- Email: [email protected]
3) Treated With Interferon (IFN) or Pegylated Interferon and Ribavirin (PEG IFN+RBV)
HCV-5 patients were included in the analyses irrespective of treatment duration. Primary outcome was pooled event rates for SVR using random-effects modeling. Influence analysis to ensure robustness of pooled estimate was conducted by the removal of each study one by one to determine the effect of omission on study summary estimates. Heterogeneity was assessed using the Cochrane's Q and I2 statistics. Publication bias was evaluated using the Begg's and Egger's tests and by visual inspection of corresponding funnel plots. Results: A total of 10 studies met the inclusion criteria with a total patient number of 423. Overall SVR (irrespective of types of IFN or duration of therapy) was 59.1% (95% CI: 54.0%64.2%). There was no evidence of heterogeneity (I2 = 10.77, p=0.34). There was no evidence of publication bias on Begg's (p-value = 0.89) and Egger's test (p-value = 0.49) or by visual inspection of corresponding funnel plots. SVR for IFN+RBV for 48 weeks (n=66) was 60.7% (95% CI: 49.0%-72.3%) and for PEG IFN+RBV for 48 weeks (n=255) was 57.2% (95% CI: 51.2%-63.2%). Current data is insufficient to calculate overall SVR to IFN or PEG IFN plus RBV treatment for 24 weeks. Conclusions: SVR to either IFN or PEG IFN plus RBV in treatment-naïve HCV-5 patients was approximately 60%. However, current data is insufficient to evaluate the predictive value of variable duration of treatment (24 vs. 48 weeks), presence or absence of cirrhosis, early response to therapy, viral loads (low vs. high) or level of fibrosis (mild vs. advanced). Optimal treatment duration for HCV-5 patients with PEG IFN+RBV remains to be established.
*Values represent percent of respondents correctly answering questions; ** P < 0.001, Chisquare for overall comparison Su1072 Treatment of Chronic Hepatitis C Genotype 1 (G1) Infection With Boceprevir (Victrelis®) in German Real-Life: Impact of Hemoglobin Decline on Virologic Response Gerlinde Teuber, Peter Buggisch, Hanns Löhr, Hermann Steffens, Michael Kraus, Christine John, Peter Geyer, Bernd Weber, Thomas Witthoeft, Andreas Herrmann, Mark Hoesl, Uwe Naumann, Tarek Dahhan, Dagmar Hartmann, Bernd Dreher, Manfred Bilzer
AASLD Abstracts
Background: Triple therapy of chronic hepatitis C G1 infection with the HCV protease inhibitor boceprevir is accompanied by hematological alterations such as hemoglobin (Hb) decline. Data regarding the severity of Hb decline caused by triple therapy in real-life are still scarce and were evaluated in the present interim analysis of the German NOVUS observational study. Methods: From April 2012 until November 2013, 469 patients with G1 infection were recruited in the ongoing NOVUS study by 96 practices and hospital ambulances in Germany. Patients were treated with pegylated interferons (PegIFN) and ribavirin (RBV) together with boceprevir for 24 to 44 weeks after a 4 week lead-in period with PegIFN/RBV according to the discretion of the responsible physician. The present interim analysis was restricted to 155 untreated and 85 previously treated patients who have started treatment at least 8 months ago. Results: Of 240 patients 221 had documented Hb values at baseline and at least one Hb measurement during triple therapy. Maximal Hb decline (median) was 4.0 and 4.4 g/dL in female and male patients (P=0.0574). A significantly higher Hb decline of 4.5 g/dL occurred in patients >50 years in comparison to 3.8 g/dL in patients ≤50 years (P=0.0002). Hb declines were distributed as follows: <1 g/dL: 3.2%; ≥1 - <2 g/dL: 5.9%; ≥2 - <3 g/dL: 12.7%; ≥3 - <4 g/dL: 21.3%; ≥4 - <5 g/dL: 28.1%; ≥5 - <6 g/dL: 18.1%; ≥6 g/dL: 10.9%. Regarding a possible impact of Hb decline on virologic response there was a trend towards higher virology response rates at treatment week (TW) 8, TW12 and TW24 when patients achieved a Hb decline ≥3 g/dL (Table). Interestingly, treatment discontinuation rates until week 24 were significantly lower in patients with Hb declines ≥ 3 g/dL (Table). Hb alterations during triple therapy were managed by RBV dose reductions in 51% while 2.5% received blood transfusions. Only one patient was treated with erythropoietin and one patient discontinued triple therapy because of anemia. Conclusions: In the present real-life cohort of previously untreated and previously treated patients Hb declines caused by boceprevir triple therapy are more pronounced in patients older than 50 years. There is no evidence for a negative impact of Hb declines ≥3 g/dL on virologic response rates. In German real-life these alterations are managed by RBV dose reductions without the use of erythropoietin and only few patient need blood transfusions.
Su1074 Meta-Analysis: Sustained Virologic Response (SVR) in Patients With Infection With Hepatitis C Virus Genotype 5 (HCV-5) Versus Genotype 1 (HCV-1) and HCV Genotype 2/3 (HCV -2/3) Treated With Interferon (IFN) or Pegylated Interferon and Ribavirin (PEG IFN+RBV) Pardha Devaki, David S. Jencks, Sharad Nangia, Vidyasagargoud Marupakula, Mindie H. Nguyen Background and Aim: Current international consensus is to treat HCV-5 infected patients with PEG IFN+RBV for 48 weeks. Many authors consider that treatment response of HCV5 is similar to HCV-2/3 and so 24 weeks of treatment may be adequate. Studies have also shown that response to treatment for HCV-5 is better than with HCV-1. Our aim was to compare treatment response to standard IFN or PEG IFN and RBV between HCV-5 and HCV-1 and HCV 2/3. Methods: Literature search using Medline and EMBASE databases was conducted in July 2013. Abstracts from recent major gastroenterological association meetings (DDW and EASL 2011-2013 and AASLD 2011, 2012) were also reviewed for pertinent studies. All searches and data extraction were performed independently by 2 authors (PD and DJ). Inter-reviewer discrepancies were resolved by joint review of the original articles. Studies comparing the treatment response to IFN or PEG IFN plus RBV in HCV-5 to HCV-1 or HCV 2/3 patients were included in the analyses irrespective of treatment duration (HCV 2/3 patients were predominantly treated with 24 weeks of therapy and HCV5 and HCV-1 patients were treated for 48 weeks). Primary outcome was to compare treatment efficacy in HCV-5 to HCV-1 or HCV-2/3 using random-effects modeling. Heterogeneity was assessed using the Cochrane's Q and I2 statistics. Results: A total of 13,927 patients from 4 studies were included in the analyses. Overall SVR was 59.1% (95% CI: 51.5%-66.7%; I2 = 0, p=0.89) for HCV-5, 41.6% (35.1%-48.2%; I2 = 83.25, p<0.001) for HCV-1 and 68.6% (59.8%-77.3%; I2 = 41.4, p=0.16) for HCV-2/3. When compared to HCV-1 patients, HCV-5 patients treated for 48 weeks had higher SVR, OR 1.43 (1.10-1.87, p=0.01). When compared to HCV-2/3 patients, there was no statistically significant difference in SVR in HCV-5 patients, OR 0.89 (0.76-1.05, p=0.18). When the study that included both IFN and PEG IFN without SVR data for the different IFN types was excluded, analysis of only patients treated with PEG IFN+RBV showed summary estimates for SVR to be 57.1% (48.3%-65.8%; I2 = 0, p=0.95) for HCV-5, 68% (57.3%-78.7%; I2 = 59.6, p=0.08) for HCV-2/3, and 43.8% (37.5%-50.1%; I2 = 85.01, p<0.001) for HCV-1. SVR for HCV-5 treated for 48 weeks was significantly higher than HCV-1 (OR=1.30, 1.06-1.60, p=0.01), but the difference was
^ Chi-square test Su1073 Sustained Virological Response (SVR) to Standard Interferon (IFN) or Pegylated Interferon (PEG IFN) and Ribavirin (RBV) in Patients With Hepatitis C Virus Genotype 5 (HCV-5): Results of a Meta-Analysis of 423 Patients From 10 Individual Studies Pardha Devaki, David S. Jencks, Vidyasagargoud Marupakula, Sharad Nangia, Mindie H. Nguyen Background and Aim: HCV-5 is the predominant HCV genotype in South Africa and is also found in parts of certain European countries (France, the Netherlands, etc...). Current international consensus is to treat HCV-5 infected patients with PEG IFN+RBV for 48 weeks; however, these recommendations are based on mostly small studies with many reporting variable SVR rates. Our aim was to determine the overall SVR rate to combination therapy in treatment-naïve HCV-5 patients. Methods: Medline and EMBASE search using search term "Hepatitis C and genotype 5 "[Mesh] OR "Hepatitis C and South Africa [Mesh] OR "Hepatitis C and novel genotypes"[Mesh]) was conducted in July 2013. Abstracts from recent major gastroenterological association meetings (DDW and EASL 2011-2013 and AASLD 2011, 2012) were also reviewed for pertinent studies. All searches and data extraction were performed independently by 2 authors (PD and DJ). Inter-reviewer discrepancies were resolved by joint review of the original articles and reconciled with other co-authors as needed. Studies evaluating the efficacy of IFN or PEG IFN plus RBV in treatment-naive
S-981
AASLD Abstracts
not statistically significant compared to SVR in HCV-2/3 (OR=0.87, 0.71-1.06, p=0.16). Conclusions: In clinical practice, combination therapy for 48 weeks is more effective in HCV-5 patients than in patients with HCV-1. However, HCV-5 patients treated for 48 weeks had similar SVR compared to patients with HCV-2/3 treated for 24 weeks. When studies with only PEG IFN+RBV treatment are included, therapy was more effective in HCV-5 compared to HCV-1, but was similar to HCV-2/3. More studies are needed to determine the optimal duration of therapy in HCV-5 patients. N = number of patients ITPA gene polymorphisms and reduction of Hemoglobin (Hb) to less than 10g/dl
N = number of patients Su1077 Vitamin D and B12 Supplementation and Sustained Virologic Response in Chronic Hepatitis C Patients Treated With Pegylated Interferon and Ribavirin Catalina Mihai, Mihaela Dranga, Vasile Drug, Cristina Cijevschi Prelipcean
AASLD Abstracts
Su1075
Background. Vitamin D level seems to be an independent predictor of outcome in chronic hepatitis C patients. Vitamin B12 is a natural inhibitor of hepatitis C virus replication. There are some studies which reported that supplementation with vitamin D or vitamin B12 may improve sustained virologic response (SVR) in chronic hepatitis C (CHC) but the data are still conflincting. Aim: to assess the SVR in naïve patients with CHC treated with pegylated interferon α and ribavirin after supplementation with vitamin D and/or vitamin B12 . Methods. We randomized 92 naïve patients with CHC in four groups: group A (20 patients) received standard of care (SOC): pegylated interferon α + ribavirin; group B (24 patients): SOC + vitamin D (1000 UI vitamin D3 - colecalciferol/day); group C (25 patients): SOC + vitamin B12 (5000 μg/month intramuscular); group D (23 patients): SOC + vitamin D + vitamin B12. In Romania almost all CHC patients (99%) are genotype 1b. We analyzed SVR (undetectable serum HCV-RNA 24 weeks after completing treatment) in these four groups, counting also baseline viral load and fibrosis (detected by transient elastography -Fibroscan). Results. The SVR was improved by vitamin (especially vitamin B12) supplementation but without statistical significance: 45% in group A, 50% in group B (p=0.770), 56% in group C (p = 0,554) and 65.2% in group D (p=0.13). There are no SVR differences in the four groups depending the fibrosis. The percentage of non-responders, relapsers and treatment discontinuation due to adverse events was similar in the four groups. The best response was in patients in group 4 with high baseline viral load (>800 000 UI/ml): 73.3% (p=0.04). Conclusions: supplementation with vitamin B12 and with association between vitamin B12 and vitamin D may increase SVR in naïve, genotype 1, CHC patients treated with pegylated interferon and ribavirin, especially in those with high baseline viral load. Further studies are necessary to confirm this findings and to analyze the role of vitamin supplementation in triple therapy or direct antiviral agents therapy.
Boceprevir -Associated Resource Use Is Less Per SVR Achieved Compared to Telaprevir - A Pragmatic Head-to-Head Randomized Controlled Trial Perica Davitkov, Amy Hirsch, Apoorva Chandar, Anita Compan, Marina G. Silveira, Donald Anthony, Robert A. Bonomo, Yngve Falck-Ytter Background and Aims: Improved genotype 1 hepatitis C viral response rates for the two currently available protease inhibitors (PI) boceprevir and telaprevir is offset by an increased rate of severe adverse events and higher cost compared to peg-interferon and ribavirin alone. The comparative cost per SVR achieved for boceprevir vs. telaprevir has not been studied. We compared resource use of boceprevir vs. telaprevir based triple therapy in a pragmatic randomized controlled head-to-head trial. Methods: We prospectively recorded treatment expenditures of 50 HCV genotype patients randomized 1:1 to either boceprevir or telaprevir in combination with peg-interferon alpha 2a and weight based ribavirin. Patients were followed through an open-label, pragmatic RCT at a VA Medical Center liver clinic while receiving usual care. We estimated drug acquisition cost and costs of clinical services used to treat patients and reimbursement costs based on the Medicare fee schedule and other published data. SVR4 was defined as an undetectable viral load 4 weeks after the end of treatment. Results: The majority of enrolled patients were men (98%) with an average age of 59 years. Forty four percent were African American, 48% were Caucasian and 4% were Hispanic or Latino. Liver biopsy results showed advanced fibrosis or cirrhosis (stage 3 and 4) in 13 (26%) patients. 12/25 patients in each group achieved SVR4. Patients in the boceprevir group had on average 13 outpatient visits related to their HCV treatment vs. 9 outpatient visits in the telaprevir group. Mean cost of standard triple therapy with telaprevir, IFN/RBV and routine care was $26,962 ($363 - $30,505) per patient vs. $18,670 ($7,958 - $32,877) in the boceprevir group. Additionally, adverse event management (additional outpatient visits, ED evaluations, hospitalizations and additional medications, such as growth factors) was $14,801 vs. $24,594 for boceprevir and telaprevir respectively. In the boceprevir group, 6 patients received epoetin-α, 1 filgrastim, 4 patients required additional outpatient visits and 1 patient emergency department (ED) evaluation. In the telaprevir group, 7 patients received epoetin-α, 1 filgrastim, 3 patient requiring additional outpatient visits, 2 patients needed ED evaluation and 2 patients were briefly hospitalized. On an intention-to-treat basis, total cost per SVR4 was $40,635 for boceprevir vs. $58,114 for telaprevir. Conclusions: The total cost (drug acquisition cost plus cost of care, such as adverse effect management) per SVR achieved was substantially higher for telaprevir based triple therapy compared to boceprevir.
Mo1000 Octreotide and Celecoxib Synergistically Ameliorate Portal Hypertension of the Cirrhotic Rats Through Dual Inhibitory Effects on the Angiogenesis and Sinusoidal Remodeling Chengwei Tang, Jinhang Gao, Shilei Wen Background: Angiogenesis and sinusoidal remodeling are the critical factors leading to portal hypertension in cirrhosis. Non-cytotoxic drugs including octreotide and celecoxib could reduce angiogenesis in hepatocellular carcinoma and gastric adenocarcinoma. However, the effect of octreotide and celecoxib on the anti-angiogenesis and sinusoidal remodeling of cirrhotic liver remains unclear. Methods: Peritoneal injection (i.p.) of TAA was employed to induce liver cirrhosis (200 mg/kg every 3 days for 16 weeks). 36 male Sprague-Dawley rats were randomized into control, TAA and TAA+O+C with 12 animals in each group. TAA+O+C group received TAA plus octreotide (50 μg/kg/day) and celecoxib (20 mg/kg/ day) from the initiation of TAA administration. TAA group received TAA plus placebo and control group received injections of normal saline (1mL i.p., every 3 days for 16 weeks). Scanning electron microscope (SEM) of liver sinusoidal endothelial cells (LSEC) and hepatic vascular casting, hematoxylin-eosin staining (HE), Masson trichrome staining (MT) were applied to evaluation of sinusoidal remodeling, fibrosis and angiogenesis. Portal pressure was also measured. Additionally, immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and Western blot for alpha-smooth muscle actin ( α-SMA) and collagen III, CD31, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), hypoxia-inducible factor-1 alpha (HIF-1α), phosphorylated extracellular signal-regulated kinase (p-ERK) and c-fos were determined. Results: Compared with TAA group, liver fibrosis and portal pressure in TAA+O+C group were significantly decreased by 63.1% and 33.4% (p < 0.01), respectively. And the mRNA levels of α-SMA and collagen III in TAA+O+C group were also reduced by 53.1% and 63.6% (p < 0.01). Histological sections, vascular casts of hepatic portal vein by SEM, IHC and qRT-PCR for CD31 showed that hepatic and intestinal angiogenesis in TAA+O+C group were markedly reduced when compared with TAA group. Sinusoidal remodeling induced by TAA (such as impaired LSEC fenestrae, reduced sinusoidal diameter and increased sinusoidal branching) was also ameliorated after octreotide and celecoxib treatment. The up-regulation of VEGF, VEGFR-2, HIF-1 α, p-ERK and c-fos induced by TAA administration were significantly inhibited after octreotide and celecoxib treatment. Conclusions: Long term administration of octreotide and celecoxib synergistically ameliorate portal hypertension and fibrosis in cirrhotic rat model by the inhibitory effects on the intrahepatic/extrahepatic angiogenesis and sinusoidal remodeling, The synergistically effect afforded by octreotide and celecoxib may attribute to the modulation on VEGF/VEGFR-2
Su1076 Influence of ITPA Genotype Polymorphisms on Treatment Outcome and Anemia in Chronic HCV-4 Infection Reham Al swaff, Ahmed A. Monis, Essam Abu Alanain Background: Among HCV therapy-associated hematologic adverse effects, anemia is particularly important because of its implication in treatment outcome and its frequency. Recently, two functional variants in the inosine triphosphatase (ITPA) gene, which encodes for ITPA on chromosome 20, have been associated with RBV-induced anemia. Aim of the study: To investigate and clarify the impact of ITPA genotype polymorphisms on treatment outcome and anemia in Egyptian patients with chronic HCV-4 infection. Methods: In this prospective, observational study, 90 HCV-4 infected patients treated with Peg-IFN plus RBV were enrolled. Two SNPs within or adjacent to ITPA gene (rs1127354 and rs7270101) were genotyped. The impact of ITPA genotype polymorphisms on treatment outcome and anemia was examined. Results: The overall Sustained Virologic Response (SVR) rate was 38.9%. 92.2% of patients had CC subtype of rs1127354 whereas 85.6% had AA subtype of rs7270101. Insignificant differences were found between the different subtypes of rs1127354 and rs7270101 as regards the SVR rates (p= 0.8, 0.3 respectively). Reduction of hemoglobin level (<10 g/dl) during treatment was significantly greater in patients with CC subtype of rs1127354 than in other subtypes (p= 0.05); however the SVR rate in this subtype was comparable to other subtypes. Conclusion: Polymorphisms at rs1127354 in the ITPA gene significantly influence the hemoglobin level during combination therapy for chronic HCV-4 infection. ITPA gene polymorphisms and SVR
AASLD Abstracts
S-982
*Values represent percent of respondents correctly answering questions; ** P < 0.001, Chisquare for overall comparison Su1072 Treatment of Chronic Hepatitis C Genotype 1 (G1) Infection With Boceprevir (Victrelis®) in German Real-Life: Impact of Hemoglobin Decline on Virologic Response Gerlinde Teuber, Peter Buggisch, Hanns Löhr, Hermann Steffens, Michael Kraus, Christine John, Peter Geyer, Bernd Weber, Thomas Witthoeft, Andreas Herrmann, Mark Hoesl, Uwe Naumann, Tarek Dahhan, Dagmar Hartmann, Bernd Dreher, Manfred Bilzer
AASLD Abstracts
Background: Triple therapy of chronic hepatitis C G1 infection with the HCV protease inhibitor boceprevir is accompanied by hematological alterations such as hemoglobin (Hb) decline. Data regarding the severity of Hb decline caused by triple therapy in real-life are still scarce and were evaluated in the present interim analysis of the German NOVUS observational study. Methods: From April 2012 until November 2013, 469 patients with G1 infection were recruited in the ongoing NOVUS study by 96 practices and hospital ambulances in Germany. Patients were treated with pegylated interferons (PegIFN) and ribavirin (RBV) together with boceprevir for 24 to 44 weeks after a 4 week lead-in period with PegIFN/RBV according to the discretion of the responsible physician. The present interim analysis was restricted to 155 untreated and 85 previously treated patients who have started treatment at least 8 months ago. Results: Of 240 patients 221 had documented Hb values at baseline and at least one Hb measurement during triple therapy. Maximal Hb decline (median) was 4.0 and 4.4 g/dL in female and male patients (P=0.0574). A significantly higher Hb decline of 4.5 g/dL occurred in patients >50 years in comparison to 3.8 g/dL in patients ≤50 years (P=0.0002). Hb declines were distributed as follows: <1 g/dL: 3.2%; ≥1 - <2 g/dL: 5.9%; ≥2 - <3 g/dL: 12.7%; ≥3 - <4 g/dL: 21.3%; ≥4 - <5 g/dL: 28.1%; ≥5 - <6 g/dL: 18.1%; ≥6 g/dL: 10.9%. Regarding a possible impact of Hb decline on virologic response there was a trend towards higher virology response rates at treatment week (TW) 8, TW12 and TW24 when patients achieved a Hb decline ≥3 g/dL (Table). Interestingly, treatment discontinuation rates until week 24 were significantly lower in patients with Hb declines ≥ 3 g/dL (Table). Hb alterations during triple therapy were managed by RBV dose reductions in 51% while 2.5% received blood transfusions. Only one patient was treated with erythropoietin and one patient discontinued triple therapy because of anemia. Conclusions: In the present real-life cohort of previously untreated and previously treated patients Hb declines caused by boceprevir triple therapy are more pronounced in patients older than 50 years. There is no evidence for a negative impact of Hb declines ≥3 g/dL on virologic response rates. In German real-life these alterations are managed by RBV dose reductions without the use of erythropoietin and only few patient need blood transfusions.
Su1074 Meta-Analysis: Sustained Virologic Response (SVR) in Patients With Infection With Hepatitis C Virus Genotype 5 (HCV-5) Versus Genotype 1 (HCV-1) and HCV Genotype 2/3 (HCV -2/3) Treated With Interferon (IFN) or Pegylated Interferon and Ribavirin (PEG IFN+RBV) Pardha Devaki, David S. Jencks, Sharad Nangia, Vidyasagargoud Marupakula, Mindie H. Nguyen Background and Aim: Current international consensus is to treat HCV-5 infected patients with PEG IFN+RBV for 48 weeks. Many authors consider that treatment response of HCV5 is similar to HCV-2/3 and so 24 weeks of treatment may be adequate. Studies have also shown that response to treatment for HCV-5 is better than with HCV-1. Our aim was to compare treatment response to standard IFN or PEG IFN and RBV between HCV-5 and HCV-1 and HCV 2/3. Methods: Literature search using Medline and EMBASE databases was conducted in July 2013. Abstracts from recent major gastroenterological association meetings (DDW and EASL 2011-2013 and AASLD 2011, 2012) were also reviewed for pertinent studies. All searches and data extraction were performed independently by 2 authors (PD and DJ). Inter-reviewer discrepancies were resolved by joint review of the original articles. Studies comparing the treatment response to IFN or PEG IFN plus RBV in HCV-5 to HCV-1 or HCV 2/3 patients were included in the analyses irrespective of treatment duration (HCV 2/3 patients were predominantly treated with 24 weeks of therapy and HCV5 and HCV-1 patients were treated for 48 weeks). Primary outcome was to compare treatment efficacy in HCV-5 to HCV-1 or HCV-2/3 using random-effects modeling. Heterogeneity was assessed using the Cochrane's Q and I2 statistics. Results: A total of 13,927 patients from 4 studies were included in the analyses. Overall SVR was 59.1% (95% CI: 51.5%-66.7%; I2 = 0, p=0.89) for HCV-5, 41.6% (35.1%-48.2%; I2 = 83.25, p<0.001) for HCV-1 and 68.6% (59.8%-77.3%; I2 = 41.4, p=0.16) for HCV-2/3. When compared to HCV-1 patients, HCV-5 patients treated for 48 weeks had higher SVR, OR 1.43 (1.10-1.87, p=0.01). When compared to HCV-2/3 patients, there was no statistically significant difference in SVR in HCV-5 patients, OR 0.89 (0.76-1.05, p=0.18). When the study that included both IFN and PEG IFN without SVR data for the different IFN types was excluded, analysis of only patients treated with PEG IFN+RBV showed summary estimates for SVR to be 57.1% (48.3%-65.8%; I2 = 0, p=0.95) for HCV-5, 68% (57.3%-78.7%; I2 = 59.6, p=0.08) for HCV-2/3, and 43.8% (37.5%-50.1%; I2 = 85.01, p<0.001) for HCV-1. SVR for HCV-5 treated for 48 weeks was significantly higher than HCV-1 (OR=1.30, 1.06-1.60, p=0.01), but the difference was
^ Chi-square test Su1073 Sustained Virological Response (SVR) to Standard Interferon (IFN) or Pegylated Interferon (PEG IFN) and Ribavirin (RBV) in Patients With Hepatitis C Virus Genotype 5 (HCV-5): Results of a Meta-Analysis of 423 Patients From 10 Individual Studies Pardha Devaki, David S. Jencks, Vidyasagargoud Marupakula, Sharad Nangia, Mindie H. Nguyen Background and Aim: HCV-5 is the predominant HCV genotype in South Africa and is also found in parts of certain European countries (France, the Netherlands, etc...). Current international consensus is to treat HCV-5 infected patients with PEG IFN+RBV for 48 weeks; however, these recommendations are based on mostly small studies with many reporting variable SVR rates. Our aim was to determine the overall SVR rate to combination therapy in treatment-naïve HCV-5 patients. Methods: Medline and EMBASE search using search term "Hepatitis C and genotype 5 "[Mesh] OR "Hepatitis C and South Africa [Mesh] OR "Hepatitis C and novel genotypes"[Mesh]) was conducted in July 2013. Abstracts from recent major gastroenterological association meetings (DDW and EASL 2011-2013 and AASLD 2011, 2012) were also reviewed for pertinent studies. All searches and data extraction were performed independently by 2 authors (PD and DJ). Inter-reviewer discrepancies were resolved by joint review of the original articles and reconciled with other co-authors as needed. Studies evaluating the efficacy of IFN or PEG IFN plus RBV in treatment-naive
S-981
AASLD Abstracts
not statistically significant compared to SVR in HCV-2/3 (OR=0.87, 0.71-1.06, p=0.16). Conclusions: In clinical practice, combination therapy for 48 weeks is more effective in HCV-5 patients than in patients with HCV-1. However, HCV-5 patients treated for 48 weeks had similar SVR compared to patients with HCV-2/3 treated for 24 weeks. When studies with only PEG IFN+RBV treatment are included, therapy was more effective in HCV-5 compared to HCV-1, but was similar to HCV-2/3. More studies are needed to determine the optimal duration of therapy in HCV-5 patients. N = number of patients ITPA gene polymorphisms and reduction of Hemoglobin (Hb) to less than 10g/dl
N = number of patients Su1077 Vitamin D and B12 Supplementation and Sustained Virologic Response in Chronic Hepatitis C Patients Treated With Pegylated Interferon and Ribavirin Catalina Mihai, Mihaela Dranga, Vasile Drug, Cristina Cijevschi Prelipcean
AASLD Abstracts
Su1075
Background. Vitamin D level seems to be an independent predictor of outcome in chronic hepatitis C patients. Vitamin B12 is a natural inhibitor of hepatitis C virus replication. There are some studies which reported that supplementation with vitamin D or vitamin B12 may improve sustained virologic response (SVR) in chronic hepatitis C (CHC) but the data are still conflincting. Aim: to assess the SVR in naïve patients with CHC treated with pegylated interferon α and ribavirin after supplementation with vitamin D and/or vitamin B12 . Methods. We randomized 92 naïve patients with CHC in four groups: group A (20 patients) received standard of care (SOC): pegylated interferon α + ribavirin; group B (24 patients): SOC + vitamin D (1000 UI vitamin D3 - colecalciferol/day); group C (25 patients): SOC + vitamin B12 (5000 μg/month intramuscular); group D (23 patients): SOC + vitamin D + vitamin B12. In Romania almost all CHC patients (99%) are genotype 1b. We analyzed SVR (undetectable serum HCV-RNA 24 weeks after completing treatment) in these four groups, counting also baseline viral load and fibrosis (detected by transient elastography -Fibroscan). Results. The SVR was improved by vitamin (especially vitamin B12) supplementation but without statistical significance: 45% in group A, 50% in group B (p=0.770), 56% in group C (p = 0,554) and 65.2% in group D (p=0.13). There are no SVR differences in the four groups depending the fibrosis. The percentage of non-responders, relapsers and treatment discontinuation due to adverse events was similar in the four groups. The best response was in patients in group 4 with high baseline viral load (>800 000 UI/ml): 73.3% (p=0.04). Conclusions: supplementation with vitamin B12 and with association between vitamin B12 and vitamin D may increase SVR in naïve, genotype 1, CHC patients treated with pegylated interferon and ribavirin, especially in those with high baseline viral load. Further studies are necessary to confirm this findings and to analyze the role of vitamin supplementation in triple therapy or direct antiviral agents therapy.
Boceprevir -Associated Resource Use Is Less Per SVR Achieved Compared to Telaprevir - A Pragmatic Head-to-Head Randomized Controlled Trial Perica Davitkov, Amy Hirsch, Apoorva Chandar, Anita Compan, Marina G. Silveira, Donald Anthony, Robert A. Bonomo, Yngve Falck-Ytter Background and Aims: Improved genotype 1 hepatitis C viral response rates for the two currently available protease inhibitors (PI) boceprevir and telaprevir is offset by an increased rate of severe adverse events and higher cost compared to peg-interferon and ribavirin alone. The comparative cost per SVR achieved for boceprevir vs. telaprevir has not been studied. We compared resource use of boceprevir vs. telaprevir based triple therapy in a pragmatic randomized controlled head-to-head trial. Methods: We prospectively recorded treatment expenditures of 50 HCV genotype patients randomized 1:1 to either boceprevir or telaprevir in combination with peg-interferon alpha 2a and weight based ribavirin. Patients were followed through an open-label, pragmatic RCT at a VA Medical Center liver clinic while receiving usual care. We estimated drug acquisition cost and costs of clinical services used to treat patients and reimbursement costs based on the Medicare fee schedule and other published data. SVR4 was defined as an undetectable viral load 4 weeks after the end of treatment. Results: The majority of enrolled patients were men (98%) with an average age of 59 years. Forty four percent were African American, 48% were Caucasian and 4% were Hispanic or Latino. Liver biopsy results showed advanced fibrosis or cirrhosis (stage 3 and 4) in 13 (26%) patients. 12/25 patients in each group achieved SVR4. Patients in the boceprevir group had on average 13 outpatient visits related to their HCV treatment vs. 9 outpatient visits in the telaprevir group. Mean cost of standard triple therapy with telaprevir, IFN/RBV and routine care was $26,962 ($363 - $30,505) per patient vs. $18,670 ($7,958 - $32,877) in the boceprevir group. Additionally, adverse event management (additional outpatient visits, ED evaluations, hospitalizations and additional medications, such as growth factors) was $14,801 vs. $24,594 for boceprevir and telaprevir respectively. In the boceprevir group, 6 patients received epoetin-α, 1 filgrastim, 4 patients required additional outpatient visits and 1 patient emergency department (ED) evaluation. In the telaprevir group, 7 patients received epoetin-α, 1 filgrastim, 3 patient requiring additional outpatient visits, 2 patients needed ED evaluation and 2 patients were briefly hospitalized. On an intention-to-treat basis, total cost per SVR4 was $40,635 for boceprevir vs. $58,114 for telaprevir. Conclusions: The total cost (drug acquisition cost plus cost of care, such as adverse effect management) per SVR achieved was substantially higher for telaprevir based triple therapy compared to boceprevir.
Mo1000 Octreotide and Celecoxib Synergistically Ameliorate Portal Hypertension of the Cirrhotic Rats Through Dual Inhibitory Effects on the Angiogenesis and Sinusoidal Remodeling Chengwei Tang, Jinhang Gao, Shilei Wen Background: Angiogenesis and sinusoidal remodeling are the critical factors leading to portal hypertension in cirrhosis. Non-cytotoxic drugs including octreotide and celecoxib could reduce angiogenesis in hepatocellular carcinoma and gastric adenocarcinoma. However, the effect of octreotide and celecoxib on the anti-angiogenesis and sinusoidal remodeling of cirrhotic liver remains unclear. Methods: Peritoneal injection (i.p.) of TAA was employed to induce liver cirrhosis (200 mg/kg every 3 days for 16 weeks). 36 male Sprague-Dawley rats were randomized into control, TAA and TAA+O+C with 12 animals in each group. TAA+O+C group received TAA plus octreotide (50 μg/kg/day) and celecoxib (20 mg/kg/ day) from the initiation of TAA administration. TAA group received TAA plus placebo and control group received injections of normal saline (1mL i.p., every 3 days for 16 weeks). Scanning electron microscope (SEM) of liver sinusoidal endothelial cells (LSEC) and hepatic vascular casting, hematoxylin-eosin staining (HE), Masson trichrome staining (MT) were applied to evaluation of sinusoidal remodeling, fibrosis and angiogenesis. Portal pressure was also measured. Additionally, immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and Western blot for alpha-smooth muscle actin ( α-SMA) and collagen III, CD31, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), hypoxia-inducible factor-1 alpha (HIF-1α), phosphorylated extracellular signal-regulated kinase (p-ERK) and c-fos were determined. Results: Compared with TAA group, liver fibrosis and portal pressure in TAA+O+C group were significantly decreased by 63.1% and 33.4% (p < 0.01), respectively. And the mRNA levels of α-SMA and collagen III in TAA+O+C group were also reduced by 53.1% and 63.6% (p < 0.01). Histological sections, vascular casts of hepatic portal vein by SEM, IHC and qRT-PCR for CD31 showed that hepatic and intestinal angiogenesis in TAA+O+C group were markedly reduced when compared with TAA group. Sinusoidal remodeling induced by TAA (such as impaired LSEC fenestrae, reduced sinusoidal diameter and increased sinusoidal branching) was also ameliorated after octreotide and celecoxib treatment. The up-regulation of VEGF, VEGFR-2, HIF-1 α, p-ERK and c-fos induced by TAA administration were significantly inhibited after octreotide and celecoxib treatment. Conclusions: Long term administration of octreotide and celecoxib synergistically ameliorate portal hypertension and fibrosis in cirrhotic rat model by the inhibitory effects on the intrahepatic/extrahepatic angiogenesis and sinusoidal remodeling, The synergistically effect afforded by octreotide and celecoxib may attribute to the modulation on VEGF/VEGFR-2
Su1076 Influence of ITPA Genotype Polymorphisms on Treatment Outcome and Anemia in Chronic HCV-4 Infection Reham Al swaff, Ahmed A. Monis, Essam Abu Alanain Background: Among HCV therapy-associated hematologic adverse effects, anemia is particularly important because of its implication in treatment outcome and its frequency. Recently, two functional variants in the inosine triphosphatase (ITPA) gene, which encodes for ITPA on chromosome 20, have been associated with RBV-induced anemia. Aim of the study: To investigate and clarify the impact of ITPA genotype polymorphisms on treatment outcome and anemia in Egyptian patients with chronic HCV-4 infection. Methods: In this prospective, observational study, 90 HCV-4 infected patients treated with Peg-IFN plus RBV were enrolled. Two SNPs within or adjacent to ITPA gene (rs1127354 and rs7270101) were genotyped. The impact of ITPA genotype polymorphisms on treatment outcome and anemia was examined. Results: The overall Sustained Virologic Response (SVR) rate was 38.9%. 92.2% of patients had CC subtype of rs1127354 whereas 85.6% had AA subtype of rs7270101. Insignificant differences were found between the different subtypes of rs1127354 and rs7270101 as regards the SVR rates (p= 0.8, 0.3 respectively). Reduction of hemoglobin level (<10 g/dl) during treatment was significantly greater in patients with CC subtype of rs1127354 than in other subtypes (p= 0.05); however the SVR rate in this subtype was comparable to other subtypes. Conclusion: Polymorphisms at rs1127354 in the ITPA gene significantly influence the hemoglobin level during combination therapy for chronic HCV-4 infection. ITPA gene polymorphisms and SVR
AASLD Abstracts
S-982