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S2085 Prevalence of Celiac Disease in Established Liver Disease and Cryptogenic Transaminase Elevation: A Systematic Review
AGA Abstracts
psychiatric disorder. 2 pts in each group discontinued treatment due to non-adherence. 15 (34.9%) pts achieved SVR, 7 (16.3%) relpased and 21 (48.8%) were non-responders. Conclusions: 1) In a tertiary Liver Center the prevalence of Psychiatric illness is almost 35% of HCV infected individuals. 2) About 70% of pts with Psychiatric illness are not candidates for IFN therapy mainly due to poor control of their Psychiatric illness. 3) 9.3% of HCV infected pts have Bipolar Disorder and Schizophrenia. 4) Only 22.6% of pts with HCV and Bipolar Disorder or Schizophrenia were stable to begin IFN based therapy. In summary: pts with controlled disease can be successfully treated with IFN based therapy under close monitoring with 28% drop-out due to an exacerbation of psychiartric illness and 51% end of treatment virologic response. Pts with Schizophrenia are more likely to tolerate IFN therapy than Bipolar Disorder pts.
S2086 Autoimmunity in Sclerosing Cholangitis (SC): Association SC with Autoimmune Pancreatitis (SC-AIP) and PSC Kazuichi Okazaki, Hideaki Miyoshi, Kazushige Uchida Background & Aim: Autoimmune pancreatitis (AIP) is a unique distinctive disease, in which sclerosing changes of the bile duct named as “sclerosing cholangitis with autoimmune pancreatitis (SC-AIP)” similar to primary sclerosing cholangitis (PSC) are often observed as extra-pancreatic lesions. As the clinical symptoms, laboratory findings and cholangiographic images in the patients with SC-AIP remarkably improve by steroid therapy, SC-AIP seems to be different from PSC. However, pathogenesis and pathophysiology of AIP, SC-AIP and PSC remain still unclear. To clarify them, we studied the clinical and immunological differences among AIP, SC-AIP and PSC. Materials and methods: We experienced 54 patients with AIP (mean age: 64yr, male/female: 37/17) diagnosed by Japanese clinical diagnostic criteria for AIP (J Gastroenterol. 2006;41:626-631), who showed SC-AIP in 32 patients (60%), sialadenitis in 7 (13%), retroperitoneal fibrosis in 5 (9%), hilar lymphnode swelling in 5 (9%), interstitial nephritis in 4 (7%), chronic thyroiditis in 4 (7%) and pseudotumor of the liver in one (2%). Three patients with IgG4-assoiciated SC without AIP and 5 with PSC were also studied. Fifteen patients with alcoholic chronic pancreatitis, 15 with idiopathic pancreatitis, and 15 healthy volunteers were served as controls. We studied clinical findings, lymphocytes subsets of the peripheral blood (regulatory T cells (Treg), Th1, Th2, Th17) by flowcytometry, and immunohistochemistry in the liver and pancreas by using anti-CD4, anti-CD25, anti-Foxp3, anti-IL-10, anti-IL-17, anti-TGF-b and anti-IgG4 antibodies. Results: 1) Clinical findings and laboratory data remarkably improved in patients with AIP and SCAIP, but not in PSC. 2) CD4+CD25+CDRA+naïve Tregs in the peripheral blood significantly decreased in the patients with AIP compared with other disease controls (P<0.05), whereas CD4+CD25+CDRA- memory Tregs and IL-10 positive T-cells significantly increased in AIP (P<0.05). 2) Abundant Tregs and IgG4-positive plasmacytes (>10/HPF) infiltrate in the pancreas of AIP, but not in that of control pancreatitis. Similarly, these two type cells infiltrate in the periportal area in the liver of SC-AIP and IgG4-associated SC without AIP, but not in the liver of PSC. Conclusion: The mechanism of the development of SC-AIP or IgG4associated SC without AIP may be different from typical PSC. From the viewpoint of IgG4, SC-AIP and IgG4-associated SC without AIP may be a single disease entity, in which Tregs may induce proliferation of IgG4-positive plasmacytes.
S2084 Significant Prevalence of Histologic Disease in Chronic Hepatitis B Patients with Mildly Elevated Serum Alanine Aminotrasferase Levels Philip S. Tsang, Ruel T. Garcia, Huy N. Trinh, Jeanine Phan, Nghiem B. Ha, Huy A. Nguyen, Khanh K. Nguyen, Emmet B. Keeffe, Mindie H. Nguyen Background: Serum alanine aminotransferase (ALT) remains the most accessible test for monitoring chronic hepatitis B virus (HBV) infection, but appropriate action when ALT levels are only mildly elevated is ambiguous in standard guidelines. A retrospective study was conducted to investigate the prevalence of significant liver disease in a patient population with mildly elevated serum ALT levels at a community clinic. Methods: 193 consecutive treatment-naïve patients with chronic HBV infection undergoing liver biopsy were selected and divided into 2 groups according to hepatitis B e antigen (HBeAg) status. Patients were further divided into cohorts based on their highest ALT elevation during pre-biopsy followup and whether it was 1-1.5 times the upper limit of normal (ULN, <30 U/L for men and <19U/L for women), 1.5-2×ULN, or >2×ULN. The presence of significant liver disease was evaluated by percutaneous core liver biopsy and defined if the Batts-Ludwig scale was either 1) ≥ stage II fibrosis, or 2) stage I fibrosis with ≥ grade 2 inflammation. Results: The mean observation time was 18 months, with a median of 3 ALT measurements and 2 HBV DNA tests in that period. In all cohorts there was a substantial fraction of patients with significant disease (Table 1). Of the 193 patients, 126 were HBeAg-negative (67 were HBe-Ag positive). HBeAg-negative patients were older (mean: 49 ± 11 years vs. 39 ± 9, p<0.0001), had lower HBV DNA load and had a higher prevalence of disease (62.7% vs. 47.8%, p=0.046). Following adjustments for age, HBeAg status and HBV DNA load were not predictors of significant histology. Age >35 years, male gender, and increasing ALT levels were predictors for significant histology on multivariate analysis. As compared to 1-1.5×ULN cohort, the odds ratio (OR) was 3.70, p=0.02 for the 1.5-2×ULN cohort and 10.46, p<0.001 for the >2xULN cohort. The age ranges showed similar risk increases: OR=3.27, p=0.02 for ages 36-50 (vs. age ≤ 35) and 8.11, p<0.001 for ages >50. The increases in liver disease with ALT cohort and with age were more marked in the HBeAg-negative patients (by the magnitude of increase and by the smaller P-value, Table 1). Male gender was also an independent predictor (OR=2.15, p=0.03). Conclusion: A substantial proportion of patients with mildly elevated ALT levels have significant liver disease. The prevalence increases with the degree of elevation and with age >35. Table 1: Prevalence of Significant Liver Disease
S2087 Does Presence of SPINK-1 Variant Alter the Course of Pancreatitis? Bimaljit S. Sandhu, Shelley C. Smith, Andres D. Mogollon, Patrik Vitazka, Andrea Ferreira-Gonzalez, Alvin M. Zfass, Doumit BouHaidar, Arun J. Sanyal Background: Prevalence and impact of serine protease inhibitor Kazal type 1(SPINK-1) variants on the natural course of idiopathic pancreatitis (IP) remains unclear. We aimed to assess the prevalence of SPINK-1 variants in patients with IP and its impact on the natural course. Patients and Methods: A retrospective-prospective study was conducted on 143 consecutive subjects with chronic pancreatitis (CP). CP was diagnosed by presence of clinical signs and symptoms, laboratory and suggestive radiographic findings. All subjects gave a written informed consent. Detailed history, including onset of symptoms, type of pain (type A or B), number of flares requiring hospital admission or increase in pain medication use, alcohol use, smoking and family history were recorded. Genetic tests including mutations in cationic trypsinogen gene, SPINK-1, and cystic fibrosis transmembrane conductance regulator (CFTR) were performed on all the subjects. CP was graded into equivocal, mild, moderate and severe using the Cambridge classification. Exocrine failure (defined by presence of steatorrhea and/or fecal elastase < 200µg/gm), diabetes and pain were the outcome variables. Ordinal variables were compared using Fisher's exact test and numerical values by one way ANOVA. Results: Seventeen subjects (11.9%) had IP. Five (3.5%) subjects were SPINK-1 variants and all of them were Caucasian. None of these had a family history of CP. Two of these subjects had a short history of alcohol use, not typical of alcohol induced pancreatitis. None of the subjects with alcoholic pancreatitis were SPINK-1 variant. SPINK1 variant subjects (n=5) were then compared with true IP subjects (n=12). SPINK-1 variants had a younger age at onset (mean and SEM: 32.4±6.1) than the IP group (41.2±3.4) (p= 0.25). Over a median follow up of 6 yrs (range 0.8-19.8 yrs), SPINK-1 positive subjects had significantly higher number of acute flares (11.8±1.5) as compared to the IP group (4±0.98) (p=0.006). Exocrine failure developed in 4 (80%) with SPINK-1 variants and in 6 (50%) IP subjects (p=0.51). Diabetes developed in 2 (40%) of SPINK-1 variants and 2 (16.7%) of IP subjects (p=0.31). Most of the subjects with SPINK-1 variants were in advanced Cambridge stage (moderate=1 & severe=3). Conclusions: SPINK-1 variants are prevalent in about 3.5% of subjects with CP. Subjects with SPINK-1 variants have younger age of onset and might accelerate the development of CP in the subjects with moderate alcohol use. SPINK-1 variants predispose the patients to a higher risk of having recurrent flares. All subjects with borderline alcohol history and IP should be screened for SPINK-1 mutations.
S2085 Prevalence of Celiac Disease in Established Liver Disease and Cryptogenic Transaminase Elevation: A Systematic Review Erin McGeeney, Bruce R. Bacon, Fasiha Kanwal Background: Numerous case reports and population-based studies indicate that liver involvement is present in up to 55% of patients with celiac disease (CD). Moreover, data also suggest that CD may be prevalent in patients with chronic liver disease (CLD), including nonspecific chronic transaminase elevation (CTE) and non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to address the following questions: (i) What is the prevalence of CD in patients with CTE or NAFLD? (ii) Is the prevalence of CD in CTE or NAFLD higher than in healthy controls? (iii) What serologic test for CD demonstrates the best PPV in patients with CTE and NAFLD? Methods: We conducted a literature search of PubMed from 1963 to November 2007 to identify studies evaluating patients with CLD, CTE or NAFLD for CD. We selected articles that utilized serological screening [IgA antigliadin antibodies (AGA), endomysial antibodies (EmA), or tissue-transglutaminase antibodies (tTG)] followed by a confirmatory small-bowel biopsy for CD diagnosis. We then performed a meta-analysis to compare the relative risk (RR) of CD in patients with CTE and NALFD compared to healthy controls. We also calculated the PPV of each serological test for CD in patients with CTE and NAFLD. Results: 24 studies from 1994-2007 met our inclusion criteria, of which eight were controlled. Of these, there were 2583 patients with CLD, including 178 with CTE and 115 with NAFLD. The number of normal controls was 4049. The prevalence of CD in patients with CTE and NAFLD was 4.9% (95% CI 2%-8%) and 2.7% (95% CI 3%-8%), respectively. Patients with CTE were 8 times more likely (RR 8.7, 95% CI 2.2-34.6) to have histologically confirmed CD compared to healthy controls. The PPV for IgA AGA, EmA, and tTG in detecting CD in CTE or NAFLD were 62.5, 88.9, and 69, respectively. Conclusion: CD is relatively common in patients with CTE. These data indicate that clinicians should screen patients with CTE for underlying CD. IgA EmA has the highest PPV for CD in this setting. Additional studies are needed to more clearly define the impact of CD screening in routine clinical practice and to determine the effectiveness of gluten-free diet in this patient population.
AGA Abstracts
S2088 TLR2, TLR4, and CD14 Polymorphisms Are Associated with Acute Pancreatitis in Japan Yasuhiko Takagi, Atsushi Masamune, Kiyoshi Kume, Tooru Shimosegawa Background and Aim: Factors underlying genetic predisposition for development of acute pancreatitis (AP) are largely unknown. Toll-like receptors (TLRs) are proteins involved in recognition of foreign pathogen-associated molecular patterns and activation of innate immunity. Among human TLRs, TLR2 recognizes the peptidoglycan of gram-positive bacteria whereas TLR4 recognizes lipopolysaccharide from gram-negative bacteria. CD14 is a coreceptor for TLR2 and TLR4. Recent studies have suggested a role of TLRs 2 and 4 in the development of AP. We here examined the association between the polymorphisms in the TLR2, TLR4 and CD14 genes with AP in Japan. Methods: This study was approved by the Ethics Committee of Tohoku University School of Medicine. A total of 100 (65 males and 35 females) unrelated patients with AP and 150 unrelated healthy volunteers were enrolled
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psychiatric disorder. 2 pts in each group discontinued treatment due to non-adherence. 15 (34.9%) pts achieved SVR, 7 (16.3%) relpased and 21 (48.8%) were non-responders. Conclusions: 1) In a tertiary Liver Center the prevalence of Psychiatric illness is almost 35% of HCV infected individuals. 2) About 70% of pts with Psychiatric illness are not candidates for IFN therapy mainly due to poor control of their Psychiatric illness. 3) 9.3% of HCV infected pts have Bipolar Disorder and Schizophrenia. 4) Only 22.6% of pts with HCV and Bipolar Disorder or Schizophrenia were stable to begin IFN based therapy. In summary: pts with controlled disease can be successfully treated with IFN based therapy under close monitoring with 28% drop-out due to an exacerbation of psychiartric illness and 51% end of treatment virologic response. Pts with Schizophrenia are more likely to tolerate IFN therapy than Bipolar Disorder pts.
S2086 Autoimmunity in Sclerosing Cholangitis (SC): Association SC with Autoimmune Pancreatitis (SC-AIP) and PSC Kazuichi Okazaki, Hideaki Miyoshi, Kazushige Uchida Background & Aim: Autoimmune pancreatitis (AIP) is a unique distinctive disease, in which sclerosing changes of the bile duct named as “sclerosing cholangitis with autoimmune pancreatitis (SC-AIP)” similar to primary sclerosing cholangitis (PSC) are often observed as extra-pancreatic lesions. As the clinical symptoms, laboratory findings and cholangiographic images in the patients with SC-AIP remarkably improve by steroid therapy, SC-AIP seems to be different from PSC. However, pathogenesis and pathophysiology of AIP, SC-AIP and PSC remain still unclear. To clarify them, we studied the clinical and immunological differences among AIP, SC-AIP and PSC. Materials and methods: We experienced 54 patients with AIP (mean age: 64yr, male/female: 37/17) diagnosed by Japanese clinical diagnostic criteria for AIP (J Gastroenterol. 2006;41:626-631), who showed SC-AIP in 32 patients (60%), sialadenitis in 7 (13%), retroperitoneal fibrosis in 5 (9%), hilar lymphnode swelling in 5 (9%), interstitial nephritis in 4 (7%), chronic thyroiditis in 4 (7%) and pseudotumor of the liver in one (2%). Three patients with IgG4-assoiciated SC without AIP and 5 with PSC were also studied. Fifteen patients with alcoholic chronic pancreatitis, 15 with idiopathic pancreatitis, and 15 healthy volunteers were served as controls. We studied clinical findings, lymphocytes subsets of the peripheral blood (regulatory T cells (Treg), Th1, Th2, Th17) by flowcytometry, and immunohistochemistry in the liver and pancreas by using anti-CD4, anti-CD25, anti-Foxp3, anti-IL-10, anti-IL-17, anti-TGF-b and anti-IgG4 antibodies. Results: 1) Clinical findings and laboratory data remarkably improved in patients with AIP and SCAIP, but not in PSC. 2) CD4+CD25+CDRA+naïve Tregs in the peripheral blood significantly decreased in the patients with AIP compared with other disease controls (P<0.05), whereas CD4+CD25+CDRA- memory Tregs and IL-10 positive T-cells significantly increased in AIP (P<0.05). 2) Abundant Tregs and IgG4-positive plasmacytes (>10/HPF) infiltrate in the pancreas of AIP, but not in that of control pancreatitis. Similarly, these two type cells infiltrate in the periportal area in the liver of SC-AIP and IgG4-associated SC without AIP, but not in the liver of PSC. Conclusion: The mechanism of the development of SC-AIP or IgG4associated SC without AIP may be different from typical PSC. From the viewpoint of IgG4, SC-AIP and IgG4-associated SC without AIP may be a single disease entity, in which Tregs may induce proliferation of IgG4-positive plasmacytes.
S2084 Significant Prevalence of Histologic Disease in Chronic Hepatitis B Patients with Mildly Elevated Serum Alanine Aminotrasferase Levels Philip S. Tsang, Ruel T. Garcia, Huy N. Trinh, Jeanine Phan, Nghiem B. Ha, Huy A. Nguyen, Khanh K. Nguyen, Emmet B. Keeffe, Mindie H. Nguyen Background: Serum alanine aminotransferase (ALT) remains the most accessible test for monitoring chronic hepatitis B virus (HBV) infection, but appropriate action when ALT levels are only mildly elevated is ambiguous in standard guidelines. A retrospective study was conducted to investigate the prevalence of significant liver disease in a patient population with mildly elevated serum ALT levels at a community clinic. Methods: 193 consecutive treatment-naïve patients with chronic HBV infection undergoing liver biopsy were selected and divided into 2 groups according to hepatitis B e antigen (HBeAg) status. Patients were further divided into cohorts based on their highest ALT elevation during pre-biopsy followup and whether it was 1-1.5 times the upper limit of normal (ULN, <30 U/L for men and <19U/L for women), 1.5-2×ULN, or >2×ULN. The presence of significant liver disease was evaluated by percutaneous core liver biopsy and defined if the Batts-Ludwig scale was either 1) ≥ stage II fibrosis, or 2) stage I fibrosis with ≥ grade 2 inflammation. Results: The mean observation time was 18 months, with a median of 3 ALT measurements and 2 HBV DNA tests in that period. In all cohorts there was a substantial fraction of patients with significant disease (Table 1). Of the 193 patients, 126 were HBeAg-negative (67 were HBe-Ag positive). HBeAg-negative patients were older (mean: 49 ± 11 years vs. 39 ± 9, p<0.0001), had lower HBV DNA load and had a higher prevalence of disease (62.7% vs. 47.8%, p=0.046). Following adjustments for age, HBeAg status and HBV DNA load were not predictors of significant histology. Age >35 years, male gender, and increasing ALT levels were predictors for significant histology on multivariate analysis. As compared to 1-1.5×ULN cohort, the odds ratio (OR) was 3.70, p=0.02 for the 1.5-2×ULN cohort and 10.46, p<0.001 for the >2xULN cohort. The age ranges showed similar risk increases: OR=3.27, p=0.02 for ages 36-50 (vs. age ≤ 35) and 8.11, p<0.001 for ages >50. The increases in liver disease with ALT cohort and with age were more marked in the HBeAg-negative patients (by the magnitude of increase and by the smaller P-value, Table 1). Male gender was also an independent predictor (OR=2.15, p=0.03). Conclusion: A substantial proportion of patients with mildly elevated ALT levels have significant liver disease. The prevalence increases with the degree of elevation and with age >35. Table 1: Prevalence of Significant Liver Disease
S2087 Does Presence of SPINK-1 Variant Alter the Course of Pancreatitis? Bimaljit S. Sandhu, Shelley C. Smith, Andres D. Mogollon, Patrik Vitazka, Andrea Ferreira-Gonzalez, Alvin M. Zfass, Doumit BouHaidar, Arun J. Sanyal Background: Prevalence and impact of serine protease inhibitor Kazal type 1(SPINK-1) variants on the natural course of idiopathic pancreatitis (IP) remains unclear. We aimed to assess the prevalence of SPINK-1 variants in patients with IP and its impact on the natural course. Patients and Methods: A retrospective-prospective study was conducted on 143 consecutive subjects with chronic pancreatitis (CP). CP was diagnosed by presence of clinical signs and symptoms, laboratory and suggestive radiographic findings. All subjects gave a written informed consent. Detailed history, including onset of symptoms, type of pain (type A or B), number of flares requiring hospital admission or increase in pain medication use, alcohol use, smoking and family history were recorded. Genetic tests including mutations in cationic trypsinogen gene, SPINK-1, and cystic fibrosis transmembrane conductance regulator (CFTR) were performed on all the subjects. CP was graded into equivocal, mild, moderate and severe using the Cambridge classification. Exocrine failure (defined by presence of steatorrhea and/or fecal elastase < 200µg/gm), diabetes and pain were the outcome variables. Ordinal variables were compared using Fisher's exact test and numerical values by one way ANOVA. Results: Seventeen subjects (11.9%) had IP. Five (3.5%) subjects were SPINK-1 variants and all of them were Caucasian. None of these had a family history of CP. Two of these subjects had a short history of alcohol use, not typical of alcohol induced pancreatitis. None of the subjects with alcoholic pancreatitis were SPINK-1 variant. SPINK1 variant subjects (n=5) were then compared with true IP subjects (n=12). SPINK-1 variants had a younger age at onset (mean and SEM: 32.4±6.1) than the IP group (41.2±3.4) (p= 0.25). Over a median follow up of 6 yrs (range 0.8-19.8 yrs), SPINK-1 positive subjects had significantly higher number of acute flares (11.8±1.5) as compared to the IP group (4±0.98) (p=0.006). Exocrine failure developed in 4 (80%) with SPINK-1 variants and in 6 (50%) IP subjects (p=0.51). Diabetes developed in 2 (40%) of SPINK-1 variants and 2 (16.7%) of IP subjects (p=0.31). Most of the subjects with SPINK-1 variants were in advanced Cambridge stage (moderate=1 & severe=3). Conclusions: SPINK-1 variants are prevalent in about 3.5% of subjects with CP. Subjects with SPINK-1 variants have younger age of onset and might accelerate the development of CP in the subjects with moderate alcohol use. SPINK-1 variants predispose the patients to a higher risk of having recurrent flares. All subjects with borderline alcohol history and IP should be screened for SPINK-1 mutations.
S2085 Prevalence of Celiac Disease in Established Liver Disease and Cryptogenic Transaminase Elevation: A Systematic Review Erin McGeeney, Bruce R. Bacon, Fasiha Kanwal Background: Numerous case reports and population-based studies indicate that liver involvement is present in up to 55% of patients with celiac disease (CD). Moreover, data also suggest that CD may be prevalent in patients with chronic liver disease (CLD), including nonspecific chronic transaminase elevation (CTE) and non-alcoholic fatty liver disease (NAFLD). We performed a systematic review to address the following questions: (i) What is the prevalence of CD in patients with CTE or NAFLD? (ii) Is the prevalence of CD in CTE or NAFLD higher than in healthy controls? (iii) What serologic test for CD demonstrates the best PPV in patients with CTE and NAFLD? Methods: We conducted a literature search of PubMed from 1963 to November 2007 to identify studies evaluating patients with CLD, CTE or NAFLD for CD. We selected articles that utilized serological screening [IgA antigliadin antibodies (AGA), endomysial antibodies (EmA), or tissue-transglutaminase antibodies (tTG)] followed by a confirmatory small-bowel biopsy for CD diagnosis. We then performed a meta-analysis to compare the relative risk (RR) of CD in patients with CTE and NALFD compared to healthy controls. We also calculated the PPV of each serological test for CD in patients with CTE and NAFLD. Results: 24 studies from 1994-2007 met our inclusion criteria, of which eight were controlled. Of these, there were 2583 patients with CLD, including 178 with CTE and 115 with NAFLD. The number of normal controls was 4049. The prevalence of CD in patients with CTE and NAFLD was 4.9% (95% CI 2%-8%) and 2.7% (95% CI 3%-8%), respectively. Patients with CTE were 8 times more likely (RR 8.7, 95% CI 2.2-34.6) to have histologically confirmed CD compared to healthy controls. The PPV for IgA AGA, EmA, and tTG in detecting CD in CTE or NAFLD were 62.5, 88.9, and 69, respectively. Conclusion: CD is relatively common in patients with CTE. These data indicate that clinicians should screen patients with CTE for underlying CD. IgA EmA has the highest PPV for CD in this setting. Additional studies are needed to more clearly define the impact of CD screening in routine clinical practice and to determine the effectiveness of gluten-free diet in this patient population.
AGA Abstracts
S2088 TLR2, TLR4, and CD14 Polymorphisms Are Associated with Acute Pancreatitis in Japan Yasuhiko Takagi, Atsushi Masamune, Kiyoshi Kume, Tooru Shimosegawa Background and Aim: Factors underlying genetic predisposition for development of acute pancreatitis (AP) are largely unknown. Toll-like receptors (TLRs) are proteins involved in recognition of foreign pathogen-associated molecular patterns and activation of innate immunity. Among human TLRs, TLR2 recognizes the peptidoglycan of gram-positive bacteria whereas TLR4 recognizes lipopolysaccharide from gram-negative bacteria. CD14 is a coreceptor for TLR2 and TLR4. Recent studies have suggested a role of TLRs 2 and 4 in the development of AP. We here examined the association between the polymorphisms in the TLR2, TLR4 and CD14 genes with AP in Japan. Methods: This study was approved by the Ethics Committee of Tohoku University School of Medicine. A total of 100 (65 males and 35 females) unrelated patients with AP and 150 unrelated healthy volunteers were enrolled
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