|
1
|
Luo YW, Huang AL, Tang KF. Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection: Regulation, association, and therapeutic implications. World J Gastroenterol 2025; 31:100864. [PMID: 39958440 PMCID: PMC11752700 DOI: 10.3748/wjg.v31.i6.100864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 12/07/2024] [Accepted: 12/20/2024] [Indexed: 01/10/2025] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Mounting evidence has indicated the presence of hepatic SARS-CoV-2 infection and liver injury in patients with coronavirus disease 2019 (COVID-19). Understanding the mechanisms of hepatic SARS-CoV-2 infection is crucial for addressing COVID-19-related liver pathology and developing targeted therapies. This editorial discusses the significance of ACE2 in hepatic SARS-CoV-2 infection, drawing on the research by Jacobs et al. Their findings indicate that hepatic ACE2 expression, frequency of hepatic SARS-CoV-2 infection, and severity of liver injury are elevated in patients with pre-existing chronic liver diseases. These data suggest that hepatic ACE2 could be a promising therapeutic target for COVID-19.
Collapse
Affiliation(s)
- Yu-Wei Luo
- Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
| | - Ai-Long Huang
- Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
| | - Kai-Fu Tang
- Key Laboratory of Molecular Biology on Infectious Disease, Ministry of Education, Chongqing Medical University, Chongqing 400016, China
| |
Collapse
|
|
2
|
Suoh M, Esmaili S, Eslam M, George J. Metabolic (dysfunction)-associated fatty liver disease metrics and contributions to liver research. Hepatol Int 2024; 18:1740-1755. [PMID: 39412611 PMCID: PMC11632019 DOI: 10.1007/s12072-024-10731-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 09/06/2024] [Indexed: 12/11/2024]
Abstract
BACKGROUND The international consensus to revise non-alcoholic fatty liver disease to metabolic (dysfunction)-associated fatty liver disease (MAFLD) in 2020 attracted significant attention. The impact of the MAFLD definition on the research community has not been objectively assessed. We conducted an analysis of systematically collected literature on MAFLD to understand its research impact. METHODS From PubMed, Web of Science, and Scopus, the literature adopting MAFLD, written in English, and published from 2020 to 10 October 2023 was collected. The publication metrics, including publication counts, publishing journals, author countries, author keywords, and citation information, were analyzed to evaluate the research impact and key topics on MAFLD. RESULTS 1469 MAFLD-related papers were published in 434 journals with a steady increase in the number. The intense publishing and citations activity on MAFLD indicates the large impact of the redefinition. Topic assessment with keyword and citation analysis revealed a transition from the proposal and discussion of the redefinition to clinical characterization of MAFLD with a focus on metabolic dysfunction. Moreover, the diagnostic criteria for MAFLD showed better performance in predicting hepatic and extrahepatic outcomes compared to NAFLD. The publications were from 99 countries with evidence of strong regional and global collaboration. Multiple international societies and stakeholders have endorsed MAFLD for its utility in clinical practice, improving patient management and promoting multidisciplinary care, while alleviating stigma. CONCLUSION This survey provides a quantitative measure of the considerable international impact and contributions of the MAFLD definition towards liver research and as part of the spectrum of cardiometabolic disorders.
Collapse
Affiliation(s)
- Maito Suoh
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia
| | - Saeed Esmaili
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia
| | - Mohammed Eslam
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia.
| |
Collapse
|
|
3
|
Cui J, Wang L, Ghavamian A, Li X, Wang G, Wang T, Huang M, Ru Q, Zhao X. Long-term antibody response after the third dose of inactivated SARS-CoV-2 vaccine in MASLD patients. BMC Gastroenterol 2024; 24:329. [PMID: 39350092 PMCID: PMC11441169 DOI: 10.1186/s12876-024-03402-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 09/04/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) patients are at an elevated risk of developing severe coronavirus disease 2019 (COVID-19). The objective of this study was to assess antibody responses and safety profiles six months after the third dose of the inactivated acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in MASLD patients. METHODS This study included MASLD patients and healthy volunteers without a history of SARS-CoV-2 infection. Blood samples were collected six months after receiving the third dose of the inactivated vaccine to measure the levels of neutralizing antibodies (NAbs) and anti-spike IgG antibodies against SARS-CoV-2. RESULTS A total of 335 participants (214 MASLD patients and 121 healthy volunteers) were enrolled. The seroprevalence of NAb was 61.7% (132 of 214) in MASLD patients and 74.4% (90 of 121) in healthy volunteers, which was a significant difference (p = 0.018). Statistically significant differences in IgG seroprevalence were also observed between MASLD patients and healthy volunteers (p = 0.004). Multivariate analysis demonstrated that the severity of MASLD (OR, 2.97; 95% CI, 1.32-6.68; p = 0.009) and age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.004) were independent risk factors for NAb negativity in MASLD patients. Moderate/severe MASLD patients had a lower NAb seroprevalence than mild MASLD patients (45.0% vs. 65.5%, p = 0.016). CONCLUSION Lower antibody responses were observed in MASLD patients six months after their third dose of the inactivated vaccine than in healthy volunteers, providing further assistance in monitoring patients who are more vulnerable to hypo-responsiveness to SARS-CoV-2 vaccines.
Collapse
Affiliation(s)
- Jin Cui
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Lianbang Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Armin Ghavamian
- Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China
| | - Xuemei Li
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China
| | - Gongzheng Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Tao Wang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Min Huang
- Department of Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
| | - Qi Ru
- Department of Ultrasound, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, China.
| | - Xinya Zhao
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Jinan, Shandong, 250021, China
| |
Collapse
|
|
4
|
Yang CC, Tsai YW, Wang SH, Wu JY, Liu TH, Hsu WH, Huang PY, Chuang MH, Sheu MJ, Lai CC. The effectiveness of oral anti-SARS-CoV-2 agents in non-hospitalized COVID-19 patients with nonalcoholic fatty liver disease: a retrospective study. Front Pharmacol 2024; 15:1321155. [PMID: 38425651 PMCID: PMC10902026 DOI: 10.3389/fphar.2024.1321155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 02/01/2024] [Indexed: 03/02/2024] Open
Abstract
Background: The effectiveness of the novel oral antiviral agents, nirmatrelvir plus ritonavir and molnupiravir, in treating COVID-19 in patients with nonalcoholic fatty liver disease is unclear. Objective: To assess the effectiveness of novel oral antiviral agents against COVID-19 among patients with nonalcoholic fatty liver diseases. Methods: This retrospective cohort study used the TriNetX Research Network to identify non-hospitalized patients with COVID-19 and nonalcoholic fatty liver disease between 1 January 2022, and 30 June 2023. Propensity score matching was used to form two matched cohorts treated with or without nirmatrelvir-ritonavir or molnupiravir. Results: In the two matched cohorts of 6,358 patients each, the use of novel oral antiviral agents was associated with a significantly lower risk of all-cause emergency department visits, hospitalization, or mortality (6.59% versus 8.24%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70-0.91). The novel antiviral group had a significantly lower risk of all-cause emergency department visits (HR, 0.85; 95% CI, 0.74-0.99). Additionally, the incidence of hospitalization was significantly lower in the oral antiviral group than in the control group (HR, 0.71; 95% CI, 0.55-0.90). There were no deaths in the oral antiviral group but 12 deaths in the control group. Conclusion: Novel oral antiviral agents are beneficial for treating COVID-19 in patients with nonalcoholic fatty liver disease.
Collapse
Affiliation(s)
- Chun-Chi Yang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Ya-Wen Tsai
- Center for Integrative Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan
| | - Su-Hung Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Jheng-Yan Wu
- Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan
| | - Ting-Hui Liu
- Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan
| | - Wan-Hsuan Hsu
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Po-Yu Huang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Min-Hsiang Chuang
- Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Ming-Jen Sheu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Chih-Cheng Lai
- Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| |
Collapse
|
|
5
|
Buchynskyi M, Oksenych V, Kamyshna I, Kamyshnyi O. Exploring Paxlovid Efficacy in COVID-19 Patients with MAFLD: Insights from a Single-Center Prospective Cohort Study. Viruses 2024; 16:112. [PMID: 38257811 PMCID: PMC10819977 DOI: 10.3390/v16010112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 01/04/2024] [Accepted: 01/10/2024] [Indexed: 01/24/2024] Open
Abstract
This study investigates the intricate interplay between Metabolic-associated Fatty Liver Disease (MAFLD) and COVID-19, exploring the impact of MAFLD on disease severity, outcomes, and the efficacy of the antiviral agent Paxlovid (nirmatrelvir/ritonavir). MAFLD, affecting a quarter of the global population, emerges as a potential risk factor for severe COVID-19, yet the underlying pathophysiological mechanisms remain elusive. This study focuses on the clinical significance of Paxlovid, the first orally bioavailable antiviral agent granted Emergency Use Authorization in the United States. Notably, outcomes from phase II/III trials exhibit an 88% relative risk reduction in COVID-19-associated hospitalization or mortality among high-risk patients. Despite conflicting data on the association between MAFLD and COVID-19 severity, this research strives to bridge the gap by evaluating the effectiveness of Paxlovid in MAFLD patients with COVID-19, addressing the scarcity of relevant studies.
Collapse
Affiliation(s)
- Mykhailo Buchynskyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Valentyn Oksenych
- Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Oleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| |
Collapse
|
|
6
|
Huang T, Zheng D, Song Y, Pan H, Qiu G, Xiang Y, Wang Z, Wang F. Demonstration of the impact of COVID-19 on metabolic associated fatty liver disease by bioinformatics and system biology approach. Medicine (Baltimore) 2023; 102:e34570. [PMID: 37657050 PMCID: PMC10476796 DOI: 10.1097/md.0000000000034570] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 07/13/2023] [Indexed: 09/03/2023] Open
Abstract
BACKGROUND Severe coronavirus disease 2019 (COVID-19) has caused a great threat to human health. Metabolic associated fatty liver disease (MAFLD) is a liver disease with a high prevalence rate. Previous studies indicated that MAFLD led to increased mortality and severe case rates of COVID-19 patients, but its mechanism remains unclear. METHODS This study analyzed the transcriptional profiles of COVID-19 and MAFLD patients and their respective healthy controls from the perspectives of bioinformatics and systems biology to explore the underlying molecular mechanisms between the 2 diseases. Specifically, gene expression profiles of COVID-19 and MAFLD patients were acquired from the gene expression omnibus datasets and screened shared differentially expressed genes (DEGs). Gene ontology and pathway function enrichment analysis were performed for common DEGs to reveal the regulatory relationship between the 2 diseases. Besides, the hub genes were extracted by constructing a protein-protein interaction network of shared DEGs. Based on these hub genes, we conducted regulatory network analysis of microRNA/transcription factors-genes and gene - disease relationship and predicted potential drugs for the treatment of COVID-19 and MAFLD. RESULTS A total of 3734 and 589 DEGs were screened from the transcriptome data of MAFLD (GSE183229) and COVID-19 (GSE196822), respectively, and 80 common DEGs were identified between COVID-19 and MAFLD. Functional enrichment analysis revealed that the shared DEGs were involved in inflammatory reaction, immune response and metabolic regulation. In addition, 10 hub genes including SERPINE1, IL1RN, THBS1, TNFAIP6, GADD45B, TNFRSF12A, PLA2G7, PTGES, PTX3 and GADD45G were identified. From the interaction network analysis, 41 transcription factors and 151 micro-RNAs were found to be the regulatory signals. Some mental, Inflammatory, liver diseases were found to be most related with the hub genes. Importantly, parthenolide, luteolin, apigenin and MS-275 have shown possibility as therapeutic agents against COVID-19 and MAFLD. CONCLUSION This study reveals the potential common pathogenesis between MAFLD and COVID-19, providing novel clues for future research and treatment of MAFLD and severe acute respiratory syndrome coronavirus 2 infection.
Collapse
Affiliation(s)
- Tengda Huang
- Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Sichuan, Chengdu, China
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Dawei Zheng
- The College of Life Sciences, Sichuan University, Chengdu, China
| | - Yujia Song
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Hongyuan Pan
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Guoteng Qiu
- Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Yuchu Xiang
- The College of Life Sciences, Sichuan University, Chengdu, China
| | - Zichen Wang
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Fang Wang
- Innovation Center of Nursing Research, Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Sichuan, Chengdu, China
| |
Collapse
|
|
7
|
Samarasinghe SM, Hewage AS, Siriwardana RC, Tennekoon KH, Niriella MA, De Silva S. Genetic and metabolic aspects of non-alcoholic fatty liver disease (NAFLD) pathogenicity. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2023; 24:53. [DOI: 10.1186/s43042-023-00433-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 08/21/2023] [Indexed: 01/03/2025] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease showing a rising prevalence globally. Genetic predisposition plays a key role in the development and progression of the disease pathogenicity.
Main body
This paper summarizes genetic associations based on their influence on several metabolic aspects such as lipid metabolism, glucose metabolism, hepatic iron accumulation and cholesterol metabolism toward the NAFLD pathogenicity. Furthermore, we present variations in some epigenetic characters and the microRNA profile with regard to NAFLD.
Conclusion
As reported in many studies, the PNPLA3 rs738409 variant seems to be significantly associated with NAFLD susceptibility. Other gene variants like TM6SF2 rs58542926, MBOAT7 rs641738 and GCKR variants also appear to be more prevalent among NAFLD patients. We believe these genetic variants may provide insights into new trends in developing noninvasive biomarkers and identify their suitability in clinical practice in the future.
Graphical abstract
Collapse
|
|
8
|
Jagirdhar GSK, Pattnaik H, Banga A, Qasba RK, Rama K, Reddy ST, Bucharles ACF, Kashyap R, Elmati PR, Bansal V, Bains Y, DaCosta T, Surani S. Association of Non-Alcoholic Fatty Liver Disease and Metabolic-Associated Fatty Liver Disease with COVID-19-Related Intensive Care Unit Outcomes: A Systematic Review and Meta-Analysis. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1239. [PMID: 37512051 PMCID: PMC10386363 DOI: 10.3390/medicina59071239] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/13/2023] [Accepted: 06/27/2023] [Indexed: 07/30/2023]
Abstract
Background and Objective: The association of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) with intensive care unit (ICU) admissions and the need for mechanical ventilation and disease severity in COVID-19 patients. Material and Methods: A systematic literature review was conducted on the databases: Cochrane, Embase, PubMed, ScienceDirect, and the Web of Science from January 2019 to June 2022. Studies evaluating MAFLD using laboratory methods, non-invasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259), and PRISMA guidelines were followed. The NIH quality assessment tool was used for quality assessment. RevMan version 5.3 software was used for pooled analysis. A sensitivity analysis was performed to assess the result's stability. Results: A total of 37,974 patients from 17 studies were assessed for the association between MAFLD and ICU admission. A total of 3396 COVID-19 patients required ICU admission: 1236 (20.41%) in the MAFLD group and 2160 (6.77%) in the non-MAFLD group. The odds ratio was 1.86 for ICU admission, p = 0.007, and a (95% CI) of [1.18-2.91]. A total of 37,166 patients from 13 studies were included in the need for invasive mechanical ventilation analysis. A total of 1676 patients required mechanical ventilation: 805 in the MAFLD group (14.20% of all MAFLD patients) and 871 patients in the non-MAFLD group (2.76% of all non-MAFLD patients). The odds ratio was 2.05, p = 0.02, and a (95% CI) of [1.12-3.74]. A total of 5286 patients from 14 studies were included in the COVID-19 disease severity analysis. Severe COVID-19 was seen in 1623 patients, with 33.17% (901/2716) of MAFLD patients and 28.09% (722/2570) of non-MAFLD patients having severe disease. The odds ratio was 1.59 for disease severity, p = 0.010, and a (95% CI) of [1.12-2.26]. Conclusions: Our meta-analysis suggests that there are significantly increased odds of ICU admissions, a need for invasive mechanical ventilation, and disease severity in MAFLD patients who acquire COVID-19.
Collapse
Affiliation(s)
| | | | - Akshat Banga
- Sawai Man Singh Medical College, Jaipur 302004, India
| | - Rakhtan K Qasba
- Green Life Medical College and Hospital, Dhaka 1205, Bangladesh
| | | | | | | | - Rahul Kashyap
- Critical Care Medicine, Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA
| | - Praveen Reddy Elmati
- Interventional Pain Medicine, University of Louisville, Louisville, KY 40202, USA
| | - Vikas Bansal
- Division of Nephrology and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA
| | - Yatinder Bains
- Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, USA
| | - Theodore DaCosta
- Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, USA
| | - Salim Surani
- Pulmonary, Critical Care & Pharmacy, Texas A&M University, College Station, TX 79016, USA
| |
Collapse
|
|
9
|
Jagirdhar GSK, Qasba RK, Pattnaik H, Rama K, Banga A, Reddy ST, Flumignan Bucharles AC, Kashyap R, Elmati PR, Bansal V, Bains Y, DaCosta T, Surani S. Association of non-alcoholic fatty liver and metabolic-associated fatty liver with COVID-19 outcomes: A systematic review and meta-analysis. World J Gastroenterol 2023; 29:3362-3378. [PMID: 37377589 PMCID: PMC10292144 DOI: 10.3748/wjg.v29.i21.3362] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/25/2023] [Accepted: 04/28/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) are on the rise like any other liver disease, and tend to affect 25% of the United States population. The impact of NAFLD and MAFLD on patients with coronavirus disease 2019 (COVID-19) remains unclear.
AIM To identify the association of NAFLD and MAFLD with mortality, hospitalization, hospital length of stay, and supplemental oxygen utilization in COVID-19 patients.
METHODS A systematic review of literature on Cochrane, Embase, PubMed, ScienceDirect, and Web of Science databases was conducted from January 2019 to July 2022. Studies that evaluated NAFLD/MAFLD using laboratory methods, noninvasive imaging, or liver biopsy were included. The study protocol was registered in PROSPERO (ID CRD42022313259) and PRISMA guidelines were followed. The National Institutes of Health quality assessment tool was used to assess the quality of the studies. Pooled analysis was conducted using software Rev Man version 5.3. The stability of the results was assessed using sensitivity analysis.
RESULTS Thirty-two studies with 43388 patients were included in the meta-analysis of whom 8538 (20%) patients were observed to have NAFLD. There were 42254 patients from 28 studies included in the mortality analysis. A total of 2008 patients died from COVID-19; 837 (10.52%) in the NAFLD group and 1171 (3.41%) in the non-NAFLD group. The odds ratio (OR) was 1.38 for mortality with a 95% confidence interval (95%CI) = 0.97-1.95 and P = 0.07. A total of 5043 patients from eight studies were included in the hospital length of stay analysis. There were 1318 patients in the NAFLD group and 3725 patients in the non-NAFLD group. A qualitative synthesis showed that the mean difference in hospital length of stay was about 2 d between the NAFLD and non-NAFLD groups with a 95%CI = 0.71-3.27 and P = 0.002. For hospitalization rates, the OR was 3.25 with a 95%CI of 1.73-6.10 and P = 0.0002. For supplemental oxygen utilization, the OR was 2.04 with a 95%CI of 1.17-3.53 and P = 0.01.
CONCLUSION Our meta-analysis suggests that there are increased odds of hospitalization, longer hospital length of stay, and increased use of supplemental oxygen in NAFLD/MAFLD patients.
Collapse
Affiliation(s)
| | - Rakhtan K Qasba
- Department of Medicine, Green Life Medical College and Hospital, Dhaka 1205, Bangladesh
| | - Harsha Pattnaik
- Department of Medicine, Lady Hardinge Medical College, New Delhi 110001, India
| | - Kaanthi Rama
- Department of Medicine, Gandhi Medical College, Telangana 500003, India
| | - Akshat Banga
- Department of Medicine, Sawai Man Singh Medical College, Jaipur 302004, Rajistan, India
| | - Shiva Teja Reddy
- Department of Medicine, Gandhi Medical College, Telangana 500003, India
| | | | - Rahul Kashyap
- Research, WellSpan Health, York, PA 17403, United States
| | - Praveen Reddy Elmati
- Department of Interventional Pain Medicine, University of Louisville, Louisville, KY 40292, United States
| | - Vikas Bansal
- Department of Internal Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Yatinder Bains
- Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, United States
| | - Theodore DaCosta
- Department of Gastroenterology, Saint Michaels Medical Center, Newark, NJ 07102, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, TX 77843, United States
| |
Collapse
|
|
10
|
Akkiz H. Unraveling the Molecular and Cellular Pathogenesis of COVID-19-Associated Liver Injury. Viruses 2023; 15:1287. [PMID: 37376587 DOI: 10.3390/v15061287] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Revised: 05/02/2023] [Accepted: 05/04/2023] [Indexed: 06/29/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) continues to cause substantial morbidity and mortality. Most infections are mild; however, some patients experience severe and potentially fatal systemic inflammation, tissue damage, cytokine storm, and acute respiratory distress syndrome. Patients with chronic liver disease have been frequently affected, experiencing high morbidity and mortality. In addition, elevated liver enzymes may be a risk factor for disease progression, even in the absence of underlying liver disease. While the respiratory tract is a primary target of SARS-CoV-2, it has become evident that COVID-19 is a multisystemic infectious disease. The hepatobiliary system might be influenced during COVID-19 infection, ranging from a mild elevation of aminotransferases to the development of autoimmune hepatitis and secondary sclerosing cholangitis. Furthermore, the virus can promote existing chronic liver diseases to liver failure and activate the autoimmune liver disease. Whether the direct cytopathic effects of the virus, host reaction, hypoxia, drugs, vaccination, or all these risk factors cause liver injury has not been clarified to a large extent in COVID-19. This review article discussed the molecular and cellular mechanisms involved in the pathogenesis of SARS-CoV-2 virus-associated liver injury and highlighted the emerging role of liver sinusoidal epithelial cells (LSECs) in virus-related liver damage.
Collapse
Affiliation(s)
- Hikmet Akkiz
- Department of Gastroenterology and Hepatology, Medical Faculty, Bahçeşehir University, Istanbul 34349, Turkey
| |
Collapse
|
|
11
|
Simão AL, Palma CS, Izquierdo-Sanchez L, Putignano A, Carvalho-Gomes A, Posch A, Zanaga P, Girleanu I, Henrique MM, Araújo C, Degre D, Gustot T, Sahuco I, Spagnolo E, Carvalhana S, Moura M, Fernandes DAE, Banales JM, Romero-Gomez M, Trifan A, Russo FP, Stauber R, Berenguer M, Moreno C, Gonçalves J, Cortez-Pinto H, Castro RE. Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease. JHEP Rep 2023; 5:100697. [PMID: 36844943 PMCID: PMC9939238 DOI: 10.1016/j.jhepr.2023.100697] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 01/10/2023] [Accepted: 01/21/2023] [Indexed: 02/22/2023] Open
Abstract
Background & Aims The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study. Results Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.
Collapse
Affiliation(s)
- André Lopes Simão
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Carolina Santos Palma
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Laura Izquierdo-Sanchez
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
| | - Antonella Putignano
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Angela Carvalho-Gomes
- Hepatology & Liver Transplantation Unit, La Fe University Hospital, University of Valencia, CIBER-EHD and IIS La Fe, Valencia, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, “Instituto de Salud Carlos III” (ISCIII), Madrid, Spain
| | - Andreas Posch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Paola Zanaga
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Irina Girleanu
- ‘Grigore T. Popa’ University of Medicine and Pharmacy, ‘St. Spiridon’ Emergency Hospital, Institute of Gastroenterology and Hepatology, Iasi, Romania
| | - Mariana Moura Henrique
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Carlos Araújo
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Delphine Degre
- Institute for Medical Immunology, Erasme Campus, Brussels, Belgium
| | - Thierry Gustot
- Institute for Medical Immunology, Erasme Campus, Brussels, Belgium
| | - Iván Sahuco
- Hepatology & Liver Transplantation Unit, La Fe University Hospital, University of Valencia, CIBER-EHD and IIS La Fe, Valencia, Spain
| | - Elia Spagnolo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Sofia Carvalhana
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Miguel Moura
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
| | - Diogo AE. Fernandes
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Jesus M. Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, “Instituto de Salud Carlos III” (ISCIII), Madrid, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
- Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - Manuel Romero-Gomez
- Digestive Diseases Department, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (IBIS: HUVRocío/CSIC/US), University of Seville, Seville, Spain
| | - Anca Trifan
- ‘Grigore T. Popa’ University of Medicine and Pharmacy, ‘St. Spiridon’ Emergency Hospital, Institute of Gastroenterology and Hepatology, Iasi, Romania
| | - Francesco Paolo Russo
- Gastroenterology and Multivisceral Transplant Unit, Azienda Ospedale-Università di Padova, Padua, Italy
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Rudolf Stauber
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Marina Berenguer
- Hepatology & Liver Transplantation Unit, La Fe University Hospital, University of Valencia, CIBER-EHD and IIS La Fe, Valencia, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases, CIBERehd, “Instituto de Salud Carlos III” (ISCIII), Madrid, Spain
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - João Gonçalves
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Helena Cortez-Pinto
- Departamento de Gastrenterologia, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal
- Clínica Universitária de Gastrenterologia, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Rui E. Castro
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| |
Collapse
|
|
12
|
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.
Collapse
Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
| |
Collapse
|
|
13
|
Buchynskyi M, Kamyshna I, Oksenych V, Zavidniuk N, Kamyshnyi A. The Intersection of COVID-19 and Metabolic-Associated Fatty Liver Disease: An Overview of the Current Evidence. Viruses 2023; 15:v15051072. [PMID: 37243158 DOI: 10.3390/v15051072] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 04/23/2023] [Accepted: 04/26/2023] [Indexed: 05/28/2023] Open
Abstract
The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. With our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is a pervasive public health concern intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and MAFLD is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among MAFLD patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of MAFLD on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.
Collapse
Affiliation(s)
- Mykhailo Buchynskyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Iryna Kamyshna
- Department of Medical Rehabilitation, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Valentyn Oksenych
- Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
| | - Nataliia Zavidniuk
- Department of Infectious Diseases with Epidemiology, Dermatology and Venerology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| | - Aleksandr Kamyshnyi
- Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine
| |
Collapse
|
|
14
|
Valentino MS, Marzuillo P, Esposito C, Bartiromo M, Nardolillo M, Villani AV, Maresca A, Furcolo G, Guarino S, Miraglia del Giudice E, Di Sessa A. The Impact of COVID-19 Pandemic Lockdown on the Relationship between Pediatric MAFLD and Renal Function. J Clin Med 2023; 12:jcm12052037. [PMID: 36902824 PMCID: PMC10003972 DOI: 10.3390/jcm12052037] [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: 12/31/2022] [Revised: 02/26/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
BACKGROUND Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease (e.g., obesity, diabetes, chronic kidney disease (CKD), and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). METHODS A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. RESULTS At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all p < 0.05). Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. CONCLUSIONS Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted.
Collapse
Affiliation(s)
- Maria Sole Valentino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Claudia Esposito
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Mario Bartiromo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Michele Nardolillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Annalisa Valentina Villani
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Alessandro Maresca
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Giuseppe Furcolo
- Unità Operativa Complessa di Pediatria e Pronto Soccorso Pediatrico, AORN Moscati, 83100 Avellino, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
- Correspondence: ; Tel.: +39-0815445465
| |
Collapse
|
|
15
|
Chakraborty R, Sharma D, Kapoor DU, Dwivedi A, Khabiya R, Sen S. Implications of metabolic dysfunction associated fatty liver disease in COVID-19. World J Clin Cases 2023; 11:1275-1286. [PMID: 36926128 PMCID: PMC10013103 DOI: 10.12998/wjcc.v11.i6.1275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/20/2022] [Accepted: 01/31/2023] [Indexed: 02/24/2023] Open
Abstract
Metabolic associated fatty liver disorder (MAFLD) characterizes the contributing etiologies (i.e., type 2 diabetes mellitus, metabolic syndrome, overweight) of individuals with fatty liver disease that affects 1/3rd of the world population. In 2020, the coronavirus disease 2019 (COVID-19) crisis was unprecedented, and people with different comorbidities became more susceptible to the infection caused by severe acute respiratory syndrome coronavirus 2. MAFLD patients are frequently obese with added metabolic menace like diabetes, hypertension, and dyslipidemia leading to greater jeopardy of COVID-19. MAFLD patients are 4 to 6-fold more prone towards infections. COVID-19 induces liver injury with elevated levels of aspartate aminotransferase and alanine aminotransferase and insignificantly elevated bilirubin. Hence, MAFLD in COVID-19 patients worsens the condition significantly. The evidence highlighting the interaction between MAFLD and altered liver functioning in COVID-19 suggested that COVID-19 patients with pre-existing MAFLD are at greater risk of morbidity or intensive care unit admission. Direct hepatic injury, enhanced levels of inflammatory cytokines, declined hepatic mitochondrial activity, and compromised immunity are considered as some underlying mechanisms. The main focus of this review is to discuss the implications of metabolic dysfunction associated with fatty liver disease in COVID-19 patients. The review systematically analyzes the effect of striking two worldwide pandemics (MAFLD and COVID-19) together in the present era.
Collapse
Affiliation(s)
- Raja Chakraborty
- Institute of Pharmacy, Assam Don Bosco University, Guwahati 782402, Assam, India
| | - Deepak Sharma
- School of Medical Sciences, Adamas University, Kolkata 700126, West Bengal, India
| | - Devesh U Kapoor
- Department of Pharmacy, Dr. Dayaram Patel Pharmacy College, Bardoli 394601, Gujarat, India
| | - Akanksha Dwivedi
- Department of Pharmacy, Acropolis Institute of Pharmaceutical Education & Research, Indore 453771, Madhya Pradesh, India
| | - Rakhi Khabiya
- Department of Pharmacy, Acropolis Institute of Pharmaceutical Education & Research, Indore 453771, Madhya Pradesh, India
| | - Saikat Sen
- Faculty of Pharmaceutical Science, Assam down town University, Guwahati 781026, Assam, India
| |
Collapse
|
|
16
|
Miranda C, Garlatti E, Da Porto A, Rinaldo E, Grazioli S, Zanette G, Tonizzo M. Liver injury in COVID-19 patients with non-alcoholic fatty liver disease: an update. Arch Med Sci Atheroscler Dis 2023; 8:e1-e10. [PMID: 37153375 PMCID: PMC10161789 DOI: 10.5114/amsad/160950] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 02/06/2023] [Indexed: 05/09/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has revolutionized the priorities of the medical society worldwide. Although most patients infected with SARS-CoV-2 exhibit respiratory symptoms, other organs may also be involved, including the liver, often resulting in liver injury. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its prevalence is expected to increase together with the epidemics of type 2 diabetes and obesity. Data about liver injury during COVID-19 are numerous, while overviews of this infection in patients with NAFLD, both in terms of respiratory and liver, are emerging. In this review, we summarise the current research focusing on COVID-19 in NAFLD patients and discuss the association between liver injury in COVID-19 subjects and non-alcoholic fatty liver disease.
Collapse
Affiliation(s)
- Cesare Miranda
- Clinic of Endocrinology and Metabolism Diseases, Pordenone Hospital, Pordenone, Italy
| | - Elena Garlatti
- Internal Medicine, Santa Maria degli Angeli Hospital, Pordenone, Italy
| | - Andrea Da Porto
- Department of Medicine, Clinica Medica, University of Udine, Udine, Italy
| | - Elena Rinaldo
- Clinic of Endocrinology and Metabolism Diseases, Pordenone Hospital, Pordenone, Italy
| | - Silvia Grazioli
- Internal Medicine, Santa Maria degli Angeli Hospital, Pordenone, Italy
| | - Giorgio Zanette
- Clinic of Endocrinology and Metabolism Diseases, Pordenone Hospital, Pordenone, Italy
| | - Maurizio Tonizzo
- Internal Medicine, Santa Maria degli Angeli Hospital, Pordenone, Italy
| |
Collapse
|
|
17
|
Lempesis IG, Karlafti E, Papalexis P, Fotakopoulos G, Tarantinos K, Lekakis V, Papadakos SP, Cholongitas E, Georgakopoulou VE. COVID-19 and liver injury in individuals with obesity. World J Gastroenterol 2023; 29:908-916. [PMID: 36844135 PMCID: PMC9950870 DOI: 10.3748/wjg.v29.i6.908] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/18/2022] [Accepted: 01/09/2023] [Indexed: 02/10/2023] Open
Abstract
Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.
Collapse
Affiliation(s)
- Ioannis G Lempesis
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, B15 2TT, United Kingdom
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht 616 6200, Netherlands
| | - Eleni Karlafti
- Department of Emergency, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki 546 21, Greece
| | - Petros Papalexis
- Unit of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
- Department of Biomedical Sciences, University of West Attica, Athens 12243, Greece
| | - George Fotakopoulos
- Department of Neurosurgery, General University Hospital of Larisa, Larisa 41221, Greece
| | | | - Vasileios Lekakis
- Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Stavros P Papadakos
- Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens 11527, Greece
| | | |
Collapse
|
|
18
|
Nevola R, Criscuolo L, Beccia D, Delle Femine A, Ruocco R, Imbriani S, Alfano M, Villani A, Russo A, Perillo P, Marfella R, Adinolfi LE, Sasso FC, Marrone A, Rinaldi L. Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination. World J Gastroenterol 2023; 29:800-814. [PMID: 36816617 PMCID: PMC9932424 DOI: 10.3748/wjg.v29.i5.800] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/12/2022] [Accepted: 01/18/2023] [Indexed: 02/06/2023] Open
Abstract
Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease.
Collapse
Affiliation(s)
- Riccardo Nevola
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Livio Criscuolo
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Domenico Beccia
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Augusto Delle Femine
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Rachele Ruocco
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Simona Imbriani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Maria Alfano
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Angela Villani
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Antonio Russo
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Pasquale Perillo
- Internal Medicine and Hepatology Unit, Ospedale Evangelico Betania, Naples 80147, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Luigi Elio Adinolfi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Aldo Marrone
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| | - Luca Rinaldi
- Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy
| |
Collapse
|
|
19
|
Gupta T, Sharma H. COVID-19 and the liver: Are footprints still there? World J Gastroenterol 2023; 29:656-669. [PMID: 36742164 PMCID: PMC9896610 DOI: 10.3748/wjg.v29.i4.656] [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: 09/13/2022] [Revised: 10/13/2022] [Accepted: 11/21/2022] [Indexed: 01/20/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases. An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems. It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction. Additionally, liver function abnormalities were noted in patients with severe COVID-19. Profound cytokine storm, direct viral infection, drugs and reactivation of viral infections were causes of deranged liver functions. Here, we discuss the relation between COVID-19 and chronic liver disease, specifically cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease (NAFLD), as well as the liver manifestations of COVID-19. The metabolic syndrome, obesity, diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide. Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19. Recently, COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis. The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.
Collapse
Affiliation(s)
- Tarana Gupta
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| | - Hemant Sharma
- Department of Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak 124001, Haryana, India
| |
Collapse
|
|
20
|
Baldelli L, Marjot T, Barnes E, Barritt AS, Webb GJ, Moon AM. SARS-CoV-2 Infection and Liver Disease: A Review of Pathogenesis and Outcomes. Gut Liver 2023; 17:12-23. [PMID: 36457261 PMCID: PMC9840920 DOI: 10.5009/gnl220327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/31/2022] [Accepted: 09/07/2022] [Indexed: 12/03/2022] Open
Abstract
The impact of the coronavirus disease 2019 (COVID-19) pandemic has been immense, and it continues to have lasting repercussions. While the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus primarily infects the respiratory system, other organ systems are affected, including the liver. Scientific knowledge on the role of SARS-CoV-2 infection and liver injury has evolved rapidly, with recent data suggesting specific hepatotropism of SARS-CoV-2. Moreover, additional concerns have been raised in regard to long-term liver damage, related to emerging cases of post-COVID-19 cholangiopathy and chronic cholestasis. Great effort has also been focused on studying how specific subpopulations with chronic medical conditions might be disproportionately impacted by COVID-19. One such population includes individuals with chronic liver disease (CLD) and cirrhosis, with an expanding body of research indicating these patients being particularly susceptible to adverse outcomes. In this review, we provide an updated summary on the current pathogenesis and mechanism of liver injury in the setting of SARS-CoV-2 infection, the association between health outcomes and SARS-CoV-2 infection in patients with CLD, and the unique consequences of the COVID-19 pandemic on the routine care of patients with CLD.
Collapse
Affiliation(s)
- Luke Baldelli
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Thomas Marjot
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Oxford Liver Unit, Translational Gastroenterology Unit, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK
| | - A. Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| | - Gwilym J. Webb
- Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Andrew M. Moon
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC, USA
| |
Collapse
|
|
21
|
Papagiouvanni I, Kotoulas SC, Pataka A, Spyratos DG, Porpodis K, Boutou AK, Papagiouvannis G, Grigoriou I, Vettas C, Goulis I. COVID-19 and liver injury: An ongoing challenge. World J Gastroenterol 2023; 29:257-271. [PMID: 36687117 PMCID: PMC9846934 DOI: 10.3748/wjg.v29.i2.257] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/29/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.
Collapse
Affiliation(s)
- Ioanna Papagiouvanni
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Thessaloniki, Greece
| | | | - Athanasia Pataka
- Department of Respiratory Medicine, G Papanikolaou Hospital, Resp Failure Unit, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Dionisios G Spyratos
- Pulmonary Department, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Konstantinos Porpodis
- Pulmonary Department, Aristotle University of Thessaloniki, Thessaloniki 57001, Greece
| | - Afroditi K Boutou
- Pulmonary Department, G Papanikolaou Hospital, Resp Failure Unit, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Georgios Papagiouvannis
- Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus
| | - Ioanna Grigoriou
- Respiratory Failure Clinic, Papanikolaou General Hospital, Thessloniki 57001, Greece
| | - Christos Vettas
- Fourth Department of Internal Medicine, Hippokration General Hospital, Thessaloniki 54642, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokration General Hospital, Thessaloniki 54642, Greece
| |
Collapse
|
|
22
|
Dietrich CG, Geier A, Merle U. Non-alcoholic fatty liver disease and COVID-19: Harmless companions or disease intensifier? World J Gastroenterol 2023; 29:367-377. [PMID: 36687116 PMCID: PMC9846932 DOI: 10.3748/wjg.v29.i2.367] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 11/09/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
The pandemics of coronavirus disease 2019 (COVID-19) and non-alcoholic fatty liver disease (NAFLD) coexist. Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD, while preexisting liver damage from NAFLD may influence the course of COVID-19. However, the prognostic relevance of this interaction, though, is unclear. Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19. Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity. Striking molecular similarities of cytokine pathways in both diseases, including postacute sequelae of COVID-19, suggest common pathways for chronic low-activity inflammation. This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.
Collapse
Affiliation(s)
| | - Andreas Geier
- Division of Hepatology, Department of Medicine II, University Hospital Wuerzburg, Wuerzburg 97080, Germany
| | - Uta Merle
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg 69120, Germany
| |
Collapse
|
|
23
|
Zsichla L, Müller V. Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors. Viruses 2023; 15:175. [PMID: 36680215 PMCID: PMC9863423 DOI: 10.3390/v15010175] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/04/2023] [Accepted: 01/04/2023] [Indexed: 01/11/2023] Open
Abstract
The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.
Collapse
Affiliation(s)
- Levente Zsichla
- Institute of Biology, Eötvös Loránd University, 1117 Budapest, Hungary
- National Laboratory for Health Security, Eötvös Loránd University, 1117 Budapest, Hungary
| | - Viktor Müller
- Institute of Biology, Eötvös Loránd University, 1117 Budapest, Hungary
- National Laboratory for Health Security, Eötvös Loránd University, 1117 Budapest, Hungary
| |
Collapse
|
|
24
|
Brandi N, Spinelli D, Granito A, Tovoli F, Piscaglia F, Golfieri R, Renzulli M. COVID-19: Has the Liver Been Spared? Int J Mol Sci 2023; 24:1091. [PMID: 36674607 PMCID: PMC9866733 DOI: 10.3390/ijms24021091] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/03/2023] [Accepted: 01/04/2023] [Indexed: 01/09/2023] Open
Abstract
The liver is a secondary and often collateral target of COVID-19 disease but can lead to important consequences. COVID-19 might directly cause a high number of complications in patients with pre-existing chronic liver disease, increasing their risk of hepatic decompensation. Moreover, it also determines indirect consequences in the management of patients with liver disease, especially in those suffering from decompensated cirrhosis and HCC, as well as in the execution of their follow-up and the availability of all therapeutic possibilities. Liver imaging in COVID-19 patients proved to be highly nonspecific, but it can still be useful for identifying the complications that derive from the infection. Moreover, the recent implementation of telemedicine constitutes a possible solution to both the physical distancing and the re-organizational difficulties arising from the pandemic. The present review aims to encompass the currently hypothesized pathophysiological mechanisms of liver injury in patients with COVID-19 mediated by both the direct invasion of the virus and its indirect effects and analyze the consequence of the pandemic in patients with chronic liver disease and liver tumors, with particular regard to the management strategies that have been implemented to face this worldwide emergency and that can be further improved.
Collapse
Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Daniele Spinelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| |
Collapse
|
|
25
|
Hu WS, Jiang FY, Shu W, Zhao R, Cao JM, Wang DP. Liver injury in COVID-19: A minireview. World J Gastroenterol 2022; 28:6716-6731. [PMID: 36620342 PMCID: PMC9813934 DOI: 10.3748/wjg.v28.i47.6716] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 11/02/2022] [Accepted: 11/23/2022] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has escalated into a global tragedy afflicting human health, life, and social governance. Through the increasing depth of research and a better understanding of this disease, it has been ascertained that, in addition to the lungs, SARS-CoV-2 can also induce injuries to other organs including the liver. Liver injury is a common clinical manifestation of COVID-19, particularly in severe cases, and is often associated with a poorer prognosis and higher severity of COVID-19. This review focuses on the general existing information on liver injury caused by COVID-19, including risk factors and subpopulations of liver injury in COVID-19, the association between preexisting liver diseases and the severity of COVID-19, and the potential mechanisms by which SARS-CoV-2 affects the liver. This review may provide some useful information for the development of therapeutic and preventive strategies for COVID-19-associated liver injury.
Collapse
Affiliation(s)
- Wen-Shu Hu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Fang-Ying Jiang
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Wen Shu
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Rong Zhao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - Ji-Min Cao
- Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| | - De-Ping Wang
- Department of Physiology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
| |
Collapse
|
|
26
|
Domovitz T, Ayoub S, Werbner M, Alter J, Izhaki Tavor L, Yahalom-Ronen Y, Tikhonov E, Meirson T, Maman Y, Paran N, Israely T, Dessau M, Gal-Tanamy M. HCV Infection Increases the Expression of ACE2 Receptor, Leading to Enhanced Entry of Both HCV and SARS-CoV-2 into Hepatocytes and a Coinfection State. Microbiol Spectr 2022; 10:e0115022. [PMID: 36314945 PMCID: PMC9769977 DOI: 10.1128/spectrum.01150-22] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 09/28/2022] [Indexed: 11/09/2022] Open
Abstract
Recent studies suggest the enhancement of liver injury in COVID-19 patients infected with Hepatitis C virus (HCV). Hepatocytes express low levels of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor, raising the possibility of HCV-SARS-CoV-2 coinfection in the liver. This work aimed to explore whether HCV and SARS-CoV-2 coinfect hepatocytes and the interplay between these viruses. We demonstrate that SARS-CoV-2 coinfects HCV-infected Huh7.5 (Huh7.5HCV) cells. Both viruses replicated efficiently in the coinfected cells, with HCV replication enhanced in coinfected compared to HCV-mono-infected cells. Strikingly, Huh7.5HCV cells were eight fold more susceptible to SARS-CoV-2 pseudoviruses than naive Huh7.5 cells, suggesting enhanced SARS-CoV-2 entry into HCV-preinfected hepatocytes. In addition, we observed increased binding of spike receptor-binding domain (RBD) protein to Huh7.5HCV cells, as well as enhanced cell-to-cell fusion of Huh7.5HCV cells with spike-expressing Huh7.5 cells. We explored the mechanism of enhanced SARS-CoV-2 entry and identified an increased ACE2 mRNA and protein levels in Huh7.5HCV cells, primary hepatocytes, and in data from infected liver biopsies obtained from database. Importantly, higher expression of ACE2 increased HCV infection by enhancing its binding to the host cell, underscoring its role in the HCV life cycle as well. Transcriptome analysis revealed that shared host signaling pathways were induced in HCV-SARS-CoV-2 coinfection. This study revealed complex interactions between HCV and SARS-CoV-2 infections in hepatocytes, which may lead to the increased liver damage recently reported in HCV-positive COVID-19 patients. IMPORTANCE Here, we provide the first experimental evidence for the coexistence of SARS-CoV-2 infection with HCV, and the interplay between them. The study revealed a complex relationship of enhancement between the two viruses, where HCV infection increased the expression of the SARS-CoV-2 entry receptor ACE2, thus facilitating SARS-CoV-2 entry, and potentially, also HCV entry. Thereafter, SARS-CoV-2 infection enhanced HCV replication in hepatocytes. This study may explain the aggravation of liver damage that was recently reported in COVID-19 patients with HCV coinfection and suggests preinfection with HCV as a risk factor for severe COVID-19. Moreover, it highlights the possible importance of HCV treatment for coinfected patients. In a broader view, these findings emphasize the importance of identifying coinfecting pathogens that increase the risk of SARS-CoV-2 infection and that may accelerate COVID-19-related co-morbidities.
Collapse
Affiliation(s)
- Tom Domovitz
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Samer Ayoub
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Michal Werbner
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Joel Alter
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lee Izhaki Tavor
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Yfat Yahalom-Ronen
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Evgeny Tikhonov
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Tomer Meirson
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel
| | - Yaakov Maman
- The Lab of Genomic Instability and Cancer, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Nir Paran
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Tomer Israely
- Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
| | - Moshe Dessau
- The Laboratory of Structural Biology of Infectious Diseases, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Meital Gal-Tanamy
- Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| |
Collapse
|
|
27
|
Shiri Aghbash P, Ebrahimzadeh Leylabadlo H, Fathi H, Bahmani M, Chegini R, Bannazadeh Baghi H. Hepatic Disorders and COVID-19: From Pathophysiology to Treatment Strategy. Can J Gastroenterol Hepatol 2022; 2022:4291758. [PMID: 36531832 PMCID: PMC9754839 DOI: 10.1155/2022/4291758] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 10/31/2022] [Accepted: 11/12/2022] [Indexed: 12/13/2022] Open
Abstract
Following the SARS-CoV-2 outbreak and the subsequent development of the COVID-19 pandemic, organs such as the lungs, kidneys, liver, heart, and brain have been identified as priority organs. Liver diseases are considered a risk factor for high mortality from the COVID-19 pandemic. Besides, liver damage has been demonstrated in a substantial proportion of patients with COVID-19, especially those with severe clinical symptoms. Furthermore, antiviral medications, immunosuppressive drugs after liver transplantation, pre-existing hepatic diseases, and chronic liver diseases such as cirrhosis have also been implicated in SARS-CoV-2-induced liver injury. As a result, some precautions have been taken to prevent, monitor the virus, and avoid immunocompromised and susceptible individuals, such as liver and kidney transplant recipients, from being infected with SARS-CoV-2, thereby avoiding an increase in mortality. The purpose of this review was to examine the impairment caused by SARS-CoV-2 infection and the impact of drugs used during the pandemic on the mortality range and therefore the possibility of preventive measures in patients with liver disease.
Collapse
Affiliation(s)
- Parisa Shiri Aghbash
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Hamidreza Fathi
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tabriz, Iran
| | - Mohaddeseh Bahmani
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Rojin Chegini
- Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
28
|
A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes. Nat Commun 2022; 13:7430. [PMID: 36473860 PMCID: PMC9726889 DOI: 10.1038/s41467-022-35158-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 11/21/2022] [Indexed: 12/12/2022] Open
Abstract
The breakdown of toll-like receptor (TLR) tolerance results in tissue damage, and hyperactivation of the TLRs and subsequent inflammatory consequences have been implicated as risk factors for more severe forms of disease and poor outcomes from various diseases including COVID-19 and metabolic (dysfunction) associated fatty liver disease (MAFLD). Here we provide evidence that membrane bound O-acyltransferase domain containing 7 (MBOAT7) is a negative regulator of TLR signalling. MBOAT7 deficiency in macrophages as observed in patients with MAFLD and in COVID-19, alters membrane phospholipid composition. We demonstrate that this is associated with a redistribution of arachidonic acid toward proinflammatory eicosanoids, induction of endoplasmic reticulum stress, mitochondrial dysfunction, and remodelling of the accessible inflammatory-related chromatin landscape culminating in macrophage inflammatory responses to TLRs. Activation of MBOAT7 reverses these effects. These outcomes are further modulated by the MBOAT7 rs8736 (T) MAFLD risk variant. Our findings suggest that MBOAT7 can potentially be explored as a therapeutic target for diseases associated with dysregulation of the TLR signalling cascade.
Collapse
|
|
29
|
Elghannam MT, Hassanien MH, Ameen YA, ELattar GM, ELRay AA, Turky EA, ELTalkawy MD. COVID-19 and liver diseases. EGYPTIAN LIVER JOURNAL 2022; 12:43. [PMID: 35880136 PMCID: PMC9301896 DOI: 10.1186/s43066-022-00202-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 07/06/2022] [Indexed: 12/15/2022] Open
Abstract
Coronavirus causes an outbreak of viral pneumonia that spread throughout the world. Liver injury is becoming more widely recognized as a component of the clinical picture of COVID-19 infection. Hepatitis with serum ALT elevation has been reported in up to half of patients. Patients with CLD were at a higher risk of decompensation with liver failure, hospitalization, and mortality. The percentage of acute liver injury (ALI) varied from 5 to 28%. COVID-19 hinders HCV elimination by 2030. It is recommended to continue treatment of chronic HCV and chronic HBV if already receiving treatment. Consider using antiviral therapy to prevent viral flare-ups in patients with occult or resolved HBV and COVID-19 who are receiving immunosuppressive agents. Patients with AIH do not have an increased risk of adverse outcomes even in high-risk areas. There is an association between MAFLD and disease progression. Patients with any type of cancer are at a higher risk of infection and are more likely to develop more severe clinical outcomes. Most societies advise against immunosuppressant modifications in patients with mild COVID-19, whereas in rare cases such as severe lymphopenia, worsening pneumonia, or bacterial or fungal superinfection, reduction or discontinuation of antiproliferative agents and lymphocyte-depleting therapies has been suggested.
Collapse
|
|
30
|
Chi ZC. Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases. Shijie Huaren Xiaohua Zazhi 2022; 30:783-794. [DOI: 10.11569/wcjd.v30.i18.783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.
Collapse
Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
| |
Collapse
|
|
31
|
Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications. Metabolites 2022; 12:metabo12100912. [PMID: 36295814 PMCID: PMC9611210 DOI: 10.3390/metabo12100912] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 09/11/2022] [Accepted: 09/19/2022] [Indexed: 11/17/2022] Open
Abstract
Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota’s link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body’s systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.
Collapse
|
|
32
|
Fukunaga S, Nakano D, Tsutsumi T, Kawaguchi T, Eslam M, Yoshinaga S, Abe H, Nouno R, Joh S, Mitsuyama K, George J, Torimura T. Lean/normal-weight metabolic dysfunction-associated fatty liver disease is a risk factor for reflux esophagitis. Hepatol Res 2022; 52:699-711. [PMID: 35585481 DOI: 10.1111/hepr.13795] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/06/2022] [Accepted: 05/15/2022] [Indexed: 12/12/2022]
Abstract
AIM Reflux esophagitis is associated with metabolic dysfunction. Recently, fatty liver has been redefined as metabolic dysfunction-associated fatty liver disease (MAFLD). We investigated the impact of MAFLD and its subtypes on the incidence of reflux esophagitis. METHODS This multicenter, observational cohort study enrolled 9100 consecutive health-check examinees who underwent esophagogastroduodenoscopy and ultrasonography. All patients were classified into the MAFLD or non-MAFLD group. Based on the Asian cut-off value for body mass index (BMI), the MAFLD group was further classified into the lean/normal-weight (BMI <23 kg/m2 ) and overweight/obese (BMI ≥23 kg/m2 ) subgroups. The impact of MAFLD and its subtypes on the cumulative incidence of reflux esophagitis was evaluated using multivariable Cox proportional hazards regression analysis. RESULTS MAFLD was diagnosed in 26.5% (2416/9100) of patients. Multivariable Cox proportional hazards regression analysis indicated that MAFLD (hazard ratio [HR] 1.2183; 95% confidence interval [CI] 1.0954-1.3550; p = 0.0003), hiatal hernia, and aging were independent risk factors for reflux esophagitis. Stratification analysis indicated that cumulative incidence of reflux esophagitis among patients with MAFLD was significantly higher in the lean/normal-weight than in the overweight/obese group (HR 1.3274; 95% CI 1.0043-1.7547; p = 0.0466). Among various metabolic factors, visceral adiposity was the only independent metabolic risk factor for reflux esophagitis (HR 2.8331; 95% CI 1.0201-7.8691; p = 0.0457) in the lean/normal-weight MAFLD group. CONCLUSIONS MAFLD, in particular lean/normal-weight MAFLD, is independent risk factor for reflux esophagitis. Furthermore, visceral adiposity was identified as the most strong metabolic risk factor for reflux esophagitis in lean/normal-weight patients with MAFLD.
Collapse
Affiliation(s)
- Shuhei Fukunaga
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Dan Nakano
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Tsubasa Tsutsumi
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Takumi Kawaguchi
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia
| | - Shinobu Yoshinaga
- Medical Examination Section, Medical Examination Part Facilities, Public Utility Foundation Saga Prefectural Health Promotion Foundation, Saga, Japan
| | | | | | | | - Keiichi Mitsuyama
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia
| | - Takuji Torimura
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| |
Collapse
|
|
33
|
Chen H, Chen Q. COVID-19 Pandemic: Insights into Interactions between SARS-CoV-2 Infection and MAFLD. Int J Biol Sci 2022; 18:4756-4767. [PMID: 35874945 PMCID: PMC9305262 DOI: 10.7150/ijbs.72461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/23/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an ongoing global health pandemic. Since 2019, the pandemic continues to cast a long shadow on all aspects of our lives, bringing huge health and economic burdens to all societies. With our in-depth understanding of COVID-19, from the initial respiratory tract to the later gastrointestinal tract and cardiovascular systems, the multiorgan involvement of this infectious disease has been discovered. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named nonalcoholic fatty liver disease (NAFLD), is a major health issue closely related to metabolic dysfunctions, affecting a quarter of the world's adult population. The association of COVID-19 with MAFLD has received increasing attention, as MAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19 symptoms. In this review, we provide an update on the interactions between COVID-19 and MAFLD and its underlying mechanisms.
Collapse
Affiliation(s)
- Hanfei Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
| | - Qiang Chen
- Cancer Center, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.,MOE Frontier Science Centre for Precision Oncology, University of Macau, Taipa, Macau SAR, China
| |
Collapse
|
|
34
|
Hayat U, Ashfaq MZ, Johnson L, Ford R, Wuthnow C, Kadado K, El Jurdi K, Okut H, Kilgore WR, Assi M, Siddiqui AA. The Association of Metabolic-Associated Fatty Liver Disease with Clinical Outcomes of COVID-19: A Systematic Review and Meta-Analysis. Kans J Med 2022; 15:241-246. [PMID: 35899064 PMCID: PMC9311786 DOI: 10.17161/kjm.vol15.16522] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 05/16/2022] [Indexed: 02/06/2023] Open
Abstract
Introduction Metabolic-associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome (MS). MAFLD patients have a higher prevalence of COVID-19. MAFLD also is associated with worse clinical outcomes of COVID-19, such as disease severity, intensive care unit (ICU) admission rate, and higher mortality rates. However, this evidence has not been well characterized in the literature. This meta-analysis aimed to determine the clinical outcomes of COVID-19 among MAFLD patients compared to the non-MAFLD group. Methods A comprehensive search was conducted in the Cumulative Index of Nursing and Allied Health (CINAHL), PubMed/Medline, and Embase for studies reporting MAFLD prevalence among COVID-19 patients and comparing clinical outcomes such as severity, ICU admission, and mortality among patients with and without MAFLD. The pooled prevalence of MAFLD among COVID-19 patients and the pooled odds ratios (OR) with 95% confidence intervals (CI) for clinical outcomes of COVID-19 were calculated. Results Sixteen observational studies met inclusion criteria involving a total of 11,484 overall study participants, including 1,746 MAFLD patients. The prevalence of COVID-19 among MAFLD patients was 0.29 (95% CI: 0.19-0.40). MAFLD was associated with the COVID-19 disease severity OR 3.07 (95% CI: 2.30-4.09). Similarly, MAFLD was associated with an increased risk of ICU admission compared to the non-MAFLD group OR 1.46 (95% CI: 1.12-1.91). Lastly, the association between MAFLD and COVID-19 mortality was not statistically significant OR 1.45 (95% CI: 0.74-2.84). Conclusions In this study, a high percentage of COVID-19 patients had MAFLD. Moreover, MAFLD patients had an increased risk of COVID-19 disease severity and ICU admission rate.
Collapse
Affiliation(s)
- Umar Hayat
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | | | - Luke Johnson
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Ryan Ford
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Chelsea Wuthnow
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Kevin Kadado
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Katia El Jurdi
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - Hayrettin Okut
- Office of Research, University of Kansas School of Medicine-Wichita, Wichita, KS
| | - William Ransom Kilgore
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
- Ascension Medical Group, Wichita, KS
| | - Maha Assi
- Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS
- Infectious Diseases Consultants, Wichita, KS
| | - Ali A Siddiqui
- Division of Gastroenterology, Centura Healthcare, Denver, CO
| |
Collapse
|
|
35
|
Neuman MG, Seitz HK, Teschke R, Malnick S, Johnson-Davis KL, Cohen LB, German A, Hohmann N, Moreira B, Moussa G, Opris M. Molecular, Viral and Clinical Features of Alcohol- and Non-Alcohol-Induced Liver Injury. Curr Issues Mol Biol 2022; 44:1294-1315. [PMID: 35723310 PMCID: PMC8947098 DOI: 10.3390/cimb44030087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/06/2022] [Accepted: 03/14/2022] [Indexed: 01/08/2023] Open
Abstract
Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented.
Collapse
Affiliation(s)
- Manuela G. Neuman
- In Vitro Drug Safety and Biotechnology and the Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L5, Canada; (G.M.); (M.O.)
- Correspondence:
| | - Helmut K. Seitz
- Centre of Liver and Alcohol Diseases, Ethianum Clinic and Department of Clinical Pharmacology and Pharmacoepidemiology, Faculty of Medicine, University of Heidelberg, 69115 Heidelberg, Germany; (H.K.S.); (N.H.); (B.M.)
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Hanau, Academic Teaching Hospital of the Medical Faculty, Goethe University Frankfurt/Main, 60323 Frankfurt, Germany;
| | - Stephen Malnick
- Department of Internal Medicine C. Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Rehovot 76100, Israel; (S.M.); (A.G.)
| | - Kamisha L. Johnson-Davis
- Department of Pathology, University of Utah Health Sciences Centre and Division of Toxicology, ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84115, USA;
| | - Lawrence B. Cohen
- Division of Gastroenterology, Sunnybrook Health Sciences Centre and Department of Medicine, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M4N 3N5, Canada;
| | - Anit German
- Department of Internal Medicine C. Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Rehovot 76100, Israel; (S.M.); (A.G.)
| | - Nicolas Hohmann
- Centre of Liver and Alcohol Diseases, Ethianum Clinic and Department of Clinical Pharmacology and Pharmacoepidemiology, Faculty of Medicine, University of Heidelberg, 69115 Heidelberg, Germany; (H.K.S.); (N.H.); (B.M.)
| | - Bernhardo Moreira
- Centre of Liver and Alcohol Diseases, Ethianum Clinic and Department of Clinical Pharmacology and Pharmacoepidemiology, Faculty of Medicine, University of Heidelberg, 69115 Heidelberg, Germany; (H.K.S.); (N.H.); (B.M.)
| | - George Moussa
- In Vitro Drug Safety and Biotechnology and the Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L5, Canada; (G.M.); (M.O.)
| | - Mihai Opris
- In Vitro Drug Safety and Biotechnology and the Department of Pharmacology and Toxicology, Temerity Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L5, Canada; (G.M.); (M.O.)
- Family Medicine Clinic CAR, 010362 Bucharest, Romania
| |
Collapse
|
|
36
|
Ozkurt Z, Çınar Tanrıverdi E. COVID-19: Gastrointestinal manifestations, liver injury and recommendations. World J Clin Cases 2022; 10:1140-1163. [PMID: 35211548 PMCID: PMC8855202 DOI: 10.12998/wjcc.v10.i4.1140] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/28/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has caused a pandemic that affected all countries with nearly 270 million patients and 5 million deaths, as of as of December, 2021. The severe acute respiratory syndrome coronavirus 2 virus targets the receptor, angiotensin-converting enzyme 2, which is frequently found in human intestinal epithelial cells, bile duct epithelial cells, and liver cells, and all gastrointestinal system organs are affected by COVID-19 infection. The aim of this study is to review the gastrointestinal manifestations and liver damage of COVID-19 infection and investigate the severe COVID-19 infection risk in patients that have chronic gastrointestinal disease, along with current treatment guidelines. A literature search was conducted on electronic databases of PubMed, Scopus, and Cochran Library, consisting of COVID-19, liver injury, gastrointestinal system findings, and treatment. Liver and intestinal involvements are the most common manifestations. Diarrhea, anorexia, nausea/vomiting, abdominal pain are the most frequent symptoms seen in intestinal involvement. Mild hepatitis occurs with elevated levels of transaminases. Gastrointestinal involvement is associated with long hospital stay, severity of the disease, and intensive care unit necessity. Treatments and follow-up of patients with inflammatory bowel diseases, cirrhosis, hepatocellular carcinoma, or liver transplant have been negatively affected during the pandemic. Patients with cirrhosis, hepatocellular carcinoma, auto-immune diseases, or liver transplantation may have a greater risk for severe COVID-19. Diagnostic or therapeutic procedures should be restricted with specific conditions. Telemedicine should be used in non-urgent periodic patient follow up. COVID-19 treatment should not be delayed in patients at the risk group. COVID-19 vaccination should be prioritized in this group.
Collapse
Affiliation(s)
- Zulal Ozkurt
- Department of Infectious Disease, Atatürk University, School of Medicine, Erzurum 25100, Turkey
| | - Esra Çınar Tanrıverdi
- Department of Medical Education, Atatürk University, School of Medicine, Erzurum 25100, Turkey
| |
Collapse
|
|
37
|
Devi J, Raees A, Butt AS. Redefining non-alcoholic fatty liver disease to metabolic associated fatty liver disease: Is this plausible? World J Hepatol 2022; 14:158-167. [PMID: 35126845 PMCID: PMC8790389 DOI: 10.4254/wjh.v14.i1.158] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 06/17/2021] [Accepted: 12/22/2021] [Indexed: 02/06/2023] Open
Abstract
Recently, a single letter change has taken the world by storm. A group of experts have developed a consensus to upgrade the term non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD), suggesting that MAFLD would more accurately reflect not only the disease pathogenesis but would also help in patient stratification for management with NAFLD. However, the difference of opinion exists, which has made the NAFLD vs MAFLD debate the current talk of the town. This review will focus on the plausibility and implications of redefining NAFLD as MAFLD.
Collapse
Affiliation(s)
- Jalpa Devi
- Department of Gastroenterology, Liaquat University of Medical and Health Sciences, Jamshoro 74800, Pakistan
| | - Aimun Raees
- Department of Gastroenterology, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Amna Subhan Butt
- Department of Gastroenterology, Aga Khan University Hospital, Karachi 74800, Pakistan.
| |
Collapse
|
|
38
|
Liver Injury in Patients with COVID-19 without Underlying Liver Disease. J Clin Med 2022; 11:jcm11020308. [PMID: 35054003 PMCID: PMC8778101 DOI: 10.3390/jcm11020308] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 12/20/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and-where it is particularly challenging-on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. MATERIAL AND METHODS We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. RESULTS Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. CONCLUSIONS (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values.
Collapse
|
|
39
|
Al-Omary A, Byth K, Weltman M, George J, Eslam M. The importance and impact of recognizing metabolic dysfunction-associated fatty liver disease in patients with chronic hepatitis C. J Dig Dis 2022; 23:33-43. [PMID: 34902220 DOI: 10.1111/1751-2980.13071] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 11/20/2021] [Accepted: 12/08/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Metabolic dysfunction-associated fatty liver disease (MAFLD) can develop in any patient, including those with chronic hepatitis C (CHC). The recently proposed diagnostic criteria for MAFLD provide a unique opportunity to investigate the impact of concomitant fatty liver in patients with another established cause for their liver disease. The objective of our study was to assess the characteristics and outcomes of patients with a dual etiology liver disease. METHODS We evaluated 1181 patients including 744 with CHC and 437 with MAFLD. All patients in both cohorts underwent liver biopsy indicating disease activity and fibrosis stage. RESULTS Nearly half (43.1%) the patients with CHC had concomitant MAFLD. Comparing patients with CHC alone with those with a dual etiology disease, we found that the latter had more severe liver injury, hepatic inflammation and fibrosis (all P < 0.001). Interestingly, lean or normal-weight patients with CHC and MAFLD had a similar fibrosis stage compared to the two other subgroups of MAFLD (obesity and/or diabetes mellitus). There was no statistical significance in hepatic steatosis and fibrosis between genotype 3 CHC and MAFLD group compared to other genotypes. CONCLUSIONS Patients with CHC and concomitant MAFLD had more severe liver disease than those with viral hepatitis alone. Recognizing coexisting MAFLD in patients with CHC is important for the delivery of holistic care.
Collapse
Affiliation(s)
- Ahmed Al-Omary
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia.,Nepean Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Karen Byth
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Martin Weltman
- Nepean Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| |
Collapse
|
|
40
|
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.
Collapse
Affiliation(s)
- Sirina Ekpanyapong
- Division of Gastroenterology and HepatologyDepartment of MedicineRajavithi HospitalBangkokThailand
| | | | - K. Rajender Reddy
- Division of Gastroenterology and HepatologyDepartment of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| |
Collapse
|
|
41
|
Madan K, Rastogi R, Bhargava R, Dagar V, Singla V, Sahu A, Singh P, Garg P, Aggarwal B, Singh RK. Is Fatty Liver Associated with Increased Mortality and Morbidity in Coronavirus Disease 2019 (COVID-19) Pneumonia? J Clin Exp Hepatol 2022; 12:1320-1327. [PMID: 35469129 PMCID: PMC9020647 DOI: 10.1016/j.jceh.2022.04.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 04/12/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Fatty liver has been shown to be associated with severe COVID-19 disease without any impact on mortality. This is based on heterogenous criteria for defining both fatty liver as well as the severity parameters. This study aimed to study the impact of fatty liver on the mortality and severity of disease in patients with COVID-19 pneumonia. METHODS In a case control study design, patients with COVID-19 pneumonia (COVID-19 computed tomography severity index [CTSI] on high-resolution computed tomography chest of ≥1) with fatty liver (defined as liver to spleen attenuation index ≤5 on noncontrast computed tomography cuts of upper abdomen) were compared with those without fatty liver. The primary outcome measure was in-hospital mortality, and the secondary outcome measures were CTSI score, need for intensive care unit (ICU) care, need for ventilatory support, duration of ICU stay, and duration of hospital stay. RESULTS Of 446 patients with COVID-19 pneumonia, 289 (64.7%)admitted to Max Hospital, Saket, India, between January 1, 2021, and October 30, 2021, had fatty liver. Fifty-nine of 446 patients died during the index admission. In-hospital mortality was not different between patients with fatty liver (38 [13.24%]) or without fatty liver (21 [13.81%]). COVID-19 CTSI score was found to be significantly higher among patients who had fatty liver (13.40 [5.16] vs 11.81 [5.50]; P = 0.003). There was no difference in the requirement of ICU (94 [32%] vs 62 [39.49%]; P = 0.752), requirement of ventilatory support (27 [9.34%] vs 14 [8.91%]; P = 0.385), duration of ICU stay (8.29 [6.87] vs 7.07 [5.71] days; P = 0.208), and duration of hospital stay (10.10 [7.14] vs 10.69 [8.13] days; P = 0.430) between the groups with fatty liver or no fatty liver. Similarly, no difference was found in primary or secondary outcomes measure between the group with severe fatty liver vs mild/moderate or no fatty liver. High total leucocyte count and Fibrosis-4 (FIB-4) index were independently associated with mortality. CONCLUSIONS Fatty liver may not be associated with increased mortality or clinical morbidity in patients who have COVID-19 pneumonia.
Collapse
Affiliation(s)
- Kaushal Madan
- Max Centre for Gastroenterology, Hepatology & Endoscopy, Max Hospitals, Saket, New Delhi 110017, India
- Address for correspondence: Dr Kaushal Madan, Principal Director and Head, Clinical Hepatology, Centre for Gastroenterology, Hepatology & Endoscopy, Max Institute of Liver and GI Sciences, Max Hospitals, Saket, New Delhi 110017, India.
| | - Ruchi Rastogi
- Department of Radiodiagnosis, Max Hospitals, Saket, New Delhi 110017, India
| | - Richa Bhargava
- Max Centre for Gastroenterology, Hepatology & Endoscopy, Max Hospitals, Saket, New Delhi 110017, India
| | - Vineeta Dagar
- Department of Radiodiagnosis, Max Hospitals, Saket, New Delhi 110017, India
| | - Vikas Singla
- Max Centre for Gastroenterology, Hepatology & Endoscopy, Max Hospitals, Saket, New Delhi 110017, India
| | - Amit Sahu
- Department of Radiodiagnosis, Max Hospitals, Saket, New Delhi 110017, India
| | - Pankaj Singh
- Max Centre for Gastroenterology, Hepatology & Endoscopy, Max Hospitals, Saket, New Delhi 110017, India
| | - Pallavi Garg
- Max Centre for Gastroenterology, Hepatology & Endoscopy, Max Hospitals, Saket, New Delhi 110017, India
| | - Bharat Aggarwal
- Department of Radiodiagnosis, Max Hospitals, Saket, New Delhi 110017, India
| | | |
Collapse
|
|
42
|
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] [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.
Collapse
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
| |
Collapse
|
|
43
|
Tao Z, Li Y, Cheng B, Zhou T, Gao Y. Risk of Severe COVID-19 Increased by Metabolic Dysfunction-associated Fatty Liver Disease: A Meta-analysis. J Clin Gastroenterol 2021; 55:830-835. [PMID: 34406175 PMCID: PMC8500209 DOI: 10.1097/mcg.0000000000001605] [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] [Indexed: 12/15/2022]
Abstract
BACKGROUND The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronavirus disease-2019 (COVID-19) patients and whether it affects the outcomes of COVID-19 requires investigation. GOALS The aim was to determine the prevalence of MAFLD among COVID-19 patients and its influence on the outcomes of COVID-19 by meta-analysis. METHODS Our study protocol has been registered on PROSPERO (CRD42021242243). The studies published on PubMed, Embase, Cochrane Library, and Web of Science before March 11, 2021 were screened. The Newcastle-Ottawa scale (NOS) and Agency for Healthcare Research and Quality scale were used to assess the quality of the studies. Pooled analysis was conducted using the software RevMan version 5.3 and Stata version 15.0 SE. The stability of the results was assessed by sensitivity analysis. Publication bias was evaluated using funnel plots, Egger test, and trim-and-fill analysis. RESULTS Seven studies covering 2141 COVID-19 patients were included. It was confirmed that MAFLD increased the risk of severe COVID-19 (odds ratios: 1.80, 95% confidence interval: 1.53-2.13, P<0.00001). No association was found between the presence of MAFLD and the occurrence of COVID-19 death. The pooled prevalence of MAFLD among COVID-19 patients was 36% (95% confidence interval: 0.23-0.49, P<0.00001). Sensitivity analysis confirmed that the initial results were stable. CONCLUSIONS MAFLD can increase the incidence of severe COVID-19, but the correlation between MAFLD and COVID-19 death has not been confirmed. Further investigation is needed to explore the possible mechanism of this association. Since MAFLD is common among patients infected with SARS-CoV-2, more care should be given to COVID-19 patients with underlying MAFLD.
Collapse
|
|
44
|
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.
Collapse
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
| |
Collapse
|
|
45
|
Idalsoaga F, Ayares G, Arab JP, Díaz LA. COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence. J Clin Transl Hepatol 2021; 9:760-768. [PMID: 34722191 PMCID: PMC8516829 DOI: 10.14218/jcth.2020.00140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/16/2021] [Accepted: 05/13/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules ("cytokine storm"), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.
Collapse
Affiliation(s)
- Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gustavo Ayares
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Centro de Envejecimiento y Regeneración (CARE), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Díaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Correspondence to: Luis Antonio Díaz, Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Marcoleta 367, Santiago 8330024, Chile. ORCID: https://orcid.org/0000-0002-8540-4930. Tel/Fax:+56-2-2354-3820, E-mail:
| |
Collapse
|
|
46
|
Gaspar R, Castelo Branco C, Macedo G. Liver and COVID-19: From care of patients with liver diseases to liver injury. World J Hepatol 2021; 13:1367-1377. [PMID: 34786172 PMCID: PMC8568576 DOI: 10.4254/wjh.v13.i10.1367] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/11/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
The global pandemic of coronavirus disease 2019 (COVID-19) changed dramatically all priorities on medical society and created several challenges for clinicians caring for patients with liver diseases. We performed a comprehensive review about how COVID-19 can affect the liver, the influence of liver diseases on the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 severity and also some strategies to overcome all the challenges clinicians have to face in the management of patients with liver diseases in a period of time when all the focus turned on COVID-19. We analyze the relationship between COVID-19 and non-alcoholic fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune liver disease, cirrhosis, hepatocellular carcinoma and liver transplantation, as well as the approach to SARS-CoV-2 vaccination.
Collapse
Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| | - Catarina Castelo Branco
- Department of Internal Medicine, Centro Hospitalar e Universitário do Porto, Porto 4100, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| |
Collapse
|
|
47
|
Omar AS, Kaddoura R, Orabi B, Hanoura S. Impact of COVID-19 pandemic on liver, liver diseases, and liver transplantation programs in intensive care units. World J Hepatol 2021; 13:1215-1233. [PMID: 34786163 PMCID: PMC8568568 DOI: 10.4254/wjh.v13.i10.1215] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 06/25/2021] [Accepted: 09/06/2021] [Indexed: 02/06/2023] Open
Abstract
Emerging worldwide data have been suggesting that coronavirus disease 2019 (COVID-19) pandemic consequences are not limited to the respiratory and cardiovascular systems but encompass adverse gastrointestinal manifestations including acute liver injury as well. Severe cases of liver injury associated with higher fatality rates were observed in critically ill patients with COVID-19. Intensive care units (ICU) have been the center of disposition of severe cases of COVID-19. This review discusses the pathogenesis of acute liver injury in ICU patients with COVID-19, and analyzes its prevalence, consequences, possible drug-induced liver injury, and the impact of the pandemic on liver diseases and transplantation programs.
Collapse
Affiliation(s)
- Amr Salah Omar
- Department of Cardiothoracic Surgery, Hamad Medical Corporation, Doha 3050, DA, Qatar
- Department of Critical Care Medicine, Beni Suef University, Beni Suef 61355, Egypt
- Department of Medicine, Weill Cornell Medical College, Doha 3050, Qatar
| | - Rasha Kaddoura
- Department of Pharmacy, Heart Hospital, Hamad Medical Corporation, Doha 3050, DA, Qatar
| | - Bassant Orabi
- Department of Pharmacy, Heart Hospital, Hamad Medical Corporation, Doha 3050, DA, Qatar
| | - Samy Hanoura
- Department of Cardiothoracic Surgery, Hamad Medical Corporation, Doha 3050, DA, Qatar
- Department of Anesthesia, Alazhar University, Cairo 6050, Egypt
- Department of Anesthesia, Weill Cornell Medical College, Doha 3050, DA, Qatar
| |
Collapse
|
|
48
|
Ruiz-Margáin A, Román-Calleja BM, Moreno-Guillén P, González-Regueiro JA, Kúsulas-Delint D, Campos-Murguía A, Flores-García NC, Macías-Rodríguez RU. Nutritional therapy for hepatocellular carcinoma. World J Gastrointest Oncol 2021; 13:1440-1452. [PMID: 34721776 PMCID: PMC8529929 DOI: 10.4251/wjgo.v13.i10.1440] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/23/2021] [Accepted: 08/09/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and presents together with cirrhosis in most cases. In addition to commonly recognized risk factors for HCC development, such as hepatitis B virus/hepatitis C virus infection, age and alcohol/tobacco consumption, there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat, type of cooking (generation of heterocyclic amines) and contamination of foods with aflatoxins. On the contrary, protective nutritional factors include diets rich in fiber, fruits and vegetables, n-3 polyunsaturated fatty acids and coffee. While the patient is being evaluated for staging and treatment of HCC, special attention should be paid to nutritional support, including proper nutritional assessment and therapy by a multidisciplinary team. It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis, and therefore they could present with severe malnutrition. Cirrhosis-related complications should be properly addressed and considered for nutritional care. In addition to traditional methods, functional testing, phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment. Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer. Supplementation with branched-chain amino acids is also recommended as it improves response to treatment, nutritional status and survival, and finally physical exercise must be encouraged and adapted to individual needs.
Collapse
Affiliation(s)
- Astrid Ruiz-Margáin
- Liver Nutrition Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
- Liver Fibrosis and Nutrition Lab, MICTLÁN-Network (Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases- Research Network), Mexico City 14080, Mexico
| | - Berenice M Román-Calleja
- Liver Nutrition Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Paulina Moreno-Guillén
- Liver Nutrition Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - José A González-Regueiro
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Deyanira Kúsulas-Delint
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Alejandro Campos-Murguía
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Nayelli C Flores-García
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| | - Ricardo Ulises Macías-Rodríguez
- Liver Fibrosis and Nutrition Lab, MICTLÁN-Network (Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases- Research Network), Mexico City 14080, Mexico
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
| |
Collapse
|
|
49
|
Xu Y, Yang X, Bian H, Xia M. Metabolic dysfunction associated fatty liver disease and coronavirus disease 2019: clinical relationship and current management. Lipids Health Dis 2021; 20:126. [PMID: 34602072 PMCID: PMC8487451 DOI: 10.1186/s12944-021-01564-z] [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] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 09/20/2021] [Indexed: 02/07/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.
Collapse
Affiliation(s)
- Yanlan Xu
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of Geriatrics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, China
| | - Xinyu Yang
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Hua Bian
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Fudan Institute for Metabolic Diseases, Shanghai, 200032, China.
| | - Mingfeng Xia
- Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Fudan Institute for Metabolic Diseases, Shanghai, 200032, China.
| |
Collapse
|
|
50
|
Non-Alcoholic Fatty Liver Disease and COVID-19-Two Pandemics Hitting at the Same Time. ACTA ACUST UNITED AC 2021; 57:medicina57101057. [PMID: 34684094 PMCID: PMC8540462 DOI: 10.3390/medicina57101057] [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] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/29/2021] [Accepted: 10/01/2021] [Indexed: 01/08/2023]
Abstract
The COVID-19 pandemic was and still is a global burden with more than 178,000,000 cases reported so far. Although it mainly affects respiratory organs, COVID-19 has many extrapulmonary manifestations, including, among other things, liver injury. Many hypotheses have been proposed to explain direct and indirect impacts of the SARS-CoV-2 virus on the liver. Studies have shown that around 15–30% of patients with COVID-19 have underlying liver disease, and 20–35% of patients with COVID-19 had altered liver enzymes at admission. One of the hypotheses is reactivation of an underlying liver disease, such as non-alcoholic fatty liver disease (NAFLD). Some studies have shown that NAFLD is associated with severe COVID-19 and poor outcome; nevertheless, other studies showed no significant difference between groups in comparing complications and clinical outcomes. Patients with NAFLD may suffer severe COVID-19 due to other comorbidities, especially cardiovascular diseases. The link between NAFLD and COVID-19 is not clear yet, and further studies and research are needed.
Collapse
|