COVID-19-associated hepatic injury: Difference between revisions

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==Overview==
==Overview==
According to 12 clinical studies, 14.8%-53% of [[COVID-19]] patients have [[Hepatic failure|liver impairment]], suggesting COVID-19-associated hepatic injury, a common complication observed among [[COVID-19]] patients. With the number of cases increasing, [[Liver function tests|abnormal liver function test]] results have been observed in some patients with [[COVID-19]], making this organ the most frequently damaged outside of the [[respiratory system]].
According to 12 clinical studies, 14.8%-53% of [[COVID-19]] patients have [[Hepatic failure|liver impairment]], suggesting COVID-19-associated hepatic injury, a common [[Complications|complication]] observed among [[COVID-19]] patients. With the number of cases increasing, [[Liver function tests|abnormal liver function test]] results have been observed in some patients with [[COVID-19]], making this organ the most frequently damaged outside of the [[respiratory system]].


==Historical Perspective==
==Historical Perspective==
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The exact mechanism of [[Hepatic impairment|liver injury]] is still unclear. There are several proposed mechanisms in an effort to understand the pathogenesis of [[Hepatic failure|hepatic injury]] but the hepatic complications in [[COVID-19]] patients are described as multifactorial and heterogenous. A few of the proposed mechanisms include:
The exact mechanism of [[Hepatic impairment|liver injury]] is still unclear. There are several proposed mechanisms in an effort to understand the pathogenesis of [[Hepatic failure|hepatic injury]] but the hepatic complications in [[COVID-19]] patients are described as multifactorial and heterogenous. A few of the proposed mechanisms include:
===Hepatic Injury through ACE2 receptors===
===Hepatic Injury through ACE2 receptors===
:* S protein facilitates [[SARS-CoV-2]] to enter host cells through binding to [[ACER2|ACE2 receptors]]. [[ACER2|ACE2]] is the primary receptors that enable the entry of [[SARS-CoV]] into different target tissues, including [[Hepatocyte|hepatic cells]].<ref name="pmid32009228">{{cite journal| author=Xu X, Chen P, Wang J, Feng J, Zhou H, Li X | display-authors=etal| title=Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. | journal=Sci China Life Sci | year= 2020 | volume= 63 | issue= 3 | pages= 457-460 | pmid=32009228 | doi=10.1007/s11427-020-1637-5 | pmc=7089049 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32009228  }} </ref><ref name="pmid32094589">{{cite journal| author=Letko M, Marzi A, Munster V| title=Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. | journal=Nat Microbiol | year= 2020 | volume= 5 | issue= 4 | pages= 562-569 | pmid=32094589 | doi=10.1038/s41564-020-0688-y | pmc=7095430 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32094589  }} </ref>
:* S protein facilitates [[SARS-CoV-2]] to enter host cells through binding to [[ACER2|ACE2 receptors]]. [[ACER2|ACE2]] is the primary receptors that enable the entry of [[SARS-CoV]] into different target tissues, including [[Hepatocyte|hepatic cells]].<ref name="pmid32009228">{{cite journal| author=Xu X, Chen P, Wang J, Feng J, Zhou H, Li X | display-authors=etal| title=Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. | journal=Sci China Life Sci | year= 2020 | volume= 63 | issue= 3 | pages= 457-460 | pmid=32009228 | doi=10.1007/s11427-020-1637-5 | pmc=7089049 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32009228  }} </ref><ref name="pmid32094589">{{cite journal| author=Letko M, Marzi A, Munster V| title=Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. | journal=Nat Microbiol | year= 2020 | volume= 5 | issue= 4 | pages= 562-569 | pmid=32094589 | doi=10.1038/s41564-020-0688-y | pmc=7095430 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32094589  }} </ref>
:* According to a biopsy performed in a  [[COVID-19]] patient after death, moderate [[Steatosis|microvascular steatosis]], and mild portal and lobular activity in liver tissue were observed.<ref name="pmid32085846">{{cite journal| author=Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C | display-authors=etal| title=Pathological findings of COVID-19 associated with acute respiratory distress syndrome. | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= 420-422 | pmid=32085846 | doi=10.1016/S2213-2600(20)30076-X | pmc=7164771 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32085846  }} </ref>
:* According to a biopsy performed in a  [[COVID-19]] patient after death, moderate [[Steatosis|microvascular steatosis]], and mild portal and lobular activity in liver tissue were observed.<ref name="pmid32085846">{{cite journal| author=Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C | display-authors=etal| title=Pathological findings of COVID-19 associated with acute respiratory distress syndrome. | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= 420-422 | pmid=32085846 | doi=10.1016/S2213-2600(20)30076-X | pmc=7164771 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32085846  }} </ref>
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===Antibody-mediated Hepatic Injury===
===Antibody-mediated Hepatic Injury===
:*Antibody-mediated liver injury may occur in patients with [[Severe acute respiratory syndrome|SARS]].<ref name="TiradoYoon2003">{{cite journal|last1=Tirado|first1=Sol M. Cancel|last2=Yoon|first2=Kyoung-Jin|title=Antibody-Dependent Enhancement of Virus Infection and Disease|journal=Viral Immunology|volume=16|issue=1|year=2003|pages=69–86|issn=0882-8245|doi=10.1089/088282403763635465}}</ref> It involves the binding of a virus-specific antibody to [[Fc receptor|Fc receptors]] (FcR) and [[complement receptor]] (CR) that enables the virus to enter immune cells such as [[Granulocyte|granulocytes]], [[Monocyte|monocytes]], and [[Macrophage|macrophages]]. The virus can damage the liver by constant replication in these [[White blood cells|immune cells]].<ref name="WangTseng2014">{{cite journal|last1=Wang|first1=Sheng-Fan|last2=Tseng|first2=Sung-Pin|last3=Yen|first3=Chia-Hung|last4=Yang|first4=Jyh-Yuan|last5=Tsao|first5=Ching-Han|last6=Shen|first6=Chun-Wei|last7=Chen|first7=Kuan-Hsuan|last8=Liu|first8=Fu-Tong|last9=Liu|first9=Wu-Tse|last10=Chen|first10=Yi-Ming Arthur|last11=Huang|first11=Jason C.|title=Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins|journal=Biochemical and Biophysical Research Communications|volume=451|issue=2|year=2014|pages=208–214|issn=0006291X|doi=10.1016/j.bbrc.2014.07.090}}</ref> Further investigation is required to understand whether [[SARS-CoV-2]] causes liver injury through this pathway.
:*Antibody-mediated liver injury may occur in patients with [[Severe acute respiratory syndrome|SARS]].<ref name="TiradoYoon2003">{{cite journal|last1=Tirado|first1=Sol M. Cancel|last2=Yoon|first2=Kyoung-Jin|title=Antibody-Dependent Enhancement of Virus Infection and Disease|journal=Viral Immunology|volume=16|issue=1|year=2003|pages=69–86|issn=0882-8245|doi=10.1089/088282403763635465}}</ref> It involves the binding of a virus-specific antibody to [[Fc receptor|Fc receptors]] (FcR) and [[complement receptor]] (CR) that enables the virus to enter immune cells such as [[Granulocyte|granulocytes]], [[Monocyte|monocytes]], and [[Macrophage|macrophages]]. The virus can damage the liver by constant replication in these [[White blood cells|immune cells]].<ref name="WangTseng2014">{{cite journal|last1=Wang|first1=Sheng-Fan|last2=Tseng|first2=Sung-Pin|last3=Yen|first3=Chia-Hung|last4=Yang|first4=Jyh-Yuan|last5=Tsao|first5=Ching-Han|last6=Shen|first6=Chun-Wei|last7=Chen|first7=Kuan-Hsuan|last8=Liu|first8=Fu-Tong|last9=Liu|first9=Wu-Tse|last10=Chen|first10=Yi-Ming Arthur|last11=Huang|first11=Jason C.|title=Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins|journal=Biochemical and Biophysical Research Communications|volume=451|issue=2|year=2014|pages=208–214|issn=0006291X|doi=10.1016/j.bbrc.2014.07.090}}</ref> Further investigation is required to understand whether [[SARS-CoV-2]] causes liver injury through this pathway.


===Cytokine-mediated Hepatic Injury===
===Cytokine-mediated Hepatic Injury===
:*Historical data on [[SARS-CoV]] and [[Middle East respiratory syndrome coronavirus infection causes|MERS-CoV]] suggest that cytokine storm including [[interleukin]] (IL), [[Tumour necrosis factor|tumor necrosis factor]] (TNF), and [[endotoxin]] and [[systemic inflammatory response syndrome]] played a major role in liver impairment among infected patients.<ref name="WongLam2004">{{cite journal|last1=Wong|first1=C. K.|last2=Lam|first2=C. W. K.|last3=Wu|first3=A. K. L.|last4=Ip|first4=W. K.|last5=Lee|first5=N. L. S.|last6=Chan|first6=I. H. S.|last7=Lit|first7=L. C. W.|last8=Hui|first8=D. S. C.|last9=Chan|first9=M. H. M.|last10=Chung|first10=S. S. C.|last11=Sung|first11=J. J. Y.|title=Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome|journal=Clinical & Experimental Immunology|volume=136|issue=1|year=2004|pages=95–103|issn=00099104|doi=10.1111/j.1365-2249.2004.02415.x}}</ref><ref name="ChannappanavarPerlman2017">{{cite journal|last1=Channappanavar|first1=Rudragouda|last2=Perlman|first2=Stanley|title=Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology|journal=Seminars in Immunopathology|volume=39|issue=5|year=2017|pages=529–539|issn=1863-2297|doi=10.1007/s00281-017-0629-x}}</ref><ref name="MahallawiKhabour2018">{{cite journal|last1=Mahallawi|first1=Waleed H.|last2=Khabour|first2=Omar F.|last3=Zhang|first3=Qibo|last4=Makhdoum|first4=Hatim M.|last5=Suliman|first5=Bandar A.|title=MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile|journal=Cytokine|volume=104|year=2018|pages=8–13|issn=10434666|doi=10.1016/j.cyto.2018.01.025}}</ref>
:*Historical data on [[SARS-CoV]] and [[Middle East respiratory syndrome coronavirus infection causes|MERS-CoV]] suggest that cytokine storm including [[interleukin]] (IL), [[Tumour necrosis factor|tumor necrosis factor]] (TNF), and [[endotoxin]] and [[systemic inflammatory response syndrome]] played a major role in liver impairment among infected patients.<ref name="WongLam2004">{{cite journal|last1=Wong|first1=C. K.|last2=Lam|first2=C. W. K.|last3=Wu|first3=A. K. L.|last4=Ip|first4=W. K.|last5=Lee|first5=N. L. S.|last6=Chan|first6=I. H. S.|last7=Lit|first7=L. C. W.|last8=Hui|first8=D. S. C.|last9=Chan|first9=M. H. M.|last10=Chung|first10=S. S. C.|last11=Sung|first11=J. J. Y.|title=Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome|journal=Clinical & Experimental Immunology|volume=136|issue=1|year=2004|pages=95–103|issn=00099104|doi=10.1111/j.1365-2249.2004.02415.x}}</ref><ref name="ChannappanavarPerlman2017">{{cite journal|last1=Channappanavar|first1=Rudragouda|last2=Perlman|first2=Stanley|title=Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology|journal=Seminars in Immunopathology|volume=39|issue=5|year=2017|pages=529–539|issn=1863-2297|doi=10.1007/s00281-017-0629-x}}</ref><ref name="MahallawiKhabour2018">{{cite journal|last1=Mahallawi|first1=Waleed H.|last2=Khabour|first2=Omar F.|last3=Zhang|first3=Qibo|last4=Makhdoum|first4=Hatim M.|last5=Suliman|first5=Bandar A.|title=MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile|journal=Cytokine|volume=104|year=2018|pages=8–13|issn=10434666|doi=10.1016/j.cyto.2018.01.025}}</ref>
:*A high serum levels of [[Interleukin 2|interleukin-2]], [[Interleukin 6|interleukin-6]], [[Interleukin 7|interleukin-7]], [[Interleukin 10|interleukin-10]], [[Tumor necrosis factors|tumor necrosis factor-α]], [[Granulocyte colony stimulating factor|granulocyte-colony stimulating factor]], [[Interferon|interferon-inducible protein-10]], [[Chemotactic|monocyte chemotactic protein 1]], [[Macrophage inflammatory protein|macrophage inflammatory protein 1 alpha]], [[T helper 17 cell|Th17]], and [[Cytotoxic T cell|CD8 T cells]] are observed in severe cases of [[COVID-19]].<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="CaiHuang2020">{{cite journal|last1=Cai|first1=Qingxian|last2=Huang|first2=Deliang|last3=Ou|first3=Pengcheng|last4=Yu|first4=Hong|last5=Zhu|first5=Zhibin|last6=Xia|first6=Zhang|last7=Su|first7=Yinan|last8=Ma|first8=Zhenghua|last9=Zhang|first9=Yiming|last10=Li|first10=Zhiwei|last11=He|first11=Qing|last12=Liu|first12=Lei|last13=Fu|first13=Yang|last14=Chen|first14=Jun|title=COVID‐19 in a designated infectious diseases hospital outside Hubei Province, China|journal=Allergy|volume=75|issue=7|year=2020|pages=1742–1752|issn=0105-4538|doi=10.1111/all.14309}}</ref><ref name="LiuSun2020">{{cite journal|last1=Liu|first1=Yanli|last2=Sun|first2=Wenwu|last3=Li|first3=Jia|last4=Chen|first4=Liangkai|last5=Wang|first5=Yujun|last6=Zhang|first6=Lijuan|last7=Yu|first7=Li|year=2020|doi=10.1101/2020.02.17.20024166}}</ref><ref name="WanYi2020">{{cite journal|last1=Wan|first1=Suxin|last2=Yi|first2=Qingjie|last3=Fan|first3=Shibing|last4=Lv|first4=Jinglong|last5=Zhang|first5=Xianxiang|last6=Guo|first6=Lian|last7=Lang|first7=Chunhui|last8=Xiao|first8=Qing|last9=Xiao|first9=Kaihu|last10=Yi|first10=Zhengjun|last11=Qiang|first11=Mao|last12=Xiang|first12=Jianglin|last13=Zhang|first13=Bangshuo|last14=Chen|first14=Yongping|year=2020|doi=10.1101/2020.02.10.20021832}}</ref><ref name="DiaoWang2020">{{cite journal|last1=Diao|first1=Bo|last2=Wang|first2=Chenhui|last3=Tan|first3=Yingjun|last4=Chen|first4=Xiewan|last5=Liu|first5=Ying|last6=Ning|first6=Lifeng|last7=Chen|first7=Li|last8=Li|first8=Min|last9=Liu|first9=Yueping|last10=Wang|first10=Gang|last11=Yuan|first11=Zilin|last12=Feng|first12=Zeqing|last13=Wu|first13=Yuzhang|last14=Chen|first14=Yongwen|year=2020|doi=10.1101/2020.02.18.20024364}}</ref>
:*A high serum levels of [[Interleukin 2|interleukin-2]], [[Interleukin 6|interleukin-6]], [[Interleukin 7|interleukin-7]], [[Interleukin 10|interleukin-10]], [[Tumor necrosis factors|tumor necrosis factor-α]], [[Granulocyte colony stimulating factor|granulocyte-colony stimulating factor]], [[Interferon|interferon-inducible protein-10]], [[Chemotactic|monocyte chemotactic protein 1]], [[Macrophage inflammatory protein|macrophage inflammatory protein 1 alpha]], [[T helper 17 cell|Th17]], and [[Cytotoxic T cell|CD8 T cells]] are observed in severe cases of [[COVID-19]].<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref><ref name="CaiHuang2020">{{cite journal|last1=Cai|first1=Qingxian|last2=Huang|first2=Deliang|last3=Ou|first3=Pengcheng|last4=Yu|first4=Hong|last5=Zhu|first5=Zhibin|last6=Xia|first6=Zhang|last7=Su|first7=Yinan|last8=Ma|first8=Zhenghua|last9=Zhang|first9=Yiming|last10=Li|first10=Zhiwei|last11=He|first11=Qing|last12=Liu|first12=Lei|last13=Fu|first13=Yang|last14=Chen|first14=Jun|title=COVID‐19 in a designated infectious diseases hospital outside Hubei Province, China|journal=Allergy|volume=75|issue=7|year=2020|pages=1742–1752|issn=0105-4538|doi=10.1111/all.14309}}</ref><ref name="LiuSun2020">{{cite journal|last1=Liu|first1=Yanli|last2=Sun|first2=Wenwu|last3=Li|first3=Jia|last4=Chen|first4=Liangkai|last5=Wang|first5=Yujun|last6=Zhang|first6=Lijuan|last7=Yu|first7=Li|year=2020|doi=10.1101/2020.02.17.20024166}}</ref><ref name="WanYi2020">{{cite journal|last1=Wan|first1=Suxin|last2=Yi|first2=Qingjie|last3=Fan|first3=Shibing|last4=Lv|first4=Jinglong|last5=Zhang|first5=Xianxiang|last6=Guo|first6=Lian|last7=Lang|first7=Chunhui|last8=Xiao|first8=Qing|last9=Xiao|first9=Kaihu|last10=Yi|first10=Zhengjun|last11=Qiang|first11=Mao|last12=Xiang|first12=Jianglin|last13=Zhang|first13=Bangshuo|last14=Chen|first14=Yongping|year=2020|doi=10.1101/2020.02.10.20021832}}</ref><ref name="DiaoWang2020">{{cite journal|last1=Diao|first1=Bo|last2=Wang|first2=Chenhui|last3=Tan|first3=Yingjun|last4=Chen|first4=Xiewan|last5=Liu|first5=Ying|last6=Ning|first6=Lifeng|last7=Chen|first7=Li|last8=Li|first8=Min|last9=Liu|first9=Yueping|last10=Wang|first10=Gang|last11=Yuan|first11=Zilin|last12=Feng|first12=Zeqing|last13=Wu|first13=Yuzhang|last14=Chen|first14=Yongwen|year=2020|doi=10.1101/2020.02.18.20024364}}</ref>


===COVID-19 medical therapy-induced Hepatic Injury===
===COVID-19 medical therapy-induced Hepatic Injury===
:*[[COVID-19]] medical therapy includes [[Antibiotic|antibiotics]], [[Antiviral drug (patient information)|antivirals]], and [[Steroid|steroids]] similar to the treatment for [[SARS|SARS infection]]. These medications are on the whole likely reasons for liver injury during [[COVID-19|COVID‐19]], however not yet being obvious.<ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref>
:*[[COVID-19]] medical therapy includes [[Antibiotic|antibiotics]], [[Antiviral drug (patient information)|antivirals]], and [[Steroid|steroids]] similar to the treatment for [[SARS|SARS infection]]. These medications are on the whole likely reasons for liver injury during [[COVID-19|COVID‐19]], however not yet being obvious.<ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref>
:*Most [[Antipyretic|antipyretic medications]] contain [[Acetaminophen|paracetamol]], which is commonly perceived as a typical explanation behind liver injury.<ref>{{cite journal|doi=10.3969/j.issn.1672-5069.2020.02.001}}</ref>
:*Most [[Antipyretic|antipyretic medications]] contain [[Acetaminophen|paracetamol]], which is commonly perceived as a typical explanation behind liver injury.<ref>{{cite journal|doi=10.3969/j.issn.1672-5069.2020.02.001}}</ref>
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===Sepsis-induced COVID-19-associated Hepatic Injury===
===Sepsis-induced COVID-19-associated Hepatic Injury===
:*[[Sepsis]] can also be considered as a contributing factor to COVID-19-associated hepatic injury and can impair the prognosis of [[COVID-19]]. Sepsis is a dysregulated immune response to an infection that leads to psychological stress and [[Multiple organ dysfunction syndrome|multiple organ dysfunction]].<ref name="LelubreVincent2018">{{cite journal|last1=Lelubre|first1=Christophe|last2=Vincent|first2=Jean-Louis|title=Mechanisms and treatment of organ failure in sepsis|journal=Nature Reviews Nephrology|volume=14|issue=7|year=2018|pages=417–427|issn=1759-5061|doi=10.1038/s41581-018-0005-7}}</ref>
:*[[Sepsis]] can also be considered as a contributing factor to COVID-19-associated hepatic injury and can impair the prognosis of [[COVID-19]]. Sepsis is a dysregulated immune response to an infection that leads to psychological stress and [[Multiple organ dysfunction syndrome|multiple organ dysfunction]].<ref name="LelubreVincent2018">{{cite journal|last1=Lelubre|first1=Christophe|last2=Vincent|first2=Jean-Louis|title=Mechanisms and treatment of organ failure in sepsis|journal=Nature Reviews Nephrology|volume=14|issue=7|year=2018|pages=417–427|issn=1759-5061|doi=10.1038/s41581-018-0005-7}}</ref>
:*The pathophysiology of sepsis-related liver injury incorporates [[Hypoxemia|hypoxic liver injury]] because of [[ischemia]] and [[shock]], [[cholestasis]] because of altered [[Bile acid malabsorption|bile metabolism]], hepatocellular injury because of drug toxicity, or overwhelming [[inflammation]].<ref name="StrnadTacke2016">{{cite journal|last1=Strnad|first1=Pavel|last2=Tacke|first2=Frank|last3=Koch|first3=Alexander|last4=Trautwein|first4=Christian|title=Liver — guardian, modifier and target of sepsis|journal=Nature Reviews Gastroenterology & Hepatology|volume=14|issue=1|year=2016|pages=55–66|issn=1759-5045|doi=10.1038/nrgastro.2016.168}}</ref>
:*The pathophysiology of sepsis-related liver injury incorporates [[Hypoxemia|hypoxic liver injury]] because of [[ischemia]] and [[shock]], [[cholestasis]] because of altered [[Bile acid malabsorption|bile metabolism]], hepatocellular injury because of drug toxicity, or overwhelming [[inflammation]].<ref name="StrnadTacke2016">{{cite journal|last1=Strnad|first1=Pavel|last2=Tacke|first2=Frank|last3=Koch|first3=Alexander|last4=Trautwein|first4=Christian|title=Liver — guardian, modifier and target of sepsis|journal=Nature Reviews Gastroenterology & Hepatology|volume=14|issue=1|year=2016|pages=55–66|issn=1759-5045|doi=10.1038/nrgastro.2016.168}}</ref>


===Ischemia-reperfusion-induced Hepatic Injury===
===Ischemia-reperfusion-induced Hepatic Injury===
:*[[Ischemia]] and [[Hypoxia (medical)|hypoxia]] as a result of [[COVID-19]] infection can result in [[metabolic acidosis]], [[Calcium|calcium overloading]], and changes in [[Mitochondrial membrane|mitochondrial membrane permeability]]. These factors have impacted [[Hepatic failure|hepatic injury]] manifested as very high [[Transaminase|aminotransferase]] concentrations in serum.<ref name="pmid26125267">{{cite journal| author=Li J, Li RJ, Lv GY, Liu HQ| title=The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. | journal=Eur Rev Med Pharmacol Sci | year= 2015 | volume= 19 | issue= 11 | pages= 2036-47 | pmid=26125267 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26125267  }} </ref>
:*[[Ischemia]] and [[Hypoxia (medical)|hypoxia]] as a result of [[COVID-19]] infection can result in [[metabolic acidosis]], [[Calcium|calcium overloading]], and changes in [[Mitochondrial membrane|mitochondrial membrane permeability]]. These factors have impacted [[Hepatic failure|hepatic injury]] manifested as very high [[Transaminase|aminotransferase]] concentrations in serum.<ref name="pmid26125267">{{cite journal| author=Li J, Li RJ, Lv GY, Liu HQ| title=The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. | journal=Eur Rev Med Pharmacol Sci | year= 2015 | volume= 19 | issue= 11 | pages= 2036-47 | pmid=26125267 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26125267  }} </ref>


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==Differentiating COVID-19-associated hepatic injury from other causes of hepatic injury==
==Differentiating COVID-19-associated hepatic injury from other causes of hepatic injury==
*There are different etiologies of hepatic injury in general but a hepatic injury in a patient having [[COVID-19]] infection itself can be due to different reasons. Although different etiologies of the liver disease show some difference in biochemistry, we lack sufficient data to suggest a specific biochemical factor characteristic, pathognomic of [[COVID-19]] related liver injury.  Abnormal [[Liver function tests|liver biochemical markers]] at the time of diagnosis can give a clue of [[chronic liver disease]] in a patient.
*There are different etiologies of hepatic injury in general but a hepatic injury in a patient having [[COVID-19]] infection itself can be due to different reasons. Although different etiologies of the liver disease show some difference in biochemistry, we lack sufficient data to suggest a specific biochemical factor characteristic, pathognomic of [[COVID-19]] related liver injury.  Abnormal [[Liver function tests|liver biochemical markers]] at the time of diagnosis can give a clue of [[chronic liver disease]] in a patient.
* Deteriorating [[liver function tests]] during the course of hospitalization may point towards [[drug induced liver injury]] or complication of COVID-19.
* Deteriorating [[liver function tests]] during the course of [[hospitalization]] may point towards [[drug induced liver injury]] or complication of COVID-19.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
* In a cohort of 41 [[COVID-19]] patients, levels of [[Aspartate transaminase|aspartate aminotransferase]] increased by 15 (37%) patients. Among these 15 patients, eight (62%) of 13 ICU patients and seven (25%) of 28 non-ICU patients.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref>
* In a cohort of 41 [[COVID-19]] patients, levels of [[Aspartate transaminase|aspartate aminotransferase]] increased by 15 (37%) patients. Among these 15 patients, eight (62%) of 13 [[ICU]] patients and seven (25%) of 28 non-ICU patients.<ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref>
* According to a single-center study of 99 [[COVID-19]] patients. A wide range of [[Liver function tests|liver function abnormality]] was observed among 43 patients, with [[Alanine transaminase|alanine aminotransferase]] (ALT) or [[Aspartate transaminase|aspartate aminotransferase]] (AST) above the normal range. A severe [[Liver function tests|liver function abnormality]] was observed in one patient (ALT 7590 U/L, AST 1445 U/L).<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>
* According to a single-center study of 99 [[COVID-19]] patients. A wide range of [[Liver function tests|liver function abnormality]] was observed among 43 patients, with [[Alanine transaminase|alanine aminotransferase]] (ALT) or [[Aspartate transaminase|aspartate aminotransferase]] (AST) above the normal range. A severe [[Liver function tests|liver function abnormality]] was observed in one patient (ALT 7590 U/L, AST 1445 U/L).<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>


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|0–2%†
|0–2%†
|}<br />
|}<br />
In addition, abnormal liver function test in cases of [[COVID-19]] is often transient and often simultaneously combined with increased enzymes from muscle and heart; these laboratory changes can return to normal without liver-related morbidity and mortality.
In addition, abnormal [[liver function test]] in cases of [[COVID-19]] is often transient and often simultaneously combined with increased enzymes from muscle and heart; these laboratory changes can return to normal without liver-related [[morbidity]] and [[mortality]].


===Gender===
===Gender===
Although  is very limited data available, the incidence of liver injury associated with [[COVID-19]] is reported to be higher in males.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
Although  is very limited data available, the [[incidence]] of liver injury associated with [[COVID-19]] is reported to be higher in males.<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>


==Risk Factors==
==Risk Factors==
*Common risk factors in the development of hepatic complications include:<ref name="LiXiao2020">{{cite journal|last1=Li|first1=Yueying|last2=Xiao|first2=Shu‐Yuan|title=Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.25973}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref>
*Common risk factors in the development of hepatic [[complications]] include:<ref name="LiXiao2020">{{cite journal|last1=Li|first1=Yueying|last2=Xiao|first2=Shu‐Yuan|title=Hepatic involvement in COVID‐19 patients: Pathology, pathogenesis, and clinical implications|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.25973}}</ref><ref name="pmid32345544">{{cite journal |vauthors=Su TH, Kao JH |title=The clinical manifestations and management of COVID-19-related liver injury |journal=J. Formos. Med. Assoc. |volume=119 |issue=6 |pages=1016–1018 |date=June 2020 |pmid=32345544 |pmc=7180368 |doi=10.1016/j.jfma.2020.04.020 |url=}}</ref>
**[[Chronic liver disease]]
**[[Chronic liver disease]]
**[[Hypoxemia]]
**[[Hypoxemia]]
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*[[ICU]] patients had higher levels of [[ALT]] and [[AST]] and a more reduced level of serum albumin indicating severe liver damage affecting its synthetic ability.
*[[ICU]] patients had higher levels of [[ALT]] and [[AST]] and a more reduced level of serum albumin indicating severe liver damage affecting its synthetic ability.
*Total [[bilirubin]] and [[direct bilirubin]]: The data from limited studies show a higher incidence of [[hyperbilirubinemia]] in patients who required aggressive management during the course of their disease or died.<ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
*Total [[bilirubin]] and [[direct bilirubin]]: The data from limited studies show a higher incidence of [[hyperbilirubinemia]] in patients who required aggressive management during the course of their disease or died.<ref name="TianYe2020">{{cite journal|last1=Tian|first1=Dandan|last2=Ye|first2=Qing|title=Hepatic complications of COVID‐19 and its treatment|journal=Journal of Medical Virology|year=2020|issn=0146-6615|doi=10.1002/jmv.26036}}</ref>
*[[LDH]] levels- a study reported the incidence of LDH levels to be highest followed by AST and ALT and suggested that LDH can be used as an early alarm tp prompt further analysis for [[COVID-19]].<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
*[[LDH]] levels- a study reported the incidence of [[LDH]] levels to be highest followed by [[AST]] and [[ALT]] and suggested that [[LDH]] can be used as an early alarm tp prompt further analysis for [[COVID-19]].<ref name="FanChen2020">{{cite journal|last1=Fan|first1=Zhenyu|last2=Chen|first2=Liping|last3=Li|first3=Jun|last4=Cheng|first4=Xin|last5=Yang|first5=Jingmao|last6=Tian|first6=Cheng|last7=Zhang|first7=Yajun|last8=Huang|first8=Shaoping|last9=Liu|first9=Zhanju|last10=Cheng|first10=Jilin|title=Clinical Features of COVID-19-Related Liver Functional Abnormality|journal=Clinical Gastroenterology and Hepatology|volume=18|issue=7|year=2020|pages=1561–1566|issn=15423565|doi=10.1016/j.cgh.2020.04.002}}</ref>
* Glycoprotein [[gamma-glutamyltransferase]] (GGT) may point towards [[hepatobiliary]] involvement.
* Glycoprotein [[gamma-glutamyltransferase]] (GGT) may point towards [[hepatobiliary]] involvement.
*[[PTA]] (INR) provides a good estimate of liver synthetic function.
*[[PTA]] (INR) provides a good estimate of liver synthetic function.
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===X-ray===
===X-ray===
*There are no x-ray findings associated with [[COVID-19]]-associated hepatic injury.
*There are no [[X-ray]] findings associated with [[COVID-19]]-associated hepatic injury.
*However, an x-ray may be helpful in the diagnosis of complications of [[COVID-19]] such as [[COVID-19-associated pneumonia]] which is the most common finding associated with [[COVID-19]] infection.
*However, an [[X-ray]] may be helpful in the diagnosis of complications of [[COVID-19]] such as [[COVID-19-associated pneumonia]] which is the most common finding associated with [[COVID-19]] infection.
*The x-ray finidings on [[COVID-19]] can be viewed by [[COVID-19 x ray|clicking here]].
*The x-ray finidings on [[COVID-19]] can be viewed by [[COVID-19 x ray|clicking here]].


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===CT scan===
===CT scan===
*There are no CT scan findings associated with [[COVID-19]]-associated hepatic injury.
*There are no [[CT scan]] findings associated with [[COVID-19]]-associated hepatic injury.
*Chest CT scan may be helpful in suggesting other organ involvement in the [[COVID-19]] which is a multi-organ [[disease]].  
*Chest [[CT scan]] may be helpful in suggesting other organ involvement in the [[COVID-19]] which is a multi-organ [[disease]].
*The CT scan findings in [[COVID-19]] can be viewed by [[COVID-19 CT scan|clicking here]]
*The [[CT scan]] findings in [[COVID-19]] can be viewed by [[COVID-19 CT scan|clicking here]]


===MRI===
===MRI===
*There are no MRI findings associated with [[COVID-19]]-associated hepatic injury.
*There are no [[MRI]] findings associated with [[COVID-19]]-associated hepatic injury.


===Other Imaging Findings===
===Other Imaging Findings===
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===Primary Prevention===
===Primary Prevention===
*The disease itself is associated with [[COVID-19]] infection so prevention of the [[infection]] itself is the most promising primary prevention strategy at the moment.
*The disease itself is associated with [[COVID-19]] infection so prevention of the [[infection]] itself is the most promising [[primary prevention]] strategy at the moment.
*There are no available vaccines against [[COVID-19]] at the moment. There have been rigorous efforts in order to develop a [[vaccine]] for [[COVID-10|novel coronavirus]] and several vaccines are in the later phases of trials.<ref name="urlNIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)">{{cite web |url=https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins |title=NIH clinical trial of investigational vaccine for COVID-19 begins &#124; National Institutes of Health (NIH) |format= |work= |accessdate=}}</ref>
*There are no available vaccines against [[COVID-19]] at the moment. There have been rigorous efforts in order to develop a [[vaccine]] for [[COVID-10|novel coronavirus]] and several vaccines are in the later phases of trials.<ref name="urlNIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)">{{cite web |url=https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins |title=NIH clinical trial of investigational vaccine for COVID-19 begins &#124; National Institutes of Health (NIH) |format= |work= |accessdate=}}</ref>
*The only prevention for [[COVID-19]] associated hepatic injury is the prevention and early diagnosis of the [[coronavirus-19]] infection itself. According to the [[CDC]], the measures include:<ref name="urlHow to Protect Yourself & Others | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html |title=How to Protect Yourself & Others &#124; CDC |format= |work= |accessdate=}}</ref>
*The only prevention for [[COVID-19]] associated hepatic injury is the prevention and early [[diagnosis]] of the [[coronavirus-19]] infection itself. According to the [[CDC]], the measures include:<ref name="urlHow to Protect Yourself & Others | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html |title=How to Protect Yourself & Others &#124; CDC |format= |work= |accessdate=}}</ref>
**Frequent handwashing with soap and water for at least 20 seconds or using a [[alcohol rub|alcohol based hand sanitizer]] with at least 60% alcohol.
**Frequent handwashing with soap and water for at least 20 seconds or using a [[alcohol rub|alcohol based hand sanitizer]] with at least 60% alcohol
**Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you.
**Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you
**Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs.
**Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs
**Cleaning and [[Disinfectant|disinfecting]].
**Cleaning and [[Disinfectant|disinfecting]]
*At this time, the only effective measures for the primary prevention of COVID-19 related liver damage include prevention of itself [[COVID-19]]. [[Drug induced liver injury]] can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with antiviral drugs.
*At this time, the only effective measures for the [[primary prevention]] of COVID-19 related liver damage include prevention of itself [[COVID-19]]. [[Drug induced liver injury]] can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with [[antiviral drugs]].


===Secondary prevention===
===Secondary prevention===
*Effective measures for the secondary prevention of contact tracing as it helps reduce the spread of the disease.<ref name="urlContact Tracing for COVID-19 | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/php/contact-tracing/contact-tracing-plan/contact-tracing.html |title=Contact Tracing for COVID-19 &#124; CDC |format= |work= |accessdate=}}</ref>
*Effective measures for the [[secondary prevention]] of contact tracing as it helps reduce the spread of the disease.<ref name="urlContact Tracing for COVID-19 | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/php/contact-tracing/contact-tracing-plan/contact-tracing.html |title=Contact Tracing for COVID-19 &#124; CDC |format= |work= |accessdate=}}</ref>
*In unexplained abnormal [[Liver function tests|hepatic biochemical tests]], [[CXR]], Chest [[CT scan]] or nasopharyngeal swab [[RT-PCR]] should be performed to diagnose the infection and treat it timely.
*In unexplained abnormal [[Liver function tests|hepatic biochemical tests]], [[CXR]], Chest [[CT scan]] or [[nasopharyngeal]] [[Cotton swab|swab]] [[RT-PCR]] should be performed to diagnose the infection and treat it timely.


==References==
==References==

Revision as of 05:56, 15 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2] Javaria Anwer M.D.[3]

Overview

According to 12 clinical studies, 14.8%-53% of COVID-19 patients have liver impairment, suggesting COVID-19-associated hepatic injury, a common complication observed among COVID-19 patients. With the number of cases increasing, abnormal liver function test results have been observed in some patients with COVID-19, making this organ the most frequently damaged outside of the respiratory system.

Historical Perspective

Classification

There is no formal classification of liver damage associated with COVID-19 but, we attempt to divide the entity based on the etiology and mechanism of liver damage:[21][22][8][23][24][25][26][27]

To browse the classification of COVID-19, Click here.

Pathophysiology

The exact mechanism of liver injury is still unclear. There are several proposed mechanisms in an effort to understand the pathogenesis of hepatic injury but the hepatic complications in COVID-19 patients are described as multifactorial and heterogenous. A few of the proposed mechanisms include:

Hepatic Injury through ACE2 receptors

Antibody-mediated Hepatic Injury

Cytokine-mediated Hepatic Injury

COVID-19 medical therapy-induced Hepatic Injury

Sepsis-induced COVID-19-associated Hepatic Injury

Ischemia-reperfusion-induced Hepatic Injury

Clinical Features

Differentiating COVID-19-associated hepatic injury from other causes of hepatic injury

  • There are different etiologies of hepatic injury in general but a hepatic injury in a patient having COVID-19 infection itself can be due to different reasons. Although different etiologies of the liver disease show some difference in biochemistry, we lack sufficient data to suggest a specific biochemical factor characteristic, pathognomic of COVID-19 related liver injury. Abnormal liver biochemical markers at the time of diagnosis can give a clue of chronic liver disease in a patient.
  • Deteriorating liver function tests during the course of hospitalization may point towards drug induced liver injury or complication of COVID-19.

Epidemiology and Demographics

Liver test abnormalities from various COVID-19 studies[9]
Author Group Number of patients Alanine

aminotransferase (IU)

Aspartate

aminotransferase (IU)

Prothrombin

time (s)

Bilirubin (μmol/L) Elevated lactate

dehydrogenase, creatinine kinase, or myoglobin

Mortality (%)
Guan et al (2020)[19] ICU or death 67 Not known Not known Not known Not known Yes 22% (day 51)
Huang et al (2020)[18] ICU 13 49 (29–115) 44 (32–70) 12·2 (11·2–13·4) 14·0 (11·9–32·9) Yes 38% (day 37)
Chen et al (2020)[4] Hospitalised 99 39 (22–53) 34 (26–48) 11·3 (1·9) 15·1 (7·3) Yes 11% (day 24)
Wang et al (2020)[47] ICU 36 35 (19–57) 52 (30–70) 13·2 (12·3–14·5) 11·5 (9·6–18·6) Yes 17% (day 34)
Shi et al (2020)[48] Hospitalised 81 46 (30) 41 (18) 10·7 (0·9) 11·9 (3·6) Unclear 5% (day 50)
Xu et al (2020)[49] Hospitalised 62 22 (14–34) 26 (20–32) Not known Not known Unclear 0% (day 34)
Yang et al (2020)[3] ICU 52 Not known Not known 12·9 (2·9)* 19·5 (11·6)* Not described 62% (day 28)
Extracted from all

studies above

Chronic liver

disease

42 Not known Not known Not known Not known Not known 0–2%†


In addition, abnormal liver function test in cases of COVID-19 is often transient and often simultaneously combined with increased enzymes from muscle and heart; these laboratory changes can return to normal without liver-related morbidity and mortality.

Gender

Although is very limited data available, the incidence of liver injury associated with COVID-19 is reported to be higher in males.[42]

Risk Factors

  • Common risk factors in the development of hepatic complications include:[23][27]
    • Chronic liver disease
    • Hypoxemia
    • Hyper‐inflammatory reactions during COVID-19 infection
    • Critical COVID-19 infection - liver injury being more prevalent in patients with a critical disease (especially ICU admissions) rather mild cases, makes a severe coronavirus infection a risk factor.

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

  • Laboratory findings consistent with the diagnosis of COVID-19-associated hepatic injury include abnormal Liver function tests specially raised AST.
  • Research has shown elevated ALT and AST levels in the blood of patients with liver injury on admission. AST elevation is more common than ALT, which reflects a possible source outside of liver.[26]
  • Serum albumin levels were found to get lower during the course of hospitalization. The tests is a measure of synthetic function of the liver.
  • ICU patients had higher levels of ALT and AST and a more reduced level of serum albumin indicating severe liver damage affecting its synthetic ability.
  • Total bilirubin and direct bilirubin: The data from limited studies show a higher incidence of hyperbilirubinemia in patients who required aggressive management during the course of their disease or died.[24]
  • LDH levels- a study reported the incidence of LDH levels to be highest followed by AST and ALT and suggested that LDH can be used as an early alarm tp prompt further analysis for COVID-19.[42]
  • Glycoprotein gamma-glutamyltransferase (GGT) may point towards hepatobiliary involvement.
  • PTA (INR) provides a good estimate of liver synthetic function.
  • Alkaline phosphatase (ALP) is higher in patients.[27]
  • Levels of IL‐2‐receptor (IL‐2R), IL‐4, IL‐6, IL‐18, IL‐10, TNF‐α were significantly increased IL‐6 in the serum of COVID‐19 patients are significantly increased and correlate with disease severity.[52]

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT scan

MRI

  • There are no MRI findings associated with COVID-19-associated hepatic injury.

Other Imaging Findings

  • There are no other imaging findings associated with COVID-19-associated hepatic injury.

Other Diagnostic Studies

Treatment

Medical Therapy

Currently there is no specific treatmentthe for patient with COVID-19 associated liver injury. The mainstay of medical therapy is to target the viral infection and control and prevent inflammation.[24][27]

Surgery

  • Surgical intervention is not recommended for the management of COVID-19-associated hepatic injury.

Primary Prevention

  • The disease itself is associated with COVID-19 infection so prevention of the infection itself is the most promising primary prevention strategy at the moment.
  • There are no available vaccines against COVID-19 at the moment. There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.[53]
  • The only prevention for COVID-19 associated hepatic injury is the prevention and early diagnosis of the coronavirus-19 infection itself. According to the CDC, the measures include:[54]
    • Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% alcohol
    • Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you
    • Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs
    • Cleaning and disinfecting
  • At this time, the only effective measures for the primary prevention of COVID-19 related liver damage include prevention of itself COVID-19. Drug induced liver injury can be prevented by carefully selecting the drug with a known mechanism of action, not using more than two drugs, and avoiding large doses of hormones along with antiviral drugs.

Secondary prevention

References

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