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ABSTRACT: Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis in several developing countries. Information on cellular immune responses during acute hepatitis E is limited. We therefore studied peripheral blood mononuclear cells (PBMCs) from patients with acute hepatitis E and healthy adult subjects who lacked anti-HEV antibodies for enumeration of various T-cell subsets using flow cytometry and to assess HEV-specific T effector cell responses using interferon-gamma ELISPOT assays. The patients showed increased numbers of CD8(+) cells and CD4(+) CD8(+) cells compared with healthy controls. In addition, the proportion of PBMCs that produced interferon-gamma in response to recombinant HEV open reading frame (ORF) 2 and ORF 3 proteins were found to be higher in patients than in healthy controls. Using pools of 15-mer overlapping peptides corresponding to these recombinant proteins, the immunodominant regions in these proteins for interferon-gamma-producing cells were mapped to regions corresponding to amino acids 181-249 and 301-489 of HEV ORF2 protein. These data provide evidence for the activation of effector T cells during acute hepatitis E. These responses may play a role in viral clearance from the host in patients with HEV infection.
Journal of Viral Hepatitis 10/2011; 18(10):e603-8. · 4.09 Impact Factor
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ABSTRACT: Hepatitis E, which is endemic to resource-poor regions of the world, is largely an acute and self-limiting disease, but some patients have an increased susceptibility to develop fulminant hepatitis. The pathogenesis of hepatitis E in humans is poorly characterized. To understand the metabolic pathways involved in the pathophysiology of hepatitis E, we have used (1) H nuclear magnetic resonance spectroscopy to quantify various metabolites in the plasma and urine of the patients with hepatitis E. These were compared with specimens from patients with acute hepatitis B as disease controls and healthy volunteers. Data were analysed using chemometric statistical methods and metabolite databases. The main metabonomic changes found in patients with hepatitis E, but not in those with hepatitis B, included increased plasma levels of L-isoleucine, acetone, and glycerol, reduced plasma levels of glycine, and reduced urinary levels of imidazole, 3-aminoisobutanoic acid, 1-methylnicotinamide, biopterin, adenosine, 1-methylhistidine, and salicyluric acid. Patients with hepatitis E or B both showed increased levels of plasma and urinary L-proline and decreased levels of various other metabolites. Pathway analysis tools suggest the involvement of glycolysis, tricarboxylic acid cycle, urea cycle, and amino acid metabolism in patients with acute hepatitis E. These findings may help better understand the clinical and biochemical manifestations in this disease and the underlying pathophysiologic processes. Based on our findings, it would be worthwhile determining whether patients with hepatitis E are more prone to develop lactic acidosis and ketosis compared with other forms of viral hepatitis.
Journal of Viral Hepatitis 10/2011; 18(10):e591-602. · 4.09 Impact Factor
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ABSTRACT: Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis in several developing countries but has recently been shown to cause chronic hepatitis in immunosuppressed persons. Other hepatotropic viruses that cause chronic infection have been shown to infect peripheral blood mononuclear cells (PBMCs) and to persist in those cells. We therefore decided to look for evidence of replication of HEV in PBMCs obtained from patients with acute hepatitis E, using strand-specific assays for positive and negative HEV RNA. Of the 44 patients with acute hepatitis E during an outbreak in India, including 27 with detectable IgM anti-HEV and 19 with detectable serum HEV RNA, 11 had detectable HEV RNA in their PBMCs. However, of the six PBMC specimens with strong HEV RNA signal, none had detectable negative-strand HEV RNA, a marker of viral replication. These findings indicate the presence of HEV RNA but the absence of its replication in PBMCs from patients with acute hepatitis E.
Journal of Viral Hepatitis 09/2011; 18(9):668-72. · 4.09 Impact Factor
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ABSTRACT: The mechanism of liver damage in acute hepatitis E is poorly understood. In this study, we assessed the frequency and activation status of natural killer (NK) and natural killer T (NKT) cells and cytotoxic activity of NK cells in the peripheral blood mononuclear cells (PBMCs) obtained from patients with hepatitis E (n = 41) and healthy controls (n = 61). Flow cytometry was used to assess NK (CD3(-)/CD56(+)) and NKT cell (CD3(+)/CD56(+)) fractions (% of PBMCs) and activation status (CD69(+); % of NK, NKT cells). NK cell cytotoxicity was assessed using major histocompatibilities complex-deficient K562 cells as target cells. In 14 patients, the studies were repeated during the convalescence period. Patients had fewer median (range) NK cells [8.9% (2.4-47.0) vs 11.2% (2.6-35.4)] and NKT cells [8.7% (2.8-34.1) vs 13.6% (2.3-36.9)] than controls (P < 0.05 each). Activation markers were present on large proportion of NK cells [43.5% (11.2-58.6) vs 15.5% (3.0-55.8)] and NKT cells [41.5% (17.4-71.1) vs 12.8% (3.3-63.2); P < 0.05 each] from patients. NK cell cytotoxicity was similar in patients and controls. During convalescence, all the parameters normalized. In conclusion, reversible alterations in NK and NKT cell number and activation status during acute hepatitis E suggest a role of these cells in the pathogenesis of this disease.
Journal of Viral Hepatitis 07/2008; 15(12):910-6. · 4.09 Impact Factor
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ABSTRACT: Hepatitis E virus (HEV) is a major cause of acute hepatitis in many developing countries. Based on data from nonendemic regions, an animal reservoir of HEV has been proposed; however, data from HEV-endemic regions are limited. We tested sera from 200 pigs, 98 chickens, 86 goats, 58 sheep and 30 buffaloes for anti-HEV IgG using two different enzyme immunoassays. Specificity of the detected antibodies was confirmed using inhibition assays. Stool specimens from 210 pigs, 94 piglets and 37 sheep were tested for HEV-RNA using nested amplification methods; the polymerase chain reaction products were sequenced and compared with known human and swine HEV sequences. Of the 200 swine sera, 193 and 195, respectively, tested positive in the two assays. All goat sera showed anti-HEV reactivity in both the assays. Inhibition studies confirmed the HEV specificity of antibodies detected in swine and goat sera using both the assays. Sera from sheep, buffalo and chickens also showed high rates of apparent reactivity, but inhibition studies were unable to confirm the specificity of reactions in these species. One faecal specimen showed amplification using Indian swine HEV-specific primers. The genomic sequence of the amplicon from this isolate had only 76-79% nucleotide and 93% amino acid homology with human HEV isolates reported from India and other parts of the world, and most closely resembled swine HEV isolates from other parts of India. Infection with HEV or a related agent is widespread among animals in northern India. However, the swine HEV in India differs genetically from human HEV isolates, indicating that pigs may not play an important role in the spread of human hepatitis E in endemic regions.
Journal of Viral Hepatitis 06/2007; 14(5):310-7. · 4.09 Impact Factor
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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.
Journal of Viral Hepatitis 05/2007; 14(4):283-92. · 4.09 Impact Factor
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ABSTRACT: Though most patients with achalasia cardia (AC) respond to pneumatic dilation (PD), one-third experienced recurrence. Long-term follow-up studies on factors associated with various outcomes are scanty.
In this retrospective study, 126 patients (36.5 +/- 14.6 yr, 76 male) with AC (diagnosed by esophagoscopy, barium esophagogram, and/or manometry) were followed up in person or through mail. The median dysphagia-free duration was calculated by Kaplan-Meier analysis. Factors associated with nonresponse and recurrence after PD were determined using univariate and multivariate analyses.
Symptoms were dysphagia (126, 100%), chest pain (21, 17%), regurgitation (61, 48%), weight loss (33, 26%), and pulmonary symptoms (23, 18%); 5 of 126 (4%) had megaesophagus (> or =7 cm). The mean lower esophageal sphincter (LES) pressure was 38.7 +/- 16.8 mmHg. One hundred and fifteen of 126 (91%) patients responded to PD (90 (71%) to first session); 25 of these had recurrence of dysphagia after 15 +/- 17 months. Post-PD chest pain requiring hospitalization occurred in 21 of 126 (17%; one had an esophageal perforation). Post-PD LES pressure, which was assessed in 48 of 126 patients, had decreased by >50% from baseline in 14 of 29 responders, 0 of 11 nonresponders (p= 0.004, chi(2) test), and 5 of 8 relapsers. The median dysphagia-free duration by Kaplan-Meier analysis was 60 months (SE 2.7, 95% CI 54.7-65.3). On univariate analysis, male gender, pulmonary symptoms (nocturnal coughing spell, history of respiratory infection), absence of chest pain, and failure to achieve a reduction in LES pressure >50% after PD were associated with poor outcome; whereas age, grade of dysphagia, regurgitation, megaesophagus, and LES pressure before PD were not. Male gender was associated with poor outcome by multivariate-analysis.
PD is an effective and safe treatment for AC. Post-PD LES pressure measurement may be helpful in assessing response. Male patients have poorer outcomes following PD.
The American Journal of Gastroenterology 01/2005; 99(12):2304-10. · 7.28 Impact Factor
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ABSTRACT: Motility abnormalities, common in gastroesophageal reflux disease, are likely to be related to endoscopic esophagitis. We studied pH and manometry parameters in relation to the severity of esophagitis. Forty-seven patients with symptomatic gastroesophageal reflux disease for > 3 months were evaluated by: (i) endoscopy (grading of esophagitis by Savary-Miller classification); (ii) mucosal biopsy; (iii) manometry; and (iv) 24-h pH-metry. We found Savary-Miller's grades of: 0 (9 patients out of 47), I (16/47), II (16/47), III (4/47), IV (2/47). Distal esophageal contraction amplitude was lower in severe (grade II to IV) as compared with mild (grade 0 and I) esophagitis (49 [7-182] versus 83 [27-196] mmHg [P = 0.001]). The length and pressure in the lower esophageal sphincter (LES), duration and velocity of contraction in the body, number of episodes of reflux and long-duration reflux, longest reflux, median pH, per cent of time with pH < 4 and DeMeester scores were not significantly different between the two groups. The area under pH 4 showed a negative correlation with LES pressure and amplitude of distal esophageal contractions. We conclude that higher endoscopic grades of esophagitis are associated with lower amplitude of contraction in distal esophagus. Lower LES pressure and distal esophageal contraction amplitude are associated with greater area under curve for pH below 4.
Diseases of the Esophagus 01/2004; 17(1):58-62. · 1.81 Impact Factor
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ABSTRACT: Intrafamilial transmission is rare in epidemic hepatitis E; its frequency in sporadic hepatitis E is not known. We followed up 86 household contacts (age range 4-75 years, mean +/- SD 32.4 +/- 15.8; 49 males), who were family members of patients with acute sporadic hepatitis E. Of the 86 contacts, 68 (79%) tested negative for IgG anti-hepatitis E virus antibodies. Four (4.7%) had IgM anti-hepatitis E virus antibodies at the time of diagnosis of hepatitis E in the index case; two of these contacts possibly had hepatitis E virus infection acquired simultaneously with that in the index case, and two could have had intrafamilial transmission. None developed serological evidence of hepatitis E virus infection over a period of 49 +/- 18 days after the diagnosis of index case, although a majority lacked IgG antibodies to hepatitis E virus and were likely to be susceptible. This suggests that person-to-person transmission is uncommon in sporadic hepatitis E.
Journal of Viral Hepatitis 12/2003; 10(6):446-9. · 4.09 Impact Factor
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ABSTRACT: Hepatitis B virus (HBV) may occasionally be transmitted through transfusion of blood units that are hepatitis B surface antigen (HBsAg) negative but HBV DNA positive. Children with beta-thalassemia are particularly susceptible to HBV because they receive multiple blood transfusions. These children have high infection rates despite vaccination against HBV. Post-vaccination infections may be a result of viruses harbouring surface (S)-gene mutations (e.g. G587A) in a region critical for reactivity to antibody to hepatitis B surface antigen (anti-HBs). The true prevalence of HBV in individuals with beta-thalassemia has not been studied previously.
Seventy patients with beta-thalassemia (median age 6 years; range 8 months to 22 years; 49 male), who had received seven to 623 (median 61) units of blood each and three doses (10/20 micro g) of HBV vaccine (Engerix B) before presentation to us, were included in the study; 50 of the 70 patients had received transfusions prior to vaccination. Enzyme-linked immunoassay for serological markers [HBsAg, antibody to hepatitis B core antigen (anti-HBc) and quantitative anti-HBs] and polymerase chain reaction (PCR) followed by Southern hybridization for molecular detection of hepatitis B, was performed on all samples. The PCR-amplified product was cloned, sequenced and the nucleotide and deduced amino acid sequences for the HBV S and polymerase (P) genes were analysed for mutations.
Four of 70 (5.7%) individuals with beta-thalassemia were HBsAg positive and 14 (20%) were anti-HBc positive. The prevalence of serological markers increased with number of transfusions (P < 0.01). Of 70 patients, 53 (75.7%) had an anti-HBs titre of > 10 IU/l following vaccination and 17 (24.3%) were non-responders (< 10 IU/l); 22 (31.4%) of the 70 were DNA positive. The frequency of HBV infection in beta-thalassemia was similar in vaccine responders and non-responders. The virus was of subtype ayw (genotype D) in the five DNA-positive samples in which a 388-nucleotide region of the S gene was sequenced. Mutations occurred at 13 positions in the S gene and at 10 positions in the P gene. Hydrophobicity plots revealed differences in amino acid regions 117-165 and 195-211. Some of these amino acid substitutions coincided with the putative cytotoxic T-lymphocyte epitopes of both S and P proteins.
A high frequency of HBV infection was seen using molecular methods in thalassemic patients. The frequency of infection was similar in vaccine responders and non-responders. A number of mutations were observed in the S gene, which could have implications for viral replication as well as virus-host cell interaction.
Vox Sanguinis 06/2003; 84(4):292-9. · 2.86 Impact Factor
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ABSTRACT: Coeliac disease is an important cause of chronic diarrhoea, failure to thrive, and anaemia in children. Little information on the disease is available in India. This study was undertaken to determine the prevalence, clinical, anthropometric and histological profiles of coeliac disease in patients attending a tertiary referral centre in India. Coeliac disease was diagnosed in 42 (16.6%) of 246 children with chronic diarrhoea, failure to thrive, and anaemia. The mean ages at onset of symptoms and at diagnosis were 2.4 (range 0.5-10) years and 8.3 (range 3-14) years respectively, and a mean period of delay in diagnosis was 5.9 (range 1-13.5) years. Of the 42 cases, history of failure to thrive was observed in 38 (90%), chronic diarrhoea in 37 (88%), and anaemia in 6 cases. Short stature, under-nutrition, anaemia, oedema of feet, rickets, clubbing of fingers, features of vitamin A deficiency, and B-vitamin deficiency were found in 42, 26, 38, 9, 8, 6, 3, and 2 cases respectively. Onset of symptoms, such as, chronic diarrhoea and failure to thrive, was earlier in children with subtotal villous atrophy than in those with partial villous atrophy (mean +/- SD; 2.00 +/- 1.46 years vs 3.30 +/- 2.72 years; p < 0.05). Results of the study suggest that coeliac disease is not uncommon in Indian children. Coeliac disease should be considered in the differential diagnosis, particularly in children without any symptoms of diarrhoea.
Journal of Health Population and Nutrition 10/2001; 19(3):204-8. · 0.95 Impact Factor
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Indian pediatrics 01/2000; 36(12):1248-50. · 1.05 Impact Factor
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ABSTRACT: Endoscopic injection sclerotherapy (EIS) is known to produce oesophageal structural and motility changes; however, alterations in frequency and severity of gastro-oesophageal reflux (GER) following EIS have not been investigated in detail. We studied 22 patients with cirrhosis and oesophageal varices before EIS and 26 after variceal eradication with intravariceal EIS using manometry and 24 h pH monitoring. The post-EIS group had reduced oesophageal sphincter pressure (19.2+/-11.4 vs 26.1 +/-16.4 mmHg, P< 0.05) and slower velocity of oesophageal peristalsis (2.47+/-0.71 vs 3.06+/-0.77 cm/s, P< 0.01) than the pre-EIS patients. There was no difference in the amplitude or duration of the contraction. Abnormal contraction wave-forms were observed more frequently in post-EIS than in the pre-EIS patients (3/22 vs 12/26, P< 0.05). Various quantitative parameters for GER were not increased in post-EIS compared with pre-EIS patients. Abnormal GER was present in nine of 21 pre-EIS and eight of 17 post-EIS patients (no significant difference). These results suggest that although persistent oesophageal motility changes are frequent after intravariceal EIS, these do not lead to a significant increase in GER.
Journal of Gastroenterology and Hepatology 11/1998; 13(10):1033-8. · 2.87 Impact Factor
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ABSTRACT: Achalasia cardia is usually treated by pneumatic dilation or surgical esophagomyotomy. The role of esophageal manometry for objective assessment of symptom response is controversial.
To study the relationship between symptoms and manometric parameters before and after pneumatic dilation in patients with achalasia cardia.
Sixteen patients with achalasia cardia underwent esophageal manometry before and after undergoing pneumatic dilation. At each time, lower esophageal sphincter (LES) pressure and mean basal esophageal-gastric pressure gradient (MIEP-MIGP) were measured.
Good symptom response was obtained in 12 of 16 patients. Median (range) LES pressure fell from 42 (17-51) mmHg to 18 (8-39) mmHg in those patients with a good response, and from 51 (25-68) mmHg to 29.5 (23-42) mmHg in those who responded poorly. Mean intraesophageal pressure fell below mean intragastric pressure in both the groups.
Esophageal manometry does not correlate with symptom improvement after pneumatic dilation in achalasia cardia. Dysphagia may persist in spite of reversal of the MIEP-MIGP gradient.
Indian Journal of Gastroenterology 02/1998; 17(1):19-21.
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ABSTRACT: We report a woman with intestinal lymphangiectasia whose symptoms were wrongly attributed to pregnancy; the diagnosis was made in the postpartum period. She also developed alopecia and herpes zoster.
Indian Journal of Gastroenterology 11/1997; 16(4):153-4.
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Journal of Hepatology 07/1997; 26(6):1425-6. · 9.26 Impact Factor
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ABSTRACT: We report a woman with achalasia cardia who developed dysphagia for the first time during pregnancy. She was initially mistakenly treated elsewhere as hyperemesis gravidarum. The diagnosis and treatment of achalasia during pregnancy is reviewed.
Indian Journal of Gastroenterology 05/1997; 16(2):72-3.
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ABSTRACT: Colloidal bismuth subcitrate (CBS) causes endoscopic and histological improvement in gastritis and eradication of Helicobacter pylori in patients with non-ulcer dyspepsia (NUD). The effect of sucralfate, a cytoprotective drug, on endoscopic and histologic gastritis and H pylori clearance is not clear. We studied the effect of CBS and sucralfate on these features in patients with NUD.
Sixty three patients with NUD and H pylori infection were randomized to receive one of the following for four weeks: (i) CBS (240 mg twice daily) (Group 1); (ii) placebo I, similar in size, color and shape to CBS (Group 2); (iii) sucralfate (2.0 g twice daily) (Group 3) and (iv) placebo II, similar to sucralfate (Group 4). Symptoms, endoscopic and histological findings and H pylori status were assessed before and after treatment.
Similar symptomatic improvement was observed with each treatment, indicating a placebo effect. Significant endoscopic and histological improvement was observed with CBS only. CBS was better than sucralfate in inducing endoscopic and histological improvement. Clearance rate of H pylori was 46.6% with CBS, 16.6% with its placebo, 33.3% with sucralfate and 13.3% with its placebo.
CBS is more effective than sucralfate in inducing endoscopic and histologic healing of H pylori-related gastritis among NUD patients.
Indian Journal of Gastroenterology 08/1996; 15(3):90-3.
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ABSTRACT: Immunoproliferative small intestinal disease (IPSID) is a poorly recognized cause of malabsorption syndrome in India. Clinicopathological features of five patients with IPSID seen over a two-year period are described. Our data suggest that IPSID is commonly misdiagnosed as intestinal tuberculosis due to lack of awareness and reluctance to obtain small bowel biopsies. Empirical institution of anti-tubercular chemotherapy not only leads to delayed diagnosis but also possibly alters the natural history of the disease, resulting in an intermediate phase of amelioration followed by a terminal phase of lymphomatous transformation. The disease is therefore usually diagnosed at an advanced stage and hence is associated with a relatively poor outcome.
Indian Journal of Gastroenterology 05/1996; 15(2):46-8.
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Endoscopy 11/1995; 27(8):631. · 5.21 Impact Factor
