The optimal timing of hepatitis C therapy in liver transplant‐eligible patients: Cost‐effectiveness analysis of new opportunities

Different strategies of DAAs treatment are currently possible both pre‐ and postliver transplantation (LT). Clinical and economic consequences of these strategies still need to be adequately investigated; this study aims at assessing their cost‐effectiveness. A decision analytical model was created to simulate the progression of HCV‐infected patients listed for decompensated cirrhosis (DCC) or for hepatocellular carcinoma (HCC). Three DAAs treatment strategies were compared: (i) a 12‐week course of DAAs prior to transplantation (PRE‐LT), (ii) a 4‐week course of DAAs starting at the time of transplantation (PERI‐LT) and (iii) a 12‐week course of DAAs administered at disease recurrence (POST‐LT). The population was substratified according to HCC presence and, in those without HCC, according to the MELD score at listing. Data on DAAs effectiveness were estimated using a cohort of patients still followed by 11 transplant centres of the European Liver and Intestine Transplant Association and by data available in the literature. In this study, PRE‐LT treatment strategy was dominant for DCC patients with MELD<16 and cost‐effective for those with MELD16‐20, while POST‐LT strategy emerged as cost‐effective for DCC patients with MELD>20 and for those with HCC. Sensitivity analyses confirmed PRE‐LT as the cost‐effective strategy for patients with MELD≤20. In conclusion, PRE‐LT treatment is cost‐effective for patients with MELD≤20 without HCC, while treatments after LT are cost‐effective in cirrhotic patients with MELD>20 and in those with HCC. It is worth reminding, though, that the final choice of a specific regimen at the patient level will have to be personalized based on clinical, social and transplant‐related factors.     

Cost‐effectiveness and budget impact of interferon‐free direct‐acting antiviral‐based regimens for hepatitis C treatment: the French case

We evaluated the cost‐effectiveness and the budget impact of new DAA‐based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN‐based and IFN‐free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality‐adjusted life years (QALYs) and incremental cost‐effectiveness ratios (ICERs). It also assessed the budget impact over 5 years of treating all CHC‐screened patients, regardless of fibrosis, assuming ≤20 000 patients treated/year and priority to ≥F3. Sensitivity analyses were also conducted. For genotypes (G) 1–4, the initiation of IFN‐free regardless of fibrosis was a cost‐effective strategy compared to prior standard of care (SOC) initiated at stage F2: €40 400–88 300/QALY gained in G1; similar results were obtained for patients infected with G4. Considering G2–3, the most cost‐effective strategy was IFN‐based regimens regardless of fibrosis compared to prior SOC initiated at stage F2: €21 300 and €19 400/QALY gained, respectively; the strategy with IFN‐free regimens being more effective but not cost‐effective at current costs. The budget impact of treating all CHC‐screened patients over 5 years would range between 3.5 and 7.2 billion €, depending on whether one considers the least or the most expensive combination of new DAAs and whether one treats G2–3 with IFN‐based or IFN‐free new DAAs. In France, treatment initiation with new DDAs regardless of fibrosis stage is cost‐effective, but would add 3.5–7.2 billion € to an already overburdened medical care system.     

Cost‐effectiveness of sofosbuvir for the treatment of chronic hepatitis C‐infected patients

The efficacy of treatment for hepatitis C genotype 1 infection has significantly improved with the introduction of first‐generation protease inhibitors. However, there remains a need for effective treatments for patients infected with other genotypes, for nonresponders and patients unsuitable for interferon. Sofosbuvir is the first nucleotide polymerase inhibitor with pan‐genotypic activity. Sofosbuvir‐based regimens have resulted in >90% sustained virological response across treatment‐naïve genotype 1–6 patients in five phase III clinical trials of sofosbuvir administered with ribavirin or pegylated interferon and ribavirin. This analysis evaluates the cost‐effectiveness of sofosbuvir within the current licensed indication, for genotype 1–6 in the UK. A Markov model followed a cohort of 10 000 patients over lifetime, with approximately 20% initiating treatment for compensated cirrhosis. Sofosbuvir‐regimens were compared to telaprevir, boceprevir, pegylated interferon and ribavirin, or no treatment. Costs and outcomes were discounted at 3.5%. The cost perspective utilized costs applicable to the National Health Service in the UK. Sofosbuvir proved to be cost‐effective in most patient populations with incremental cost‐effectiveness ratios (ICERs) at £11 836/QALY and £7292/QALY against telaprevir and boceprevir, respectively. In genotype 3, sofosbuvir had a weighted ICER of £18 761/QALY. Sofosbuvir‐based regimens are a cost‐effective option for the majority of hepatitis C‐infected patients in the United Kingdom although the incremental cost‐effectiveness varies by genotype and regimen. Sofosbuvir and ribavirin is an alternative regimen for patients unsuitable for interferon.     

Low incidence of hepatitis B virus reactivation and subsequent hepatitis in patients with chronic hepatitis C receiving direct‐acting antiviral therapy

To determine the clinical characteristics of hepatitis B virus (HBV) reactivation in patients undergoing interferon‐free antihepatitis C virus (HCV) therapy, we examined HBV DNA in 25 HBV co‐infected patients and 765 patients with resolved HBV infection during and after treatment with direct‐acting antiviral agents (DAAs). Among those with HCV genotype 1, asunaprevir plus daclatasvir was administered to 160 patients, sofosbuvir (SOF) plus ledipasvir to 438 patients and paritaprevir plus ombitasvir and ritonavir to 25 patients. In total, 167 patients with genotype 2 were treated with SOF plus ribavirin. Three patients with an HBV DNA level ≥2000 IU/mL were treated with entecavir before anti‐HCV therapy, without reactivation of HBV. In 3 of 22 (12%) HBV surface antigen (HBsAg)‐positive patients with an HBV DNA level <2000 IU/mL, the viral load increased during treatment. However, hepatitis flare did not occur in these patients. There was no significant difference in clinical history between patients with and without HBV reactivation. Among 765 patients with resolved HBV infection, HBV reactivation occurred in 1 (0.1%) patient after initial resolution, whose HBV DNA level spontaneously decreased after DAA therapy. We compared anti‐HBs titres at baseline with those at post‐DAA therapy in 123 patients without HBsAg. There was no significant difference in anti‐HBs levels between the two points (P = .79). In conclusion, HBV reactivation was rare in HBsAg‐negative patients treated with DAA therapy. Additionally, hepatitis did not occur in HBV‐reactivated patients with a baseline HBV DNA level <2000 IU/mL before DAA therapy.     

Outcome of cutaneous psoriasis in hepatitis C virus‐infected patients treated with Direct‐Acting Antiviral therapy

Apart from chronic liver disease, hepatitis C virus (HCV) may be responsible for several extra‐hepatic manifestations. Its involvement in psoriasis development is still controversial. The aim of this study was to evaluate the possible effect of anti‐HCV direct‐acting antiviral (DAA) treatment on cutaneous psoriasis. Thirty‐seven consecutive HCV patients with cutaneous psoriasis underwent efficacious DAA treatment, and all of them were efficiently cured as shown by HCV RNA negativity 24 weeks after stopping therapy (PT24W). An expert dermatologist evaluated the skin lesions at baseline, end of treatment (EOT) and PT24W using the psoriasis area severity index (PASI) scoring system. The impact on quality of life was measured with the Dermatologic Quality of Life Index (DLQI). Six patients had a stable disease throughout the study period, whereas 31/37 patients (83.8%) showed a significant improvement of the skin lesions at EOT (P < .0001). However, 24 of these 31 patients (77.4%) had a dramatic worsening of the psoriatic lesions at PT24W compared with EOT (P < .001), with lesion severity comparable to baseline. The outcome of psoriasis during and after treatment was independent of baseline PASI score, age, sex, HCV genotype, liver disease stage and of the presence of arterial hypertension, diabetes and autoimmune diseases. In conclusion, DAA‐based HCV cure has only a transient effect on skin lesions of patients with concomitant cutaneous psoriasis.     

Epidemiology of hepatitis C virus infection in a country with universal access to direct‐acting antiviral agents: Data for designing a cost‐effective elimination policy in Spain

Accurate HCV prevalence estimates are necessary for guiding elimination policies. Our aim was to determine the HCV prevalence and assess the cost‐effectiveness of a screen‐and‐treat strategy in the Spanish population. A population‐based, cross‐sectional study (PREVHEP‐ETHON Cohort, Epidemiological sTudy of Hepatic infectiONs; NCT02749864) was performed from July 2015‐April 2017. Participants from three Spanish regions were selected using two‐stage conglomerate sampling, and stratified by age, with randomized subject selection. Anthropometric and demographic data were collected, and blood samples were taken to detect anti‐HCV antibodies/quantify HCV RNA. The cost‐effectiveness of the screening strategies and treatment were analysed using a Markov model. Among 12 246 participants aged 20‐74 (58.4% females), the overall anti‐HCV prevalence was 1.2% (95% CI 1.0‐1.4), whereas the detectable HCV‐RNA prevalence was 0.3% (0.2‐0.4). Infection rates were highest in subjects aged 50‐74 years [anti‐HCV 1.6% (1.3‐1.9), HCV RNA 0.4% (0.3‐0.6]. Among the 147 anti‐HCV + subjects, 38 (25.9%) had active infections while 109 (74.1%) had been cleared of infection; 44 (40.4%) had cleared after antiviral treatment, whereas 65 (59.6%) had cleared spontaneously. Overall, 59.8% of the anti‐HCV + participants were aware of their serological status. Considering a cost of treatment of €7000/patient, implementing screening programmes is cost‐effective across all age cohorts, particularly in patients aged 50‐54 (negative incremental cost‐effectiveness ratio which indicates a cost‐saving strategy). The current HCV burden is lower than previously estimated, with approximately 25% of anti‐HCV + individuals having an active infection. A strategy of screening and treatment at current treatment prices in Spain is cost‐effective across all age cohorts.