Improvement in health‐related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study

Little is known about the health‐related quality of life (HRQoL) burden of haemophilia B. The aim of this study was to assess HRQoL burden of haemophilia B, the benefit of recombinant factor IX (rFIX) prophylaxis and the HRQoL benefit of achieving a zero annual bleed rate. Subjects receiving rFIX (BAX326) prophylaxis or on‐demand completed the SF‐36 survey. Baseline SF‐36 scores were compared to the general US population scores to understand the HRQoL burden. Changes in SF‐36 scores between baseline and follow‐up were tested using t‐tests. Subgroup analysis was conducted to examine SF‐36 change among subjects who switched to BAX326 prophylaxis. SF‐36 scores were also compared between those with zero bleeds and those who bled during the study. Compared to the US norms, subjects reported lower average scores in all physical and several mental HRQoL domains. At follow‐up, prophylaxis subjects reported statistically significant and clinically meaningful improvements in overall physical HRQoL, as measured by the Physical Component Score (PCS) (mean change 2.60, P = 0.019), Bodily Pain (BP) (3.45, P = 0.015) and Role Physical (RP) domains (3.47, P = 0.016). Subjects who switched to prophylaxis from intermittent prophylaxis or on‐demand experienced more pronounced improvements not only in the PCS (3.21, P = 0.014), BP (3.71, P = 0.026), RP (4.43, P = 0.008) but also in Vitality (3.71, P = 0.04), Social Functioning (5.06, P = 0.002) and General Health domains (3.40, P = 0.009). Subjects achieving zero bleeds reported lower BP (P = 0.038). Prophylaxis with BAX326 significantly improved HRQoL in patients with moderately severe or severe haemophilia B by reducing bleeds.     

Adherence to prophylaxis is associated with better outcomes in moderate and severe haemophilia: results of a patient survey

Severe haemophilia is associated with bleeding into joints and development of arthropathy. Prophylactic treatment with infusion of replacement clotting factor is known to prevent bleeding, preserve joint functioning and result in higher health‐related quality of life (HRQoL) than episodic treatment; however, adhering to standard prophylaxis schedules can be difficult, and little is known about the relationship between adherence to prophylactic treatment and outcomes. The aim of this study was to assess the relationship between self‐reported adherence to prophylaxis and health outcomes, including HRQoL and bleeding episodes. Adults with haemophilia (n = 55) and caregivers of children with haemophilia (n = 55) in Australia, Canada, and the United States completed an online questionnaire which included measures of HRQoL (SF‐12v2 for adults and SF‐10 for caregivers of children), self‐reported bleeding episodes, and the VERITAS‐Pro measure of adherence to prophylaxis in haemophilia. Regression analysis was used to test the association between VERITAS‐Pro total score and outcomes. Poorer adherence (higher VERITAS‐Pro scores) was associated with a greater number of self‐reported bleeding episodes in the past year among adults (p < 0.01), more days of work/school missed among paediatric patients (p < 0.01), and lower physical health status scores among paediatric patients (p < 0.05). This study highlights the benefits of adherence to prophylaxis among those with severe haemophilia and provides evidence for the utility of the VERITAS‐Pro by demonstrating a relationship between adherence and outcomes.     

Coping in adult patients with severe haemophilia

An adequate use of coping strategies could help patients to deal with disease‐related stress. The study aim was to explore coping behaviour in adult patients with severe haemophilia and its possible determinants. Coping was assessed through three basic dimensions (task‐oriented, emotion‐oriented and avoidance coping), using the short version of the Coping Inventory for Stressful Situations (CISS‐21). Patients' scores were compared with Dutch working men (N = 374), according to three categories: low use (<P25 of normal), average use (P25–P75) and high use (>P75). Determinants were measured using questionnaires on activities (Haemophilia Activities List), participation (Impact on Participation and Autonomy Questionnaire), physical functioning [physical component of the Dutch Arthritis Impact Measurement Scales‐2 (D‐AIMS2)] and socio‐psychological health (psychological component of the D‐AIMS2). In total, 86 adults with severe haemophilia (FVIII/IX<1%) were included. The median age was 38 years (range: 18–68) with 85% affected with haemophilia A and 75% using prophylaxis. Patients with haemophilia used task‐oriented coping as frequently as the control group (P = 0.13); but used significantly less emotion‐oriented coping (57% vs. 25%, P < 0.05) and avoidance coping (P < 0.05). Emotion‐oriented coping showed a strong correlation with socio‐psychological health (r = 0.67) and weak correlations with participation (r = 0.32) and social interaction (r = 0.29). Other associations of coping strategies with patient characteristics of health status could not be demonstrated. Overall, patients predominantly used the task‐oriented approach to deal with their disease; the use of this strategy was comparable to the control group. Having a poor psychological health, less social interaction and/or less participation in daily life was associated with an increased use of emotion‐oriented coping.     

Magnetic resonance imaging and ultrasound evaluation of “healthy” joints in young subjects with severe haemophilia A

Magnetic resonance imaging (MRI) and ultrasonography (US) are increasingly used in haemophilia A (HA) to detect early joint changes. A total of 40 clinically asymptomatic joints, never involved by bleeding events [“healthy joints” (HJ)], were evaluated by MRI and, in parallel, by US in 20 young subjects with severe HA (22.45 ± 2.72 years old; no history of arthritides, of viral infections or of inhibitors against factor VIII). The same joints were evaluated in 20 matched non‐haemophilic (no‐HA) subjects (mean age 23.90 ± 2.31 years, P = 0.078 vs. HA subjects). US images were obtained with specific probe positions according to validated procedures. A validated US score and progressive (P‐MRI) and additive (A‐MRI) MRI scores were employed for data collection and analysis. The US score was higher in HA than in no‐HA subjects (3.40 ± 1.72 vs. 0.80 ± 1.10, P < 0.001). Taking into account only moderate/severe alterations, joint effusion was found in 55% of HA and in 5% of no‐HA joints (P < 0.001); synovial hypertrophy was found in 20% of HA and in none of the no‐HA joints; cartilage erosion was found in 30% of HA and in none of no‐HA joints. MRI examinations confirmed these findings and the US score correlated with the A‐MRI (r = 0.732, P < 0.001) and with the P‐MRI (r = 0.598, P < 0.001) scores. MRI and US data significantly correlated as to effusion (r = 0.819, P = 0.002), synovial hypertrophy (r = 0.633, P = 0.036) and cartilage erosion (r = 0.734, P = 0.010). Despite inherent limitations, joint US examination identified subclinical abnormalities of HJ in young subjects with severe HA.     

A longitudinal study of family structure in Swedish persons with haemophilia

Haemophilia is an X‐linked inherited rare bleeding disorder affecting mainly men. The treatment consists of replacement therapy that has been associated with severe side effects, such as blood transmitted viral infections, but has markedly improved over the last decades. The aim of this study was to study family structure over time among Swedish persons with haemophilia (PWH), focusing on children, siblings and marital status. PWH A or B were identified from the haemophilia centres and the national Patient Registry. Each PWH was compared to five age‐ and gender‐matched controls. The national Multi‐Generation Registry was used to identify children and siblings. A total of 1365 children with a father suffering from haemophilia A or B and 1938 siblings of the PWH were identified. Having one or more children was significantly less common (P = 0.003) for PWH than for controls. Significantly lower rates of having a child were also found for the subgroups of persons suffering from severe haemophilia and those infected with HIV (P < 0.001). A higher proportion of PWH, with or without HIV and/or viral hepatitis had siblings compared to the controls (P < 0.001). However, the mean number of siblings was significantly lower for persons with severe haemophilia (P = 0.001). The number of marriages and divorces did not differ between PWH and controls. Our data indicate a negative impact of HIV and viral hepatitis on family structure for PWH despite the relatively good access to treatment in Sweden over the last few decades. This was particularly true for those with a severe form of haemophilia.     

Adherence to treatment in a Western European paediatric population with haemophilia: reliability and validity of the VERITAS‐Pro scale

Treatment adherence in haemophilia is strongly associated with quality of life and the cost–benefit of treatment. Therefore, it is important to quantify and monitor it. This study aimed to validate a translation of the VERITAS‐Pro cross‐culturally and analyse treatment adherence in a Dutch population of paediatric haemophilia patients. Children aged 1–18 years with haemophilia were included from three Haemophilia Treatment Centres, on prophylactic clotting factor replacement therapy for more than 1 year. Parents and adolescents were analysed separately. The adherence scale for prophylactic therapy (VERITAS‐Pro) was translated according to international guidelines. This instrument contains a total of six subscales (‘Time’, ‘Dose’, ‘Plan’, ‘Remember’, ‘Skip’ and ‘Communicate’) each with four items. Lower scores reflect higher adherence. Overall response rate was 85%, leading to a study population of 60 children. Mean age was 10 years (SD 4.1). Internal consistency reliability: Mean Cronbach's alphas were adequate (>0.70) for total score and the subscales ‘Skip’ and ‘Communicate’. Item‐own subscale correlations were stronger than most item‐other subscale correlations. Convergent validity: Total scores were higher for non‐adherent participants compared with adherent participants according to patient infusion logs (n = 48; P < 0.05). Test–retest correlations: Significant for all scales except ‘Dose’ (n = 58; P < 0.01). This study demonstrates applicability of VERITAS‐Pro outside the United States, as total score and most subscales effectively quantified treatment adherence in a Dutch paediatric population on prophylactic therapy. Non‐adherent respondents’ total scores were significantly higher, demonstrating the ability of VERITAS‐Pro to identify non‐adherent individuals.     

Incidence,mortality rates and causes of deaths in haemophilia patients in Sweden

Sweden has been a pioneer in the treatment of haemophilia, with the first concentrate available in the 1950s. Treatment has improved over the years to its current state‐of‐the art. The aim of the current study was to evaluate the long‐term outcome of haemophilia in terms of incidence, morbidity and mortality. Patients diagnosed with haemophilia A or B registered at the national haemophilia centres and/or the Patient Registry and born before 2009 and alive in 1968 were enrolled and linked to the Cause of Death‐, Migration‐ and Medical Birth registries. Five age‐ and sex‐matched controls were selected for each patient. A total of 1431 patients with haemophilia A or B were compared with 7150 controls. The 3‐year moving average incidence rate per 100 000 population varied between 21 and 36. The hazard ratio for all‐cause mortality compared with controls was 2.2, 95% CI: [1.8; 2.7], P < 0.001 for the entire group of patients and 1.7, 95% CI: [1.3; 2.2], P < 0.001 when patients with HIV and/or viral hepatitis were excluded. The corresponding figures for the severe haemophilia subgroup were 6.6, 95% CI: [4.5; 10.0], P < 0.001 and 8.2, 95% CI [3.2; 20.8], P < 0.001 respectively. The most common causes of death were related to malignancies and the haemostatic defect. People with haemophilia were 57% less likely to die from ischaemic heart disease than controls. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, despite relatively advantageous access to clotting factor concentrates.     

Influence of medical insurance schemes and charity assistance projects on regular prophylaxis treatment of the boys with severe haemophilia A in China

Objective

To explore the influence of medical insurance policy and charity assistance projects on the uptake and discontinuation of regular prophylaxis treatment in Chinese severe haemophilia A children.

Methodology

This retrospective study was conducted on children with severe haemophilia A, who received FVIII prophylaxis treatment at 12 haemophilia centres in China from 1 November 2007 to 31 May 2013.

Results

The average duration of prophylaxis treatment received by haemophilia children significantly increased from 16.7 weeks in 2008 to 32.8 weeks in 2012 (P < .001). The main reason for prophylaxis acceptance included dissatisfaction with previous “on‐demand” regimens, availability of improved local medical insurance policies and patient/family awareness of haemophilia. The main reason for subsequent discontinuation of prophylaxis was economic instability. The upper limit of insurance was up to RMB 150 000/y (~USD: 22 000/y) for 80.1% of the insured patients and would be sufficient to cover the continuous low‐dose prophylaxis regimen. However, for many patients the burden of out‐of‐pocket copayment cost represented a risk for poor adherence to regular prophylaxis. In about two third of the patients, the annual out‐of‐pocket copayment cost amounted to >50% of their average annual disposable income. Many patients therefore required assistance from the charity assistance projects, but nonadherence remained prevalent.

Conclusion

Medical insurance policy and charity assistance projects helped haemophilia children to accept and continue prophylaxis regimens. It was the proportion of the out‐of‐pocket copayment cost rather than the upper limit of insurance reimbursement that restricted long‐term regular low‐dose prophylaxis in China.     

Progression of haemophilic arthropathy in children: a Lithuanian – Danish comparative study

Recurrent bleeding into joints initiates a sequence of events leading to a progressive joint damage in people with severe haemophilia. This is a continuous process during childhood and adolescence, therefore joint abnormalities may be minimal on physical examination in very young children – even those receiving on‐demand treatment. The aim of our study was to quantify the burden of arthropathy in Lithuanian patients who had been treated exclusively by on‐demand substitution and compare their physical joint health with age‐matched Danish patients who received prophylaxis from an early age. Boys, aged 4–17 years, with severe haemophilia and no signs of inhibitors were included in the study. Joint outcome based on the Haemophilia Joint Health Score (HJHS) was analysed in two different treatment groups and compared within the matched pairs. In total, 32 (16 in each treatment group) patients were enroled. A total of 192 joints were evaluated. Joint status according to treatment strategy was strikingly different: 27.4 for on‐demand vs. 3.3 for prophylaxis (<0.001) group. Significance of the difference in joint status comparing different treatment strategies was equally strong both in younger (4–9 years) and older (10–17 years) patient groups: 2.2 vs. 12.5 (P = 0.0002) and 3.9 vs. 36.3 (P < 0.0001) respectively. The results further demonstrate the unequivocal effect of prophylaxis on joint status and give an insight into early and late manifestations of joint impairment based on the HJHS in haemophilia patients with treatment on‐demand compared with joint changes that may develop over the time with the preventative treatment.     

Cardiovascular comorbidities are increased in US patients with haemophilia A: a retrospective database analysis

There is conflicting evidence in the literature on whether individuals with haemophilia in the USA have greater, reduced, or similar risks for cardiovascular disease as the general population. This study evaluated the prevalence of cardiovascular comorbidities among USA males with haemophilia A, relative to an unaffected general male population with similar characteristics. Males with haemophilia A and continuous insurance coverage were identified by ICD‐9‐CM code 286.0 (1 January 2007–31 December 2009) using the MarketScan^® Commercial and Medicare Research Databases. Individuals with haemophilia A were exact matched 1:3 with males without a diagnosis of haemophilia A. The prevalence of cardiovascular comorbidities identified by ICD‐9‐CM code was determined for matched cohorts. Of the study population, 2506 were grouped in the haemophilia A cohort and 7518 in the general cohort. Proportions of individuals with haemorrhagic stroke (2.0% vs. 0.5%, P < 0.001), ischemic stroke (4.7% vs. 2.7%, P < 0.001), coronary artery disease (10.7% vs. 5.8%, P < 0.001), myocardial infarction (0.8% vs. 0.3%, P = 0.003), hypertension (22.6% vs. 15.5%, P < 0.001), hyperlipidaemia (15.9% vs. 11.9%, P < 0.001), arterial thrombosis (12.1% vs. 5.9%, P < 0.001), and venous thrombosis (4.4% vs. 1.1%, P < 0.001) were significantly greater for the haemophilia A cohort. Results were consistent across most age groups, and comorbidities appeared at an earlier age in those with haemophilia A than in the general population. Among the USA haemophilia A population cardiovascular comorbidities are more prevalent and they appear earlier in life in comparison to the general male population, suggesting the need for earlier, enhanced screening for age‐related comorbidities in the haemophilia community.     

A Model Program of Community‐Based Supports for Older Adults at Risk of Nursing Facility Placement

Transitioning an older adult into a nursing facility is a major life event for older adults (care recipients, CRs) and their family caregivers (CGs). This article describes the implementation of a community living program and presents findings on important health and well‐being indicators. One hundred ninety‐one participants aged 60 and older not eligible for or currently enrolled in Medicaid and meeting four risk domains (functional, health, cognitive/emotional, informal support system) were enrolled for the 10‐month program. Two evidence‐based interventions were blended into a comprehensive community‐based approach to long‐term care that included $750 per month for home care services. Measures were conducted at baseline and 6 and 12 months. Nine (6%) participants did not complete the program because of nursing facility admission. CRs had fewer physician visits (4.1 vs 7.3, P < .001), emergency department visits (0.3 vs 1.4, P < .001), hospital stays (0.4 vs 0.9, P < .001), and total nights in the hospital (0.8 vs 5.1, P < .001) at 12 months than at baseline. Center for Epidemiologic Studies Depression Scale (CES‐D) scores also improved significantly (6.8 vs 9.4, P < .001). CGs had improvements in CES‐D scores (5.9 vs 3.9, P < .001) and CG burden (14.7 s 12.6, P = .01) from baseline to 12 months. This multicomponent program improved the physical and mental health of CGs and CRs at risk of nursing facility placement. Future studies are needed to compare the overall placement rate to determine the success of diverting nursing facility placement in this population of older adults.     

Burden of illness and costs among paediatric haemophilia patients with and without central venous access devices treated in US hospitals

Introduction

Central venous access devices (CVADs) facilitate repeated or urgent treatments for paediatric haemophilia patients, but are associated with complications. This study examined the burden of illness, healthcare utilization and costs for CVADs in a real‐world hospital setting.

Materials and Methods

This study included haemophilia patients ages ≤18 years with discharges during 2006‐2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD‐9 diagnosis codes and CVAD exposure using billing information. After matching haemophilia patients with and without CVADs on demographic and clinical characteristics, we compared infection, thrombosis, length of stay (LOS), inflation‐adjusted hospital cost (2014 $USD) and readmission outcomes using generalized estimating equation models adjusted for hospital teaching status.

Results

Among 4793 paediatric haemophilia patients treated at one of 548 hospitals, a total of 197 patients were identified with CVAD exposure. The matched sample included 310 haemophilia patients (155 CVAD and 155 non‐CVAD). CVAD cases had greater frequencies of all‐cause infections (29% vs 17%, P = .01) and thrombosis (6% vs 1%, P = .06), longer adjusted mean LOS (9.5 vs 4.7 days, P = .002), higher adjusted mean inpatient total hospitalization costs ($47200 vs $25389, P = .02) as well as more inpatient and outpatient visits at 30‐, 60‐ and 90‐days (P < .05 for all differences) compared with non‐CVAD patients.

Conclusion

Paediatric haemophilia patients with CVADs experienced greater infection rates, healthcare utilization and higher hospitalization costs compared with non‐CVAD patients. The results of this study may inform further research efforts to understand the costs and benefits of novel treatment alternatives for young haemophilia patients requiring CVADs.     

Outcome of Down syndrome associated acute lymphoblastic leukaemia treated on a contemporary protocol

We report the outcome for children and young people with Down syndrome‐associated acute lymphoblastic leukaemia (DS‐ALL) treated on a contemporary protocol. Compared with non‐DS ALL, patients with DS‐ALL had an inferior event‐free survival (65·6% vs. 87·7% at 5 years; P < 0·00005) and overall survival (70·0% vs. 92·2%; P < 0·00005). Excess treatment‐related mortality – was primarily responsible for the worse outcomes for DS‐ALL (21·6% at 5 years, vs. 3·3%, P < 0·00005). Minimal residual disease (MRD) risk status was highly discriminant for relapse in DS patients with 0/28 relapses in the MRD low risk group.     

Pan‐cancer genomic analyses reveal prognostic and immunogenic features of the tumor melatonergic microenvironment across 14 solid cancer types

We performed comprehensive genomic analyses of the melatonergic system within the tumor microenvironment and their clinical relevance across a broad spectrum of solid tumors. RNA‐seq data from The Cancer Genome Atlas (TCGA) of 14 solid tumors representing 6658 human samples were analyzed. The tumor melatonergic system was characterized by the rates of melatonin synthesis and metabolism using a two‐gene expression model (melatonin synthesis/metabolism Index). We calculated three indexes according to different melatonin metabolism isoenzymes (Index‐I [ASMT:CYP1A1], Index‐II [ASMT:CYP1A2], and Index‐III [ASMT:CYP1B1]). Samples of each cancer type were classified into two subgroups (high vs low) based on median values. Clinical outcomes, mutational burden, and neoepitope abundance were analyzed and compared. We found that the ability of the tumor microenvironment to synthesize and accumulate melatonin varied across cancer types and negatively correlated with tumor burden. Kaplan‐Meier survival analyses and multivariable modeling showed that the three indexes played different roles across different cancers and harbored prognostic values in breast cancer (adjusted hazard ratio [AHR]_Index‐II = 0.65 [0.44‐0.97]; P = 0.03), cervical cancer (AHR_Index‐I = 0.62 [0.39‐0.98]; P = 0.04), lung squamous cell carcinoma (AHR_Index‐III = 0.75 [0.56‐0.99]; P = 0.04), melanoma (AHR_Index‐I = 0.74 [0.55‐0.98]; P = 0.04), and stomach adenocarcinoma (AHR_Index‐III = 0.68 [0.41‐0.94]; P = 0.02). We further investigated its clinical relevance with tumor immunogenic features (mutational burden and neoantigen abundance), which may predict immunotherapy benefits. We observed significant negative correlations with mutational burden in the majority of tumors (P < 0.05), except cervical cancer, pancreatic adenocarcinoma, and thyroid carcinoma. Our study provides a systematic overview of the oncostatic values of the melatonergic system and highlights the utilization of this simple and promising gene signature as a prognosticator and potential predictor of response to immunotherapy.     

A cross‐sectional study of bleeding phenotype in haemophilia A carriers

Haemophilia A carriers have historically been thought to exhibit normal haemostasis. However, recent data demonstrates that, despite normal factor VIII (FVIII), haemophilia A carriers demonstrate an increased bleeding tendency. We tested the hypothesis that obligate haemophilia carriers exhibit an increase in clinically relevant bleeding. A cross‐sectional study was performed comparing haemophilia A carriers to normal women. Questionnaire assessment included a general bleeding questionnaire, condensed MCMDM‐1VWD bleeding assessment tool and Pictorial Bleeding Assessment Chart (PBAC). Laboratory assessment included complete blood count, prothrombin time, activated partial thromboplastin time, fibrinogen activity, FVIII activity (FVIII:C), von Willebrand factor antigen level, ristocetin cofactor, platelet function analyser‐100^TM and ABO blood type. Forty‐four haemophilia A carriers and 43 controls were included. Demographic features were similar. Laboratory results demonstrated a statistically significant difference only in FVIII:C (82·5 vs. 134%, P < 0·001). Carriers reported a higher number of bleeding events, and both condensed MCMDM‐1 VWD bleeding scores (5 vs. 1, P < 0·001) and PBAC scores (423 vs. 182·5, P = 0·018) were significantly higher in carriers. Haemophilia A carriers exhibit increased bleeding symptoms when compared to normal women. Further studies are necessary to fully understand the bleeding phenotype in this population and optimize clinical management.     

Improved outcome for children with non‐high risk acute lymphoblastic leukaemia after using an ALL IC‐BFM 2002‐based protocol in Shanghai,China

We report the outcome of 92 non‐high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin‐Frankfürt‐Münster (BFM) Intercontinental ALL ‐based protocol. Compared with a matched historical control group, we found a lower incidence of treatment‐related early death (1·2% vs. 10·9%, P = 0·015), a higher 6‐year event‐free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in‐hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in‐hospital days (164 vs. 296, P < 0·001). This ALL‐BFM based protocol was quite tolerable in our institution and will be extended to high‐risk patients.     

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa

The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)‐infected patients. Whether this mutation affects the therapeutic course of HIV‐HBV co‐infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)‐naïve HIV‐HBV co‐infected patients from Côte d'Ivoire, initiating ARV‐treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV‐DNA, hepatitis B “e” antigen (HBeAg) seroclearance (in HBeAg‐positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV‐initiation, median HBV‐DNA was 6.04 log₁₀ copies/mL (IQR = 3.70‐7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg‐negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24‐36). Cumulative proportion of undetectable HBV‐DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV‐DNA levels and anti‐HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti‐HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.     

Increased cancer risk in patients with haemophilia A: a nationwide population‐based 14‐year study in Taiwan

Haemostasis is associated with the development and dissemination of cancer. Whether cancer incidence is increased in haemophiliacs remains uncertain; thus, we aimed to further examine this issue. By using data from the National Health Insurance Research Database in Taiwan, we obtained a cohort of 683 patients with haemophilia A, and compared the incidence rate ratio (IRR) of cancer in this cohort with an age‐ and sex‐matched control of 6830 patients. The log‐rank test was used to compare Kaplan–Meier curve of the cumulative cancer incidence between two cohorts. Cox regressions were used to identify independent risk factors of cancer in the study patients. The cancer incidence of patients with haemophilia A was significantly higher compared to the control group (IRR 1.95, 95% CI 1.18–3.09, P = 0.008) during the 14‐year follow‐up period. The non‐lymphoma and non‐liver cancer incidence in the haemophilia A cohort remained higher than that of the matched control (P = 0.050 by the log‐rank test). The multivariate Cox proportional hazards analysis indicated that age (per year, HR 1.09, 95% CI 1.06–1.12, P < 0.001) was the only significant risk factor for cancer development in haemophilia patients. Patients with haemophilia A had higher cancer incidence than the age‐ and sex‐matched patients, especially for the elderly. With increasing life expectancy for haemophiliacs, physicians should be aware of their cancer development.