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Viral hepatitis E is an under‐estimated clinical entity with high mortality (20%–30%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis/acute liver failure and positive for either HEV‐immunoglobulin M (IgM)/HEV‐RNA and 30 pregnant women negative for HEV RNA/IgM/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5 ml blood was collected from the mother for HEV‐RNA. Replicative RNA and viral load in placental tissue were detected through Real‐Time PCR. Placental tissues from the maternal/fetal sides were stained for HEV antigen using HEV‐open reading frame‐2 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)‐1β and IL‐18 cytokine levels using Duo‐R&D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL‐1β and IL‐18 cytokine genes expression.Of the 10 HEV RNA‐positive sera, 9 had HEV RNA either in the maternal/fetal side of the placenta with the mean viral load of 137.4 IU/ml. Of the 10 HEV RNA‐positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL‐1β and IL‐18 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31 ± 4.462 vs. 8.85 ± 4.36 pg/ml; p < 0.0001*** and 2275 ± 536.9 vs. 1085 ± 531.7 pg/ml; p < 0.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra‐hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in HEV‐infected pregnant women might be contributing to the HEV pathogenesis in pregnancy. [ABSTRACT FROM AUTHOR]

Incidental intrahepatic cholangiocarcinoma (iCCA) is a rare neoplastic lesion in the explant liver specimens with an approximate incidence of 0.7%. The detection of iCCA is associated with poor prognosis in the posttransplant setting. The occurrence of a subcentimetric iCCA is very rare and poses a major diagnostic challenge to the pathologist. This article presents a rare case of subcentimetric iCCA in a young male in the background of advanced stage chronic liver disease resulting from autoimmune hepatitis possibly with chronic cholangiopathy along with the histomorphological differentials. [ABSTRACT FROM AUTHOR]

Background Acute exacerbation of Autoimmune Hepatitis (AIH) poses a significant challenge for diagnosis as it can mimic acute viral hepatitis especially in absence of autoantibodies and hypergammaglobulinemia. Aim To determine the clinical, laboratory, histopathological characteristics and response to treatment in AIH patients with acute exacerbation. Methods A retrospective analysis of 16 patients with acute exacerbation of AIH diagnosed over a period of eight years (2008–2016). Results Out of the 111 patients diagnosed with AIH, acute exacerbation of AIH was diagnosed in 16 (14.4%) patients. All patients were females with median age of 35 years. Nine patients (56%) had Type 1 AIH and seven (44%) patients were diagnosed with seronegative AIH. All 16 (100%) patients had acute viral hepatitis like illness at presentation. The median bilirubin was 4.2 mg/dl (range, 2.2–20), aspartate transaminase was 568 IU/L (range, 390–908), alanine transaminase was 430 IU/L (range, 257–1026) and serum alkaline phosphatase was 395 IU/L (range, 112–890) during symptomatic period. The histopathological examination showed underlying chronic hepatitis in 10 (71.4%) patients, only fibrosis in 2 (14.2) patients and cirrhosis with activity in 2 (14.2%). All 16 (100%) patients were treated with a combination of steroids and azathioprine. Thirteen (81%) patients achieved complete biochemical remission and three (19%) patients achieved partial remission out of which one (6%) patient succumbed to illness because of the complications of cirrhosis. Conclusion A suspicion of acute exacerbation of AIH should be considered in patients with unexplained acute hepatitis mimicking acute viral hepatitis in the absence of positive viral markers. Through evaluation with immunoserological markers and liver biopsy can clinch the diagnosis of acute exacerbation of AIH in such cases. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hepatitis is a polygenic disorder of unknown etiology, where genetic factors affect the occurrence and clinical phenotype of the disease. It has been reported as a rare disease entity in the Indian subcontinent. This study was undertaken to investigate the association of HLA alleles with autoimmune hepatitis type 1 and type 2 in north Indian population and to analyze if distinct human leukocyte antigen (HLA) alleles help in characterization of the subtypes of autoimmune hepatitis. Methods: Sixty-eight patients with autoimmune hepatitis and 128 healthy controls were recruited in the study. Out of 68 patients, 55 were diagnosed with autoimmune hepatitis type 1 and 13 with autoimmune hepatitis type 2. The patients and the controls were typed for HLA class II alleles by PCR-SSP method. Results: HLA DRB1*04 and DRB1*08 were found to be significantly associated with autoimmune hepatitis type 1 in north Indian population. It was also observed that DRB1*04, DRB1*13 were significantly associated with pediatric autoimmune hepatitis type 1 and DRB1*08 was significantly associated with adult autoimmune hepatitis type 1. DRB1*14 was significantly associated with autoimmune hepatitis type 2. Conclusion: The study indicates that autoimmune hepatitis in north Indian population is associated with HLA alleles that may help to discriminate the subtypes as autoimmune hepatitis type 1 and type 2. The study also highlights the ethnic variations in the Indian subcontinent in context to the genetic association of HLA with autoimmune diseases. [ABSTRACT FROM AUTHOR]