Alimentary Pharmacology & Therapeutics, Aug 4, 2017
across ten different countries. Previously, lean NAFLD was thought to be a phenomenon strictly se... more across ten different countries. Previously, lean NAFLD was thought to be a phenomenon strictly seen in patients of Asian background; recent analysis of other racial groups has identified a small cohort of Caucasians fitting the lean NAFLD profile. 3 Sookoian and Pirola are the first to risk stratify according to ethnicity and demonstrated no identifiable difference between Asians and Caucasians regarding the risk factors associated with lean NAFLD. More research will be required to evaluate if there are discrepancies among other ethnic populations and demographics, particularly gender. One limitation inherent to such a large meta-analysis is the lack of information specific to the most clinically relevant subset of patients with NAFLD, ie, those with NASH. Large-scale studies with histological information must be pursued as lean NASH patients are a unique and high risk phenotype that may further efforts to identify and treat the greater NASH population as a whole. Figure .
Background: Inflammation is an essential immune response; however, chronic inflammation results i... more Background: Inflammation is an essential immune response; however, chronic inflammation results in disease including Crohn's disease. Therefore, reducing the inflammation can yield a significant health benefit, and one way to achieve this is through diet. We developed a Mediterranean-inspired anti-inflammatory diet and used this diet in a 6-week intervention in a Crohn's disease population. We examined changes in inflammation and also in the gut microbiota. We compared the results of established biomarkers, C-reactive protein and the micronuclei assay, of inflammation with results from a transcriptomic approach. Results: Data showed that being on our diet for 6 weeks was able to reduce the established biomarkers of inflammation. However, using transcriptomics, we observed significant changes in gene expression. Although no single gene stood out, the cumulative effect of small changes in many genes combined to have a beneficial effect. Data also showed that our diet resulted in a trend of normalising the microbiota. Conclusions: This study showed that our Mediterranean-inspired diet appeared to benefit the health of people with Crohn's disease. Our participants showed a trend for reduced markers of inflammation and normalising of the microbiota. The significant changes in gene expression after 6 weeks highlighted the increased sensitivity of using transcriptomics when compared to the established biomarkers and open up a new era of dietary intervention studies.
BackgroundThe audit process may help improve performance indicators for colonoscopy quality but i... more BackgroundThe audit process may help improve performance indicators for colonoscopy quality but it is unclear whether this is sustained over several years.Methods44138 procedures for 28 endoscopists from 2004 to 2019 were analysed for polyp detection rate and withdrawal time. From 2012, 14 endoscopists were analysed with additional data on polyp histology and number of polyps removed.ResultsPolyp detection increased from 40.7% in 2004 to 62.2% in 2019; removal of polyps>1 cm remained constant (11%). Adenoma detection rate was 25.8% in 2012 and 28.3% in 2019. Sessile serrated polyp (SSP) detection rate increased from 4.5% to 14.7%; most of the increase was in the first 2 years of the histology part of the audit. There was a significant correlation of adenoma detection rate with mean number of adenomas (r=0.72, p=0.004) and a significant correlation of SSP detection with mean number of SSPs (r=0.85, p=0.0001).ConclusionThe audit process appears to encourage a higher rate of polyp d...
Biosimilars are a cost-effective alternative to biologics that could improve patients' access... more Biosimilars are a cost-effective alternative to biologics that could improve patients' access to expensive biological medicines. Currently, there are little data on doctors' perceptions of biosimilars and in what situations they are comfortable prescribing biosimilars. In this study, we investigated medical specialists' perceptions of biosimilars and the factors associated with the acceptance of biosimilars. A national sample of 110 of 327 medical specialists working in the areas of rheumatology, dermatology, gastroenterology, oncology and haematology completed an online questionnaire examining attitudes towards prescribing biosimilars, indication extrapolation and switching patients to a biosimilar. Most specialists held positive views of biosimilars, with between 54 and 74% confident in the safety, efficacy, manufacturing and pharmacovigilance of biosimilars. Seventy-one percent of specialists agreed that they would prescribe biosimilars for all or some conditions meet...
Background: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as az... more Background: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions. Aims: The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP. Methods: Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics. Results: Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity. Conclusions: Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.
Journal of Gastroenterology and Hepatology, Nov 1, 1999
ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an e... more ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an effect which is reversed by eradication of the bacterium. 5,6 Correa et al. have compared gastric juice ascorbic acid concentrations in different ethnic groups in New Orleans, USA, with differing risks for gastric cancer. 7 The median ascorbic acid concentration for the white population was 7.6 mg/mL for H. pylori-negative patients and 4.5 mg/mL for H. pylori-positive patients. For the black population in the same city, the median ascorbic acid was 3.4 mg/mL for H. pylori-negative and 1.11 mg/mL for
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an e... more ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an effect which is reversed by eradication of the bacterium. 5,6 Correa et al. have compared gastric juice ascorbic acid concentrations in different ethnic groups in New Orleans, USA, with differing risks for gastric cancer. 7 The median ascorbic acid concentration for the white population was 7.6 mg/mL for H. pylori-negative patients and 4.5 mg/mL for H. pylori-positive patients. For the black population in the same city, the median ascorbic acid was 3.4 mg/mL for H. pylori-negative and 1.11 mg/mL for
OBJECTIVE Failure to effectively reassure patients can lead to patients becoming distressed and s... more OBJECTIVE Failure to effectively reassure patients can lead to patients becoming distressed and seeking further medical care. Whilst existing studies have identified that patients' psychological and demographic characteristics can impact patient reassurance, little research has explored specific predictors of patient reassurance following a colonoscopy. This study investigates demographic and psychological predictors of patient reassurance after receiving normal test results following a colonoscopy. METHODS Eighty-five participants receiving colonoscopies due to gastrointestinal symptoms were recruited from two endoscopy clinics. Patients provided demographic information and completed questionnaires assessing illness perceptions, health-related anxiety, hypochondriasis, somatisation and state and trait anxiety prior to the colonoscopy, as well as reassurance the day after the colonoscopy. Seventy-three participants provided complete data and were included in the analyses. Pearson's correlations and hierarchical linear regression were conducted to examine the associations between the baseline variables and patient reassurance after the colonoscopy. RESULTS Health-related anxiety, hypochondriasis and four items from the Brief Illness Perceptions Questionnaire (consequence, identity, concern, and emotional response beliefs) were negatively correlated with reassurance (r's ranged from -0.28 to -0.54, P < .05). The hierarchical linear regression demonstrated that in the fully adjusted model, only consequence beliefs (i.e. negative beliefs regarding the impact of gastrointestinal symptoms) remained a robust predictor of reassurance (β = -0.56, P = .005). CONCLUSION This study extends existing research on patient reassurance and is the first study to demonstrate that illness beliefs predicted reassurance following a colonoscopy. These findings suggest that targeting consequence beliefs may be a useful intervention for improving patient reassurance following clinical investigations.
Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidog... more Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidoglycan, are responsible for increased susceptibility to Crohn's disease (CD). TLRs and their related plant counterparts, the disease-resistance R proteins, undergo alternative splicing as a means of controlling activity. Here we report that regions of NOD2 RNA transcripts that encode the N-terminal and leucine-rich repeat (LRR) domains are alternatively spliced, potentially creating at least eight putative NOD2 variants. The most common variant is a short truncated isoform designated NOD2-short which terminates at residue position 820 leaving three LRR domains. An N-terminally spliced variant designated NOD2-190 contains only CARD1 and a partial CARD2 domain. The expression of transcripts encoding full-length and alternatively spliced forms of NOD2 was altered in blood mononuclear cells and monocytic cell lines stimulated by bacterial products. NOD2-short and NOD2-190 were inactive and unresponsive to muramyl dipeptide (MDP), but did not antagonize the activity of wild-type NOD2. Alternative splicing of NOD2 transcripts represents a potential mechanism by which the intracellular bacterial sensing activity of NOD2 is altered or down-regulated.
Journal of Gastroenterology and Hepatology, Nov 1, 2007
Background and Aim: Toll-like receptors (TLRs) have been identified as susceptibility genes for C... more Background and Aim: Toll-like receptors (TLRs) have been identified as susceptibility genes for Crohn's disease (CD) in some, but not all, studies. Here we examined the association between candidate disease-susceptibility polymorphisms in the TLR2, TLR4 and TLR9 genes and CD in a New Zealand Caucasian population. Methods: The frequency of gene polymorphisms was examined in 182 CD patients and in 188 ethnically matched controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: We could not detect any significant difference in the allele frequencies of polymorphisms in the TLR2 (R753Q, 0.029 vs 0.016, P = 0.25), TLR4 (D299G and T399I, 0.085 vs 0.071, P = 0.49; and 0.085 vs 0.082, P = 0.90), and TLR9 (-1237T/C, 0.154 vs 0.148, P = 0.82) genes between controls and patients, respectively. There was no evidence that the variant TLR alleles were associated with disease phenotype. However, combination of the datasets of published studies with our dataset confirmed that the TLR4 polymorphism 299G (P = 0.0005; OR of 1.42 [95% CI 1.17-1.74]) and the TLR9 polymorphism -1237C (P = 0.0416; OR of 1.33 [95% CI 1.01-1.75]) are associated with CD. Conclusions: There was no evidence that the above variants of the TLR2, TLR4 and TLR9 genes are major risk factors for CD or influence disease phenotype in our New Zealand case-control study. Nevertheless, the significance of the TLR4 299G and TLR9 -1237C associations with CD worldwide was confirmed by a meta-analysis test using our datasets and datasets from previously published studies.
The immunomodulatory and cytotoxic properties of 6-MP and azathioprine are mediated by conversion... more The immunomodulatory and cytotoxic properties of 6-MP and azathioprine are mediated by conversion of 6MP to its thiopurine metabolites: 6-TG and 6-methylmercaptopurine (6-MMP). It is suggested that leukopenia and hepatotoxicity correlate with elevated 6TG and 6MMP levels respectively. RBC 6TG levels >23OpmoV8x10 8 correlate with clinical response in some studies. Aim of this study was to study the usefulness of 6MP metabolites in assessing therapeutic response and toxicity of 6MP in our pediatric population. Methods: 6MP metabolite levels from 54 children with IBD on 6MP >4 months were measured at Prometheus Labs, CA. Response to 6MP was defined as clinical remission (PCDAI<lO or closed fistulae) in patients weaned off corticosteroids or on low dose prednisone «O.3mgl kg/day). Complete blood counts and alanine aminotransferase (ALT) were assessed simultaneously. Results: Mean 6TG level was 226 in patients in remission and 208 in patients in relapse. Among patients in relapse, 36% had 6TG levels> 230, compared with 30% of patients in remission. Of 37 patients with 6TG levels<230, 21 (57%) were in remission vs. nine (50%) of 18 patients with 6TG levels>230. Leukopenia (WBC<4000) was observed in five (9%) patients, all had significant elevations in 6TG levels (43Ovs214; p<0.05). None of the nine patients with 6MMP >5550 (6140-19805), had elevated ALT. Two (4%) patients with ALT >2x N had mean 6MMP level of only 2987. In 32 patients 6MMP was undetectable. six of whom also had undetectable 6TG probably reflecting poor compliance. Thiopurine methyl-transferase (TPMT) genotyping was performed in 12 patients, eight had normal TPMT and 4 patients had intermediate TPMT.
Alimentary Pharmacology & Therapeutics, Aug 4, 2017
across ten different countries. Previously, lean NAFLD was thought to be a phenomenon strictly se... more across ten different countries. Previously, lean NAFLD was thought to be a phenomenon strictly seen in patients of Asian background; recent analysis of other racial groups has identified a small cohort of Caucasians fitting the lean NAFLD profile. 3 Sookoian and Pirola are the first to risk stratify according to ethnicity and demonstrated no identifiable difference between Asians and Caucasians regarding the risk factors associated with lean NAFLD. More research will be required to evaluate if there are discrepancies among other ethnic populations and demographics, particularly gender. One limitation inherent to such a large meta-analysis is the lack of information specific to the most clinically relevant subset of patients with NAFLD, ie, those with NASH. Large-scale studies with histological information must be pursued as lean NASH patients are a unique and high risk phenotype that may further efforts to identify and treat the greater NASH population as a whole. Figure .
Background: Inflammation is an essential immune response; however, chronic inflammation results i... more Background: Inflammation is an essential immune response; however, chronic inflammation results in disease including Crohn's disease. Therefore, reducing the inflammation can yield a significant health benefit, and one way to achieve this is through diet. We developed a Mediterranean-inspired anti-inflammatory diet and used this diet in a 6-week intervention in a Crohn's disease population. We examined changes in inflammation and also in the gut microbiota. We compared the results of established biomarkers, C-reactive protein and the micronuclei assay, of inflammation with results from a transcriptomic approach. Results: Data showed that being on our diet for 6 weeks was able to reduce the established biomarkers of inflammation. However, using transcriptomics, we observed significant changes in gene expression. Although no single gene stood out, the cumulative effect of small changes in many genes combined to have a beneficial effect. Data also showed that our diet resulted in a trend of normalising the microbiota. Conclusions: This study showed that our Mediterranean-inspired diet appeared to benefit the health of people with Crohn's disease. Our participants showed a trend for reduced markers of inflammation and normalising of the microbiota. The significant changes in gene expression after 6 weeks highlighted the increased sensitivity of using transcriptomics when compared to the established biomarkers and open up a new era of dietary intervention studies.
BackgroundThe audit process may help improve performance indicators for colonoscopy quality but i... more BackgroundThe audit process may help improve performance indicators for colonoscopy quality but it is unclear whether this is sustained over several years.Methods44138 procedures for 28 endoscopists from 2004 to 2019 were analysed for polyp detection rate and withdrawal time. From 2012, 14 endoscopists were analysed with additional data on polyp histology and number of polyps removed.ResultsPolyp detection increased from 40.7% in 2004 to 62.2% in 2019; removal of polyps>1 cm remained constant (11%). Adenoma detection rate was 25.8% in 2012 and 28.3% in 2019. Sessile serrated polyp (SSP) detection rate increased from 4.5% to 14.7%; most of the increase was in the first 2 years of the histology part of the audit. There was a significant correlation of adenoma detection rate with mean number of adenomas (r=0.72, p=0.004) and a significant correlation of SSP detection with mean number of SSPs (r=0.85, p=0.0001).ConclusionThe audit process appears to encourage a higher rate of polyp d...
Biosimilars are a cost-effective alternative to biologics that could improve patients' access... more Biosimilars are a cost-effective alternative to biologics that could improve patients' access to expensive biological medicines. Currently, there are little data on doctors' perceptions of biosimilars and in what situations they are comfortable prescribing biosimilars. In this study, we investigated medical specialists' perceptions of biosimilars and the factors associated with the acceptance of biosimilars. A national sample of 110 of 327 medical specialists working in the areas of rheumatology, dermatology, gastroenterology, oncology and haematology completed an online questionnaire examining attitudes towards prescribing biosimilars, indication extrapolation and switching patients to a biosimilar. Most specialists held positive views of biosimilars, with between 54 and 74% confident in the safety, efficacy, manufacturing and pharmacovigilance of biosimilars. Seventy-one percent of specialists agreed that they would prescribe biosimilars for all or some conditions meet...
Background: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as az... more Background: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions. Aims: The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP. Methods: Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics. Results: Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity. Conclusions: Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.
Journal of Gastroenterology and Hepatology, Nov 1, 1999
ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an e... more ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an effect which is reversed by eradication of the bacterium. 5,6 Correa et al. have compared gastric juice ascorbic acid concentrations in different ethnic groups in New Orleans, USA, with differing risks for gastric cancer. 7 The median ascorbic acid concentration for the white population was 7.6 mg/mL for H. pylori-negative patients and 4.5 mg/mL for H. pylori-positive patients. For the black population in the same city, the median ascorbic acid was 3.4 mg/mL for H. pylori-negative and 1.11 mg/mL for
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an e... more ascorbic acid in gastric juice is markedly decreased in the presence of H. pylori infection: an effect which is reversed by eradication of the bacterium. 5,6 Correa et al. have compared gastric juice ascorbic acid concentrations in different ethnic groups in New Orleans, USA, with differing risks for gastric cancer. 7 The median ascorbic acid concentration for the white population was 7.6 mg/mL for H. pylori-negative patients and 4.5 mg/mL for H. pylori-positive patients. For the black population in the same city, the median ascorbic acid was 3.4 mg/mL for H. pylori-negative and 1.11 mg/mL for
OBJECTIVE Failure to effectively reassure patients can lead to patients becoming distressed and s... more OBJECTIVE Failure to effectively reassure patients can lead to patients becoming distressed and seeking further medical care. Whilst existing studies have identified that patients' psychological and demographic characteristics can impact patient reassurance, little research has explored specific predictors of patient reassurance following a colonoscopy. This study investigates demographic and psychological predictors of patient reassurance after receiving normal test results following a colonoscopy. METHODS Eighty-five participants receiving colonoscopies due to gastrointestinal symptoms were recruited from two endoscopy clinics. Patients provided demographic information and completed questionnaires assessing illness perceptions, health-related anxiety, hypochondriasis, somatisation and state and trait anxiety prior to the colonoscopy, as well as reassurance the day after the colonoscopy. Seventy-three participants provided complete data and were included in the analyses. Pearson's correlations and hierarchical linear regression were conducted to examine the associations between the baseline variables and patient reassurance after the colonoscopy. RESULTS Health-related anxiety, hypochondriasis and four items from the Brief Illness Perceptions Questionnaire (consequence, identity, concern, and emotional response beliefs) were negatively correlated with reassurance (r's ranged from -0.28 to -0.54, P < .05). The hierarchical linear regression demonstrated that in the fully adjusted model, only consequence beliefs (i.e. negative beliefs regarding the impact of gastrointestinal symptoms) remained a robust predictor of reassurance (β = -0.56, P = .005). CONCLUSION This study extends existing research on patient reassurance and is the first study to demonstrate that illness beliefs predicted reassurance following a colonoscopy. These findings suggest that targeting consequence beliefs may be a useful intervention for improving patient reassurance following clinical investigations.
Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidog... more Mutated variants of NOD2, a cytosolic Toll-like receptor (TLR) that recognizes bacterial peptidoglycan, are responsible for increased susceptibility to Crohn's disease (CD). TLRs and their related plant counterparts, the disease-resistance R proteins, undergo alternative splicing as a means of controlling activity. Here we report that regions of NOD2 RNA transcripts that encode the N-terminal and leucine-rich repeat (LRR) domains are alternatively spliced, potentially creating at least eight putative NOD2 variants. The most common variant is a short truncated isoform designated NOD2-short which terminates at residue position 820 leaving three LRR domains. An N-terminally spliced variant designated NOD2-190 contains only CARD1 and a partial CARD2 domain. The expression of transcripts encoding full-length and alternatively spliced forms of NOD2 was altered in blood mononuclear cells and monocytic cell lines stimulated by bacterial products. NOD2-short and NOD2-190 were inactive and unresponsive to muramyl dipeptide (MDP), but did not antagonize the activity of wild-type NOD2. Alternative splicing of NOD2 transcripts represents a potential mechanism by which the intracellular bacterial sensing activity of NOD2 is altered or down-regulated.
Journal of Gastroenterology and Hepatology, Nov 1, 2007
Background and Aim: Toll-like receptors (TLRs) have been identified as susceptibility genes for C... more Background and Aim: Toll-like receptors (TLRs) have been identified as susceptibility genes for Crohn's disease (CD) in some, but not all, studies. Here we examined the association between candidate disease-susceptibility polymorphisms in the TLR2, TLR4 and TLR9 genes and CD in a New Zealand Caucasian population. Methods: The frequency of gene polymorphisms was examined in 182 CD patients and in 188 ethnically matched controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: We could not detect any significant difference in the allele frequencies of polymorphisms in the TLR2 (R753Q, 0.029 vs 0.016, P = 0.25), TLR4 (D299G and T399I, 0.085 vs 0.071, P = 0.49; and 0.085 vs 0.082, P = 0.90), and TLR9 (-1237T/C, 0.154 vs 0.148, P = 0.82) genes between controls and patients, respectively. There was no evidence that the variant TLR alleles were associated with disease phenotype. However, combination of the datasets of published studies with our dataset confirmed that the TLR4 polymorphism 299G (P = 0.0005; OR of 1.42 [95% CI 1.17-1.74]) and the TLR9 polymorphism -1237C (P = 0.0416; OR of 1.33 [95% CI 1.01-1.75]) are associated with CD. Conclusions: There was no evidence that the above variants of the TLR2, TLR4 and TLR9 genes are major risk factors for CD or influence disease phenotype in our New Zealand case-control study. Nevertheless, the significance of the TLR4 299G and TLR9 -1237C associations with CD worldwide was confirmed by a meta-analysis test using our datasets and datasets from previously published studies.
The immunomodulatory and cytotoxic properties of 6-MP and azathioprine are mediated by conversion... more The immunomodulatory and cytotoxic properties of 6-MP and azathioprine are mediated by conversion of 6MP to its thiopurine metabolites: 6-TG and 6-methylmercaptopurine (6-MMP). It is suggested that leukopenia and hepatotoxicity correlate with elevated 6TG and 6MMP levels respectively. RBC 6TG levels >23OpmoV8x10 8 correlate with clinical response in some studies. Aim of this study was to study the usefulness of 6MP metabolites in assessing therapeutic response and toxicity of 6MP in our pediatric population. Methods: 6MP metabolite levels from 54 children with IBD on 6MP >4 months were measured at Prometheus Labs, CA. Response to 6MP was defined as clinical remission (PCDAI<lO or closed fistulae) in patients weaned off corticosteroids or on low dose prednisone «O.3mgl kg/day). Complete blood counts and alanine aminotransferase (ALT) were assessed simultaneously. Results: Mean 6TG level was 226 in patients in remission and 208 in patients in relapse. Among patients in relapse, 36% had 6TG levels> 230, compared with 30% of patients in remission. Of 37 patients with 6TG levels<230, 21 (57%) were in remission vs. nine (50%) of 18 patients with 6TG levels>230. Leukopenia (WBC<4000) was observed in five (9%) patients, all had significant elevations in 6TG levels (43Ovs214; p<0.05). None of the nine patients with 6MMP >5550 (6140-19805), had elevated ALT. Two (4%) patients with ALT >2x N had mean 6MMP level of only 2987. In 32 patients 6MMP was undetectable. six of whom also had undetectable 6TG probably reflecting poor compliance. Thiopurine methyl-transferase (TPMT) genotyping was performed in 12 patients, eight had normal TPMT and 4 patients had intermediate TPMT.
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