Estimating the net value of treating hepatitis C virus using sofosbuvir-velpatasvir in India.

Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) have been groundbreaking for their high efficacy across disease genotypes and lack of severe side effects. This study uses a cost-of-illness (COI) approach to estimate the net value conferred by this class of drugs using the cost and efficacy of one of these novel drug combinations, sofosbuvir and velpatasvir (SOF/VEL), recently licensed for generic manufacture in India. This study considers COI of lifetime earnings lost by patients and potential secondarily infected individuals due to disability and premature death from HCV infection. Expected net benefits of treatment are substantial for non-cirrhotic (NC) and compensated cirrhotic (CC) patients (ranging from 5,98,003 INR for NC women to 1,05,25,504 INR for CC men). Increased earnings are not sufficient to fully offset cost of treatment for decompensated cirrhotic individuals but treatment may still be justified on the basis of the intrinsic value of health improvements and other treatment benefits.

Frailty Status Predicts New Long-term Care Insurance Certification in Hepatitis C Patients Receiving Antiviral Therapy.

BACKGROUND/AIM: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy. PATIENTS AND METHODS: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification. RESULTS: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification. CONCLUSION: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy.

Cost-effectiveness of a "treat-all" strategy using Direct-Acting Antivirals (DAAs) for Japanese patients with chronic hepatitis C genotype 1 at different fibrosis stages.

AIM: To evaluate the cost-effectiveness of therapeutic strategies initiated at different stages of liver fibrosis using three direct-acting antivirals (DAAs), sofosbuvir-ledipasvir (SL), glecaprevir-pibrentasvir (GP), and elbasvir plus grazoprevir (E/G), for Japanese patients with chronic hepatitis C (CHC) genotype 1. METHODS: We created an analytical decision model reflecting the progression of liver fibrosis stages to evaluate the cost-effectiveness of alternative therapeutic strategies applied at different fibrosis stages. We compared six treatment strategies: treating all patients regardless of fibrosis stage (TA), treating individual patients with one of four treatments starting at four respective stages of liver fibrosis progression (F1S: withholding treatment at stage F0 and starting treatment from stage F1 or higher, and three successive options, F2S, F3S, and F4S), and administering no antiviral treatment (NoRx). We adopted a lifetime horizon and Japanese health insurance payers' perspective. RESULTS: The base case analysis showed that the incremental quality-adjusted life years (QALY) gain of TA by SL, GP, and E/G compared with the strategies of starting treatments for patients with the advanced fibrosis stage, F2S, varied from 0.32 to 0.33, and the incremental cost-effectiveness ratios (ICERs) were US$24,320, US$18,160 and US$17,410 per QALY, respectively. On the cost-effectiveness acceptability curve, TA was most likely to be cost-effective, with the three DAAs at the willingness to pay thresholds of US$50,000. CONCLUSIONS: Our results suggested that administration of DAA treatment for all Japanese patients with genotype 1 CHC regardless of their liver fibrosis stage would be cost-effective under ordinary conditions.

Decentralised hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system.

BACKGROUND: Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. METHODS: The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. FINDINGS: Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31-55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. INTERPRETATION: This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection. FUNDING: Médecins Sans Frontières.

Metformin monotherapy for adults with type 2 diabetes mellitus.

BACKGROUND: Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM. Despite this, the effects of metformin on patient-important outcomes are still not clarified. OBJECTIVES: To assess the effects of metformin monotherapy in adults with T2DM. SEARCH METHODS: We based our search on a systematic report from the Agency for Healthcare Research and Quality, and topped-up the search in CENTRAL, MEDLINE, Embase, WHO ICTRP, and ClinicalTrials.gov. Additionally, we searched the reference lists of included trials and systematic reviews, as well as health technology assessment reports and medical agencies. The date of the last search for all databases was 2 December 2019, except Embase (searched up 28 April 2017). SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least one year's duration comparing metformin monotherapy with no intervention, behaviour changing interventions or other glucose-lowering drugs in adults with T2DM. DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles/records, assessed risk of bias, and extracted outcome data independently. We resolved discrepancies by involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall certainty of the evidence by using the GRADE instrument. MAIN RESULTS: We included 18 RCTs with multiple study arms (N = 10,680). The percentage of participants finishing the trials was approximately 58% in all groups. Treatment duration ranged from one to 10.7 years. We judged no trials to be at low risk of bias on all 'Risk of bias' domains. The main outcomes of interest were all-cause mortality, serious adverse events (SAEs), health-related quality of life (HRQoL), cardiovascular mortality (CVM), non-fatal myocardial infarction (NFMI), non-fatal stroke (NFS), and end-stage renal disease (ESRD). Two trials compared metformin (N = 370) with insulin (N = 454). Neither trial reported on all-cause mortality, SAE, CVM, NFMI, NFS or ESRD. One trial provided information on HRQoL but did not show a substantial difference between the interventions. Seven trials compared metformin with sulphonylureas. Four trials reported on all-cause mortality: in three trials no participant died, and in the remaining trial 31/1454 participants (2.1%) in the metformin group died compared with 31/1441 participants (2.2%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on SAE: in two trials no SAE occurred (186 participants); in the other trial 331/1454 participants (22.8%) in the metformin group experienced a SAE compared with 308/1441 participants (21.4%) in the sulphonylurea group (very low-certainty evidence). Two trials reported on CVM: in one trial no CVM was observed and in the other trial 4/1441 participants (0.3%) in the metformin group died of cardiovascular reasons compared with 8/1447 participants (0.6%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on NFMI: in two trials no NFMI occurred, and in the other trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 15/1441 participants (1.0%) in the sulphonylurea group (very low-certainty evidence). One trial reported no NFS occurred (very low-certainty evidence). No trial reported on HRQoL or ESRD. Seven trials compared metformin with thiazolidinediones (very low-certainty evidence for all outcomes). Five trials reported on all-cause mortality: in two trials no participant died; the overall RR was 0.88, 95% CI 0.55 to 1.39; P = 0.57; 5 trials; 4402 participants). Four trials reported on SAE, the RR was 0,95, 95% CI 0.84 to 1.09; P = 0.49; 3208 participants. Four trials reported on CVM, the RR was 0.71, 95% CI 0.21 to 2.39; P = 0.58; 3211 participants. Three trial reported on NFMI: in two trials no NFMI occurred and in one trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 25/1456 participants (1.7%) in the thiazolidinedione group. One trial reported no NFS occurred. No trial reported on HRQoL or ESRD. Three trials compared metformin with dipeptidyl peptidase-4 inhibitors (one trial each with saxagliptin, sitagliptin, vildagliptin with altogether 1977 participants). There was no substantial difference between the interventions for all-cause mortality, SAE, CVM, NFMI and NFS (very low-certainty evidence for all outcomes). One trial compared metformin with a glucagon-like peptide-1 analogue (very low-certainty evidence for all reported outcomes). There was no substantial difference between the interventions for all-cause mortality, CVM, NFMI and NFS. One or more SAEs were reported in 16/268 (6.0%) of the participants allocated to metformin compared with 35/539 (6.5%) of the participants allocated to a glucagon-like peptide-1 analogue. HRQoL or ESRD were not reported. One trial compared metformin with meglitinide and two trials compared metformin with no intervention. No deaths or SAEs occurred (very low-certainty evidence) no other patient-important outcomes were reported. No trial compared metformin with placebo or a behaviour changing interventions. Four ongoing trials with 5824 participants are likely to report one or more of our outcomes of interest and are estimated to be completed between 2018 and 2024. Furthermore, 24 trials with 2369 participants are awaiting assessment. AUTHORS' CONCLUSIONS: There is no clear evidence whether metformin monotherapy compared with no intervention, behaviour changing interventions or other glucose-lowering drugs influences patient-important outcomes.

A financial incentive program to improve appointment attendance at a safety-net hospital-based primary care hepatitis C treatment program.

INTRODUCTION: Hepatitis C (HCV) infection is a significant health threat, with increasing incidence rates in the setting of the opioid crisis. Many patients miss appointments and cannot initiate treatment. We implemented financial incentives to improve appointment attendance in a primary care-based HCV treatment setting. METHODS: We conducted a systems-level financial incentives intervention at the Adult Primary Care HCV Treatment Program at Boston Medical Center which provides care to many patients with substance use disorders. From April 1 to June 30, 2017, we provided a $15 gift card to patients who attended appointments with an HCV treatment provider. We evaluated the effectiveness of the incentives by 1) conducting a monthly interrupted time series analysis to assess trends in attendance January 2016-September 2017; and 2) comparing the proportion of attended appointments during the intervention to a historical comparison group in the previous year, April 1 to June 30, 2016. RESULTS: 327 visits were scheduled over the study period; 198 during the intervention and 129 during the control period. Of patient visits in the intervention group, 72.7% were attended relative to 61.2% of comparison group visits (p = 0.03). Appointments in the intervention group were more likely to be attended (adjusted odds ratio 1.94, 95% confidence interval 1.16-3.24). Interrupted time series analysis showed that the intervention was associated with an average increase of 15.4 attended visits per 100 appointments scheduled, compared to the period prior to the intervention (p = 0.01). CONCLUSIONS: Implementation of a financial incentive program was associated with improved appointment attendance at a safety-net hospital-based primary care HCV treatment program. A randomized trial to establish efficacy and broader implementation potential is warranted.

Cost-Effectiveness Analysis of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin Regimen for Patients Infected With Chronic Hepatitis C Virus Genotype 1 in Malaysia.

OBJECTIVES: The combination of pegylated-interferon and ribavirin (PegIFN+RBV) is currently the gold standard in treating chronic hepatitis C virus (HCV) patients in Malaysia and is reimbursed by the Malaysian authorities. This analysis evaluated the cost-effectiveness (CE) of the ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin (OBT/PTV/r+DSB±RBV) regimen as compared with the PegIFN+RBV or no treatment in chronic HCV Genotype 1 (GT1) treatment-naïve and treatment-experienced cirrhotic and noncirrhotic patients in Malaysia. METHODS: A Markov model based on previously published CE models of HCV was adapted for the Malaysian public healthcare payer perspective, based on good modeling practices. Treatment attributes included efficacy, regimen duration, and EQ-5D treatment-related health utility. Transitional probabilities and health state health utilities were derived from previous studies. Costs were derived from Malaysian data sources. Costs and outcomes were discounted at 3.0% per year. Deterministic and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainties around key variables. RESULTS: Based on the analysis, patients treated with the OBT/PTV/r+DSB±RBV showed less frequent progression to compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths when compared with standard care (ie, PegIFN+RBV or no treatment). At a price of MYR 1846/day, the OBT/PTV/r+DSB±RBV regimen is cost-effective over PegIFN+RBV and yields better outcomes in terms of life-years (LYs) gained and quality-adjusted life-years (QALYs) at a higher cost, which is still well below the implied willingness to pay threshold of MYR 384 503/QALY. CONCLUSION: The OBT/PTV/r+DSB±RBV regimen is cost-effective for treatment naïve, treatment experienced, cirrhotic, and noncirrhotic GT1 chronic HCV patients in Malaysia.

Real-world cost-effectiveness of pan-genotypic Sofosbuvir-Velpatasvir combination versus genotype dependent directly acting anti-viral drugs for treatment of hepatitis C patients in the universal coverage scheme of Punjab state in India.

BACKGROUND: We undertook this study to assess the incremental cost per quality adjusted life year (QALY) gained with the use of pan-genotypic sofosbuvir (SOF) + velpatasvir (VEL) for HCV patients, as compared to the current treatment regimen under the universal free treatment scheme in Punjab state. METHODOLOGY: A Markov model depicting natural history of HCV was developed to simulate the progression of disease. Three scenarios were compared: I (Current Regimen)-use of SOF + daclatasvir (DCV) for non-cirrhotic patients and ledipasvir (LDV) or DCV with SOF ± ribavirin (RBV) according to the genotype for cirrhotic patients; II-use of SOF + DCV for non-cirrhotic patients and use of SOF+VEL for compensated cirrhotic patients (with RBV in decompensated cirrhosis patients) and III-use of SOF+VEL for both non-cirrhotic and compensated cirrhotic patients (with RBV in decompensated cirrhosis patients). The lifetime costs, life-years and QALYs were assessed for each scenario, using a societal perspective. All the future costs and health outcomes were discounted at an annual rate of 3%. Finally, the incremental cost per QALY gained was computed for each of scenario II and III, as compared to scenario I and for scenario III as compared to II. In addition, we evaluated the lifetime costs and QALYs among HCV patients for each of scenario I, II and III against the counterfactual of 'no universal free treatment scheme' scenario which involves patients purchasing care in routine setting of from public and private sector. RESULTS: Each of the scenarios I, II and III dominate over the no universal free treatment scheme scenario, i.e. have greater QALYs and lesser costs. The use of SOF+VEL only for cirrhotic patients (scenario II) increases QALYs by 0.28 (0.03 to 0.71) per person, and decreases the cost by ₹ 5,946 (₹ 1,198 to ₹ 14,174) per patient, when compared to scenario I. Compared to scenario I, scenario III leads to an increase in QALYs by 0.44 (0.14 to 1.01) per person, and is cost-neutral. While the mean cost difference between scenario III and I is-₹ 2,676 per patient, it ranges from a cost saving of ₹ 14,835 to incurring an extra cost of ₹ 3,456 per patient. For scenario III as compared II, QALYs increase by 0.16 (0.03 to 0.36) per person as well as costs by ₹ 3,086 per patient which ranges from a cost saving of ₹ 1,264 to incurring an extra cost of ₹ 6,344. Shift to scenario II and III increases the program budget by 5.5% and 60% respectively. CONCLUSION: Overall, the use of SOF+VEL is highly recommended for the treatment of HCV infection. In comparison to the current practice (scenario I), scenario II is a dominant option. Scenario III is cost-effective as compared to scenario II at a threshold of one-time GDP per capita. If budget is an important constraint, velpatasvir should be given to HCV infected cirrhotic patients. However, if no budget constraint, universal use of velpatasvir for HCV treatment is recommended.

Paritaprevir, ritonavir, ombitasvir, and dasabuvir treatment in renal transplant patients with hepatitis C virus infection.

BACKGROUND/AIMS: The Social Security System of our country reimburses only paritaprevir, ritonavir, ombitasvir, and dasabuvir (PrOD) regime in treatment-naive patients with hepatitis C regardless of kidney disease. Most of our renal transplant (RT) recipients were treated with PrOD. The aim of the present study was to investigate the efficacy and safety of PrOD in RT patients with hepatitis C virus (HCV) infection in a single center real-life experience. MATERIALS AND METHODS: RT recipients with a post-transplant follow-up of at least 1 year were included in the study. The patients were treated and monitored according to the guidelines. Blood levels of immunosuppressive patients were closely followed up and adjusted. RESULTS: A total of 21 (12 male and nine female) patients were assessed. The age of the patients was 50.8±8.5 years. Ten patients were infected with G1a, 10 patients with G1b, and one patient with G4 HCV. Two patients had compensated cirrhosis. Eighteen patients were treatment-naive, and three were peginterferon+ribavirin-experienced. Sustained virologic response (SVR12) was achieved in all patients. None of the patients discontinued the treatment. Cyclosporine (Csa) and tacrolimus (Tac) doses were reduced to once a day to once a week to maintain the blood level within normal range. The most common adverse effect was anemia in patients receiving ribavirin. Renal functions did not change during the treatment period. CONCLUSION: In this real-life experience, all of the 21 PrOD-treated RT recipients reached SVR12. Tac or Csa serum levels were maintained within the normal range with close monitoring. PrOD regime can be successfully and safely used in RT recipients with HCV infection with close follow-up.

A Cost-Effectiveness Analysis of Shortened Direct-Acting Antiviral Treatment in Genotype 1 Noncirrhotic Treatment-Naive Patients With Chronic Hepatitis C Virus.

BACKGROUND: Direct-acting antivirals are successful in curing hepatitis C virus infection in more than 95% of patients treated for 12 weeks, but they are expensive. Shortened treatment durations, which may have lower cure rates, have been proposed to reduce costs. OBJECTIVES: To evaluate the lifetime cost-effectiveness of different shortened treatment durations for genotype 1 noncirrhotic treatment-naive patients. METHODS: Assuming a UK National Health Service perspective, we used a probabilistic decision tree and Markov model to compare 3 unstratified shortened treatment durations (8, 6, and 4 weeks) against a standard 12-week treatment duration. Patients failing shortened first-line treatment were re-treated with a 12-week treatment regimen. Parameter inputs were taken from published studies. RESULTS: The 8-week treatment duration had an expected incremental net monetary benefit of £7737 (95% confidence interval £3242-£11 819) versus the standard 12-week treatment, per 1000 patients. The 6-week treatment had a positive incremental net monetary benefit, although some uncertainty was observed. The probability that the 8- and 6-week treatments were the most cost-effective was 56% and 25%, respectively, whereas that for the 4-week treatment was 17%. Results were generally robust to sensitivity analyses, including a threshold analysis that showed that the 8-week treatment was the most cost-effective at all drug prices lower than £40 000 per 12-week course. CONCLUSIONS: Shortening treatments licensed for 12 weeks to 8 weeks is cost-effective in genotype 1 noncirrhotic treatment-naive patients. There was considerable uncertainty in the estimates for 6- and 4-week treatments, with some indication that the 6-week treatment may be cost-effective.

Cost-Effectiveness Analysis of Early Treatment of Chronic HCV with Sofosbuvir/Velpatasvir in Italy.

BACKGROUND: Chronic Hepatitis C virus (cHCV) is a major health issue worldwide. New effective direct-acting anti-viral (DAA) drugs such as the combination sofosbuvir/velpatasvir, represent an important turning point, given the high sustained virologic response (SVR) rates associated with their use. OBJECTIVES: To estimate the cost and effects of two different treatment strategies based on sofosbuvir/velpatasvir. Strategy 1: treating all patients, including those in the early stages of fibrosis; Strategy 2: reserving treatments for patients at more advanced stages of disease (≥ F3). The analysis compares the incremental cost-effectiveness ratio (ICER) of Strategy 1 versus Strategy 2 in a cohort of HCV-infected patients and a cohort of hepatitis C virus (HCV)-human immunodeficiency virus (HIV) patients. METHODS: A Markov model simulating the natural history of the disease was built considering a 60-year time horizon and two cohorts of 1000 patients aged ≥ 35 years. Disease morbidity was classified according to the METAVIR classification. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses (PSA). RESULTS: In both cohorts, Strategy 1 results in higher resource consumption and a greater number of quality-adjusted life-years (QALYs) compared with Strategy 2. The ICERs for the cohort of HCV patients and the cohort of co-infected HCV/HIV patients ranged between €15,555-74,804/QALY and €10,708-55,138/QALY, respectively, depending on the assumed cost of the treatment. In the PSA, the ICER distribution remained below the threshold of €30,000/QALY in 96 and 97% of the scenarios in the cohorts of HCV and HCV/HIV patients, respectively. CONCLUSIONS: Extending the treatment of HCV to patients at an early stage of HCV infection is estimated to be cost effective from the perspective of the Italian Healthcare System.

Cost-effectiveness of generic pan-genotypic sofosbuvir/velpatasvir versus genotype-dependent direct-acting antivirals for hepatitis C treatment.

BACKGROUND AND AIM: Treatment of hepatitis C virus (HCV) infection with low-cost generic direct-acting antivirals (DAAs) available in India and other developing countries needs determination of HCV genotype ("genotype-dependent" regimens). Generic velpatasvir, a DAA that obviates the need for genotype determination ("pan-genotypic" regimen), recently became available but is costlier. The aim of this study was to evaluate the cost-effectiveness of genotype-dependent versus pan-genotypic DAA treatments in India. METHODS: A previously validated microsimulation model, adapted to Indian population, was used to compare the costs and long-term outcomes of three scenarios: no treatment, treatment with genotype-dependent regimens, and treatment with pan-genotypic regimen. Input parameters were derived from literature. Using a payer's perspective and lifetime time horizon, quality-adjusted life-years (QALYs), total costs, and incremental cost-effectiveness ratio were calculated. Both deterministic and probabilistic sensitivity analyses were also conducted. RESULTS: At the current price ($US223 for 4 weeks), pan-genotypic regimen was cost-saving compared with no treatment. Compared with genotype-dependent regimens, it increased QALYs by 0.92 and increased costs by $US107 but was deemed cost-effective with an incremental cost-effectiveness ratio of $US242 per QALY gained. Probabilistic sensitivity analysis also supported the cost-effectiveness of pan-genotypic regimen. At the reduced price of $US188 for 4 weeks, the pan-genotypic regimen will become cost-neutral to genotype-dependent regimens (current price: $US100 for 4 weeks). CONCLUSIONS: At current prices, velpatasvir-based pan-genotypic regimen is cost-effective for HCV treatment in India where generic drugs are available. A reduction in the prices of pan-genotypic regimen has the potential to make its use cost-saving while simplifying treatment in community-level programs aimed at HCV elimination.

Direct acting antivirals for the treatment of hepatitis C in ethnic minority populations.

INTRODUCTION: Direct acting antivirals (DAA's) have revolutionized the treatment of hepatitis C (HCV). However, questions persist concerning their efficacy in minority populations. AREAS COVERED: In this review, the authors review outcomes for treatment of HCV by race and ethnicity among the clinical trials that have led to the current recommended treatments for HCV. The authors highlight the efficacy and safety differences by race and ethnicity. They also highlight deficiencies within the literature including small populations of racial/ethnic minorities within HCV clinical trials. DAA's can achieve cure rates for HCV over 95% with the use of once daily medications that have minimal side effects and few significant drug-drug interactions. Regimens with high pan-genotypic efficacy have further simplified treatment paradigms. The purpose of this review is to describe the data on DAA's in treating HCV in racial/ethnic populations. EXPERT OPINION: While the overall data in racial/ethnic minority populations is sparse, DAA's appear to have high efficacy in curing HCV in diverse racial/ethnic populations. Although achieving high sustained virologic response (SVR) rates, there are also data that suggests that some disparities in SVR persist, especially when considering shorter regimens for HCV treatment in racial/ethnic populations.

Safety assessment in Child A cirrhotic patients treated with Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with Ribavirin.

BACKGROUND: In our country, the national program for hepatitis C virus treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir was approved for patients with stage four of liver fibrosis and stage three associated with specific comorbidities. Our aim was to analyze the characteristics associated with the presence of adverse events in patients receiving this antiviral regimen, with ribavirin in cirrhotic patients. METHODS: We prospectively studied a cohort of adults with hepatitis C virus infection with Child A cirrhosis, treated for 12 weeks with ombitasvir/paritaprevir/ritonavir/dasabuvir and ribavirin, which have been followed in an infectious diseases tertiary-care hospital. RESULTS: We included 137 adult patients diagnosed with compensated cirrhosis, hepatitis C virus genotype 1b infected, 82 (60%) previously treated. We recorded 201 adverse events in 98 (71.5%) patients, with a median number of events per patient of one. The intensity of adverse events was classified as mild, moderate and severe in 50%, 36% and 14% of cases, respectively. Forty-five (22%) episodes required medical intervention. The most frequently reported adverse events were pruritus 34(35%), asthenia 22(22%) and insomnia 15(15%). The presence of severe adverse events was associated with the presence of comorbidities (p = 0.01, OR : 9.5, 95% CI : 1.2-74.3) and with the presence of associated medication (p = 0.02, OR : 3.9, 95% CI : 1.08-14.2). At the end of current treatment, 136 (99.2%) patients had undetectable viral load. CONCLUSION: We found a high number of adverse events, but most of them were mild or moderate and only one quarter of them required medical intervention. Only severe adverse events were associated with comorbidities and associated medication.

Future Considerations for the Evaluation of Hepatitis C Virus Treatments in Pan-Genotypic Therapy for Noncirrhotic Treatment-Naive Patients.

Given the recent approval of the first pan-genotypic chronic hepatitis C virus (HCV) therapy, managed care, health systems, and clinicians will need to evaluate current practices related to essential laboratory assessments used to select therapy. Historically, clinicians and payers required a battery of tests to determine HCV genotype, viral load, degree of fibrosis, and organ function. In light of current and forthcoming approvals of pan-genotypic therapy, clinicians and payers can expect a more competitive marketplace and a downward curve in the price of therapy. Ultimately, this development will lead to the cost of screenings and assessments having an increased role in selecting an optimal HCV therapy. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. All authors contributed to study concept and design. Calabrese took the lead in data collection, along with Shaya. Data interpretation was performed by Calabrese and Hynicka, along with Rodriguez de Bittner and Shaya. The manuscript was written and revised by Calabrese and Hynicka, along with Rodriguez de Bittner and Shaya.

The Role of e-Health in Optimizing Task-Shifting in the Delivery of Antiviral Therapy for Chronic Hepatitis C.

PURPOSE: Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model. METHODS: In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics. RESULTS: From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic. CONCLUSIONS: We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

HCV management in resource-constrained countries.

With the arrival of all-oral directly acting antiviral (DAA) therapy with high cure rates, the promise of hepatitis C virus (HCV) eradication is within closer reach. The availability of generic DAAs has improved access to countries with constrained resources. However, therapy is only one component of the HCV care continuum, which is the framework for HCV management from identifying patients to cure. The large number of undiagnosed HCV cases is the biggest concern, and strategies to address this are needed, as risk factor screening is suboptimal, detecting <20% of known cases. Improvements in HCV confirmation through either reflex HCV RNA screening or ideally a sensitive point of care test are needed. HCV notification (e.g., Australia) may improve diagnosis (proportion of HCV diagnosed is 75%) and may lead to benefits by increasing linkage to care, therapy and cure. Evaluations for cirrhosis using non-invasive markers are best done with a biological panel, but they are only moderately accurate. In resource-constrained settings, only generic HCV medications are available, and a combination of sofosbuvir, ribavirin, ledipasvir or daclatasvir provides sufficient efficacy for all genotypes, but this is likely to be replaced with pangenetypic regimens such as sofosbuvir/velpatasvir and glecaprevir/pibrentaasvir. In conclusion, HCV management in resource-constrained settings is challenging on multiple fronts because of the lack of infrastructure, facilities, trained manpower and equipment. However, it is still possible to make a significant impact towards HCV eradication through a concerted effort by individuals and national organisations with domain expertise in this area.