2022 Feb 7;28(5):570-587. doi: 10.3748/wjg.v28.i5.570. J. Int. Article The laboratory data suggested that a combination of hemolysis and viral-induced cholestasis was responsible for the intense hyperbilirubinemia in at least five patients. There are several limitations and confounding factors that my present as potential bias and therefore results should be interpreted with caution. See this image and copyright information in PMC. High Bilirubin Levels: Symptoms, Causes, Tests, and Treatments Gastroenterol. Biomed. Cite this article. A detailed study selection process based on PRISMA flow chart is presented in Fig. Hence, there is a growing need to compare the laboratory liver function tests conducted in the primary studies with a comparator or a control group. United Eur. on the prevalence of abnormal liver enzyme levels in confirmed COVID-19 patients, reported the pooled prevalence of elevated ALT, AST, and TB among patients with COVID-19 as 18%, 21% and 6% respectively26. This site needs JavaScript to work properly. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. The current analysis included all types of study designs, patients of any age or gender with a confirmed diagnosis of the COVID-19 disease. Med. Pattern of liver injury in adult patients with COVID-19: A retrospective analysis of 105 patients. COVID-19 and the liver: little cause for concern Shi, H. et al. Provided by the Springer Nature SharedIt content-sharing initiative. Chronic liver conditions such as cirrhosis or viral hepatitis, which produce inflammation and liver scarring, commonly cause increased bilirubin. 2023 Healthline Media LLC. & Yang, Z. Krishnan A, Prichett L, Tao X, Alqahtani SA, Hamilton JP, Mezey E, Strauss AT, Kim A, Potter JJ, Chen PH, Woreta TA. Article Further controlled studies and larger sample size observational studies are needed with adequate reporting of other liver function parameters are warranted. Available online at: Hariri LP, North CM, Shih AR, Israel RA, Maley JH, Villalba JA, et al. Systematic review with meta-analysis: Liver manifestations and outcomes in COVID-19. Shang, J. et al.Cell entry mechanisms of SARS-CoV-2. Poverty 9, 45. https://doi.org/10.1186/s40249-020-00662-x (2020). Cytomegalovirus infection in liver transplant recipients: Current approach to diagnosis and management. Pharmacol. We have presented an in depth analysis of pooled mean data for liver chemistries and each of the liver function test markers in patients diagnosed with SARS-CoV-2 infection upon hospital admission. Liver Int. Lobar pneumonia is a common disease usually caused by any one of a variety of bacteria (e.g., S. pneumonia, Haemophilus influenza, S. aureus, or P. aeruginosa). Res. More common causes of elevated liver enzymes include: PMC Transl. The data on the proportion of patients who had the abnormal (higher or lower) liver function tests were expressed as a percentage in narrative synthesis. Although different things can cause hepatitis, the most common cause is a virus, such as CMV. A total of 17 studies reported on the changes in levels of TB of the included patients. Hepatol. WebWhat Could Cause High Bilirubin? The pooled mean of aPTT was found to be 28.97s [26.91, 31.04] with a significant level of heterogeneity (I2=100%, P<0.00001). Cause High Bilirubin Indian J. Pediatr. Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G. & Group, P. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Immunol. 18, 15611566. WebTotal and direct bilirubin levels during the course of Epstein-Barr virus infection. Huang, Y. et al. Hepatitis: This happens when your liver becomes inflamed, often due to a viral infection. volume11, Articlenumber:10599 (2021) 5.8% (4/69) of patients in the elevated serum total bilirubin (STB) group died, compared to 0.6% (11/1,719) of patients in the non-elevated STB group. The degree of agreement between review authors was 94% (33 studies agreed/35 studies) for inclusion of eligible studies and 92% for data extraction. Additionally, we found elevated levels of GGT, PtT, and ALP in several studies. Med. Lancet Respir. Coronavirus disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update. and Huang et al. Kulkarni, A. V. et al. By Mayo Clinic Staff Many diseases and conditions can contribute to elevated liver enzymes. By continuing you agree to the Infect. and transmitted securely. Therefore, we conducted a comprehensive systematic review with meta-analysis on the pooled mean of LFTs to provide an overview of the available evidence on the impact of SARS-CoV-2 infection on the liver function abnormalities. Here are answers to frequently asked questions about hepatitis C, Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. Keywords: Although we did not find any increase in the coagulation time, nevertheless the physicians need to be vigilant and closely monitor the coagulation profile of the patients with COVID-19. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series. Unauthorized use of these marks is strictly prohibited. High Bilirubin Levels (Hyperbilirubinemia): Symptoms, https://doi.org/10.1093/cid/ciaa199 (2020). (2002). Only Zhang et al. WebOpen Metrics Abstract Introduction: Acute liver failure (ALF) is a life-threatening condition that remains challenging for physicians despite several advances in supportive care. We have shown in this systematic review with meta-analysis that most of the liver enzymes and coagulation parameters in patients diagnosed with SARS-CoV-2 infection are not significantly impacted by COVID-19. Thus, as a result of reported inconsistency in findings for profile of liver chemistries in patients affected by COVID-19, a number of systematic reviews and meta-analyses have recently been published with a focus on the prevalence of abnormalities in liver biochemistry profile among patients affected by COVID-19 based on clinical severity and mortality of the disease26,29,35,36,37,38. National Library of Medicine Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China. Last medically reviewed on June 14, 2022. Another recent systematic review of available evidence on liver function tests found that although most of studies report significantly higher prevalence of liver test abnormalities in more severe hospitalized or non-surviving COVID-19 patients than milder cases, and given that other studies do not report significant changes in liver function tests of COVID-19 patients irrespective of severity, therefore in COVID-19 patients liver function abnormalities may not be a major characteristic35. Zhu, W. et al. Careers. Methods: A retrospective cohort study was conducted in patients hospitalized with COVID-19 in Leishenshan Hospital in Wuhan, China. (2.68%, n=4) (Fig. 2022 Nov 18;25(11):105444. doi: 10.1016/j.isci.2022.105444. 8, 420422. In most cases, higher bilirubin levels will lead to jaundice between 1 and 3 days after birth. Bilirubin levels can peak as high as 18 mg/dL on the fourth or fifth day, and jaundice typically clears up within 2 weeks as the liver matures. Epub 2022 Oct 25. When its inflamed, your liver cant easily process bilirubin, leading to a A sensitivity analysis was performed by removing the studies with higher outliers to validate the robustness of the analyzed meta-data. Internet Explorer). 28, 234239. Some patients with severe or critical COVID-19 have been (2020). Box 3354, Riyadh, 11211, Saudi Arabia, Internal Medicine Department, Salmaniya Medical Complex, Manama, Bahrain, School of Science, RMIT University, Melbourne, VIC, 3000, Australia, Organ Transplant Center & Department of Surgery, King Faisal Specialist Hospital & Research Centre (Gen. Org) MBC 96, AlFaisal University, P.O. PubMed Of note, none of the studies evaluated the proportion and mean changes in total protein. sharing sensitive information, make sure youre on a federal Mil. Infect. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis. & Lian, N. Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study. Meszaros, M. et al. J. Pathol. Xu, Z. et al. Google Scholar. Yang, X. et al. Scientific Reports 40, 9981004 (2020). -, Zheng J. SARS-CoV-2: an emerging coronavirus that causes a global threat. An elevation of PtT was reported by Zhang et al. Table 2 summarizes the main characteristics of eligible studies. Garrido, I., Liberal, R. & Macedo, G. COVID-19 and liver diseaseWhat we know on 1st May 2020. Int J Biol Sci. Egger, M., Smith, G. D., Schneider, M. & Minder, C. Bias in meta-analysis detected by a simple, graphical test. Statistical heterogeneity of data was assessed using the I2 statistics with the random effect model applied when substantial heterogeneity was present (I2>50% or P0.10)42. Infect. Abnormal liver function or symptoms consistent with CMV hepatitis can prompt healthcare professionals to obtain further tests, including: The above tests are used to help differentiate between an active disease, a latent disease, and a past exposure. Lei, F. et al. Aging (Albany NY) 12, 1389513904. Hao, S. R. et al. Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany. J. Gen. Intern. Key search terms related to COVID-19 and liver were used (see full list in Table 1). It can lead to liver problems (called CMV hepatitis) for those with weakened immune systems. Copyright 2020 Liu, Li, Long, Zeng, Gao, Zeng, Chen, Wang, Li, Hu, Guo, Li and Wu. While mild to moderate hepatic dysfunction is commonly encountered in infectious mononucleosis induced by Epstein-Barr virus (EBV), clinical jaundice with high bilirubin levels (greater than or equal to 6.0 mg/dL [greater than or equal to 103 mumol/L] is only occasionally encountered. Rev. Intensiva 42, 444453. Box 3354, Riyadh, 11211, Saudi Arabia, You can also search for this author in Wang, Z., Yang, B., Li, Q., Wen, L. & Zhang, R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. We reported a case of hyperbilirubinemia with a mild COVID-19 patient which rapidly increased total serum bilirubin (TSB). Qi, X. et al. We assessed abnormalities in liver chemistry profiles of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), total bilirubin, albumin, globulin and total protein. Analysis of baseline liver biochemical parameters in 324 cases with novel coronavirus pneumonia in Shanghai area. Bethesda, MD 20894, Web Policies Accessibility at Yale. Lancet Gastroenterol. It is produced when red blood cells are destroyed. Longitudinal association between markers of liver injury and mortality in COVID-19 in China. By submitting a comment you agree to abide by our Terms and Community Guidelines. Medline, Embase databases and Google Scholar as well as relevant reviews were searched to identify appropriate studies from inception to 31st of August 2020. Clinical features and treatment of COVID-19 patients in northeast Chongqing. Hepatol. Journals & The proportion of patients with an elevation of AST ranged from 3.75% (n=3)49 to 36% (n=9)47. Unfortunately, no health care systems were prepared to combat this pandemic effectively resulting in major distress among all governments, health care professionals, researchers and communities worldwide5. Virol. Available evidence suggest that SARS-CoV-2 primarily invades the upper respiratory system and progressively infects the lower respiratory tract6. https://doi.org/10.1016/j.ijid.2020.03.004, https://doi.org/10.1016/j.molmed.2020.02.008, https://doi.org/10.1186/s40249-020-00646-x, https://doi.org/10.26355/eurrev_202002_20378, https://doi.org/10.1016/j.jinf.2020.02.018, https://doi.org/10.1007/s12098-020-03263-6, https://doi.org/10.1136/gutjnl-2020-320926, https://doi.org/10.1007/s11606-020-05762-w, https://doi.org/10.1016/j.jhep.2020.04.010, https://doi.org/10.1016/s2468-1253(20)30057-1, https://doi.org/10.1186/s40249-020-00662-x, https://doi.org/10.1101/2020.02.03.931766, https://doi.org/10.1016/j.biopha.2020.110195, https://doi.org/10.2353/ajpath.2006.051296, https://doi.org/10.1016/S2468-1253(20)30126-6, https://doi.org/10.1016/s2213-2600(20)30079-5, https://doi.org/10.1136/flgastro-2020-101689, https://doi.org/10.1016/j.clinre.2020.04.012, https://doi.org/10.1016/j.medin.2017.10.003, https://doi.org/10.1016/j.cgh.2020.04.002, https://doi.org/10.1016/j.jhep.2020.04.006, https://doi.org/10.1016/j.ijid.2020.03.053, https://doi.org/10.1016/j.jinf.2020.03.019, https://doi.org/10.1016/s1473-3099(20)30086-4, https://doi.org/10.1016/s0140-6736(20)30183-5, https://doi.org/10.1016/s2213-2600(20)30076-x, https://doi.org/10.1016/j.jinf.2020.02.016, https://doi.org/10.3760/cma.j.cn501113-20200229-00076, https://doi.org/10.3760/cma.j.cn501113-20200226-00070, https://doi.org/10.1016/j.tmaid.2020.101606, https://doi.org/10.14309/ajg.0000000000000717, https://doi.org/10.1186/s40779-020-00256-6, https://doi.org/10.1007/s00204-020-02734-1, http://creativecommons.org/licenses/by/4.0/, Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans. BioRxiv (2020). https://doi.org/10.1016/s2213-2600(20)30076-x (2020). 3B). Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Int. Bilirubin might build up in your blood if: Your body breaks down too many red blood cells too fast. [Clinical picture of infectious mononucleosis in childhood]. During December 2019, an outbreak of a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in the Wuhan City, China1. A first step in understanding SARS pathogenesis. Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: A scoping review. Causes Bookshelf https://doi.org/10.26355/eurrev_202002_20378 (2020). Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). [Analysis of viral capsid anti-antigen antibodies of the Epstein Barr virus in infectious mononucleosis. N. Engl. official website and that any information you provide is encrypted Gastroenterol. The presence of SARS-COV-2 was confirmed using the molecular based technique of Reverse Transcriptase polymerase chain reaction (RT-PCR), while the diagnosis was based on the Chinese Center for Disease Prevention and Control (CDC) guidelines or WHO interim guidance. Acute cytomegalovirus hepatitis in an immunocompetent host as a reason for upper right abdominal pain. Correlates of illness severity in infectious mononucleosis. (3.75%, n=3) and Yang et al. KaplanMeier curves for survival in patients with COVID-19 according to elevated serum total bilirubin (STB) levels. We reported a case of hyperbilirubinemia with a mild COVID-19 patient which rapidly increased total serum bilirubin (TSB). 52, 584599 (2020). Causes Diagnosis Treatment Summary High bilirubin levels, or hyperbilirubinemia , means you have an excessive accumulation of bilirubin. Bilirubin is a brownish-yellow substance that forms as red blood cells break down at the end of their normal life cycle. 2C). CMV hepatitis is diagnosed when bilirubin is elevated, and/or elevated liver enzymes are present, along with finding CMV and no other causes for hepatitis. J. Hepatol. After 2 days increased total serum bilirubin. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: A retrospective, multi-centre case series. 10.1002/hep.31301 Disease. Li, M. Y., Li, L., Zhang, Y. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. Liver Int. https://doi.org/10.18632/aging.103720 (2020). Article The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. and J.A. The Progression of Hepatitis C: What Are the Stages? (2020). Aweimer A, Petschulat L, Jettkant B, Kditz R, Finkeldei J, Dietrich JW, Breuer T, Draese C, Frey UH, Rahmel T, Adamzik M, Buchwald D, Useini D, Brechmann T, Hosbach I, Bnger J, Ewers A, El-Battrawy I, Mgge A. Sci Rep. 2023 Mar 29;13(1):5143. doi: 10.1038/s41598-023-31944-7. Emerging evidence suggest association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the development of many liver abnormalities. Sun, J. et al. Any damage or inflammation can impact its functioning. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Arentz, M. et al. WebLiver involvement, such as mild liver damage that can cause temporary jaundice, a yellow discoloration of the skin and whites of the eyes due to abnormally high levels of bilirubin According to the Centers for Disease Control and Prevention (CDC), in the United States, approximately 1 in 3 children are infected by the time theyre 5 years old. Contact and Causes Diagnosis Treatment Summary High bilirubin levels, or hyperbilirubinemia , means you have an excessive accumulation of bilirubin. Liu Z, Hu D, Li J, Xia Q, Gong Y, Li Z, Wu Q, Yi M, Huang Y, Wu M, Guo L, Wu X. Subgroup analysis was planned where sufficient data from eligible studies was available. https://doi.org/10.1016/j.molmed.2020.02.008 (2020). Adams, D. H. & Hubscher, S. G. Systemic viral infections and collateral damage in the liver. Gut. Chronic liver conditions such as cirrhosis or viral hepatitis, which produce inflammation and liver scarring, commonly cause increased bilirubin. Expert Rev. In people with healthy immune systems, CMV hepatitis is rare and typically treatable. Elevated liver enzymes Causes Shopping cart Lung histopathology in COVID-19 as compared to SARS and H1N1 influenza: a systematic review. Although Wang et al. Get the most important science stories of the day, free in your inbox. For CMV hepatitis, the main focus is prevention. J. Med. https://doi.org/10.1007/s12098-020-03263-6 (2020). Effect of COVID-19 on liver abnormalities: a systematic Disclaimer. Bookshelf 383(21), 20302040 https://doi.org/10.1056/NEJMoa2022926. 26, 483495. Several potential mechanisms have been proposed. Poverty 9, 29. https://doi.org/10.1186/s40249-020-00646-x (2020). Epub 2022 Jan 31. Another limitation is the lack of sufficient data on the proportion of patients with changes in liver function parameters at discharge.

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