HCV ActivMHC Clas

WonseoD.-Y. ChY.-J. Ch

ReducedWith Feca

YasuhisaR. Iwakir

January 2015 Abstracts 217

ates Protein Kinase R and Attenuates Interferon-Induceds I Expression to Circumvent CD8D T-Cell Responses

k Kang, P. S. Sung, S.-H. Park, S. Yoon,ang, S. Kim, K. H. Han, J. K. Kim, B. Rehermann,wae, and E.-C. Shin

PredictorFailure: D

Vinit Sha

BACKGROUND AND AIMS: Major histocompatibility complex(MHC) class I-restricted CD8þ T cells are required forclearance of hepatitis C virus (HCV) infection. MHC class Iexpression is up-regulated by type I and II interferons(IFNs). This study aimed to investigate the effect of HCVinfection on IFN-induced expression of MHC class I andits regulatory mechanisms.

METHODS: HCV cell culture system (HCVcc)-infectedHuh-7.5 cells with the genotype 2a Japanese fulminanthepatitis-1 strain were analyzed by flow cytometry,metabolic labeling, immunoprecipitation, and immuno-blotting analyses. Protein kinase R (PKR) was knockeddown with lentiviruses expressing small hairpin RNAs.Functional effects of MHC class I regulation by HCV weredemonstrated in co-culture studies, using HCV-specificCD8þ T cells.

RESULTS: Baseline level of MHC class I was not affected byHCV infection. However, IFN-induced expression of MHCclass I was notably attenuated in HCV-infected cells. Thiswas associated with replicating HCV RNA, not viral pro-tein. HCV infection reduced IFN-induced synthesis ofMHC class I protein and induced phosphorylation of PKRand eIF2a. IFN-induced MHC class I expression wasrestored by small hairpin RNA-mediated knockdown ofPKR in HCV-infected cells. Co-culture of HCV-specificCD8þ T cells and HCV-infected cells expressing HLA-A2demonstrated that HCV infection reduced the effectorfunctions of HCV-specific CD8þ T cells; these wererestored by small hairpin RNA-mediated knockdown ofPKR.

CONCLUSIONS: IFN-induced expression of MHC class I isattenuated in HCV-infected cells by activation of PKR,which reduces the effector functions of HCV-specificCD8þ T cells. This appears to be an important mecha-nism by which HCV circumvents antiviral adaptive im-mune responses.

Incidence of Colorectal Cancers With Repeated Screeningl Immunochemical Tests

Sakata, N. Sakata, A. Nakayama, R. Shimoda,i, M. Mizuguchi, and K. Fujimoto

BACKGROUND AND AIMS: Screening for fecal occult blood testwith fecal immunochemical tests (FIT), a widely utilizedtest for colorectal cancer (CRC) screening in Japan, hasreduced the mortality from CRC in the country. Thisstudy aimed to evaluate the importance of repeated FITscreening by comparing the incidence of CRC in patientsundergoing initial and repeated screening.

METHODS: Participants aged �40 years in Saga, Japan,were invited to undergo a 2-day FIT. FIT was analyzed bylatex agglutination immune-turbidimetry. The presence

of CRC in FIT positive (�100ng/mL) subjects was veri-fied by colonoscopy, and CRC incidence rates calculated.

RESULTS: From 2005 to 2007, 55,595 individuals wereinvited to undergo CRC screening, including 47,168 un-dergoing repeated and 8427 undergoing initialscreening. Of the 5832 FIT-positive subjects, 4615 wereassessed by colonoscopy and 114 subjects were diag-nosed as having CRC. Of these 114 patients, 67 had earlyand 47 had advanced CRC. The incidence of CRC was63% lower in the repeated than in the initial screeninggroup (P < .0001). The rate of curative endoscopictreatment for early CRC was higher in the repeated thanin the initial screening group. Overall survival was longerin screened subjects than in those who visited hospitalswith clinical symptoms.

CONCLUSIONS: Repeated annual CRC screening with FITreduced the incidence of CRC compared with initialscreening.

s of Mortality in Patients With Acute on Chronic Livero We Need Sub Classification?

h

BACKGROUND AND AIMS: To describe the clinical andbiochemical profiles of acute on chronic liver failure(ACLF) and effect of acute insult and associated organfailure on mortality.

METHODS: Patients were classified as ACLF-1 (only liverfailure), ACLF-2 (liver plus one organ failure), ACLF-3(liver plus two organ failures), and ACLF-4 (liver plus �3organ failures).

RESULTS: Study included 369 patients (median age, 44(15–75) years; male/female 335:34). Median valueswere: serum bilirubin, 16 (5–63.7) mg %; CTP score11(6–15); MELD score, 27(6–64); hospital stay, 8 (1–82)days; haemoglobin, 10.3 (4.6–15.7) g%; total leucocytecount (TLC), 11.1 (2.3 –65) 10

ˇ

3/?; platelet count, 123(21–521) 10

ˇ

3/?; international normalized ratio, 2.1(1.5–11); creatinine, 1 (0.3–9.1) mg %; Acute insultsincluded alcoholic hepatitis (n ¼ 206, 55.8%), unknownaetiology (n ¼ 49, 13.3 %), hepatitis B virus (HBV)reactivation (n ¼ 45, 12.2%) and acute hepatitis E (n ¼26, 7%). Aetiologies of chronic liver disease includedalcoholism (n ¼ 330, 64%), HBV infection (n ¼ 35, 11%)and cryptogenic cirrhosis (n ¼ 67, 21%). At admission,prevalence of ascites was 89.4% (n ¼ 330), hepatic en-cephalopathy (HE), 49.3% (n ¼ 182); septicaemia, 13%(n ¼ 4/8); chest infection, 18.2% (n ¼ 67); spontaneousbacterial peritonitis, 10% (n ¼ 37), and acute kidneyinjury, 46.1% (n ¼ 170). Overall, 173 (46.9%) patientshad ACLF-1; 105 (28.5%) ACLF-2; 45 (12.2%) ACLF-3and 46 (12.6%) ACLF-4. Mortality was 32.3% (n ¼ 56) inACLF-1, 54.2% (n ¼ 57) in ACLF-2, 71.1% (n ¼ 32) inACLF-3 and 97.8% (n ¼ 45) in ACLF-4. Baseline TLC,Child C status and �2 organ failures at presentation orduring hospital stay were independent predictors ofmortality.

218 Abstracts Clinical Gastroenterology and Hepatology Vol. 13, No. 1

CONCLUSIONS: Loss of �2 organ functions at presentationor during hospital stay, baseline TLC and Child C pre-dicted mortality in ACLF.

The EfficHemorrha

Thitithep

Effect ofon SympPatients W

AnastasiM. Abdu

acy of Tranexamic Acid in Upper Gastrointestinalge: A Double-Blind Randomized Controlled Trial

Limvorapitak and Apichat Piriyakarnon

Antiviral TWith HepStudy

Yao-Chuand Chu

BACKGROUND AND AIMS: Upper gastrointestinal haemor-rhage is one of the major problems for which patients arebrought to the emergency department. Endoscopy is themain diagnostic tool and treatment for upper gastroin-testinal haemorrhage. Nevertheless, in regional hospitals,not every patient receives immediate endoscopy. Medicalhaemostasis might be beneficial during this period.Proton-pump inhibitors (PPIs) and octreotide analoguesare widely used and proven useful. Tranexamic acid is anantifibrinolytic agent that is generally prescribed formultiple organ haemostasis. This study aimed to deter-mine whether tranexamic acid administration to uppergastrointestinal haemorrhage patients while waiting forendoscopy aids in improving clinical outcomes, anddecreasing mortality and rebleeding risk.

METHODS: A prospective, double blind, randomized studywas performed in patients who encountered uppergastrointestinal haemorrhage at Khon Kaen hospital.Patients were randomized to tranexamic acid or placeboas adjunct to conventional treatment prior to endoscopy.The primary outcome was presence of blood in stomachon endoscopy. The secondary outcomes included mor-tality rate, rebleeding rate, and need for transfusion.

RESULTS: One hundred twenty-eight patients wereenrolled. After randomization, 63 received tranexamicacid and 65 received placebo. On endoscopy, presence ofblood in stomach was found significantly less often inpatients receiving tranexamic acid vs placebo (19.0% vs41.5%; P ¼ .007). Mortality rate, rebleeding rate, needfor transfusion, need for surgery and length of stay werenot significantly different in the two groups. No in-admission complications were reported in patientsreceiving tranexamic acid.

CONCLUSION: Administration of tranexamic acid prior toendoscopy reduces the amount of blood retained in thestomach and Results in improved clinical outcomes.

Acupoint-Catgut Embedment Combined With Medicationtoms, Quality of Life, and Inflammatory Mediators ofith Irritable Bowel Syndrome

a Yoveline Joyo, A. Srilestari, C. Simadibrata, andllah

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is ahigh-burden, functional, gastrointestinal disorder thatcauses substantial impact on patients’ quality of life(QoL). Current medical treatments are inadequate inrelieving symptoms. Acupoint-catgut embedment is amethod that uses surgical catgut embedded in acupoints

to provide continuous stimulation and achieve thera-peutic effect. This study aimed to establish the effect ofacupoint-catgut embedment combined with medicationon symptoms, QoL, and inflammatory mediators in pa-tients with IBS.

METHODS: This double blind, randomized controlled trialinvolved 50 IBS patients randomly allocated to catgut-embedding therapy plus medication or only medication.Catgut-embedding therapy was given three times at ST25 Tianshu, ST 36 Zusanli, and ST 37 Shangjuxu every 10days. IBS-severity scoring system (IBS-SSS) and IBS-QoLquestionnaires were used to measure the primaryoutcome. Serum levels of interleukin (IL)-10 and IL-6were measured by ELISA.

RESULTS: At one month, both scores were significantlylower with catgut-embedding therapy plus medicationversus medication only (IBS-SSS: 133.20 vs 260.00,P < .001 and IBS-QoL scores: 52.16 vs 68.76, P < .001).There were no significant differences in the baselinelevels of anti-inflammatory (IL-10) and pro-inflamma-tory (IL-6) mediators between groups. After one-monthtreatment, the mean levels of IL-10 were significantlyincreased with catgut-embedding therapy plus medica-tion vs medication only (0.60 pg/mL vs 0.28 pg/mL,P ¼ .045), while IL-6 levels were decreased (2.10 pg/mLvs. 2.99 pg/mL, P ¼ .162).

CONCLUSION: The Results suggest that acupoint-catgutembedment plus medication is more effective thanmedication only in alleviating symptoms and enhancingQoL of IBS patients.

reatment and Risk of End-Stage Renal Disease in Patientsatitis C Virus Infection: A Nationwide Total Population

n Hsu, Jaw-Town Lin, Hsiu J. Ho, Chi-Yang Chang,n-Ying Wu

BACKGROUND AND AIMS: We aimed to investigate whetherantiviral treatment for hepatitis C virus (HCV) infectionis associated with attenuation in the risk of end-stagerenal disease (ESRD).

METHODS: This nationwide cohort study screened 293,480Taiwanese residents diagnosed with HCV infection from1997 through 2011, based on analysis of the TaiwanNational Health Insurance Research Database. Thosewith physical or psychiatric conditions that mightconfound or be contraindicated for antiviral treatmentwere excluded. A total of 12,384 eligible patients whohad received pegylated interferon plus ribavirin betweenOctober 1, 2003 and December 31, 2010 were enrolledand matched with 24,768 untreated controls (1:2) inpropensity scores. Occurrence of ESRD was comparedbetween treated and untreated cohorts after adjustmentfor confounders.

RESULTS: The 8-year cumulative incidence of ESRD wassignificantly lower in the treated (0.15%; 95% confi-dence interval [CI], 0.04%–0.26%) vs the untreated