Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine.

Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis worldwide and kills more Americans than 59 other infections, including HIV and tuberculosis, combined. While direct-acting antiviral (DAA) treatments are effective, limited uptake of therapy, particularly in high-risk groups, remains a substantial barrier to eliminating HCV. We developed a long-acting DAA system (LA-DAAS) capable of prolonged dosing and explored its cost-effectiveness. We designed a retrievable coil-shaped LA-DAAS compatible with nasogastric tube administration and the capacity to encapsulate and release gram levels of drugs while resident in the stomach. We formulated DAAs in drug-polymer pills and studied the release kinetics for 1 mo in vitro and in vivo in a swine model. The LA-DAAS was equipped with ethanol and temperature sensors linked via Bluetooth to a phone application to provide patient engagement. We then performed a cost-effectiveness analysis comparing LA-DAAS to DAA alone in various patient groups, including people who inject drugs. Tunable release kinetics of DAAs was enabled for 1 mo with drug-polymer pills in vitro, and the LA-DAAS safely and successfully provided at least month-long release of sofosbuvir in vivo. Temperature and alcohol sensors could interface with external sources for at least 1 mo. The LA-DAAS was cost-effective compared to DAA therapy alone in all groups considered (base case incremental cost-effectiveness ratio $39,800). We believe that the LA-DAA system can provide a cost-effective and patient-centric method for HCV treatment, including in high-risk populations who are currently undertreated.

Progress Toward Hepatitis C Virus Elimination: Therapy and Implementation.

The World Health Organization has called for the elimination of hepatitis C virus (HCV) as a public health threat by 2030. Highly effective direct-acting antiviral agents provide the therapeutic tools required for elimination. In the absence of a vaccine, HCV elimination will require enhanced primary prevention and an increase in the proportions of people diagnosed and treated. Given that globally only 20% of people with chronic HCV are diagnosed, and around 5% have initiated HCV treatment, the task ahead is enormous. But, global public health needs optimism, and countries currently on track for HCV elimination provide a pathway forward.

[QOL Assessment in Chronic Hepatitis C Patients Receiving Ledipasvir/ Sofosbuvir or Simeprevir/Peginterferon/Ribavirin in Clinical Practice].

Recently, a clinical study using a Chronic Liver Disease Questionnaire (CLDQ) showed that ledipasvir/sofosbuvir (LDV/SOF)-treated patients' QOL was more favorable than that of IFN/ribavirin (RBV)-treated patients. However, no study has reported QOL assessment in clinical practice. In this study, we compared the QOL between patients treated with LDV/SOF and those treated with simeprevir (SMV)/peginterferon (Peg-IFN)/RBV to provide QOL information in clinical practice. The subjects were 169 patients with type I chronic hepatitis C or compensated cirrhosis C (Child-Pugh Grade A) who were treated with SMV/Peg-IFN/RBV or LDV/SOF in Hitachi General Hospital. The QOL was assessed ≥2 weeks after the start of administration using the Japanese version of the CLDQ (Kida et al., 2008 version). The total CLDQ score in the LDV/SOF group was significantly higher than in the SMV/Peg-IFN/RBV group (6.59 vs. 6.38, respectively, p=0.007). In particular, the scores for 4 domains (abdominal symptoms, systemic symptoms, activity, and emotional function) in the former were significantly higher than in the latter (p<0.05). Furthermore, the rates of patients scoring 7 (no symptom) on 8 items in the former were significantly higher than in the latter (p<0.05). In clinical practice, LDV/SOF-treated patients' QOL was more favorable than that of those receiving conventional treatment with IFN and RBV. This study may make it possible for health care professionals to provide clinical QOL information on LDV/SOF therapy to patients. Furthermore, QOL information may promote decision-making for treatment, leading to effective treatment.

Decentralized care with generic direct-acting antivirals in the management of chronic hepatitis C in a public health care setting.

BACKGROUND & AIMS: The prevalence of anti-hepatitis C virus antibody in Punjab, India is 3.6%, with 728,000 people estimated to have viremic chronic hepatitis C (CHC). The Mukh-Mantri Punjab Hepatitis C Relief Fund, launched on 18th June 2016, provides no-cost generic direct-acting antivirals (DAAs) with sofosbuvir + ledipasvir ±â€¯ribavirin or sofosbuvir + daclatasvir ±â€¯ribavirin with the goal of eliminating CHC from Punjab. We assessed the safety and efficacy of decentralized treatment of CHC in a public health care setting. METHODS: Primary care providers from 3 university and 22 district hospitals were trained to provide algorithm-based DAA treatment and supervised by telehealth clinics conducted fortnightly. The diagnosis of cirrhosis was based on clinical and radiological evidence, including aspartate aminotransferase-to-platelet ratio index (APRI ≥2.0) and FIB-4 score (>3.25), or on liver stiffness measurement ≥12.5 kPa on Fibroscan®. RESULTS: We enrolled 48,088 individuals with CHC (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhosis; 69.9% genotype [GT] 3) between 18th June 2016 to 31st July 2018. While 36,250 (75.4%) patients completed treatment, 5,497 (11.4%) had treatment interruptions and 6,341 (13.2%) patients are currently ongoing treatment. Sustained virological response at 12 weeks after treatment completion (SVR12) was achieved in 91.6% of patients per protocol, 67.6% in intention-to-treat (ITT) analysis, where all interruptions were treated as failures, and 91.2% in a modified ITT analysis where all patients with successful SVR12 in the interruptions arm were included as cured. SVR12 rates in patients with and without cirrhosis and GT3 versus non-GT3 were comparable. The SVR12 rate was 84.4% in patients who had treatment interruptions. CONCLUSION: Decentralized care of patients with CHC using generic all-oral DAA regimens is safe and effective regardless of genotype or presence of cirrhosis. ClinicalTrials.gov number: NCT01110447. LAY SUMMARY: We assessed the safety and efficacy of public health care using no-cost all-oral generic direct-acting antiviral drugs against hepatitis C in the state of Punjab, India. The goal is elimination of chronic hepatitis C (CHC) by 2030 and involves primary care providers at 25 sites in the state. We enrolled 48,088 individuals (63.8% male; mean age 42.1 years; 80.5% rural; 14.8% compensated cirrhotic; 69.9% genotype 3) between 18th June 2016 to 31st July 2018. Cure was achieved in 91.6% of patients, demonstrating that decentralized care of CHC with generic all-oral regimens is safe and effective.

Sofosbuvir-Based Regimens for Chronic Hepatitis C in a Well-Insured U.S. Population: Patient Characteristics, Treatment Adherence, Effectiveness, and Health Care Costs, 2013-2015.

BACKGROUND: Chronic hepatitis C (CHC) is a leading cause of morbidity and mortality and has imposed a high health care burden in the United States. Direct-acting antiviral (DAA) regimens are well tolerated and highly effective for CHC therapy but were initially marketed at a high price. Studies of their real-world use with a nationwide population are limited. OBJECTIVE: To examine patient characteristics, treatment adherence, effectiveness, and health care costs in a large U.S. population with commercial and Medicare supplemental insurance plans who received simeprevir (SIM), sofosbuvir (SOF), or ledipasvir/sofosbuvir (LED/SOF) during the years 2013-2015. METHODS: Patients with at least 1 diagnosis code for CHC and at least 1 claim for SIM, SOF, or LED/SOF prescriptions were selected. The date of the first claim for SIM, SOF, or LED/SOF was defined as the index date. Analyses were stratified by 4 regimens: SOF + SIM ± ribavirin (RBV), SOF + peginterferon alpha-2a or 2b (PEG) + RBV, SOF + RBV, and LED/SOF ± RBV. Adherence was defined by the proportion of days covered (PDC) ≥ 80%. Sustained virologic response (SVR12) was defined as a hepatitis C virus (HCV) RNA load of ≤ 25 IU/mL measured at ≥ 12 weeks following the end of the days supply of the last DAA refill. Health care costs such as DAA drug costs and medical costs (inpatient costs plus outpatient costs) were described. RESULTS: Of 10,808 CHC patients, approximately two thirds were male, and mean age was 55 years. The proportion of patients with compensated cirrhosis among each regimen ranged from 7.4% in LED/SOF ± RBV to 13.8% in SOF + SIM ± RBV, and the proportion of patients with decompensated cirrhosis ranged from 3.9% in LED/SOF ± RBV to 10.7% in SOF + SIM ± RBV. The majority of patients (89.0%) used the newer regimen LED/SOF ± RBV in 2015. Adherence rates were estimated at 80.5%, 81.5%, 85.7%, and 91.4% for SOF + SIM ± RBV (n = 1,761); SOF + PEG + RBV (n = 1,314); SOF + RBV (n = 1,994); and LED/SOF ± RBV (n = 5,739), respectively. Regimen-specific adherence predictors included sex, age group, payer type, health plan, and treatment option with RBV. Being born during 1945-1965, liver disease severity, and Charlson Comorbidity Index levels did not predict adherence in any regimen. Overall SVR12 was 92.6% in 203 patients with available HCV RNA results: 100% (41/41) in SOF + SIM ± RBV; 83.3% (25/30) in SOF + PEG + RBV; 90.6% (29/32) in SOF + RBV; and 93% (93/100) in LED/SOF ± RBV. While the drug costs for these DAA regimens were initially high, they had decreased 18.9% (P < 0.001) during 2013-2015. Medical costs decreased 9.2% (P < 0.001) 1 year after the index dates. CONCLUSIONS: These results indicate that DAA drug costs decreased steadily during 2013-2015 and that 89% of patients on SOF-based DAA regimens took newer, lower-cost regimens with adherence rates above 80%. Available data show that SVR12 rates were close to those obtained in clinical studies. Medical costs also significantly decreased 1 year after the index dates. DISCLOSURES: No outside funding supported this study. All authors are U.S. federal employees of the Centers for Disease Control and Prevention. The authors declare that they have no competing interests. The findings and conclusions in this research are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Cost-effectiveness of sofosbuvir plus ribavirin therapy for hepatitis C virus genotype 2 infection in South Korea.

BACKGROUND AND AIM: For genotype 2 chronic hepatitis C (CHC), the efficacy and safety of sofosbuvir plus ribavirin therapy (SOF + RBV) was better than pegylated interferon plus ribavirin therapy (PR) at a greater drug cost. This study investigated the cost-effectiveness of SOF + RBV compared with PR for treatment-naïve genotype 2 CHC in South Korea. METHODS: Using a decision analytic Markov model, a cost-effectiveness analysis comparing SOF + RBV with PR or no treatment for treatment-naïve genotype 2 CHC was performed with probabilistic and deterministic sensitivity analyses from the payer's perspective in 2017. Three cohorts of patients aged 40-49, 50-59, and 60-69 years were simulated to progress through the fibrosis stages F0-F4 to end-stage liver disease, hepatocellular carcinoma, or death. Published and calculated data on the clinical efficacy of the regimen, health-related quality of life, costs, and transition probabilities were used. RESULTS: While the incremental cost-effectiveness ratio for PR was dominant over no treatment, the incremental cost-effectiveness ratios for SOF + RBV were $20 058 for the patients in their 40s, $19 662 for those in their 50s, and $22 278 for those in their 60s compared with PR. Probabilistic sensitivity analysis indicated an 89.0% probability for the SOF + RBV to be cost-effective at a willingness to pay of $29 754.4 (per-capita gross domestic product in 2017) for the patients in their 40s and 94.1% and 89.1% for the patients in their 50s and 60s, respectively. CONCLUSIONS: The SOF + RBV is a cost-effective option for genotype 2 treatment-naïve CHC patients, especially for the patients with liver cirrhosis in Korea.

Cost-effectiveness analysis of Daclatasvir/Sofosbuvir for the treatment of the HCV patients failed after the first line with second generation of DAAs in Italy.

BACKGROUND: Daclatasvir (DCV) combinated with Sofosbuvir (SOF) has shown good efficacy and safety profile for HCV patients. The aim was to evaluate the cost-effectiveness of DCV/SOF regimen versus HCV alternative treatments for patients who failed to achieve the SVR12 after a first DAA treatment from Italian perspective (PITER cohort). METHODS: A Markov model of HCV chronically infected patients was used to develop two scenarios: 1) DCV+ SOF versus Ledipasvir (LDV)+ SOF in Genotype (Gt)1 and Gt4; 2) DCV+ SOF versus no retreatment option in Gt1, Gt3, and Gt4. The percentage of patients who failed the first line with SOF/Simeprevir/Ribavirin (RBV) or SOF/RBV and were retreated or not according to evidences from PITER cohort, were used to populate the model. HCV resources consumption and SVR rates were quantified using PITER data. Transition probabilities and utility rates were derived from the literature. The outcomes were expressed in terms of Quality adjusted life years (QALYs). Probabilistic sensitivity analysis (PSA) was performed considering a cost-effectiveness threshold of € 30,000/QALY. RESULTS: In the base-case analysis, DCV+ SOF represents a cost-effectiveness therapy with ICERs lower than the threshold. The PSA showed robust results, ICERs remain below the threshold in 94% and 99% simulations in Scenario 1 and 2, respectively.

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.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Benefit-risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient population and hepatitis C virus genotype: U. S. Food and Drug Administration's evaluation.

On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed-dose combination (FDC), an interferon-free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have: • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing a nonstructural protein 5A (NS5A) inhibitor; and • genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor. Approval was based on an acceptable safety profile and high sustained virological response rates 12 weeks after the end of treatment (SVR12) in two phase 3 clinical trials in subjects previously treated with a direct-acting antiviral (DAA) regimen. In POLARIS-1, 96% of SOF/VEL/VOX-treated subjects achieved SVR12. In POLARIS-4, 98% of SOF/VEL/VOX-treated subjects achieved SVR12. A key and challenging question in evaluating the data was determining the contribution of VOX to SOF/VEL and how this differed depending on the genotype and patient population. In this article, we provide our perspective on the issues considered in making these determinations, especially regarding the POLARIS-4 data in subjects who have previously been treated with a chronic HCV regimen containing sofosbuvir without an NS5A inhibitor. Conclusion: We seek to provide context as to why a broad indication was given for NS5A inhibitor-experienced patients (HCV genotypes 1-6) while the indication for NS5A inhibitor- naïve patients was limited to HCV genotypes 1a and 3 only. (Hepatology 2018;67:482-491).

Rational Heart Transplant From a Hepatitis C Donor: New Antiviral Weapons Conquer the Trojan Horse.

BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely used for orthotopic heart transplantation (HT) owing to post-transplantation risks. New highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. On daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir (400 mg)-velpatasvir (100 mg) (Epclusa; Gilead) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy). RESULTS: We report the kinetics of acute hepatitis C viremia and therapeutic response to treatment with a new pangenotypic antiviral agent after donor-derived acute HCV infection transmitted incidentally with successful cardiac transplantation to an HCV-negative recipient. Prompt resolution of viremia was noted by the 1st week of a 12 week course of antiviral therapy. Sustained virologic remission continued beyond 12 weeks after completion of HCV therapy (SVR-12). CONCLUSIONS: The availability of effective pangenotypic therapy for HCV may expand donor availability. The feasibility of early versus late treatment of HCV remains to be determined through formalized protocols. We hypothesize pharmacoeconomics to be the greatest limitation to widespread availability of this promising tool.

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.

Cost-effectiveness of the highly effective direct-acting antivirals in the treatment of chronic hepatitis C in Hong Kong.

BACKGROUND AND AIM: In Asia-Pacific where cost is a major concern, peginterferon plus ribavirin (PR) often remain as the standard of care in chronic hepatitis C (CHC) treatment, while the direct-acting antivirals (DAAs) are commonly recommended as retreatment. Newer DAAs can achieve a sustained virological response (SVR) of nearly 100% with pan-genotypic coverage, that is "Highly Effective DAAs." We aimed to investigate the most desirable cost range for the Highly Effective DAAs using Hong Kong as an example. METHODS: Markov modeling was performed using PR as the reference strategy. The cost-effectiveness of the Highly Effective DAAs was compared with sofosbuvir-PR (first-line and rescue) and boceprevir-PR therapies. A 50-year-old genotype 1b hepatitis C virus (HCV) infected treatment-naïve patient with METAVIR F3 was used as the base case scenario to reflect the commonest HCV genotype in Hong Kong. RESULTS: The use of PR would incur a lifetime cost of US$35,854 and effectiveness of 14.85 quality-adjusted life-year (QALY). Sofosbuvir-PR as first-line treatment was dominated by other regimes. If Sofosbuvir-PR rescue therapy was used, the drug cost of Highly Effective DAAs should be set below US$43,553, with a cost-effectiveness ratio (CER) of US$3035/QALY compared with PR. In regions where Boceprevir-PR was still used as first-line therapy, the desirable drug cost of Highly Effective DAAs would be below US$56,985 to achieve a CER of US$5427/QALY. CONCLUSIONS: The most desirable costs of the Highly Effective DAAs would be below US$43,553 if Sofosbuvir-PR rescue therapy is used and below US$56,985 if Boceprevir-PR therapy is used.

Cost-Effectiveness of Treating Hepatitis C with Sofosbuvir/Ledipasvir in Germany.

BACKGROUND: Infections with the hepatitis C virus (HCV) are a global public health problem. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. Newly introduced direct acting antivirals, especially interferon-free regimens, have improved rates of sustained viral response above 90% in most patient groups and allow treating patients who were ineligible for treatment in the past. These new regimens have replaced former treatment and are recommended by current guidelines. However, there is an ongoing discussion on high pharmaceutical prices. Our aim was to assess the long-term cost-effectiveness of treating hepatitis C genotype 1 patients with sofosbuvir/ledipasvir (SOF/LDV) treatment in Germany. MATERIAL AND METHODS: We used a Markov cohort model to simulate disease progression and assess cost-effectiveness. The model calculates lifetime costs and outcomes (quality-adjusted life years, QALYs) of SOF/LDV and other strategies. Patients were stratified by treatment status (treatment-naive and treatment-experienced) and absence/presence of cirrhosis. Different treatment strategies were compared to prior standard of care. Sensitivity analyses were performed to evaluate model robustness. RESULTS: Base-case analyses results show that in treatment-naive non-cirrhotic patients treatment with SOF/LDV dominates the prior standard of care (is more effective and less costly). In cirrhotic patients an incremental cost-effectiveness ratio (ICER) of 3,383 €/QALY was estimated. In treatment-experienced patients ICERs were 26,426 €/QALY and 1,397 €/QALY for treatment-naive and treatment-experienced patients, respectively. Robustness of results was confirmed in sensitivity analyses. CONCLUSIONS: Our analysis shows that treatment with SOF/LDV is cost-effective compared to prior standard of care in all patient groups considering international costs per QALY thresholds.

Decompensated HCV patients with co morbidities including HIV who are medically treated are shown to minimize decompensation related admissions and healthcare cost: A case series.

Hepatitis C virus infection is a hot topic for both effective treatment and elevated cost. This case series describes the cost saving for the healthcare system of any nation of treating HCV in many situations, including that of overt cirrhosis. Case#1 is of a HCV/HIV infected cirrhotic patient with MELD score of 17, Child Pugh score B, recurrent esophageal bleeds ceased after successful treatment with sofosbuvir and simepravir. Case#2 is a patient also co-infected with HCV/HIV MELD score of 18, Child Pugh score B, with grade 3 esophageal varices and frequent bleed with significant anemia. With a regimen of sofosbuvir and ribavirin the patient had no more hospitalization for GI bleed. HCV infection is still underdiagnosed, picking up on it early, sufficient treatment and follow up may reduce healthcare costs in the long run by significant measures.