Consensus recommendations for the treatment and management of patients with Fabry disease on migalastat: a modified Delphi study

Objective: Fabry disease is a progressive disorder caused by deficiency of the α-galactosidase A enzyme (α-Gal A), leading to multisystemic organ damage with heterogenous clinical presentation. The addition of the oral chaperone therapy migalastat to the available treatment options for Fabry disease is not yet universally reflected in all treatment guidelines. These consensus recommendations are intended to provide guidance for the treatment and monitoring of patients with Fabry disease receiving migalastat. Methods: A modified Delphi process was conducted to determine consensus on treatment decisions and monitoring of patients with Fabry disease receiving migalastat. The multidisciplinary panel comprised 14 expert physicians across nine specialties and two patients with Fabry disease. Two rounds of Delphi surveys were completed and recommendations on the use of biomarkers, multidisciplinary monitoring, and treatment decisions were generated based on statements that reached consensus. Results: The expert panel reached consensus agreement on 49 of 54 statements, including 16 that reached consensus in round 1. Statements that reached consensus agreement are summarized in recommendations for migalastat treatment and monitoring, including baseline and follow-up assessments and frequency. All patients with Fabry disease and an amenable mutation may initiate migalastat treatment if they have evidence of Fabry-related symptoms and/or organ involvement. Treatment decisions should include holistic assessment of the patient, considering clinical symptoms and organ involvement as well as patient-reported outcomes and patient preference. The reliability of α-Gal A and globotriaosylsphingosine as pharmacodynamic response biomarkers remains unclear. Conclusion: These recommendations build on previously published guidelines to highlight the importance of holistic, multidisciplinary monitoring for patients with Fabry disease receiving migalastat, in addition to shared decision-making regarding treatments and monitoring throughout the patient journey. (Figure presented.)

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma

Background & Aims: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. Methods: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). Results: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3–12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3–12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. Conclusions: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population

Screening for hepatitis B in chemotherapy patients: survey of current oncology practices

Hepatitis B virus (HBV) reactivation occurs in up to 78% of patients receiving cytotoxic chemotherapy for nonhepatic malignancies. Reactivation can lead to hepatic dysfunction, jaundice and fulminant hepatic failure. Current recommendations include screening patients at risk for HBV prior to immunosuppressive therapy and initiating antiviral prophylaxis in patients with chronic HBV. To investigate current practice among oncologists regarding HBV screening and antiviral prophylaxis in candidates for chemotherapy. A survey was sent to American Medical Association registered oncologists assessing demographics and HBV screening practices. Statistical analysis was performed using Fisher's exact test. In all, 265 responses were received. Office-based physicians were less likely to screen for HBV prior to chemotherapy (P 15 years, with no difference in screening practices between groups (P = N.S.). Responders screen for HBV as follows: never - 20%, only in the presence of abnormal liver biochemistries - 30%, risk factors or history of hepatitis - 38%. In patients with known HBV, 75% of oncologists refer to specialists, 7% initiate therapy, while 15% do not refer or initiate therapy, most of whom are in an office setting (P = 0.02). Twenty per cent of oncologists never screen for HBV prior to initiating chemotherapy. Office-based physicians were less likely to screen, treat or refer to a specialist prior to chemotherapy. Greater education regarding risk of HBV reactivation is needed for clinicians treating patients with immunosuppressive therapies

Antigens drive memory IgE responses in human allergy via the nasal mucosa.

Natural allergen contact induces an increase of IgE levels and sensitivity but the mechanisms underlying the allergen-specific memory responses are poorly understood. Furthermore, it has not been studied whether allergen exposure affects the molecular reactivity profiles in patients. The aim of this study was to analyze the influence of nasal allergen encounter on the molecular profile and magnitude of memory IgE responses and on systemic sensitivity. METHODS: We investigated allergen-specific IgE, IgG subclass and IgM responses to defined allergen molecules (grass pollen: Phl p 1, Phl p 2 and Phl p 5; birch pollen: Bet v 1 and Bet v 2) in allergic patients in response to natural as well as to controlled nasal and dermal allergen exposure. Changes in systemic sensitivity were monitored by skin prick testing and by basophil histamine release experiments. RESULTS: Respiratory antigen exposure boosted IgE levels to a pre-established profile of allergen molecules without inducing significant IgM responses or new IgE specificities in allergic individuals. The importance of the route of allergen contact is demonstrated by an increase of systemic IgE levels and sensitivity after nasal exposure. In vitro sensitisation of basophils with pre- and post-seasonal serum samples suggests an allergen-induced elevation of specific IgE as a cause for the increased allergen-specific sensitivity. CONCLUSION: The characteristics of the allergen-driven antibody responses indicate a direct activation of an established pool of IgE memory cells with defined specificities as an underlying mechanism. Our finding that nasal allergen contact is a major factor for the boosting of memory IgE and systemic sensitivity may open new therapeutic possibilities

Palliative Care and Health Care Utilization for Patients With End-Stage Liver Disease at the End of Life

Background & aimsThere has been increased attention on ways to improve the quality of end-of-life care for patients with end-stage liver disease; however, there have been few reports of care experiences for patients during terminal hospitalizations. We analyzed data from a large national database to increase our understanding of palliative care for and health care utilization by patients with end-stage liver disease.MethodsWe performed a cross-sectional, observational study to examine terminal hospitalizations of adults with decompensated cirrhosis using data from the National Inpatient Sample from 2009 through 2013. We collected data on palliative care consultation and total hospital costs, and performed multivariate regression analyses to identify factors associated with palliative care consultation. We also investigated whether consultation was associated with lower costs.ResultsAmong hospitalized adults with terminal decompensated cirrhosis, 30.3% received palliative care; the mean cost per hospitalization was $48,551 ±$1142. Palliative care consultation increased annually, and was provided to 18.0% of patients in 2009 and to 36.6% of patients in 2013 (P < .05). The mean cost for the terminal hospitalization did not increase significantly ($47,969 in 2009 to$48,956 in 2013, P = .77). African Americans, Hispanics, Asians, and liver transplant candidates were less likely to receive palliative care, whereas care in large urban teaching hospitals was associated with a higher odds of receiving consultation. Palliative care was associated with lower procedure burden-after adjusting for other factors, palliative care was associated with a cost reduction of $10,062.ConclusionsPalliative care consultation for patients with end-stage liver disease increased from 2009 through 2013. Palliative care consultation during terminal hospitalizations is associated with lower costs and procedure burden. Future research should evaluate timing and effects of palliative care on quality of end-of-life care in this population