Hepatitis E virus infection and fulminant hepatic failure during pregnancy

Jilani, Nishat; Das, Bhudev C.; Husain, Syed Akhtar; Baweja, U; Chattopadhya, D; Gupta, Ram Kumar; Sardana, Sarita; Kar, Premashis

doi:10.1111/j.1440-1746.2007.04913.x

Cited by 211 publications

(209 citation statements)

References 39 publications

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“…It is well established that T-cell-mediated immunity is highly decreased during pregnancy owing to marked reduction in T-cells and increased B cell counts (26)(27)(28). Recently, low CD4 and high CD8 T-cell counts and a decreased CD4/CD8 ratio leading to a low or loss of immunity in pregnant women was demonstrated (29). This finding indicates that HEV infection induces high production of CD8 cells, which appear to be recognized by specific viral proteins that are expressed specifically in liver cells ( Figure 8).…”

Section: Discussionmentioning

confidence: 99%

Selective Suppression of NF-kBp65 in Hepatitis Virus-Infected Pregnant Women Manifesting Severe Liver Damage and High Mortality

Prusty

Hedau

Singh

et al. 2007

Mol Med

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Fulminant hepatitis in Asian pregnant women is generally caused by hepatitis E virus infection, and extremely high mortality is most common in them. Decreased cell-mediated immunity is considered a major cause of death in these cases, but what exactly influences decreased immunity and high mortality specifically during pregnancy is not known. We used electrophoretic mobility shift assays, immunoblotting, and immunohistochemical analysis to study the expression and DNA binding activity of NF-kB p50 and NF-kB p65 in pregnant fulminant hepatic failure (FHF) patients and compared them with their nonpregnant counterparts. In both PBMC and postmortem liver biopsy specimens the DNA-binding activity of NF-kB was very high in samples from pregnant FHF patients compared with those from nonpregnant women as well as pregnant women with acute viral hepatitis (AVH) without FHF. Further dissection of the NF-kB complex in supershift assays demonstrated complete absence of p65 in the NF-kB complex, which is formed by homodimerization of the p50 component in pregnant FHF patients. Western blotting and immunohistochemical analysis of the expression of p50 and p65 proteins both showed higher levels of p50 expression and a complete absence or a minimal expression of p65, indicating its nonparticipation in NF-kB-dependent transactivation in pregnant FHF patients. We suggest that the exclusion of p65 from the NF-kB transactivation complex seems to be a crucial step that may cause deregulated immunity and severe liver damage, leading to the death of the patient. Our findings provide a molecular basis, for developing novel therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Selective Suppression of NF-kBp65 in Hepatitis Virus-Infected Pregnant Women Manifesting Severe Liver Damage and High Mortality

Prusty

Hedau

Singh

et al. 2007

Mol Med

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“…18-20 CCL 4 -treated animal models of ALF also illustrated the recruitment of circulatory monocyte-and macrophage-associated damage. 18 Induction of M2-like macrophages in the liver is also associated with liver fibrosis and necrosis in ALF resulting from hepatitis B virus (HBV) infection.…”

mentioning

confidence: 93%

Impaired monocyte‐macrophage functions and defective toll‐like receptor signaling in hepatitis E virus‐infected pregnant women with acute liver failure

et al. 2015

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Acute viral hepatitis resulting due to hepatitis E viral infection (AVH-E) is often serious in pregnancy and could result in acute liver failure (ALF). The role of monocytes and macrophages (mono-macs) in the pathogenesis of AVH-E and development of ALF-E in pregnancy is unclear. We investigated the functions of mono-macs in pregnant (P), AVH-E (n 5 44), ALF-E (n 5 12), healthy controls (HC; n 5 20) and compared with nonpregnant (NP) AVH-E (n 5 10), ALF-E (n 5 5), and HC (n 5 10). We also recruited non-hepatitis E virus-related pregnant (P), ALF-NE (n 5 5) and non-pregnant (NP), ALF-NE (n 5 12) patients with ALF. Mono-macs, dendritic cell (DC) phenotypes, and Toll-like receptor (TLR) expressions were studied by flow cytometry and reverse-transcriptase polymerase chain reaction. Mono-macs functionality was determined by analyzing their phagocytic activity and reactive oxygen species (ROS) generation by using flow cytometry. Frequency of mono-macs and DCs was increased during HEV infection compared to HC (P < 0.001). Macrophages were increased (P < 0.002) in ALF-E(P) compared to ALF-NE(P). The macrophage phagocytic activity and Escherichia coli-induced ROS production was significantly impaired in ALF-E(P) compared to AVH-E(P) (P < 0.001), ALF-E(NP), and ALF-NE(P) patients (P < 0.02). TLR3 and TLR9 expression and downstream MYD88 signalling molecules IRF3 and IRF7 were significantly down-regulated in ALF-E(P) (P < 0.00) compared to AVH-E(P) and ALF-NE(P). Conclusion: Functionality of mono-macs is impaired in pregnant ALF-E patients compared to AVH-E(P). Reduced TLR3 and TLR7 expression and TLR downstream-signaling molecules in pregnant ALF-E patients suggests inadequate triggers for the innate immune responses contributing to development and severity of ALF-E. Studies using TLR agonists to activate mono-macs may be of use and in vitro studies should be undertaken using patient samples. (HEPATOLOGY

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“…64 In human studies which include HEV infected pregnant females, a decrease in peripheral CD4 count with increase in CD8 count and altered CD4/ CD8 ratio have been documented. 65 Further, human studies have also documented increase in levels of Th2 associated cytokines (IL4, IL5, IL10 and IL13) and in-vitro obtunded lymphoproliferative response subsequent to nonspecific mitogens like phytohemagglutinin (PHA). 66 These documentations logically indicate that during pregnancy immune responses get altered, particularly to viral infections and make pregnant females susceptible to such infections.…”

Section: Malnutritionmentioning

confidence: 99%