Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes
Background:. Hepatitis-E virus (HEV)-induced liver failure during pregnancy leads to maternal and fetal complications. This study investigates the HEV-associated metabolomic and immunological changes to elucidate the worsening of obstetric outcomes in patients with acute liver failure (ALF) due to...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Health/LWW
2025-02-01
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| Series: | Hepatology Communications |
| Online Access: | http://journals.lww.com/10.1097/HC9.0000000000000608 |
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| author | Anoushka Saxena Minal Prabhjyoti Pahwa Jaswinder Singh Maras Hamda Siddiqui Jayesh Kumar Sevak Yedla Manikya Mala Shakun Tyagi Shiv K. Sarin Nirupama Trehanpati |
| author_facet | Anoushka Saxena Minal Prabhjyoti Pahwa Jaswinder Singh Maras Hamda Siddiqui Jayesh Kumar Sevak Yedla Manikya Mala Shakun Tyagi Shiv K. Sarin Nirupama Trehanpati |
| author_sort | Anoushka Saxena |
| collection | DOAJ |
| description | Background:. Hepatitis-E virus (HEV)-induced liver failure during pregnancy leads to maternal and fetal complications. This study investigates the HEV-associated metabolomic and immunological changes to elucidate the worsening of obstetric outcomes in patients with acute liver failure (ALF) due to HEV.
Methods:. Pregnant women with (i) acute viral hepatitis, IgM HEV positive (AVH-E, n = 31, Gr.I), (ii) acute liver failure (ALF-E, n = 15, Gr.II), (iii) acute hepatitis but negative for viral infections (non-HEV, n = 30, Gr.III), and healthy (HC, n = 21, Gr.IV) were evaluated at delivery for plasma untargeted metabolomics, cytokine, and immune profiling.
Results:. AVH-E and ALF-E (Gr.I, II) showed elevated TNF-α, IL-1β, IL-9, IL-22, and IL-33 compared to HC. In addition, in ALF-E, IFN-γ and IL-12p70 were decreased, but MIP-1α, fractalkine, SDF-1α, IL-22, and IL-33 were increased compared to AVH-E. Both AVH-E and ALF-E had decreased choline, sn-glycero-3-phosphocholine, O-palmitoyl-r-carnitine, and increased taurocholic acid. However, patients with ALF-E had a 2–5-fold decline in these metabolites with raised taurochenodeoxycholic acid. ALF-E showed increased naive T/B cells, decreased CD4, CD8 Tcm, Tem, and plasmablasts, compared to AVH-E contributing to higher failed inductions, preterm births, maternal complications like eclampsia, disseminated intravascular coagulation, preterm premature rupture of membranes, small-for-gestational-age infants, higher rates of intrauterine death, abortion, and mortality.
Conclusions:. HEV infection reduces choline, phosphocholine, and palmitoyl carnitine, enhancing inflammation in ALF-E, while increasing taurocholic and taurochenodeoxycholic acids impairs the immune response. These factors together likely contribute to severe obstetric complications, including higher failed inductions, intrauterine death, and maternal and fetal mortality in ALF-E. |
| format | Article |
| id | doaj-art-0e2ab3e12fb04192a6faa32efba29053 |
| institution | Kabale University |
| issn | 2471-254X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wolters Kluwer Health/LWW |
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| series | Hepatology Communications |
| spelling | doaj-art-0e2ab3e12fb04192a6faa32efba290532025-02-05T02:10:59ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2025-02-019210.1097/HC9.0000000000000608HC90000000000000608Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomesAnoushka Saxena0Minal1Prabhjyoti Pahwa2Jaswinder Singh Maras3Hamda Siddiqui4Jayesh Kumar Sevak5Yedla Manikya Mala6Shakun Tyagi7Shiv K. Sarin8Nirupama Trehanpati9 1 Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India 2 Department of Obstetrics and Gynaecology, Maulana Azad Medical College, New Delhi, India 1 Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India 1 Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India 1 Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India 1 Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India 2 Department of Obstetrics and Gynaecology, Maulana Azad Medical College, New Delhi, India 2 Department of Obstetrics and Gynaecology, Maulana Azad Medical College, New Delhi, India 3 Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India 1 Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, IndiaBackground:. Hepatitis-E virus (HEV)-induced liver failure during pregnancy leads to maternal and fetal complications. This study investigates the HEV-associated metabolomic and immunological changes to elucidate the worsening of obstetric outcomes in patients with acute liver failure (ALF) due to HEV. Methods:. Pregnant women with (i) acute viral hepatitis, IgM HEV positive (AVH-E, n = 31, Gr.I), (ii) acute liver failure (ALF-E, n = 15, Gr.II), (iii) acute hepatitis but negative for viral infections (non-HEV, n = 30, Gr.III), and healthy (HC, n = 21, Gr.IV) were evaluated at delivery for plasma untargeted metabolomics, cytokine, and immune profiling. Results:. AVH-E and ALF-E (Gr.I, II) showed elevated TNF-α, IL-1β, IL-9, IL-22, and IL-33 compared to HC. In addition, in ALF-E, IFN-γ and IL-12p70 were decreased, but MIP-1α, fractalkine, SDF-1α, IL-22, and IL-33 were increased compared to AVH-E. Both AVH-E and ALF-E had decreased choline, sn-glycero-3-phosphocholine, O-palmitoyl-r-carnitine, and increased taurocholic acid. However, patients with ALF-E had a 2–5-fold decline in these metabolites with raised taurochenodeoxycholic acid. ALF-E showed increased naive T/B cells, decreased CD4, CD8 Tcm, Tem, and plasmablasts, compared to AVH-E contributing to higher failed inductions, preterm births, maternal complications like eclampsia, disseminated intravascular coagulation, preterm premature rupture of membranes, small-for-gestational-age infants, higher rates of intrauterine death, abortion, and mortality. Conclusions:. HEV infection reduces choline, phosphocholine, and palmitoyl carnitine, enhancing inflammation in ALF-E, while increasing taurocholic and taurochenodeoxycholic acids impairs the immune response. These factors together likely contribute to severe obstetric complications, including higher failed inductions, intrauterine death, and maternal and fetal mortality in ALF-E.http://journals.lww.com/10.1097/HC9.0000000000000608 |
| spellingShingle | Anoushka Saxena Minal Prabhjyoti Pahwa Jaswinder Singh Maras Hamda Siddiqui Jayesh Kumar Sevak Yedla Manikya Mala Shakun Tyagi Shiv K. Sarin Nirupama Trehanpati Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes Hepatology Communications |
| title | Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes |
| title_full | Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes |
| title_fullStr | Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes |
| title_full_unstemmed | Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes |
| title_short | Immune-metabolic shifts in acute liver failure caused by HEV infection during pregnancy and their association with obstetric outcomes |
| title_sort | immune metabolic shifts in acute liver failure caused by hev infection during pregnancy and their association with obstetric outcomes |
| url | http://journals.lww.com/10.1097/HC9.0000000000000608 |
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