Hepatitis: Puri P

Anand AC, Puri P. · Army Hospital R & R, New Delhi, India. · Trop Gastroenterol. · Pubmed #18972765 No free full text.

Abstract: Rapid evolution and development in the treatment strategy of chronic hepatitis B (CHB) has taken place in the last decade. Six agents have been so far approved by the FDA for the management of HBV infection including two parenteral drugs (interferon alpha2b and pegylated interferon alpha-2a) and four oral nucleotide/nucleosides (lamivudine, adefovir dipivoxil, entecavir, and telbivudine). The two parenteral drugs have significant side effects and limited rates of HBeAg seroconversion. Lamivudine and Adefovir have been plagued by significant levels of drug resistance.The newer drugs entecavir and telbivudine have been in focus recently with claims of increased potency, with low side effects and lesser drug resistance. While these new drugs are definitely a welcome addition to the family of antiviral drugs against HBV, they are not necessarily a cure for all the evils of their predecessors.

Puri P, Sanyal AJ. · Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University Health System, 1200 East Broad Street, Richmond, VA 23298, USA. · Clin Liver Dis. · Pubmed #17164118 No free full text.

Abstract: Hepatitis C, nonalcoholic fatty liver characterized by hepatic steatosis, and obesity inflict significant health and economic burdens on the Western world. Insulin resistance is the key player in these disease processes. Complex interplay between these conditions results in the ultimate phenotype of liver disease. This article focuses on the current understanding of host and viral interactions as well as on consequent clinical implications.

Anand AC, Puri P. · Department of Medicine, Armed Forces Medical College, Pune, India. · J Gastroenterol Hepatol. · Pubmed #16105116 No free full text.

Abstract: Jaundice is not an unusual accompaniment of malaria. It can occur due to intravascular hemolysis, disseminated intravascular coagulation, and, rarely, 'malarial hepatitis'. Although the primary schizogony of the malarial parasite always leads to the rupture of the infected hepatocyte, alteration of the hepatic functions is uncommonly recorded due to this event. Histologically, the hepatitis or the actual inflammation in the liver has never been demonstrated. Nonetheless, the term 'malarial hepatitis' (MH) has been used in the literature to describe the occurrence of hepatocellular jaundice in patients with Plasmodium falciparum infection. The authors' own data and review of the literature indicate that it is not an uncommon entity. In endemic areas, jaundice is seen in approximately 2.5% of patients with falciparum malaria. It also appears to be a heterogeneous syndrome and one can recognize two clinical subsets. In one group there was an acute, virulent presentation with coma, renal failure and in some cases even hemorrhagic manifestations. It is only in this setting that jaundice signified a 'severe' disease as noted by the World Health Organization action program. This presentation is often confused with acute viral hepatitis and acute hepatic failure in non-endemic areas, but can be clinically differentiated.

Srivastava R, Aggarwal R, Jameel S, Puri P, Gupta VK, Ramesh VS, Bhatia S, Naik S. · Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. · Viral Immunol. · Pubmed #17425421 links to  free full text

Abstract: Hepatitis E virus (HEV) causes acute viral hepatitis and is endemic in the developing world. Few data are available on cellular immune responses in HEV infection. Using flow cytometry, we studied the frequencies of peripheral blood CD4(+) /CD8(+) T cells secreting interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-4 in 21 patients with acute hepatitis E and 18 healthy controls, after stimulation with the HEV capsid (ORF2) protein. Cytokine levels in serum specimens and culture supernatants of ORF2-stimulated peripheral blood mononuclear cells (PBMCs) were estimated in enzyme-linked immunosorbent assays. In addition, cytokine mRNA transcripts were measured in PBMCs by reverse transcription-polymerase chain reaction. In patients with acute hepatitis E, although the total CD4(+) population was expanded, the proportions of CD4(+)/CD69(+) and CD8(+) /CD69(+) cells producing IFN-gamma, TNF-alpha, and IL-4 in response to HEV ORF2 stimulation were unchanged. However, IFN-gamma levels in the supernatants and IFN-gamma mRNA transcripts in cells were elevated in ORF2-stimulated PBMCs in acute hepatitis E; levels of IL-2 or TNF-alpha were unchanged. Our findings suggest that CD4(+) IFN-gamma-secreting cells, which do not belong either to the helper T cell type 1 or type 2 phenotype, as is the case with natural killer T cells, may be involved in the pathogenesis of hepatitis E. Further, the limited immune reactivity we detected in peripheral blood cells may be related to the sequestration of immune events to the intrahepatic compartment, which is the major disease site.

Aggarwal R, Shukla R, Jameel S, Agrawal S, Puri P, Gupta VK, Patil AP, Naik S. · Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. · J Viral Hepat. · Pubmed #17381721 links to  free full text

Abstract: Little data are available on cellular immune responses during infection with hepatitis E virus (HEV). We therefore mapped CD4 T-cell epitopes in open reading frame (ORF)2 and ORF3 proteins of HEV using lymphocyte proliferation assays and overlapping peptide libraries. Proliferation of peripheral blood mononuclear cells from 40 patients with acute hepatitis E and 21 healthy controls with recombinant HEV ORF2 protein or pools of overlapping HEV ORF2/ORF3 peptides was measured. HLA-DQB1 and HLA-DRB1 alleles were also determined. Mononuclear cells from patients with hepatitis E more often showed significant proliferation on stimulation with recombinant ORF2 protein than controls (32/40 vs 7/21), and had higher median (range) stimulation indices [2.6 (0.9-15.2) vs 1.3 (0.6-12.9)]. Peptide pools corresponding to amino acids 73-156, 289-372, 361-444 and 505-588 of HEV ORF2 protein were associated with significant proliferation. Individual peptides in these pools did not show a clear pattern of stimulation. HEV ORF3 peptide pools did not induce proliferative responses. Lymphocyte proliferation in response to the peptide pool corresponding to amino acids 289-372 of HEV ORF2 protein was associated with presence of HLA-DRB1 allele 010X. These data on mapping of T-cell epitopes in HEV proteins may prove useful for designing HEV vaccines and for studying the immunopathogenesis of hepatitis E.

Hooda AK, Puri P, Narula AS, Raychaudhury N, Varghese SJ, Basu A. · Department of Nephrology, Command Hospital, Central Command, Lucknow 226 002, India. · Indian J Gastroenterol. · Pubmed #17264433 No free full text.

Abstract: Fibrosing cholestatic hepatitis (FCH) is a severe and progressive form of liver dysfunction seen in organ transplant recipients and immunosuppressed patients; it is usually associated with hepatitis B virus infection. We report 36-year-old man, a renal transplant recipient, also developed FCH with hepatitis C virus infection and succumbed to it.