Wataru Fukuda

Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan

Background Although the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial. Objectives To investigate the incidence and risk factors for HBV reactivation in patients with RD. Methods We performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded. Results Among 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3–182 months; median, 66 months). Conclusions The incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.

Low body mass index is associated with impaired quality of life in patients with rheumatoid arthritis.

To investigate the relationship between quality of life (QOL) and rheumatoid chachesia, malnutrition in patients with rheumatoid arthritis (RA).

Contribution of rheumatoid arthritis disease activity and disability to rheumatoid cachexia

This cross-sectional study was done to show how nutritional indices influence each other and the contributions made by inflammation to the development of rheumatoid cachexia. We studied 295 female patients with rheumatoid arthritis (RA). We chose five nutritional indices: body mass index (BMI), arm muscle area (AMA), triceps skinfold thickness (TSF), which were obtained via anthropometric measurements, and serum albumin and cholesterol. Clinical indicators of RA included disease duration, C-reactive protein (CRP) and Disease Activity Score 28 (DAS28). We performed a bivariate correlation test between the nutritional indices and multiple regression analysis for each nutritional index. Mean AMA was low, 87.3% of the normal value, whereas TSF was not different. Muscle protein expressed by AMA decreased according to RA duration, whereas visceral protein indicated by serum albumin decreased with an increase in RA activity. The continuation of inflammation appears to be essential for a decrease in muscle protein in rheumatoid cachexia. DAS28 showed a positive contribution to BMI in the regression model, and the increase in RA disease activity causes an increase in BMI via an accumulation of tissue fat.

SAT0140 Prevalence of Reactivation of Hepatitis B Virus (HBV) in Patients with Resolved Hbv Hepatitis on Immunosuppressive Therapy for Rheumatic Disease: Multicentre Prospective Observational Study in Japan

Background Although the reactivation of hepatitis B virus (HBV) is recognized as a serious complication in patients with connective tissue disease (CTD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors of reactivation remain controversial. Objectives We performed a multicentre, observational, prospective study across 16 Japanese Red Cross hospitals to clarify the prevalence and pathophysiology of HBV reactivation in patients with CTD. We report the results of 2-year observations in patients with resolved HBV infection. Methods Patients with CTD, treated with a dose of ≥5 mg/day prednisolone, and/or synthetic or biological ISDs, with negative HBs antigen and positive anti HBs and/or HBc antibody (Ab), were enrolled. HBV-DNA (RT-PCR) and related data were registered regularly. Results Among 1040 patients, including 950 rheumatoid arthritis, HBV-DNA was detected in 32 patients (1.75/100 person-years), and >2.1 log copy/ml was observed in 9 cases (0.49/100 person-years) over 1–2 years of observation. None of the reactivated patients, including six treated with a nucleic acid analogue, showed overt hepatitis. Low HBs Ab titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in 3 patients with positive HBs Ab and negative HBc Ab. The risk of reactivation among the different types of ISDs was not statistically different. The intervals from the start of ISD to reactivation were longer than previous reports (4–157 months, average 58.9 months). Conclusions HBV reactivation with ISD was 1.75/100 person-years in CTD patients with resolved HBV infection. Overt hepatitis was observed in none of the reactivated patients, and low HBs antibody titres and advanced age were risk factors for reactivation. Patients with positive HBs Ab and negative HBc Ab are not free from the risk of reactivation of HBV. References B. J Hepatol 2012: 57. 167–185 Disclosure of Interest None declared

Rapamycin Improves Mortality Following Intestinal Ischemia-Reperfusion via the Inhibition of Remote Lung Inflammation in Mice.

Background/Aims: Acute-phase intestinal ischemia-reperfusion (I-R) injury can result in multiple organ failure, which may sometimes be fatal. However, no reliable treatment for this clinical state is available. Rapamycin has been reported to protect heart, brain and kidney against I-R injury. The aim of this study was to examine whether rapamycin could protect mice against I-R-induced intestinal and remote organ injury. Methods: Ischemia was induced in the intestine of C57BL/6 mice by occluding the superior mesenteric artery for 1 h. Mice received rapamycin at a dose of 5 mg/kg or vehicle by the intraperitoneal injection 1 h before ischemia. The survival rate, inflammatory responses in the intestine and the lung, bacteria cultured from lung tissue and the phagocytic capacity of alveolar macrophages were examined. Results: Treatment with rapamycin improved survival rate after intestinal I-R. Histological and biochemical parameters of I-R-induced intestinal injury/inflammation were similar in both rapamycin-treated and untreated mice. However, signs of lung injury/inflammation were significantly attenuated in rapamycin-treated mice compared to control mice. The reduction of lung bacteria and the increase in phagocytic activity were accompanied in mice treated with rapamycin. Conclusion: Rapamycin improved mortality following intestinal I-R via the inhibition of remote lung inflammation in mice.

Tu1996 Rapamycin Reduced the Mortality in Mice Injured by Intestinal Ischemia-Reperfusion Through the Inhibition of Remote Organ Failure

Rapamycin Reduced the Mortality in Mice Injured by Intestinal IschemiaReperfusion Through the Inhibition of Remote Organ Failure Takaya Iida, Yuji Naito, Tomohisa Takagi, Kazuhiro Katada, Katsura Mizushima, Yasuki Higashimura, Syunsuke Kishimoto, Kentaro Suzuki, Hideki Horie, Wataru Fukuda, Yutaka Inada, Yukiko Uehara, Munehiro Kugai, Hiroyuki Yoriki, Toshifumi Tsuji, Akifumi Fukui, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Nobuaki Yagi, Toshikazu Yoshikawa

Su2063 Partially Hydrolyzed Guar Gum (PHGG) Inhibits Castor Oil-Induced Diarrhea in Rats Through the Inhibition of Substance P Production

Partially Hydrolyzed Guar Gum (PHGG) Inhibits Castor Oil-Induced Diarrhea in Rats Through the Inhibition of Substance P Production Kentaro Suzuki, Yuji Naito, Kazuhiro Kamada, Syunsuke Kishimoto, Yukiko Uehara, Hideki Horie, Wataru Fukuda, Yutaka Inada, Takaya Iida, Munehiro Kugai, Toshifumi Tsuji, Hiroyuki Yoriki, Akifumi Fukui, Yasuki Higashimura, Katsura Mizushima, Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Zenta Yasukawa, Makoto Tokunaga, Tsutomu Okubo, Lekh R. Juneja, Toshikazu Yoshikawa

Mo1823 Involvement of MDR1 in Intestinal Epithelial Injury Caused by Acetylsalicylic Acid

Introduction Intestinal fibrosis (IF) is a major complication of chronic inflammation of the intestinal tissue in inflammatory bowel disease (IBD). IF can cause narrowing of the intestinal lumen, which may lead to stricture formation. Currently, adequate models are lacking to study the mechanism of intestinal fibrosis in IBD. Our aim is to develop an ex vivo model for IF by using mouse precision-cut intestinal slice (PCIS). In addition, regional differences in the onset of fibrosis in the bowel will be studied. In PCIS all cell types are present in their original tissue-matrix environment. As fibrosis is a multicellular phenomenon, PCIS can be used as a model to study the early onset of intestinal fibrosis. Methods Mouse jejunum, ileum and colon were excised and prepared as segments embedded in agarose. PCIS (estimated 300-400 μm) were prepared and incubated up to 48 hr. ATP content of the PCIS was used to assess the general viability. To study the early onset of fibrosis, the gene expression of different fibrosis markers: Pro-Collagen 1 A1 (COL1A1), Heat Shock Protein 47 (HSP47), alpha-Smooth Muscle Actin (SMA) and Fibronectin (FN1) was determined in PCIS after 48 hr of incubation. Results Mouse PCIS from the different regions of the bowel were viable up to 48 hr in culture. After 48 hr of incubation of PCIS, HSP47 and FN1 gene expression was significantly up-regulated, compared to PCIS directly after slicing, in jejunum (3.9 and 3.6 fold, respectively) and in ileum (4.5 and 4.9 fold, respectively). Gene expression of Col1A1 (0.7 fold) was only down-regulated in PCIS from the colon. SMA gene expression was down-regulated in PCIS from all the regions of the intestine. PCIS from jejunum cultured in the presence of 5ng/mL Transforming-Growth Factor (TGF)β1 for 48 hr, HSP47 (1.2 fold), FN1 (4.6 fold) and COL1A1 (2.0 fold) were significantly upregulated compared to control PCIS after 48 hr of incubation. In addition, in PCIS from Ileum incubated with 5ng/mL TGF-β1, the gene expression of HSP47 (1.9 fold) and FN1 (3.9 fold) was significantly increased. In PCIS from the colon cultured for 48 hr in the presence of 5ng/ml TGF-β1, the gene expression of fibrosis markers was not affected. Conclusion Mouse PCIS from different regions of the bowel can successfully be cultured for 48 hr. Fibrosis markers are induced by incubation up to 48 hr and by addition of TGFβ1 in jejunum and ileum PCIS, but not in colon PCIS. We are the first to show that regional differences in the onset of intestinal fibrosis can be measured using PCIS.