Modelling the potential effectiveness of hepatitis C screening and treatment strategies during pregnancy in Egypt and Ukraine.

BACKGROUND & AIMS: HCV test and treat campaigns currently exclude pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine. METHODS: Country-specific probabilistic decision models were developed to simulate a cohort of pregnant women. We compared five strategies: S0, targeted risk-based screening and deferred treatment (DT) to after pregnancy/breastfeeding; S1, World Health Organization (WHO) risk-based screening and DT; S2, WHO risk-based screening and targeted treatment (treat women with risk factors for HCV vertical transmission [VT]); S3, universal screening and targeted treatment during pregnancy; S4, universal screening and treatment. Maternal and infant HCV outcomes were projected. RESULTS: S0 resulted in the highest proportion of women undiagnosed: 59% and 20% in Egypt and Ukraine, respectively, with 0% maternal cure by delivery and VT estimated at 6.5% and 7.9%, respectively. WHO risk-based screening and DT (S1) increased the proportion of women diagnosed with no change in maternal cure or VT. Universal screening and treatment during pregnancy (S4) resulted in the highest proportion of women diagnosed and cured by delivery (65% and 70%, respectively), and lower levels of VT (3.4% and 3.6%, respectively). CONCLUSIONS: This is one of the first models to explore HCV screening and treatment strategies in pregnancy, which will be critical in informing future care and policy as more safety/efficacy data emerge. Universal screening and treatment in pregnancy could potentially improve both maternal and infant outcomes. IMPACT AND IMPLICATIONS: In the context of two lower middle-income countries with high HCV burdens (Egypt and Ukraine), we designed a decision analytic model to explore five different HCV testing and treatment strategies for pregnant women, with the assumption that treatment was safe and efficacious for use in pregnancy. Assuming direct-acting antiviral treatment during pregnancy would reduce vertical transmission, our findings indicate that the provision of universal (rather than risk-based targeted) screening and treatment would provide the greatest maternal and infant benefits. While future trials are needed to assess the safety and efficacy of direct-acting antivirals in pregnancy and their impact on vertical transmission, there is increasing recognition that the elimination of HCV cannot leave entire subpopulations of pregnant women and young children behind. Our findings will be critical for policymakers when developing improved screening and treatment recommendations for pregnant women.

Assessing complex interventions: a systematic review of outcomes used in randomised controlled trials on STI partner notification in high-income countries.

BACKGROUND: Partner notification interventions are complex and assessing their effectiveness is challenging. By reviewing the literature on the effectiveness of partner notification interventions, our aim was to evaluate the choice, collection, and interpretation of outcomes and their impact on study findings. METHODS: We conducted a systematic review of individual-level randomised controlled trials evaluating the effectiveness of partner notification interventions for bacterial STIs, HIV or sexually transmitted HCV in high-income countries since 2000. Partner notification interventions included assisted patient referral interventions and expedited treatment. The content analysis was carried out through a narrative review. RESULTS: In the 9 studies that met the inclusion criteria, 16 different outcomes were found. In most studies, one or two outcomes assessing partner notification practices were associated with an outcome reflecting STI circulation through index case reinfections. These outcomes assessed the main expected effects of partner notification interventions. However, partner notification is composed of a succession of actions between the intervention on the index case and the testing and/or treatment of the notified partners. Intermediate outcomes were missing so as to better understand levers and barriers throughout the process. Potential changes in participants' sexual behaviour after partner notification, e.g. condom use, were outcomes reported in only two studies assessing interventions including counselling. Most outcomes were collected through interviews, some weeks after the intervention, which might lead to desirability and attrition biases, respectively. Assessment of the effectiveness of partner notification interventions on partner testing/treatment was limited by the collection of data from index cases. Few data describing index cases and their partners were provided in the studies. Additional data on the number and type of exposed partners and the proportion of partners already aware of their infection before being notified would help to interpret the results. CONCLUSIONS: These insights would help to understand why and under what conditions the intervention is considered effective and therefore can be replicated or adapted to other populations and contexts.

Impact of test-and-treat and risk reduction strategies on HCV transmission among MSM living with HIV in France: a modelling approach.

OBJECTIVE: Since the early 2000s, there has been an epidemic of HCV occurring among men who have sex with men (MSM) living with HIV, mainly associated with high-risk sexual and drug-related behaviours. Early HCV diagnosis and treatment, and behavioural risk-reduction, may be effective to eliminate HCV among MSM living with HIV. DESIGN: We developed a deterministic dynamic compartmental model to simulate the impact of test-and-treat and risk-reduction strategies on HCV epidemic (particularly on incidence and prevalence) among MSM living with HIV in France. We accounted for HIV and HCV cascades of care, HCV natural history and heterogeneity in HCV risk behaviours. The model was calibrated to primary HCV incidence observed between 2014 and 2017 among MSM living with HIV in care (ANRS CO4-French hospital database on HIV (FHDH)). RESULTS: With current French practices (annual HCV screening and immediate treatment), total HCV incidence would fall by 70%, from 0.82/100 person-years in 2015 to 0.24/100 person-years in 2030. It would decrease to 0.19/100 person-years in 2030 with more frequent screening and to 0.19 (0.12)/100 person-years in 2030 with a 20% (50%) risk-reduction. When combining screening every 3 months with a 50% risk-reduction, HCV incidence would be 0.11/100 person-years in 2030, allowing to get close to the WHO target (90% reduction from 2015 to 2030). Similarly, HCV prevalence would decrease from 2.79% in 2015 to 0.48% in 2030 (vs 0.71% with current practices). CONCLUSION: Combining test-and-treat and risk-reduction strategies could have a marked impact on the HCV epidemic, paving the way to HCV elimination among MSM living with HIV.

A tool to predict progression of non-alcoholic fatty liver disease in severely obese patients.

BACKGROUND & AIMS: Severely obese patients are a growing population at risk of non-alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective was to provide a tool allowing general practitioners to identify and refer the patients most at risk, and specialists to estimate disease progression and adapt the therapeutic strategy. METHODS: This predictive tool is based on a Markov model simulating steatosis, fibrosis and non-alcoholic steatohepatitis (NASH) evolution. This model was developped from data of 1801 severely obese, bariatric surgery candidates, with histological assessment, integrating duration of exposure to risk factors. It is then able to predict current disease severity in the absence of assessment, and future cirrhosis risk based on current stage. RESULTS: The model quantifies the impact of sex, body-mass index at 20, diabetes, age of overweight onset, on progression. For example, for 40-year-old severely obese patients seen by the general practitioners: (a) non-diabetic woman overweight at 20, and (b) diabetic man overweight at 10, without disease assessment, the model predicts their current risk to have NASH or F3-F4: for (a) 5.7% and 0.6%, for (b) 16.1% and 10.0% respectively. If those patients have been diagnosed F2 by the specialist, the model predicts the 5-year cirrhosis risk: 1.8% in the absence of NASH and 6.0% in its presence for (a), 10.3% and 26.7% respectively, for (b). CONCLUSIONS: This model provides a decision-making tool to predict the risk of liver disease that could help manage severely obese patients.

Hepatitis C virus (HCV) incidence among men who have sex with men (MSM) living with HIV: results from the French Hospital Database on HIV (ANRS CO4-FHDH) cohort study, 2014 to 2017.

BackgroundDespite the availability of highly effective direct-acting antivirals (DAAs) and the expected treatment as prevention (TasP) effect, transmission of hepatitis C virus (HCV) persists in men who have sex with men (MSM) who engage in high-risk sexual behaviours.AimWe aimed to estimate the incidence of primary HCV infection among MSM living with HIV in France when DAA was readily available.MethodsWe used data from a large French hospital cohort of persons living with HIV (ANRS CO4-FHDH) prospectively collected between 2014 and 2017. HCV incidence rates were calculated using person-time methods for HCV-negative MSM at inclusion who had serological follow-up from 1 January 2014 to 31 December 2017. Sensitivity analyses were performed by varying the main assumptions to assess their impact on the results.ResultsOf 14,273 MSM living with HIV who were initially HCV-seronegative, 330 acquired HCV during follow-up over 45,866 person-years (py), resulting in an overall estimated incidence rate of 0.72/100 py (95% CI: 0.65-0.80). HCV incidence significantly decreased from 0.98/100 py (95% CI: 0.81-1.19) in 2014 to 0.45/100 py (95% CI: 0.35-0.59) in 2017 (54% decrease; 95% CI: 36-67). This trend was confirmed by most of the sensitivity analyses.ConclusionThe primary incidence of HCV was halved for MSM living with HIV between 2014 and 2017. This decrease may be related to unrestricted DAA availability in France for individuals living with HIV. Further interventions, including risk reduction, are needed to reach HCV micro-elimination in MSM living with HIV.

A Model to Identify Heavy Drinkers at High Risk for Liver Disease Progression.

BACKGROUND & AIMS: Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression. METHODS: We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy. We collected data from both cohorts on patient history and disease stage at the time of hospitalization. For the development cohort, severity of the disease was scored by the METAVIR (due to the availability of liver histology reports); in the validation cohort only the presence of liver complications was assessed. We developed a model of ALD progression and occurrence of liver complications (hepatocellular carcinoma and/or liver decompensation) in association with exposure to alcohol, age at the onset of heavy drinking, amount of alcohol intake, sex and body mass index. The model was fitted to the development cohort and then evaluated in the validation cohort. We then tested the ability of the model to predict disease progression for any patient profile (baseline evaluation). Patients with a 5-y weighted risk of liver complications greater than 5% were considered at high risk for disease progression. RESULTS: Model results are given for the following patient profiles: men and women, 40 y old, who started drinking at an age of 25 y, drank 150 g/day, and had a body mass index of 22 kg/m2 according to the disease severity at baseline evaluation. For men with baseline F0-F2 fibrosis, the model estimated the probabilities of normal liver, steatosis, or steatohepatitis at baseline to be 31.8%, 61.5% and 6.7%, respectively. The 5-y weighted risk of liver complications was 1.9%, ranging from 0.2% for men with normal liver at baseline evaluation to 10.3% for patients with steatohepatitis at baseline. For women with baseline F0-F2 fibrosis, probabilities of normal liver, steatosis, or steatohepatitis at baseline were 25.1%, 66.5% and 8.4%, respectively; the 5-y weighted risk of liver complications was 3.2%, ranging from 0.5% for women with normal liver at baseline to 14.7% for patients with steatohepatitis at baseline. Based on the model, men with F3-F4 fibrosis at baseline have a 24.5% 5-y weighted risk of complications (ranging from 20.2% to 34.5%) and women have a 30.1% 5-y weighted risk of complications (ranging from 24.7% to 41.0%). CONCLUSIONS: We developed a Markov model that integrates data on level and duration of alcohol use to identify patients at high risk of liver disease progression. This model might be used to adapt patient care pathways.

Securing sustainable funding for viral hepatitis elimination plans.

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct-acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries' health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro-elimination approach in specific populations is less complex and less costly than country-wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO.

Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients: Results of a prospective, nationwide study.

BACKGROUND: Recent data suggest that alcohol-related hepatocellular carcinoma (HCC) is diagnosed at a later stage. The aim of this study was to compare HCC characteristics and outcomes in an alcohol-related group (group A) and a non-alcohol-related group (group NA). METHODS: A total of 1207 patients with newly diagnosed HCC were prospectively included between May 2008 and October 2009. Patients with multiple causes (alcohol plus another cause) were excluded. Patients were followed every year for 5 years. Recorded variables, including etiologies were tested as prognostic factors of survival in a multivariate Cox model after adjustments for a lead-time bias. RESULTS: In all, 894 patients were analyzed: 582 (65.1%) were in group A, and 312 (34.9%) were in group NA. Alcohol-related HCC was more likely to be diffuse and detected in patients with a worse performance status and worse liver function. After adjustments for a lead-time bias, the median overall survival (OS) was 9.7 and 5.7 months in groups NA and A, respectively (P = .0002), and 5.8 and 5.0 months in alcohol-abstinent and alcohol non-abstinent groups, respectively (P = .09). The prognostic role of alcohol disappeared when survival was assessed at each Barcelona Clinic Liver Cancer (BCLC) stage. Patients with HCC detected during a cirrhosis follow-up program (n = 199 [22.3% of the whole cohort]) had increased lead time-adjusted median OS in comparison with patients with HCC diagnosed incidentally (11.7 vs 5.4 months; P < .0001). CONCLUSIONS: In comparison with patients with non-alcohol-related HCC, patients with alcohol-related HCC have reduced OS, mainly because of worse liver function and tumor characteristics at diagnosis, as attested by similar survival within each BCLC stage. Cancer 2018;124:1964-72. © 2018 American Cancer Society.

Assessing the cost-effectiveness of hepatitis C screening strategies in France.

BACKGROUND & AIMS: In Europe, hepatitis C virus (HCV) screening still targets people at high risk of infection. We aim to determine the cost-effectiveness of expanded HCV screening in France. METHODS: A Markov model simulated chronic hepatitis C (CHC) prevalence, incidence of events, quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio (ICER) in the French general population, aged 18 to 80 years, undiagnosed for CHC for different strategies: S1 = current strategy targeting the at risk population; S2 = S1 and all men between 18 and 59 years; S3 = S1 and all individuals between 40 and 59 years; S4 = S1 and all individuals between 40 and 80 years; S5 = all individuals between 18 and 80 years (universal screening). Once CHC was diagnosed, treatment was initiated either to patients with fibrosis stage ≥F2 or regardless of fibrosis. Data were extracted from published literature, a national prevalence survey, and a previously published mathematical model. ICER were interpreted based on one or three times French GDP per capita (€32,800). RESULTS: Universal screening led to the lowest prevalence of CHC and incidence of events, regardless of treatment initiation. When considering treatment initiation to patients with fibrosis ≥F2, targeting all people aged 40-80 was the only cost-effective strategy at both thresholds (€26,100/QALY). When we considered treatment for all, although universal screening of all individuals aged 18-80 is associated with the highest costs, it is more effective than targeting all people aged 40-80, and cost-effective at both thresholds (€31,100/QALY). CONCLUSIONS: In France, universal screening is the most effective screening strategy for HCV. Universal screening is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of HCV eradication, this strategy should be implemented. LAY SUMMARY: In the context of highly effective and well tolerated therapies for hepatitis C virus that are now recommended for all patients, a reassessment of hepatitis C screening strategies is needed. An effectiveness and cost-effectiveness study of different strategies targeting either the at-risk population, specific ages or all individuals was performed. In France, universal screening is the most effective strategy and is cost-effective when treatment is initiated regardless of fibrosis stage. From an individual and especially from a societal perspective of hepatitis C virus eradication, this strategy should be implemented.

Are targeted treatment recommendations in chronic hepatitis C tailored to diagnostic methods of fibrosis?

BACKGROUND & AIMS: The progression of chronic HCV infection varies significantly depending on patient characteristics. The goal of the present study was to evaluate the consequences of targeted and universal therapy for HCV-related morbidity-mortality based on the use of non-invasive diagnostic tests in France, Italy and the UK. METHODS: A country-specific Markov model was used to predict clinical outcomes in patients with chronic HCV mono-infection over 5years. Therapeutic strategies used in the three countries analysed: no treatment, targeted therapy based on stage of fibrosis (F2- or F3-scenario), treatment regardless of stage of fibrosis (universal analysis), base-case analysis and yearly assessments. RESULTS: Universal therapy is the most effective strategy and reduced the 5-year incidence of cirrhosis by 12.0-17.7, liver complications by 4.2-5.3 and liver deaths by 3.7-4.7, vs. no treatment. In base-case analysis, the F2-scenario using FibroScan or patented blood biomarkers reduces the 5-year incidence of cirrhosis by 2.7-4.0, liver complications by 3.5-3.7 and liver deaths by 3.3-3.7, vs. no treatment. The results of the F3-scenario are poor for the incidence of cirrhosis, and moderately effective for the liver complications. The alternative analysis with a yearly assessment of fibrosis improves the impact of targeted therapy. CONCLUSION: By quantifying the impact of different strategies of targeted therapy and universal therapy, this study could help health agencies and experts to draft therapeutic guidelines for HCV-related fibrosis. LAY SUMMARY: The impact of different treatment strategies was evaluated in three countries, France, Italy and UK, using a mathematical model. This analysis showed that: i) A prioritization strategy of HCV treatment for patients with advanced disease would decrease the overall impact of treatment on morbidity and mortality; and ii) A strategy initiating HCV treatment to all would already show a benefit in reducing 5-year morbidity and mortality.

Hepatitis C treatment as prevention of viral transmission and liver-related morbidity in persons who inject drugs.

UNLABELLED: Hepatitis C virus (HCV) seroprevalence remains high in people who inject drug (PWID) populations, often above 60%. Highly effective direct-acting antiviral (DAA) regimens (90% efficacy) are becoming available for HCV treatment. This therapeutic revolution raises the possibility of eliminating HCV from this population. However, for this, an effective cascade of care is required. In the context of the available DAA therapies, we used a dynamic individual-based model including a model of the PWID social network to simulate the impact of improved testing, linkage to care, and adherence to treatment, and of modified treatment recommendation on the transmission and on the morbidity of HCV in PWID in France. Under the current incidence and cascade of care, with treatment initiated at fibrosis stage ≥F2, HCV prevalence decreased from 42.8% to 24.9% (95% confidence interval: 24.8-24.9) after 10 years. Changing treatment initiation criteria to treat from F0 was the only intervention leading to a substantial additional decrease in prevalence, which fell to 11.6% (95% CI: 11.6-11.7) at 10 years. Combining this change with improved testing, linkage to care, and adherence to treatment decreased HCV prevalence to 7.0% (95% CI: 7.0-7.1) at 10 years and avoided 15% (95% CI: 14-17) and 29% (95% CI: 28-30) of cirrhosis complications over 10 and 40 years, respectively. CONCLUSIONS: Major decreases in prevalent HCV infections occur only when treatment is initiated at early stages of fibrosis, suggesting that systematic treatment in PWID, where incidence remains high, would be beneficial. However, elimination within the 10 next years will be difficult to achieve using treatment alone, even with a highly improved cascade of care.

Severe liver disease related to chronic hepatitis C virus infection in treatment-naive patients: epidemiological characteristics and associated factors at first expert centre visit, France, 2000 to 2007 and 2010 to 2014.

Given recent profound improvements in the effectiveness of antiviral treatment for chronic Hepatitis C virus (HCV) infection, we aimed to describe the characteristics of patients referred to hepatology expert centres in France from 2000 to 2007 and from 2010 to 2014, and to identify factors associated with severe liver disease at their first visit for evaluation. We analysed data from two sources covering all of France: the former hepatitis C surveillance network, which included patients between 2000 and 2007, and the ANRS CO22 HEPATHER multi-centre cohort, which included patients between 2012 and 2014. Severe liver disease (SLD) was defined as the presence of either cirrhosis (histological, biochemical or clinical) or hepatocellular carcinoma. Multivariable Poisson regression models were used to identify the factors associated with SLD in complete-case analysis and after multiple imputation. Overall, 16,851 patients were included in the analysis and SLD was diagnosed in 11.6%. SLD at first visit was significantly associated with known risk factors (male sex, history of excessive alcohol intake, HCV genotype 3), late referral to hepatologists after diagnosis and HCV diagnosis at an older age. Providing earlier specialised care and treatment may be an important target for public health action.

How to optimize hepatitis C virus treatment impact on life years saved in resource-constrained countries.

UNLABELLED: In resource-constrained countries where the prevalence of hepatitis C virus (HCV) disease is usually high, it is important to know which population should be treated first in order to increase treatment effectiveness. The aim was to estimate the effectiveness of different HCV treatment eligibility scenarios in three different countries. Using a Markov model, we estimated the number of life-years saved (LYS) with different treatment eligibility scenarios according to fibrosis stage (F1-F4 or F3-4), compared to base case (F2-F4), at a constant treatment rate, of patients between 18 and 60 years of age, at stages F0/F1 to F4, without liver complications or coinfections, chronically infected by HCV, and treated with pegylated interferon (IFN)/ribavirin or more-efficacious therapies (i.e. IFN free). We conducted the analysis in Egypt (prevalence = 14.7%; 45,000 patients treated/year), Thailand (prevalence = 2.2%; 1,000 patients treated/year), and Côte d'Ivoire (prevalence = 3%; 150 patients treated/year). In Egypt, treating F1 patients in addition to ≥F2 patients (SE1 vs. SE0) decreased LYS by 3.9%. Focusing treatment only on F3-F4 patients increased LYS by 6.7% (SE2 vs. SE0). In Thailand and Côte d'Ivoire, focusing treatment only on F3-F4 patients increased LYS by 15.3% and 11.0%, respectively, compared to treating patients ≥F2 (ST0 and SC0, respectively). Treatment only for patients at stages F3-F4 with IFN-free therapies would increase LYS by 16.7% versus SE0 in Egypt, 22.0% versus ST0 in Thailand, and 13.1% versus SC0 in Côte d'Ivoire. In this study, we did not take into account the yearly new infections and the impact of treatment on HCV transmission. CONCLUSION: Our model-based analysis demonstrates that prioritizing treatment in F3-F4 patients in resource-constrained countries is the most effective scenario in terms of LYS, regardless of treatment considered.

2014 French guidelines for hepatitis B and C screening: a combined targeted and mass testing strategy of chronic viruses namely HBV, HCV and HIV.

BACKGROUND & AIMS: Worldwide and, to a lesser extent, in France, a minority of individuals infected with hepatitis B (HBV) and C (HCV) is aware of its status. Given the current availability of highly effective anti-HBV and anti-HCV agents, the high rate of undiagnosed people, associated with individual and community prejudices (liver disease worsening, persistence of a hidden transmission reservoir and medicoeconomic burden of delayed care), is unacceptable. METHODS: On the occasion of the first French general report on viral hepatitis, new recommendations for HBV and HCV testing were issued. We aim to introduce the new French strategy for HBV and HCV screening, and to describe the underlying epidemiological data. RESULTS: These recommendations comprise various items. First, the screening of chronic viruses, namely HBV, HCV and HIV, should be quasi-systematically combined. Second, the targeted screening of groups at risk of viral exposure must be strengthened. Third, routine testing for each of these three viruses should be offered at least once to men of 18-60 years old who had never been tested. In parallel, in pregnant women, in addition to HIV-HBV screening, currently recommended HCV testing should be routinely performed during the first trimester of pregnancy. In order to best achieve the target populations, community initiatives that propose testing actions should be encouraged, particularly those including rapid point-of-care tests. CONCLUSIONS: Overall, these recommendations aim to define a comprehensive testing strategy for chronic viral infections, emphasizing both targeted screening and mass screening and considering jointly HBV, HCV and HIV.

Hepatitis C virus treatment in the real world: optimising treatment and access to therapies.

Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in 'hard-to-treat' groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world.

Hepatocellular carcinoma screening in patients with compensated hepatitis C virus (HCV)-related cirrhosis aware of their HCV status improves survival: a modeling approach.

UNLABELLED: Because of the ongoing debate on the benefit of ultrasound (US) screening for hepatocellular carcinoma (HCC), we assessed the impact of screening on hepatitis C virus (HCV)-related compensated cirrhosis patients aware of their HCV status. A Markov model simulated progression from HCC diagnosis to death in 700 patients with HCV-related compensated cirrhosis aware of their HCV status to estimate life expectancy (LE) and cumulative death at 5 years. Five scenarios were compared: S1, no screening; S2, screening by currently existing practices (57% access and effectiveness leading to the diagnosis of 42% at Barcelona Clinic Liver Cancer stage [BCLC-0/A]); S3, S2 with increased access (97%); S4, S2 with an efficacy of screening close to that achieved in a randomized controlled trial leading to the diagnosis of 87% of patients at stage BCLC-0/A; S5, S3+S4. The analysis was corrected for lead-time bias. Currently existing practices of HCC screening increased LE by 11 months and reduced HCC mortality at 5 years by 6% compared to no screening (P = 0.0013). Compared to current screening practices, we found that: 1) increasing the rate of access to screening would increase LE by 7 months and reduce HCC mortality at 5 years by 5% (P = 0.045); 2) optimal screening would increase LE by 14 months and reduce HCC mortality at 5 years by 9% (P = 0.0002); 3) the combination of an increased rate of access and optimal effectiveness of HCC screening would increase LE by 31 months and decrease HCC mortality at 5 years by 20% (P < 0.0001). CONCLUSION: The present study shows that US screening for HCC in patients with compensated HCV-related cirrhosis aware of their HCV status improves survival and emphasizes the crucial role of screening effectiveness.

Effectiveness and cost-effectiveness of immediate versus delayed treatment of hepatitis C virus-infected patients in a country with limited resources: the case of Egypt.

BACKGROUND: Because of logistical and economic issues, in Egypt, as in other resource-limited settings, decision makers should determine for which patients hepatitis C virus (HCV) treatment should be prioritized. We assessed the effectiveness and cost-effectiveness of different treatment initiation strategies. METHODS: Using a Markov model, we simulated HCV disease in chronically infected patients in Egypt, to compare lifetime costs, quality-adjusted life expectancy (QALE), and the incremental cost-effectiveness ratio (ICER) of different treatment initiation strategies. RESULTS: Immediate treatment of patients at stages F1/F2/F3 was less expensive and more effective than delaying treatment until more severe stages or not providing treatment (in patients diagnosed at F1: QALE = 18.32 years if treatment at F1 vs 18.22 if treatment at F2). Treatment of F4 patients was more effective than no treatment at all (QALE = 10.33 years vs 8.77 years) and was cost-effective (ICER = $1915/quality-adjusted life-year [QALY]). When considering that affordable triple therapies, including new direct-acting antivirals, will be available starting in 2016, delaying treatment until stage F2, then treating all patients regardless of their disease stage after 2016, was found to be cost-effective (ICER = $33/QALY). CONCLUSIONS: In Egypt, immediate treatment of patients with fibrosis stage F1-F3 who present to care is less expensive and more effective than delaying treatment. However, immediate treatment at stage F1 is only slightly more effective than waiting for disease to progress to stage F2 before starting treatment and is sensitive to the forthcoming availability of new treatments. Treating patients at stage F4 is highly effective and cost-effective. In Egypt, decision makers should prioritize treatment for F4 patients and delay treatment for F1 patients who present to care.

Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141).

BACKGROUND & AIMS: In treatment-naive patients mono-infected with genotype 1 chronic HCV, treatments with telaprevir/boceprevir (TVR/BOC)-based triple therapy are standard-of-care. However, more efficacious direct-acting antivirals (IFN-based new DAAs) are available and interferon-free (IFN-free) regimens are imminent (2015). METHODS: A mathematical model estimated quality-adjusted life years, cost and incremental cost-effectiveness ratios of (i) IFN-based new DAAs vs. TVR/BOC-based triple therapy; and (ii) IFN-based new DAAs initiation strategies, given that IFN-free regimens are imminent. The sustained virological response in F3-4/F0-2 was 71/89% with IFN-based new DAAs, 85/95% with IFN-free regimens, vs. 64/80% with TVR/BOC-based triple therapy. Serious adverse events leading to discontinuation were taken as: 0-0.6% with IFN-based new DAAs, 0% with IFN-free regimens, vs. 1-10% with TVR/BOC-based triple therapy. Costs were €60,000 for 12weeks of IFN-based new DAAs and two times higher for IFN-free regimens. RESULTS: Treatment with IFN-based new DAAs when fibrosis stage ⩾F2 is cost-effective compared to TVR/BOC-based triple therapy (€37,900/QALY gained), but not at F0-1 (€103,500/QALY gained). Awaiting the IFN-free regimens is more effective, except in F4 patients, but not cost-effective compared to IFN-based new DAAs. If we decrease the cost of IFN-free regimens close to that of IFN-based new DAAs, then awaiting the IFN-free regimen becomes cost-effective. CONCLUSIONS: Treatment with IFN-based new DAAs at stage ⩾F2 is both effective and cost-effective compared to TVR/BOC triple therapy. Awaiting IFN-free regimens and then treating regardless of fibrosis is more efficacious, except in F4 patients; however, the cost-effectiveness of this strategy is highly dependent on its cost.

Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt.

BACKGROUND: Data on HCV-related cirrhosis progression are scarce in developing countries in general, and in Egypt in particular. The objective of this study was to estimate the probability of death and transition between different health stages of HCV (compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma) for an Egyptian population of patients with HCV-related cirrhosis. METHODS: We used the "elicitation of expert opinions" method to obtain collective knowledge from a panel of 23 Egyptian experts (among whom 17 were hepatologists or gastroenterologists and 2 were infectiologists). The questionnaire was based on virtual medical cases and asked the experts to assess probability of death or probability of various cirrhosis complications. The design was a Delphi study: we attempted to obtain a consensus between experts via a series of questionnaires interspersed with group response feedback. RESULTS: We found substantial disparity between experts' answers, and no consensus was reached at the end of the process. Moreover, we obtained high death probability and high risk of hepatocellular carcinoma. The annual transition probability to death was estimated at between 10.1% and 61.5% and the annual probability of occurrence of hepatocellular carcinoma was estimated at between 16.8% and 58.9% (depending on age, gender, time spent in cirrhosis and cirrhosis severity). CONCLUSIONS: Our results show that eliciting expert opinions is not suited for determining the natural history of diseases due to practitioners' difficulties in evaluating quantities. Cognitive bias occurring during this type of study might explain our results.