Background: Various environmental factors have been reported to play key role in the development ... more Background: Various environmental factors have been reported to play key role in the development of oral squamous cell carcinoma (OSCC). A lesser known risk factor of oral cancer in India is the uncontrolled use of areca nut chewing. In North-East India, Areca nut, locally called as “Tamol” in Assam, is raw betel nut, lime and betel leaf without tobacco, which are more effective as compared to dried which can be the important contributing factor for OSCC. Objectives: The aim of the study was to detect the association between XRCC1 polymorphisms and increased risk of OSCC in tamol chewers population in Assam, India. Methods: 50 OSCC patients, 50 tamol chewers and 50 controls were enrolled in the study. XRCC1 Arg399Gln polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: There was a significant association for XRCC1 codon 399 (Arg/Gln+Gln/Gln) (p<0.05; OR=1.909, CI= 0.8622- 4.227) with the wild type in cancer...
Objective: Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality i... more Objective: Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in the world. Numerous genomic and proteomic studies have been carried out across the globe to understand cancer biology related to HCC. Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is also known as cluster of differentiation 209. The current study was designed to investigate the association of mutation in DC-SIGN promoter region in HCC patients and healthy controls and to analyze the association of these mutations as a risk factor for HCC development from India. Materials and Methods: total of 40 cases of HCC and 40 healthy controls without any underlying liver diseases were included in the study. A total of 5 ml of peripheral blood samples were collected, and genomic DNA was isolated using phenol–chloroform method. Polymerase chain reaction amplification was carried out for DC gene, and the amplicons were subjected to direct sequencing (Macrogen, Korea). Mutations were analyzed comparing these sequences with those published sequences from the database using bioinformatics software. Results: A total of eight point mutations were observed in the HCC cases. The natures of mutation observed were deletion, transition, and transversion. All mutations were located in the 19th chromosome at nine different loci (51,079, 51,493, 51,561, 51,124, 51,125, 51,127, 51,169, 51,170, and 51,172). Conclusion: Mutation in the promoter region of the DC-SIGN gene may be a possible risk factor for the development of HCC in India. The findings of the study reveal the possible role of these mutants with HCC, and future large-scale prospective studies will further validate the findings of the current study.
Asian Pacific journal of cancer prevention : APJCP, Jan 26, 2018
Background/objective: HCC is a multistep process starting from chronic hepatitis that progress th... more Background/objective: HCC is a multistep process starting from chronic hepatitis that progress through cirrhosis to HCC. MicroRNA expression level was found to be deregulated in HCC. To find out whether the expression level of miR-34a and miR-183 was deregulated in HCC compared to controls without HCC. Methods: Real time quantitative PCR was done to find out the miRNA expression level in terms of Ct value followed by statistical analysis. Results: Over-expression of miR-183 and under-expression of miR-34a in HCC was detected. All changes in expression level of miR-34a and miR-183 were found to be due to HCC compared to controls without HCC. So both miR-34a and miR-183 were suitable to differentiate HCC from Cirrhosis and chronic hepatitis with an efficient diagnostic power of sensitivity, specificity and expression level. But they might not have any role in patients’ survival. Conclusion: miR- 34a and miR-183 might be considered as potential markers of HCC screening molecule in addi...
Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer death. Methylenetetra... more Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer death. Methylenetetrahydrofolate reductase (MTHFR) plays an role in processing amino acids in proteins. This study is designed with an aim to find out whether the mutations or single nucleotide polymorphism (SNPs) in the MTHFR gene could be one of the factors of HCC. 105 cases of HCC and 240 controls were enrolled. Serological and biological status for all the cases and controls were assessed using peripheral blood. Genomic DNA was isolated followed by PCR amplification of polymorphic sites of MTHFR A1298C and MTHFR C677T followed by RFLP. Amplification success was monitored and verified by 2.5-3% agarose gel electrophoresis. Statistical analysis has been performed in all the cases and controls. Mean ages (± SD) of HCC and controls were 56.55 (± 10.53) and 48.1 (±10.6) years, respectively. AA, AC, CC genotype of MTHFR A1298C was found in 12 of 105, 9 of 105 and 80 of 105 in HCC, 58 of 240, 26 of 240 and 153 ...
This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepati... more This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol as risk factors in a cohort of hepatocellular carcinoma (HCC) patients from India. The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated. A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona-2000 EASL conference were included in the study. The blood samples were evaluated for serological evidence of HBV and HCV infection, viral load, and genotypes using serological tests, reverse transcription-polymerase chain reaction, and restriction fragment length polymorphism. The male/female ratio for the HCC cases was 5.87:1. Majority of the HCC patients (33.9%) were 50 to 59 years of age, with a mean age of 4±13.23 years. More than half the cases (60.8%) had underlying cirrhosis at presentation. Among the HCC patients, 68.9% were HBV related, 21.3% were HCV related, 18.8% were al...
Sir, Most adults infected with hepatitis B virus (HBV) recover and develop protective antibodies.... more Sir, Most adults infected with hepatitis B virus (HBV) recover and develop protective antibodies. However, approximately 5 per cent of adults remain chronically infected with HBV and are at risk for developing end-stage liver disease and hepatocellular carcinoma1. Chemokine receptor 5 (CCR5) is a gene located on short (p) arm at position 21 on chromosome2. CCR5 is critical in regulating T cell functions by mediating recruitment, polarization, activation and differentiation of type 1 cytokine secreting T helper and cytotoxic T cells. A 32 bp deletion in the coding region of CCR5 gene leads to complete loss of the functional CCR5 protein synthesis. This mutation was found to be associated with reduced risk of HIV susceptibility3. CCR5 deficiency is particularly intriguing because it offers a potential means to enhance the T-cell response to HBV by blocking CCR5. CCR5Δ32 homozygous mutation is known to provide genetic protection against HBV persistence4. So, we hypothesize that CCR5Δ32 heterozygous mutation may have an additive effect in nucleoside analogue treatment response in chronic HBV patients so that simultaneous administration of a CCR5 blocking agent, along with an anti-HBV agent may increase HBV clearance through augmentation of the T-cell response to HBV antigens. This pilot study was designed to analyze the CCR5 polymorphism in chronic HBV patients with respect to HBV DNA clearance following treatment using different types of nucleos(t)ide analogues (lamivudine/adefovir/telbuvidine). The study was conducted in the Department of Medicine, Maulana Azad Medical College (MAMC), New Delhi, India during 2008-10. The study protocol was approved by the ethics committee of MAMC and prior written informed consent was taken from each patient. The study group consisted of 45 consecutive chronic hepatitis B patients; 15 new patients and 30 patients from our previous study5. Test for liver functions, serological tests for hepatitis B surface antigen (HBsAg), anti-HBe (antibody to hepatitis B e antigen), HBeAg, anti-Hbc IgG (IgG antibody against HBV core antigen), anti-HCV, HBV DNA and HBV viral load were assessed at baseline for inclusion of patients and after treatment. Liver biopsy was done in all patients to assess severity of disease before the start of therapy and at the end of 6 months and assessed as described earlier5. The biopsy specimens were scored according to the original criteria of Knodell histological activity index (HAI)6. HBV DNA was extracted from serum by using the standard phenol chloroform method. Detection of HBV DNA was carried out using primers as described earlier7 to amplify part of the surface gene. Hepatitis B viral load estimations were performed by real time PCR (RT-PCR) method5. A 204 bp fragment denotes the CCR5 wild type allele while a 172 bp fragment denotes the CCR5∆32 mutant allele. The patients included were conveniently selected to receive either lamivudine or adefovir or telbivudine (100, 10 and 600 mg, respectively) daily for a period of six months (15 patients in each group). Qualitative values were correlated with Chi-square or Fisher exact tests. P<0.05 was considered statistically significant. Quantitative values are expressed as means and ranges, and were compared using the Student's t-test or the Mann-Whitney non-parametric U test. There was a significant reduction in the serum alanine aminotransferase (ALT in IU/l) levels after treatment for six months (P<0.0001) as compared to baseline values, and results were similar in all drug groups. Compared to baseline, there was a significant (P<0.05) reduction in total bilirubin (mg/dl) levels which was also similar in all drug groups. All the patients remained HBsAg positive at the end of 6 months in all the groups. Four (8.89%) patients seroconverted from HBeAg positive to negative state. Ten of 45 (22.22%) patients became HBV DNA negative, which included four patients each in the adefovir and telbivudine group while two patients in the lamivudine group. There was significant (P<0.001) reduction in serum viral load after six months of therapy; the mean reduction was 1.92, 2.06 and 2.65 log copies per ml with respect to serum HBV DNA adefovir, lamivudine and telbivudine groups, respectively. There was a non significant reduction with respect to HAI score and fibrosis score after treatment for six months and the results were similar in all the drug groups. Of the 45 patients, five (11.11%) were found to have CCR5Δ32 heterozygous (+/-) genotype and the remaining 40 patients (88.8%) were of CCR5 (+/+) genotype. Of the four patients who seroconverted from HBeAg positive to negative state, CCR5Δ32 (+/-) mutation was found in two patients. The frequency of CCR5Δ32 mutations did not relate with biochemical, virological and histological parameters. There was no difference in response to therapy when patients were categorized on the basis of the response pattern with respect to different drug groups, and the distribution of…
To study the role of heat shock protein A1L (HSPA1L) and A1B (HSPA1B) polymorphisms and subsequen... more To study the role of heat shock protein A1L (HSPA1L) and A1B (HSPA1B) polymorphisms and subsequent risk of hepatocellular carcinoma (HCC) in India. Subjects enrolled included 185 cases of HCC, 182 cases of chronic hepatitis (CH) and 200 healthy controls. Genomic DNA was typed for HSPA1L2437 and HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. Other risk factors were also analysed. Hepatitis B virus (HBV) infection, older age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;35 years and high aflatoxin level in urine increased the risk of HCC. The frequencies of HSPA1L BB genotype and B allele in HCC were more than in CH [odds ratio (OR): 9.83; P = 0.000], but also in HBV-related HCC than Chronic Hepatitis B (CHB) [OR: 3.44; P = 0.004] and HCV-related HCC compared to CHC [OR: 6.32; P = 0.010]. The frequency of HSPA1B genotype in the homozygous state was more in CH [OR: 6.01; P = 0.001] and is a good marker to predict the risk of HCV-related CH (CHC) compared to controls. HCV-related HCC has a higher frequency of the B allele of HSPA1B than healthy controls [OR: 3.95; P = 0.000] and CHC [OR: 2.35; P = 0.000], respectively. The frequencies increased further significantly in CHC compared to healthy controls [OR: 9.26; P = 0.000]. The risk for the development of CH and HCC compared to healthy controls irrespective of the aetiology was significant in terms of the HSPA1B marker than HSPA1L in the Indian population.
The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regi... more The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P…
Background: Various environmental factors have been reported to play key role in the development ... more Background: Various environmental factors have been reported to play key role in the development of oral squamous cell carcinoma (OSCC). A lesser known risk factor of oral cancer in India is the uncontrolled use of areca nut chewing. In North-East India, Areca nut, locally called as “Tamol” in Assam, is raw betel nut, lime and betel leaf without tobacco, which are more effective as compared to dried which can be the important contributing factor for OSCC. Objectives: The aim of the study was to detect the association between XRCC1 polymorphisms and increased risk of OSCC in tamol chewers population in Assam, India. Methods: 50 OSCC patients, 50 tamol chewers and 50 controls were enrolled in the study. XRCC1 Arg399Gln polymorphisms were determined by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: There was a significant association for XRCC1 codon 399 (Arg/Gln+Gln/Gln) (p<0.05; OR=1.909, CI= 0.8622- 4.227) with the wild type in cancer...
Objective: Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality i... more Objective: Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in the world. Numerous genomic and proteomic studies have been carried out across the globe to understand cancer biology related to HCC. Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is also known as cluster of differentiation 209. The current study was designed to investigate the association of mutation in DC-SIGN promoter region in HCC patients and healthy controls and to analyze the association of these mutations as a risk factor for HCC development from India. Materials and Methods: total of 40 cases of HCC and 40 healthy controls without any underlying liver diseases were included in the study. A total of 5 ml of peripheral blood samples were collected, and genomic DNA was isolated using phenol–chloroform method. Polymerase chain reaction amplification was carried out for DC gene, and the amplicons were subjected to direct sequencing (Macrogen, Korea). Mutations were analyzed comparing these sequences with those published sequences from the database using bioinformatics software. Results: A total of eight point mutations were observed in the HCC cases. The natures of mutation observed were deletion, transition, and transversion. All mutations were located in the 19th chromosome at nine different loci (51,079, 51,493, 51,561, 51,124, 51,125, 51,127, 51,169, 51,170, and 51,172). Conclusion: Mutation in the promoter region of the DC-SIGN gene may be a possible risk factor for the development of HCC in India. The findings of the study reveal the possible role of these mutants with HCC, and future large-scale prospective studies will further validate the findings of the current study.
Asian Pacific journal of cancer prevention : APJCP, Jan 26, 2018
Background/objective: HCC is a multistep process starting from chronic hepatitis that progress th... more Background/objective: HCC is a multistep process starting from chronic hepatitis that progress through cirrhosis to HCC. MicroRNA expression level was found to be deregulated in HCC. To find out whether the expression level of miR-34a and miR-183 was deregulated in HCC compared to controls without HCC. Methods: Real time quantitative PCR was done to find out the miRNA expression level in terms of Ct value followed by statistical analysis. Results: Over-expression of miR-183 and under-expression of miR-34a in HCC was detected. All changes in expression level of miR-34a and miR-183 were found to be due to HCC compared to controls without HCC. So both miR-34a and miR-183 were suitable to differentiate HCC from Cirrhosis and chronic hepatitis with an efficient diagnostic power of sensitivity, specificity and expression level. But they might not have any role in patients’ survival. Conclusion: miR- 34a and miR-183 might be considered as potential markers of HCC screening molecule in addi...
Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer death. Methylenetetra... more Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer death. Methylenetetrahydrofolate reductase (MTHFR) plays an role in processing amino acids in proteins. This study is designed with an aim to find out whether the mutations or single nucleotide polymorphism (SNPs) in the MTHFR gene could be one of the factors of HCC. 105 cases of HCC and 240 controls were enrolled. Serological and biological status for all the cases and controls were assessed using peripheral blood. Genomic DNA was isolated followed by PCR amplification of polymorphic sites of MTHFR A1298C and MTHFR C677T followed by RFLP. Amplification success was monitored and verified by 2.5-3% agarose gel electrophoresis. Statistical analysis has been performed in all the cases and controls. Mean ages (± SD) of HCC and controls were 56.55 (± 10.53) and 48.1 (±10.6) years, respectively. AA, AC, CC genotype of MTHFR A1298C was found in 12 of 105, 9 of 105 and 80 of 105 in HCC, 58 of 240, 26 of 240 and 153 ...
This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepati... more This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol as risk factors in a cohort of hepatocellular carcinoma (HCC) patients from India. The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated. A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona-2000 EASL conference were included in the study. The blood samples were evaluated for serological evidence of HBV and HCV infection, viral load, and genotypes using serological tests, reverse transcription-polymerase chain reaction, and restriction fragment length polymorphism. The male/female ratio for the HCC cases was 5.87:1. Majority of the HCC patients (33.9%) were 50 to 59 years of age, with a mean age of 4±13.23 years. More than half the cases (60.8%) had underlying cirrhosis at presentation. Among the HCC patients, 68.9% were HBV related, 21.3% were HCV related, 18.8% were al...
Sir, Most adults infected with hepatitis B virus (HBV) recover and develop protective antibodies.... more Sir, Most adults infected with hepatitis B virus (HBV) recover and develop protective antibodies. However, approximately 5 per cent of adults remain chronically infected with HBV and are at risk for developing end-stage liver disease and hepatocellular carcinoma1. Chemokine receptor 5 (CCR5) is a gene located on short (p) arm at position 21 on chromosome2. CCR5 is critical in regulating T cell functions by mediating recruitment, polarization, activation and differentiation of type 1 cytokine secreting T helper and cytotoxic T cells. A 32 bp deletion in the coding region of CCR5 gene leads to complete loss of the functional CCR5 protein synthesis. This mutation was found to be associated with reduced risk of HIV susceptibility3. CCR5 deficiency is particularly intriguing because it offers a potential means to enhance the T-cell response to HBV by blocking CCR5. CCR5Δ32 homozygous mutation is known to provide genetic protection against HBV persistence4. So, we hypothesize that CCR5Δ32 heterozygous mutation may have an additive effect in nucleoside analogue treatment response in chronic HBV patients so that simultaneous administration of a CCR5 blocking agent, along with an anti-HBV agent may increase HBV clearance through augmentation of the T-cell response to HBV antigens. This pilot study was designed to analyze the CCR5 polymorphism in chronic HBV patients with respect to HBV DNA clearance following treatment using different types of nucleos(t)ide analogues (lamivudine/adefovir/telbuvidine). The study was conducted in the Department of Medicine, Maulana Azad Medical College (MAMC), New Delhi, India during 2008-10. The study protocol was approved by the ethics committee of MAMC and prior written informed consent was taken from each patient. The study group consisted of 45 consecutive chronic hepatitis B patients; 15 new patients and 30 patients from our previous study5. Test for liver functions, serological tests for hepatitis B surface antigen (HBsAg), anti-HBe (antibody to hepatitis B e antigen), HBeAg, anti-Hbc IgG (IgG antibody against HBV core antigen), anti-HCV, HBV DNA and HBV viral load were assessed at baseline for inclusion of patients and after treatment. Liver biopsy was done in all patients to assess severity of disease before the start of therapy and at the end of 6 months and assessed as described earlier5. The biopsy specimens were scored according to the original criteria of Knodell histological activity index (HAI)6. HBV DNA was extracted from serum by using the standard phenol chloroform method. Detection of HBV DNA was carried out using primers as described earlier7 to amplify part of the surface gene. Hepatitis B viral load estimations were performed by real time PCR (RT-PCR) method5. A 204 bp fragment denotes the CCR5 wild type allele while a 172 bp fragment denotes the CCR5∆32 mutant allele. The patients included were conveniently selected to receive either lamivudine or adefovir or telbivudine (100, 10 and 600 mg, respectively) daily for a period of six months (15 patients in each group). Qualitative values were correlated with Chi-square or Fisher exact tests. P<0.05 was considered statistically significant. Quantitative values are expressed as means and ranges, and were compared using the Student's t-test or the Mann-Whitney non-parametric U test. There was a significant reduction in the serum alanine aminotransferase (ALT in IU/l) levels after treatment for six months (P<0.0001) as compared to baseline values, and results were similar in all drug groups. Compared to baseline, there was a significant (P<0.05) reduction in total bilirubin (mg/dl) levels which was also similar in all drug groups. All the patients remained HBsAg positive at the end of 6 months in all the groups. Four (8.89%) patients seroconverted from HBeAg positive to negative state. Ten of 45 (22.22%) patients became HBV DNA negative, which included four patients each in the adefovir and telbivudine group while two patients in the lamivudine group. There was significant (P<0.001) reduction in serum viral load after six months of therapy; the mean reduction was 1.92, 2.06 and 2.65 log copies per ml with respect to serum HBV DNA adefovir, lamivudine and telbivudine groups, respectively. There was a non significant reduction with respect to HAI score and fibrosis score after treatment for six months and the results were similar in all the drug groups. Of the 45 patients, five (11.11%) were found to have CCR5Δ32 heterozygous (+/-) genotype and the remaining 40 patients (88.8%) were of CCR5 (+/+) genotype. Of the four patients who seroconverted from HBeAg positive to negative state, CCR5Δ32 (+/-) mutation was found in two patients. The frequency of CCR5Δ32 mutations did not relate with biochemical, virological and histological parameters. There was no difference in response to therapy when patients were categorized on the basis of the response pattern with respect to different drug groups, and the distribution of…
To study the role of heat shock protein A1L (HSPA1L) and A1B (HSPA1B) polymorphisms and subsequen... more To study the role of heat shock protein A1L (HSPA1L) and A1B (HSPA1B) polymorphisms and subsequent risk of hepatocellular carcinoma (HCC) in India. Subjects enrolled included 185 cases of HCC, 182 cases of chronic hepatitis (CH) and 200 healthy controls. Genomic DNA was typed for HSPA1L2437 and HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. Other risk factors were also analysed. Hepatitis B virus (HBV) infection, older age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;35 years and high aflatoxin level in urine increased the risk of HCC. The frequencies of HSPA1L BB genotype and B allele in HCC were more than in CH [odds ratio (OR): 9.83; P = 0.000], but also in HBV-related HCC than Chronic Hepatitis B (CHB) [OR: 3.44; P = 0.004] and HCV-related HCC compared to CHC [OR: 6.32; P = 0.010]. The frequency of HSPA1B genotype in the homozygous state was more in CH [OR: 6.01; P = 0.001] and is a good marker to predict the risk of HCV-related CH (CHC) compared to controls. HCV-related HCC has a higher frequency of the B allele of HSPA1B than healthy controls [OR: 3.95; P = 0.000] and CHC [OR: 2.35; P = 0.000], respectively. The frequencies increased further significantly in CHC compared to healthy controls [OR: 9.26; P = 0.000]. The risk for the development of CH and HCC compared to healthy controls irrespective of the aetiology was significant in terms of the HSPA1B marker than HSPA1L in the Indian population.
The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regi... more The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P…
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