Ajit Sood

ESI Hospital Mumbai, Mumbai, Mahārāshtra, India

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Publications (153)393.99 Total impact

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    ABSTRACT: Both intestinal tuberculosis and Crohn's disease are chronic granulomatous inflammatory diseases of the bowel having overlap of clinical, endoscopic, radiological, and histological features. Differentiating between the two disorders is relevant not only in Asian countries but also in the West. In spite of diagnostic criteria for both diseases being available, still the dilemma of segregating the two diseases remains. Nearly one third of the patients with Crohn's disease may receive anti-tuberculosis treatment also. Diagnosis should be based on the combination of all disease-specific and corroborative evidences.
    Current Gastroenterology Reports 11/2014; 16(11):418.
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    ABSTRACT: Studies in European populations have contributed to a better understanding of the genetics of complex diseases, for example, in coeliac disease (CeD), studies of over 23 000 European samples have reported association to the HLA locus and another 39 loci. However, these associations have not been evaluated in detail in other ethnicities. We sought to better understand how disease-associated loci that have been mapped in Europeans translate to a disease risk for a population with a different ethnic background. We therefore performed a validation of European risk loci for CeD in 497 cases and 736 controls of north Indian origin. Using a dense-genotyping platform (Immunochip), we confirmed the strong association to the HLA region (rs2854275, P=8.2 × 10(-49)). Three loci showed suggestive association (rs4948256, P=9.3 × 10(-7), rs4758538, P=8.6 × 10(-5) and rs17080877, P=2.7 × 10(-5)). We directly replicated five previously reported European variants (P<0.05; mapping to loci harbouring FASLG/TNFSF18, SCHIP1/IL12A, PFKFB3/PRKCQ, ZMIZ1 and ICOSLG). Using a transferability test, we further confirmed association at PFKFB3/PRKCQ (rs2387397, P=2.8 × 10(-4)) and PTPRK/THEMIS (rs55743914, P=3.4 × 10(-4)). The north Indian population has a higher degree of consanguinity than Europeans and we therefore explored the role of recessively acting variants, which replicated the HLA locus (rs9271850, P=3.7 × 10(-23)) and suggested a role of additional four loci. To our knowledge, this is the first replication study of CeD variants in a non-European population.European Journal of Human Genetics advance online publication, 23 July 2014; doi:10.1038/ejhg.2014.137.
    European journal of human genetics: EJHG 07/2014; · 3.56 Impact Factor
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    ABSTRACT: Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.
    Human Genetics 07/2014; · 4.63 Impact Factor
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    ABSTRACT: Globally, around 150 million people are infected with hepatitis C virus (HCV). India contributes a large proportion of this HCV burden. The prevalence of HCV infection in India is estimated at between 0.5% and 1.5%. It is higher in the northeastern part, tribal populations and Punjab, areas which may represent HCV hotspots, and is lower in western and eastern parts of the country. The predominant modes of HCV transmission in India are blood transfusion and unsafe therapeutic injections. There is a need for large field studies to better understand HCV epidemiology and identify high-prevalence areas, and to identify and spread awareness about the modes of transmission of this infection in an attempt to prevent disease transmission.
    Journal of Clinical and Experimental Hepatology. 06/2014; 4(2):106-116.
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    ABSTRACT: The estimated prevalence of hepatitis C virus (HCV) infection in India is between 0.5 and 1.5% with hotspots showing much higher prevalence in some areas of northeast India, in some tribal populations and in certain parts of Punjab. Genotype 3 is the most prevalent type of infection. Recent years have seen development of a large number of new molecules that are revolutionizing the treatment of hepatitis C. Some of the new directly acting agents (DAAs) like sofosbuvir have been called game-changers because they offer the prospect of interferon-free regimens for the treatment of HCV infection. These new drugs have not yet been approved in India and their cost and availability is uncertain at present. Till these drugs become available at an affordable cost, the treatment that was standard of care for the whole world before these newer drugs were approved should continue to be recommended. For India, cheaper options, which are as effective as the standard-of-care (SOC) in carefully selected patients, are also explored to bring treatment within reach of poorer patients. It may be prudent to withhold treatment at present for selected patients with genotype 1 or 4 infection and low levels of fibrosis (F1 or F2), and for patients who are non-responders to initial therapy, interferon intolerant, those with decompensated liver disease, and patients in special populations such as stable patients after liver and kidney transplantation, HIV coinfected patients and those with cirrhosis of liver.
    Journal of Clinical and Experimental Hepatology. 06/2014; 4(2):117–140.
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    ABSTRACT: Over 100 ulcerative colitis (UC) loci have been identified by genome-wide association studies (GWASs) primarily in Caucasians (CEUs). Many of them have weak effects on disease susceptibility, and the bulk of the heritability cannot be ascribed to these loci. Very little is known about the genetic background of UC in non-CEU groups. Here we report the first GWAS on UC in a genetically distinct north Indian (NI) population.
    Gut 05/2014; · 10.73 Impact Factor
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    Gut 04/2014; · 10.73 Impact Factor
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    ABSTRACT: Skin and soft tissue infections (SSTI) are an important cause of morbidity and mortality in patients with cirrhosis. This prospective study aimed to analyze the clinical profile and factors affecting outcome of SSTIs in cirrhotics. All cirrhotics hospitalized between September 2007 and August 2010 were included. Frequency, site, extent, and type of SSTI were noted. Of 1,395 cirrhotics, 19.4 % (n = 271) had bacterial infections, out of which 32.8 % (89/271) had SSTI. Alcohol was the predominant etiological factor for cirrhosis; 95.2 % belonged to Child class B/C, and 67 % gave history of barefoot walking. The most common site of SSTI was the lower limbs (87.1 %), cellulitis was the most common type (61.2 %), and gram-negative bacilli (GNB) is the most common organism (86.7 %). Mortality rate was 23.5 %. Serum creatinine and model for end-stage liver disease (MELD) score were independent predictors of mortality. SSTIs in cirrhotics were common and mostly involved the lower limbs. Cellulitis was the most common type, and GNB was the most common organism. Serum creatinine and MELD score were independent predictors of mortality.
    Indian Journal of Gastroenterology 04/2014;
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    ABSTRACT: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia–Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia. A working group consisting of members from Asia–Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia–Pacific region both in terms of what exists and what needs to be done. The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian–Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized. Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia–Pacific region define extent of problem and get prepared to handle impending epidemic of CD.
    Journal of Gastroenterology and Hepatology 04/2014; 29(4):666-77. · 3.33 Impact Factor
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    ABSTRACT: Results of treatment of chronic hepatitis C (CHC) with pegylated interferon plus ribavirin (PEG-RBV) are mainly available from well-designed clinical trials, and only few 'real-life' studies which give a true picture of success of therapy are available. Such data in Indian patients is scarce. This prospective study aimed to evaluate the efficacy, safety, and factors associated with sustained virological response (SVR) in Indian CHC patients treated with PEG-RBV in 'real-life' setting. All treatment-naïve patients with CHC/compensated cirrhosis treated with PEG-RBV between January 2004 and December 2010 were included. Of 592 patients started on treatment, 524 (88.5 %) completed therapy (mean ± SD age-42.0 ± 12.1 years; 74.3 % males). Genotype 3 (73.6 %) was the commonest, followed by genotype 1 (19.3 %). In intention to treat analysis, SVR rates for 'all' patients, genotype 1 and genotype 3 patients were 72.3 % (428/592), 57 % (65/114), and 78.2 % (341/436), respectively (in per-protocol analysis-81.7 %, 69.1 %, and 85.3 %, respectively). Noncirrhotics had better SVR rates compared to cirrhotics treated for the same duration. About 20 % patients had both low viral load and achieved rapid virological response (RVR). Factors significantly associated with SVR were age <40 years, absence of cirrhosis, RVR, and no reduction in interferon dose. SVR rates in CHC patients treated in 'real-life' setting in India were better than those reported in western population. Therapy should be prolonged for patients with cirrhosis, while one-fifth of patients may qualify for abbreviated therapy. Factors significantly associated with SVR were age <40 years, absence of cirrhosis, RVR, and no reduction in interferon dose.
    Indian Journal of Gastroenterology 03/2014;
  • Journal of Clinical and Experimental Hepatology. 03/2014; 4:S18.
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    ABSTRACT: Recent historical periods in Europe have been characterized by severe epidemic events such as plague, smallpox, or influenza that shaped the immune system of modern populations. This study aims to identify signals of convergent evolution of the immune system, based on the peculiar demographic history in which two populations with different genetic ancestry, Europeans and Rroma (Gypsies), have lived in the same geographic area and have been exposed to similar environments, including infections, during the last millennium. We identified several genes under evolutionary pressure in European/Romanian and Rroma/Gipsy populations, but not in a Northwest Indian population, the geographic origin of the Rroma. Genes in the immune system were highly represented among those under strong evolutionary pressures in Europeans, and infections are likely to have played an important role. For example, Toll-like receptor 1 (TLR1)/TLR6/TLR10 gene cluster showed a strong signal of adaptive selection. Their gene products are functional receptors for Yersinia pestis, the agent of plague, as shown by overexpression studies showing induction of proinflammatory cytokines such as TNF, IL-1β, and IL-6 as one possible infection that may have exerted evolutionary pressures. Immunogenetic analysis showed that TLR1, TLR6, and TLR10 single-nucleotide polymorphisms modulate Y. pestis-induced cytokine responses. Other infections may also have played an important role. Thus, reconstruction of evolutionary history of European populations has identified several immune pathways, among them TLR1/TLR6/TLR10, as being shaped by convergent evolution in two human populations with different origins under the same infectious environment.
    Proceedings of the National Academy of Sciences 02/2014; 111(7):2668-73. · 9.81 Impact Factor
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    ABSTRACT: Studies on water resources and hydrogeology of an area have become much easier with the help of Remote Sensing Technology. As an attempt to evaluate hydrogeology and ground water conditions of the tehsil Talwandi Sabo, Bathinda district, a hydromorphogeological map of the area was prepared through visual interpretation of satellite imagery. The study shows that the study area, a part of the Indo-Gangetic alluvial plain, is occupied by a large number of sand-dune complexes deposited by the ancient Satluj River while traversing the area during the past. Later on reworking of sand-dunes by aeolian action and their physical removal for agricultural purposes resulted in the present landscape of a plain land with sanddune complexes. Unconsolidated Quaternary alluvial sediments consisting of fine to medium-grained sand with admixture of kankar and some clay constitute the aquifer system of the area. Studies show that ground water occurs under both confined and unconfined conditions with water table at shallow depths. But the quality of the ground water is poor to marginal in most of the area except in the vicinity of main canal (Kotla Branch) where water seepage from canals has made the ground water good in quality.
    Journal of the Indian Society of Remote Sensing 01/2014; 23(2):47-56. · 0.53 Impact Factor
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    ABSTRACT: Response to antiviral therapy for hepatitis C virus (HCV) depends upon the genotype and host immune response. IL28b gene mutations have been shown to modulate host antiviral immune response against genotype 1. However, the predictive value of IL28b polymorphism in genotype 3 HCV patients is largely unknown. The association of IL28b polymorphism with virological response was studied in 356 patients with genotype 3 chronic HCV undergoing treatment with peg-interferon and ribavirin and was compared with matched controls. IL28b genotyping followed by DNA sequencing was performed to identify the CC, CT, or TT genotypes. Two log reduction of HCV RNA at Day 7 (Quick Viral Response, QVR) and HCV RNA negativity at Day 28 (Rapid Viral Response, RVR) were analyzed with CC and non-CC genotypes in addition to other predictors of response. The associations of alleles with the response patterns were predicted. Sustained viral response was seen in 250 (70.2%) patients and the IL28b genotype CC/CT/TT distribution was 61.1%; 30.5%; and 8.4%, respectively. The non-CC genotypes were significantly higher in non-responders when compared to responders (67.6% vs. 38.9%, P < 0.001). Interestingly, the rapid viral response in responders was observed in 72.7% with the CC genotype and in 27.2% with the non-CC genotype (P < 0.001). Multivariate analysis showed CC genotype as an independent factor predicting the sustained viral response in patients infected with HCV genotype 3. In conclusion, the IL28b CT/TT genotype strongly correlates with treatment non-response in patients infected with HCV genotype 3 and CC genotype of IL28b is associated with higher quick viral response. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 01/2014; · 2.37 Impact Factor
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    ABSTRACT: Previous studies have attempted to link hygiene hypothesis with IBD. However most of these studies come from developed countries where the level of hygiene is high and universal. Very little data is available from developing countries. The present study explores the truth of hygiene hypotheses and other risk factors for ulcerative colitis (UC) in a North Indian population where the prevalence of UC has been increasing.
    Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology. 01/2014; 27(3):219-223.
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    Annals of gastroenterology : quarterly publication of the Hellenic Society of Gastroenterology. 01/2014; 27(3):284.
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide, with an increased incidence in South Asia. In order to describe the effect of surveillance for HCC with biannual ultrasound and alpha-fetoprotein (AFP) on diagnosis and survival in an Indian population a retrospective cohort-control study was performed at two liver clinics in India. The medical records of 3,258 patients with cirrhosis who received surveillance for HCC were reviewed, and 100 patients who developed HCC identified. Sixty-four cirrhotic patients diagnosed with HCC during the same time period without a history of surveillance were included and survival, BCLC stage at diagnosis, and treatment were compared. Patients who underwent surveillance were more likely to be diagnosed with potentially curable or treatable BCLC Stage 0/A disease and Stage B/C disease respectively, than late Stage D disease (χ2 = 0.0007). Patients diagnosed at an earlier stage of HCC lived significantly longer after diagnosis than patients diagnosed at a later stage (Stage 0/A: 15.6 ± 14.2 months vs. Stage B/C: 9.43 ± 19.7 months vs. Stage D: 5.59 ± 11.9 months; p = 0.0006). While treatment for HCC improved overall survival, only 28% of eligible patients received treatment, explaining the lack of survival benefit noted in the surveillance group. Surveillance for HCC led to detection of HCC at earlier stages. The impact of surveillance on improved mortality could not be evaluated given the limited number of patients who received treatment. HCC surveillance has the potential to improve survival in South Asian patients with cirrhosis only if improvements in access to appropriate treatment are made.
    SpringerPlus 01/2014; 3:610.
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    ABSTRACT: Introduction. Standard treatment for patients with chronic hepatitis C genotype 1 (CHC G-1) infection includes pegylated interferon plus ribavirin (PEG-RBV) for 48 weeks. Shorter treatment regimen would be more acceptable due to lower cost and fewer side-effects. We aimed to compare the efficacy of 36 week PEG-RBV therapy with standard 48 week therapy in CHC G-1 patients who achieve complete early virological response (cEVR). Material and methods. Consecutive treatment-naïve patients with CHC G-1 were treated with pegylated interferon a2b (1.5 μg/kg/week) or α2a (180 μg/week) and weight based ribavirin. Patients who achieved cEVR at 12 weeks [undetectable HCV RNA irrespective of RVR (rapid virological response)] were randomized into- group A (48 weeks therapy) and group B (36 weeks therapy). Primary end-point was achievement of sustained virological response (SVR) at 24 weeks of follow up. Results. Out of the total 166 patients started on treatment, 112 (69.3%) achieved cEVR, and were randomized into group A (n = 59) and group B (n = 53). Fifty-five (93.2%) patients in group A and 50 (94.3%) in group B completed therapy. The overall SVR rate in group A was 79.6% (47/59) and group B was 84.9% (45/53) (p = 0.622). SVR rates in the two groups were comparable in all patient sub-groups according to factors like viral load (≤ or > 400,000 IU/mL), RVR (achieved/not achieved), age (≤ or > 40 years), body mass index (≤ or > 27) and cirrhosis (present/absent). Conclusion. In CHC G-1 patients who achieve cEVR, 36 weeks PEG-RBV therapy is as effective as standard 48 weeks therapy, irrespective of other host or virological factors.
    Annals of hepatology. 01/2014; 13(5):503-509.
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    ABSTRACT: Using the Immunochip for genotyping we identified 39 non-HLA loci associated to celiac disease (CeD), an immune-mediated disease with a worldwide frequency of ∼1%. The most significant non-HLA signal mapped to the intronic region of 70 kb in the LPP gene. Our aim was to fine-map and identify possible functional variants in the LPP locus. We performed a meta-analysis in a cohort of 25,169 individuals from six different populations previously genotyped using Immunochip. Imputation using data from the Genome of the Netherlands and 1000 Genomes projects, followed by meta-analysis, confirmed the strong association signal on the LPP locus (rs2030519, P=1.79x10(-49)), without any novel associations. The conditional analysis on this top SNP indicated association to a single common haplotype. By performing haplotype analyses in each population separately, as well as in a combined group of the four populations that reach the significant threshold after correction (P<0.008), we narrowed down the CeD-associated region from 70 kb to 2.8 kb (P=1.35x10(-44)). By intersecting regulatory data from the ENCODE project, we found a functional SNP, rs4686484 (P=3.12x10(-49)), that maps to several B-cell enhancer elements and a highly conserved region. This SNP was also predicted to change the binding motif of the transcription factors IRF4, IRF11, Nkx2.7 and Nkx2.9, suggesting its role in transcriptional regulation. We later found significantly low levels of LPP mRNA in CeD biopsies compared to controls, thus our results suggest that rs4686484 is the functional variant in this locus, while LPP expression is decreased in CeD.
    Human Molecular Genetics 12/2013; · 7.69 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in all parts of the world. We analyzed the clinical presentation, etiology, and tumor characteristics of HCC presenting to our hospital. All patients diagnosed to have HCC from September 2007 to August 2010 were prospectively enrolled. HCC was diagnosed according to EASL criteria-USG/CT/MRI of the abdomen and/or serum alpha-fetoprotein and/or histology (where indicated). Detailed clinical and laboratory parameters were noted. Barcelona Clinic Liver Cancer (BCLC) staging was done. One hundred and twenty-eight patients (22 females, mean±SD; age, 49.8 ± 10.2 years) were diagnosed to have HCC. Underlying cirrhosis was present in 99.2 %. Hepatitis C virus infection, alone (21.9 %) or with alcohol (22.9 %) was the most common etiological factor, followed by alcohol alone; 33.6 % of the patients had more than one etiological factor. Most patients (83.5 %) presented with features of decompensated cirrhosis. HCC leading to decompensation of cirrhosis was the first presentation of the liver disease in nearly one third of the cases. Serum alpha-fetoprotein was >200 ng/mL in 67.2 % of the patients, while it was normal in 18.7 % of the patients. The mean±SD size of HCC was 5.3 ± 2.9 cm. HCC was multicentric in 57 %, and portal vein thrombosis was present in 34.4 %. About 66 % of the patients belonged to BCLC stage C or D. Hepatitis C virus infection was the most common cause of HCC in Punjab. One-third of the patients had multiple etiological factors and almost all had underlying cirrhosis and presented at advanced stage.
    Indian Journal of Gastroenterology 09/2013;

Publication Stats

1k Citations
393.99 Total Impact Points

Institutions

  • 2014
    • ESI Hospital Mumbai
      Mumbai, Mahārāshtra, India
  • 2006–2014
    • Punjab Remote Sensing Centre
      Ludhiana, Punjab, India
    • Punjab Medical College
      Fyzabad, Uttar Pradesh, India
  • 2002–2014
    • Christian Medical College Ludhiana
      • Department of Gastroenterology
      Ludhiana, Punjab, India
  • 1990–2014
    • Dayanand Medical College & Hospital
      • • Department of Gastroenterology
      • • Department of Medicine
      Ludhiana, Punjab, India
  • 2012
    • All India Institute of Medical Sciences
      New Dilli, NCT, India
  • 2010
    • Groote Schuur Hospital
      Kaapstad, Western Cape, South Africa
  • 2007–2008
    • University of Delhi
      • Department of Genetics
      Delhi, NCT, India
  • 2004
    • Christian Medical College Vellore
      Velluru, Tamil Nādu, India