19, 0 80-1 78) was not

Conclusions: Younger (<40y) HCV L

19, 0.80-1.78) was not.

Conclusions: Younger (<40y) HCV LT recipients have significantly reduced graft survival, higher rates of re-LT and HCV-related death than older HCV recipients. This suggests a more aggressive natural history for HCV disease post-LT and identifies a group in need of early consideration of HCV therapy. Disclosures: Norah Terrault - Advisory Committees or Review Panels: Eisai, Biotest; Consulting: BMS, Merck; Grant/Research Support: Eisai, Biotest, Vertex, Gilead, AbbVie, Novartis, Merck The following people have nothing to disclose: Varun Saxena, Jennifer L. Dodge, John P. Roberts Background/Aims: To identify the impact of portal vein thrombosis (PVT) on post liver transplant Selleck Birinapant (LT) outcomes along with other covariates and assess factors associated with complications amongst PVT patients. Methods: Fer-1 in vitro Retrospective cohort study of 621 adult LT recipients (University of Alberta, London Health Sciences Centre) between 01/2002-12/2012. PVT

was identified in 147 (24%) patients and 474 (76%) non-PVT patients served as controls. Cox survival analysis was performed to determine independent associations with overall mortality. Results: Demographic factors (mean age 53, 69% male) were similar between groups. There were also no differences in mean MELD (PVT 19 vs. controls 19, p=0.9) and Child Pugh scores (10 vs. 10, p=0.9) on the day of LT. Donor factors (mean DRI:1.6 vs. 1.5, p=0.2) were similar. Using Cox multivariable survival analysis, covariates independently associated with overall mortality included Age (adjusted Hazard ratio ∼ aHR 1.02, p=0.015) and requiring ICU support pre-LT (aHR 2.17, p=0.006), but not PVT (p=0.67). 5-year survival was similar between PVT and controls (75%,p= 0.8). In comparing PVT patients who did not survive (n=32) with PVT survivors (n=115), non-survivors (n=32) were more likely to have complete thrombus occlusion (38% vs. 13%, p=0.027) and

hepatofugal flow (31% vs. 13%, p=0.08). Non-survivors were more likely require thrombectomy (69 vs. 31%, p=0.08) and develop reocclusion post-LT (16% vs. 3%, p=0.024). Anti-coagulation rates were similar between groups. Conclusion: Well-selected LT patients who had PVT prior to LT have similar post-LT outcomes with Ketotifen controls when adjusting for donor and recipient factors. Subgroups of PVT LT patients who did worse post-LT (complete thrombosis pre-LT, thrombectomy at LT and reocclusion post-LT) warrant closer evaluation in listing and management post-LT. Adjusted survival (Cox) for PVT LT recipients vs. controls (p=0.67). Disclosures: Constantine J. Karvellas – Grant/Research Support: Merck; Speaking and Teaching: Gambro The following people have nothing to disclose: Filipe S. Cardoso, Malcolm M. Wells, Fayaz A. Handoo, Lukasz Kwapisz, Mansour G. Alghanem, Norman Kneteman, Paul Marotta, Bandar Al-Judaibi Background.

In conjunction with INR and a suitable mathematical model describ

In conjunction with INR and a suitable mathematical model describing these mechanisms, however,

Selleck Acalabrutinib aminotransferase levels do contain sufficient information to estimate the timing and amount of overdose. Our model cannot distinguish patients with high overdose amounts and early administration of N-Ac from patients with low overdose amounts and delayed treatment because in both cases AST, ALT, and INR levels are low. However, this ambiguity affects only patients who are predicted to recover. Some patients with unique characteristics, such as those with significant muscle damage, may not fit the model. Muscle damage increases the level of AST, which may lead to poor estimation of liver damage. Because ALT and INR values are not affected by muscle damage, this effect may be minimal. Further studies are warranted to determine whether more refinements are needed for special patient groups. Our treatment

of all patients as having the same parameter values is unrealistic. Well-known covariates of disease severity such as age,38 chronic alcohol use,39, 40 starvation or malnutrition,41 and interactions with other drugs42, 43, 44 may affect the parameter values of an individual. In some cases these differences will not affect the accuracy of predictions of outcome. Model predictions derive from the amount of unconjugated NAPQI that results from a given dose, but that amount may depend on patient characteristics. For example, alcoholics may make excessive NAPQI because of elevated p-450 levels, or individuals may have decreased levels of GSH because of starvation, competition from other drugs, STA-9090 mouse or genetic variation. These differences might make the model estimates of initial dose seem overly high, but the outcome could still be accurately predicted because these patients have

more unconjugated NAPQI than is typical for the overdose amount. James et al.45 show that APAP protein adduct levels may be used as specific biomarkers of APAP toxicity. If measurements were routinely available, adducts could easily be added to our model, and might provide additional ifenprodil predictive value. However, the correlation of protein adducts with AST and their similar kinetics lead us to predict this effect would be small, although their more direct relationship to liver damage might reduce noise and make them a superior predictor. Gregory et al.46 found that individuals with overdose amounts greater than 10 g did not have significantly different mortality than those reporting smaller overdoses in patients with eventual hepatic encephalopathy. The authors suggest that this may be due to inaccurate reporting of dosing information by patients with eventual hepatic encephalopathy, or from a plateau effect in APAP overdose amount, such that above a threshold the effect of APAP overdose ceases to be additive. A plateau is built into our model, but at 20 g rather than 10 g.

The teeth were restored with the following dowel systems: custom-

The teeth were restored with the following dowel systems: custom-shaped electrical glass fiber (CSG), ZrO2-containing tapered glass fiber (TZG), unidirectional

silica zirconium fiber (USZ), tapered glass fiber with high elastic modulus (HEG), Al2O3-containing tapered glass fiber (TAG), parallel-sided, serrated translucent glass fiber (STG), double-tapered quartz fiber with low elastic modulus (LEQ), parallel-sided, serrated opaque glass fiber (SOG), and stainless steel (SSP) (Table 1). Ninety freshly extracted, caries-free mandibular second premolar teeth were selected for this study. A manual scaler (Hu-Friedy Mfg. Co. Inc.; Leimen, Germany) was used to remove all external debris and soft tissue on the root surface. The Opaganib purchase anatomic crowns of the teeth were sectioned CH5424802 order using a water-cooled diamond disc (Hyperflex 911, Komet Braesseler GmbH; Lemgo, Germany) to leave a root length of 14.5 mm, which is the average root length of this tooth.[9] The teeth were assigned to one of nine groups of ten teeth each. The buccolingual and mesiodistal root dimensions were assessed with one-way ANOVA to demonstrate any significant differences among the groups. There were no significant differences among

the groups (p = 1.0). Using tapered rotary instruments (ProFile Ni-Ti, Dentsply Maillefer; Ballaigues, Switzerland), root canal preparations were made to a size of 0.46 mm. Irrigation was carried out using 1 ml of 5.2% NaOCl solution between each file and 2 ml of saline solution after preparation. For all groups, dowel spaces were prepared to a depth of

10 mm,[10, 11] with the drills of the PJ34 HCl dowel systems supplied by the manufacturer or with universal Peeso reamers, if recommended by the manufacturer. Dowel diameters were selected according to the manufacturers’ recommendations for mandibular premolar teeth (Table 1). All of the dowels were shortened to a length of 14.5 mm with a water-cooled diamond disc. Before dowel cementation, to ensure removal of the smear layer, the root canals were irrigated with 2 ml of 17% EDTA solution and 2 ml of 5.2% NaOCl solution, then rinsed with 5 ml of water and dried with paper points (Diadent Group International; Chongju City, Korea).[12] Specific surface conditioning procedures for each dowel system were performed according to the manufacturers’ instructions (Table 1). The root canal fillings were not made,[13] and a size #40 gutta-percha was placed at the apical part of the roots through the apical end, to avoid obturation of the excess resin cement. Cementation of the dowels was accomplished with a self-cure adhesive resin cement system (Multilink Automix, Ivoclar Vivadent; Schaan, Liechtenstein). As per instruction manual procedures, primer A and primer B, which are supplied with the Multilink system, were mixed in 1/1 portions and applied into the prepared root canals with a brushing technique, using an endodontic applicator, for 15 seconds.

“There is currently no published study comparing prevalenc

“There is currently no published study comparing prevalence of non-alcoholic fatty liver disease (NAFLD) and associated factors among diabetics of different ethnicity in the Asia-Pacific region. Cross-sectional study of consecutive patients in the Diabetic Clinic in University of Malaya Medical Centre. The Global Physical Activity Questionnaire and a semiquantitative food-frequency questionnaire were used to assess physical activity and dietary

intake, respectively. Diagnosis of NAFLD was ultrasound-based and following exclusion of significant alcohol intake. Data for 399 patients were analyzed (mean age 62.3 ± 10.5 years, 43.1% men). The racial distribution was Chinese 43.6%, Indian 33.1%, Malay 22.3%, and others 1.0%. The prevalence of NAFLD was 49.6%. On univariate analysis, factors associated with NAFLD were age learn more < 65

years, race, obesity, central obesity, glycated www.selleckchem.com/products/Imatinib-Mesylate.html hemoglobin ≥ 7.0%, and elevated serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels. Patients with low physical activity were more likely to have NAFLD (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.06–2.63, P = 0.020). The prevalence of NAFLD was highest among Malays (60.7%), followed by Indians (51.5%), and lowest among Chinese (42.0%) consistent with higher prevalence of central obesity and higher percentage calorie intake from fat in the former groups of patients. On multivariate analysis, independent factors associated with NAFLD were central obesity (OR = 2.20, 95% CI = 1.29–3.75, P = 0.004) and elevated serum ALT level (OR = 1.98, 95% CI = 1.21–3.25, P = 0.007). NAFLD was seen in half of a cohort of diabetic patients and was independently associated with central obesity and elevated serum ALT level. Prevalence of NAFLD was different and paralleled the difference in prevalence of central obesity and in percentage calorie intake from fat among the different ethnic groups. “
“Liver transplantation (LT) is a unique model to study hepatitis

C virus (HCV) entry into hepatocytes. Recent in vitro studies suggest significant changes in the expression Molecular motor of the HCV receptors claudin-1 and occludin after HCV infection. Our aims were: (1) to characterize claudin-1 and occludin expression in grafts from LT recipients and (2) to explore their potential influence on early HCV kinetics and their changes after HCV infection. We included 42 HCV-infected LT recipients and 19 uninfected controls. Claudin-1 and occludin were detected in paraffin-embedded liver biopsies obtained during reperfusion and 3 and 12 months after LT. HCV receptors were characterized by confocal immunofluorescence microscopy; quantification and colocalization studies were performed with dedicated software. Claudin-1 and occludin expression were restricted to the apical pole of hepatocytes.

Our analyses employed log-binomial regression models to calculate

Our analyses employed log-binomial regression models to calculate both unadjusted and race/ethnicity-adjusted prevalence ratios. However, when assessing alleles without a high prior probability of association (i.e., alleles not included in Table 1) we corrected the P-values for multiple comparisons via permutation resampling using PROC MULTTEST; a method that empirically incorporates correlations within and between loci.26 Because some prior studies have described variation in HLA associations by race,27, 28 we assessed potential heterogeneity

in click here effect estimates (i.e., interaction) by race/ethnicity. In contrast, we did not expect to observe heterogeneity by HIV-serostatus or CD4+ T-cell count among HIV-seropositive women. A variety of sources suggest that HCV infection generally occurs prior to HIV infection in new IDU,29–31 and therefore that the majority HCV RNA clearance/persistence occurs without relation to HIV. It is possible, however, that HIV preceded HCV RAD001 price infection in some women. For completeness, therefore, we assessed heterogeneity by HIV serostatus/CD4+ T-cell count (HIV-seronegative, HIV-seropositive with CD4+ T-cell count ≥500 cells/mm3, and HIV-seropositive with CD4+ T-cell count <500 cells/mm3). Lastly, we examined whether groups of HLA alleles

that act as ligand for killer immunoglobulin-like receptors (KIR) were associated with HCV infection and HCV viremia. KIR play a major role in the activation of natural killer (NK) cells and the innate immune response and specific combinations of KIR and HLA ligands have been associated with clearance of HCV RNA.32, 33 These ligand groups were Bw4 reflecting 141 HLA-B alleles, Cw group 1 reflecting 48 HLA-Cw alleles, and Cw group 2 reflecting 43 HLA-Cw alleles.32 All statistical analyses were performed using SAS 9.1 (SAS Institute,

Cary, NC). Selected characteristics of the 758 HCV-seropositive women with and without detectable HCV RNA are shown in Table 2A. Most HCV-seropositive women reported IDU, and this did not vary according to C-X-C chemokine receptor type 7 (CXCR-7) HCV RNA positivity. The HCV RNA-positive women, though, were more likely than those who were HCV RNA-negative to be Black, non-Hispanic. HIV-seroprevalence did not differ between HCV RNA-positive/-negative women, but the CD4+ T-cell counts were significantly lower among those HIV-seropositives who had detectable HCV RNA. HCV genotype was determined for 226 of the women with detectable HCV viremia. The genotype distribution among these women was: 1a in 125 (55%) of the 226 women; 1b in 65 (29%); type 1 but with undetermined subtype in 8 (4%); 2a in 3 (1%); 2b in 6 (3%); 3a in 14 (6%); 3d in 1 (<1%); and 4a in 4 (2%) women.

The 16S rDNA sequence showed 99% similarity with the homologous g

The 16S rDNA sequence showed 99% similarity with the homologous genes of the aster yellows group phytoplasma (16SrI group), and the phytoplasma was designed as CWBp-BJ. Phylogenetic and computer-simulated restriction fragment length polymorphism (RFLP) analysis of the 16S rDNA gene INCB024360 concentration revealed that CWBp-BJ belongs to subgroup 16SrI-B. This is the first report of a phytoplasma associated with cabbage witches’-broom in China. “
“Phytophthora capsici is an oomycete known as the causal

agent of wilting disease in Capsicum spp., which causes rotting of roots, crowns, stems, leaves and fruits. To date, little is known about the production of phytotoxic metabolites by P. capsici or their role in the infection process. As part of a project directed towards the isolation and identification of phytotoxins produced by a strain of P. capsici pathogenic to habanero pepper (Capsicum chinense), we have evaluated the effect of factors such as aeration, light and culture medium on the production of mycelium and phytotoxic metabolites by P. capsici. The results showed that culturing P. capsici in potato dextrose broth (PDB) containing habanero pepper leaf infusion, in the dark and under still conditions, results

in a high production of mycelium and a high phytotoxicity Everolimus supplier of the culture filtrate, in the shortest period of time. “
“Fusarium head blight (FHB), also called scab, is a devastating and insidious ADAMTS5 disease of cereals including wheat (Triticum spp.) and barley (Hordeum vulgare L.) worldwide. Apart from direct yield losses, the most serious concern about FHB is the contamination of the crop with mycotoxins,

which pose a health risk to human and livestock. Recent research reported that phylogenetic species F. asiaticum (Fa) and F. graminearum (Fg) were the major causal agents of FHB from infected wheat heads in China. To investigate the population structure of Fusarium species in China by species-specific as well as the chemotype-specific markers, sequence-related amplified polymorphism (SRAP) markers were screened on representative isolates of F. asiaticum-NIV, F. asiaticum- 3ADON and F. graminearum-15ADON to find amplification products characteristic of either species or chemotypes. Selected amplified fragments were cloned and sequenced so that sequence-characterized amplified region (SCAR) primer pairs could be developed which permit specific detection of Fusarium species using conventional PCR. Primer pairs SCAR-Fa1 and SCAR-Fg1 were confirmed to be able to amplify specific products only in F. asiaticum and F. graminearum isolates, respectively. These species-specific primers were applied to determine genetic division of F. asiaticum and F. graminearum isolates collected in Yangtze–Huaihe valley. The results indicated that F.

Unintentional injection rate of pancreatic duct was not significa

Unintentional injection rate of pancreatic duct was not significantly different between two groups. Mean size of CBD was not significantly different between asymptomatic and symptomatic group (11.4 ± 3.5 vs 10.5 ± 4.7, p = 0.165). Asymptomatic group experienced

significantly more post ERCP pancreatitis than symptomatic group (23.5% vs 7.8%, p = 0.049). There was no significant difference in post ERCP complications of bleeding, infection and perforation between two groups. Conclusion: Performing ERCP for removal of CBD stone in asymptomatic patients showed significantly increased risk of post ERCP pancreatitis. Key Word(s): 1. endoscopic retrograde cholangiopancreatography complication common bile duct stone Presenting Author: TAE NYEUN KIM Additional Authors: KOOK HYUN KIM, KYEONG OK KIM, SI HYUNG LEE, BYUNG IK JANG Corresponding Author: TAE NYEUN Torin 1 datasheet KIM Affiliations: Yeungnam University College of Medicine, Yeungnam University College of Medicine, Yeungnam University College of Medicine, Yeungnam University College of Medicine Objective: Endoscopic common bile duct stone removal is relatively difficult in

patients with a history of Billroth-II gastrectomy and endoscopic sphincterectomy (ES) with conventional sphincterotome Enzalutamide research buy may increase complication risks. The aims of this study was to evaluate the safety and effectiveness of endoscopic papillary large balloon dilation (EPLBD) in patients with B- II gastrectomy. Methods: A review of 53 patients with a history of B-II gastrectomy who underwent

ERCP for treatment of common duct stones from January 2010 to December 2012 were conducted retrospectively. Patietns with hepatobiliary cancer, pancreatic cancer, common bile duct stricture and concomitant pancreatitis were excluded. Results: Of 53 patients, 31 patients were enrolled. The median age was 70.2 ± 7.1 years and male to female ratio was 2.9:1. Patients who underwent ES or EPLBD for management of CBD stones were 16 and 15, respectively. Florfenicol Mechanical lithotripsy was performed in 7 patients (4 in ES group, 3 in EPLBD group). The median size of balloon was 11.3 ± 1.4 mm (range 10–15 mm). The median duration of balloon expansion was 33.1 ± 14.0 s (range 20–60 s). The overall stone removal rate was 96.8% (30/31). Overall incidence of post-ERCP pancreatitis was 0%. Post-ERCP bleeding occurred in 1 patient within EPLBD group. No significant difference in the incidence of post-ERCP bleeding was observed between the two groups (p = 0.48). Cholangitis was not observed in this study. Conclusion: EPLBD seems to be an effective and safe procedure for CBD stone removal in patients with billroth II gastrectomy. Key Word(s): 1.

In response to liver injury, HSCs undergo an activation process a

In response to liver injury, HSCs undergo an activation process and transform into myofibroblast-like cells, a process characterized by loss of vitamin A and expression of α-smooth muscle actin (α-SMA).3, 4 Activated HSCs promote collagen synthesis and secretion. In addition, these cells produce a number of cytokines such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), which play important roles in the development of liver fibrosis.5, 6 The involvement of reactive oxygen species (ROS) in liver fibrogenesis

has been documented. The activation and expression of various mediators are regulated by ROS by way of the redox-sensitive protein kinases and transcription Imatinib factors in HSCs.7, 8 Recently, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, originally identified

as a major source of ROS in phagocytes, was shown to play a key role in cellular signaling. NOX is a catalytic subunit of NADPH oxidase, a multisubunit enzyme composed of membrane-bound NOX and p22phox, associated with several cytosolic regulatory learn more subunits including p47phox. In recent years, several isoforms of NOX have been identified.9 NOX2 (gp91phox) is the phagocytic form of NOX, whereas NOX1 is a newly identified form that has been implicated in the pathogenesis of hypertension and inflammatory pain.10, 11 Previously, it was reported that mice lacking p47phox, a cytosolic subunit of NADPH oxidase, demonstrated reduced liver injury and fibrosis after bile duct ligation (BDL).12 In transgenic mice overexpressing Rac1, another cytosolic subunit necessary for enzyme activation, greater numbers of activated HSCs, increased liver damage, tuclazepam and fibrosis were demonstrated following treatment with

carbon tetrachloride (CCl4).13 In line with these findings, reduced liver fibrosis was demonstrated in mice lacking NOX2 treated with CCl4.14 Furthermore, NOX2 was recently shown to play a key role in activation of HSCs following phagocytosis of apoptotic hepatocytes.15 A considerable amount of evidence thus suggests a critical role for the NOX2 isoform of NADPH oxidase in liver fibrogenesis. On the other hand, little is known about the role of NOX1 in the pathogenesis of liver fibrosis, although induction of NOX1 mRNA in the activated HSCs was reported.12 This led us to investigate whether the NOX1 isoform of NADPH oxidase is involved in the development of liver fibrosis using mice deficient in the Nox1 gene. We here report that NOX1 promotes the proliferation of HSCs and liver fibrogenesis by inactivating phosphatase and tensin homolog (PTEN). NOX1 thus positively regulates the Akt/FOXO4 pathway to reduce a cell cycle suppressor, p27kip1.

pylori infection plays a significant role in gastric carcinogenes

pylori infection plays a significant role in gastric carcinogenesis. The risk of gastric

cancer increased threefold for the H. pylori-infected group compared with the non-infected group. In some studies, the incidence rate of metachronous gastric cancer decreased GSK-3 phosphorylation with H. pylori eradication after endoscopic resection of EGC.[27, 28] In a multicenter study of 544 patients with endoscopic resection of EGC, the incidence rate of metachronous gastric cancer was significantly reduced in the H. pylori eradication group compared with the non-eradication group. However, another retrospective study of 268 patients with endoscopic resection of EGC showed contradictory results, in that there was no significant difference in metachronous gastric cancer between the eradication group and the non-eradication group.[29, 30] Considering the high incidence of gastric cancer in Korea, H. pylori eradication is necessary to prevent metachronous gastric cancer after endoscopic resection of EGC. Information is lacking about the role learn more of H. pylori eradication in preventing metachronous gastric cancer after partial gastrectomy rather than endoscopic resection of EGC. Statement 4. H. pylori eradication is helpful for the prevention of gastric cancer in some patients with atrophic

gastritis/intestinal metaplasia. Level of evidence C, Grade of recommendation 2 Experts’ opinions: completely agree (14.8%), mostly agree (70.4%), partially agree (11.1%), mostly disagree (3.7%), completely disagree (0%), not sure (0%) H. pylori plays an important role in gastric carcinogenesis; in particular, it is an important cause of 71–95% of non-cardiac

gastric cancers.[31] H. pylori colonizes the gastric mucosa and triggers a series 2-hydroxyphytanoyl-CoA lyase of inflammatory reactions leading to cancer. The current model for gastric carcinogenesis begins with chronic gastritis, proceeds to mucosal atrophy, followed by intestinal metaplasia, dysplasia, and finally, carcinoma.[32] In H. pylori-positive patients with severe atrophic gastritis, the incidence rate of gastric cancer is 4.9 times higher than H. pylori-positive patients without atrophic gastritis and 14.5 times higher than H. pylori-negative patients without atrophic gastritis.[33, 34] In addition, in H. pylori-positive patients with intestinal metaplasia, the incidence of gastric cancer was 6.4 times greater than in H. pylori-positive patients without intestinal metaplasia, and 10.9 times greater in the Korean study.[10] Therefore, atrophic gastritis and intestinal metaplasia are considered important precancerous lesions in gastric carcinogensis.[33] In a Korean study, the mean prevalence of atrophic gastritis in the antrum and body was 42.5% and 20.1%, while the mean prevalence of intestinal metaplasia was 28.6% and 21.2%, respectively.[35, 36] In other studies, the age-adjusted prevalence of atrophic gastritis was 42.7% for men and 38.1% for women, and the prevalence of intestinal metaplasia was 42.5% for men and 32.

Statistical analysis with MANOVA Results: From the multivariate

Statistical analysis with MANOVA. Results: From the multivariate analysis regression, simultaneously Child Turcotte Pugh classification, esophageal varices, ascites, hepatic encephalopathy, haemoglobin, platelet, albumin, sodium, Ferrostatin-1 cost potassium, calcium, proteinuria, sex, weight, and age were affecting significantly for the occurrence of hepatorenal syndrome with correlation

within 67% (R = 0.676, P = 0.006). In a partially analysis from the multivariate regression, Child Turcotte Pugh classification (B = 24.743, P = 0.000) is independent factors for affecting the occurrence of hepatorenal syndrome. Conclusion: The Child Turcotte Pugh classification is independent good factor for affecting the occurrence of hepatorenal syndrome. Key Word(s): 1. liver cirrhosis; 2. hepatorenal syndrome; 3. Child Turcotte Pugh Presenting Author: MICHIO KOGAME Additional Authors: MIE SHINOHARA, KOJI ISHII,

MASAO SHINOHARA, TAKASHI IKEHARA, HIDENARI NAGAI, MANABU WATANABE, YOSHINORI IGARASHI, YASUKIYO SUMINO Corresponding Author: MICHIO KOGAME Affiliations: Toho University School of Medicine, Jcho Tokyo Kamata Medical Center, Toho University School of Medicine, Toho University School of Medicine, Toho University School of Medicine, Toho University School of Medicine, Toho University School of Medicine, Toho University School of Medicine Objective: Genetic variation in the interleukin 28B (IL-28B) region is Daporinad clinical trial known to be associated with sustained virological response (SVR) to pegylated (PEG)-interferon (IFN)-alpha and ribavirin (RBV) in patients having chronic hepatitis C (CHC) genotype 1b and high

viral load. The SVR rate in Japan was recently shown to be approximately 80∼90% in patients with the IL-28B responder genotype, and only 50% in patients with the IL-28B non-responder genotype when they were treated with a new protease inhibitor combined with PEG-IFN plus RBV (new triple therapy). The aim of this study was to clarify the efficacy of low-dose and long-term administration of PEG-IFN-alpha 2a in CHC patients who failed to obtain SVR by prior PEG-IFN plus RBV combination therapy. Methods: Sixteen CHC patients (average: 61, range: 43–80 years, male/female = 10/6) infected with high Benzatropine viral loads of genotype 1b hepatitis C virus (HCV), who had received PEG-IFN plus RBV therapy for a median 48 (range: 24–96) weeks but had not obtained SVR, were examined in this study. Patients were divided into 3 groups based on the results of the previous PEG-IFN plus RBV regimen: a relapse group (n = 6; serum hepatitis C virus (HCV)-RNA was undetectable by RT-PCR during therapy, but patients became positive less than 24 weeks after the termination of therapy), a break-through group (n = 4; serum HCV-RNA was undetectable by RT-PCR, but patients became positive during therapy), and a null group (n = 6; serum HCV-RNA was detected by RT-PCR during therapy).