver disease (adjusted HR, 3.37; 95% CI, 1.58-7.16). In the group with COVID-19, alkaline phosphatase (ALP) increased (R = 0.192, P < 0.0001) and albumin declined (R = -0.123, P = 0.0004) over time in patients who died. Conclusion: In this United Kingdom population, liver biochemistry is commonly deranged in patients with COVID-19. Baseline hypoalbuminemia and rising ALP over time could be prognostic markers for death, but investigation of larger cohorts is required to develop a better understanding of the relationship between liver biochemistry and disease outcome.
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Affiliation(s)
- Tingyan Wang
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Nuffield Department of MedicineUniversity of OxfordOxfordUnited Kingdom
| | - David A. Smith
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
| | - Cori Campbell
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Nuffield Department of MedicineUniversity of OxfordOxfordUnited Kingdom
| | - Steve Harris
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Department of Computer ScienceUniversity of OxfordOxfordUnited Kingdom
| | - Hizni Salih
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
| | - Kinga A. Várnai
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
| | - Kerrie Woods
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
| | - Theresa Noble
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
| | - Oliver Freeman
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
| | - Zuzana Moysova
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology UnitJohn Radcliffe HospitalOxford University HospitalsOxfordUnited Kingdom
| | - Gwilym J. Webb
- Cambridge Liver UnitAddenbrooke's HospitalCambridgeUnited Kingdom
| | - Jim Davies
- National Institute for Health Research (NIHR) Oxford Biomedical Research CentreOxfordUnited Kingdom
- Department of Computer ScienceUniversity of OxfordOxfordUnited Kingdom
| | - Eleanor Barnes
- Nuffield Department of MedicineUniversity of OxfordOxfordUnited Kingdom
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
| | - Philippa C. Matthews
- Oxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
- Department of Infectious Diseases and MicrobiologyOxford University Hospitals National Health Service Foundation TrustOxfordUnited Kingdom
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19
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Vidal-Cevallos P, Higuera-De-La-Tijera F, Chávez-Tapia NC, Sanchez-Giron F, Cerda-Reyes E, Rosales-Salyano VH, Servin-Caamaño A, Vázquez-Medina MU, Méndez-Sánchez N. Lactate-dehydrogenase associated with mortality in hospitalized patients with COVID-19 in Mexico: a multi-centre retrospective cohort study. Ann Hepatol 2021; 24:100338. [PMID: 33647501 PMCID: PMC7908830 DOI: 10.1016/j.aohep.2021.100338] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/15/2021] [Accepted: 02/18/2021] [Indexed: 02/08/2023]
Abstract
INTRODUCTION AND OBJECTIVES As of January 2021, over 88 million people have been infected with COVID-19. Almost two million people have died of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high SOFA score and a D-Dimer >1 µg/mL identifies patients with high risk of mortality. High lactate dehydrogenase (LDH) levels on admission are associated with severity and mortality. Different degrees of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormalities have been reported in these patients, its association with a mortality risk remains controversial. The aim of this study was to explore the correlation between LDH and in-hospital mortality in Mexican patients admitted with COVID-19. MATERIALS & METHODS We performed a retrospective multi-centre cohort study with 377 hospitalized patients with confirmed SARS-CoV-2 in three centres in Mexico City, Mexico, who were ≥18 years old and died or were discharged between April 1 and May 31, 2020. RESULTS A total of 377 patients were evaluated, 298 (79.1%) patients were discharged, and 79 (20.9%) patients died during hospitalization. Non-survivors were older, with a median age of 46.7 ± 25.7 years old, most patients were male. An ALT > 61 U/l (OR 3.45, 95% CI 1.27-9.37; p = 0.015), C-reactive protein (CRP) > 231 mg/l (OR 4.71, 95% CI 2.35-9.46; p = 0.000), LDH > 561 U/l (OR 3.03, 95% CI 1.40-6.55; p = 0.005) were associated with higher odds for in-hospital death. CONCLUSIONS Our results indicate that higher levels of LDH, CRP, and ALT are associated with higher in-hospital mortality risk in Mexican patients admitted with COVID-19.
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Affiliation(s)
- Paulina Vidal-Cevallos
- Liver Research Unit, Medica Sur Clinic & Foundation and Faculty of Medicine. National Autonomous University of Mexico, Mexico City, Mexico; National Autonomous University of Mexico. Mexico City, Mexico, 14050, Mexico
| | - Fatima Higuera-De-La-Tijera
- Gastroenterology and Hepatology Department, Mexico's General Hospital "Dr. Eduardo Liceaga". Dr. Balmis 148, col. Doctores, C.P. 06720, Mexico City, Mexico
| | - Norberto C Chávez-Tapia
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation. Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Francisco Sanchez-Giron
- Director of the Clinical Pathology Laboratory, Medica Sur Clinic and Foundation. Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Eira Cerda-Reyes
- Academic Coordinator, Central Military Hospital, Periférico Blvrd Manuel Ávila Camacho s/n, col. Militar, C.P. 11200, Mexico City, Mexico
| | - Victor Hugo Rosales-Salyano
- Internal Medicine Department, Mexico's General Hospital "Dr. Eduardo Liceaga". Dr. Balmis 148, col. Doctores, C.P. 06720, Mexico City, Mexico
| | - Alfredo Servin-Caamaño
- Internal Medicine Department, Mexico's General Hospital "Dr. Eduardo Liceaga". Dr. Balmis 148, col. Doctores, C.P. 06720, Mexico City, Mexico
| | - Martín Uriel Vázquez-Medina
- Superior School of Medicine, National Polytechnic Institute Salvador Díaz Mirón S/N, Miguel Hidalgo, Casco de Santo Tomas, C.P. 11340, Mexico City, Mexico
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic & Foundation and Faculty of Medicine. National Autonomous University of Mexico, Mexico City, Mexico; National Autonomous University of Mexico. Mexico City, Mexico, 14050, Mexico.
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20
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Wu Y, Ma Z, Guo X, Li H, Tang Y, Meng H, Yu H, Peng C, Chu G, Wang X, Teng Y, Zhang Q, Zhu T, Wang B, Tong Z, Feng R, Zhao H, Lu H, Qi X. Characteristics and in-hospital outcomes of COVID-19 patients with abnormal liver biochemical tests. Ann Hepatol 2021; 24:100349. [PMID: 33862291 PMCID: PMC8056851 DOI: 10.1016/j.aohep.2021.100349] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 04/07/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Yanyan Wu
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Postgraduate College, Jinzhou Medical University, Jinzhou, 121000, P.R. China
| | - Zhuang Ma
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Department of Respiratory Medicine, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Xiaozhong Guo
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China
| | - Hongyu Li
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China
| | - Yufu Tang
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Hao Meng
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Hao Yu
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Chengfei Peng
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Guiyang Chu
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Information Section of Medical Security Center, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China
| | - Xinwei Wang
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Yue Teng
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Quanyu Zhang
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Tianyi Zhu
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Department of Respiratory Medicine, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; No. 7 Department of Infectious Diseases, Wuhan Huoshenshan Hospital, Wuhan, 430113, P.R. China
| | - Bing Wang
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Section of Medical Service, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China
| | - Zhenhua Tong
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Section of Medical Service, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China
| | - Ruirui Feng
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Postgraduate College, Jinzhou Medical University, Jinzhou, 121000, P.R. China
| | - Haitao Zhao
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Department of Respiratory Medicine, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Section of Medical Service, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China
| | - Hui Lu
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China.
| | - Xingshun Qi
- COVID-19 Study Group, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China; Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, 110840, P.R. China.
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21
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Aloisio E, Colombo G, Arrigo C, Dolci A, Panteghini M. Sources and clinical significance of aspartate aminotransferase increases in COVID-19. Clin Chim Acta 2021; 522:88-95. [PMID: 34411557 PMCID: PMC8366047 DOI: 10.1016/j.cca.2021.08.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Aspartate aminotransferase (AST) is often increased in COVID-19 and, in some studies, AST abnormalities were associated with mortality risk. METHODS 2054 hospitalized COVID-19 patients were studied. To identify sources of AST release, correlations between AST peak values and other biomarkers of tissue damage, i.e., alanine aminotransferase (ALT) for hepatocellular damage, creatine kinase (CK) for muscle damage, lactate dehydrogenase for multiorgan involvement, alkaline phosphatase and γ-glutamyltransferase for cholestatic injury, and C-reactive protein (CRP) for systemic inflammation, were performed and coefficients of determination estimated. The role of AST to predict death and intensive care unit admission during hospitalization was also evaluated. All measurements were performed using standardized assays. RESULTS AST was increased in 69% of patients. Increases could be fully explained by summing the effects of hepatocellular injury [AST dependence from ALT, 66.8% [95% confidence interval (CI): 64.5-69.1)] and muscle damage [AST dependence from CK, 42.6% (CI: 39.3-45.8)]. We were unable to demonstrate an independent association of AST increases with worse outcomes. CONCLUSION The mechanisms for abnormal AST in COVID-19 are likely multifactorial and a status related to tissue suffering could play a significant role. The clinical significance of AST elevations remains unclear.
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Affiliation(s)
- Elena Aloisio
- Clinical Pathology Unit, ASST Fatebenefratelli-Sacco, Milan, Italy.
| | - Giulia Colombo
- Clinical Pathology Unit, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Claudia Arrigo
- Clinical Pathology Unit, ASST Fatebenefratelli-Sacco, Milan, Italy
| | - Alberto Dolci
- Clinical Pathology Unit, ASST Fatebenefratelli-Sacco, Milan, Italy; Department of Biomedical and Clinical Sciences 'Luigi Sacco', Università degli Studi, Milan, Italy
| | - Mauro Panteghini
- Clinical Pathology Unit, ASST Fatebenefratelli-Sacco, Milan, Italy; Department of Biomedical and Clinical Sciences 'Luigi Sacco', Università degli Studi, Milan, Italy
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22
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Sivandzadeh GR, Askari H, Safarpour AR, Ejtehadi F, Raeis-Abdollahi E, Vaez Lari A, Abazari MF, Tarkesh F, Bagheri Lankarani K. COVID-19 infection and liver injury: Clinical features, biomarkers, potential mechanisms, treatment, and management challenges. World J Clin Cases 2021; 9:6178-6200. [PMID: 34434987 PMCID: PMC8362548 DOI: 10.12998/wjcc.v9.i22.6178] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 05/07/2021] [Accepted: 06/25/2021] [Indexed: 02/06/2023] Open
Abstract
It is hypothesized that liver impairment caused by coronavirus disease 2019 (COVID-19) infection might play a central role in severe clinical presentations. Liver injury is closely associated with severe disease and, even with antiviral drugs, have a poor prognosis in COVID-19 patients. In addition to the common hepatobiliary disorders caused by COVID-19, patients with pre-existing liver diseases demand special considerations during the current pandemic. Thus, it is vital that upon clinical presentation, patients with concurrent pre-existing liver disease associated with metabolic dysfunction and COVID-19 be managed properly to prevent liver failure. Careful monitoring and early detection of liver damage through biomarkers after hospitalization for COVID-19 is underscored in all cases, particularly in those with pre-existing metabolic liver injury. The purpose of this study was to determine most recent evidence regarding causality, potential risk factors, and challenges, therapeutic options, and management of COVID-19 infection in vulnerable patients with pre-existing liver injury. This review aims to highlight the current frontier of COVID-19 infection and liver injury and the direction of liver injury in these patients.
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Affiliation(s)
- Gholam Reza Sivandzadeh
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Hassan Askari
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Ali Reza Safarpour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Fardad Ejtehadi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
| | - Ehsan Raeis-Abdollahi
- Department of Medical Sciences, Qom Medical Branch, Islamic Azad University, Qom 1417613151, Iran
| | - Armaghan Vaez Lari
- Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz 6135715794, Iran
| | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran 1417653761, Iran
| | - Firoozeh Tarkesh
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz 7193635899, Iran
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23
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Ding ZY, Li GX, Chen L, Shu C, Song J, Wang W, Wang YW, Chen Q, Jin GN, Liu TT, Liang JN, Zhu P, Zhu W, Li Y, Zhang BH, Feng H, Zhang WG, Yin ZY, Yu WK, Yang Y, Zhang HQ, Tang ZP, Wang H, Hu JB, Liu JH, Yin P, Chen XP, Zhang B. Association of liver abnormalities with in-hospital mortality in patients with COVID-19. J Hepatol 2021; 74:1295-1302. [PMID: 33347952 PMCID: PMC7749734 DOI: 10.1016/j.jhep.2020.12.012] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 11/25/2020] [Accepted: 12/01/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.
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Affiliation(s)
- Ze-Yang Ding
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Gan-Xun Li
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Lin Chen
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Chang Shu
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Jia Song
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Wei Wang
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Yu-Wei Wang
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Qian Chen
- Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Guan-Nan Jin
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, Hubei, China
| | - Tong-Tong Liu
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Jun-Nan Liang
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Peng Zhu
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Wei Zhu
- Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Yong Li
- Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Bin-Hao Zhang
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Huan Feng
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Wan-Guang Zhang
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Zhen-Yu Yin
- Medical team supporting Hubei and Department of Hepatobiliary Surgery, ZhongShan Hospital of Xiamen University, Xiamen, 361004, Fujian, China
| | - Wen-Kui Yu
- First branch of medical teams from Nanjing to support Hubei and Department of Critical Care Medicine, the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, Jiangsu, China
| | - Yang Yang
- Medical team supporting Hubei and Department of Hepatic Surgery and Liver transplantation Center, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, Guangdong, China
| | - Hua-Qiu Zhang
- Department of Neurosurgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Zhou-Ping Tang
- Department of Neurology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Hui Wang
- Department of Gynecological Oncology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Jun-Bo Hu
- Department of Gastrointestinal Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, Hubei, China.
| | - Ji-Hong Liu
- Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Ping Yin
- Department of Epidemiology and Biostatistics and State Key Laboratory of Environment Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
| | - Bixiang Zhang
- Hepatic Surgery Center, and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
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24
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Campos-Varela I, Villagrasa A, Simon-Talero M, Riveiro-Barciela M, Ventura-Cots M, Aguilera-Castro L, Alvarez-Lopez P, Nordahl EA, Anton A, Bañares J, Barber C, Barreira-Diaz A, Biagetti B, Camps-Relats L, Ciudin A, Cocera R, Dopazo C, Fernandez A, Jimenez C, Jimenez MM, Jofra M, Gil C, Gomez-Gavara C, Guanozzi D, Guevara JA, Lobo B, Malagelada C, Martinez-Camprecios J, Mayorga L, Miret E, Pando E, Pérez-Lopez A, Pigrau M, Prio A, Rivera-Esteban JM, Romero A, Tasayco S, Vidal-Gonzalez J, Vidal L, Minguez B, Augustin S, Genesca J. The role of liver steatosis as measured with transient elastography and transaminases on hard clinical outcomes in patients with COVID-19. Therap Adv Gastroenterol 2021; 14:17562848211016567. [PMID: 34104210 PMCID: PMC8170328 DOI: 10.1177/17562848211016567] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 04/12/2021] [Indexed: 02/04/2023] Open
Abstract
Liver injury has been widely described in patients with Coronavirus disease 2019 (COVID-19). We aimed to study the effect of liver biochemistry alterations, previous liver disease, and the value of liver elastography on hard clinical outcomes in COVID-19 patients. We conducted a single-center prospective observational study in 370 consecutive patients admitted for polymerase chain reaction (PCR)-confirmed COVID-19 pneumonia. Clinical and laboratory data were collected at baseline and liver parameters and clinical events recorded during follow-up. Transient elastography [with Controlled Attenuation Parameter (CAP) measurements] was performed at admission in 98 patients. All patients were followed up until day 28 or death. The two main outcomes of the study were 28-day mortality and the occurrence of the composite endpoint intensive care unit (ICU) admission and/or death. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated at admission in 130 patients (35%) and 167 (45%) patients, respectively. Overall, 14.6% of patients presented the composite endpoint ICU and/or death. Neither ALT elevations, prior liver disease, liver stiffness nor liver steatosis (assessed with CAP) had any effect on outcomes. However, patients with abnormal baseline AST had a higher occurrence of the composite ICU/death (21% versus 9.5%, p = 0.002). Patients ⩾65 years and with an AST level > 50 U/ml at admission had a significantly higher risk of ICU and/or death than those with AST ⩽ 50 U/ml (50% versus 13.3%, p < 0.001). In conclusion, mild liver damage is prevalent in COVID-19 patients, but neither ALT elevation nor liver steatosis influenced hard clinical outcomes. Elevated baseline AST is a strong predictor of hard outcomes, especially in patients ⩾65 years.
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Affiliation(s)
- Isabel Campos-Varela
- Liver Unit, Department of Internal Medicine,
Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron, 119-129, Barcelona,
08035, Spain
- Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos
III, Madrid, Spain
| | - Ares Villagrasa
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Macarena Simon-Talero
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos
III, Madrid, Spain
| | - Mar Riveiro-Barciela
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos
III, Madrid, Spain
| | - Meritxell Ventura-Cots
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos
III, Madrid, Spain
| | - Lara Aguilera-Castro
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Patricia Alvarez-Lopez
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Emilie A Nordahl
- Department of Clinical Pharmacology, Vall
d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Adrian Anton
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Juan Bañares
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Claudia Barber
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Ana Barreira-Diaz
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Betina Biagetti
- Department of Endocrinology, Vall d’Hebron
Barcelona Hospital Campus, Barcelona, Spain
| | - Laura Camps-Relats
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Andrea Ciudin
- Department of Endocrinology, Vall d’Hebron
Barcelona Hospital Campus, Barcelona, Spain
| | - Raul Cocera
- Department of Urology, Vall d’Hebron Barcelona
Hospital Campus, Barcelona, Spain
| | - Cristina Dopazo
- Department of Hepatobiliar Surgery and Liver
Transplant, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Andrea Fernandez
- Department of Hepatobiliar Surgery and Liver
Transplant, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Cesar Jimenez
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maria M Jimenez
- Department of Hematology, Vall d’Hebron
Barcelona Hospital Campus, Barcelona, Spain
| | - Mariona Jofra
- Department of Hepatobiliar Surgery and Liver
Transplant, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Clara Gil
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Concepción Gomez-Gavara
- Department of Hepatobiliar Surgery and Liver
Transplant, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Danila Guanozzi
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Jorge A Guevara
- Department of Endoscopy, Vall d’Hebron
Barcelona Hospital Campus, Barcelona, Spain
| | - Beatriz Lobo
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Carolina Malagelada
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Joan Martinez-Camprecios
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Luis Mayorga
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Enric Miret
- Department of Urology, Vall d’Hebron Barcelona
Hospital Campus, Barcelona, Spain
| | - Elizabeth Pando
- Department of Hepatobiliar Surgery and Liver
Transplant, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Ana Pérez-Lopez
- Department of Hematology, Vall d’Hebron
Barcelona Hospital Campus, Barcelona, Spain
| | - Marc Pigrau
- Department of Endoscopy, Vall d’Hebron
Barcelona Hospital Campus, Barcelona, Spain
| | - Alba Prio
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jesus M Rivera-Esteban
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Alba Romero
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Stephanie Tasayco
- Department of Gastroenterology, Vall d’Hebron
Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona,
Spain
| | - Judit Vidal-Gonzalez
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Laura Vidal
- Department of Hepatobiliar Surgery and Liver
Transplant, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Beatriz Minguez
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos
III, Madrid, Spain
| | - Salvador Augustin
- Liver Unit, Department of Internal Medicine,
Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron, 119-129, Barcelona,
08035, Spain
| | - Joan Genesca
- Liver Unit, Hospital Universitari Vall
d’Hebron, Vall d’Hebron Institut of Reseach (VHIR), Vall d’Hebron Barcelona
Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos
III, Madrid, Spain
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25
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Premkumar M, Kedarisetty CK. Cytokine Storm of COVID-19 and Its Impact on Patients with and without Chronic Liver Disease. J Clin Transl Hepatol 2021; 9:256-264. [PMID: 34007808 PMCID: PMC8111101 DOI: 10.14218/jcth.2021.00055] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/11/2021] [Accepted: 04/01/2021] [Indexed: 01/08/2023] Open
Abstract
The coronavirus pandemic has resulted in increased rates of hepatic decompensation, morbidity and mortality in patients suffering from existing liver disease, and deranged liver biochemistries in those without liver disease. In patients with cirrhosis with coronavirus disease 2019 (COVID-19), new onset organ failures manifesting as acute-on-chronic liver failure have also been reported. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) also directly binds to enterocytes and cholangiocytes via the angiotensin converting enzyme receptor 2, although the lung remains the portal of entry. Superadded with the COVID-19 related bystander hepatitis, a systemic inflammatory response is noted due to unregulated macrophage activation syndrome and cytokine storm. However, the exact definition and diagnostic criteria of the 'cytokine storm' in COVID-19 are yet unclear. In addition, inflammatory markers like C-reactive protein, ferritin, D-dimer and procalcitonin are frequently elevated. This in turn leads to disease progression, activation of the coagulation cascade, vascular microthrombi and immune-mediated injury in different organ systems. Deranged liver chemistries are also noted due to the cytokine storm, and synergistic hypoxic or ischemic liver injury, drug-induced liver injury, and use of hepatotoxic antiviral agents all contribute to deranged liver chemistry. Control of an unregulated cytokine storm at an early stage may avert disease morbidity and mortality. Several immunomodulator drugs and repurposed immunosuppressive agents have been used in COVID-19 with varying degrees of success.
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Affiliation(s)
- Madhumita Premkumar
- Departments of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Ahmad A, Ishtiaq SM, Khan JA, Aslam R, Ali S, Arshad MI. COVID-19 and comorbidities of hepatic diseases in a global perspective. World J Gastroenterol 2021; 27:1296-1310. [PMID: 33833483 PMCID: PMC8015303 DOI: 10.3748/wjg.v27.i13.1296] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/17/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023] Open
Abstract
The worldwide outbreak of coronavirus disease 2019 (COVID-19) has challenged the priorities of healthcare system in terms of different clinical management and infection transmission, particularly those related to hepatic-disease comorbidities. Epidemiological data evidenced that COVID-19 patients with altered liver function because of hepatitis infection and cholestasis have an adverse prognosis and experience worse health outcomes. COVID-19-associated liver injury is correlated with various liver diseases following a severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) infection that can progress during the treatment of COVID-19 patients with or without pre-existing liver disease. SARS-CoV-2 can induce liver injury in a number of ways including direct cytopathic effect of the virus on cholangiocytes/hepatocytes, immune-mediated damage, hypoxia, and sepsis. Indeed, immediate cytopathogenic effects of SARS-CoV-2 via its potential target, the angiotensin-converting enzyme-2 receptor, which is highly expressed in hepatocytes and cholangiocytes, renders the liver as an extra-respiratory organ with increased susceptibility to pathological outcomes. But, underlying COVID-19-linked liver disease pathogenesis with abnormal liver function tests (LFTs) is incompletely understood. Hence, we collated COVID-19-associated liver injuries with increased LFTs at the nexus of pre-existing liver diseases and COVID-19, and defining a plausible pathophysiological triad of COVID-19, hepatocellular damage, and liver disease. This review summarizes recent findings of the exacerbating role of COVID-19 in pre-existing liver disease and vice versa as well as international guidelines of clinical care, management, and treatment recommendations for COVID-19 patients with liver disease.
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Affiliation(s)
- Aqsa Ahmad
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Syeda Momna Ishtiaq
- Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Junaid Ali Khan
- Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Rizwan Aslam
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Sultan Ali
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
| | - Muhammad Imran Arshad
- Institute of Microbiology, University of Agriculture Faisalabad, Faisalabad 38040, Punjab, Pakistan
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27
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Parigi TL, Vespa E, Pugliese N. COVID-19, ACEI/ARBs, and Gastrointestinal Symptoms: The Jury Is Still Out on the Association. Gastroenterology 2021; 160:1896-1897. [PMID: 32682762 PMCID: PMC7365072 DOI: 10.1053/j.gastro.2020.06.095] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 06/11/2020] [Accepted: 06/16/2020] [Indexed: 01/22/2023]
Affiliation(s)
| | | | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
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28
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Di Giorgio A, Hartleif S, Warner S, Kelly D. COVID-19 in Children With Liver Disease. Front Pediatr 2021; 9:616381. [PMID: 33777864 PMCID: PMC7991080 DOI: 10.3389/fped.2021.616381] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 02/19/2021] [Indexed: 12/15/2022] Open
Abstract
Background: The global pandemic caused by novel Coronavirus SARS-CoV-2 disease (COVID-19) is a major threat to the general population and for patients with pre-existing chronic conditions. We report data concerning SARS-CoV-2 infection in children with chronic liver disease (CLD). Methods: A literature review using the online database PubMed was performed to summarize available findings on the association between pre-existing liver disease and COVID-19 infection in children. Results: Children with COVID-19 have preserved effector and immunosuppressive components resulting in a milder disease compared to adults. The most common hepatic manifestation is an elevation of hepatic transaminases. Liver damage may be directly caused by viral infection of liver cells, by medications or by the chronic hypoxia seen in COVID-19 patients. A multicenter study reported that the majority of children with a CLD remained healthy during the outbreak. Similarly, studies reported that children on immunosuppressive treatment, including patients with autoimmune liver disease (AILD) and liver transplantation (LT), maintained good health during the outbreak without experiencing major complications even if infected with COVID-19. Conclusion: COVID-19-related liver injury presents with a mild elevation of transaminases, although its clinical significance is unclear. Children with CLD, including those with AILD and post-LT, do not have an increased risk for severe disease course of SARS-CoV-2 infection with little or no liver dysfunction. These data highlight the necessity to ensure normal standards of care while adhering to national Covid-19 guidelines, and particularly to maintain immunosuppressive medication to prevent relapse or rejection. Further research is required to evaluate the differences in clinical course between immunosuppressed adults and children and in particular whether asymptomatic infection is a concern.
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Affiliation(s)
- Angelo Di Giorgio
- Paediatric Liver, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Steffen Hartleif
- Paediatric Gastroenterology and Hepatology, University Children's Hospital, University of Tübingen, Tübingen, Germany
| | - Suzan Warner
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- The Liver Unit, Birmingham Women's and Children's Hospital, University of Birmingham, Birmingham, United Kingdom
| | - Deirdre Kelly
- The Liver Unit, Birmingham Women's and Children's Hospital, University of Birmingham, Birmingham, United Kingdom
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29
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Shafran N, Issachar A, Shochat T, Shafran IH, Bursztyn M, Shlomai A. Abnormal liver tests in patients with SARS-CoV-2 or influenza - prognostic similarities and temporal disparities. JHEP Rep 2021; 3:100258. [PMID: 33644724 PMCID: PMC7902222 DOI: 10.1016/j.jhepr.2021.100258] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 01/25/2021] [Accepted: 02/15/2021] [Indexed: 02/08/2023] Open
Abstract
Background & Aims Abnormal liver tests are common in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but a possible direct role of the virus in liver injury and its association with short-term outcomes are controversial. Therefore, we aimed to compare the pattern of abnormal liver tests in patients with SARS-CoV-2 with those of patients infected with influenza, a non-hepatotropic respiratory virus, and their association with worse outcomes during hospitalisation. Methods We performed a retrospective cohort study of 1,737 hospitalised patients (865 with influenza and 872 with SARS-CoV-2) in a tertiary medical centre. We defined abnormal liver tests as alanine transaminase or aspartate transaminase ≥40 IU/ml at any time-point during hospitalisation. Results Abnormal liver tests were mild to moderate in most patients regardless of infection type, but the majority of patients with influenza had a transaminase peak earlier during hospitalisation compared with patients with SARS-CoV-2. Abnormal liver tests correlated with markers of severe disease in either influenza or SARS-CoV-2 infections, and were associated with death, occurring mainly in patients with severe liver test abnormalities (>200 IU/L) (38.7% and 60% of patients with influenza or SARS-CoV-2, respectively). In multivariate analysis, controlling for age, sex, lymphopaenia, and C-reactive protein, liver test abnormalities remained significantly associated with death for influenza (odds ratio 4.344; 95% CI 2.218-8.508) and SARS-CoV-2 (odds ratio 3.898; 95% CI 2.203-6.896). These results were confirmed upon propensity score matching. Conclusions Abnormal liver tests during hospitalisation with SARS-CoV-2 or influenza infections are common, may differ in their time course, and reflect disease severity. They are associated with worse outcomes, mainly in patients with severe liver test abnormalities, regardless of infection type. Lay summary Coronavirus disease 2019 (COVID-19) is a serious global health pandemic, the causative agent of which is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Abnormal liver tests are common among SARS-CoV-2 infected patients and are often associated with worse outcomes. Herein, we compare the pattern of abnormal liver tests and their association with disease severity between 2 major non-hepatotropic respiratory viruses: SARS-CoV-2 and influenza. We show that abnormal liver tests are common in both infections, may slightly differ in their kinetics, and are associated with worse outcomes, especially in patients with severe liver test abnormalities. These results strongly suggest that abnormal liver tests in SARS-CoV-2 patients reflect disease severity, rather than a virus-mediated direct liver injury, and should be closely followed in admitted patients.
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Key Words
- ALKP, alkaline phosphatase
- ALT, alanine transaminase
- AST, aspartate transaminase
- BOSmin, minimal blood oxygen saturation
- COVID-19
- COVID-19, coronavirus disease 2019
- CRP, C-reactive protein
- GGT, gamma-glutamyl transferase
- Liver injury
- Respiratory tract infections
- SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
- SBPmin, minimal systolic blood pressure
- WBC count, white blood cell count
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Affiliation(s)
- Noa Shafran
- Department of Medicine D, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Assaf Issachar
- The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.,The Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Tzippy Shochat
- Bio-Statistical Unit, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel
| | - Inbal Haya Shafran
- Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
| | - Michael Bursztyn
- Department of Medicine D, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.,Hadassah-Hebrew University Medical Center, Mount-Scopus, Jerusalem, Israel
| | - Amir Shlomai
- Department of Medicine D, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.,The Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.,The Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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30
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Vespa E, Pugliese N, Colapietro F, Aghemo A. Stay (GI) Healthy: COVID-19 and Gastrointestinal Manifestations. TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY 2021; 23:179-189. [PMID: 33521703 PMCID: PMC7825983 DOI: 10.1016/j.tige.2021.01.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
SARS-CoV-2 is the virus responsible for COVID-19, whose clinical spectrum ranges widely, both in terms of severity and multi-organicity. SARS-CoV-2 mainly involves the respiratory tract, causing from a flu-like syndrome to interstitial pneumonia and acute respiratory distress syndrome. Although its entry receptor, angiotensin-converting-enzyme 2, is typically expressed in epithelial cells of the airways, extra-pulmonary involvement has been consistently demonstrated since the beginning of the outbreak. Gastrointestinal manifestations in COVID-19 may be explained by the abundant expression of ACE2 in the digestive tract. Moreover, not only COVID-19 patients often present with GI symptoms (diarrhea, nausea/vomiting, abdominal pain) and liver tests abnormalities, but there are also data showing active viral replication in the GI tract and possible fecal-oral transmission. Aim of this review is to summarize the evidence regarding prevalence and clinical significance of GI involvement and liver abnormalities in patients with COVID-19, providing the reader with evidence-based recommendations on the management of these conditions.
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Affiliation(s)
- Edoardo Vespa
- Department of Biomedical Sciences, Humanitas University,Via Rita Levi Montalcini, 20090 Pieve Emanuele, Milan, Italy,Internal Medicine and Hepatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University,Via Rita Levi Montalcini, 20090 Pieve Emanuele, Milan, Italy,Internal Medicine and Hepatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University,Via Rita Levi Montalcini, 20090 Pieve Emanuele, Milan, Italy,Internal Medicine and Hepatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University,Via Rita Levi Montalcini, 20090 Pieve Emanuele, Milan, Italy,Internal Medicine and Hepatology Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy,Correspondence Address correspondence to: Alessio Aghemo, MD, PhD Department of Biomedical Sciences Humanitas University, Via Rita Levi Montalcini, 20090 Pieve Emanuele – Milan, Italy; Internal Medicine and Hepatology Division, Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy
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31
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Higher Mortality and Intensive Care Unit Admissions in COVID-19 Patients with Liver Enzyme Elevations. Microorganisms 2020; 8:microorganisms8122010. [PMID: 33339330 PMCID: PMC7766471 DOI: 10.3390/microorganisms8122010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 12/13/2020] [Accepted: 12/14/2020] [Indexed: 12/14/2022] Open
Abstract
The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive adults with COVID-19. The elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to the highest level between COVID-19 diagnosis and hospital discharge was categorized according to a standardized toxicity grade scale. In total, 799 patients were included in this study, 39% of which were female, with a mean age of 69.9 (±16.0) years. Of these patients, 225 (28.1%) developed LEE of grade ≥2 after a median of three days (interquartile range (IQR): 0–8 days) from the diagnosis of COVID-19, and they were estimated to have a higher hazard of death or ICU admission (adjusted hazard ratio (aHR): 1.46, 95% confidence interval (CI): 1.14–1.88). The clinical and laboratory variables associated with the development of LEE were male sex, higher respiratory rate, higher gamma glutamyl transpeptidase (GGT) and lower albumin levels at baseline. Among the analyzed treatments, steroids, tocilizumab and darunavir/ritonavir correlated with LEE. In conclusion, LEE were associated with mortality and ICU admission among COVID-19 patients. While the origin of LEE is probably multifactorial, LEE evaluation could add information to the clinical and laboratory variables that are commonly evaluated during the course of COVID-19.
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Hanafy AS, Abd-Elsalam S. Challenges in COVID-19 drug treatment in patients with advanced liver diseases: A hepatology perspective. World J Gastroenterol 2020; 26:7272-7286. [PMID: 33362383 PMCID: PMC7739155 DOI: 10.3748/wjg.v26.i46.7272] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 11/06/2020] [Accepted: 11/21/2020] [Indexed: 02/06/2023] Open
Abstract
The global incidence of coronavirus disease 2019 (COVID-19) continues to increase despite health care efforts. The disease is caused by coronavirus 2 with high transmission and mortality rates. Little is known about the management of COVID-19 in advanced liver disease. The aim of work was to propose a plan for management of this drastic disease in case of this specific population with review of medications that could be suitable for advanced liver disease. All the guidelines and medications available for treatment of COVID-19 were reviewed with selection of the less toxic medications that could be used in advanced liver disease. Drugs suitable to manage COVID-19 in patients with liver disease might include remdesivir intravenously, nitazoxanide + sofosbuvir, ivermectin, tocilizumab, convalescent plasma, and low molecular weight heparin in certain situations. Advanced liver disease is associated with portal hypertension and splenomegaly with reduction of blood elements and immune dysfunction and impaired T cell function. Thus, when confronted by cytokine storm as an immune response to COVID-19, there may be an increase in the mortality rate of these patients. Through this review, a plan to treat COVID-19 in this special group of patients with advanced cirrhosis is proposed.
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Bertolini A, van de Peppel IP, Bodewes FA, Moshage H, Fantin A, Farinati F, Fiorotto R, Jonker JW, Strazzabosco M, Verkade HJ, Peserico G. Abnormal Liver Function Tests in Patients With COVID-19: Relevance and Potential Pathogenesis. Hepatology 2020; 72:1864-1872. [PMID: 32702162 PMCID: PMC7404414 DOI: 10.1002/hep.31480] [Citation(s) in RCA: 187] [Impact Index Per Article: 37.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/19/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Anna Bertolini
- Department of PediatricsUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Ivo P. van de Peppel
- Department of PediatricsUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Frank A.J.A. Bodewes
- Department of PediatricsUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Han Moshage
- Department of Gastroenterology and HepatologyUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Alberto Fantin
- Department of GastroenterologyVeneto Institute of OncologyPadovaItaly
| | - Fabio Farinati
- Gastroenterology UnitDepartment of Surgery, Oncology and GastroenterologyUniversity of PadovaPadovaItaly
| | - Romina Fiorotto
- Section of Digestive Diseases, Liver CenterDepartment of Internal MedicineYale UniversityNew HavenCT
| | - Johan W. Jonker
- Department of PediatricsUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Mario Strazzabosco
- Section of Digestive Diseases, Liver CenterDepartment of Internal MedicineYale UniversityNew HavenCT
| | - Henkjan J. Verkade
- Department of PediatricsUniversity of GroningenUniversity Medical Center GroningenGroningenThe Netherlands
| | - Giulia Peserico
- Department of GastroenterologyVeneto Institute of OncologyPadovaItaly
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Boettler T, Marjot T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Jalan R, Moreau R, Cornberg M, Berg T. Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic. JHEP Rep 2020; 2:100169. [PMID: 32835190 PMCID: PMC7402276 DOI: 10.1016/j.jhepr.2020.100169] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 07/26/2020] [Indexed: 02/06/2023] Open
Abstract
During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, EASL and ESCMID published a position paper to provide guidance for physicians involved in the care of patients with chronic liver disease. While some healthcare systems are returning to a more normal routine, many countries and healthcare systems have been, or still are, overwhelmed by the pandemic, which is significantly impacting on the care of these patients. In addition, many studies have been published focusing on how COVID-19 may affect the liver and how pre-existing liver diseases might influence the clinical course of COVID-19. While many aspects remain poorly understood, it has become increasingly evident that pre-existing liver diseases and liver injury during the disease course must be kept in mind when caring for patients with COVID-19. This review should serve as an update on the previous position paper, summarising the evidence for liver disease involvement during COVID-19 and providing recommendations on how to return to routine care wherever possible.
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Key Words
- ACE2, angiotensin-converting enzyme 2
- ACLF, acute-on-chronic liver failure
- COVID-19
- COVID-19, coronavirus disease 2019
- Cancer
- Cirrhosis
- ERC, endoscopic retrograde cholangiography
- HCC, hepatocellular carcinoma
- IL-6, interleukin-6
- LT, liver transplant
- Liver
- MELD, model for end-stage liver disease
- NAFLD
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- OGD, oesophagogastroduodenoscopy
- SARS-CoV-2, severe acute respiratory syndrome coronavirus 2
- Telemedicine
- Transplantation
- ULN, upper limit of normal
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Affiliation(s)
- Tobias Boettler
- Department of Medicine II, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, UK
| | - Philip N. Newsome
- National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Mario U. Mondelli
- Division of Infectious Diseases and Immunology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Mojca Maticic
- Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Slovenia
| | - Elisa Cordero
- Department of Medicine, University of Seville, Clinical Unit of Infectious Diseases University Hospital Virgen del Rocio, Institute of Biomedicine, Sevilla, CSIC, Spain
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
| | - Richard Moreau
- Inserm, Université de Paris, U1149, Centre de Recherche sur l'Inflammation (CRI), UMRS1149, Paris, France
- Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- Centre for Individualised Infection Medicine (CIIM), Hannover, Germany
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
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Bernal-Monterde V, Casas-Deza D, Letona-Giménez L, de la Llama-Celis N, Calmarza P, Sierra-Gabarda O, Betoré-Glaria E, Martínez-de Lagos M, Martínez-Barredo L, Espinosa-Pérez M, M. Arbones-Mainar J. SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization. Biomedicines 2020; 8:biomedicines8090328. [PMID: 32899640 PMCID: PMC7555293 DOI: 10.3390/biomedicines8090328] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/24/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.
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Affiliation(s)
- Vanesa Bernal-Monterde
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (V.B.-M.); (D.C.-D.); (O.S.-G.); (E.B.-G.)
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
| | - Diego Casas-Deza
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (V.B.-M.); (D.C.-D.); (O.S.-G.); (E.B.-G.)
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
| | - Laura Letona-Giménez
- Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (L.L.-G.); (M.M.-d.L.); (L.M.-B.); (M.E.-P.)
| | | | - Pilar Calmarza
- Clinical Biochemistry Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain;
| | - Olivia Sierra-Gabarda
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (V.B.-M.); (D.C.-D.); (O.S.-G.); (E.B.-G.)
| | - Elena Betoré-Glaria
- Gastroenterology Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (V.B.-M.); (D.C.-D.); (O.S.-G.); (E.B.-G.)
| | - María Martínez-de Lagos
- Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (L.L.-G.); (M.M.-d.L.); (L.M.-B.); (M.E.-P.)
| | - Lucía Martínez-Barredo
- Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (L.L.-G.); (M.M.-d.L.); (L.M.-B.); (M.E.-P.)
| | - María Espinosa-Pérez
- Internal Medicine Department, Miguel Servet University Hospital, 50009 Zaragoza, Spain; (L.L.-G.); (M.M.-d.L.); (L.M.-B.); (M.E.-P.)
| | - Jose M. Arbones-Mainar
- Instituto de Investigación Sanitaria (IIS) Aragon, 50009 Zaragoza, Spain
- Translational Research Unit, Miguel Servet University Hospital, Instituto Aragonés de Ciencias de la Salud, 50009 Zaragoza, Spain
- Centro de Investigación Biomédica en Red Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto Salud Carlos III, 28029 Madrid, Spain
- Correspondence: ; Tel.: +34-976-769-565
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Ponziani FR, Del Zompo F, Nesci A, Santopaolo F, Ianiro G, Pompili M, Gasbarrini A. Liver involvement is not associated with mortality: results from a large cohort of SARS-CoV-2-positive patients. Aliment Pharmacol Ther 2020; 52:1060-1068. [PMID: 32628793 PMCID: PMC7361563 DOI: 10.1111/apt.15996] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/10/2020] [Accepted: 07/04/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is frequently associated with liver test abnormalities. AIMS To describe the evolution of liver involvement during SARS-CoV-2 infection and its effect on clinical course and mortality. METHODS Data of 515 SARS-CoV-2-positive patients were collected at baseline and during follow-up, last evaluation or death. Stratification based on need for hospitalisation, severe disease and admission to intensive care unit (ICU) was performed. The association between liver test abnormalities (baseline and peak values) and ICU admission or death was also explored. RESULTS Liver test abnormalities were found in 161 (31.3%) patients. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were increased in 20.4%, 19% and 13.6% of patients, respectively. Baseline liver test abnormalities were associated with increased risk of ICU admission (OR 2.19 [95% CI 1.24-3.89], P = 0.007) but not with mortality (OR 0.84 [95% CI 0.49-1.41], P = 0.51). Alkaline phosphatase (ALP) peak values were correlated with risk of death (OR 1.007 [95% CI 1.002-1.01], P = 0.005) along with age, multiple comorbidities, acute respiratory distress syndrome, ICU admission and C-reactive protein. Alterations of liver tests worsened within 15 days of hospitalisation; however, in patients with the longest median follow-up, the prevalence of liver test alterations decreased over time, returning to around baseline levels. CONCLUSIONS In SARS-CoV-2-positive patients without pre-existing severe chronic liver disease, baseline liver test abnormalities are associated with the risk of ICU admission and tend to normalise over time. The ALP peak value may be predictive of a worse prognosis.
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Affiliation(s)
- Francesca Romana Ponziani
- Internal Medicine, Gastroenterology and HepatologyFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly,Catholic University of the Sacred HeartRomeItaly
| | - Fabio Del Zompo
- Internal Medicine, Gastroenterology and HepatologyFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly
| | - Antonio Nesci
- Angiology and Vascular DiseasesFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly
| | - Francesco Santopaolo
- Internal Medicine, Gastroenterology and HepatologyFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly
| | - Gianluca Ianiro
- Internal Medicine, Gastroenterology and HepatologyFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly,Catholic University of the Sacred HeartRomeItaly
| | - Maurizio Pompili
- Internal Medicine, Gastroenterology and HepatologyFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly,Catholic University of the Sacred HeartRomeItaly
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology and HepatologyFondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly,Catholic University of the Sacred HeartRomeItaly
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Yeoman A, Maggs DR, Gardezi SAA, Haboubi HN, Yahya MI, Yousuf F, Czajkowski MA. Incidence, pattern and severity of abnormal liver blood tests among hospitalised patients with SARS-COV2 (COVID-19) in South Wales. Frontline Gastroenterol 2020; 12:89-94. [PMID: 33617606 PMCID: PMC7873537 DOI: 10.1136/flgastro-2020-101532] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 06/26/2020] [Accepted: 07/12/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION SARS-CoV-2 (COVID-19) is a novel coronavirus that emerged in Wuhan, China in late 2019 and since become a global pandemic. As such, its clinical behaviour is a subject of much interest. Initial reports suggested a significant proportion of patients have abnormal liver blood tests. Gwent has experienced one of the highest incidences of COVID-19 infection in the UK, which itself has among the highest COVID-19 impacts worldwide. METHOD We set out to report the incidence, clinical pattern and severity of liver blood test abnormalities in hospitalised patients with confirmed COVID-19 in our institution over a 3-week period. Data on clinical outcomes such as admission to intensive therapy unit (ITU), hospital discharge and mortality were recorded. RESULTS 318 hospitalised COVID-19 positive had liver blood tests available for analysis. Ninety-seven patients (31%) had one or more abnormal liver blood tests and were abnormal admission in 64%. Liver tests were predominantly cholestatic (72%) in contrast to other studies to date. Male gender and abnormal liver blood tests were associated with ITU admission. CONCLUSIONS Almost one-third of admissions with COVID-19 have abnormal LBTs which are typically mild and are associated with male gender. Importantly, we have identified that cholestatic patterns dominate but were not clearly associated with ITU admission or death.
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Affiliation(s)
- Andrew Yeoman
- Gwent Liver Unit, Aneurin Bevan University Health Board, Newport, UK
| | - Daniel Raun Maggs
- Gwent Liver Unit, Aneurin Bevan University Health Board, Newport, UK
| | - Syed A A Gardezi
- Gwent Liver Unit, Aneurin Bevan University Health Board, Newport, UK
| | | | | | - Fidan Yousuf
- Gwent Liver Unit, Aneurin Bevan University Health Board, Newport, UK
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