Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin HCV genotype 1 patients

Original Article

Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice

Authors •L. I. Backus,
author notes Corresponding author1.Department of Veterans Affairs, Population Health Services, Palo Alto Health Care System, Palo Alto, CA, USA
First published: 13 June 2016
Full publication history •DOI: 10.1111/apt.13696

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Summary
Background Real-world data are needed to inform hepatitis C virus (HCV) treatment decisions.

Aim

To assess the comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) vs. ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± RBV in genotype 1 HCV patients treated in routine medical practice.

Methods

Observational intent-to-treat cohort of genotype 1 patients initiating 8 or 12 weeks of LDV/SOF ± RBV or 12 weeks of OPrD ± RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10 weeks after end of treatment.
Results 6961 patients initiated LDV/SOF (N = 4478), LDV/SOF + RBV (N = 1269), OPrD (N = 297), and OPrD + RBV (N = 917) at 126 facilities. Intention-to-treat SVR rates were 91.4% (3813/4170) for LDV/SOF, 90.0% (1098/1220) for LDV/SOF + RBV, 95.1% (269/283) for OPrD and 85.8% (746/869) for OPrD + RBV. SVR rates in those completing 8 weeks of LDV/SOF were 91.7% (1223/1333) and 12 weeks of LDV/SOF 94.6% (2475/2615), LDV/SOF + RBV 92.2% (1033/1120), OPrD 98.0% (248/253) and OPrD + RBV 95.5% (705/738). Significant predictors of SVR were African American race (OR 0.71, 95%CI 0.59–0.86, P < 0.001), body mass index (BMI) > 30 kg/m2 (OR 0.73, 95% CI 0.60–0.89, P = 0.002), FIB4 > 3.25 (OR 0.60, 95% CI 0.49–0.72, P < 0.001), OPrD + RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48–0.76, P < 0.001) and subtype 1b (OR 1.38, 95% CI 1.11–1.71, P = 0.003). For those completing 12 weeks, FIB-4 > 3.25 and high BMI remained significant predictors.

Conclusions

In this robust real-world cohort, SVR rates were similar to clinical trials. FIB-4 > 3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD + RBV likely arose from excess early discontinuation as these factors were no longer
significant, when limited to patients completing a 12-week course.

Introduction

The landscape of antiviral therapy for chronic hepatitis C virus (HCV) infection continues to advance as all-oral options expand. Sustained virological response (SVR) rates reported in clinical trials with all-oral regimens are consistently above 90% for most HCV-infected patient populations and have become the expected norm. Because of the rapidity with which HCV therapies are progressing and the absence of comparative clinical trials, providers are left to extrapolate information to make clinical decisions about medication selection. Emerging real-world data of individual therapies have demonstrated results comparable to registration trials, however, comparative effectiveness evaluations are needed to determine whether clinical differences exist between regimens.[1-6] Comparative effectiveness analyses will become increasingly important as patients, providers, healthcare systems and managed care organisations consider additional nuances of convenience, drug interactions, treatment duration and ultimately cost effectiveness.

Ledipasvir/sofosbuvir (LDV/SOF) and ombitasvir/paritaprevir/ritonavir plus dasabuvir (OPrD) have been extensively evaluated individually in clinical trials of HCV-infected adults. The SVR rates in LDV/SOF trials of genotype 1 patients with and without cirrhosis ranged from 94% to 99% and in OPrD trials SVR rates ranged from 89% to 99%.[7-14] While these outcomes appear similar, differences in study design and patient populations prevent direct cross-study comparison of results.
Hepatitis C virus disproportionally affects the veteran population and the Department of Veterans Affairs (VA) is the largest US provider of healthcare to HCV-infected individuals caring for nearly 5% of all individuals in the US with HCV infection.[15, 16] Thus, ongoing evaluation of the effectiveness of HCV antiviral regimens remains a priority for VA.[17] With the rapid uptake of all-oral HCV regimens across the VA system and the diverse HCV-infected veteran population receiving these regimens, we examined SVR rates and comparative effectiveness of LDV/SOF ± ribavirin (RBV) vs. OPrD ± RBV in genotype 1 HCV-infected veterans treated in routine medical practice.

Materials and methods

This was an observational intent-to-treat cohort analysis of HCV-infected veterans receiving LDV/SOF ± RBV or OPrD ± RBV from VA. Data for this study were obtained from the VA's national Clinical Case Registry for HCV, an extract of the VA electronic medical record that contains demographics, laboratory results, pharmacy information and International Classification of Diseases diagnosis codes from inpatient hospitalisations, outpatient visits and problem lists of HCV-infected veterans seen at all VA medical facilities.[18]

Eligible subjects included all genotype 1 HCV-infected veterans from any VA facility nationwide who initiated 8 or 12 weeks of VA-prescribed LDV/SOF ± RBV or 12 weeks of OPrD ± RBV by 31 March 2015 with an end of treatment (EOT) by 14 July 2015 and a days supply less than or equal to 91 days. For patients who received multiple courses of therapy, only the first course was included. The choice of regimen and timing of follow-up visits and laboratory testing was at the discretion of the provider as patients were treated in routine practice. The present cohort includes 4356 treatment naïve patients treated with LDV/SOF ± RBV who were reported on previously.[19] Patients were excluded if they changed regimens without a treatment interruption (n = 64), had a baseline HCV RNA ≤1000 IU/mL (n = 218), had a liver transplant (n = 141), or had genotype subtype 1a and received OPrD without RBV (n = 16).

Treatment outcome

Patients were considered to have SVR if they had HCV RNA results below the limit of quantification on all HCV RNA tests after the EOT including at least one test 10 weeks or more after the EOT. The 10 week time point was chosen to account for variability of clinic visits and of laboratory testing draws in clinical practice. Patients were categorised as not achieving SVR if they had a HCV RNA above the limit of quantification after the EOT, had no HCV RNA testing after the EOT and a HCV RNA above the limit of quantification on their last HCV RNA test while on treatment or died while on treatment or within 10 weeks of the EOT. Patients with HCV RNA below the limit of quantification on their last HCV viral load test, either on treatment or after the EOT, but no test 10 weeks of more after the EOT were excluded from the SVR analysis. The EOT was calculated as the last day covered by prescriptions of LDV/SOF or OPrD using the dates the medication was dispensed and the days’ supply. HCV RNA was categorised as above or below the lower limit of quantification based on the locally reported HCV RNA result of which 98% utilised assays with a lower limit of quantification of 15 U/mL or less. Patients were followed from the initiation of LDV/SOF ± RBV or OPrD ± RBV through 29 February 2016, allowing for more than 32 weeks of follow-up after the EOT for all patients in the cohort.

Control variables

Demographic and other baseline variables were determined at the time of treatment initiation and included age, gender, race/ethnicity, diabetes, HIV coinfection, history of decompensated liver disease (defined by oesophageal variceal haemorrhage, hepatic coma, hepatorenal syndrome or spontaneous bacterial peritonitis), prescribed proton pump inhibitor use, prior HCV antiviral treatment experience and HCV genotype 1 subtype. Subtype 1a included patients with reported results of 1a, mixed 1a/1b or 1 with subtype unspecified. Prior virological response was based on the most recent VA course of HCV antiviral treatment and categorised as relapse, partial response, null response and not defined. Baseline values for height and weight used to calculate body mass index (BMI) and the laboratory tests for alanine aminotransferase, aspartate aminotransferase, platelets and baseline HCV RNA were defined as the value within 1 year before and closest to the treatment start date. A FIB-4 score >3.25 at the start of treatment using baseline laboratory values was used as a marker of advanced liver disease.[20, 21] Patients with FIB-4 ≤ 3.25 were considered to be ‘noncirrhotic’.

In VA, HCV antiviral prescriptions are frequently filled for quantities less than 28 days. Patients were considered to have completed 8 weeks of LDV/SOF if they had received between 49 and 63 days’ worth of medication and 12 weeks LDV/SOF ± RBV or OPrD ± RBV if they received between 77 and 91 days’ worth of medication.

Statistical analysis

Univariate comparisons used the Pearson chi-squared test with Yates’ continuity correction for categorical variables. Multivariate logistic regression models were constructed to model SVR. Models included age, gender, race/ethnicity, diabetes, history of decompensated liver disease, treatment experience, BMI, FIB-4, genotype 1 subtype, and regimen. In a sensitivity analysis proton pump inhibitor use was included in the model. A set of models with the above baseline variables was constructed with all patients and with only patients who completed 12 weeks of treatment.
For all comparisons, a P < 0.01 was considered statistically significant. All analyses were performed using R version 3.1 (R Foundation for Statistical Computing, Vienna, Austria).
The protocol was approved by the Stanford University Institutional Review Board and the VA Palo Alto Health Care System Research and Development Committee.

Results

In total, 6961 patients with HCV genotype 1 initiated LDV/SOF ± RBV (n = 5747) or OPrD ± RBV (n = 1214) at 126 VA facilities. The mean age for the cohort was 61.4 years, 96.3% were male, 36.0% were African-American, 31.5% had diabetes, 3.2% had a history of decompensated liver disease, 23.6% were treatment experienced, 35.4% had a BMI ≥30 kg/m², and 29.5% had a FIB-4 > 3.25.

Baseline characteristics for the cohort by regimen appear in Table 1. For the cohort, 64.3% (n = 4478) received LDV/SOF, 18.2% (n = 1269) received LDV/SOF + RBV, 4.3% (n = 297) received OPrD and 13.2% (n = 917) received OPrD + RBV. Patients who received LDV/SOF+RBV were most likely to be treatment-experienced and to have markers of advanced liver disease including a history of decompensated liver disease, lower mean platelet count, higher mean FIB-4 score, and FIB-4 > 3.25.

Table 1. Baseline characteristics and 4 week on-treatment response of genotype 1 patients receiving ledipasvir/sofosbuvir- or ombitasvir/paritaprevir/ritonavir plus dasabuvir-based regimens with durations of 12 weeks or less

	Genotype 1 cohort (N = 6961)	LDV/SOF (N = 4478)	LDV/SOF + RBV (N = 1269)	OPrD (N = 297)	OPrD + RBV (N = 917)
Continuous variables reported as mean ± s.d. (range). Categorical variables reported as % (n). ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; DAA, direct-acting antiviral; LDV/SOF, ledipasvir/sofosbuvir; OPrD, ombitasvir/paritaprevir/ritonavir + dasabuvir; PEG, pegylated interferon; SOF, sofosbuvir; RBV, ribavirin. *Some patients received more than one prior DAA regimen and are included in the count for each regimen they received.
Age (years)	61.4 ± 6.2 (24.5–90.8)	61.2 ± 6.5 (25.3–90.8)	61.9 ± 5.2 (24.5–86.2)	62.3 ± 5.9 (28.5–77.2)	61.5 ± 6.0 (26.7–85.3)
Gender, male	96.3 (6703)	95.9 (4295)	97.2 (1233)	96.3 (286)	96.9 (889)
Race/ethnicity
African-American	36.0 (2506)	38.2 (1712)	29.0 (368)	46.8 (139)	31.3 (287)
Caucasian	51.6 (3591)	50.5 (2263)	54.5 (692)	43.4 (129)	55.3 (507)
Hispanic	5.4 (376)	4.5 (304)	8.0 (102)	4.0 (12)	6.4 (59)
Other/multiple	7.0 (488)	6.7 (300)	8.4 (107)	5.7 (17)	7.0 (64)
Diabetes	31.5 (2195)	30.3 (1357)	37.7 (479)	33.3 (99)	28.4 (260)
Proton pump inhibitor	27.7 (1927)	26.3 (1178)	35.4 (449)	25.3 (75)	24.5 (225)
HIV coinfected	4.5 (310)	5.3 (237)	3.7 (47)	2.4 (7)	2.1 (19)
Decompensated liver disease	3.2 (224)	1.9 (87)	8.6 (109)	0.7 (2)	2.8 (26)
Any treatment experience	23.6 (1645)	16.0 (718)	53.0 (673)	19.2 (57)	21.5 (197)
DAA experience (% of treatment experienced)	44.1 (726)	39.1 (281)	62.4 (420)	7.0 (4)	10.7 (21)
Prior SOF + simeprevir (n)*	71	12	57	0	2
Prior SOF + PEG + RBV or SOF + RBV (n)*	131	29	96	0	6
Prior boceprevir (n)*	494	222	253	4	15
Prior telaprevir (n)*	74	21	53	0	0
Prior treatment response	N = 1645	N = 718	N = 673	N = 57	N = 197
Relapse	29.9 (492)	24.0 (172)	39.2 (264)	14.0 (8)	24.4 (48)
Partial	10.2 (167)	9.1 (65)	10.1 (68)	21.1 (12)	11.2 (22)
Null	11.3 (186)	9.6 (69)	11.1 (75)	12.3 (7)	17.8 (35)
Unknown	48.6 (800)	57.4 (412)	39.5 (266)	52.6 (30)	46.7 (92)
BMI (kg/m2)	28.8 ± 5.3 (15.8–65.2)	28.5 ± 5.2 (15.8–65.2)	30.0 ± 5.5 (16.4–60.1)	28.2 ± 5.0 (16.0–53.7)	28.8 ± 5.3 (17.6–58.5)
BMI (kg/m2)
<25	23.1 (1605)	24.8 (1109)	17.9 (227)	24.2 (72)	21.5 (197)
25–29	41.6 (2893)	41.6 (1863)	37.6 (477)	49.8 (148)	44.2 (405)
≥30	35.4 (2463)	33.6 (1506)	44.5 (565)	25.9 (77)	34.4 (315)
ALT (U/L)	74.1 ± 56.5 (8–659)	71.4 ± 55.9 (8–659)	80.3 ± 52.3 (13–445)	62.6 ± 50.7 (13–552)	82.4 ± 64.3 (11–560)
AST (U/L)	64.4 ± 45.5 (6–614)	60.5 ± 43 (6–614)	76.6 ± 48.2 (11–503)	50.6 ± 34.8 (14–322)	70.4 ± 52.1 (13–499)
Platelets (Κ/μL)	185.6 ± 69.9 (6–759)	194.4 ± 68.2 (6–661)	150.3 ± 67.9 (22–759)	214.6 ± 59.6 (81–421)	181.8 ± 66.7 (32–470)
FIB-4	3.2 ± 3.7 (0.1–185.0)	2.8 ± 3.8 (0.1–185.0)	4.7 ± 4.1 (0.5–34.7)	2.0 ± 1.2 (0.3–10.0)	3.3 ± 2.9 (0.4–27.3)
FIB-4	N = 6936	N = 4460	N = 1267	N = 296	N = 913
≤3.25	70.5 (4889)	76.4 (3406)	47.8 (605)	89.5 (265)	67.1 (613)
>3.25	29.5 (2047)	23.6 (1054)	52.2 (662)	10.5 (31)	32.9 (300)
HCV RNA (log IU/mL)	6.2 ± 0.7 (3.0–7.9)	6.2 ± 0.7 (3.1–7.9)	6.2 ± 0.7 (3.0–7.8)	6.3 ± 0.6 (3.9–7.6)	6.3 ± 0.7 (3.0–7.8)
HCV RNA (IU/mL)
<6 000 000	82.0 (5705)	82.7 (3705)	84.6 (1073)	76.8 (228)	76.2 (699)
≥6 000 000	18.0 (1256)	17.3 (773)	15.4 (196)	23.2 (69)	23.8 (218)
HCV subtype 1b	27.3 (1897)	24.2 (1085)	23.4 (297)	100.0 (297)	23.8 (218)
IL28B polymorphism	N = 989	N = 598	N = 204	N = 33	N = 154
CC	20.3 (201)	22.6 (135)	15.2 (31)	9.1 (3)	20.8 (32)
CT	54.0 (534)	52.7 (315)	58.3 (119)	51.5 (17)	53.9 (83)
TT	25.7 (254)	24.7 (148)	26.5 (54)	39.4 (13)	25.3 (39)

Among patients who received LDV/SOF, 3.6% (n = 159) discontinued treatment before 8 weeks, 32.7% (n = 1464) received 8 weeks, 1.7% (n = 77) discontinued treatment between 8 and 12 weeks and 62.0% (n = 2778) received 12 weeks. In total, 94.7% completed either an 8 or 12 week course. Among people who received LDV/SOF + RBV, 8.1% (103/1269) discontinued treatment prior to completing 12 weeks. Among patients who received OPrD or OPrD+RBV, 11.4% (34/297) and 15.2% (140/917) of patients, respectively, discontinued treatment prior to completing a 12 week course. Significantly more patients receiving OPrD + RBV discontinued treatment prior to completing a 12-week course compared to those receiving LDV/SOF + RBV (P < 0.001).

Sustained virological response results were available for 94.0% (n = 6542) of patients in the cohort, including 24 patients who died while on treatment or shortly after who were categorised as no SVR. Four hundred nineteen patients whose last HCV RNA was undetectable, but occurred while still on treatment (n = 123) or less than 10 weeks after the EOT (n = 296), were excluded from the SVR analysis. Three hundred five patients had an undetectable HCV RNA obtained 10–11 weeks after the EOT and were included in the SVR analysis for reasons described previously.

Among 4170 LDV/SOF patients 91.4% achieved SVR; among 1220 LDV/SOF + RBV patients 90.0% achieved SVR; among 283 OPrD patients 95.1% achieved SVR and among 869 OPrD + RBV patients 85.8% achieved SVR (Table 2). For patients who received LDV/SOF, the SVR rates differed statistically based on categories of race/ethnicity, BMI, and FIB-4. For patients who received LDV/SOF + RBV, the SVR rates differed statistically based on proton pump inhibitor use and FIB-4. No statistically significant differences in SVR were observed according to baseline patient characteristics among patients receiving either OPrD or OPrD + RBV, and responses were generally similar to that observed in the overall population. SVR data for treatment naïve and experienced patients by subgroup can be found in Table S1A and B.

(Table 2).  SVR rates by regimen for genotype 1 patients receiving ledipasvir/sofosbuvir- or ombitasvir/paritaprevir/ritonavir plus dasabuvir-based regimens with durations of 12 weeks or less

Click On Image To Enlarge

For patients who completed an 8 week course of LDV/SOF or a 12 week course of LDV/SOF ± RBV or OPrD ± RBV, SVR rates were consistently higher overall and among subgroups when compared to the intention-to-treat SVR rates (Table 3). With regard to the impact of treatment duration among patients who received LDV/SOF, the SVR rate in those who received 8 weeks was 91.7% (1223/1333) and 94.6% (2475/2615) in those who received 12 weeks. An SVR rate of 92.2% (1033/1120) was achieved in patients completing 12 weeks of LDV/SOF + RBV and 95.5% (705/738) in those completing 12 weeks of OPrD+RBV. In genotype 1b patients who received 12 weeks of OPrD, an SVR rate of 98.0% (248/253) was achieved. In 1098 patients who met the Food and Drug Administration (FDA) labelling considerations for a shortened LDV/SOF course consisting of treatment-naïve, without cirrhosis (defined as FIB-4 ≤ 3.25), and a baseline HCV RNA <6 000 000 IU/mL and who completed 8 weeks of LDV/SOF therapy, the SVR rate was 93.2% (1023/1098). In 905 patients who also met the FDA considerations for a shortened LDV/SOF course but nevertheless received 12 weeks of LDV/SOF therapy, the SVR rate was 96.6% (874/905)(P = 0.001 compared to 8 week course).

Table 3. SVR rates by regimen for genotype 1 patients receiving ledipasvir/sofosbuvir- or ombitasvir/paritaprevir/ritonavir plus dasabuvir-based regimens who received 8 or 12 weeks of LDV/SOF and 12 weeks of all other regimens

Click On Image To Enlarge

In multivariate analysis, significant independent predictors of decreased odds of SVR were African American race (OR 0.71, 95% CI 0.59–0.86, P < 0.001), BMI ≥30 kg/m² (OR 0.73, 95% CI 0.60–0.89, P = 0.002), FIB-4 > 3.25 (OR 0.60, 95% CI 0.49–0.72, P < 0.001) and use of OPrD + RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48–0.76, P < 0.001) (Table 4). Genotype subtype 1b was an independent predictor of increased odds of SVR (OR 1.38, 95% CI 1.11–1.71, P = 0.003). Age, gender, diabetes, history of decompensated liver disease and treatment experience did not predict SVR. In the sensitivity analysis proton pump inhibitor use was not associated with a difference in the odds of achieving SVR (0.85, 95% CI 0.71–1.03, P = 0.09). In models limited to patients receiving 12 weeks of treatment, only BMI ≥30 kg/m² (OR 0.66, 95% CI 0.49–0.88, P = 0.004) and FIB4 > 3.25 remained significant (OR 0.46, 95% CI 0.35–0.60, P < 0.001).

Table 4. Odds ratios for sustained virological response in multivariate model for genotype 1 patients treated with ledipasvir/sofosbuvir- or ombitasvir/paritaprevir/ritonavir plus dasabuvir-based regimens

	Intention-to-treat OR (95% CI), N = 6525	Received 12 weeks OR (95% CI), N = 4720
BMI, body mass index; CI, confidence interval; LDV/SOF, ledipasvir/sofosbuvir; OPrD, ombitasvir/paritaprevir/ritonavir+dasabuvir; OR, odds ratio; RBV, ribavirin; ref., reference; SVR, sustained virological response. †Subtype 1a includes 1a, mixed 1a/1b and 1 with subtype unspecified. **P < 0.01, ***P < 0.001.
Age <55 years (ref. 55–64)	1.37 (0.98–1.94)	1.36 (0.83–2.37)
Age ≥65 years (ref. 55–64)	1.17 (0.96–1.43)	1.26 (0.94–1.70)
Female (ref. Male)	2.23 (1.26–4.38)	2.51 (1.04–8.23)
African American (ref. Caucasian)	0.71 (0.59–0.86)***	0.86 (0.64–1.14)
Hispanic (ref. Caucasian)	0.77 (0.54–1.12)	1.00 (0.59–1.81)
Other/multiple (ref. Caucasian)	0.87 (0.62–1.23)	0.81 (0.51–1.34)
Diabetes (ref. no diabetes)	1.01 (0.83–1.22)	1.08 (0.82–1.42)
Decompensated liver disease (ref. no)	0.60 (0.41–0.90)	0.87 (0.51–1.54)
Treatment experienced (ref. naïve)	0.90 (0.73–1.11)	0.90 (0.67–1.21)
BMI <25 kg/m2 (ref. 25–29 kg/m2)	0.77 (0.61–0.96)	0.99 (0.69–1.44)
BMI ≥30 kg/m2 (ref. 25–29 kg/m2)	0.73 (0.60–0.89)**	0.66 (0.49–0.88)**
FIB-4 > 3.25 (ref. ≤3.25)	0.60 (0.49–0.72)***	0.46 (0.35–0.60)***
HCV subtype 1b (ref. 1a†)	1.38 (1.11–1.71)**	1.44 (1.04–2.02)
LDV/SOF + RBV (ref. LDV/SOF)	1.07 (0.84–1.37)	0.87 (0.64–1.19)
OPrD (ref. LDV/SOF)	1.27 (0.74–2.37)	1.68 (0.71–4.93)
OPrD+RBV (ref. LDV/SOF)	0.60 (0.48–0.76)***	1.22 (0.83–1.84)

Discussion

In this robust comparative effectiveness analysis of LDV/SOF ± RBV vs. OPrD ± RBV in genotype 1 HCV-infected veterans treated in routine medical practice, high SVR rates were achieved overall (86–95%) and within subgroups (83–100%). In multivariate models, OPrD + RBV was found to be less effective than LDV/SOF and patients receiving the former were 40% less likely to achieve SVR. However, in patients who completed a 12-week treatment course there was no difference in effectiveness. Similar to clinical trials, curative all-oral treatment has become a reality for over 90% of patients treated in the real-world, even in those with characteristics previously associated with poorer outcomes. This analysis demonstrates the real-world comparative effectiveness of all-oral DAA regimens in individuals with genotype 1 HCV infection that clinicians, patients and payers have anticipated.

The current HCV treatment landscape remains complex despite increasingly more effective HCV regimens, with variability in outcomes for patients with previous treatment experience, genotype subtype, race, degree of underlying liver disease and other comorbid conditions.[7, 8, 13, 14, 22-24] Because of the large sample size in this cohort, we were able to do robust subgroup analyses to examine differences among these characteristics and identify where challenges remain.
Despite SVR rates higher than any previously reported among veterans with advanced liver disease, the presence of advanced liver disease as indicated by a FIB-4 score greater than 3.25 remained a significant negative predictor of response with an apparent impact for treatment naïve and treatment experienced patients and across all regimens.[5, 23, 25] Over 2000 patients with advanced liver disease were included in this cohort. In multivariate models, the presence of advanced liver disease predicted reduced odds of achieving SVR by 40% independent of treatment experience and regimen. Absolute SVR rates in treatment naïve patients were generally four to five percent lower in those with advanced liver disease compared to those without advanced liver disease for patients who received LDV/SOF (87.6% vs. 92.6%), who received LDV/SOF + RBV (90.0% vs. 94.7%), and who received OPrD (91.7% vs. 96.1%). Current AASLD/IDSA treatment guidelines and FDA labelling recommend LDV/SOF for 12 weeks in treatment naïve patients with cirrhosis based largely on data from 34 patients in the ION-1 trial.[7, 26, 27] However, our observation of SVR rate of 87.6% with LDV/SOF in 889 treatment naïve patients with FIB4 scores >3.25 indicate SVR rates with this regimen may be below the 90% bar for which all-oral regimen expectations have been set and other treatment options might need to be considered in such patients.

In treatment experienced patients with and without advanced liver disease, reductions of 5–8% in SVR rates were seen in patients who received LDV/SOF (85.5% vs. 93.5%), who received LDV/SOF + RBV (85.4% vs. 90.9%), and who received OPrD + RBV (82.1% vs. 89.6%). The reduced SVR rates in the low to mid-80s in treatment experienced patients with advanced liver disease in this study mirror the 86% and 82% SVR rates observed in ION-2 in treatment-experienced cirrhotic patients receiving 12 weeks of LDV/SOF and LDV/SOF + RBV respectively.[8] In the TURQUOISE-II study SVR rates were 87% and 95% in treatment experienced cirrhotic null responders treated for 12 and 24 weeks respectively with OPrD+RBV.[14] The large number of patients included in our study coupled with the similar results obtained from ION-2 and TURQUOISE-II suggest that lower SVR rates may be expected in cirrhotic patients and particularly treatment-experienced cirrhotic patients treated in routine clinical practice. Extended treatment of 24 weeks in such patients may be warranted to achieve higher SVR rates.

In this cohort, SVR data were available for over 2300 African Americans. Multivariate modelling indicated African American race was associated with a 29% reduction in the odds of SVR. This effect was observed in multivariate models of the overall cohort but not in models limited to patients completing a 12 week treatment course suggesting that the reduced odds of SVR for African Americans arose in large part from excess early treatment discontinuations and from diminished effectiveness of 8-week LDV/SOF in African Americans, which has also been observed in retrospective analyses of the ION clinical trials.[22] Numerically lower SVR rates were observed in African Americans compared to Caucasians treated with LDV/SOF, OPrD and OPrD+RBV. In patients who received a full 12 weeks of treatment, SVR rates in African Americans were higher than in the intention-to-treat analysis and the numeric differences in SVR rates between African Americans and Caucasians were diminished.

This study included over 2300 patients with a BMI at or above 30 kg/m², and in the overall cohort those with high BMI were 27% less likely to achieve SVR. As one might expect, the effect of BMI on SVR was not dependent on whether the patient completed therapy and, as such, high BMI remained a negative predictor of response in those who completed a 12-week treatment course. For such patients, additional treatment options may need to be considered to optimise SVR rates.
Shorter 8 week regimens were widely used in treatment-naïve patients with baseline HCV RNA below 6 000 000 IU/mL without cirrhosis. We could only assess the use of 8 week LDV/SOF regimens in patients who completed therapy because we were unable to otherwise determine if the original provider intent was to treat for 8 or 12 weeks using the available electronic data. Although the difference in SVR rates between those who completed 8 weeks and those who completed 12 weeks was numerically small at 3.4% it was statistically significant suggesting that to optimise a patient's likelihood of SVR the 12-week duration may be preferred.

Real-world SVR rates achieved with these treatment regimens were remarkably high. The large differences between real-world effectiveness and clinical trial efficacy previously observed with HCV antiviral treatment have now been almost eliminated with the use of potent all-oral regimens. Most of the small decrement in observed effectiveness in this real-world cohort may be explained in large part by higher early discontinuation rates. Early discontinuations rates were highest in those receiving OPrD + RBV (15.2%), followed by OPrD (11.4%), LDV/SOF + RBV (8.1%) and LDV/SOF (5.3%). Clinical trials tend to have early discontinuation rates of less than 3%.[7-14] Higher early discontinuation rates had the greatest impact on SVR rates in those receiving OPrD + RBV with a nearly 10% difference in SVR rates comparing intention-to-treat (85.8%) to those who completed 12 weeks (95.5%). While we did not examine reasons for early discontinuation, adverse effects and adherence are often recognised as contributing factors. Setting appropriate expectations about potential medication side effects and continued emphasis on adherence and persistence will remain important elements in maximising treatment success. Any remaining decrement in clinical effectiveness compared to clinical trial efficacy may be explained by differences in patient populations. For example, higher BMI in our cohort was identified as a significant negative predictor of SVR.

Given the high SVR rates achieved in clinical practice even among subgroups, regimen selection will depend increasingly upon nuanced considerations. Genotype subtype, presence of cirrhosis, prior treatment regimen or presence of pre-existing resistance associated polymorphisms currently determines the need for RBV and subsequent length of treatment for certain regimens. Potential for drug interactions and comorbidities may limit use of a particular agent. Enough options presently exist to allow providers some flexibility in selecting regimens tailored to meet individual patient characteristics or needs without sacrificing effectiveness. Expectations for high SVRs have been set and now validated in real-world cohorts, thus regimen subtleties together with cost considerations and insurance coverage will be key determinants for utilisation.

While this study includes one of the largest cohorts of diverse HCV-infected patients treated in clinical practice published to date, there are limitations. Specific reasons for early discontinuation (i.e. adverse events, poor tolerability, social or behavioural issues) could not be determined from the electronic data. Duration of treatment and early treatment discontinuation rates were determined based on the cumulative dispensed days’ supply which may overestimate the treatment duration as patients may have discontinued treatment even with medication in their possession. In VA, many prescriptions are filled for small quantities (e.g. 2-week supplies) which would limit the extent of the overestimation. Baseline resistance testing was not performed thus we were unable to assess the impact of this factor.

Conclusions

In this large real-world cohort of genotype 1 HCV-infected veterans treated with LDV/SOF-based or OPrD-based therapy, high SVR rates comparable to clinical trials were observed and were consistently high across all subgroups evaluated. Odds of SVR were reduced in African Americans compared to Caucasians, those receiving OPrD + RBV compared to LDV/SOF, those with advanced liver disease and those with BMI ≥30 kg/m² compared to those with lower BMI. Reduced odds of SVR for African Americans and those receiving OPrD + RBV arose in large part from early discontinuation as these predictors no longer had a significant impact on odds of SVR in those who completed a 12-week course. Advanced liver disease and higher BMI, however, persisted as significant negative predictors of SVR even when considering only those patients who completed a 12-week course. For patients with advanced liver disease and high BMI longer durations of therapy or additional treatment options may still be needed to increase SVR rates. Real-world experience from large diverse cohorts such as this is necessary to better inform and refine HCV management strategies.

Authorship

Guarantor of the article: Lisa I. Backus.
Author contributions: Drs Backus, Belperio, Loomis and Mole: Study concept and design. Drs Backus, Belperio, Shahoumian, Loomis and Mole: Analysis and interpretation of data; Drs Backus, Belperio: drafting of the manuscript, Drs Backus, Belperio and Mole: Critical revision of the manuscript for important intellectual content; Dr Shahoumian: Statistical analysis. This statement acknowledges that all authors approved the final version of the article, including the authorship list.

Acknowledgement

Declaration of personal and financial interests: None.

Source http://onlinelibrary.wiley.com/enhanced/doi/10.1111/apt.13696

Survival rates rise with new hepatitis C treatments

Survival rates rise with new hepatitis C treatments

Just a few years ago the outlook for treating patients with chronic hepatitis C was grim.

For almost a year, patients would receive a complicated regimen of shots and up to 18 pills a day with drugs that caused major side effects. After that, there was a six-month follow-up period to see if the treatment was successful.

And the cure rate was less than 50 percent.

Thanks to recent research ― some of it conducted in San Antonio ― most patients now can be cured with direct-acting antivirals, a gentler combination of drugs in one or a few pills with only a few months of treatment. Continuing research is promising for new treatments for the groups of patients who don’t respond well to the new standard therapy.

“The good news is patients should know that a paradigm shift has occurred as we now can give all-oral therapy that is simple, safe and highly effective with cure rates of about 95 percent for most patient populations,” said Dr. Eric Lawitz, professor in the School of Medicine at the UT Health Science Center San Antonio.

Lawitz and Dr. Fred Poordad, also a professor of medicine at the UT Health Science Center, see patients at the Texas Liver Institute in San Antonio. They have been researching cures for hepatitis C for years with great success. They have presented oral presentations at international liver meetings and published peer-reviewed articles in major journals that have changed the standard of care for patients.

The FDA-approved drugs they have evaluated include Harvoni (a combination of ledipasvir and sofosbuvir), Olysio (simeprevir), Viekira Pak (ombitasvir, paritaprevir and ritonavir packaged with dasabuvir tablets), Zepatier (elbasvir and grazoprevir) and Daklinza (daclatasvir).

‘Silent epidemic’
The tragedy of hepatitis C is that is that it has no symptoms until the disease progresses, so patients can have the disease for many years and not know it.

“For that reason it is often called a silent epidemic,” Poordad said. “If not identified early, the disease can progress to cirrhosis of the liver, liver cancer and the need for a liver transplant. And even if the patient receives a liver transplant, the disease must be cured or it can infect the new liver 

What causes hepatitis C?
According to the Centers for Disease Control, hepatitis C is the leading blood-borne disease in the U.S. Although some people have only a mild form of the disease, 75 percent to 85 percent of patients who become infected with the hepatitis C virus will develop a chronic infection. This is estimated to be more than 3.5 million people in the nation.

The virus spreads through contact with the blood of an infected person. This often occurs through sharing needles, syringes or other equipment used in drug use. Another common way is through needle-stick injuries in a health-care setting. Mothers with hepatitis C can pass the disease on to their unborn children. Less common ways of spreading the virus are by sharing toothbrushes and razors, or by having sexual contact with a person who has hepatitis C. Some people contracted the disease years ago through blood transfusions before widespread screening of the blood supply began in 1992.

Find out if you have hepatitis C
According to the CDC, baby boomers ― people born between 1945 and 1965 ― are five times more likely to be infected with hepatitis C than other adults. “You can find out if you have hepatitis C through a simple blood test at your doctor’s office. All you have to do is request it,” Poordad said.

More information about hepatitis C, the blood test for the virus, and the newest treatments are available at the CDC website, www.cdc.gov.

Continue reading...

Blood-born molecules could predict those who will develop liver cancer

Blood-born molecules could predict those who will develop liver cancer

(PHILADELPHIA) - Hepatocellular carcinoma, the most common type of liver cancer, is increasing in incidence in the United States, and infection with the Hepatitis B virus (HBV) causes about 50 percent of cases. However, it can be difficult to identify who is most likely to develop this cancer. Although earlier research had discovered molecular signatures associated with HBV-driven liver cancer, new research from Thomas Jefferson University has proven that this panel of microRNAs can also predict the patients at high risk for developing the disease before the cancer develops, via a blood test.

The researchers, led by Hushan Yang, Ph.D., an Associate Professor of Medical Oncology and researcher at the Sidney Kimmel Cancer Center at Jefferson studied a large cohort of HBV-infected patients, some of whom eventually developed liver cancer, and analyzed their molecular signature from blood samples. Of the 373 HBV patients who were originally cancer free, 40 developed cancer over a median follow up of 4.5 years. The researchers analyzed a panel of 24 microRNAs -- small molecules that regulate gene activity -- and showed that 15 of these microRNAs had changed their normal gene expression pattern before patients developed cancer, suggesting these molecules could be used to predict patients with a high likelihood of developing cancer. The study was published in the journal Oncotarget,

Earlier studies had identified the 24 microRNAs that Dr. Yang and colleagues studied. However, it was unclear whether those microRNAs caused the cancer, or were a result of already occurring cancerous processes. By following this cohort of patients prospectively, and using blood samples taken at least one year before liver cancer diagnosis, the researchers were able to answer that question for the first time. In addition, prior studies analyzed samples taken from patient biopsies, which require invasive procedures, whereas the current study showed that microRNAs circulating in the blood could predict disease.

"This research confirms previous work on microRNAs and liver cancer and goes further to show that these microRNAs may be able to predict the development of liver cancer through a non-invasive blood test," says first author Chun Wang, a visiting scholar in the Department of Medical Oncology.

The current non-invasive test for determining cancer risk among HBV patients is a diagnostic for the molecule alpha-fetoprotein (AFP). It is also associated with Hepatitis C infections, but it isn't always a good predictor of disease. In fact, the Jefferson researchers identified 15 out of 16 patients, or 94 percent of patients who were misclassified as cancer-free by AFP. Likewise, in the 57 patients who were deemed at high risk of developing liver cancer by AFP, the microRNA testing correctly reclassified 33, or 58 percent, as low risk.

Although the panel of 15 microRNAs was useful, it wasn't perfect. "We need to find more microRNAs that may predict liver cancer in order to sharpen this tool for identifying high risk patients," says Dr. Yang. "Through collaboration with Dr. Hann in the Department of Medicine at Jefferson, we continue to work on improving this diagnostic method."

The work was supported by a Tobacco Grant from the Pennsylvania Department of Health, National Cancer Institute Grant CA159047, American Cancer Society Research Scholar Grant 123741-RSG-13-003-01-CCE, and a V Scholar Grant from the V Foundation for Cancer Research. The authors report no conflicts of interest.

Source: Thomas Jefferson University

TGIF Rewind: Big pharmaceuticals and the Hepatitis C drug trail dubbed a 'miracle cure'

Rewind: News and Views

Welcome to TGIF rewind, a look back at this weeks hepatitis C headlines with updates from around the web.

In The News

Big pharmaceuticals and the Hepatitis C drug trail dubbed a 'miracle cure'
What would you do if you had a potentially lethal illness, knew of a "miracle" cure which would most likely fix the problem in three months by taking one pill a day, but you couldn't afford to buy the medicine from the drug company which owned the patent? This is the position that "Patient Zero" found himself in. And he, with a doctor and a group of campaigning mates, found an answer – one that they believe costs up to 30 times less than the drug company might expect them to pay.

CDC
State Reporting Requirements for Viral Hepatitis

Check out new site w/ info on state reporting requirements for viral hepatitis

Drug and biotech industry trade groups give Martin Shkreli the boot

Former hedge fund manager Martin Shkreli has the Internet ablaze after hiking the price of the drug that's been on the market for decades. Here's what happened. (Gillian Brockell/The Washington Post)

Health Care Industry Mergers Side Effect of Affordable Care Act

Many are worried that the huge consolidations will dampen competition and push up health care prices over time...

One senator's push to fund hepatitis C treatment for veterans

Many veterans who fought to protect and defend our country are still fighting to get the support they need from the federal government...

Why people don't trust drug makers
Insurers and pharmacy benefit managers - not drug companies - are the ones who determine what patients pay for medications. Consider the controversy surrounding the hepatitis C drug Sovaldi. When the medicine came on the market, it quickly became ...

Rhode Island Medicaid Denied 65% of Hep C Treatment Requests in 2015
It's a move that, while saving the state millions of dollars, is keeping hundreds of sick patients from accessing a cure.

How Much Did Medicaid Programs Spend on Sovaldi in 2014?

Concern about drug costs has been particularly acute for state Medicaid programs, which face both limited budgets and high Hepatitis C prevalence among beneficiaries (higher than in the general population). And perhaps with good reason: In 2014, the ...

Sofosbuvir-velpatasvir combo effective in all HCV genotypes

By: MADHU RAJARAMAN, Internal Medicine News Digital Network

September 23, 2015 

A once-daily, fixed-dose combination of sofosbuvir (SOF) plus velpatasvir (VEL) had high success rates for the treatment of all six genotypes of hepatitis C virus, manufacturer Gilead Sciences reported.

In three of four phase III trials (ASTRAL-1, ASTRAL-2, and ASTRAL-3), 1,035 HCV patients were given the drug combination for 12 weeks. In the fourth trial (ASTRAL-4), 267 HCV patients with decompensated cirrhosis were randomized to receive either the SOF/VEL combination for 12 weeks with or without ribavirin or 24 weeks of just SOF/VEL. The primary efficacy endpoint for all studies was a sustained virological response at 12 weeks, the company said in a statement.

The FDA has designated the SOF/VEL combination as “breakthrough therapy” status, granted to “investigational medicines that may offer major advances in treatment over existing options,” the statement said.Results showed that 98% of patients in the first three trials achieved the efficacy endpoint. In the ASTRAL-4 study, 94% of patients in the SOF/VEL plus ribavirin group achieved sustained virological response at 12 weeks. The rates of success in patients receiving the SOF/VEL combination for 12 or 24 weeks were 83% and 86%, respectively. The most common adverse effects were fatigue, nausea, and headache.

mrajaraman@frontlinemedcom.com

Press Release

Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating Fixed-Dose Sofosbuvir/Velpatasvir (GS-5816) Pan-Genotypic

Two HCV Drugs to Be Discontinued

The Food and Drug Administration (FDA) announced that Rebetol(ribavirin; Merck) capsules and PegIntron (peginterferon alfa-2b; Merck) for Injection are being discontinued. The decision is business-related and not due to safety or efficacy issues with the drugs.

Rebetol is a nucleoside analogue indicated for chronic hepatitis C in combination with interferon alfa-2b (pegylated and nonpegylated), in patients ≥3 years of age with compensated liver disease. It is supplied as 200mg capsules in 56-, 70-, and 84-count bottles. The Rebetol discontinuation is effective February 1, 2016.

PegIntron is an antiviral indicated for treatment of chronic hepatitis C in patients with compensated liver disease. It is supplied as 50mcg/0.5mL, 80mcg/0.5mL, 120mcg/0.5mL, and 150mcg/0.5mL single-use vials and single-use pre-filled pens. No effective date is available for the PegIntron discontinuation.

For more information call (888) 463-6332 or visit FDA.gov.
Source
http://www.empr.com/safety-alerts-and-recalls/rebetol-pegintron-to-be-discontinued/article/440426/

Conatus Announces emricasan Phase 2 study reduces liver portal hypertension predominantly due to NASH or HCV

A player in J&J's hep C cocktail helps hustle a quick cure 

September 17, 2015 | By John Carroll
Gilead has already made a megablockbuster fortune out of its hepatitis C cure. But the race to cure patients faster (and probably cheaper) is still on. And Achillion today posted some new data from small studies that show its NS5A inhibitor odalasvir (or ACH-3102) could feature prominently in one of the new cocktail therapies now in development at Johnson & Johnson...

Around The Web

NATAP

Hepatitis C virus infection: a risk factor for Parkinson's disease
"In summary, our study not only demonstrated a significantly positive association between HCV infection and Parkinson's disease (PD) from a large population-based epidemiological study but also proved the dopaminergic neuronal toxicity by HCV in vitro at the molecular level through an increase in cytokines induced by HCV. Epidemiologically, we found that anti-HCV(+) patients had statistically significant increased risk of developing PD in the population-based study. 

Excluding people who use drugs or alcohol from access to hepatitis C treatments - Is this fair, given the available data? - EDITORIAL 

Revolutionary new drugs to cure hepatitis C virus (HCV) infection represent one of the most important breakthroughs in clinical medicine in recent decades. However, high pricing of these well-tolerated, highly efficacious all-oral regimens and high demand (actual or anticipated) has led many payers in the United States and other countries to exclude people who have recently used illicit drugs, injectable drugs or alcohol (with the definitions of "use" varying by jurisdiction) from access to these treatments

N Engl J Med 

Correspondence

Early Patterns of Sofosbuvir Utilization by State Medicaid Programs

N Engl J Med 2015; 373:1279-1281 September 24, 2015 

DOI: 10.1056/NEJMc1506108

To the Editor:

The cure rates associated with sofosbuvir, a new treatment for hepatitis C virus (HCV), have been remarkable.1 However, the high cost of the drug has raised concerns,2 particularly in regard to socioeconomically disadvantaged populations with a high prevalence of HCV infection, such as Medicaid beneficiaries. Demand for new HCV drugs in Medicaid populations drove historic surges in spending on drugs in 2014, the first full year during which sofosbuvir was available since its approval by the Federal Drug Administration (FDA) in late 2013.3 Given its recent introduction to the market, little is known about state-level utilization and spending patterns for sofosbuvir...

Healio 

NICE recommends software to diagnose, monitor liver fibrosis
“As well as meaning that people with chronic hepatitis B or C could avoid having invasive liver biopsies, the associated savings of more than £400 per person ...

Interferon-based therapy still common for HCV among veterans
In a retrospective study, researchers found that the uptake of direct-acting antivirals, specifically Victrelis and Incivek, increased among veterans with HCV over time…

Editorial

HCV Guidelines: A Living Breathing Document

The guidelines for hepatitis C have been updated twice in the month of August.

The first update incorporated the approval of daclatasvir (Daklinza, Bristol-Myers Squibb) in the United States and, based on that approval, modified treatment recommendations for most of the treatment groups..

Lucinda Porter
Hepatitis C: The Evolution of Treatment
Last week I discussed the history of hepatitis C. This week I focus on the evolution of hepatitis C treatment...

Healthy You

Green Tea Hidden Dangers: Teen Contracts Acute Hepatitis After Drinking Three Cups Per Day
A young woman has contracted hepatitis after drinking three cups of Chinese green tea per day.
Doctors have now warned of the hidden dangers of consuming too much of the herbal tea, which they believe was to blame for the teenager contracting acute hepatitis...

Over long term, diet and exercise are best to prevent diabetes

In a head-to-head comparison over 15 years, diet and exercise outperformed the drug metformin in preventing people at high risk for diabetes from developing the disease.

Metformin Link to Vitamin B12 Deficiency, Neuropathy, in Diabetes

Researchers link 4 years of metformin use to a net worsening of peripheral neuropathy in type 2 diabetes, even after accounting for improvements from HbA1c lowering.

Medscape Medical News, September 25, 2015 

Rethinking Drinking 

Explore calculators, interactive worksheets, and more that will help you take a look at your drinking habits and understand how they may affect your health...

Off Topic

Should Dr Oz, a Prominent Surgeon, Be Fired for Quackery?
Last spring, 10 physicians wrote to Columbia University, where Dr Mehmet Oz is employed, demanding his removal for promoting quack remedies on TV. Should he be? See what your colleagues think.

Scientists stop and search malware hidden in shortened URLs on Twitter
Intelligent system created to stop and search malware links
Engineering and Physical Sciences Research Council

Cyber-criminals are taking advantage of real-world events with high volumes of traffic on Twitter in order to post links to websites which contain malware.

To combat the threat, computer scientists have created an intelligent system to identify malicious links disguised in shortened urls on Twitter. They will test the system in the European Football Championships next summer. The research is co-funded by the Engineering and Physical Sciences Research Council (EPSRC) and the Economic and Social Research Council (ESRC).

In the recent study the Cardiff University team identified potential cyber-attacks within five seconds with up to 83% accuracy and within 30 seconds with up to 98% accuracy, when a user clicked on a URL posted on Twitter and malware began to infect the device.

The scientists collected tweets containing URLs during the 2015 Superbowl and cricket world cup finals, and monitored interactions between a website and a user's device to recognise the features of a malicious attack. Where changes were made to a user's machine such as new processes created, registry files modified or files tampered with, these showed a malicious attack.

The team subsequently used system activity such as bytes and packets exchanged between device and remote endpoint, processor use and network adapter status to train a machine classifier to recognise predictive signals that can distinguish between malicious and benign URLs.

Dr Pete Burnap, Director of the Social Data Science Lab at Cardiff University, and lead scientist on the research, said: "Unfortunately the high volume of traffic around large scale events creates a perfect environment for Cyber-criminals to launch surreptitious attacks. It is well known that people use online social networks such as Twitter to find information about an event.

"Attackers can hide links to malicious servers in a post masquerading as an attractive or informative piece of information about the event.

"URLs are always shortened on Twitter due to character limitations in posts, so it's incredibly difficult to know which are legitimate. Once infected the malware can turn your computer into a zombie computer and become part of a global network of machines used to hide information or route further attacks.

"In a 2013 report from Microsoft these 'drive-by downloads' were identified as one of the most active and commercial risks to Cyber security.

"At the moment many existing anti-virus solutions identify malware using known code signatures, which make it difficult to detect previous unseen attacks."

Professor Omer Rana, Principal investigator on the project which is also includes Royal Holloway, University of London, City University London, the University of Plymouth and Durham University said:

"We are trying to build systems that can help law enforcement authorities make decisions in a changing Cyber Security landscape. Social media adds a whole new dimension to network security risk. This work contributes to new insight into this and we hope to take this forward and develop a real-time system that can protect users as they search for information about real-world events using new forms of information sources.

"We have the European Football Championships coming up next summer, which will provide a huge spike in Twitter traffic and we expect to stress-test our system using this event."

Professor Philip Nelson, Chief Executive, EPSRC said: "Using social media is an integral part of modern life, vital to organisations, businesses and individuals. The UK needs to operate in a resilient and secure environment and this research will help combat these criminal Cyber-attacks."

Hope everyone has a wonderful weekend.

Tina

Conatus Announces emricasan Phase 2 study reduces liver portal hypertension predominantly due to NASH or HCV

Press Release

Conatus Announces Top-line Results From Multicenter Phase 2 Portal Hypertension Clinical Trial in Patients With Liver Cirrhosis

September 23, 2015 16:01 ET | Source: Conatus Pharmaceuticals

- Emricasan Significantly Lowered Portal Pressure in Patients With Severe Portal Hypertension -

- Conference Call and Webcast Presentation at 8:30 a.m. ET on Thursday, September 24 -

SAN DIEGO, Sept. 23, 2015 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ:CNAT) today announced that the company's exploratory Phase 2 Portal Hypertension (PH) clinical trial of emricasan, a first-in-class, orally active pan-caspase inhibitor, met the following primary endpoints: a) a clinically meaningful and statistically significant change from baseline in hepatic venous pressure gradient (HVPG), a measurement of pressure in the portal vein, in patients with liver cirrhosis and severe portal hypertension (HVPG ≥12 mmHg); and b) a statistically significant change from baseline in cleaved Cytokeratin 18 (cCK18), a mechanism-specific biomarker of excessive cell death that contributes to chronic inflammation, in the total evaluable liver cirrhosis patient population.

The open-label PH trial was conducted at nine U.S. sites and enrolled 23 patients (22 evaluable) with portal hypertension and compensated liver cirrhosis that was predominantly due to nonalcoholic steatohepatitis (NASH) or hepatitis C virus (HCV), including patients with active HCV infection and patients who had a sustained viral response (SVR) to antiviral therapy. Portal hypertension, or elevated blood pressure in the major vein feeding into the liver, was confirmed by HVPG measurement >5 mmHg at baseline and measured again after treatment with 25 mg of emricasan orally twice daily for 28 days. Patients were divided according to the HVPG therapeutic threshold of 12 mmHg, which indicates more severe portal hypertension. Reducing the HVPG to below 12 mmHg or reducing HVPG by ≥10% or ≥20% has been strongly associated with clinical benefit in this patient population.

The HVPG endpoint was analyzed in: a) patients with baseline HVPG values ≥12 mmHg (N=12); b) patients with baseline HVPG values <12 mmHg (N=10); and c) all evaluable patients (N=22). HVPG measurement was standardized, and tracings were evaluated by a single expert reader not otherwise involved in the PH trial. HVPG decreased by a mean of 3.7 mmHg from the mean baseline of 20.6 mmHg in the higher baseline HVPG group (p<0.003), with 8 of 12 achieving a ≥10% decrease, 4 of 12 achieving a ≥20% decrease, and 2 of 12 achieving reductions below 12 mmHg. The changes from baseline HVPG were not statistically significant in the lower baseline HVPG group (+1.9 mmHg mean increase from mean baseline of 8.1 mmHg; p=0.12) or the total evaluable patient population (–1.1 mmHg from mean baseline of 15.2 mmHg; p=0.26). The cCK18 endpoint, analyzed in the total evaluable patient population, showed a statistically significant reduction (p<0.03) from baseline. Consistent with results from prior trials, emricasan was safe and well tolerated in the PH trial, with no dose-limiting toxicities and no drug-related serious adverse events. Detailed results are expected to be presented in a future scientific forum.

As liver cirrhosis progresses, portal pressure increases and hepatic function is eventually lost. Importantly, portal hypertension is largely responsible for events of hepatic decompensation including variceal bleeding, ascites, and encephalopathy, which contribute substantially to morbidity and mortality in these patients. By lowering elevated portal pressures, emricasan has the potential to decrease the risk of hepatic decompensation in liver cirrhosis patients over the short term, and may improve both liver function and structure over the long term through anti-inflammatory and anti-fibrotic effects.

David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus, said, "We were excited to demonstrate that a drug candidate with the potential to achieve long-term resolution of fibrosis and cirrhosis also has the ability to induce a rapid and clinically meaningful reduction of severe portal hypertension. The reduction of portal pressure over a relatively short time frame in the patients with therapeutically relevant portal hypertension may reflect the initial impact of emricasan on the hyperdynamic circulation that is the predominant contributor to portal hypertension as cirrhosis progresses and/or a direct effect upon intrahepatic vasculature resistance. Future studies will be needed to assess the relative contribution of these mechanisms to the observed clinical effect. Decreasing HVPG has been identified by the FDA (U.S. Food and Drug Administration) as a validated, objective measure that may be acceptable as a surrogate endpoint for clinical trials of patients with liver cirrhosis. These results set the stage for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension."

"These results demonstrate that emricasan can cause a clinically meaningful improvement in portal hypertension in the liver cirrhosis patients who need it most," said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. "Specifically, patients with therapeutically relevant baseline portal hypertension showed meaningful decreases in HVPG. We believe the results from this trial establish the near-term effects of emricasan on portal hypertension. We are evaluating emricasan's potential longer-term effects on liver function and liver structure in our other two ongoing clinical trials: the Phase 2 Liver Cirrhosis (LC) trial and the Phase 2b post-transplant trial."

"Even though the number of patients in this trial was small," added Dr. Hagerty, "Conatus was encouraged by the consistency of responses in patients with portal hypertension and cirrhosis due primarily to NASH or HCV. These results further support our view that apoptosis and inflammation are important common mechanisms for progressive liver disease across multiple etiologies, and that treatment with emricasan is likely to provide both short- and long-term clinical benefits."

Conference Call/Webcast/Presentation

Conatus will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, September 24, to discuss the top-line results and provide a mechanism-focused overview of liver cirrhosis and portal hypertension. To access the conference call, please dial 877-312-5857 (domestic) or 970-315-0455 (international) at least five minutes prior to the start time and refer to conference ID 45793794. An associated presentation and live and archived audio webcast of the call will be available in the Investor Center of the company's website at http://ir.conatuspharma.com/events.cfm.

About Emricasan Clinical Development

To date, emricasan has been studied in over 600 subjects in fifteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing. The company's ongoing Phase 2 LC trial is evaluating emricasan's potential medium-term effect on liver function using two other potential surrogate clinical endpoints – Model for End-Stage Liver Disease (MELD) score and Child-Pugh-Turcotte (CPT) status. The company also is evaluating emricasan's potential longer-term effects on liver structure in its ongoing Phase 2b clinical trial in post-orthotopic liver transplant (POLT) recipients who have reestablished liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection and have successfully achieved a SVR following HCV antiviral therapy (POLT-HCV-SVR). The company currently is developing a strategy for initial registration of emricasan as a potential treatment for patients with liver cirrhosis.

About Conatus Pharmaceuticals

Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease. Emricasan is a first-in-class, orally active pan-caspase inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis. Conatus believes that by reducing the activity of these enzymes, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.

Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward looking statements, including statements regarding: presenting detailed results of the PH trial in a future scientific forum; emricasan's potential to decrease risk of hepatic decompensation; emricasan's potential to improve both liver function and structure through anti-inflammatory and anti-fibrotic effects; emricasan's potential to achieve long-term resolution of fibrosis and cirrhosis; emricasan's potential impact on hyperdynamic circulation and/or intrahepatic vasculature resistance; the acceptability of HVPG as a surrogate endpoint for clinical trials of patients with liver cirrhosis; whether the results from the PH trial establish the near-term effects of emricasan on portal hypertension or allow for future Phase 2b clinical trials in patients with cirrhosis and therapeutically relevant portal hypertension; emricasan's longer-term effects on liver function and liver structure; the importance of apoptosis as a common mechanism for progressive liver disease and that inhibiting apoptosis with emricasan is likely to be of both short- and long-term clinical benefit; the utility of MELD and CPT as potential surrogate clinical endpoints; the potential for emricasan to be a treatment for liver cirrhosis patients; and emricasan's potential to interrupt the disease progression across the spectrum of liver disease. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including: Conatus' ability to initiate and successfully complete current and future clinical trials; Conatus' ability to evaluate emricasan's potential medium-term and longer-term effects on liver function and liver structure in its other two ongoing clinical trials; Conatus' ability to develop a registration strategy and pathway for emricasan; Conatus' dependence on its ability to obtain regulatory approval for, and then successfully commercialize emricasan, which is Conatus' only drug candidate; Conatus' reliance on third parties to conduct its clinical trials, enroll subjects, manufacture its preclinical and clinical drug supplies and manufacture commercial supplies of emricasan, if approved; the potential that earlier clinical trials may not be predictive of future results; potential adverse side effects or other safety risks associated with emricasan that could delay or preclude its approval; results of future clinical trials of emricasan; the potential for competing products to limit the clinical trial enrollment opportunities for emricasan in certain indications; the uncertainty of the FDA's and other regulatory agencies' approval processes and other regulatory requirements; Conatus' ability to fully comply with numerous federal, state and local laws and regulatory requirements applicable to it; Conatus' limited operating history and its ability to operate successfully as a public company; Conatus' ability to obtain additional financing in order to complete the development and commercialization of emricasan; and those risks described in Conatus' prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in Conatus' forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, Conatus does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.MEDIA: David Schull Russo Partners, LLC (858) 717-2310 INVESTORS: Alan Engbring Conatus Pharmaceuticals Inc. (858) 376-2637

Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating Fixed-Dose Sofosbuvir/Velpatasvir (GS-5816) Pan-Genotypic

Gilead's new pan-genotype hep C combo scores stellar results in PhIII
September 21, 2015 | By John Carroll
Gilead has proved once again that it knows how to cure hepatitis C for a heavy concentration of patients, posting some stellar pangenotype data from a slate of four late-stage studies that combined its blockbuster Sovaldi with the experimental NS5A inhibitor velpatasvir. And the Big Biotech says it's ready to step up with new marketing applications with an eye to continuing its domination.

Press Release
Gilead Announces SVR12 Rates from Four Phase 3 Studies Evaluating a Once-Daily, Fixed-Dose Combination of Sofosbuvir (SOF) and Velpatasvir (VEL) (GS-5816) for the Treatment of All Six Hepatitis C Genotypes

If Approved, SOF/VEL Would be the First All-Oral Pan-Genotypic Single Tablet Regimen for Chronic HCV-

- U.S. NDA and European MAA Submissions Planned for Q4 2015 -

FOSTER CITY, Calif.--(BUSINESS WIRE)--Sep. 21, 2015-- Gilead Sciences, Inc.(Nasdaq:GILD) today announced topline results from four international Phase 3 clinical studies (ASTRAL-1, ASTRAL-2, ASTRAL-3 and ASTRAL-4) evaluating a once-daily, fixed-dose combination of the nucleotide analog polymerase inhibitor sofosbuvir (SOF) with velpatasvir (VEL), an investigational pangenotypic NS5Ainhibitor, for the treatment of genotype 1-6 chronic hepatitis C virus (HCV) infection.

In the ASTRAL-1, ASTRAL-2, and ASTRAL-3 studies, 1,035 patients with genotype 1-6 HCV infection received 12 weeks of SOF/VEL. Among these patients, 21 percent had compensated cirrhosis and 28 percent had failed prior treatments. The ASTRAL-4 study randomized 267 patients with decompensated cirrhosis (Child-Pugh class B) to receive 12 weeks of SOF/VEL with or without ribavirin (RBV), or 24 weeks of SOF/VEL. The primary endpoint for all studies was SVR12.

The intent-to-treat SVR12 rates observed in the ASTRAL studies are summarized in the table below. Complete results from all four studies will be presented at future scientific conferences.

Of the 1,035 patients treated with SOF/VEL for 12 weeks in the ASTRAL-1, ASTRAL-2 and ASTRAL-3 studies, 1,015 (98 percent) achieved the primary efficacy endpoint of SVR12. Of the 20 patients who did not achieve SVR12, 13 patients (1.3 percent) experienced virologic failure and seven did not complete an SVR12 visit (e.g., lost to follow-up). Twelve of the 13 virologic failure patients relapsed (two genotype 1 HCV-infected patients and 10 genotype 3 HCV-infected patients). There was one patient with documented reinfection. No patients with genotype 2, 4, 5 or 6 HCV infection had virologic failure.

Patients treated with SOF/VEL for 12 weeks in these three studies had similar adverse events compared with placebo-treated patients in ASTRAL-1. Two patients (0.2 percent) treated with SOF/VEL for 12 weeks, one each in ASTRAL-1 and ASTRAL-2, discontinued treatment due to adverse events. The most common adverse events were headache, fatigue and nausea.

In ASTRAL-4, patients with Child-Pugh class B cirrhosis receiving SOF/VEL+RBV achieved higher SVR12 rates than patients receiving SOF/VEL for 12 or 24 weeks. Among genotype 1 and 3 patients treated with SOF/VEL+RBV for 12 weeks, the SVR12 rates were 96 percent and 85 percent, respectively.

The most common adverse events across all arms of ASTRAL-4 were fatigue, nausea and headache. Anemia, a common side effect associated with RBV, was reported in 31 percent of patients in the SOF/VEL+RBV arm and in 4 percent and 3 percent of patients treated with SOF/VEL for 12 or 24 weeks, respectively. Treatment emergent serious adverse events occurred in 18 percent of patients and nine patients died. The majority of serious adverse events and deaths were associated with advanced liver disease.

“The ASTRAL study results demonstrate that a 12-week course of therapy with the first fixed-dose combination of two pan-genotypic compounds can provide high cure rates for patients with all HCV genotypes,” said Norbert Bischofberger, Ph.D., Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. “We are pleased to have now brought forward our second single tablet regimen for HCV infection that complements Harvoni, our first single tablet regimen approved specifically for patients with genotype 1 infection and which could eliminate the need for HCV genotype testing. We look forward to advancing the regulatory submissions for the SOF/VEL fixed-dose combination.”

The U.S. Food and Drug Administration has assigned the SOF/VEL fixed-dose combination a Breakthrough Therapy designation, which is granted to investigational medicines that may offer major advances in treatment over existing options.

The SOF/VEL fixed-dose combination is an investigational product and its safety and efficacy have not yet been established.

About the ASTRAL Studies

The double-blind, placebo-controlled ASTRAL-1 trial enrolled 740 patients with chronic genotype 1, 2, 4, 5 or 6 HCV infection randomized to SOF/VEL or placebo for 12 weeks.

The open-label ASTRAL-2 study evaluated the use of SOF/VEL or SOF+RBV for 12 weeks in 266 genotype 2 HCV-infected patients.

The open-label ASTRAL-3 study evaluated the use of SOF/VEL for 12 weeks or SOF+RBV for 24 weeks in 552 genotype 3 HCV-infected patients.

The ASTRAL-1 study met its primary endpoint of statistical superiority to the pre-specified SVR12 goal of 85 percent (p<0.001). ASTRAL-2 and ASTRAL-3 also met their respective endpoints. In ASTRAL-2, the SVR12 rate among genotype 2 HCV-infected patients receiving SOF/VEL for 12 weeks was statistically superior to the SVR12 rate for patients receiving SOF+RBV for 12 weeks (p=0.018). In ASTRAL-3, the SVR12 rate among genotype 3 HCV-infected patients receiving SOF/VEL for 12 weeks was statistically superior to that of patients treated with SOF+RBV for 24 weeks (p<0.001).

The open-label ASTRAL-4 study evaluated the use of SOF/VEL with or without RBV for 12 weeks and SOF/VEL for 24 weeks in 267 HCV-infected patients with Child-Pugh class B cirrhosis, regardless of genotype.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may be unable to file for U.S. regulatory approval of the SOF/VEL fixed-dose combination in the currently anticipated timelines. In addition, the FDA and other regulatory agencies may not approve the SOF/VEL fixed-dose combination, and any marketing approvals, if granted, may have significant limitations on its use. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2015, as filed with theU.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full Prescribing Information for Sovaldi and Harvoni are available atwww.gilead.com.

Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc. or its related companies.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

View source version on businesswire.com:
http://www.businesswire.com/news/home/20150921005402/en/

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Investors
Patrick O’Brien, 650-522-1936
or
Media
Cara Miller, 650-522-1616

Hepatitis C Weekend Review

Weekend Recap

Welcome to Weekend Reading, hope you are all enjoying the weekend!

For me Saturday is a great day to catch up on any HCV news or research I missed during the week. If you have the time click on today's topics for general information about hepatitis C, the cost of treatment, other health news, as well as interim study results using all-oral direct-acting antiviral therapy for the treatment of chronic hepatitis C.

Weekend recap provided by; Lucinda Porter, NATAP, Healio, HCV Advocate, Hepatitis Resource Center Blog, World Journal Of Hepatology, and The Body, along with media news and headlines from across the web.

Lucinda Porter 
What We Talk About When We Talk About Hepatitis C
Since 2007, more people have died every year from hepatitis C than from HIV. Fortunately, the latest hepatitis C medications can cure nearly everyone in a relatively quick, easy fashion. 

NATAP

Pharmacokinetics and safety of co-administered paritaprevir plus ritonavir, ombitasvir, and dasabuvir in hepatic impairment 

Paritaprevir, ombitasvir, and dasabuvir are direct-acting antivirals for treatment of chronic hepatitis C virus (HCV) infection. The aim of this study was to characterize the effects of mild, moderate, and severe hepatic impairment on the pharmacokinetics of these drugs.

Sofosbuvir plus Simeprevir Treatment of Recurrent Genotype 1 Hepatitis C after Liver Transplant

Patients with recurrent hepatitis C (HCV) infection post liver-transplant can be difficult to treat safely and effectively. A prior (COSMOS) study in non-transplant HCV patients, using sofosbuvir plus simeprevir, had high efficacy and tolerability in treating HCV genotype 1 patients, even prior non-responders to interferon therapy and those with cirrhosis. Our aim was to evaluate the efficacy of sofosbuvir and simeprevir in genotype 1 HCV post-liver transplant patients.

Harvoni in Advanced Liver Disease 

In this large-scale trial that evaluated the efficacy of all-oral direct-acting antiviral therapy in patients with HCV genotype 1 and decompensated cirrhosis, and post-transplant patients with cirrhosis, 12 or 24 weeks of treatment with ledipasvir-sofosbuvir and ribavirin resulted in high rates of response.

Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection, 2006-2010 

Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population.

Healio

Odalasvir/Sovaldi yields 100% SVR in HCV genotype 1
Achillion announced additional interim results of its phase 2 pilot study of odalasvir in combination with Sovaldi, in which 100% of patients with hepatitis C virus…

September Issue of HCV Next
HCV Next provides an overview of current hepatitis C topics, as well as content on all forms of viral hepatitis, and other liver related disease.
Topic Highlights
Pediatric HCV: Small Patients, Big DecisionsHCV Guidelines: A Living Breathing Document
Caffeine Decreases Risk of Hepatic Fibrosis in Male HCV Patients
Liver Disease Expected to Increase in Switzerland Over Time
HCV may Increase Risk for Coronary Atherosclerosis in MSM
SVR Leads to Survival Benefit Among HCV Patients

HCV Advocate 

September Mid-Month Newsletter

by Alan Franciscus, Editor-in-Chief
This month’s column is about cirrhosis—the causes, how it develops, the tests to identify it, the symptoms of cirrhosis and effect of hepatitis C treatment on cirrhosis and the effect of cirrhosis on treatment.

Newly Diagnosed
Have you recently found out that you have hepatitis C? Being diagnosed with this brings up a lot of feelings and questions about hepatitis C. In this guide you will find information to help you find answers to your questions. This information is basic and assumes that you have very little knowledge about hepatitis C. Hopefully it reassures you. How can information about a disease be reassuring? We believe that once you get the facts, the future will look a little brighter.

Hepatitis Resource Center Blog
Hepatitis C-Salvage Study Grazoprevir and Elbasvir Plus Ribavirin: Final 24-week Follow-up Results
In the C-SALVAGE study, an interferon free combination of grazoprevir (an NS3/4A protease inhibitor) and elbasvir (an NS5A inhibitor) with ribavirin was used to treat patients with chronic HCV genotype 1 infection who had previously failed triple therapy with pegylated interferon and ribavirin plus an earlier-generation protease inhibitor.

Recent Posts
New HCV Peer-Reviewed PDFs For Free!
HCV Drug Costs: A Treatment Access Barrier
Tx Options for HCV GT 1 or 4 Non-responders
Two DAA regimen in cirrhotic HCV GT1b patients

World Journal Of Hepatology
Psychosocial assessment and monitoring in the new era of non-interferon-alpha hepatitis C virus treatments
The recently Food and Drug Administration approved direct-acting antiviral regimens for hepatitis C virus (HCV), ledipasvir/sofosbuvir regimen and the ombitasvir/paritaprevir/ritonavir and dasabuvir regimen, have demonstrated great efficacy, and thus far seem to have short treatment timelines and relatively benign side effect profiles. Depression has not emerged as a side effect of these treatments. With efficacious regimens that include no interferon-alpha and no ribavirin, there may no longer be a need for strong psychosocial assessment and monitoring built into the routine of HCV treatment. Good history-taking, strong pharmaceutical review, and reliable consultative relationships should be adequate for meeting psychosocial needs in HCV treatment

Assessing cardiovascular risk in hepatitis C: An unmet need.
Chronic hepatitis C is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Furthermore, hepatitis C virus seems to be an independent risk factor for cardiovascular diseases due to its association with insulin resistance, diabetes and steatosis. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after achieving the eradication of the virus.

Of Interest
Novel plan to curb drug costs seeks candidates' attention

The outcry gained momentum after the introduction last year of a $1,000-a-pill cure for hepatitis C. The 45-page plan seeks to rein in the overall cost of drugs ...

2015 Kelly Report: Health Disparities In America
History has shown us that the lack of access to healthcare, health insurance, and health providers has contributed to the gaps we observe in national health outcomes.

Big Pharma
Summary - Gilead Sciences at the Morgan Stanley Global Healthcare Conference
Gilead Provides An Update: Review And Analysis Of Wednesday's Q&A
Next-gen hep C combo plans clarified
Apparently we will have to wait until November, the month of the AASLD meeting, for details of the combo of Sovaldi with GS-5816 (sofosbuvir/velpatasvir), rather than this quarter. It appears that GILD is planning to go with this combo as a 12-week treatment for genotypes 2-6 in developed countries, and for all genotypes in regions where genotyping is not readily available..

Will The Next Hepatitis C Drugs Hit It Big?

Over the last two years, hepatitis C has produced the most epic drug launches in history. But as the fanfare dies down, investors face a key question: How much longer can this drug pipeline pop?

Healthy You And The Flu
Hepatitis C or No Hepatitis C, Get a Flu Shot
I have opinions on various issues, but when it comes to scientific proof, I don't waste my time arguing facts. The earth is round, and it travels around the sun. The only place where humans and dinosaurs coexisted was on the Flintstones. I just got my flu shot.

Things to know about the flu shot: Lots of options this year

WASHINGTON (AP) -- Give flu vaccine another chance: This year's version got a recipe change that should make it more effective after last winter's misery from a nasty surprise strain of virus....

Americans urged to get annual influenza vaccine

WASHINGTON, D.C. ― Everyone 6 months of age and older should receive an annual influenza vaccine, health officials advised at a press conference held by the National Foundation for Infectious Diseases.

In addition to flu vaccines, the panel also recommended pneumococcal vaccines for people aged 65 and older and for adults aged 19-64 with certain chronic health conditions, such as diabetes or heart disease.

Acetaminophen

Health Canada proposes new liver damage labeling for acetaminophen
Health Canada announced it is requesting input from clinicians and other healthcare professionals on proposed revisions to the labeling standard for nonprescription acetaminophen products, in an effort to encourage consumers to use them more safely, according to a press release from Health Canada.

Insulin Pens

Shake, shake, shake your NPH insulin pen before injecting
(Reuters Health) - A warning for people who use insulin pens: Not shaking your NPH insulin pen before injecting can result in wide variations in your insulin level and blood sugar control, researchers from Italy report.

Recall
California dairy recalls soft cheeses due to possible Listeria link
- California company Karoun Dairies has recalled a number of soft cheese products due to possible association with Listeria cases over five years in nine states, the U.S. Centers for Disease Control and Prevention said on Friday.

Awareness

Hepatitis C: Testing could save your life

If a simple blood test could improve your long-term health or possibly save your life, would you have it done? The answer for most people is a resounding “Yes.” Testing for hepatitis C which entails a basic blood draw and analysis, can be the difference between serious health complications later in life or a manageable — in some cases curable — condition.

In The News
Homeless Veteran Stand Down an infusion of hope for veterans in ...
Prescott Daily Courier-10 hours ago
Free haircuts, HIV and Hepatitis C screenings, pet care facilities, and three hot meals, were just a sample of what these in-need veterans were able to obtain on ...

Achillion Reports 100% SVR12 From Second Cohort of Patients in the Previously-Completed Six Week Phase 2 Trial Evaluating Odalasvir (ACH-3102) and Sofosbuvir for Genotype 1 HCV ("Proxy Study")

- 100% SVR12 reported for all patients treated for six- (n=18) or eight-weeks (n=12)
- Odalasvir (ACH-3102) is the subject of an exclusive, worldwide development and commercialization license granted to Janssen

FDA Grants Fast Track Designation to Can-Fite's CF102 in the Treatment of Liver Cancer
U.S. Food and Drug Administration (FDA) has granted the Company's drug candidate CF102 Fast Track designation as a second line treatment for hepatocellular carcinoma (HCC), the most common form of liver cancer. CF102 had already received the FDA's Orphan Drug designation.

Clinical Thought - How I Use Resistance Testing to Guide Management of Patients With Chronic Hepatitis C

Recently, I have begun to hear many questions from colleagues and trainees regarding the use of resistance testing in the management of HCV-infected patients. To be honest, my answers to their questions are not always straightforward, as this is a rapidly evolving area of discussion in the field and I am confident that my opinion will evolve along with the data.

Study Shows Increase in Hepatitis C Rate Among Some HIV-Positive Men 
Researchers conducted an analysis of studies that spanned more than two decades and found that outbreaks of sexually transmitted hepatitis C is increasing among men who are HIV positive and have sex with other men

Redoing the Math: New York State Revises Its Estimate of People With HIV

The NYS Plan to End AIDS relies on increasing the number of HIV-positive people in the state who have an undetectable viral load, since being virally suppressed both improves their health and lowers the chance of HIV transmission to their partners.

Mathematical models estimate that to achieve the state's goal of only 750 new HIV infections per year, the percent of people virally suppressed will need to be over 80%. Since only an estimated 42% were virally suppressed in 2013, the state had a long way to go to achieve its goal.

But NYS recently lowered its estimate of the number of people with HIV in the state, which significantly increases the percent who are virally suppressed. Let's examine how that was done.

Feel Good Video

Sophia just wants to dance, but she found that difficult to do when she was diagnosed with scoliosis and was forced to wear a brace for 23 hours a day. Two years ago, a large tumor was found growing on her spinal cord, and she had major surgery at St. Jude Children's Research Hospital in Memphis to remove it. A year later, the tumor returned and Sophia underwent radiation and advanced proton therapy. Her physician at Willis Knighton Proton Therapy Center, Dr. Ben Wilkinson, promised Sophia he would learn the dance to Watch Me (Whip/Nae Nae) once radiation and therapy were complete. Dr. Wilkinson went one step further and surprised the 12-year-old with a flash mob from the staff. Now that's how you celebrate!

Whenever I watch videos like this I cry, do you?
See you all soon.
Tina