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

Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.

Hepatitis B virus (HBV) is the most important causative agent of blood borne hepatitis in humans. Hepatitis D Virus (HDV) infection occurs either as a coinfection or superinfection in HBV carriers. Hepatitis C virus (HCV) is the major cause of transfusion non-A, non-B hepatitis and continues to be a major cause of human liver disease throughout the world. The present study was conducted on 70 clinically diagnosed cases of viral hepatitis to study the prevalence of parenterally transmitted viral hepatitis. The serum samples were tested for HBsAg, HBeAg, IgM anti-HBc, anti-HBe, anti-HCV and anti-HDV using separate ELISA kits. Of the 70 serum samples tested, 28 (40%) were positive for HBsAg out of which 3 (4.28%) were positive for HBeAg also. Five (7.1%) of the HBsAg positive cases tested positive for IgM anti-HBc also. HBsAg alone was found in 17 (24.28%) cases. The prevalence of anti-HCV was 3 (4.28%) in 70 cases. Thus early screening of clinically diagnosed cases of viral hepatitis is essential for establishing diagnosis and treatment to prevent long term sequelae.

Decompensated cirrhosis (DC) is susceptible to infections and sepsis. Neutrophils and monocytes provide the first line of defense to encounter infection. We aimed to evaluate proteins related to neutrophils functionality in sepsis. 70 (DC), 40 with sepsis, 30 without (w/o) sepsis and 15 healthy controls (HC) plasma was analyzed for proteomic analysis, cytokine bead array, endotoxin, cell free DNA and whole blood cells were analyzed for nCD64-mHLADR index, neutrophils-monocytes, functionality and QRT-PCR. nCD64-mHLADR index was significantly increased (p < 0.0001) with decreased HLA-DR expression on total monocytes in sepsis (p = 0.045). Phagocytic activity of both neutrophils and monocytes were significantly decreased in sepsis (p = 0.002 and p = 0.0003). Sepsis plasma stimulated healthy neutrophils, showed significant increase in NETs (neutrophil extracellular traps) and cell free DNA (p = 0.049 and p = 0.04) compared to w/o sepsis and HC. Proteomic analysis revealed upregulated- DNAJC13, TMSB4X, GPI, GSTP1, PNP, ANPEP, COTL1, GCA, APOA1 and PGAM1 while downregulated- AHSG, DEFA1,SERPINA3, MPO, MMRN1and PROS1 proteins (FC > 1.5; p < 0.05) associated to neutrophil activation and autophagy in sepsis. Proteins such as DNAJC13, GPI, GSTP1, PNP, ANPEP, COTL1, PGAM1, PROS1, MPO, SERPINA3 and MMRN1 showed positive correlation with neutrophils activity and number, oxidative burst activity and clinical parameters such as MELD, MELD Na and Bilirubin. Proteomic analysis revealed that faulty functionality of neutrophils may be due to the autophagy proteins i.e., DNAJC13, AHSG, TMSB4X, PROS1 and SERPINA3, which can be used as therapeutic targets in decompensated cirrhosis patients with sepsis.