Features of Liver Injury in COVID-19 Clinical Particularities

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1		Cristina Maria Marginean	--	1791	2023-04-06 14:10:33	\|
2	format correct	Jessie Wu	Meta information modification	1791	2023-04-07 05:17:45	\|

This entry is adapted from the peer-reviewed paper 10.3390/gastroent14020012

COVID-19 clinical presentation falls on a wide spectrum, from mild cases complaining of minor symptoms to severe illness with multiorgan dysfunctions and death. Multiple organ injuries have been described in COVID-19, such as pulmonary affliction, acute kidney damage, liver injury, stroke, cardiovascular and digestive tract disorders.

COVID-19 liver injury patients

1. Clinical Correlations between SARS-CoV-2 Infection and Underlying Chronic Liver Disease

1.1. COVID-19 and Liver Cirrhosis

Ongoing studies are currently trying to determine the relationship between SARS-CoV-2 and chronic liver disease patients regarding their susceptibility to infection. To date, published studies have not suggested that patients with underlying chronic liver disease could have an increased susceptibility to SARS-CoV-2 infection ^[1], and United States medical data have indicated a reduced rate of positive testing among patients with liver cirrhosis ^[2]^[3]. However, chronic liver disease, including liver cirrhosis, is unlikely to protect against contracting SARS-CoV-2 infection. The lower rate of positive tests is probably due to strict adherence to prophylactic measures (e.g., social distancing and wearing a protective mask).

Patients with liver cirrhosis infected with SARS-CoV-2 show a gradual increase in morbidity and mortality related to the severity of liver disease, assessed by the Child–Pugh class. Thus, an increase in mortality was observed in patients with cirrhosis of Child–Pugh C, whose survivals decrease to 10% once subjected to mechanical ventilation. COVID-19 disease-related mortality was significantly associated with the severity of underlying liver cirrhosis, with the risk of death increasing in parallel with the severity class of liver disease: CP-A class 1.90%, CP-B 4.14%, and CP-C 9.32%, according to ongoing studies ^[4]. Strong evidence for increased disease severity in patients associated both COVID-19 and cirrhosis was presented in a large meta-analysis evaluating clinical data obtained from over 900,000 patients ^[5].

Cirrhosis disrupts both the local immunity of the liver and systemic immunity. This immune impairment may account for susceptibility to severe forms of COVID-19 and grave outcomes observed in this group ^[6].

Although acute mortality in patients with liver cirrhosis and COVID-19 is increased, in those patients who survive the initial episode, the risk of death or readmission at 90 days is similar to the risk observed in patients with liver cirrhosis without COVID-19 ^[7]. Therefore, except for the acute infectious period, the SARS-CoV-2 condition does not appear to precipitate liver disease progression.

On the other hand, other studies using multivariable analysis have published results depicting no correlation between cirrhosis and COVID-19 mortality ^[8]^[9]. A recent study performed by Simon et al. in 2021 did not find a specific relation between COVID-19 and the outcome or clinical course of cirrhosis ^[10].

1.2. COVID-19 and MAFLD

The etiology of liver diseases could influence the clinical evolution of SARS-CoV-2 infection. Risk factors associated with higher morbidity and mortality rates in SARS-CoV-2 infection are represented by age, obesity, and diabetes. However, there are inconsistencies in the literature regarding the influence of metabolic-associated fatty liver disease (MAFLD) on the clinical course of the SARS-CoV-2 condition, related to the difficulties in the differential diagnosis of MAFLD and other metabolic comorbidities ^[11]^[12].

Some reports describe a strong association between MAFLD and the progression of SARS-CoV-2 infection. Some studies show that people with MAFLD have an increased risk of symptomatic SARS-CoV-2 disease, a higher risk of progression to severe forms, and a longer time for viral clearance ^[13]. In MAFLD, the polarization status of macrophages could be disrupted, modulating inflammatory response to SARS-CoV-2 ^[13].

A meta-analysis of available data shows that among MAFLD patients with SARS-CoV-2 infection, obesity increases the risk of severe SARS-CoV-2 disease. These findings support the specific role of MAFLD in modulating susceptibility to SARS-CoV-2 infection and progression (Table 1) ^[14].

Table 1. Association between obesity and COVID-19 infection severity in patients with MAFLD (adapted from Asemota et al., 2022 ^[14]).

	OR	95% CI	p
Unadjusted	5.77	1.19–27.91	0.029
Model I	6.25	1.23–31.71	0.027
Model II	6.32	1.16–34.54	0.033

Model I: adjusted for age and gender. Model II: adjusted for age, gender, smoker status, type II diabetes mellitus, arterial hypertension, and dyslipidemia.

MAFLD is associated not only with COVID-19 but also with other systemic disorders, such as hyperglycemia, insulin resistance, altered immune status, obesity, vitamin D deficiency, diverticulosis, and anemia of chronic disease, through systemic inflammation ^[15]^[16]^[17].

1.3. COVID-19 and Chronic Hepatitis

A study of 1193 patients by Ronderos et al. ^[18] showed that chronic hepatitis C was correlated with increased in-hospital mortality in acute SARS-CoV-2 infection. Patients with chronic hepatitis C might have an increased risk of severe respiratory complications without previous comorbidity or COVID-19 liver damage ^[19]. The effects are correlated with the extrahepatic manifestations of HCV infection, which stimulate ACE2/TMPRSS mechanisms, and endothelial dysfunction and are secondary to the inflammatory process. However, more available data are needed for a clear conclusion.

A study conducted on 2482 patients by Kang et al. ^[20] documented the paradoxical relation between chronic hepatitis B and SARS-CoV-2 infection—the condition does not increase the risk of developing severe forms of COVID-19 and does not negatively influence disease outcomes, even if it appears that preexisting B virus infection and treatment with antiviral agents have a protective effect, decreasing the risk of contracting SARS-CoV-2 infection. The outcome of SARS-CoV-2 infection in HBV patients depends on the previous stage of chronic liver disease, described by Shanshan Yang et al. in a large study ^[21].

1.4. COVID-19 and Autoimmune Hepatitis

Many authors have focused their studies on the evolution of autoimmune hepatitis (AIH) in patients with SARS-CoV-2 infection. It was postulated that immunosuppressive treatment of AIH would increase these patients’ risk of SARS-CoV-2 infection. Still, a prevalence of severe forms of COVID-19 was not observed, probably due to the prevention effect of a systemic inflammatory response by immunosuppressive therapy. Conversely, immunosuppressive treatment increases the time of SARS-CoV-2 virus clearance, and these patients become a source of contamination for a prolonged period ^[22].

An international multicentric study by Efe et al. related to outcomes of COVID-19 in patients with autoimmune hepatitis revealed that patients with AIH were not at higher risk for a worse prognosis with COVID-19 than other related causes of CLD ^[23].

A recent study, documented by Ashley L. Faulx et al. in 2021, suggested that AIH does not determine a more severe prognosis in co-infection with COVID-19, even in those patients receiving immunosuppressive drugs; thus, immunosuppressive treatment should not be interrupted in patients with AIH who develop severe forms of COVID-19, as there are no conclusive indications of worsening the clinical outcome in these patients ^[24].

Other studies on the relation between immunosuppressive medication and the prognosis of COVID-19 in patients diagnosed with AIH have concluded that systemic glucocorticoids or immunosuppressive therapy prescribed before the onset of COVID-19 was significantly associated with COVID-19-increased severity in patients with AIH ^[25].

Neeraj Kumar et al. describe a case of severe evolution of COVID-19 in a young man with autoimmune hepatitis, considering that morbidity in COVID-19 associated with liver disease is due to hyperinflammation and cytokine storm with increased IL-6 levels. Significant cytokine release and inflammatory responses affect both the onset and severity of disease progression. Consequently, a rapid and appropriate diagnostic evaluation and accurate estimation and prognosis are necessary ^[26].

1.5. COVID-19 and Vascular Diseases

A study conducted by Baiges et al. on patients with SARS-CoV-2 infection and underlying vascular liver diseases, including Budd–Chiari syndrome, portosinusoidal vascular disease and noncirrhotic splanchnic vein thrombosis, revealed a higher risk of SARS-CoV-2 infection and a higher risk of severe forms of COVID-19 ^[27]. Further studies in this area are needed.

2. COVID-19 and Cholangitis

Secondary sclerosing cholangitis is a chronic condition characterized by progressive fibrosis and biliary tract destruction, which can lead to biliary cirrhosis.

Post-COVID-19 cholangiopathy is a unique concept, defined as a variant of secondary sclerosing cholangitis. It can be determined by SARS-CoV-2 infection, or it can be drug induced. Cholangiopathy may be present in many other associated diseases, such as AIDS, cholangiolithiasis, diffuse intrahepatic metastases, and histiocytosis C ^[28].

The molecular mechanism can be explained due to the predominance of the ACE2 receptor in cholangiocytes. The presence of viral receptors on the host cell’s surface significantly determines viral tropism. The penetration of SARS-CoV-2 in the host’s cells is mediated by the S protein, which specifically interacts with ACE2 and transmembrane serine protease 2 (TMPRSS2) receptors. ACE2 expression is relatively low in hepatocytes and is significantly increased in cholangiocytes, while transmembrane serine protease 2 expression is higher in hepatocytes.

The binding of SARS-CoV-2 to the ACE2-receptors in cholangiocytes affects the barrier and the biliary acid transport mechanism by affecting gene regulation, leading to cholestasis ^[29].

Diagnosis depends on history, clinical evaluation, biological tests, and imaging studies.

In a study of 2047 patients admitted in hospital with COVID-19, 12 patients with severe COVID-18 developed cholangiopathy syndrome characterized by cholestasis and biliary tract abnormalities similar to the particularities observed in patients with secondary sclerosing cholangitis.

Histologic features included inflammation, strictures, cholangiocyte injury with microvascular anomalies, and fibrosis periportal hepatocytes metaplasia ^[28].

Biliary tract disorder in COVID-19 patients can be suspected when clinical and biological tests reveal cholestasis and elevated liver enzymes. Biliary imaging methods confirm the diagnosis of secondary sclerosing cholangitis.

Further research is needed to assess the pathogenesis in cholangiopathy associated with SARS-CoV-2 infection and to find preventive and optimal therapeutic measures ^[30].

3. COVID-19 and High-Risk Groups

According to their immunocompromised status, liver transplant recipients have an increased risk of severe clinical forms of SARS-CoV-2 infection. A retrospective study conducted by Colmenero et al. in hospitalized patients with liver transplants and COVID-19 highlighted a mortality rate of 18%, lower than in the general population, despite the evidence of a more severe disease outcome ^[31]^[32]. Similar results were cited in another multicentric study on 112 patients conducted by Rabbie et al., showing a mortality rate of 22.3%, lower than in patients without liver transplants ^[33].

This is due to these patients’ immunomodulatory therapy, which can improve the systemic inflammatory response, reducing mortality ^[32]^[34]. However, immunosuppressive treatment can delay viral clearance, arguing for more severe clinical evolution ^[29]. An increased risk of severe forms and exitus in transplanted patients was correlated with young age, metabolic syndrome association, prescription of antibiotics and vasopressor treatment ^[33].

Pregnant women are a high-risk population category for severe outcomes of SARS-CoV-2 infection, with an increased prevalence of premature births. Among important maternal mortality causes are HELLP syndrome, hemolysis, liver cytolysis and preeclampsia. The studies carried out support an increased risk of preeclampsia in pregnant women with SARS-CoV-2 infection, suggesting a possible overlap of physiopathological hypotheses ^[35].

Risk factors correlated with severe forms of COVID-19 in pregnant women include smoking, obesity, diabetes, and preeclampsia ^[36]^[37].

Although pregnancy is not associated with increased susceptibility to contracting SARS-CoV-2 infection, pregnant women are at higher risk of severe outcomes ^[35]^[38] and complications, such as preeclampsia or HELLP syndrome ^[35]^[39]^[40]. Thrombocytopenia, increased liver enzymes and hemolysis are markers present both in HELLP syndrome and in patients with multiorgan dysfunction in critical condition ^[35], suggesting that SARS-CoV-2 infection has similarities with HELLP syndrome in pregnant women ^[32] and raises real challenges in the differential diagnosis. It is assumed that there is a pathogenetic link between SARS-CoV-2 and HELLP syndrome, an association that requires extensive future research.

References

Noor, M.T.; Manoria, P. Immune Dysfunction in Cirrhosis. J. Clin. Transl. Hepatol. 2017, 5, 50–58.
Fan, V.S.; Dominitz, J.A.; Eastment, M.C.; Locke, E.R.; Green, P.; Berry, K.; O’Hare, A.M.; Shah, J.A.; Crothers, K.; Ioannou, G.N. Risk Factors for Testing Positive for Severe Acute Respiratory Syndrome Coronavirus 2 in a National United States Healthcare System. Clin. Infect. Dis. 2021, 73, e3085–e3094.
Ioannou, G.N.; Liang, P.S.; Locke, E.; Green, P.; Berry, K.; O’Hare, A.M.; Shah, J.A.; Crothers, K.; Eastment, M.C.; Fan, V.S.; et al. Cirrhosis and Severe Acute Respiratory Syndrome Coronavirus 2 Infection in US Veterans: Risk of Infection, Hospitalization, Ventilation, and Mortality. Hepatology 2021, 74, 322–335.
Marjot, T.; Moon, A.M.; Cook, J.A.; Abd-Elsalam, S.; Aloman, C.; Armstrong, M.J.; Pose, E.; Brenner, E.J.; Cargill, T.; Catana, M.-A.; et al. Outcomes Following SARS-CoV-2 Infection in Patients with Chronic Liver Disease: An International Registry Study. J. Hepatol. 2021, 74, 567–577.
Nagarajan, R.; Krishnamoorthy, Y.; Rajaa, S.; Hariharan, V.S. COVID-19 Severity and Mortality among Chronic Liver Disease Patients: A Systematic Review and Meta-Analysis. Prev. Chronic Dis. 2022, 19, E53.
Wang, Y.; Hu, M.; Yang, H. Cirrhosis Is an Independent Predictor for COVID-19 Mortality: A Meta-Analysis of Confounding Cofactors-Controlled Data. J. Hepatol. 2023, 78, e28–e31.
Bajaj, J.S.; Garcia-Tsao, G.; Wong, F.; Biggins, S.W.; Kamath, P.S.; McGeorge, S.; Chew, M.; Pearson, M.; Shaw, J.; Kalluri, A.; et al. Cirrhosis Is Associated with High Mortality and Readmissions over 90 Days Regardless of COVID-19: A Multicenter Cohort. Liver Transpl. 2021, 27, 1343–1347.
Bushman, D.; Davidson, A.; Pathela, P.; Greene, S.K.; Weiss, D.; Reddy, V.; New York City Fatal Case-Control Study Team; Latash, J. Risk Factors for Death among Hospitalized Patients Aged 21–64 Years Diagnosed with COVID-19—New York City, March 13–April 9, 2020. J. Racial Ethn. Health Disparities 2022, 9, 1584–1599.
Castilla, J.; Guevara, M.; Miqueleiz, A.; Baigorria, F.; Ibero-Esparza, C.; Navascués, A.; Trobajo-Sanmartín, C.; Martínez-Baz, I.; Casado, I.; Burgui, C.; et al. Risk Factors of Infection, Hospitalization and Death from SARS-CoV-2: A Population-Based Cohort Study. J. Clin. Med. 2021, 10, 2608.
Simon, T.G.; Hagström, H.; Sharma, R.; Söderling, J.; Roelstraete, B.; Larsson, E.; Ludvigsson, J.F. Risk of Severe COVID-19 and Mortality in Patients with Established Chronic Liver Disease: A Nationwide Matched Cohort Study. BMC Gastroenterol. 2021, 21, 439.
Eslam, M.; Newsome, P.N.; Sarin, S.K.; Anstee, Q.M.; Targher, G.; Romero-Gomez, M.; Zelber-Sagi, S.; Wai-Sun Wong, V.; Dufour, J.-F.; Schattenberg, J.M.; et al. A New Definition for Metabolic Dysfunction-Associated Fatty Liver Disease: An International Expert Consensus Statement. J. Hepatol. 2020, 73, 202–209.
Stan, I.S.; Biciuşcă, V.; Durand, P.; Petrescu, A.M.; Oancea, D.M.; Ciuciulete, A.R.; Petrescu, M.; Udriştoiu, I.; Camen, G.C.; Bălteanu, M.A.; et al. Diagnostic and Prognostic Significance of Hepatic Steatosis in Patients with Chronic Hepatitis C. Rom. J. Morphol. Embryol. 2021, 62, 765–775.
Bucurica, S.; Ionita Radu, F.; Bucurica, A.; Socol, C.; Prodan, I.; Tudor, I.; Sirbu, C.A.; Plesa, F.C.; Jinga, M. Risk of New-Onset Liver Injuries Due to COVID-19 in Preexisting Hepatic Conditions—Review of the Literature. Medicina 2023, 59, 62.
Asemota, J.; Aduli, F. The Impact of Nonalcoholic Fatty Liver Disease on the Outcomes of Coronavirus Disease 2019 Infection. Clin. Liver Dis. 2022, 19, 29–31.
Adenote, A.; Dumic, I.; Madrid, C.; Barusya, C.; Nordstrom, C.W.; Rueda Prada, L. NAFLD and Infection, a Nuanced Relationship. Can. J. Gastroenterol. Hepatol. 2021, 2021, 5556354.
Singer, C.E.; Vasile, C.M.; Popescu, M.; Popescu, A.I.S.; Marginean, I.C.; Iacob, G.A.; Popescu, M.D.; Marginean, C.M. Role of Iron Deficiency in Heart Failure—Clinical and Treatment Approach: An Overview. Diagnostics 2023, 13, 304.
Pantic, I.; Lugonja, S.; Rajovic, N.; Dumic, I.; Milovanovic, T. Colonic Diverticulosis and Non-Alcoholic Fatty Liver Disease: Is There a Connection? Medicina 2022, 58, 38.
Ronderos, D.; Omar, A.M.S.; Abbas, H.; Makker, J.; Baiomi, A.; Sun, H.; Mantri, N.; Choi, Y.; Fortuzi, K.; Shin, D.; et al. Chronic Hepatitis-C Infection in COVID-19 Patients Is Associated with in-Hospital Mortality. World J. Clin. Cases 2021, 9, 8749–8762.
Afify, S.; Eysa, B.; Hamid, F.A.; Abo-Elazm, O.M.; Edris, M.A.; Maher, R.; Abdelhalim, A.; Abdel Ghaffar, M.M.; Omran, D.A.; Shousha, H.I. Survival and Outcomes for Co-Infection of Chronic Hepatitis C with and without Cirrhosis and COVID-19: A Multicenter Retrospective Study. World J. Gastroenterol. 2021, 27, 7362–7375.
Kang, S.H.; Cho, D.-H.; Choi, J.; Baik, S.K.; Gwon, J.G.; Kim, M.Y. Association between Chronic Hepatitis B Infection and COVID-19 Outcomes: A Korean Nationwide Cohort Study. PLoS ONE 2021, 16, e0258229.
Yang, S.; Wang, S.; Du, M.; Liu, M.; Liu, Y.; He, Y. Patients with COVID-19 and HBV Coinfection Are at Risk of Poor Prognosis. Infect. Dis. 2022, 11, 1229–1242.
Kushner, T.; Cafardi, J. Chronic Liver Disease and COVID-19: Alcohol Use Disorder/Alcohol-Associated Liver Disease, Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Autoimmune Liver Disease, and Compensated Cirrhosis. Clin. Liver Dis. 2020, 15, 195–199.
Efe, C.; Dhanasekaran, R.; Lammert, C.; Ebik, B.; Higuera-de la Tijera, F.; Aloman, C.; Rıza Calışkan, A.; Peralta, M.; Gerussi, A.; Massoumi, H.; et al. Outcome of COVID-19 in Patients with Autoimmune Hepatitis: An International Multicenter Study. Hepatology 2021, 73, 2099–2109.
Marjot, T.; Buescher, G.; Sebode, M.; Barnes, E.; Barritt, A.S.; Armstrong, M.J.; Baldelli, L.; Kennedy, J.; Mercer, C.; Ozga, A.-K.; et al. SARS-CoV-2 Infection in Patients with Autoimmune Hepatitis. J. Hepatol. 2021, 74, 1335–1343.
Efe, C.; Lammert, C.; Taşçılar, K.; Dhanasekaran, R.; Ebik, B.; Higuera-de la Tijera, F.; Calışkan, A.R.; Peralta, M.; Gerussi, A.; Massoumi, H.; et al. Effects of Immunosuppressive Drugs on COVID-19 Severity in Patients with Autoimmune Hepatitis. Liver Int. 2022, 42, 607–614.
Kumar, N.; Satyapriya, S.; Tahaseen, S.M.; Singh, K.; Kumar, A. Severe Progression of Autoimmune Hepatitis in a Young COVID-19 Adult Patient: A Case Report. J. Acute Dis. 2022, 11, 161.
Baiges, A.; Cerda, E.; Amicone, C.; Téllez, L.; Alvarado-Tapias, E.; Puente, A.; Fortea, J.I.; Llop, E.; Rocha, F.; Orts, L.; et al. Impact of SARS-CoV-2 Pandemic on Vascular Liver Diseases. Clin. Gastroenterol. Hepatol. 2022, 20, 1525–1533.e5.
Roth, N.C.; Kim, A.; Vitkovski, T.; Xia, J.; Ramirez, G.; Bernstein, D.; Crawford, J.M. Post-COVID-19 Cholangiopathy: A Novel Entity. Am. J. Gastroenterol. 2021, 116, 1077–1082.
Zhao, B.; Ni, C.; Gao, R.; Wang, Y.; Yang, L.; Wei, J.; Lv, T.; Liang, J.; Zhang, Q.; Xu, W.; et al. Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Ductal Organoids. Protein Cell 2020, 11, 771–775.
Yip, T.C.-F.; Lui, G.C.-Y.; Wong, V.W.-S.; Chow, V.C.-Y.; Ho, T.H.-Y.; Li, T.C.-M.; Tse, Y.-K.; Hui, D.S.-C.; Chan, H.L.-Y.; Wong, G.L.-H. Liver Injury Is Independently Associated with Adverse Clinical Outcomes in Patients with COVID-19. Gut 2021, 70, 733–742.
Colmenero, J.; Rodríguez-Perálvarez, M.; Salcedo, M.; Arias-Milla, A.; Muñoz-Serrano, A.; Graus, J.; Nuño, J.; Gastaca, M.; Bustamante-Schneider, J.; Cachero, A.; et al. Epidemiological Pattern, Incidence, and Outcomes of COVID-19 in Liver Transplant Patients. J. Hepatol. 2021, 74, 148–155.
Nasa, P.; Alexander, G. COVID-19 and the Liver: What Do We Know so Far? World J. Hepatol. 2021, 13, 522–532.
Rabiee, A.; Sadowski, B.; Adeniji, N.; Perumalswami, P.V.; Nguyen, V.; Moghe, A.; Latt, N.L.; Kumar, S.; Aloman, C.; Catana, A.M.; et al. Liver Injury in Liver Transplant Recipients with Coronavirus Disease 2019 (COVID-19): U.S. Multicenter Experience. Hepatology 2020, 72, 1900–1911.
Mehta, P.; McAuley, D.F.; Brown, M.; Sanchez, E.; Tattersall, R.S.; Manson, J.J.; HLH Across Speciality Collaboration, UK. COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression. Lancet 2020, 395, 1033–1034.
Nasa, P.; Juneja, D.; Jain, R.; Nasa, R. COVID-19 and Hemolysis, Elevated Liver Enzymes and Thrombocytopenia Syndrome in Pregnant Women-Association or Causation? World J. Virol. 2022, 11, 310–320.
Gao, Y.-D.; Ding, M.; Dong, X.; Zhang, J.-J.; Kursat Azkur, A.; Azkur, D.; Gan, H.; Sun, Y.-L.; Fu, W.; Li, W.; et al. Risk Factors for Severe and Critically Ill COVID-19 Patients: A Review. Allergy 2021, 76, 428–455.
Lassi, Z.S.; Ana, A.; Das, J.K.; Salam, R.A.; Padhani, Z.A.; Irfan, O.; Bhutta, Z.A. A Systematic Review and Meta-Analysis of Data on Pregnant Women with Confirmed COVID-19: Clinical Presentation, and Pregnancy and Perinatal Outcomes Based on COVID-19 Severity. J. Glob. Health 2021, 11, 05018.
Allotey, J.; Stallings, E.; Bonet, M.; Yap, M.; Chatterjee, S.; Kew, T.; Debenham, L.; Llavall, A.C.; Dixit, A.; Zhou, D.; et al. Clinical Manifestations, Risk Factors, and Maternal and Perinatal Outcomes of Coronavirus Disease 2019 in Pregnancy: Living Systematic Review and Meta-Analysis. BMJ 2020, 370, m3320.
van Lieshout, L.C.E.W.; Koek, G.H.; Spaanderman, M.A.; van Runnard Heimel, P.J. Placenta Derived Factors Involved in the Pathogenesis of the Liver in the Syndrome of Haemolysis, Elevated Liver Enzymes and Low Platelets (HELLP): A Review. Pregnancy Hypertens. 2019, 18, 42–48.
Conde-Agudelo, A.; Romero, R. SARS-CoV-2 Infection during Pregnancy and Risk of Preeclampsia: A Systematic Review and Meta-Analysis. Am. J. Obs. Gynecol. 2022, 226, 68–89.e3.

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Subjects: Gastroenterology & Hepatology

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Cristina Maria Marginean

Eliza Cinteza

Corina Maria Vasile

Mihaela Popescu

Viorel Biciusca

Anca Oana Docea

Radu Mitrut

Marian Sorin Popescu

Paul Mitrut

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Update Date: 07 Apr 2023

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