Zahid Hussain

King Saud University, Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia

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Publications (17)34.06 Total impact

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    ABSTRACT: Background/Aim. This study aims to investigate whether the SNPs of CXCR1 gene, could predict the likelihood of viral persistence and/or disease progression. Material and methods. We investigated the association of two different SNPs (rs2234671, and rs142978743) in 598 normal healthy controls and 662 HBV patients from a Saudi ethnic population. The HBV patients were categorized into inactive carriers (n = 428), active carriers (n = 162), cirrhosis (n = 54) and Cirrhosis-HCC (n = 18) sub-groups. Genetic variants in CXCR1 were determined by polymerase chain reaction (PCR)-based DNA direct sequencing. Results. The frequency of the risk allele 'C' for the SNP, rs2234671 was found to be insignificant when the patient group was compared to the uninfected control group, however, a significant distribution of the allele 'C' of rs2234671 was observed among active HBV carriers + cirrhosis + cirrhosis - HCC vs. inactive HBV carriers with an OR = 1.631 (95% C.I. 1.016-2.616) and p = 0.032. However, no significant association was observed for rs142978743 when the distribution of risk allele was analyzed among the different patient groups (i.e. inactive carriers, active carriers, cirrhosis and HCC). Furthermore, the most common haplotype, Haplo-1 (AG), was found to have an insignificant frequency distribution between HBV cases and controls, while the same haplotype was found to be significantly distributed when active carriers + cirrhosis + cirrhosis - HCC patients were compared to inactive HBV carriers with a frequency of 0.938 and p = 0.0315. Haplo-2 (AC) was also found to be significantly associated with a frequency of 0.058 and p = 0.0163. Conclusion. The CXCR1 polymorphism, rs2234671 was found to be associated with chronic HBV infection and may play a role in disease activity.
    Annals of hepatology: official journal of the Mexican Association of Hepatology 03/2013; 12(2):220-7. · 1.67 Impact Factor
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    ABSTRACT: DNA methylation is a fundamental epigenetic mechanism in regulating the expression of genes controlling crucial cell functions in cancer development. Gene silencing via CpG island methylation/demethylation in the promoter region is one of the mechanisms by which different genes are inactivated/activated in human cancers. Tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to antagonize matrix metalloproteinase (MMP) activity and to suppress tumor growth, angiogenesis, invasion, and metastasis. TIMP-2 expression has been found to be both upregulated and downregulated in various cancers. The inconsistent TIMP-2 expression and unclear epigenetic regulation lead us to investigate its role in colorectal cancer in the presence of a methylating agent. Highly invasive human colorectal cells SW-620 were treated with the methyl donor S-adenosylmethionine (SAM) and its effect was evaluated by cell proliferation, cell cycle, invasion and migration assay. The ability of SAM to down regulate a panel of activated prometastatic, angiogenesis and growth- and cell cycle-regulatory genes was evaluated using end-point and real-time PCR. Treatment of SW-620 with SAM diminished cell proliferation and altered cell cycle kinetic G2/M phase cell cycle arrest. An in vitro matrigel invasion assay of SAM-treated cells showed a significant reduction in the invasive potential compared to untreated SW-620 cells. Treatment of SW-620 cells with SAM resulted in activation of TIMP-2 and inhibition of the expression of genes such as MMP (MMP-2, MT1-MMP), urokinase plasminogen activator, and vascular endothelial growth factors. The level of expression of tumor suppressor and apoptotic genes was not significantly higher compared to the untreated control. No changes in the levels of expression of genes (growth and cell cycle regulator), such as TGF-β, Smad2, Smad4, and p21 were observed. Our data support the hypothesis that TIMP-2, along with other prometastatic genes, is hypomethylated and expressed differently in colorectal cancer. Further in-depth analysis is warranted to confirm the promoter region CpG methylation pattern of the TIMP-2 gene.
    Genetics and molecular research: GMR 01/2013; 12(2):1106-1118. · 0.99 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) is the major causative agent of chronic liver complications including cirrhosis and hepatocellular carcinoma (HCC). Individuals infected with HBV show a wide spectrum of disease manifestations ranging from asymptomatic carriers to HCC. TLR3 is part of the innate immune system that recognizes double-stranded RNA (dsRNA) and provides early immune response to exogenous antigens. The genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in the TLR3 could be considered as factors for the susceptibility to viral pathogens including HBV. Due to lack of knowledge on the role of TLR3 polymorphisms in HBV infection, this study investigated the distribution of nine SNPs in the TLR3 gene and its association with Saudi Arabian patients infected with HBV. A total of 707 patients and 600 uninfected controls were examined for different parameters including the nine SNPs (rs5743311, rs5743312, rs1879026, rs5743313, rs5743314, rs5743315, rs111611328, rs78726532 and a newly identified SNP located at position 184322913 of chr4). The association analysis confirmed that only one SNP, rs1879026 (G/T), showed a significant difference (P = 0.0480; OR = 0.809, 95% CI = 0.655-0.999) in the distribution between HBV carriers and uninfected controls. While, the rest of the SNPs showed no significant association with regards to HBV infection or in the progression to cirrhosis of the liver and HCC. Furthermore, haplotype analysis revealed that one haplotype GCGA (rs1879026, rs5743313, rs5743314, and rs5743315, respectively), was associated significantly with HBV infection in this population. These findings indicate that genetic variations in the TLR3 gene could affect the outcome of HBV infection among Saudis.
    Journal of Medical Virology 09/2012; 84(9):1353-9. · 2.37 Impact Factor
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    ABSTRACT: Besides the host immune response, genetic and environmental factors play crucial roles in the manifestation of hepatitis B virus (HBV) infection. "Regulated on activation normal T-cell expressed and secreted" factor (RANTES) plays a vital role in CD4(+), CD8(+) T-lymphocyte and dendritic cell activation and proliferation in inflammation. Single nucleotide polymorphisms (SNPs) in the RANTES gene are associated with several viral and non-viral diseases. Association studies have invariably indicated a lack of association between RANTES gene SNPs and HBV infection in ethnic populations, even though RANTES gene SNPs exhibit distinct ethnic distributions. Despite the high prevalence of HBV infections in Saudi Arabia, no studies have been made concerning a possible relationship between RANTES gene polymorphisms and susceptibility to and progression of HBV infection. We examined -403G>A and -28C>G RANTES gene variants in 473 healthy controls and 484 HBV patients in ethnic Saudi populations. Significant differences were found in the genotype and allele distributions of the SNPs between the controls and the HBV patients. Both SNPs were significantly linked to viral clearance in these subjects. Our data demonstrate for the first time in a Saudi population, a relationship between the RANTES gene polymorphisms and the clinical course of HBV infection and underscore the importance of evaluating the genetic background of the affected individual to determine how it may affect disease progression.
    Genetics and molecular research: GMR 01/2012; 11(2):855-62. · 0.99 Impact Factor
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    ABSTRACT: Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population. In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus. Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter. Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%). Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.
    Virology Journal 01/2011; 8:254. · 2.09 Impact Factor
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    ABSTRACT: Patients undergoing hemodialysis are at high risk for Hepatitis C virus infection. Anti-HCV antibody detection is widely used for screening this infection but is not sensitive for window period detection. An ELISA to detect the HCV Core Antigen has recently become available. To investigate the utility of the HCV core Antigen ELISA in the detection of HCV infection in hemodialysis patients and to compare with 3rd generation ELISA validated by real-time PCR. Two hundred fifty hemodialysis patients were included in the study. Anti-HCV antibodies and Total HCVcAg was determined by third generation ELISA kits. HCV RNA was determined using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and sensitivity of the two assays was confirmed by estimating viral load using real-time PCR. Forty-three out of 250 (17.2%) patients were positive for anti-HCV antibodies and HCVcAg. 13/250 (5.2%) were positive for HCVcAg but anti-HCV negative, which is statistically significant (P<0.05). All 13 were confirmed viremic by in-house nested RT-PCR leading to specificity of 100%. Viral load of 49,258+/-28,682 copies/mL were detected in HCVcAg positive cases in comparison to 239,383+/-107,805 copies/mL in the only anti-HCV positive group (P<0.001). False negative cases for HCVcAg assay accounted for 2/250 (0.8%) in which the viral load was 306+/-461 copies/mL which was significantly lower in comparison to HCVcAg positive group (P<0.001, t-test=9.982). Total HCVcAg ELISA is an accurate serological marker for early identification of HCV infection, than is possible by currently used serological assay. It will be useful for patients undergoing hemodialysis who have a longer window period due to immunosuppressed state. It is both a cost-effective and a less labor-intensive alternative to PCR, enhancing its clinical utility.
    Clinical biochemistry 05/2008; 41(7-8):447-52. · 2.02 Impact Factor
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    ABSTRACT: To determine mutations in the SRY gene in two sisters with 46, XY karyotype. Case report. Jamia Millia Islamia, New Delhi, and CSIRO Human Nutrition, Adelaide, Australia. Two sisters aged 23 and 27 years old with primary amenorrhea. Endocrine, mutations in the SRY gene, and DNA binding ability. LH, FSH, and testosterone levels, DNA sequence findings. We found a new point mutation in the SRY gene in patient 1 at position +275 (A>T), which results in amino acid change (K92M). In patient 2, we found a double mutation in the SRY gene at two different loci. The first mutation is a substitution of C at +352, resulting in a change of amino acid (A118P), and second is deletion of T, resulting in a frame shift within a highly conserved DNA-binding motif-high mobility group box at +379 (T127IfsX179). Electrophoretic mobility shift assay showed that mutant K92M and A118P show reduced and greatly reduced binding ability, respectively. These mutations have the potential to interfere with protein-DNA binding activity and nuclear localization necessary for interactions of these proteins with DNA. Our results suggest involvement of the SRY gene in sex reversal, which supports the relationship between SRY alterations, gonadal dysgenesis, and/or primary infertility, and provides further evidence of a high-mobility group box significance in DNA-binding/-bending properties.
    Fertility and sterility 03/2008; 90(4):1199.e1-8. · 3.97 Impact Factor
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    ABSTRACT: Human hepatitis A, a widespread infectious disease that is hyperendemic in vast areas of the world, results in the infection of the liver. Different human HAV strains of diverse geographic origin are remarkably closely related. HAV exploits all known mechanisms of genetic variation to ensure survival, including mutation and genetic recombination. The aim of the study was to undertake an in-depth analysis of the mutation in three groups: (i) mild acute hepatitis (m-AH), (ii) severe acute hepatitis (s-AH), and (iii) fulminant hepatitis (FHF) A patients, who were tested positive for HAV RNA. A total of 500 patients of acute viral hepatitis (AVH) were screened for HAV-IgM positivity from January 2003 to December 2004. HAV RNA positivity was subject to reverse transcription of RNA followed by polymerase chain reaction (RT-PCR) for the detection of HAV RNA. The HAV RNA positive cases were subject to single-stranded conformational polymorphism (SSCP). Out of 500 acute cases of hepatitis, 80 (16%) were positive for HAV-IgM. HAV RNA was detected in 34 (42.5%) cases by RT-PCR. Twenty-four (70.5%) were m-AH, seven (20.5%) were s-AH, and three (8.8%) were FHF. All the positive samples were subject to SSCP. No mobility shift was observed with respect to any screened samples by PCR-SSCP. Four (m-AHI-54, m-AHI-80, s-AHI-341 and FHFI-195 suspected cases were directly sequenced to prove that there was no point mutation. SSCP demonstrates no mobility shift in the VP1/P2A region of the HAV genome. No point mutation was observed in the four suspected cases by sequencing. However a large study from different geographical locations is needed to achieve a logical conclusion about the existence of HAV mutation in the Indian population.
    Digestive Diseases and Sciences 03/2008; 53(2):506-10. · 2.26 Impact Factor
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    Clinical Biochemistry - CLIN BIOCHEM. 01/2008; 41(18):1493-1493.
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    ABSTRACT: Hepatitis B is one of the most important causes of chronic viral hepatitis world wide. Mutations in the precore region of the hepatitis B virus (HBV) genome are frequently found in hepatitis B envelope antigen-negative cases. Data from India on the HBV genotype-associated distribution of precore mutations are limited. Our objective in this study was to genotype and detect the precore mutant with a point mutation from G to A at nucleotide 1896 using ligase chain reaction (LCR) and direct sequencing. A total of 115 cases of chronic liver disease were screened. The cases were evaluated on the basis of history, clinical examination, liver function profile, and serological test for HBV infection, which includes HBsAg, anti HBcIgG, HBeAg using commercially available ELISA kits. The cases, which were HBeAg+, HBeAg-, and HBV DNA+, were subjected to LCR and confirmed by direct sequencing. Of 115 chronic liver disease cases, 50 (43.5%) cases were HBV DNA positive. All cases were subjected to LCR; 11 (22%) cases confirmed the presence of precore mutants, while the remaining 39 (78%) were classified as the wild form of the virus. HBV genotyping by direct sequencing revealed that genotype D was predominant in both wild and mutant forms of the virus. We conclude that the HBV genotype distribution was not significantly different between precore mutants and the wild form of the virus (P>0.05). North Indian patients with genotype D were more likely to have persistent HBV infection with precore mutants. HBV genotypes correlate with the clinical outcome of chronic HBV infection.
    Digestive Diseases and Sciences 02/2007; 52(2):565-9. · 2.26 Impact Factor
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    ABSTRACT: To undertake analysis of hepatitis A viral load, alanine aminotransferase (ALT), and viral genotypes with duration of viremia, and to correlate these parameters with CD4(+)/ CD8(+) lymphocyte populations that control cell-mediated immunity. Cell counts were carried out using fresh whole blood collected in EDTA vials using a fluorescence activated cell sorter. Hepatitis A virus (HAV) RNA was extracted from blood serum, reverse transcribed into cDNA and quantified by Real-Time polymerase chain reaction and was genotyped. Among 11 patients, 10 could be analyzed completely. Of these, 3 had severe acute hepatitis (s-AH) and the remainder had a self-limited acute hepatitis A (AHA), with one patient with fulminant disease (encephalopathy Grade IV) dying on the 4th d. The ALT level was significantly higher both in AHA (1070.9 +/- 894.3; P = 0.0014) and s-AH (1713.9 +/- 886.3; P = 0.001) compared to normal controls (23.6 +/- 7.2). The prothrombin time in s-AH patients (21.0 +/- 2.0; P = 0.02) was significantly higher than in AHA (14.3 +/- 1.1; P = 0.44). The CD4(+)/CD8(+) ratio in AHA patients (1.17 +/- 0.11; P = 0.22) and s-AH (0.83 +/- 0.12; P = 0.0002) were lower than seen in normal healthy controls (1.52). Self-limited cases had peak viral load at the beginning of analysis while in s-AH patients this occurred at the 15th or 30th d. In acute and severe groups, one patient each belonged to genotype IA, with the remaining 8 cases belonging to genotype IIIA. The only fulminant hepatic failure case belonged to genotype IA. HAV viral load and ALT values collected during the entire course of the self-limited infection were directly correlated but this was not the case for s-AH patients. Based on a small-scale study, the persistently higher viral load of s-AH might be due to diminished cellular immunity and hemolysis. The duration of viremia was dependent on the host, as the viral genotype had no apparent role in clinical outcome of AVH and s-AH cases.
    World Journal of Gastroenterology 09/2006; 12(29):4683-8. · 2.55 Impact Factor
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    ABSTRACT: Data from India on hepatitis B virus (HBV) genotype related differences in clinical progression and outcome of acute and fulminant hepatitis B are limited. Sera from patients with acute hepatitis B (AHB) (n=80), fulminant hepatitis B (FHB) (n=40) and asymptomatic HBsAg carriers (ASC) (n=40) were tested for HBV genotype using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and type-specific primers-based PCR (TSP-PCR). The genotype distribution for 160 patients with HBV related hepatitis/carriers were as follows: A, 3/80 (3.7%) in AHB, 2/40 (5%) in FHB and 7/40 (17.5%) in ASC; D, 77/80 (96.2%) in AHB, 38/40 (95%) in FHB and 33/40 (82.5%) in ASC. C, 0; B, 0; E, 0; F, 0 (p<0.01, genotype D versus A). Compared with genotype D, genotype A patients had no significant clinical or biochemical differences (p>0.05). HBV genotypes A and D were found to be prevalent in patients with HBV related acute and fulminant hepatitis from New Delhi, India. Genotype D was the dominant genotype prevalent in all patient categories while genotype A was solely responsible for AHB leading to chronic hepatitis B in 3.7% of the cases from this region.
    Hepatology Research 07/2006; 35(2):79-82. · 2.07 Impact Factor
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    ABSTRACT: Hepatitis A (HAV) is endemic in India and most of the population is infected asymptomatically in early childhood with lifelong immunity. Because of altered epidemiology and decreasing endemicity, the pattern of acute HAV infection is changing from asymptomatic childhood infection to an increased incidence of symptomatic disease in the 18-40 age group. The aims of the present study were to assess whether the proportion of adults with acute HAV infection has been increasing over the years and to analyze the seroprevalence of immunoglobulin G (IgG) anti-HAV antibodies in young adults above the age of 15 years as well as in cases of chronic liver disease. Sera collected from 3495 patients with acute (1932) and chronic (1563) liver disease attending the Medical Outpatient Department of Lok Nayak Hospital during the previous five years (1999-2003) were tested for various serological markers of acute (HBsAg, HBcIgM, anti-HCV, HEV-IgM, and HAV-IgM) and chronic (HBsAg, HBcIgG, HBeAg, and anti-HCV) hepatitis. In addition, 500 normal healthy attendants of the patients above the age of 15 years were tested for IgG anti-HAV as controls. Of 1932 patients with acute viral hepatitis, 221 (11.4%) were positive for immunoglobulin M (IgM) anti-HAV. The patients who were IgM anti-HAV negative included hepatitis B (321 patients), C (39 patients), E (507 patients) and unclassified (844 patients). Although the frequency of HAV infection among children had increased (10.6% to 22.0%) in the 5-year period, the frequency of HAV infection among adults had also increased (3.4% to 12.3%) during the same period. A total of 300 patients with chronic liver diseases that were etiologically related to hepatitis B (169), C (73) or dual infection (10) and alcoholic liver injury (48) were tested for the presence of IgG anti-HAV antibody; 98% (294/300) were positive for the antibody. Although universal vaccination against HAV is not currently indicated, selective vaccination of the high-risk population, based on their serological evidence of HAV antibody, would be a rational and cost-effective approach.
    Journal of Gastroenterology and Hepatology 05/2006; 21(4):689-93. · 3.33 Impact Factor
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    ABSTRACT: (1) To gain information on immune responses to an accelerated schedule of 0, 1, and 2 mo in paramedical staff and BDS students who are at an increased risk of getting hepatitis B infection and come under high risk groups. (2) To assess the efficacy and safety of Enivac-HB in different age groups, using genetically modified yeast strain Pichia pastoris, a new recombinant hepatitis B vaccine developed and manufactured in India. A prospective, comparative, and single blinded trial of rapid (0, 1, and 2 mo) hepatitis B immunization schedule was reported. A total of three hundred and seven (212 females and 95 males) healthy volunteers divided into three age groups (18-29, 30-39, and 40-49) were enrolled after screening for markers of hepatitis B. All the volunteers received 20 mg of the vaccine intramuscularly at 0, 1, and 2 mo. Geometric mean titers were calculated pre and post vaccination. Before immunization the GMT was 0.0124 mIU/mL. One month after the administration of the third dose of recombinant vaccine 296/307 (96.5%) subjects achieved seroprotective levels of anti-HBs. The geometric mean anti-HBs titers achieved after one month of the third dose was 2 560.0 mIU/mL. The geometric mean anti-HBs titer of males was 2 029.0 mIU/mL, while that of the females was 2 759.0 mIU/mL. In the age group of 18-29 years, anti-HBs titer was 3 025.0 mIU/mL, while that in the age group of 30-39 years was 2 096.0 mIU/mL. In third age group of 40-49 years, anti-HBs titer was 1 592.0 mIU/mL. Hyper-responses (anti-HBs> or =100 mIU/mL) were shown in 88.0% (271/307) of subjects. Eleven (3.5%) subjects responded poorly to the vaccine in the age group of 40-49 years. There was only mild pain at the site of injection otherwise there were no other adverse drug reactions (ADRs). This vaccine (Enivac-HB) is safe and efficacious, providing significant protection after the third dose and rapid hepatitis B immunization schedule of 0, 1, and 2 mo can be recommended whenever rapid protection is the goal.
    World Journal of Gastroenterology 12/2005; 11(45):7165-8. · 2.55 Impact Factor
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    ABSTRACT: Viral hepatitis caused by hepatitis A virus (HAV) infection is a worldwide disease; in most cases, it causes an acute self-limited illness. The nucleotide sequence analysis of HAV has classified the virus in seven different genotypes, which include human (I-III and VII) and simian (IV-VI) groups. Most human strains belong to the genotype I, which has been divided into sub-genotypes IA and IB. The present study has been carried out to determine the prevalence of HAV genotypes from northern India and to correlate with their clinical characteristics. Peripheral venous blood collected from 546 cases of acute viral hepatitis was employed for enzyme-linked immunosorbent assays (ELISA) for the serological detection of hepatitis A-C and E viruses. A nested reverse transcription RT-PCR was performed to detect HAV genome, and the positive samples were sequenced to determine the HAV genotypes. Of 73 (13.4%) cases positive for IgM anti-HAV, 29 (39.7%) were positive for HAV RNA. Genotyping was done for 27 (93%) positive cases by direct nucleotide sequencing. Phylogenetic analysis revealed that 15 (55.6%) isolates belonged to genotype 1A, while 12 (44.4%) isolates to IIIA genotype. The results suggest that both genotypes IA and IIIA are almost equally prevalent in northern India. A significant difference was observed with respect to the mean liver-function profile between the IgM anti-HAV-positive and the IgM anti-HAV-negative (includes hepatitis B (153), hepatitis C (57), hepatitis E (153) and unclassified (136)) cases. There is a need for further research on HAV transmission and genotype distribution in Indian sub-continent.
    Hepatology Research 06/2005; 32(1):16-24. · 2.07 Impact Factor
  • Z Hussain, P Kar, S A Husain
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    ABSTRACT: Apart from infectious or viral hepatitis, other most common non-infectious causes of hepatitis are alcohol, cholestatic, drugs and toxic materials. The most common mode that leads to liver injuries is antituberculosis drug-induced hepatitis. The severity of drug-induced liver injury varies from minor nonspecific changes in hepatic structure to fulminant hepatic failure, cirrhosis and liver cancer. Patients receiving antitubercular drug frequently develop acute or chronic hepatitis. The time required for the metabolites to reach hepatotoxic levels is much earlier with isoniazid plus rifampicin treatment than isoniazid alone and this has been shown to be synergistic rather than additive. Antituberculosis drug (ATT)-inducible cytochrome P-4502E1 (CYP2E1) is constitutively expressed in the liver. Recent studies show that polymorphism of the N-acetyltransferase 2 (NAT2) genes and glutathione-S-transferase (GST) are the major susceptibility risk factors for ATT-induced hepatitis. The hepatic NAT and GST are involved in the metabolism of several carcinogenic arylamines and drugs. The NAT2 enzyme has a genetic polymorphism in human. N-acetyltransferase 2 genes (NAT2) have been identified to be responsible for genetic polymorphism of slow and rapid acetylation in humans. Slow acetylators of NAT2 prove to develop more severe hepatotoxicity than rapid acetylators making it a significant risk factor. Deficiency of GST activity, because of homozygous null mutations at GSTM1 and GSTT1 loci, may modulate susceptibility to drug and xenobiotic-induced hepatotoxicity. Polymorphisms at GSTM1, GSTT1 and NAT2 loci had been linked to various forms of liver injury, including hepatocellular carcinoma.
    Indian journal of experimental biology 12/2003; 41(11):1226-32. · 1.20 Impact Factor
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    ABSTRACT: Background/Aims. This study investigated how HBV replication and host immune response are effected by reduced expression of TGF-β1 and HBx. Material and methods. Short interfering RNA (siRNA) knockdown technology has been used to examine the role of TGF-β1 in hepatitis B virus replication. The siTGF-β1 has been transfected along with 1.3mer HBV x-null to investigate the knockdown effect of TGF-β1 on HBV replication and host immune factors. Results. In this study, we found that diminished expression of TGF-β1 and increased expression of HBx enhances HBV replication several folds. The differential expression of TGF-β1 and HBx also stimulated transcriptional viral replicative intermediate (pgRNA) and secretion of core and 'e' antigen at translational level. Consequently, several cytokines such as IL-2, IL-8 and chemokine monocyte- chemoattractant protein (MCP-1) were increased significantly in response to stimulation of HBV replication. In contrast, TNF-α and RANTES mRNA expression increased insignificantly in response to enhanced HBV replication. Conclusions. We concluded that reduced expression of TGF-β1 together with HBx expression stimulate HBV replication and immune response, although the underlying mechanism of stimulation most likely differs.
    Annals of hepatology: official journal of the Mexican Association of Hepatology 12(3):408-15. · 1.67 Impact Factor

Publication Stats

129 Citations
34.06 Total Impact Points

Institutions

  • 2012
    • King Saud University
      • Center of Excellence in Biotechnology Research
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
  • 2003–2011
    • Maulana Azad Medical College
      • Department of Medicine
      New Delhi, NCT, India
  • 2008
    • University of Delhi
      • Department of Medicine
      Delhi, NCT, India