Antibodies used are described in the Supporting Information. Densitometric quantification of immunoblots was performed using ImageJ 1.43 software. Because inactivation of the TGF-β signaling pathway and mutation of TP53 are selleckchem common molecular events observed in human HCC, we assessed whether deletion of Tgfbr2 and Trp53 cooperate in the mouse liver to affect tumor formation. To this end, we crossed Alb-Cre transgenic mice with mice conditionally null for either Tgfbr2 and/or Trp53 to generate mice with liver-specific deletion of these genes.21-23 No liver tumors were observed in the control mice lacking Alb-Cre (Control) (Table 1). Likewise, deletion

of Tgfbr2 alone (Tgfbr2KO) did not induce liver tumors by 15 months of age. The Tgfbr2KO mice had a normal liver to body weight ratio of 0.050, which is not statistically different from the Control mice (Table 1). In contrast, deletion of Trp53, in the context of intact Tgfbr2 (Trp53KO) resulted in a significant number of mice developing tumors (P = 0.0034) as compared with the Control mice. The median lifespan for the entire Trp53KO cohort was 46.6 weeks, whereas the median lifespan for the subset of mice with tumors was 22.7 weeks. Survival curves illustrate that 52% of Trp53KO mice died by 50 weeks of age (Fig. 1). Additionally, the liver STI571 to body weight ratio was increased

nearly 2× (P = 0.0002) in the Trp53KO cohort, presumably secondary to the tumor load present in the Trp53KO mice (Table 1). Histological analysis of the primary tumors from the Trp53KO livers revealed the tumors to be both HCC and cholangiocarcinoma (CC) (Fig. 2). The click here tumors consisted of a variety of histologic subtypes, ranging from trabecular HCC with necrosis to CC with necrosis and fibrosis. Biliary hyperplasia, cholangiohepatitis, multifocal coagulative necrosis, oval cell hyperplasia, and arterial thrombosis were also noted in the adjacent

liver tissue. Of the 12 liver tumor-bearing mice, two also had multiple lung metastases that likely arose from large primary CCs. In light of the known common occurrence of TGF-β signaling inactivation and TP53 mutation in human HCC and the development of HCCs and CCs in the Trp53KO mice, we assessed the effect of Tgfbr2 deletion on liver tumor formation in these mice. Livers from mice with both inactive p53 and Tgfbr2(Trp53KO;Tgfbr2KO) were analyzed. Interestingly, the double knockout mice displayed a survival curve similar to the Control and Tgfbr2KO mice (Fig. 1). Additionally, fewer mice developed liver tumors by 15 months (Table 1, P = 0.0265) compared with the Trp53KO mice. The median lifespan for the mice with tumors was 71.6 weeks. Furthermore, the liver to body weight ratio of the tumor-bearing Trp53KO;Tgfbr2KO mice was significantly lower than the ratio of tumor-bearing Trp53KO mice (P = 0.0149).

And we investigated the dominant symptoms who meet the standards of Functional Dyspepsia through Rome III questionnaire survey after sorting them into three different groups, namely PDS, EPS and overlapped group(short for OL). Results: 108 patients match ROME-III FD diagnosis criteria except others e.g. organic dyspepsia through examination, among which there are 28 EPS(25.9%), 50 PDS(46.3%), 30 OL (27.8%). The Hp infection rate in EPS(35.71%) is higher than that in PDS(16%), and have a significant difference(p = 0.038). The rate in EPS is higher than that in overlapped subset(10%)and have a significant selleck compound difference(p = 0.021). The Hp infection rate in PDS has no statistic difference

in overlapped subset(p = 0.526). There is a negative correlation between the Hp infection and whether or not having postprandial fullness(r = -0.214,p = 0.029). The Hp infection is not related to the severity of ten symptoms(|r | < 0.2, p > 0.05). Conclusion: FD patients with Hp infection expressing EPS dominant symptoms should accepted eradicating Hp treatment. Key Word(s): 1. Functional Dyspepsia; 2. PDS; 3. EPS; 4. dominant symptoms; Presenting

Author: JEFFREYM. JOHNSTON Additional Authors: ROBYNT. CARSON, STAVROS TOURKODIMITRIS, BARBARAE. LEWIS Corresponding Author: JEFFREYM. JOHNSTON Affiliations: Forest Research Institute; Ironwood Pharmaceuticals, Inc. Objective: Linaclotide, a guanylate cyclase type-C receptor agonist, significantly improved abdominal and bowel symptoms in two Phase 3 irritable bowel

syndrome with constipation (IBS-C) trials. IBS-C is a common functional CP 868596 gastrointestinal disorder that significantly affects patients’ quality of life (QOL). Methods: In both trials, patients meeting Rome II IBS-C criteria received oral once-daily 290-μg linaclotide or placebo for 12 weeks. The IBS-QOL questionnaire, consisting of 34 items, each with a five-point response see more scale (1 = not at all to 5 = extremely or a great deal), was completed at baseline and treatment end. IBS-QOL is scored Overall and by 8 subscales (Dysphoria, Interference with Activity, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual, and Relationships). The change-from-baseline to Week 12 scores using pooled data were analyzed using analysis of covariance. IBS-QOL response rates (i.e., patients with ≥10-point and ≥14-point increase) by treatment group were compared (Cochran-Mantel-Haenszel method). Results: Changes from baseline in IBS-QOL Overall and 7/8 subscale scores (Dysphoria, Body Image, Health Worry, Sexual, Relationships, Food Avoidance, and Social Reaction) were statistically significant for linaclotide vs. placebo (Table). The percentage of responders was statistically significantly greater for linaclotide vs. placebo patients at Week 12 for IBS-QOL Overall score (64.3% linaclotide vs. 52.6% placebo for ≥10-point change; 53.8% linaclotide vs. 39.1% placebo for ≥14-point change).

However, factors predicting its development are still controversial. This study was conducted to evaluate the frequency of antituberculosis therapy-induced hepatotoxicity and the risk factors related to its development. Methods: The author reviewed retrospectively the medical records of the 2,204 patients who had taken ATT for 2 weeks or longer from January 1, 2005 through June 30, 2010 in Gyeong-Sang National university, South Korea. The patients’ demographic, social, clinical and laboratory

data were collected and analyzed for the relationships between hepatotoxicity and these various parameters. Hepatotoxicity was determined by investigation of liver tests at the time of pretreatment Rucaparib mouse and 7, 14, 30, 60, and 90 days of

ATT. Results: Two-hundred two (9.2%) out of 2,204 patients taken ATT developed hepatotoxicity. Mean age of the patients with ATT-induced hepatotoxicity was 52.5 ± 18.7 years and 130 (64.6%) patients were male. The frequency of ATT-induced hepatotoxicity was higher in the patients with abnormal baseline liver function than the ones with normal liver function (88/541, 16.3% vs. 114/1,663, 6.9%, p = 0.000), hepatitis B virus (HBV) or hepatitis C virus (HCV) infected than non-infected (28/150, 18.7% vs. 174/2,054, 8.5%, p = 0.000) SB525334 patients, and the patients with primary hepatocellular carcinoma (HCC) than the ones without it (7/17, 41.2% vs. 195/2,187, 8.9%, p = 0.000).

There was no significant relationship between the frequency selleck screening library of ATT-induced hepatotoxicity and gender, old age over 60 years or 35 years, body mass index, alcohol drink, indication of ATT, underlying diseases except HCC, and past history of ATT. Baseline LFT abnormality, underlying HCC and HBV or HCV infections were risk factors for ATT-induced hepatotoxicity on univariate and multivariate analysis. The majority of patients with ATT-induced hepatotoxicity (170/202, 84.2%) were identified within first 30 days of ATT, and hepatotoxicity occurred within first 7 days in 64 patients (31.7%). Conclusion: The frequency of ATT-induced hepatotoxicity was 9.2%, and its risk factors were abnormal baseline liver function, and underlying HBV or HCV infection and hepatocellular carcinoma. Closed monitoring should be required for the patients who have these risk factors during first 30 days of ATT, especially first 7 days. Key Word(s): 1. antituberculosis; 2. hepatotoxicity; 3. frequency; 4.

All of the patients with HBsAg

loss received entecavir as 0.5 mg. Conclusion: Our results are consistent with the previous reports. Therefore, it may be suggested that treatment with entecavir could be associated to HBsAg loss in a period of time, in both HBeAg positive and HBeAg negative HBV patients. Key Word(s): 1. viral hepatitis B; 2. entecavir; 3. HBSAG loss; Presenting Author: ALI BAHARI Additional Authors: MOHAMMAD HASHEMI, GHOLAM REZA BAHARI, ZOHREH BARI, TAHEREH FAKHARIAN, ALI MOKHTARI FAR, ABBAS ESMAEIL ZADEH, AZITA GANJI, HAMID REZA SIMA, ZAHRA MESHKAT, SINA GERAYLI, SEYED MOUSAALREZA HOSSEINI, HOOMAN MOZAFFARI, MITRA AHADI, HASAN check details VOSUGHINIA, ALIREZA BAKHSHIPOUR Corresponding

Author: ALI BAHARI Affiliations: Mashhad University of Medical Sciences; Mazandaran University of Medical Sciences Objective: Different studies have shown that single nucleotide polymorphisms (SNPs) in the gene coding for interleukin 28 (IL28B), including rs12979860 and rs8099917, influence hepatitis C viral response to treatment and accordingly, CC genotype of rs12979860 and TT genotype of rs8099917 parallel with EPZ-6438 ic50 sustained virological response. The present study assessed the distribution of these two SNP genotypes and their relation with some clinico-pathologic characteristics in a population of Iranian patients. Methods: DNA of 148 patients with chronic HCV infection were analyzed to selleckchem determine the allele frequency

of rs12979860 and rs8099917 SNPs, using Tetra-ARMS polymerase chain reaction. We also evaluated the relation between different SNP genotypes and liver function tests, viral load, pathology of liver biopsy, HCV genotype and the patient’s gender. Results: The genotype distribution of rs12979860 was: 72.3% CT, 14.2% TT and 13.5% CC. Also, the frequencies of rs8099917 genotypes were: 58.1%, 38.5% and 3.4% for TT, TG and GG, respectively. Totally, 12.1% were CC/TT and 2.7% were TT/GG (rs12979860/rs8099917, respectively). No relation was found between different genotypes of these two SNPs and the level of alanine amino-transferase (ALT), liver fibrosis, viral load, HCV genotype and the patients’ gender. Conclusion: According to our results, rs12979860 and rs8099917 genotypes are independent of the patient’s gender, severity of liver fibrosis, viral load, viral genotype and the level of ALT. Besides, although CC had the lowest frequency among rs12979860 genotypes, further studies are needed to assess the predictive power of these genotypes in this country. Key Word(s): 1. Hepatitis C; 2. IL28B ; 3. single nucleotide polymorphism; Presenting Author: YONGSEOK KIM Additional Authors: YUMI LEE, OHJUNG KWON Corresponding Author: YONGSEOK KIM Affiliations: Konyang Univ. Hospital Objective: Gallstone disease is one of the most common and costly of all digestive diseases.

For eliminating WHV DNA, total RNA from normal liver tissues or HCCs was treated with Turbo DNase (Ambion) (6 units of DNase/1 μg of RNA) for 2 hours at 37°C. The complementary DNA (cDNA) was synthesized with the High Capacity cDNA Reverse

Transcription Kit (Applied Biosystems) using the reverse http://www.selleckchem.com/products/Rapamycin.html primer for qPCR, 2579-TGGCAGATGGAGATTGAGAGC-2559 that is located in a region exclusively present on WHV pg/precore RNAs. For the subsequent qPCR (that we developed) forward primer, 2504-AGAAGACGCACTCCCT CTCCT-2524; reverse primer (also used for the RT step as described above); and a TaqMan probe, 2531-AGAA GATCTCAATCACCGCGTCGCAG-2556 were used. The numbering corresponds to the WHV7 sequence.27 qPCR was carried out with the Applied Biosystems TaqMan Gene Expression Mastermix using each primer at a concentration of 900 nM and the TaqMan probe at a concentration of 250 nM. The reaction conditions were 10 minutes at 95°C, followed by 40 cycles of 15 seconds at 95°C, and 60 seconds at 60°C. To quantify WHV pgRNA copy numbers, a 10-fold dilution series of NheI-linearized plasmid PUC-CMVWHV was used (range: 20-200,000 GE of WHV). The pgRNA copy numbers were expressed per μg of total RNA. Normal liver tissues from LL, left medial liver lobe (LM), and right lateral liver

lobe (RL) and HCCs were harvested at the end of the study and were processed together with the samples biopsied 1 week prior to wHDV superinfection. Paraffin sections of formalin-fixed tissues were immunostained Opaganib purchase with polyclonal rabbit antibodies against recombinant small δAg (1:8,000 dilution) followed by immunoperoxidase detection and hematoxylin-eosin poststaining.29 To determine whether hepadnavirus-induced HCCs are selleck compound susceptible to HDV infection, three WHV carriers (M7724, M7788, and F7807) were used at the late stage of chronic

infection, when HCCs had already developed. WHV carriers were superinfected with wHDV, using a low MOI of 0.27 HDV GE/hepatocyte. Six weeks after wHDV superinfection, woodchucks were euthanized and blood, normal liver tissues, and HCCs were examined for markers of HDV and WHV infections. Serum samples were assayed for HDV genomic RNA and WHV DNA using qPCRs as described previously.19 As shown in Fig. 1, all woodchucks quickly developed HDV viremia, and the serum HDV titers reached the WHV titers within 2 to 4 weeks. The increase of HDV titers coincided with a transient 4 to 10-fold decrease in WHV titers. The serum concentrations of HDV and WHV remained relatively high for the duration of the experiment. Thus, all WHV carriers were successfully superinfected with HDV. Woodchucks were monitored for 6 weeks following HDV superinfection assuming that this period is long enough to develop detectable HDV infection, and short enough so new HCCs likely will not develop. During necropsy at the end of the study one HCC was recovered from the liver of woodchuck M7724, five HCCs from M7788, and two HCCs from F7807.

Patients with MHE showed significant impairment in 11 scales of the SIP, the psychosocial and physical subscores, and in the total SIP. Patients received 30–60 mL of lactulose in two or three divided doses so that the patient passed two to three semi-soft stools per day. Following lactulose therapy for 3 months, both psychometric performance and HRQOL improved; MHE reversed in 64.5% of treated patients compared

with 6.7% in the no-treatment group (P < 0.0001). Significant improvement was found in five (emotional behavior, ambulation, mobility, sleep/rest and recreation and pastimes) of the 12 scales of the SIP and in the total psychosocial and physical sub-scores in the treated patients compared with the untreated patients. Improvement in HRQOL was linked to improvement in cognitive function. A recent study that compared lactulose, a probiotic and LOLA with no treatment, confirmed these findings.67 Lactulose drug discovery or lactitol, both non-absorbable, synthetic disaccharides with multiple effects on gut flora, are regarded as intestinal prebiotics.96 Dietary addition of lactulose can exert a bifidogenic effect accompanied by a favorable effect on colonic NH3 metabolism.97 A meta-analysis of randomized trials of lactulose versus placebo or no intervention in treatment of patients buy ABT-263 with MHE showed that

the treatment with lactulose was associated with improvement in psychometric (cognitive) performance.35 Prebiotics, probiotics or synbiotics (probiotics and fermentable fiber) are effective in treating patients with MHE,63–67 and can also be used as long-term therapy. Liu et al.65 showed that modulation of gut microecology and acidification of gut lumen in patients with liver cirrhosis and MHE by treatment with synbiotics resulted in increased fecal content of non-urease-producing Lactobacillus species, whereas the number of urease-producing pathogenic Escherichia coli see more and Staphylococcal species decreased. This effect persisted for 14 days after

cessation of supplementation. It was associated with a significant reduction in blood ammonia and endotoxin levels and reversal of MHE in nearly 50% of the patients. The severity of liver disease, as assessed according to CTP class, also improved in nearly 50% of the patients. In a recent randomized control trial, supplementation with probiotic yogurt resulted in a significant reversal of MHE in the group receiving yogurt compared to no treatment.63 Treatment with a probiotic preparation also improves HROQL.67 Prebiotics, probiotics or synbiotics are efficacious in the treatment of HE by decreasing bacterial urease activity, pH in the gut lumen, ammonia absorption and total ammonia in the portal blood, and by improving nutritional status of gut epithelium resulting in decreasing intestinal permeability.

With concerns growing over resistance, broadening the repertoire for DAA targets is a major priority. Here we describe the complete structure of the HCV p7 protein as a monomeric Imatinib in vivo hairpin, solved using a novel combination of chemical shift and nuclear Overhauser effect (NOE)-based methods. This represents atomic resolution information for a full-length virus-coded ion channel, or “viroporin,” whose essential functions

represent a clinically proven class of antiviral target exploited previously for influenza A virus therapy. Specific drug-protein interactions validate an allosteric site on the channel periphery and its relevance is demonstrated by the selection of novel, structurally diverse inhibitory small molecules with nanomolar potency in culture. Hit compounds represent a 10,000-fold improvement over prototypes, suppress rimantadine resistance polymorphisms at submicromolar concentrations, and show activity against other HCV genotypes. Conclusion: This proof-of-principle that structure-guided design can lead

to drug-like molecules affirms p7 as a much-needed new target in the burgeoning era of HCV DAA. (Hepatology 2014;59:408–422) ”
“Paracrine signaling selleck inhibitor between hepatic stellate cells (HSCs) and liver endothelial cells (LECs) modulates fibrogenesis, angiogenesis, and portal hypertension. However, mechanisms regulating these processes selleck chemicals are not fully defined. Sorafenib is a receptor tyrosine kinase inhibitor that blocks growth

factor signaling in tumor cells but also displays important and not yet fully characterized effects on liver nonparenchymal cells including HSCs and LECs. The aim of this study was to test the hypothesis that sorafenib influences paracrine signaling between HSCs and LECs and thereby regulates matrix and vascular changes associated with chronic liver injury. Complementary magnetic resonance elastography, micro–computed tomography, and histochemical analyses indicate that sorafenib attenuates the changes in both matrix and vascular compartments that occur in response to bile duct ligation–induced liver injury in rats. Cell biology studies demonstrate that sorafenib markedly reduces cell–cell apposition and junctional complexes, thus reducing the proximity typically observed between these sinusoidal barrier cells. At the molecular level, sorafenib down-regulates angiopoietin-1 and fibronectin, both released by HSCs in a manner dependent on the transcription factor Kruppel-like factor 6 , suggesting that this pathway underlies both matrix and vascular changes associated with chronic liver disease. Conclusion: Collectively, the results of this study demonstrate that sorafenib inhibits both matrix restructuring and vascular remodeling that accompany chronic liver diseases and characterize cell and molecular mechanisms underlying this effect.

Subsequently, for the remaining 6 years of Rodin, there was a specified data collection form so that the trial was clearly prospective and involved both generation rFVIII concentrates. This article appears to have combined the data from both study periods in their biostatistical analysis rather than analysing the results separately as well as combined. It is not clear selleck compound library how this approach may have confounded their conclusions; however, there are currently in process several well-designed prospective studies, which may confirm or contradict Rodin’s findings. Two initial aspects of the Rodin trial design

should be examined. First, patients were allocated to the products indicated by their treaters and thus were subject to the potential ‘biases’ of their treaters and/or their Hemophilia Treatment Centers’ own local guidelines, preferences, or attitudes. It is indeed possible that such treatment decisions resulted in ascertainment or selection bias. Second, although the study authors discount the possibility that centre-specific bias could have confounded their conclusions,

given that the variability of prophylaxis this website regimens and intensity of treatment have already been adjusted for, it would have been more supportive and reassuring if alternative analytical approaches for this study design had been employed to control for the risk of bias. Such statistical techniques could have included propensity score analysis [8] and centre-stratified or adjusted Cox-regression, or an assessment of deviation from the overall mean rate of inhibitor formation in different centres. In the setting of a post hoc analysis, exploring check details the potential sources of variability with multiple techniques is generally useful to distinguish robust findings from chance ones. A further methodological concern of the Rodin trial is that it relied on the Bethesda unit inhibitor levels to be measured at each individual HTC rather than performed at a central laboratory. It is not apparent whether all the HTC laboratories were standardized in their assay techniques. At first

reading this might appear irrelevant for the study, which focuses on only clinically relevant inhibitors, but this is not the case, because Rodin employed a highly laboratory-dependent definition of inhibitor clinical relevance. Of most concern in the Rodin study design is the possible deviation from the complete analysis of the entire inception cohort [9]. According to the Methods of the Rodin study, 648 ‘eligible’ patients were recruited to the study, of whom 74 were ultimately excluded from the statistical analysis. Of these, 19 in the initial cut and 30 patients in the subsequent cut were excluded for reasons related to inhibitor development/ascertainment, based on information provided in the patients’ disposition flow chart. In the third cut, two individuals had documented inhibitors, but were not included in the final statistics.

Louis, MO) to 1–15 μmol/L. HCC cell viability was determined at 72 hours after addition of 1–15 μmol/L sorafenib or DMSO by WST-8 assay using cell count reagent sulforaphane (Nacalai Tesque, Kyoto, Japan) as previously described.20 The small interfering RNA (siRNA) method was used

to knockdown ADAM9 as previously described.20 At 24 hours after transfection, the cells were analyzed for specific depletion of the messenger RNA (mRNA) of ADAM9 by real-time reverse transcription polymerase chain reaction (RT-PCR) according to the manufacturer’s instructions (Applied Biosystems, Foster City, BGB324 ic50 CA). The following siRNAs were used: ADAM9, 5′-UGUCCAAACACAUUAAUCCCGCCUG-3′; scramble control, 5′-UGUCGCACAAACACUUAACUCCCUG-3′. HCC cells were cultured with tumor necrosis factor-α protease inhibitor-I (TAPI-I, 50 μmol/L; Calbiochem, San Diego, CA) or sorafenib (1 μmol/mL) for 24 hours and the supernatants were harvested. The supernatants of cultured HCC cells were harvested at 24 hours after transfection with siRNA. The levels of soluble MICA were determined by DuoSet MICA enzyme-linked immunosorbent assay (ELISA) kit (R&D Systems, Minneapolis, MN). For the detection CH5424802 clinical trial of membrane-bound MICA, cells were incubated with anti-MICA antibody (Ab) (Santa Cruz Biotechnology, Santa Cruz, CA) and stained with phycoerythrin-goat anti-mouse

immunoglobulin (Ig) (Beckman Coulter, Fullerton, CA) as a secondary reagent and then subjected to flow cytometric analysis using a FACScan flow cytometer (Becton Dickinson, San Jose, CA). Total RNA was isolated using the RNeasy Mini Kit (Qiagen K.K., Tokyo, Japan), and was reverse transcribed using SuperScript III First-Strand Synthesis System (Invitrogen, Carlsbad, CA). The mRNA levels were evaluated using ABI-Prism 7900 Sequence Detection System (Applied Biosystems). Ready-to-use assays (Applied Biosystems)

were used for the quantification of ADAM9 (Hs00177638_m1), and β-actin (Hs99999903_m1) mRNAs according to the manufacturer’s instructions. β-Actin mRNA from each sample was quantified as an endogenous control of internal RNA. Peptides of 20 amino acid residues selleck partially overlapping each other, covering the α3 domain to the C-terminal end of MICA were synthesized by Sigma. Each peptide substrate (30 μM) was incubated with 50 nM of recombinant ADAM9 in a buffer containing 10 mM HEPES (pH 7.2) and 0.0015% Brij (Sigma). After digestion, the samples were passed over a C18 media (ZipTipC18; Millipore, Billerica, MA), eluted with acetonitrile, and analyzed by matrix-assisted laser desorption/ionization–time of flight/mass spectrometry (MALDI-TOF/MS) to determine the masses of the products and thereby the cleavage site recognized by ADAM9. An expression vector of MICA, pcDNA-MICA, was constructed by using specific complementary DNA (cDNA) from the human hepatoma-derived cell line, Huh-7, as described.

All therapy should be discontinued if the HCV RNA level is ≥100 IU/mL at week 12 or ≥10 to 15 IU/mL at week 24. Two phase 3 trials evaluated the efficacy of TVR in combination with PegIFN alfa-2a and RBV in treatment-naïve patients with

genotype 1 chronic HCV infection.16, 22 Black patients were included but not as a separate cohort and were insufficient in number to provide an adequate assessment of true response in this population. In the ADVANCE trial, patients received TVR together with PegIFN and RBV for either 8 (T8PR) or 12 (T12PR) weeks followed by GDC-0449 PegIFN and RBV alone in a response-guided paradigm.16 The TVR dose was 750 mg given by mouth every 8 hours with food (in particular, a fatty meal). Patients in the T8PR and T12PR groups who achieved an “extended RVR” (eRVR)—which for this drug was defined as undetectable (<10-15 IU/mL) HCV learn more RNA levels at weeks 4 and 12—stopped therapy at week 24, whereas those in whom an eRVR did not occur received a total of 48 weeks of PegIFN and RBV.

All patients in the control group received PegIFN and RBV therapy for 48 weeks. The overall SVR rates among patients in the T8PR and T12PR groups were 69% and 75%, respectively,16 compared with a rate of 44% in the control group (Table 2 and Fig. 3). Using the RGT approach, 58% and 57% of patients in the T12PR and T8PR groups, respectively, attained an eRVR, 89% and 83% of whom ultimately achieved an SVR.16 Thus, developing an eRVR appears to be the strongest predictor that an SVR will occur. SVR rates

were higher in TVR-containing regimens compared to SOC treatment among patients with disease characteristics found previously to be associated with a poorer response to SOC treatment. Although few black patients and other difficult-to-treat patient populations were included in the TVR phase 3 trials, an improved SVR rate was observed regardless of race, ethnicity, or level of hepatic fibrosis. With regard to race, treatment with a TVR-based regimen significantly improved find more SVR rates in black patients (T8PR, 58% and T12PR, 62%) compared to the SVR rates achieved in those treated with the SOC regimen (25%) (Fig. 3). Moreover, the SVR rate was >80% among black patients who achieved an eRVR on a TVR-based regimen. A total of 62% of patients in the T12PR group and 53% in the T8PR group with advanced fibrosis achieved an SVR, the rate improving to >80% among those with an eRVR. In the T12PR group, the impact of high versus low viral load (>800,000 or <800,000 IU/mL) on SVR rates was minimal; the SVR rate was 74% in patients with a high viral load and 78% in those with a low viral load. The ILLUMINATE trial focused on defining the utility of RGT in patients with an eRVR.