03967085

May 15, 2021, 13:33

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The paper presented all the new insights regarding the cytokine storm, including therapeutic options.

Thank you very much for your comments.

05018820

April 28, 2021, 09:29

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SARS-CoV-2 infection in people with pre-existing liver disease: Further research is warranted Henu Kumar Verma1* and Bhaskar L.V.K.S. 1. Developmental and Stem Cell Biology Lab, Institute of Experimental Endocrinology and Oncology CNR, Naples, Italy Email: henu.verma@yahoo.com 2. Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur, India. Email: lvksbhaskar@gmail.com Conflicts of Interest: The authors declare no conflict of interest. *Corresponding Author Dr. Henu Kumar Verma Researcher Institute of Experimental Endocrinology and Oncology CNR, Naples, Italy Mobile: +91 9770476810/ +39 3922185508 http://orcid.org/0000-0003-1130-8783 Email: henu.verma@yahoo.com henu.verma@ieos.cnr.it   A Commentary on “Impact of cytokine storm and systemic inflammation on liver impairment patients infected by SARS-CoV-2: Prospective therapeutic challenges.” Dear Editor Recently we have seen a paper entitled “Impact of cytokine storm and systemic inflammation on liver impairment patients infected by SARS-CoV-2: Prospective therapeutic challenges” contributed by Ali et al. in your well-regarded journal “World J Gastroenterol” [1]. Regarding this paper, we would like to draw your attention to several valuable and interesting aspects. The current scenario is that the second wave of the SARS-CoV-2 (COVID-19) pandemic is much more aggressive, with many more cases reported in various countries. As of April 2021, nearly 2.5-million deaths worldwide have been attributed to COVID-19. Based on the geographical distribution of the COVID-19 pandemic, it was found that in areas with a higher frequency, such as China, the rate of SARS-CoV-2 infected patients with liver impairment is also higher [2]. Most COVID-19 hospitalized patients have elevated liver biomarkers, primarily aminotransferase and bilirubin, which cause multi-organ failure [3, 4]. A recent review paper published in World J Gastroenterol by Ali et al. [1] shows great public health interest. In their article authors elegantly described the impact of SARS-CoV-2 on hepatic impairment conditions. Besides, they focused on several current studies that indicated the role of a hyperinflammatory state known as “cytokine storm” concerning the ACE2 receptor as the main factor for the high rate of SARS‐CoV‐2 spreading and mortality and its putative therapies [5]. The SARS-CoV-2 directly enters the host cell through surface receptors and binds to angiotensin-converting enzyme 2 (ACE2) [6]. Accumulating evidence indicated that the hepatic sharing of ACE2 after virus entry into the host cell. The underlying mechanisms of liver injury in COVID-19 patients are currently indistinguishable. RNAseq data from the human liver protein database shown that ACE2 was overexpressed in COVID19 patients. This analysis revealed a 59.7 % increase in ACE2 expression in cholangiocytes as compared to 2.6 % in hepatocytes, indicating that SARS-CoV-2 may directly bind to the ACE2 receptor and the liver may be a good host for SARS-CoV-2 [7, 8]. Histological analysis of liver biopsies of COVID-19 patients revealed moderate microvascular steatosis, mild lobular, portal activity, and T cell overexpression showing the liver injury could have been caused by either SARS-CoV-2 infection or treatment [3, 9]. A hospital-based study in China revealed elevated levels of proinflammatory cytokines, chemokines, and growth factors in COVID-19 patients compared to healthy adults [10, 11]. Further, the patients with severe COVID-19 show hepatic dysfunction or liver disorders, including chronic liver disease (CLD), hepatitis viruses [types B, C, D, and E], hepatotropic virus infection, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis with elevated platelets, neutrophils, and lymphocytes counts, resulting in the worst outcomes from Acute respiratory distress syndrome [12, 13]. There is no consensus among researchers regarding liver damage in COVID-19 patients; some studies proposed immediate cytopathic effect of the virus on hepatocytes or biliary epithelium via ACE receptors [14, 15] and others postulated inflammatory and immune-mediated liver failure in patients with multiple-organ damage [16]. However, hepatic inflammation involving cytokine activation was well-documented. A case study of COVID-19 patients demonstrated that the CRP of 20 mg/L and a lymphocyte count of 1.1 109/L were independent risk factors for liver injury [17]. The liver contains Kupffer cells, which have a high number of macrophages in the body and are cytokine producers. According to one study in Non-Alcoholic Fatty Liver Disease (NAFLD) patients, the macrophagic state's polarisation is altered, which has been linked to increased inflammatory cytokines response to SARS-CoV-2 [16]. Regardless of the precise definition, combinations of clinical manifestation and inflammatory markers (elevated plasma levels of CRP, LDH, IL-6, IL-1, TNF-α, and ferritin) could be used to define the “cytokine storm syndrome” COVID-19 patients [18-20]. Treatment with anti-IL-6 receptor monoclonal antibodies (sarilumab and tocilizumab), anti-IL-6 monoclonal antibodies (siltuximab), interleukin-1 (IL-1) Inhibitors (Anakinra, Rilonacept, and Canakinumab) and tumour necrosis factor-alpha (TNF α) inhibitors (adalimumab, etanercept and infliximab) showed promising results against SARS-CoV-2-induced cytokine storm [21-23]. In addition, corticosteroids that are known to alter the NF-kB pathway which is central to the cytokine storm were used in managing the severe SARS and MERS patients [24]. As cytokine storm is a critical life-threatening condition and has prognostic and therapeutic implications, the clinicians must recognize cytokine storm earlier to avoid intensive care admission and multi-organ damage.   Reference: 1. Ali FEM, M.Z., Ali MM, Ghogar OM., Impact of cytokine storm and systemic inflammation on liver impairment patients infected by SARS-CoV-2: Prospective therapeutic challenges. World J Gastroenterol, 2021. 27(15): p. 1531-1552. 2. Feng, G., et al., COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies. J Clin Transl Hepatol, 2020. 8(1): p. 18-24. 3. Sun, J., et al., COVID-19 and liver disease. Liver Int, 2020. 40(6): p. 1278-1281. 4. Zhang, C., L. Shi, and F.S. Wang, Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol, 2020. 5(5): p. 428-430. 5. Yongzhi, X., COVID-19-associated cytokine storm syndrome and diagnostic principles: an old and new Issue. Emerg Microbes Infect, 2021. 10(1): p. 266-276. 6. Krishnamurthy, S., R.F. Lockey, and N. Kolliputi, Soluble ACE2 as a potential therapy for COVID-19. American Journal of Physiology-Cell Physiology, 2021. 320(3): p. C279-C281. 7. Lindskog, C., The potential clinical impact of the tissue-based map of the human proteome. Expert Rev Proteomics, 2015. 12(3): p. 213-5. 8. Chai, X., et al., Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. bioRxiv, 2020: p. 2020.02.03.931766. 9. Ji, D., et al., Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study. J Hepatol, 2020. 73(2): p. 451-453. 10. Huang, C., et al., Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020. 395(10223): p. 497-506. 11. Li, J., et al., Clinical features of familial clustering in patients infected with 2019 novel coronavirus in Wuhan, China. Virus Res, 2020. 286: p. 198043. 12. Tian, D. and Q. Ye, Hepatic complications of COVID-19 and its treatment. J Med Virol, 2020. 92(10): p. 1818-1824. 13. Kudaravalli, P., et al., Case series and review of liver dysfunction in COVID-19 patients. Eur J Gastroenterol Hepatol, 2020. 32(9): p. 1244-1250. 14. Roedl, K., et al., Severe liver dysfunction complicating course of COVID-19 in the critically ill: multifactorial cause or direct viral effect? Ann Intensive Care, 2021. 11(1): p. 44. 15. Huang, C., et al., Molecular and cellular mechanisms of liver dysfunction in COVID-19. Discov Med, 2020. 30(160): p. 107-112. 16. Xu, Z., et al., Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 2020. 8(4): p. 420-422. 17. Li, L., et al., Risk factors related to hepatic injury in patients with corona virus disease 2019. medRxiv, 2020: p. 2020.02.28.20028514. 18. Chen, G., et al., Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest, 2020. 130(5): p. 2620-2629. 19. Qin, C., et al., Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis, 2020. 71(15): p. 762-768. 20. Verma, H.K., Radiological and clinical spectrum of COVID-19: A major concern for public health. World J Radiol, 2021. 13(3): p. 53-63. 21. Atal, S. and Z. Fatima, IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? Pharmaceutical medicine, 2020. 34(4): p. 223-231. 22. Sarzi-Puttini, P., et al., COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Clin Exp Rheumatol, 2020. 38(2): p. 337-342. 23. Rizk, J.G., et al., Pharmaco-Immunomodulatory Therapy in COVID-19. Drugs, 2020. 80(13): p. 1267-1292. 24. Tang, Y., et al., Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. Front Immunol, 2020. 11: p. 1708.

Firstly, thank you very much for your professional comments on the article published in World Journal of Gastroenterology. Secondly, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor, and submit it online to World Journal of Gastroenterology at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for Letter to the Editor. The article processing charge will be exempted for Letter to the Editor. The Letter to the Editor will be published online after peer review. The guidelines for Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor to promote academic communication and lead the development of this discipline.

05769618

April 17, 2021, 06:48

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Readers comment I have some corrections to improve the article value that I describe in "the following queries (Q)". Six coronaviruses reported as human-affected viruses include α- coronaviruses NL63 and 229E, low-pathogenic β-coronaviruses OC43 and HKU1, these viruses cause mild respiratory symptoms as common cold [2]. The remaining two types were identified as β-coronavirus, which unusually induced fatal respiratory tract infections [3]. Q1. In those aforementioned sentences, author mentioned six types of coronavirus, but author just describe four types “α-coronaviruses NL63 and 229E, low-pathogenic β-coronaviruses OC43 and HKU1”. Even though author mentioned the remaining two types were identified as β-coronavirus however author did not mention these two types, my suggestion is better to put remaining two types were identified as β-coronavirus Q2. First paragraph in sentence “Between 2002 and 2003, severe acute respiratory syndrome (SARS) resulted in the outbreak of SARS0[4]….Please correct typos of SARS0 Q3. Paragraph 3 “On the same day, the international committee of taxonomy named this virus as SARS-CoV-2 and classified it as coronavirus under the family Coronaviridae, subfamily Orthocoronavirinae, based on the genotypic and serological characterization”. Please correct the sentence and give the abbreviation of international committee on taxonomy of virus (ICTV)” Q4: Why author just focused on the Cytokine and ACE-2, currently there are so many gene that was reported such as TMPRSS2. It will be better if author include explanation of TMPRSS2 as well. Hoffmann, H. Kleine-Weber, S. Schroeder, N. Kruger, T. Herrler, S. Erichsen,T.S. Schiergens, G. Herrler, N.H. Wu, A. Nitsche, M.A. Muller, C. Drosten,S. Pohlmann, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and isblocked by a clinically proven protease inhibitor, Cell 181 (2) (2020) 271e280,https://doi.org/10.1016/j.cell.2020.02.052 Irham LM, Chou WH, Calkins MJ, Adikusuma W, Hsieh SL, Chang WC. Genetic variants that influence SARS‐CoV‐2 receptor TMPRSS2 expression among population cohorts from multiple continents. Biochem Res Commun. 2020;529(2):263‐269. Q5. Author mentioned “ SARS-CoV-2 may induce liver injury via a similar mechanism”. Which is the similar mechanis?. As reader I could not identified which mechanism Q6: Please cite the reference in the sentence” Patients with digestive issues and co-infected with SARS-CoV-2 show a higher risk of mortality than patients without digestive problems.” Q7: In part of Hepatitis B and COVID19. Author mentioned that “For patients with chronic hepatitis B and are in the immune tolerance phase, further tests are required to confirm whether these patients have active viral replication and repeated liver damage after co-infection with SARS-CoV-2” It is important point to elaborate more detail the Hepatitis B and COVID-19 in immune tolerance phase. It is better to mention the characterize of Immune intolerant phase. In this phase (immune tolerance phase) characterize by high level of HBV biomarkers such as HBsAg and HBeAg, but low level of ALT. it is mostly indicated the low inflammatory in this phase. Q8: In conclusion in the sentence “In this review, we concluded that the most destructive power of the virus is the generation of violent cytokine storm, which is probably the cause of high mortality rates in hepatic and nonhaptic patients”. I think it is better to not use the most destructive power of the virus is the generation of violent cytokine storm. Because current study does not perform analysis that reflect the most destructive power of the virus is the generation of violent cytokine storm,

Firstly, thank you very much for your professional comments on the article published in World Journal of Gastroenterology. Secondly, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor, and submit it online to World Journal of Gastroenterology at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for Letter to the Editor. The article processing charge will be exempted for Letter to the Editor. The Letter to the Editor will be published online after peer review. The guidelines for Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor to promote academic communication and lead the development of this discipline.

05231277

April 16, 2021, 11:59

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Should people with chronic liver disease be vaccinated against COVID-19? Coronavirus disease 2019 (COVID-19) has become a global epidemic. It is not just a threat to public health, but also a major blow to economic development and regional stability. SARS-CoV-2 enters host cells by attaching to angiotensin-converting enzyme 2 (ACE2). ACE2 is not simply located in the respiratory tract, but also in the kidney, heart, skeletal muscle, central nervous system, liver, and gastrointestinal tract. Therefore, patients with severe COVID-19 show multiple organ dysfunction. Distribution of ACE2 in liver was unique. Chai, et al found that ACE2 was more highly expressed in cholangiocytes (59.7%) than hepatocytes (2.6%). The level of ACE2 expression in cholangiocytes was comparable to that in type 2 alveolar cells of the lungs, indicating that the liver impairment in COVID‐19 may be originated from damage to the cholangiocytes in the beginning, not directly infection of hepatocytes. Of course, hepatocyte damage in severe cases can also be indirectly induced by the systemic inflammatory response and abnormal metabolism. According to previous meta-analysis, Abnormal alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin were reported in 15.0%, 15.0%, and 16.7% of all patients. However, the severity of liver impairment, clinical outcomes and mortality rate for patients under different chronic liver disease conditions co-infected with SARS-CoV-2 is less noticed. The present review summarizes the impact of SARS-CoV-2 on different chronic liver disease conditions, exhibited overexpression of ACE2 and cytokine storm overwhelming. These might worsen the liver impairment and increase the mortality rate. SARS-CoV-2 vaccines are regarded as the most effective weapon to end the epidemic. Countries around the world are working intensively to develop and produce vaccines. The consensus was reached that we should get as many people vaccinated as possible in order to achieve herd immunity. People with stable chronic liver disease conditions are capable of being included in clinical trials of mRNA BNT162b2, mRNA-1273 vaccine and CoronaVac, BBIBP-CorV Inactivated vaccine. It has proven to be safe and well tolerated. Consider the poor outcomes and high mortality rate of chronic liver disease co-infected with SARS-CoV-2 as stated in this article, the AASLD Expert Panel propose suggestions that COVID-19 vaccines should be given to all adult patients with chronic liver disease and liver transplant recipients. Moreover, patients with chronic liver disease who are receiving antiviral therapy for HBV or HCV should NOT withhold their medications while receiving the COVID-19 vaccines. Patients with hepatocellular carcinoma undergoing locoregional or systemic therapy should also be considered for vaccination without interruption of their treatment. mRNA COVID-19 vaccines are expected to have a favorable efficacy and safety profile in immunosuppressed patients and should be administered according to their standard dose and schedule. Liver transplant candidates with chronic liver disease should receive the mRNA COVID-19 vaccine prior to transplantation.

Firstly, thank you very much for your professional comments on the article published in World Journal of Gastroenterology. Secondly, we read your comments with great interest. You are welcome to format your valuable comments into a Letter to the Editor, and submit it online to World Journal of Gastroenterology at https://www.f6publishing.com. There are no restrictions on the number of words, figures (color, B/W) or authors for Letter to the Editor. The article processing charge will be exempted for Letter to the Editor. The Letter to the Editor will be published online after peer review. The guidelines for Letter to the Editor can be found at: https://www.wjgnet.com/bpg/GerInfo/219. Finally, we look forward to receiving your high-quality Letter to the Editor to promote academic communication and lead the development of this discipline.