Difference In Sustained Virological Response Research Articles

Alcohol Use and Sustained Virologic Response to Hepatitis C Virus Direct-Acting Antiviral Therapy

Some payers and clinicians require alcohol abstinence to receive direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. To evaluate whether alcohol use at DAA treatment initiation is associated with decreased likelihood of sustained virologic response (SVR). This retrospective cohort study used electronic health records from the US Department of Veterans Affairs (VA), the largest integrated national health care system that provides unrestricted access to HCV treatment. Participants included all patients born between 1945 and 1965 who were dispensed DAA therapy between January 1, 2014, and June 30, 2018. Data analysis was completed in November 2020 with updated sensitivity analyses performed in 2023. Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses for alcohol use disorder (AUD): abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD. The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks or longer after completion of DAA therapy. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% CIs of SVR associated with alcohol category. Among 69 229 patients who initiated DAA therapy (mean [SD] age, 62.6 [4.5] years; 67 150 men [97.0%]; 34 655 non-Hispanic White individuals [50.1%]; 28 094 non-Hispanic Black individuals [40.6%]; 58 477 individuals [84.5%] with HCV genotype 1), 65 355 (94.4%) achieved SVR. A total of 32 290 individuals (46.6%) were abstinent without AUD, 9192 (13.3%) were abstinent with AUD, 13 415 (19.4%) had lower-risk consumption, 3117 (4.5%) had moderate-risk consumption, and 11 215 (16.2%) had high-risk consumption or AUD. After adjustment for potential confounding variables, there was no difference in SVR across alcohol use categories, even for patients with high-risk consumption or AUD (OR, 0.95; 95% CI, 0.85-1.07). There was no evidence of interaction by stage of hepatic fibrosis measured by fibrosis-4 score (P for interaction = .30). In this cohort study, alcohol use and AUD were not associated with lower odds of SVR. Restricting access to DAA therapy according to alcohol use creates an unnecessary barrier to patients and challenges HCV elimination goals.

Experience with direct-acting antivirals in genotype 1-5 infected chronic hepatitis C patients in Turkey.

Hepatitis C virus (HCV) can cause chronic liver disease, hepatic cirrhosis, hepatocellular carcinoma, liver transplantation, and death. Early diagnosis and treatment are thus vital. We aimed to investigate the sustained virological response (SVR) rates in chronic hepatitis C patients infected with different genotypes, receiving different direct-acting antiviral treatments (DAAs). Retrospective, observational SETTING: Clinic for infectious diseases and clinical microbiology PATIENTS AND METHODS: Patients diagnosed with chronic hepatitis C who applied to our outpatient clinic between January 2016 and November 2022 and were treated with a DAA were included in the study. Treatment responses were evaluated after each patient was treated with either ledipasvir plus sofosbuvir (LDV/SOF), LDV/SOF + ribavirin (RBV), SOF+RBV, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r±DSV) ±RBV, or glecaprevir plus pibrentasvir (GLE/PIB). Sustained virological response (SVR) rates at 12 weeks (SVR12) post-treatment. 360 patients. Of 360 patients who met the inclusion criteria, 218 (60.6%) were male and 142 (39.4%) were female with no statistically significant differences in SVR between sexes (P=.252). Nearly all had a SVR (n=353, 98.1%). The median (IQR) age of the patients was 56 (30.3) years. There were 42 (11.7%), 199 (55.3%), 4 (1.1%), 106 (29.4%), 8 (2.2%) and 1 (0.3%) patient with genotypes 1a, 1b, 2, 3, 4 and 5, respectively, and SVR12 did not differ significantly between genotypes (P=.066). SVR12 response was higher in 246 (68.3%) non-injecting drug users compared to 114 (31.7%) injecting drug users (P=.005). The SVR12 response was achieved in 100% of patients with genotypes 1a, 2, 4, and 5. SVR12 response could not be obtained in 1 of 199 genotype 1b patients and 6 of 106 genotype 3 patients. The common feature of 6 reinfection patients with genotype 3 was that they were using intravenous drugs. These 6 patients were reinfected due to their continued intravenous drug use. In conclusion, DAAs provide high SVR12 rates in cirrhotic/non-cirrhotic, pegylated interferon-naive/experienced patient groups and in patients infected with all genotypes. DAAs have a high SVR12 rate in patients with chronic hepatitis C. Retrospective, single-center.

S1370 Delayed Clinical Follow Is Not Associated With Lower SVR Rates in an HCV-Infected Cohort in Mumbai, India

Introduction: Hepatitis C Virus (HCV) has a prevalence of 71 million cases worldwide. Regular follow-up can be challenging for patients in low middle income countries (LMIC) due to lack of access to healthcare facilities and transportation difficulties. Our aim was to determine if delayed vs regular follow up for patients being treated for HCV with direct acting antivirals (DAA) resulted in a difference in sustained virologic response (SVR). Methods: We conducted a retrospective cohort study of 149 patients in Mumbai, India who had received treatment for Hepatitis C from 2015 to 2021. All patients had confirmed HCV by PCR and were treated with direct acting antivirals (DAA) approved by the FDA equivalent in India. Patients were asked to present for follow up 12 weeks after end of treatment for SVR12 (sustained virologic response) testing. Results: 149 patients were included. 81 followed up on time (54%) and 68 did not (46%). The mean age at treatment in both groups was similar (51 vs 52, p = 0.29) while male/female distribution showed a significant difference (40% vs 54% male, 60% vs 46% female, p = 0.027). The most common genotype in the cohort was genotype 3 (52% vs 49%) and the second most common was genotype 1 (32% vs 20%). There was not a significant difference in genotypes between both groups (p = 1.0). History of hyperlipidemia (p = 0.12), thyroid disease (p = 0.20), and CKD (p = 0.16) did not show significant difference across both groups. On the other hand, diabetes (p = 0.026) and HTN (p < 0.01) were more prevalent in those who had delayed follow up. There was no significant difference in prior treatment experience between the two groups (p = 0.13). Change in AST and ALT from the initiation of treatment until SVR also did not show significant difference across both groups (p = 0.58, 0.38). Patients with advanced liver disease were more commonly seen in the group which did not have on-time follow up (p < 0.01). SVR was seen more in the group which did not follow up on time (94% vs 79%, p < 0.01). (Table) Conclusion: The likelihood of SVR was not impeded by delayed follow-up compared to regular follow-up in this cohort of infected patients. Further research is needed to determine if this is generalizable across different genotypes and geographic locations. Table 1. - Patients’ baseline clinical characteristics stratified against delayed vs regular follow-up Variable Overall (n=149) Delayed FU (n=68) Regular FU (n=81) P-value Age (mean ± SD) 52 ± 13 53 ± 13 51 ± 13 0.29 Sex (n, %) 0.10 Male 71 (48) 27 (40) 44 (54) Female 78 (52) 41 (60) 37 (46) Genotype (n, %) 1.0 1 46 (31) 20 (20) 26 (32) 2 1 (0.6) 0 (0) 1 (1.2) 3 75 (50) 33 (49) 42 (52) 4 4 (2.7) 2 (2.9) 2 (2.5) 5 1 (0.6) 0 (0) 1 (1.2) Not collected 22 (15) 13 (19) 9 (11) DM (n, %) 0.06 No 120 (81) 50 (74) 69 (85) Yes 29 (19) 18 (26) 12 (15) HTN (n, %) 0.03 No 96 (64) 37 (54) 59 (73) Yes 53 (36) 31 (46) 22 (27) HLD (n, %) 0.18 No 144 (97) 64 (94) 80 (99) Yes 5 (3) 4 (6) 1 (1) Thyroid Disease (n, %) 1.0 No 131 (88) 60 (88) 71 (88) Yes 18 (12) 8 (12) 10 (12) CKD (n, %) 0.38 No 137 (92) 61 (90) 76 (94) Yes 12 (8) 7 (10) 5 (6.2) Treatment Experience (n, %) 0.73 Naive 101 (68) 45 (66) 56 (69) Experienced 48 (32) 23 (34) 25 (31) Liver Status (n, %) 0.03 No Cirrhosis 56 (38) 26 (38) 30 (37) Comp Cirrhosis 68 (46) 25 (37) 43 (53) Decomp Cirrhosis 25 (17) 17 (25) 8 (10) SVR (n, %) < 0.01 No 21 (14) 4 (5.8) 17 (21) Yes 128 (86) 64 (94) 64 (79) Change in AST (mean ± SD) 35 ± 39 37 ± 38 33 ± 41 0.58 Change in ALT (mean ± SD) 42 ± 55 46 ± 64 37 ± 47 0.38

Patient Navigation Increases Linkage to Care and Receipt of Direct-acting Antiviral Therapy in Patients with Hepatitis C

Patient navigation interventions can improve health outcomes in underserved, low-income, and racial and ethnic minority groups, who often experience health disparities. We examined the effectiveness of patient navigation to improve linkage to hepatitis C virus (HCV) treatment receipt in a socioeconomically disadvantaged, racially diverse patient population. We performed a pre-post analysis evaluating the effectiveness of a patient navigation program among baby boomers who tested positive for HCV in a safety-net health system. The usual care group (June 2013 to May 2015) and patient navigation group (January 2016 to December 2017) were balanced using a stabilized inverse probability of treatment weighting approach. We used logistic regression analyses to evaluate associations between patient navigation and linkage to care for HCV treatment evaluation, treatment initiation, and sustained virologic response. Among 1353 patients (62% black, 61% uninsured, 16% homeless), 769 were in the usual care group, and 584 were in the patient navigation group. The patient navigation group had significantly higher odds of linkage to care (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.9-4.8) and treatment initiation (OR, 3.2; 95% CI, 2.3-4.2) within 6 months. The patient navigation group continued to have increased linkage to care (OR, 3.4; 95% CI, 2.7-4.3) and treatment initiation (OR 2.3; 95% CI, 1.7-3.0) at 12 months. However, there was no significant difference in sustained virologic response between the groups (86.9% vs 86.1%; P= .78). Patient navigation was associated with significantly increased linkage to care and treatment initiation among patients with HCV infection. Patient navigation programs can be used to promote HCV elimination among traditionally difficult-to-reach patient populations.

Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension.

IntroductionHigh efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups.MethodsData were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy. Evidence of PHT included at least one of the following at baseline: FibroScan ≥ 20 kPa, platelets < 100 × 109/L, or medical history consistent with PHT. The primary efficacy endpoint was SVR12; adverse events (AEs) consistent with hepatic decompensation were assessed.ResultsPHT was identified in 60.6% (208/343) and 57.1% (224/392) of the 8- and 12-week groups, respectively. For those with PHT, SVR12 was 97.6% (203/208) and 98.7% (221/224) with 8- and 12-week treatment, respectively (intention-to-treat population). For those without PHT, 97.8% (132/135) in the 8-week group and 97.6% (164/168) in the 12-week group achieved SVR12. Eight patients with PHT, and seven without, did not achieve SVR12. Similar rates of AEs were observed in the PHT and non-PHT groups. Three cases of hepatic decompensation in the PHT group, unrelated to G/P according to the investigators, were reported.ConclusionG/P treatment for 8 or 12 weeks was equally efficacious in HCV patients with features of PHT. Safety outcomes were similar between PHT and non-PHT groups, with G/P treatment well tolerated across groups.NCTsNCT03089944, NCT02642432, NCT02738138, NCT02243293, NCT02651194, NCT03235349, NCT02707952, NCT02966795, NCT03069365, NCT03219216.

Phylodynamic Analysis and Implication of HCV Genotype 4 Variability on Antiviral Drug Response and T-Cell Recognition.

Therapies for HCV care could change the prevalence and the geographic distribution of genotypes due to differences in Sustained Virologic Response (SVR). In this scenario, uncommon genotypes/subtypes, such as genotype 4, could spread from high-risk groups, replacing genotypes eradicated by antiviral drugs. Genotype eradication is also strongly influenced by the CD8+ T cell response. In this study, the genetic variability in HCV genotype 4 strains obtained from a cohort of 67 patients naïve to DAA therapy was evaluated. We found that the presence of resistance-associated substitutions (RAS) was able to affect drug responses. Next, using a prediction tool, viral mutations were identified by their ability, or lack thereof, to reduce the binding affinity with HLA, which affects T cell recognition. The Bayesian coalescent analysis suggested two different circulation clusters, one in risk groups (IDUs and MSM) and the other due to migration flows, dated to 1940 and 1915, respectively. Most of the RAS overlapped with HLA and a lack of binding mutations was observed in 96% of strains. This study describes the introduction of HCV genotype 4 in a region of the Mediterranean basin and evaluates how HCV genotype 4’s genetic variability could affect the response of antiviral drugs and CD8+ T cell recognition.

Influence of renal dysfunction on dose reduction and virologic efficacy of regimens combining ribavirin and all-oral direct acting antivirals in patients with chronic hepatitis C virus infection.

Several interferon (IFN)-free, all-oral regimens with direct acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection also include ribavirin (RBV). We investigated the influence of renal dysfunction on virologic efficacy and adverse effects in 189 patients with HCV genotype 2 infection who received combination RBV-DAA regimens. The incidence of RBV-induced anemia, RBV dose reduction, and virologic efficacy were compared according to baseline renal function as defined by the estimated glomerular filtration rate (eGFR). Patients with renal dysfunction (eGFR = 30-59mL/min/1.73m2 ) had higher rate of RBV dose reduction and more marked decreases in hemoglobin levels. These findings were more pronounced in patients with the ITPA CC genotype, who are more sensitive to RBV-induced anemia. Although there were no statistically significant differences in sustained virologic response (SVR) rates according to renal function overall (P = 0.1650), the SVR rate was significantly lower in patients who required RBV dose reduction than in those who did not (P < 0.0001). Baseline renal dysfunction could unfavorably affect the outcomes of RBV-DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN-free DAA regimens.

Efficacy and Tolerability of Ombitasvir/Paritaprevir/Ritonavir in HCV Genotype 1-infected Elderly Japanese Patients

Introduction and aim. We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients.Material and Methods. This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]).Results. No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients.Conclusion. Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.

Efficacy and Tolerability of Ombitasvir/Paritaprevir/Ritonavir in HCV Genotype 1-infected Elderly Japanese Patients

We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients. This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age &gt;65; 94% [47/50]) was lower than that in younger patients (100% [20/20]). No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79–148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients. Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.

Vitamin D deficiency in hepatitis C virus infection: what is old? what is new?

In the past few years, a growing body of clinical evidence has highlighted the risk of vitamin D deficiency in patients with chronic hepatitis C and that vitamin D levels are associated with the course of hepatitis C virus (HCV) infection, adverse effects, and treatment response to peginterferon/ribavirin. Recently, studies have found that vitamin D status is related to drug resistance and increased risk of infection in patients with liver cirrhosis. Vitamin D-related gene polymorphisms have been found to explain the interactions between vitamin D deficiency and HCV infection, offering a new perspective toward understanding the current problems such as the development of insulin resistance and racial differences in sustained virological response. Studies have been conducted to determine whether vitamin D supplementation as an adjuvant yields a better result compared with traditional HCV treatment. Here, we provide a brief review of the past and present knowledge of vitamin D in HCV infection.

Hepatitis C Virus Infection Outcomes Among Immigrants to Canada: A Retrospective Cohort Analysis

Introduction and aimHCV-infected immigrants contribute to the total prevalence in Canada and other developed nations. Little is known about engagement in care, access to service, and treatment outcomes in recipients of Direct Acting Antiviral (DAA) HCV therapies among immigrants living with HCV. Material and methodsHCV patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between 2000-2016 were identified. Immigration history, race, socioeconomic status, HCV work-up, treatment and outcome data were evaluated. HCV fibrosis assessment, treatment and sustained virologic response (SVR) were compared using logistic regression. Results2,335 HCV-infected patients were analyzed with 91% (2114) having data on immigration (23% immigrants). A median 16 years (Quartiles: 5, 29) passed from immigration to referral. Access to diagnostic procedures (Fibroscan/liver biopsy) was greater among immigrants compared to Canadian-born (78% vs. 68%, p = 0.001) and immigrants had an odds ratio of 1.72 (95% CI: 1.18-2.51) of receiving a FibroScan compared to Canadians after adjustment for demographic characteristics, HCV risk factors, and socioeconomic status. No differences in SVR were found between immigrants for IFN recipients. Among DAA recipients, rates of SVR were > 94% among all patients, 93% in Canadian-born and 98% among immigrants (p = 0.14). ConclusionNearly 80% of immigrants in this setting had access to fibrosis assessment which was higher than Canadian-born patients. Under half of both groups had initiated HCV therapy. Delays in accessing HCV care represent a missed opportunity to engage, treat and cure HCV patients. HCV screening and health care engagement at the time of immigration would optimize HCV care and therapeutic outcomes.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×109 /L, transient elastography≥21Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations.

Telemedicine Specialty Support Promotes Hepatitis C Treatment by Primary Care Providers in the Department of Veterans Affairs

BackgroundThe Department of Veterans Affairs is the largest US provider of hepatitis C treatment. Although antiviral regimens are becoming simpler, hepatitis C antivirals are not typically prescribed by primary care providers. The Veterans Affairs Extension for Community Health Outcomes (VA-ECHO) program was launched to promote primary care–based hepatitis C treatment using videoconferencing-based specialist support. We aimed to assess whether primary care provider participation in VA-ECHO was associated with hepatitis C treatment and sustained virologic response. MethodsWe identified 4173 primary care providers (n = 152 sites) responsible for 38,753 patients with chronic hepatitis C infection. A total of 6431 patients had a primary care provider participating in VA-ECHO; 32,322 patients had an unexposed primary care provider. Exposure was modeled as a patient-level time-varying covariate. Patients became exposed after primary care provider participation in ≥1 VA-ECHO session. Multivariable Cox proportional hazards frailty modeling assessed the association between VA-ECHO exposure and hepatitis C treatment. Among treated patients, modified Poisson regression assessed the relationship between exposure and sustained virologic response. ResultsAfter adjustment, exposed patients received significantly higher rates of antiviral treatment compared with unexposed patients (adjusted hazard ratio, 1.20; 95% confidence interval, 1.10-1.32; P <.01). The rate of primary care provider–initiated antiviral medication was 21.4% among treated patients reviewed on VA-ECHO teleconferences compared with 2.5% among unexposed patients (P <.01). No difference in adjusted rates of sustained virologic response was observed for patients with exposed primary care providers (P = .32), with similar crude rates for primary care providers versus specialists. ConclusionsNational implementation of VA-ECHO was positively associated with hepatitis C treatment initiation by primary care providers, without differences in sustained virologic response.

Evaluation of a Hepatitis C Patient Management Program at a University Specialty Pharmacy.

The University of Rochester (UR) Specialty Pharmacy hepatitis C patient management program offers a unique advantage of being integrated within the same health system as the University of Rochester Medical Center (URMC) Gastroenterology and Hepatology division. The primary purpose of this study was to assess treatment success through the incidence of achieving a sustained virological response (SVR) in patients served by the UR Specialty Pharmacy versus other nonintegrated pharmacies. This was a single-center retrospective cohort study in adult patients of URMC Gastroenterology and Hepatology prescribed hepatitis C treatment between January 1, 2014, and July 15, 2015. The incidence of SVR, adherence, delay in therapy initiation, early treatment discontinuation, rate of attainment of viral load measurement post-therapy completion, and predictors associated with treatment outcome were assessed. A total of 414 patients were prescribed hepatitis C virus treatment during the study period; 137 did not initiate therapy. The rate of SVR was 93% among patients at the UR Specialty Pharmacy and 89% at nonintegrated pharmacies ( P = 0.357). Adherence to therapy was 100% and 97% at the UR Specialty Pharmacy and nonintegrated pharmacies, respectively ( P = 0.046). The UR Specialty Pharmacy was associated with a 93% SVR rate and significantly greater adherence compared with nonintegrated pharmacies. Larger studies are needed to determine if a significant difference in SVR exists between integrated and nonintegrated pharmacies. This study provides a framework for other institutions to justify developing integrated hepatitis C specialty pharmacy services and evaluate their success.

Alcohol use and hepatitis C virus treatment outcomes among patients receiving direct antiviral agents

BackgroundIt is unclear whether alcohol use negatively impacts HCV treatment outcomes in the era of direct antiviral agents (DAAs). We aimed to evaluate the associations between current levels of drinking and treatment response among persons treated for HCV with DAAs in the national Veterans Affairs (VA) healthcare system. MethodsWe identified patients who initiated HCV DAAs over 18 months (1/1/14–6/30/15) and had documented alcohol screening with the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) questionnaire within one year prior to initiating therapy. DAAs included: sofosbuvir (SOF), ledipasvir/sofosbuvir (LDV/SOF) or ombitasvir-paritaprevir-ritonavir, and dasabuvir (PrOD). AUDIT-C scores were categorized as 0 (abstinence), 1–3 (low-level drinking) and 4–12 (unhealthy drinking) in men or 0, 1–2 and 3–12 in women. ResultsAmong 17,487 patients who initiated DAAs, 15,151 (87%) completed AUDIT-C screening: 10,387 (68.5%) were categorized as abstinent, 3422 (22.6%) as low-level drinking and 1342 (8.9%) as unhealthy drinking. There were no significant differences in sustained virologic response (SVR) rates between abstinent (SVR 91%; 95% CI: 91–92%), low-level drinking (SVR 93%; 95% CI 92–94%) or unhealthy drinking (SVR 91%; 95% 89–92) categories in univariable analysis or in multivariable logistic regression models. However, after imputing missing SVR data, unhealthy drinkers were less likely to achieve SVR in multivariable analysis (AOR 0.75, 95% CI 0.60-0.92). ConclusionAbsolute SVR rates were uniformly high among all persons regardless of alcohol use, with only minor differences in those who report unhealthy drinking, which supports clinical guidelines that do not recommend excluding persons with alcohol use.

Antiretroviral therapy does not affect response to chronic hepatitis C therapy in HIV-coinfected patients.

Many patients coinfected with the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are using highly active antiretroviral therapy (HAART) and HCV therapy with peginterferon (PEG-IFN) and ribavirina (RBV) because the use of direct-acting antivirals is not a reality in some countries. To know the impact of such medications in the sustained virological response (SVR) during HCV treatment is of great importance. This was a retrospective cohort study of 215 coinfected HIV/HCV patients. The patients were treated with PEG-IFN and RBV between 2007 and 2013 and analyzed by intention to treat. Treatment-experienced patients to HCV and carriers of hepatitis B were excluded. Demographic data (gender, age), mode of infection, HCV genotype, HCV viral load, hepatic fibrosis, HIV status, and type of PEG were evaluated. One hundred eighty-eight (87.4%) patients were using HAART. SVR was achieved in 55 (29.3%) patients using HAART and in 9 (33.3%) patients not using HAART (p = 0.86). There was no difference in SVR between different HAART medications and regimens using two reverse transcriptase inhibitor nucleosides (NRTIs) or the use of protease inhibitors and non-NRTIs (27.1% versus 31.5%; p = 0.61). The predictive factors for obtaining SVR were low HCV viral load, non-1 genotype, and the use of peginterferon-α2a. The use of HAART does not influence the SVR of HCV under PEG-IFN and RBV therapy in HIV/HCV coinfected patients.

Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin

The lower limits of virus detection of hepatitis C virus (HCV) RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR)] in predicting sustained virological response (SVR) in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN) and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90) and detectable but not quantifiable (< 12 IU/mL, n = 27). All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA) HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p < 0.001). We determined 4th week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002) and a good predictor of SVR [area under the curve (AUC) = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4th week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks) with PEG-IFN and ribavirin.

Comparison of Daclatasvir and Asunaprevir for Chronic HCV 1b Infection with Telaprevir and Simeprevir plus Peginterferon and Ribavirin, with a Focus on the Prevention of Occurrence and Recurrence of Hepatocellular Carcinoma

Objectives: The efficacy of the all-oral administration of daclatasvir and asunaprevir for 24 weeks was compared with that of telaprevir for 12 weeks plus pegylated interferon and ribavirin (PEG-IFN/RBV) for 24 weeks, and that of simeprevir for 12 weeks plus PEG-IFN/RBV for 24 weeks, with a focus on the prevention of occurrence and recurrence of hepatocellular carcinoma (HCC). The levels of alanine aminotransferase (ALT) and α-fetoprotein (AFP) as suppressive markers of HCC were also measured. Methods: Patients received daclatasvir and asunaprevir (n = 17), simeprevir plus PEG-IFN/RBV (n = 15) and telaprevir plus PEG-IFN/RBV (n = 25). Sustained virological response (SVR) and the mean change in the level of serum ALT, AFP and platelet (PLT) count were compared among the three groups. Results: No difference in SVR was observed in patients given daclatasvir with asunaprevir (SVR4), telaprevir plus PEG-IFN/RBV or simeprevir plus PEG-IFN/RBV (SVR24). Also, no significant difference was observed in the mean change of serum ALT, AFP or PLT count among the three groups. Conclusion: The preventive effect of the IFN-free, all-oral regimen of daclatasvir and asunaprevir was observed with a focus on the occurrence and recurrence of HCC, as was IFN-based treatment with telaprevir or simeprevir plus PEG-IFN/RBV.

Effect of Gender on the Response to Hepatitis C Treatment in an Inner-City Population

IntroductionHepatitis C virus (HCV) is the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplantation in the United States. Response to treatment has improved with the addition of direct acting protease inhibitors. However, there are limited real-world data on the role of gender in achieving a sustained virologic response (SVR). MethodsWe conducted a cross-sectional study in 70 patients treated for HCV, genotype 1 infection with pegylated alpha interferon, ribavirin, and either telaprevir or boceprevir at our inner-city liver clinic. ResultsThe SVR was significantly lower in women than in men (24% vs. 59%; p < .01). Statistical significance persisted after adjusting for age, race, genotype, prior treatment status, duration of therapy, and stage of fibrosis. The adjusted odds ratio for achieving SVR was significantly lower in women than in men (odds ratio [OR], 0.13; 95% CI, 0.03–0.58; p = .01). Relapse after completing treatment was more likely to occur in women (p = .02). Thirty-four patients (48%) did not complete therapy. Discontinuation because of loss to follow-up was more likely in women, whereas discontinuation owing to therapy limiting adverse drug events were more common in men. Discontinuation rates owing to failure of therapy were similar in men and women. ConclusionsThere was a significant difference in SVR between men and women. Both biological and nonbiological factors, the latter including access to care, adherence to therapy, and attitudes of and toward health care providers all could play a role in contributing to the observed disparity between sexes in treatment response.

Impact of Provider Type on Hepatitis C Outcomes With Boceprevir-based and Telaprevir-based Regimens

To examine the effect of provider type on outcomes and safety in a large hepatitis C virus (HCV)-infected cohort treated in routine medical practice. Nonphysician providers (NPP) are uniquely positioned to expand health care infrastructure to meet HCV treatment demands. Retrospective, observational cohort analysis of 820 HCV genotype 1-infected veterans initiated on peginterferon/ribavirin and boceprevir or telaprevir in routine medical practice at 94 VA facilities before January 1, 2012 and followed through July 30, 2013. Provider type was determined from prescription records and included physicians (MD) or NPPs (ie, nurse practitioners, physician assistants, and pharmacists). Inverse probability-of-treatment weighting and unweighted logistic regression analysis was used for comparison of sustained virologic response (SVR), treatment discontinuation rates, and adverse hematologic events. There was no significant difference in SVR by provider type overall (NPPs 52% vs. MDs 49%, P=0.33) and within patient subgroups, or in treatment discontinuation rates. In multivariate analyses, provider type was not associated with any significant difference in the odds of achieving SVR (NPP vs. MD; odds ratio 1.17; 95% confidence interval, 0.84-1.63; P=0.37 inverse probability of treatment weighting; odds ration 1.16, 95% confidence interval, 0.84-1.59, P=0.38 unweighted). Hematologic adverse event rates were similar: anemia: 57% NPP, 62% MD; thrombocytopenia: 43% NPP, 40% MD; neutropenia: 40% NPP, 39% MD. Treatment prescribed by NPPs was as likely to result in SVR as treatment prescribed by MDs, even after accounting for patient differences. Engaging more NPPs as HCV treatment providers may allow wider access to HCV treatment.