Cost effectiveness of screening immigrants for hepatitis B

Background: The prevalence of chronic hepatitis B (CHB) infection among the immigrants of North America ranges from 2 to 15%, among whom 40% develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants. Aims: The objective of this study is to estimate the health and economic effects of screening strategies for CHB among immigrants. Methods: We used the Markov model to examine the cost‐effectiveness of three screening strategies: (i) ‘No screening’; (ii) ‘Screen and Treat’ and (iii) ‘Screen, Treat and Vaccinate’ for 20–65 years old individuals who were born abroad but are currently living in Canada. Model data were obtained from the published literature. We measured predicted hepatitis B virus (HBV)‐related deaths, costs (2008 Canadian Dollars), quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratio (ICER). Results: Our results show that screening all immigrants will prevent 59 HBV‐related deaths per 10 000 persons screened over the lifetime of the cohort. Screening was associated with an increase in quality‐adjusted life expectancy (0.024 QALYs) and cost ($1665) per person with an ICER of $69 209/QALY gained compared with ‘No screening’. The ‘Screen, Treat and Vaccinate’ costs an additional $81, generates an additional 0.000022 QALYs per person, with an ICER of $3 648 123/QALY compared with the ‘Screen and Treat’. Sensitivity analyses suggested that the ‘Screen and Treat’ is likely to be moderately cost‐effective. Conclusion: We show that a selective hepatitis B screening programme targeted at all immigrants in Canada is likely to be moderately cost‐effective. Identification of silent CHB infection with the offer of treatment when appropriate can extend the lives of immigrants at reasonable cost.     

Disease burden of chronic hepatitis B among immigrants in Canada

BACKGROUND:

The prevalence of chronic hepatitis B (CHB) infection among immigrants to North America ranges from 2% to 15%, 40% of whom develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants.

OBJECTIVE:

To estimate the disease burden of CHB among immigrants in Canada using Markov cohort models comparing a cohort of immigrants with CHB versus a control cohort of immigrants without CHB.

METHODS:

Markov cohort models were used to estimate life years, quality-adjusted life years and lifetime direct medical costs (adjusted to 2008 Canadian dollars) for a cohort of immigrants with CHB living in Canada in 2006, and an age-matched control cohort of immigrants without CHB living in Canada in 2006. Parameter values were derived from the published literature.

RESULTS:

At the baseline estimate, the model suggested that the cohort of immigrants with CHB lost an average of 4.6 life years (corresponding to 1.5 quality-adjusted life years), had an increased average of $24,249 for lifetime direct medical costs, and had a higher lifetime risk for decompensated cirrhosis (12%), hepatocellular carcinoma (16%) and need for liver transplant (5%) when compared with the control cohort.

DISCUSSION:

Results of the present study showed that the socio-economic burden of CHB among immigrants living in Canada is sub-stantial. Governments and health systems need to develop policies that promote early recognition of CHB and raise public awareness regarding hepatitis B to extend the lives of infected immigrants.     

Effectiveness and cost‐effectiveness of interventions targeting harm reduction and chronic hepatitis C cascade of care in people who inject drugs: The case of France

Direct‐acting antivirals (DAAs) represent an opportunity to improve hepatitis C virus (HCV) care cascade. This combined with improved harm reduction interventions may lead to HCV elimination especially in people who inject drugs (PWID). We assessed the effectiveness/cost‐effectiveness of improvements in harm reduction and chronic hepatitis C (CHC) care cascade in PWID in France. We used a dynamic model of HCV transmission and CHC natural history and evaluated the following: improved needle/syringe programmes‐opioid substitution therapies, faster diagnosis/linkage to care, earlier treatment initiation, alone and in combination among active PWID (mean age = 36). Outcomes were as follows: life expectancy in discounted quality‐adjusted life years (QALYs); direct lifetime discounted costs; incremental cost‐effectiveness ratio (ICER); number of infections/reinfections. Under the current practice, life expectancy was 15.846 QALYs, for a mean lifetime cost of €20 762. Treatment initiation at F0 fibrosis stage alone was less effective and more costly than faster diagnosis/linkage to care combined with treatment initiation at F0, which increased life expectancy to 16.694 QALYs, decreased new infections by 37%, with a ICER = €5300/QALY. Combining these interventions with harm reduction improvements was the most effective scenario (life expectancy = 16.701 QALYs, 41% decrease in new infections) but was not cost‐effective (ICER = €105 600/QALY); it became cost‐effective with higher initial HCV incidence rates and lower harm reduction coverage than in our base‐case scenario. This study illustrated the high effectiveness, and cost‐effectiveness, of a faster diagnosis/linkage to care together with treatment from F0 with DAAs. This “Test and treat” strategy should play a central role both in improving the life expectancies of HCV‐infected patients, and in reducing HCV transmission.     

Cost‐effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis

To evaluate the cost‐effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment‐naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0‐F1) versus advanced fibrosis (F2‐F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality‐adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0‐F1 compared with F2‐F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real‐world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0‐F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2‐F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0‐F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver‐related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2‐F4 patients. In CHC treatment‐naïve GT1 patients, starting treatment with LDV/SOF in patients with F0‐F1 compared to those with F2‐F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.     

Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan

Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision‐analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state‐transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all‐oral direct‐acting anti‐virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan‐specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality‐adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness‐to‐pay threshold of ¥4‐to‐¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment‐related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness‐to‐pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness‐to‐pay thresholds. In conclusion treatment of HCV GT1b with all‐oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.     

Higher risk of hepatocellular carcinoma in chronic hepatitis B vs chronic hepatitis C after achievement of virologic response

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg‐interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow‐up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30‐3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg‐interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.     

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.     

The economics of treating chronic hepatitis C patients with peginterferon alpha-2a (40 kDa) plus ribavirin presenting with persistently normal aminotransferase

Peginterferon alpha-2a (40 kDa) plus ribavirin is effective at achieving sustained viral response compared with no treatment in patients with chronic hepatitis C (CHC) and persistently normal aminotransferase levels (PNALT). The cost-effectiveness of treating CHC in the setting of PNALT has not been assessed. Disease progression in patients with PNALT was simulated in a Markov model. The rate of fibrosis progression, quality of life and costs for each health state were based on literature estimates. The perspective of the Italian National Health Service was adopted and costs (euro 2003) and benefits were discounted at 3%. Sensitivity analyses were performed on important parameters. The primary analysis compared combination therapy with peginterferon alpha-2a (40 kDa) plus ribavirin to no treatment in a cohort of patients with mean age 45 years, and was based on findings from a multinational, randomized trial in patients with PNALT. In genotype 1 patients, the risk of cirrhosis at 30 years is forecast to fall from 32% with no treatment to 19% with combination therapy, increasing quality-adjusted life years (QALYs) by 0.74 years at an incremental cost per QALY gained of euro 16,831. The 30-year risk of cirrhosis in genotype 2 or 3 is projected to fall to 9% with combination therapy, an increase in QALYs of 1.34 years, at an incremental cost per QALY gained of euro 3,000. Thus treatment of PNALT with peginterferon alpha-2a (40 kDa) plus ribavirin is projected to reduce the incidence of cirrhosis, increase life expectancy and have an acceptable cost-effectiveness ratio from a societal perspective.     

Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all‐cause mortality and HCC in CHC patients with SVR following direct‐acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow‐up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all‐cause mortality and HCC at 2 years of follow‐up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5‐fold increased risk of all‐cause mortality and HCC (HR 7.51, 95% C.I 3.61‐13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97‐6.59, P = 0.06). In conclusion, LS is a major predictor of all‐cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.     

Cirrhosis,high age and high body mass index are risk factors for persisting advanced fibrosis after sustained virological response in chronic hepatitis C

We aimed to assess fibrosis with liver stiffness measurement long‐term after sustained virological response of chronic hepatitis C and to identify risk factors associated with persisting fibrosis. In this cross‐sectional study, patients with chronic hepatitis C and pretreatment advanced fibrosis or cirrhosis treated successfully at Karolinska University Hospital with an interferon‐containing regimen underwent liver stiffness measurement with FibroScan. The impact of potential risk factors for persisting fibrosis was estimated. We included 269 patients with a median follow‐up time of 7.7 years (range 0‐20), 84 with a follow‐up time of ≥10 years. Patients with pretreatment cirrhosis had a significantly higher median liver stiffness level (8.5 kPa 95% CI 7‐9.1) at follow‐up, than patients with advanced fibrosis (6 kPa 95% CI 5.5‐6.4). A majority improved their fibrosis stage after sustained virological response, but 24% had persisting advanced fibrosis with a liver stiffness level of ≥ 9.5 kPa. Among patients with pretreatment cirrhosis, the proportion with persisting advanced fibrosis diminished with longer follow‐up time, from 48% after <5 years to 21% after >10 years. The main risk factors for persisting advanced fibrosis were pretreatment cirrhosis, high age and body mass index. In conclusion, fibrosis improves substantially during long‐term follow‐up after sustained virological response in hepatitis C patients with pretreatment advanced liver fibrosis. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis should therefore be recommended to avoid persistence of advanced fibrosis after virological cure.     

The validity of serum markers for fibrosis staging in chronic hepatitis B and C

Assessment of liver fibrosis is critical for successful individualized disease management in persons with chronic hepatitis B (CHB) or chronic hepatitis C (CHC). We expanded and validated serum marker indices to provide accurate, reproducible and easily applied methods of fibrosis assessment. Liver biopsy results from over 284 CHB and 2304 CHC patients in the Chronic Hepatitis Cohort Study (‘CHeCS') were mapped to a F0–F4 equivalent scale. APRI and FIB‐4 scores within a 6‐month window of biopsy were mapped to the same scale. A novel algorithm was applied to derive and validate optimal cut‐offs for differentiating fibrosis levels. For the prediction of advanced fibrosis and cirrhosis, the FIB‐4 score outperformed the other serum marker indices in the CHC cohort and was similar to APRI in the CHB cohort. The area under the receiver operating characteristic curves (AUROC) for FIB‐4 in differentiating F3–F4 from F0–F2 was 0.86 (95% CI: 0.80–0.92) for CHB and 0.83 (95% CI: 0.81–0.85) for CHC. The suggested cut‐offs based on FIB‐4 model produced high positive predictive values [CHB: 90.0% for F0–F2, 100.0% for cirrhosis (F4); CHC: 89.7% for F0–F2; 82.9% for cirrhosis (F4)]. In this large observational cohort, FIB‐4 predicted the upper and lower end of liver fibrosis stage (cirrhosis and F0–F2, respectively) with a high degree of accuracy in both CHB and CHC patients.     

The number needed to treat to prevent mortality and cirrhosis‐related complications among patients with cirrhosis and HCV genotype 1 infection

Cirrhotic patients with chronic hepatitis C virus (HCV) infection remain at risk for complications following sustained virological response (SVR). Therefore, we aimed to evaluate treatment efficacy with the number needed to treat (NNT) to prevent clinical endpoints. Mortality and cirrhosis‐related morbidity were assessed in an international multicentre cohort of consecutively treated patients with HCV genotype 1 infection and cirrhosis. The NNT to prevent death or clinical disease progression (any cirrhosis‐related event or death) in one patient was determined with the adjusted (event‐free) survival among patients without SVR and adjusted hazard ratio of SVR. Overall, 248 patients were followed for a median of 8.3 (IQR 6.2–11.1) years. Fifty‐nine (24%) patients attained SVR. Among patients without SVR, the adjusted 5‐year survival and event‐free survival were 94.4% and 80.0%, respectively. SVR was associated with reduced all‐cause mortality (HR 0.15, 95% CI 0.05–0.48, P = 0.002) and clinical disease progression (HR 0.16, 95% CI 0.07–0.36, P < 0.001). The NNT to prevent one death in 5 years declined from 1052 (95% CI 937–1755) at 2% SVR (interferon monotherapy) to 61 (95% CI 54–101) at 35% SVR (peginterferon and ribavirin). At 50% SVR, which might be expected with triple therapy, the estimated NNT was 43 (95% CI 38–71). The NNT to prevent clinical disease progression in one patient in 5 years was 302 (95% CI 271–407), 18 (95% CI 16–24) and 13 (95% CI 11–17) at 2%, 35% and 50% SVR, respectively. In conclusion, the NNT to prevent clinical endpoints among cirrhotic patients with HCV genotype 1 has declined enormously with the improvement of antiviral therapy.     

Lifestyle changes and beliefs regarding disease severity in patients with chronic hepatitis C

The aim of this prospective study was to investigate beliefs regarding disease severity and lifestyle changes following hepatitis C diagnosis in patients with chronic hepatitis C (CHC). One hundred and eighty-five consecutive CHC patients were interviewed by means of self-questionnaires exploring several aspects of their disease. Most patients (93%) identified cirrhosis and liver cancer as the two main complications of CHC. More than half of patients (59%) thought that CHC was always associated with a fatal outcome whereas 3% thought that they would stay healthy. HCV viral load was the most commonly reported factor associated with disease severity. Sex life changes were reported by 107 patients (58%) whereas dietary intake changes were reported by 88 patients (48%). In multivariate analysis, changes in sex life were associated with male gender [odds ratio (OR): 2.57, 95% CI: 1.30-5.08, P < 0.007], perceived disease severity (OR: 1.02, 95% CI: 1.00-1.03, P < 0.03) and anxiety (OR: 1.05, 95% CI: 1.01-1.08, P < 0.003), whereas changes in dietary intake were associated with age (OR: 1.04, 95% CI: 1.02-1.08, P < 0.003) and anxiety (OR: 1.04, 95% CI: 1.01-1.08, P < 0.006). Our results show the considerable impact of CHC diagnosis on patients' lifestyle. They emphasize the need for improving CHC patient counselling in order to avoid unnecessary sex life and dietary intake changes.     

Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg‐positive high viral load chronic hepatitis B

The treatment option in chronic hepatitis B (CHB) patients with persistent low‐level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)‐positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg‐positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03‐19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24‐9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04‐3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41‐4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.     

Long‐term clearance of hepatitis C virus following interferon α‐2b or peginterferon α‐2b,alone or in combination with ribavirin

Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG‐IFN) α‐2b or IFN α‐2b. We conducted two phase 3b long‐term follow‐up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α‐2b and/or PEG‐IFN α‐2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow‐up studies. In total, 636 patients with SVR following treatment with IFN α‐2b and 366 with SVR following treatment with PEG‐IFN α‐2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α‐2b and three patients treated with PEG‐IFN α‐2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1–99.7%] for IFN α‐2b and 99.4% (95% CI, 97.7–99.9%) for PEG‐IFN α‐2b. Successful treatment of hepatitis C with PEG‐IFN α‐2b or IFN α‐2b leads to clinical cure of hepatitis C in the vast majority of cases.     

Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir

This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65 426 infected patients receiving entecavir or tenofovir for at least 3 months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end‐stage renal failure or a diagnosis of HCC within 3 months of starting treatment. Eligible patients (N = 27 820) were followed until HCC occurrence, completion of the allowed 3‐year regimen or 31 December 2013. During a median follow‐up of 25.1 (12.1‐35.6) months, 802 patients developed HCC, with 1‐, 2‐ and 3‐year cumulative incidence of 1.82% (95% CI, 1.66‐1.99%), 3.05% (95% CI, 2.82‐3.28%) and 4.06% (95% CI, 3.77‐4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66‐0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00‐16.90 in age <40 years; 4.69; 95% CI, 3.94‐5.59 in age ≧40 years), age (IRR, 3.38; 95% CI, 2.10‐5.47 for 40‐50 years; 6.92; 95% CI, 4.27‐11.21 for 50‐60 years; 12.50; 95% CI, 7.71‐20.25 for ≧60 years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44‐2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02‐1.58) and diabetes (IRR, 1.24; 95% CI, 1.05‐1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.     

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1–infected patients who do or do not achieve sustained virological response to therapy

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost‐effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium‐term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS ‘Payment by Results’ database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non‐SVR) with mean follow‐up of 3.5 (SVR) and 4.9 (non‐SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non‐SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5‐year post‐treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13‐fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56‐fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real‐life data for future cost‐effectiveness analyses related to the treatment for chronic HCV infection.     

Long‐term morbidity and mortality in a Canadian post‐transfusion hepatitis C cohort: Over 15 years of follow‐up

The Federal Government of Canada established a $1.1 billion compensation programme in 1999 to support individuals who acquired hepatitis C virus (HCV) through blood products between January 1986 and July 1990. We aimed to describe the morbidity and mortality of this unique post‐transfusion cohort (n = 4550) followed for over 15 years from 2000 to 2016. The age‐standardized mortality rates were compared with that of the Canadian general population and HCV cohorts from other countries. We evaluated all‐cause mortality using Kaplan‐Meier survival curves and HCV‐related and unrelated mortality using competing risk models. The age‐standardized all‐cause and HCV‐related mortality rates per 10 000 person‐years were 127 (95% CI: 117‐138) and 76 (95% CI: 69‐85) for males, and 77 (95% CI: 69‐87) and 43 (95% CI: 37‐51) for females, respectively. The risk of death of the post‐transfusion cohort was almost twice as high as the Canadian general population (rate ratio = 1.8; 95% CI: 1.7‐1.9). All‐cause, HCV‐related and HCV‐unrelated mortality were 20%, 12% and 8%, respectively at 15 years of follow‐up. By comparison, HCV‐related mortality rates per 10 000 person‐years for population‐based HCV cohorts varied from 18 and 11 in Australia to 65 and 43 in Scotland for males and females, respectively. We reported long‐term follow‐up data for the largest post‐transfusion cohort in the literature. The all‐cause mortality rates were markedly higher than that of the Canadian general population. We also showed that HCV‐related mortality were greater compared to other HCV cohorts. This suggests that continued efforts to identify and treat post‐transfusion HCV are warranted.     

Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network

Background

Consideration of cost determinants is crucial to inform delivery of public vaccination programs.

Objectives

To estimate the average total cost of laboratory‐confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs.

Methods

Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory‐confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions.

Results

Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post‐discharge, including readmission within 30 days.

Conclusion

The cost of laboratory‐confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory‐confirmed influenza cases. The true per‐patient cost of influenza‐related hospitalization has been underestimated, and prevention programs should be evaluated in this context.     

The systemic lupus erythematosus Tri‐Nation study: Cumulative indirect costs

Objective

We previously reported that patients with systemic lupus erythematosus (SLE) in the US incurred ～19% and 12% higher direct medical costs than patients in Canada and the UK, respectively, without experiencing superior outcomes expressed as disease damage or quality of life. In the present study, we compared cumulative indirect costs over 4 years in these patients.

Methods

A total of 715 patients with SLE (269 US, 231 Canada, 215 UK) were surveyed semiannually for 4 years on employment status and time lost from labor and nonlabor market activities. Cross‐country comparisons of indirect costs were performed.

Results

In the US, Canada, and the UK, mean 4‐year cumulative indirect costs (95% confidence interval [95% CI]) due to diminished labor market activity were $56,745 ($49,919, $63,571), $38,642 ($32,785, $44,500), and $42,213 ($35,859, $48,567), respectively, and cumulative indirect costs due to diminished nonlabor market activity were $5,249 ($2,766, $7,732), $5,455 ($3,290, $7,620), and $8,572 ($5,626, $11,518), respectively. Regression results showed that cumulative indirect costs (95% CI) due to diminished labor market activity in the US were $6,750 ($580, $12,910) greater than in Canada and $10,430 ($4,050, $16,800) greater than in the UK. Indirect costs due to diminished nonlabor market activity in the US were $280 (?$2,950, $3,520) less than in Canada and $2,010 (?$1,490, $5,510) less than in the UK, both results insignificant due to wide CIs.

Conclusion

Despite American patients incurring greater direct medical costs than Canadian and British patients, they do not experience superior health outcomes in terms of less productivity loss in either labor market or nonlabor market activities.