- Email: [email protected]
1381 INDICATION OF MRI LIVER IRON CONCENTRATION DETERMINATION WITHIN THE HIGH LIVER IRON OVERLOAD DIAGNOSTIC ALGORITHM
POSTERS 1379 THE COURSE OF CHRONIC HBV INFECTION IN CHILDREN. WHEN SHOULD WE INITIATE ANTIVIRAL TREATMENT? A ROMANIAN 8 YEARS FOLLOW UP STUDY O. Belei1 , I. Simedrea1 , M. Pop2 , L. Olariu1 . 1 First Pediatric Clinic, 2 Third Pediatric Clinic, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania E-mail: [email protected] Introduction: Natural history studies show that the risk of development chronic HBV infection is inversely proportional with age of acquisition: 25% of children infected at <5 years develop chronic infection, versus <10% adults. In Romania, treatment of HBV infection in children is limited to lamivudine (until 2009) and alpha2b standard interferon. Treatment of all children with chronic B hepatitis must be tempered by studying the natural history in children. Spontaneous HBeAg clearance is influenced by mode of transmission, viral load, necroinflammatory activity, immunocompetence, genotype. Aim: To investigate the rate of HBeAg/HBsAg seroconversion during childhood, spontaneous and after antiviral treatment. Methods: We retrospectively studied 176 children with chronic HBV infection and +HBeAg diagnosed between 2003–2011. The route of transmission was vertical in 92 and parenteral/unknown in 84 children. The mean age at diagnosis was 7.5 years (6 months to 16 years). In the lot with vertical transmission, 64 children emerged from HBe+Ag mothers with high viral load and 28 from HBe−/HBs+Ag mothers with low viral load. 112 children were diagnosed in the first 4 years of life. HBVmarkers, viral load, clinical and liver function were tested at least once every 6 months. Results: 24 (21%) of the 112 infected infants seroconvert in “e” system before 4 years without treatment. 3 (12%) infants with spontaneous HBeAg seroconversion emerged from HBe+Ag mothers compared to 6 (25%) from HBe−Ag mothers and 15 (63%) from noninfected mothers (p < 0.005).No spontaneous “s system” seroconversion was detected.58 children older than 4 years (HBs+Ag/HBe+Ag, hypertransaminasemia, detectable viral load, necroinflamatory activity) started antiviral treatment. HBe+Ag seroconversion and virusologic respond rate were 48% after 12 months of Interferon and 24%, respectively 45% after 12 months, respectively 24 months of Lamivudine (p < 0.005 at one year). HBsAg clearance was obtained in 2 cases (3%) after one year of Interferon and in 1 case (1.7%) after 2 years of Lamivudine. Conclusions: Maternal carrier status is very important: children of HBeAg seropositive mothers have lower rates of HBeAg seroconversion. Due to the possibility of spontaneous HBeAg seroconversion, antiviral treatment shouldn’t be initiated in the first 4 years of life. HBsAg clearance rate was higher but not statistic significant in children who had anti-HBeAb achieved under Interferon treatment. 1380 HYPERFERRITINEMIA: PHENOTYPIC CHARACTERISTICS, RELEVANCE OF HFE MUTATIONS AND MAGNETIC RESONANCE AMONG OUTPATIENT REFERRALS FOR ELEVATED SERUM FERRITIN 2 A. Castiella1 , E. Zapata1 , L. Zubiaurre1 , J.M. Alustiza ´ , M.D. De Juan3 , A. Aguirre1 , J.I. Emparanza4 , P. Otazua5 . 1 Gastroenterology, Mendaro Hospital, Mendaro, 2 Radiology, Osatek Donostia, 3 Immunology, 4 Epidemiology Unit, Donostia Hospital, Donostia, 5 Gastroenterology, Mondragon Hospital, Mondragon, Spain E-mail: [email protected] Aim: To determine the causes of elevated serum ferritin of outpatients referred to a secondary hospital. Patients-methods: January to December 2010, prospective study, included 132 consecutive patients with HF (>200 mg/L women, >300 mg/L men); Laboratory: serum ferritin, transferrin saturation, S542
serum iron, transaminases, glucose, cholesterol, triglycerides, HBV, HCV, HFE mutations. Blood presure, weight, height, BMI, alcohol intake, hypertension and/or dyslipidemia treatment, were determined; Radiology: abdominal ultrasound, MRI to determine LIC (liver iron concentration); liver biopsy. Results: 24 women, 108 men, mean age 54.42 SD 13.47 (range 23–83), Weight: 83.17 SD 15.86 (43–137); Height: 175.28 SD 55.20 (146–186), BMI: 28.80 SD 3.96 (17–39); Ferritin 579.54 SD 296.575 (206–1668), TRS 43.87 SD14.09 (12–95); Fe 134 SD 49.68 (55– 322). Ferritin >1000, 12 patients (9%), overweight (BMI ≥ 25) 48.31%, obesity (BMI ≥ 30) 40.44%, 89% overweight or obese. HFE mutations (120 patients): wt/wt 47 (39.16%); H63D/wt 38 (31.66%), H63D/H63D 21 (17.5%); C282Y/wt 6 (5%); C282Y/H63D 6 (5%) S65C/wt 2 (1.66%) – similar to controls in the same region. The genotypic frequency of the H63D/H63D mutation is more than double than in controls (17.5% vs 7.76%), the allelic frequency of the H63D mutation is 36%. The ethanol consumption revealed 77 (63.6%) without consumption; 22 with ≥60 g of ethanol/day (18.1%). The mean consumption was 20.83 SD 33.95 (0–140). Viral serology, HBV 2 (1.5%) HBsAg(+) and HCV(+) 4 (3%) – 6/132 (4.5%). Hypertension treatment in 50 patients; dyslipidemia treatment in 35. Abdominal ultrasound: suggestive of steatosis (NAFLD) in 69/132 (52.3%), normal in 44 (33.3%), other findings (14.4%). MR-LIC: 79/132. Mean LIC 36.04 (n < 36) SD32.78 (5–210), 53 normal, 22 iron overload (37–80), 4 high iron overload (>80). A 33% of patients had real iron overload and 5% high iron overload (>80). Conclusions: 1. H63D/H63D genotype appears to predispose to suffer HF (OR > 2). 2. Obesity (BMI > 30) and overweight (BMI > 25) affect 89% of HF patients. 3. MRI revealed real iron overload in 33% of the patients and only 5% had HF in the range of hemochromatosis. 1381 INDICATION OF MRI LIVER IRON CONCENTRATION DETERMINATION WITHIN THE HIGH LIVER IRON OVERLOAD DIAGNOSTIC ALGORITHM 2 A. Castiella1 , J.M. Alustiza ´ , E. Zapata1 , I. Urreta3 , J.I. Emparanza3 , M.D. De Juan4 , E. Zubillaga5 , A. Azkune5 , M.L. Rincon6 , on behalf of the Burnia Group. 1 Gastroenterology Service, Mendaro Hospital, Mendaro, 2 Radiology, Osatek Donostia, 3 Epidemiology Unit, 4 Immunology Service, 5 Internal Medicine, Donostia Hospital, Donostia, 6 Gastroenterology Service, Bidasoa Hospital, Irun, Spain E-mail: [email protected] Introduction: Magnetic Resonance Imaging (MRI) has demonstrated the capacity to exactly measure liver iron concentration (LIC) and as a non-invasive technique will take a significative place in the diagnostic algorithm of the patients with high iron overload of the liver (HIO). However, the indications for the quantification the LIC by MRI in the different clinical situations are still not well defined. Aims: To define the indications of LIC quantification by MRI within HIO diagnostic algorithm. To evaluate the utility of the transferrin saturation index (TS) and serum ferritin (SF) in the HIO diagnostic algorithm. Material and Methods: Retrospective study of all the consecutive patients studied by MRI to determine the LIC between 2002–2008. MRI results were compared to TS (n < 45%), SF (n < 300 mg/L) and genetic study (HFE gene mutations); Specificity (Sp), Sensitivity (Se), Positive predictive value (PPV) and Negative predictive value (NPV) were calculated. The gold standard for HIO diagnosis was Hepatic iron index >1.9 (LIC by MRI/age).
Journal of Hepatology 2012 vol. 56 | S389–S548
POSTERS Results: From 478 patients studied by MRI we retrieved all the other study parameters in 242 (198 men/44 women). Mean age: 52.4 (SD 13.3). From the 242 patients included, 206 were without HIO and 36 had HIO. TS was raised in 141 patients (108NHIO/ 33HIO); SF raised in 207 patients (175/35). Genetic study revealed 28 C282Y (8/20), 27 H63/H63D (23/4), 25 C282Y/H63D (23/2). For raised TS, Se was 91.7% and Sp 48%. Raised SF, Se 97% and Sp 16%, Raised TS-SF combination, Se 89%, Sp 59%. C282Y/C282Y, Se 56%, Sp 96%; H63D/H63D, Se 11%, Sp 89%; C282Y/H63D, Se 6%, Sp 89%. Combination of C282Y/C282Y and raised TS-SF, Se 50%, Sp 98% (95–99). From 22 patients with C282Y/C282Y and raised TS-SF, 18 presented HIO: PPV 82%. From 125 patients with not raised TS or SF (52%), 121 without HIO: NPV 97%. Conclusions: 61% of the patients do not need MRI for HIO diagnosis. Normal ST or SF have high NPV for HIO and the combination of raised ST and SF with C282Y/C282Y mutation has high PPV for HIO. MRI is indicated in patients with raised ST and SF and other HFE mutations. 1382 LONG-TERM EFFECTS OF TAFAMIDIS – A NEW THERAPEUTIC OPTION FOR PATIENTS WITH TRANSTHYRETIN FAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP) T. Coelho1 , L. Maia1 , A. Martins da Silva1 , M. Waddington Cruz2 , 3 V. Plante-Bordeneuve ´ , O.B. Suhr4 , I. Conceicao ¸ 5 , H. Schmidt6 , P. Trigo7 , J. Packman8 , M. Harnett9 , D.R. Grogan8 . 1 Hospital Santo Ant´ onio, Porto, Portugal; 2 HUCFF-UFRJ, Rio de Janeiro, Brazil; 3 CHU Henri Mondor, Cr´eteil, France; 4 Ume˚ a University Hospital, Ume˚ a, Sweden; 5 Hospital de Santa Maria, Lisbon, Portugal; 6 Universit¨ atsklinikum M¨ unster, M¨ unster, Germany; 7 FLENI, Buenos 8 Aires, Argentina; Pfizer Inc, New York, NY, 9 Stow, MA, USA E-mail: [email protected] Background and Aims: Until recently, liver transplantation was the sole treatment option for TTR-FAP. Despite improving quality of life and survival, particularly in patients with early-stage disease, it has several limitations. Tafamidis is a small molecule that kinetically stabilizes transthyretin (TTR). In an 18-month, randomized, doubleblind placebo-controlled trial (study Fx-005), tafamidis slowed disease progression in patients with TTR-FAP. The objectives of the present study were to assess the long-term efficacy, safety, and tolerability of tafamidis. Methods: This 12-month, open-label extension study evaluated the safety and efficacy of 20 mg oral tafamidis once daily in patients with V30M TTR-FAP who had completed study Fx-005. Patients who received tafamidis or placebo for 18 months in study Fx-005 were given tafamidis for 12 months. Efficacy measures included the Neuropathy Impairment Score-Lower Limbs (NIS-LL), Norfolk total quality of life score (TQOL) and measures of large and small nerve fiber function. The monthly rates of change in each endpoint over the 12 months of treatment in the extension study and the 18 months of the original study were compared. Treatment-related adverse events were monitored. Results: Patients who switched from 18 months of placebo to 12 months of tafamidis experienced slowing of the monthly rates of change: NIS-LL (from 0.34/month with placebo to 0.16/month with tafamidis, p = 0.0103), TQOL (from 0.61/month to −0.16/month; p = 0.0003), large – (from 0.18/month to 0.11/month; p = 0.2133), and small nerve fiber function (from 0.09/month to 0.04/month; p = 0.0551). Patients who continued on tafamidis had stable rates of change: NIS-LL (from 0.08/month in the original study to 0.11/month in the extension study; p = 0.6000), TQOL (from −0.03/month to 0.25/month; p = 0.1632), large – (from 0.06/month to 0.05/month; p = 0.9298), and small-nerve fiber function (from 0.03/month to 0.05/month, p = 0.3348). Patients treated with tafamidis for 30 months had greater preservation of neurologic function (NIS-LL 55.9%) than patients who were treated for only
12 months. The most common treatment-related AE was headache (4.7%). Conclusions: The treatment effect of tafamidis was sustained over 30 months and it was safe and well tolerated. Earlier treatment initiation preserved peripheral neurologic function. This study was sponsored by FoldRx Pharmaceuticals, acquired by Pfizer Inc in October 2010. 1383 IGG4-PLASMA CELL INFILTRATE IN THE LIVER AND COLON OF CHILDREN WITH PRIMARY SCLEROSING CHOLANGITIS E.L. Culver1,2 , A. Rodriguez3 , D. Delaney4 , J. Collier1 , P. Klenerman2 , R.W. Chapman1,2 , E. Barnes1,2 . 1 Translational Gastroenterology Unit, John Radcliffe University Hospitals NHS Trust, 2 Nuffield Department Medicine, Oxford University, 3 Pediatric Gastroenterology, 4 Histopathology, John Radcliffe University Hospitals NHS Trust, Oxford, UK E-mail: [email protected] Background and Aims: Children diagnosed with primary sclerosing cholangitis (PSC) more frequently have features of overlap with steroid-responsive autoimmune hepatitis (AIH) than adults with PSC. Since IgG4-associated cholangitis (IAC) is difficult to distinguish from PSC, we sought to determine whether children diagnosed with PSC may in fact have steroid-responsive IgG4related systemic disease (IgG4-RSD). Methods: Retrospective controlled study of 14 children with PSC in Oxford Radcliffe Hospital from 2001 to 2011. Controls included 5 children with AIH, 10 children with colitis, 12 adults with PSC and 10 adults with colitis and normal bile ducts. Serum IgG and IgG4 were measured by nephlometry. Tissue from the liver, colon, stomach and duodenum from diagnosis were immunostained with monoclonal IgG4 and CD138. A blinded pathologist calculated the mean number of IgG4-plasma cells in three high power fields (HPF). Clinical records were reviewed. Fishers Exact test was used. Results: Fourteen children, median age 13.5years (9–16 yr) and 79% male, had sclerosing cholangitis on liver histology. Six (43%) had large duct involvement and 1 (7%) had an abnormal pancreatogram. Four (29%) had autoimmune overlap and 11 of 13 (85%) had colitis. Liver IgG4-cells were >10/HPF in 6 of 14 (43%); 50% of these had >20/HPF in a peri-ductal distribution. IgG4 count was independent of fibrosis or inflammation on biopsy. Colonic IgG4-cells were >10/HPF in 8 of 13 (62%); 50% of these had >20/HPF. This was significantly associated with an elevated IgG4-cell count in the liver (p = 0.016; OR 4.0; 95% CI 1.2–13.3) but independent of the presence or severity of colitis or inflammatory markers. There was no difference in demographics, clinical presentation or treatment outcome in the groups with an elevated or normal serum/tissue IgG4 after mean follow-up of 38 months (4.6–183 mo). One child had an elevated serum and tissue IgG4, autoimmune overlap, lymphadenopathy, biliary strictures and dilated pancreatic duct, and was steroid-responsive. This may represent a childhood variant of IgG4-RSD. Conclusion: An IgG4-cell infiltrate in the liver and colon is a common feature in children previously diagnosed with PSC. Longterm follow-up of this cohort is warranted to determine the natural evolution of this disease into adulthood and long-term prognosis. 1384 LONGITUDINAL ASSESSMENT OF PATIENTS WITH CYSTIC FIBROSIS WITH LIVER STIFFNESS MEASUREMENT (FIBROSCAN® ) V. de Ledinghen1 , H. Clouzeau2 , J. Foucher1 , J. Vergniol1 , F. Chermak1 , M. Gaboreau1 , T. Lamireau2 . 1 CHU Bordeaux, Pessac, 2 CHU Bordeaux, Bordeaux, France E-mail: [email protected] Background: Hepatic involvement is frequent in patients with cystic fibrosis (CF). Liver stiffness measurement (LSM) is a non-
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serum iron, transaminases, glucose, cholesterol, triglycerides, HBV, HCV, HFE mutations. Blood presure, weight, height, BMI, alcohol intake, hypertension and/or dyslipidemia treatment, were determined; Radiology: abdominal ultrasound, MRI to determine LIC (liver iron concentration); liver biopsy. Results: 24 women, 108 men, mean age 54.42 SD 13.47 (range 23–83), Weight: 83.17 SD 15.86 (43–137); Height: 175.28 SD 55.20 (146–186), BMI: 28.80 SD 3.96 (17–39); Ferritin 579.54 SD 296.575 (206–1668), TRS 43.87 SD14.09 (12–95); Fe 134 SD 49.68 (55– 322). Ferritin >1000, 12 patients (9%), overweight (BMI ≥ 25) 48.31%, obesity (BMI ≥ 30) 40.44%, 89% overweight or obese. HFE mutations (120 patients): wt/wt 47 (39.16%); H63D/wt 38 (31.66%), H63D/H63D 21 (17.5%); C282Y/wt 6 (5%); C282Y/H63D 6 (5%) S65C/wt 2 (1.66%) – similar to controls in the same region. The genotypic frequency of the H63D/H63D mutation is more than double than in controls (17.5% vs 7.76%), the allelic frequency of the H63D mutation is 36%. The ethanol consumption revealed 77 (63.6%) without consumption; 22 with ≥60 g of ethanol/day (18.1%). The mean consumption was 20.83 SD 33.95 (0–140). Viral serology, HBV 2 (1.5%) HBsAg(+) and HCV(+) 4 (3%) – 6/132 (4.5%). Hypertension treatment in 50 patients; dyslipidemia treatment in 35. Abdominal ultrasound: suggestive of steatosis (NAFLD) in 69/132 (52.3%), normal in 44 (33.3%), other findings (14.4%). MR-LIC: 79/132. Mean LIC 36.04 (n < 36) SD32.78 (5–210), 53 normal, 22 iron overload (37–80), 4 high iron overload (>80). A 33% of patients had real iron overload and 5% high iron overload (>80). Conclusions: 1. H63D/H63D genotype appears to predispose to suffer HF (OR > 2). 2. Obesity (BMI > 30) and overweight (BMI > 25) affect 89% of HF patients. 3. MRI revealed real iron overload in 33% of the patients and only 5% had HF in the range of hemochromatosis. 1381 INDICATION OF MRI LIVER IRON CONCENTRATION DETERMINATION WITHIN THE HIGH LIVER IRON OVERLOAD DIAGNOSTIC ALGORITHM 2 A. Castiella1 , J.M. Alustiza ´ , E. Zapata1 , I. Urreta3 , J.I. Emparanza3 , M.D. De Juan4 , E. Zubillaga5 , A. Azkune5 , M.L. Rincon6 , on behalf of the Burnia Group. 1 Gastroenterology Service, Mendaro Hospital, Mendaro, 2 Radiology, Osatek Donostia, 3 Epidemiology Unit, 4 Immunology Service, 5 Internal Medicine, Donostia Hospital, Donostia, 6 Gastroenterology Service, Bidasoa Hospital, Irun, Spain E-mail: [email protected] Introduction: Magnetic Resonance Imaging (MRI) has demonstrated the capacity to exactly measure liver iron concentration (LIC) and as a non-invasive technique will take a significative place in the diagnostic algorithm of the patients with high iron overload of the liver (HIO). However, the indications for the quantification the LIC by MRI in the different clinical situations are still not well defined. Aims: To define the indications of LIC quantification by MRI within HIO diagnostic algorithm. To evaluate the utility of the transferrin saturation index (TS) and serum ferritin (SF) in the HIO diagnostic algorithm. Material and Methods: Retrospective study of all the consecutive patients studied by MRI to determine the LIC between 2002–2008. MRI results were compared to TS (n < 45%), SF (n < 300 mg/L) and genetic study (HFE gene mutations); Specificity (Sp), Sensitivity (Se), Positive predictive value (PPV) and Negative predictive value (NPV) were calculated. The gold standard for HIO diagnosis was Hepatic iron index >1.9 (LIC by MRI/age).
Journal of Hepatology 2012 vol. 56 | S389–S548
POSTERS Results: From 478 patients studied by MRI we retrieved all the other study parameters in 242 (198 men/44 women). Mean age: 52.4 (SD 13.3). From the 242 patients included, 206 were without HIO and 36 had HIO. TS was raised in 141 patients (108NHIO/ 33HIO); SF raised in 207 patients (175/35). Genetic study revealed 28 C282Y (8/20), 27 H63/H63D (23/4), 25 C282Y/H63D (23/2). For raised TS, Se was 91.7% and Sp 48%. Raised SF, Se 97% and Sp 16%, Raised TS-SF combination, Se 89%, Sp 59%. C282Y/C282Y, Se 56%, Sp 96%; H63D/H63D, Se 11%, Sp 89%; C282Y/H63D, Se 6%, Sp 89%. Combination of C282Y/C282Y and raised TS-SF, Se 50%, Sp 98% (95–99). From 22 patients with C282Y/C282Y and raised TS-SF, 18 presented HIO: PPV 82%. From 125 patients with not raised TS or SF (52%), 121 without HIO: NPV 97%. Conclusions: 61% of the patients do not need MRI for HIO diagnosis. Normal ST or SF have high NPV for HIO and the combination of raised ST and SF with C282Y/C282Y mutation has high PPV for HIO. MRI is indicated in patients with raised ST and SF and other HFE mutations. 1382 LONG-TERM EFFECTS OF TAFAMIDIS – A NEW THERAPEUTIC OPTION FOR PATIENTS WITH TRANSTHYRETIN FAMILIAL AMYLOID POLYNEUROPATHY (TTR-FAP) T. Coelho1 , L. Maia1 , A. Martins da Silva1 , M. Waddington Cruz2 , 3 V. Plante-Bordeneuve ´ , O.B. Suhr4 , I. Conceicao ¸ 5 , H. Schmidt6 , P. Trigo7 , J. Packman8 , M. Harnett9 , D.R. Grogan8 . 1 Hospital Santo Ant´ onio, Porto, Portugal; 2 HUCFF-UFRJ, Rio de Janeiro, Brazil; 3 CHU Henri Mondor, Cr´eteil, France; 4 Ume˚ a University Hospital, Ume˚ a, Sweden; 5 Hospital de Santa Maria, Lisbon, Portugal; 6 Universit¨ atsklinikum M¨ unster, M¨ unster, Germany; 7 FLENI, Buenos 8 Aires, Argentina; Pfizer Inc, New York, NY, 9 Stow, MA, USA E-mail: [email protected] Background and Aims: Until recently, liver transplantation was the sole treatment option for TTR-FAP. Despite improving quality of life and survival, particularly in patients with early-stage disease, it has several limitations. Tafamidis is a small molecule that kinetically stabilizes transthyretin (TTR). In an 18-month, randomized, doubleblind placebo-controlled trial (study Fx-005), tafamidis slowed disease progression in patients with TTR-FAP. The objectives of the present study were to assess the long-term efficacy, safety, and tolerability of tafamidis. Methods: This 12-month, open-label extension study evaluated the safety and efficacy of 20 mg oral tafamidis once daily in patients with V30M TTR-FAP who had completed study Fx-005. Patients who received tafamidis or placebo for 18 months in study Fx-005 were given tafamidis for 12 months. Efficacy measures included the Neuropathy Impairment Score-Lower Limbs (NIS-LL), Norfolk total quality of life score (TQOL) and measures of large and small nerve fiber function. The monthly rates of change in each endpoint over the 12 months of treatment in the extension study and the 18 months of the original study were compared. Treatment-related adverse events were monitored. Results: Patients who switched from 18 months of placebo to 12 months of tafamidis experienced slowing of the monthly rates of change: NIS-LL (from 0.34/month with placebo to 0.16/month with tafamidis, p = 0.0103), TQOL (from 0.61/month to −0.16/month; p = 0.0003), large – (from 0.18/month to 0.11/month; p = 0.2133), and small nerve fiber function (from 0.09/month to 0.04/month; p = 0.0551). Patients who continued on tafamidis had stable rates of change: NIS-LL (from 0.08/month in the original study to 0.11/month in the extension study; p = 0.6000), TQOL (from −0.03/month to 0.25/month; p = 0.1632), large – (from 0.06/month to 0.05/month; p = 0.9298), and small-nerve fiber function (from 0.03/month to 0.05/month, p = 0.3348). Patients treated with tafamidis for 30 months had greater preservation of neurologic function (NIS-LL 55.9%) than patients who were treated for only
12 months. The most common treatment-related AE was headache (4.7%). Conclusions: The treatment effect of tafamidis was sustained over 30 months and it was safe and well tolerated. Earlier treatment initiation preserved peripheral neurologic function. This study was sponsored by FoldRx Pharmaceuticals, acquired by Pfizer Inc in October 2010. 1383 IGG4-PLASMA CELL INFILTRATE IN THE LIVER AND COLON OF CHILDREN WITH PRIMARY SCLEROSING CHOLANGITIS E.L. Culver1,2 , A. Rodriguez3 , D. Delaney4 , J. Collier1 , P. Klenerman2 , R.W. Chapman1,2 , E. Barnes1,2 . 1 Translational Gastroenterology Unit, John Radcliffe University Hospitals NHS Trust, 2 Nuffield Department Medicine, Oxford University, 3 Pediatric Gastroenterology, 4 Histopathology, John Radcliffe University Hospitals NHS Trust, Oxford, UK E-mail: [email protected] Background and Aims: Children diagnosed with primary sclerosing cholangitis (PSC) more frequently have features of overlap with steroid-responsive autoimmune hepatitis (AIH) than adults with PSC. Since IgG4-associated cholangitis (IAC) is difficult to distinguish from PSC, we sought to determine whether children diagnosed with PSC may in fact have steroid-responsive IgG4related systemic disease (IgG4-RSD). Methods: Retrospective controlled study of 14 children with PSC in Oxford Radcliffe Hospital from 2001 to 2011. Controls included 5 children with AIH, 10 children with colitis, 12 adults with PSC and 10 adults with colitis and normal bile ducts. Serum IgG and IgG4 were measured by nephlometry. Tissue from the liver, colon, stomach and duodenum from diagnosis were immunostained with monoclonal IgG4 and CD138. A blinded pathologist calculated the mean number of IgG4-plasma cells in three high power fields (HPF). Clinical records were reviewed. Fishers Exact test was used. Results: Fourteen children, median age 13.5years (9–16 yr) and 79% male, had sclerosing cholangitis on liver histology. Six (43%) had large duct involvement and 1 (7%) had an abnormal pancreatogram. Four (29%) had autoimmune overlap and 11 of 13 (85%) had colitis. Liver IgG4-cells were >10/HPF in 6 of 14 (43%); 50% of these had >20/HPF in a peri-ductal distribution. IgG4 count was independent of fibrosis or inflammation on biopsy. Colonic IgG4-cells were >10/HPF in 8 of 13 (62%); 50% of these had >20/HPF. This was significantly associated with an elevated IgG4-cell count in the liver (p = 0.016; OR 4.0; 95% CI 1.2–13.3) but independent of the presence or severity of colitis or inflammatory markers. There was no difference in demographics, clinical presentation or treatment outcome in the groups with an elevated or normal serum/tissue IgG4 after mean follow-up of 38 months (4.6–183 mo). One child had an elevated serum and tissue IgG4, autoimmune overlap, lymphadenopathy, biliary strictures and dilated pancreatic duct, and was steroid-responsive. This may represent a childhood variant of IgG4-RSD. Conclusion: An IgG4-cell infiltrate in the liver and colon is a common feature in children previously diagnosed with PSC. Longterm follow-up of this cohort is warranted to determine the natural evolution of this disease into adulthood and long-term prognosis. 1384 LONGITUDINAL ASSESSMENT OF PATIENTS WITH CYSTIC FIBROSIS WITH LIVER STIFFNESS MEASUREMENT (FIBROSCAN® ) V. de Ledinghen1 , H. Clouzeau2 , J. Foucher1 , J. Vergniol1 , F. Chermak1 , M. Gaboreau1 , T. Lamireau2 . 1 CHU Bordeaux, Pessac, 2 CHU Bordeaux, Bordeaux, France E-mail: [email protected] Background: Hepatic involvement is frequent in patients with cystic fibrosis (CF). Liver stiffness measurement (LSM) is a non-
Journal of Hepatology 2012 vol. 56 | S389–S548
S543