Incipient primary biliary cirrhosis/autoimmune hepatitis overlap or hepatitic form of primary biliary cirrhosis: a case report

A 42 year old asymptomatic female detected as incipient Primary Biliary Cirrhosis/Autoimmune Hepatitis overlap during routine checkup. The biochemical profile showed evolution from a mildly deranged liver function test in 2004 along with increased erythrocyte sedimentation rate to a 4 times elevation of alkaline phosphatase in 2006 with mildly deranged alanine transaminase. Autoimmune markers demonstrable were Anti mitochondrial antibody M2 and sp100. Histopathology showed dual features, dominant findings were of autoimmune heptatitis. Features consistent with Primary Biliary Cirrhosis were minimal with an occasional portal tract showing paucity of bile ducts and occasional bile duct proliferation. Human leucocyte antigen DR/DQ genotype was as follows: DRB1*03, DRB1*07, DQB1*02, DQB1*04

Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine

BACKGROUND: Patients with HIV infection are at risk of co-infection with HBV, as the routes of transmission are shared and thus immunization with HBV vaccine could be protective in them. The aim of the present study was to assess the efficacy of recombinant vaccine in treatment-naive HIV positive patients and healthy controls, and to dissect out differences if any, in different limbs of immune response. METHODS: Forty HIV positive patients and 20 HIV negative controls, negative for HBsAg, HBsAbs and HBcAbs were vaccinated with three doses of 40μg and 20μg of vaccine respectively. Patients were divided into high CD4 and low CD4 group based on CD4+ lymphocytes of 200 and < 200/mm3 respectively. Group II consisted of healthy controls. Detection of phenotypic markers was done by flowcytometry. Cytokine estimation was done by sandwich ELISA. HBsAbs were estimated in serum by ELISA. RESULTS: After vaccination, CD(4)+, CD(8)+ and CD(3)+ cells increased significantly in all the groups. There was no increase in NK cell activity in patients with high CD(4)+ lymphocytes and only a marginal increase in patients with low CD(4)+ lymphocytes (170 to 293/mm3) whereas a marked increase was observed in controls (252 to 490/mm3). After vaccination, although an increase in memory cells was observed in HIV positive patients, yet HBsAb levels were significantly lower than controls (P < 0.05) indicating a functional defect of memory cells in HIV/AIDS patients. Basal IFN-γ levels were also significantly lower in HIV/AIDS patients (P < 0.01). Although the levels increased after vaccination, the peak level remained lower than in controls. HBsAb titers were much lower in HIV positive patients compared to controls. (High CD(4)+ group: 8834 mIU/ml, low CD(4)+ group: 462 mIU/ml Vs. Controls: 16,906 mIU/ml). IL-4 and IL-10 were low in patients. CONCLUSION: Despite a double dose in patients, IL-4 and IL-10, which regulate antibody response, were also lower in patients, and this together with low CD(4)+ counts and lack of T help, accounted for low HBsAb levels. Vaccination in patients with CD(4)+ lymphocytes < 50/mm(3) was ineffective. Thus early immunization is advocated in all HIV positive patients at a stage when they are still capable of mounting an adequate immune respons

Minimal hepatic encephalopathy: consensus statement of a working party of the Indian National Association for study of the liver

Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30-45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health-related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party

Ranking online consumer reviews

YesProduct reviews are posted online by the hundreds and thousands for popular products. Handling such a large volume of continuously generated online content is a challenging task for buyers, sellers and researchers. The purpose of this study is to rank the overwhelming number of reviews using their predicted helpfulness scores. The helpfulness score is predicted using features extracted from review text, product description, and customer question-answer data of a product using the random-forest classifier and gradient boosting regressor. The system classifies reviews into low or high quality with the random-forest classifier. The helpfulness scores of the high-quality reviews are only predicted using the gradient boosting regressor. The helpfulness scores of the low-quality reviews are not calculated because they are never going to be in the top k reviews. They are just added at the end of the review list to the review-listing website. The proposed system provides fair review placement on review listing pages and makes all high-quality reviews visible to customers on the top. The experimental results on data from two popular Indian e-commerce websites validate our claim, as 3–4 newer high-quality reviews are placed in the top ten reviews along with 5–6 older reviews based on review helpfulness. Our findings indicate that inclusion of features from product description data and customer question-answer data improves the prediction accuracy of the helpfulness score.Ministry of Electronics and Information Technology (MeitY), Government of India for financial support during research work through “Visvesvaraya PhD Scheme for Electronics and IT”

Reevaluation of a North India isolate of hepatitis E virus based on the full-length genomic sequence obtained following long RT-PCR

The genomic cloning and sequence of hepatitis E virus (HEV) from an epidemic in North India is reported. We describe here a simple method wherein the viral RNA was reverse transcribed and then amplified in a single step using an extra long polymerase chain reaction procedure. The full genome nucleotide sequence of this HEV isolate (called Yam-67) was made up of 7191 nucleotides, excepting the poly(A) tail and had three open reading frames: ORF1 coding for 1693 amino acids (aa), ORF2 coding for 659 aa and ORF3 coding for 122 aa. This North Indian isolate of HEV showed close sequence homology to other HEV isolates from India and Asia, but was distant from the Chinese genotype 4, Japanese, Mexican and US isolates. There is no indication from sequence analysis that this may be an atypical strain of HEV, as reported earlier

Viral Proteins Mediate Upregulation of Negative Regulatory Factors Causing Down-Modulated Dendritic Cell Functions In Chronic Hepatitis C Virus Infection

Stunted cellular immune response against a narrow range of epitopes is the hallmark of chronic hepatitis C infection, but the underneath molecular mechanisms have not been well elucidated. Suboptimal antigen presentation through defective antigen presenting cells, have been suggested. The myeloid dendritic cells as professional antigen presenting cells have been found to be phenotypically and functionally defective in chronic hepatitis C-infected patients in our recently published study. In order to find out if the maturation defects in dendritic cells (DC) are induced by the persistence of virus, we tried to differentiate CD14+ monocytes isolated from the peripheral blood of a healthy volunteer in dendritic cell culture medium containing GM-CSF and IL-4 supplemented with hepatitis C virus (HCV) proteins, core and NS5. The results indicated that a lesser number of monocytes differentiated to DC in presence of HCV proteins. Moreover, the differentiated cells depicted immature phenotype, which will not respond to the TLR-4 mediated stimulation ex vivo with significantly lesser upregulation of activation markers, HLA-DR, CD83, CD80 and CD86 as compared to cells differentiated in the absence of HCV proteins. Besides, these immature cells showed characteristics of defective antigen presentation, with significantly lower allostimulatory capacity towards lymphocytes from a healthy donor. Semi-quantitative reverse-transcription polymerase chain reaction (RT- PCR) showed upregulated expression of negative regulatory genes SOCS3, PDL1 and IDO in cells grown in presence of HCV proteins, suggesting the role of HCV and associated antigens in functional down- modulation of dendritic cells. This may correlate with the antigen persistence and maturation-defective status of dendritic cells in chronic HCV infection

Expansion of peripheral and intratumoral regulatory T-cells in hepatocellular carcinoma: A case-control study

Background: Hepatocellular carcinoma (HCC) is notorious for poor prognosis with limited therapeutic options. A better understanding of the role of regulatory T-cells (Tregs) in HCC is important for design of immunotherapy based clinical protocol. The objective of the present study was to evaluate the presence of Tregs in tumor microenvironment in patients with HCC compared to chronic hepatitis (CH). Materials and Methods: The frequency of CD4 + CD25 + Treg cells was evaluated from peripheral blood (PB) of 28 patients of HCC and 30 controls including CH cases and healthy donors using flowcytometry. Intratumoral Treg were also analyzed in tissue samples from 17 HCC cases and 15 CH cases. In addition the expression of FOXP3 and CTLA-4 was also studied by RT-PCR. Results: Frequency of CD4 + CD25 + cells in the PBMCs of HCC cases was significantly higher than in HC (10.8 ± 7.64 vs 3.05 ± 1.30, P < 0.005) and CH patients (2.88 ± 1.92, P < 0.005). Also Treg population was significantly higher in HCC tumor microenvironment compared to CH biopsies (15.8 ± 5.32 vs 5.51 ± 3.40, P < 0.05). Expression of FOXP3 and CTLA-4 was also significantly higher in HCC patients ( P < 0.05) compared to CH group. Conclusions: We provide evidence of an increased population of Treg not only in the PB but also in tumor microenvironment of HCC patients, suggesting association of enhanced Treg activity with poor immune responses to tumor antigens. These findings may in future play a significant role in designing immunotherapeutic approaches in HCC