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Uma Ramaswami,1 Michael Beck,2 Derralynn Hughes,1 Christoph Kampmann,2 Jaco Botha,3 Guillem Pintos-Morell,4 Michael L West,5 Dau-Ming Niu,6 Kathy Nicholls,7,8 Roberto Giugliani9 On behalf of the FOS Study Group 1Royal Free London NHS Foundation Trust, Lysosomal Disorders Unit, Institute of Immunity and Transplantation, London, UK; 2Centre for Paediatric and Adolescent Medicine, University Medical Centre, University of Mainz, Mainz, Germany; 3Department of Biostatistics and Programming, Takeda, Zug, Switzerland; 4Centre for Rare Diseases, University Hospital Vall d’Hebron, Barcelona, CIBERER-GCV08_IGTP Research Institute and Teaching Unit Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain; 5Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; 6Department of Paediatrics, Taipei Veterans General Hospital, Taipei, Taiwan; 7Department of Nephrology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia; 8Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia; 9Medical Genetics Service HCPA, Department of Genetics, UFRGS, and INAGEMP, Porto Alegre, BrazilCorrespondence: Uma RamaswamiLysosomal Disorders Unit, Institute of Immunity and Transplantation, 2nd Floor, Royal Free Hospital, Pond Street, London NW3 2QG, UKTel +44 207 794 0500 Ext 22492Fax +44 207 317 7665Email uma.ramaswami@nhs.netPurpose: Following the publication of 5-year agalsidase alfa enzyme replacement therapy (ERT) outcomes data from the Fabry Outcome Survey (FOS), 10-year data were analyzed.Patients and methods: FOS (ClinicalTrials.gov identifier: NCT03289065) data (April 2001 to August 2018) were retrospectively analyzed. Estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) were analyzed after treatment start (baseline) for patients with ≥3 measurements, including baseline and year 10.Results: Median (range) age (years) of the evaluable treated renal cohort at treatment start was 48.8 (17.9–67.3) for females (n=62), 34.4 (18.0–66.8) for males (n=90). With eGFR ≥60 mL/min/1.73 m2 at baseline, mean (95% CI) rate of eGFR change (eGFR/year) over 10 years was relatively stable in females (n=52; −0.55 [−1.12, +0.01]) and slightly declined in males (n=79; −1.99 [−2.45, −1.54]). With impaired kidney function (eGFR 48 g/m2.7 in females, >50 g/m2.7 in males) at baseline, mean (95% CI) LVMI/year slightly increased over 10 years in females (n=18; +1.51 [+0.91, +2.12]) and males (n=14; +0.87 (+0.19, +1.55). Without LVH at baseline, mean (95% CI) LVMI/year was stable in females (n=16; +0.52 [−0.13, +1.17]) and males (n=21; +0.57 [+0.02, +1.13]) over 10 years.Conclusion: Agalsidase alfa-treated patients with 10-year FOS data and preserved kidney function and/or normal LVMI at baseline remained largely stable; those with decreased kidney function or LVH at baseline experienced modest declines in renal function and/or increases in LVMI.Keywords: agalsidase alfa, enzyme replacement therapy, Fabry disease, cardio-renal outcomes

The article presents a case study of a 45-year-old male with invasive right atrial myxoma extirpation surgery. Topics include preoperative transthoracic echocardiogram (TTE) showing normal biventricular function and mild tricuspid regurgitation without further cardiac abnormalities; and basic monitoring containing continuous pulse oximetry, electrocardiogram (ECG), and arterial canulation for invasive blood pressure.

Abstract: Purpose: The impact of a capnoperitoneum on the known blood pressure (BP) difference of the upper and lower limb was studied in piglets. Methods: Eleven German Landrace piglets (body weight, 4.3-7.4 kg; mean body weight, 6.2 kg) were studied. Arterial lines were placed in the right carotid and right femoral artery for pressure monitoring. Intraabdominal pressure levels were increased in steps of 6 mm Hg up to 24 mm Hg. Results: We found that elevated intraabdominal pressures up to 24 mm Hg did not change the preexisting systolic BP difference between the carotid and femoral arteries. Systolic femoral artery pressure constantly remained 5% higher than its carotid counterpart. In addition, mean and diastolic values were not affected. Conclusions: Arterial BP measurements recorded at the legs of piglets when abdominal pressure is increased by up to 24 mm Hg can be used for intraoperative assessment of systemic arterial BP. [Copyright &y& Elsevier]

BACKGROUND: Fabry disease is an X-linked disease caused by a deficiency in the activity of the lysosomal enzyme alpha-galactosidase A. Affected individuals typically develop left ventricular hypertrophy (LVH) among other pathologies. OBJECTIVE: The purpose of the present study was to investigate the effect of >or=12 months of enzyme replacement therapy (ERT) with agalsidase alfa on LV mass (LVM) in men and women with Fabry disease. METHODS: This was a retrospective, blinded, pooled analysis of data from several studies assessing the effect of ERT with agalsidase alfa on LVM in patients with Fabry disease with baseline LVH. Men and women aged >or=18 years with a confirmed diagnosis of Fabry disease who had received >or=36 months of ERT with agalsidase alfa were eligible, provided they had a baseline echocardiogram and a follow-up echocardiogram at 12 and/or 36 months. Data from 4 studies were included in the present analysis. LVM was normalized to height (in meters) to the 2.7 power (LVM/h = LVM/m(2.7)). RESULTS: In total, 45 adult patients (34 men and 11 women) with a confirmed diagnosis of Fabry disease and serial echocardiograms obtained at baseline and after 12 and/or 36 months of treatment were included. The mean (SD) age of this cohort was 39.8 (10.4) years (range, 18.9-67.2 years), and the mean weight was 72.5 (13.4) kg (range, 46.7-102.9 kg). Forty-two patients were white, 2 were Hispanic, and 1 was classified as other. At baseline, 14 patients had LVH (mean LVM/h = 55.4 [5.7] g/m(2.7)). After 12 months of ERT with agalsidase alfa, LVM/h decreased significantly by 9.2 (7.9) g/m(2.7) in 9 patients (P = 0.008), and after 36 months, LVM/h decreased significantly by 5.1 (7.5) g/m(2.7) in 10 patients (P = 0.037). In patients without baseline LVH (n = 31), a significant increase in LVM/h was observed after 12 months of treatment (3.6 [5.7] g/m(2.7); P = 0.002). After 36 months of treatment, however, there was no significant change from baseline in 10 patients (2.1 [7.9] g/m(2.7); P = NS). CONCLUSION: Treatment with agalsidase alfa for 12 or 36 months was associated with reduced LVM in these patients with Fabry disease with baseline LVH, and it appeared to stabilize LVM in these patients without baseline LVH. [ABSTRACT FROM AUTHOR]

Whybra C, Kampmann C, Krummenauer F, Ries M, Mengel E, Miebach E, Baehner F, Kim K, Bajbouj M, Schwarting A, Gal A, Beck M. The Mainz Severity Score Index: a new instrument for quantifying the Anderson–Fabry disease phenotype, and the response of patients to enzyme replacement therapy. Anderson–Fabry disease (AFD) is an X-linked disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. The availability of enzyme replacement therapy (ERT) for this debilitating condition has led to the need for a convenient and sensitive instrument to monitor clinical effects in an individual patient. This study aimed to develop a scoring system – the Mainz Severity Score Index (MSSI) – to measure the severity of AFD and to monitor the clinical course of the disease in response to ERT. Thirty-nine patients (24 males and 15 females) with AFD were assessed using the MSSI immediately before and 1 year after commencing agalsidase alfa ERT. Control data were obtained from 23 patients in whom AFD was excluded. The MSSI of patients with AFD was significantly higher than that of patients with other severe debilitating diseases. The MSSI indicated that, although more men than women had symptoms classified as severe, overall, the median total severity scores were not significantly different between male and female patients. One year of ERT with agalsidase alfa led, in all patients, to a significant (p < 0.001) reduction in MSSI score (by a median of nine points). This study has shown that the MSSI score may be a useful, specific measure for objectively assessing the severity of AFD and for monitoring ERT-related treatment effects. [ABSTRACT FROM AUTHOR]

Purpose: For treatment of univentricular heart, the Fontan operation has been established as the definitive palliation. The current controversy is mainly based on the high incidence of arrhythmias after an intra-atrial lateral tunnel Fontan operation.Methods: From January 1995 until April 2002, 46 children underwent a Fontan-type operation with or without a small fenestration. In 33 patients (group I) an intracardiac tunnel and in 13 patients (group II) an extracardiac conduit procedure was performed.Principal findings: There was no perioperative mortality. All patients showed postoperative a significant increase of arterial oxygen saturation, from 76 to 86% after surgery with fenestration, or to 90.5% without fenestration respectively. In patients with fenestration procedure, the saturation rose to 90% after closure of fenestrations 9 to 12 months after operation.Conclusions: Modified Fontan operations can be performed in normothermia on the beating heart with acceptable mortality. The extracardiac conduit Fontan procedure has the benefits of less surgical injury and a higher intraoperative flexibility. [Copyright &y& Elsevier]

Aims: Fabry disease results from deficient activity of the lysosomal enzyme α-galactosidase A. Progressive accumulation of the major substrates leads, in both men and women, to progressive hypertrophic cardiomyopathy. We aimed to evaluate the utility of different electrocardiographic (ECG) parameters for assessing the degree and severity of hypertrophic cardiomyopathy in patients with Fabry disease. Methods: A total of 166 ECGs of 94 hemi- and heterozygous patients with Fabry disease were analysed and compared with echocardiographic-estimated left ventricular mass (LVM). Results: There was a significant (p < 0.0001) correlation between QRS duration (R[sup 2] = 0.59), 12-lead amplitude/duration product (R[sup 2] = 0.61), Sokolow–Lyon voltage/duration product (R[sup 2] = 0.52) and LVM. Analysis of receiver operating characteristics revealed that the 12- lead amplitude/duration product had the highest sensitivity-specificity relationship (p < 0.01 compared with the Cornell index). Conclusion: In general, ECG signs of left ventricular hypertrophy correlated well with LVM as revealed by echocardiography. Of the parameters studied, the 12-lead amplitude/duration product was the most successful at describing the severity of cardiac involvement in Fabry disease. These data suggest that ECG parameters have potential for use as a simple and cost-effective means of screening for hypertrophic cardiomyopathy in patients with Fabry disease. [ABSTRACT FROM AUTHOR]

Objective: To report initial experiences with transcatheter occlusion of atrial septal defects using a new occlusion device.Subjects: 10 children aged 1.1 to 14.9 years.Inclusion Criteria: Patients with a body weight above 10 kg, normal pulmonary resistance and an indication for surgical closure of a secundum atrial septal defect, a residual tissue rim of interatrial septum surrounding the defect of more than 5 mm, and a maximum defect diameter of 20 mm.Methods: The defects were closed by a transcatheter device (ASDOS) consisting of two umbrellas which are introduced over a guidewire loop. Both umbrellas consist of a central body and five arms formed from preshaped nitinol wire covered with a thin polyurethane patch. The central body of the distal umbrella contains a thread, the proximal umbrella contains a bolt. The two umbrellas are connected by screwing the bolt on the thread using a screwdriver catheter.Results: The implantation was performed under echocardiographic guidance; in six of 10 patients, transoesophageal echocardiography was necessary. The "stretched" diameter of the defect evaluated during balloon sizing ranged from 10 to 20 mm, and the pulmonary to systemic blood flow ratio from 1.5:1 to 2.8:1. Transcatheter closure was successfully performed in 9/10 patients using devices with a diameter of 25 mm to 40 mm. No severe complications occurred. However, in one patient with a pre-existing prolonged PR interval brief periods of second and third degree atrioventricular block occurred after the implantation but normalised within 3 d. During a follow up period of 21 to 29 weeks no device embolisation, thromboembolic complications, fractures of the implanted device, atrial perforations, pericardial effusions, obstructions of systemic or pulmonary veins, atrioventricular valve dysfunction, or other complications occurred.Conclusions: The new device is a promising transcatheter approach for the occlusion of secundum atrial septal defects in children. However, further evaluation and long term data are needed before this transcatheter technique can be recommended. [ABSTRACT FROM AUTHOR]

Abstract Background Lysosomal storage disorders (LSD) are a rare cause of non immunological hydrops fetalis (NIHF) and congenital ascites. The reported incidence is about 1%. The incidence of idiopathic NIHF is estimated to be about 18%. Patients and methods We report four cases with transient hydrops fetalis resulting from LSD and performed a literature review on LSD with NIHF and congenital ascites in combination. Results At present, 12 different LSDs are described to be associated with NIHF or congenital ascites. Most patients had a family history of NIHF, where the preceding sibling had not been examined. A diagnostic approach to the fetus with NIHF due to suspected LSD either in utero or postnatal is suggested. Transient forms of NIHF and/or ascites in association with MPS IVA, MPS VII and NPC are described for the first time in this publication. Conclusions LSD should be considered in transient hydrops. Enzymatic studies in chorionic villous sample or amniotic cultured cells, once the most common conditions associated with fetal ascites or hydrops have been ruled out, are important. This paper emphasizes the fact that LSD is significantly higher than the estimated 1% in previous studies, which is important for genetic counseling as there is a high risk of recurrence and the availability of enzyme replacement therapy for an increasing number of LSD.

Abstract Background Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy. Methods In a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes. Results Classic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13 T > G. It was associated with a milder course in this subgroup. Conclusions Disease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany.

Abstract Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2-sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies. Take-home message Expertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan-European recommendations for the diagnosis and management of this life-limiting disease.

Objective: The prevalence and potential causes of anemia among patients with Anderson-Fabry disease are unknown. Methods: We therefore examined hemoglobin concentrations of patients with Anderson-Fabry disease using a large international database, FOS- the Fabry Outcome Survey. Results: Anemia was present in 38% of 314 patients with Anderson-Fabry disease. Median hemoglobin in 143 females was 12.9 g/dl and the median hemoglobin of 171 male patients was 13.1 g/dl. The prevalence of anemia among females (hemoglobin < 12 g/dl) was 21.0%, and among males (hemoglobin < 13 g/dl) 48.5%. Among patients with normal renal function (estimated glomerular filtration rate >90 ml/min/1.73m2) and anemia, heart failure (NYHA class II to IV) and/or elevated C-reactive protein levels were documented in 72% of patients. In patients with decreased glomerular filtration rate up to 88% presented with anemia. There was also a trend for lower hemoglobin levels among patients with signs of inflammation (defined by an elevated C-reactive protein level). During enzyme replacement therapy hemoglobin levels remained unchanged in 72 patients for a follow-up of two years. Conclusions: In summary, the results of this study point to a high prevalence of anemia among patients with Anderson-Fabry disease that is in most instances related to kidney disease, heart failure, and inflammation. This finding may be of clinical relevance, because anemia is a major risk factor for patients with kidney disease, heart failure, or stroke, which are important manifestations of Anderson-Fabry disease. [ABSTRACT FROM AUTHOR]

Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi procedure. The aim was to reach a consensus regarding clinical trial design, best treatment comparator, clinical outcomes, measurement of those clinical outcomes and inclusion and exclusion criteria. Consensus results of this initiative included: the selection of the adaptative clinical trial as the ideal study design and agalsidase beta as ideal comparator treatment due to its longstanding use in FD. Renal and cardiac outcomes, such as glomerular filtration rate, proteinuria and left ventricular mass index, were prioritised, whereas neurological outcomes including cerebrovascular and white matter lesions were dismissed as a primary or secondary outcome measure. Besides, there was a consensus regarding the importance of patient-related outcomes such as general quality of life, pain, and gastrointestinal symptoms. Also, unity about lysoGb3 and Gb3 tissue deposits as useful surrogate markers of the disease was obtained. The group recognised that cardiac T1 mapping still has potential but requires further development before its widespread introduction in clinical trials. Finally, patients with end-stage renal disease or renal transplant should be excluded unless a particular group for them is created inside the clinical trial. This consensus will help to shape the future of clinical trials in FD. We note that the FDA has, coincidentally, recently published draft guidelines on clinical trials in FD and welcome this contribution. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis (MPS) encompasses a group of genetic lysosomal storage disorders, linked to reduced life expectancy and a significant lack of effective treatment options. Immunomodulatory drugs could have the potential to be a relevant medical approach, as the accumulation of undegraded substances initiates an innate immune response, which leads to inflammation and clinical deterioration. However, immunomodulators are not licensed for this indication. Consequently, we aim to provide evidence advocating fast access to innovative individual treatment trials (ITTs) with immunomodulatory drugs and high-quality evaluation of drug effects by implementing a risk-benefit model tailored for MPS. The iterative methodology of our novel decision analysis framework (DAF) involves three key steps: (i) literature review on promising treatment targets and immunomodulators in MPS; (ii) quantitative risk-benefit assessment (RBA) of selected molecules; (iii) assigning phenotypic profiles and quantitative evaluations. The results facilitate a personalized application of the model and are based on published evidence as well as interdisciplinary experts' consensus and patient perspectives. Four promising immunomodulators have been identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra is anticipated as a treatment of choice for neuronopathic MPS patients. Nevertheless, a comprehensive RBA should always be completed on an individual basis. Our evidence-based DAF tool for ITTs directly addresses the substantial unmet medical need in MPS and characterizes an initial stride toward precision medicine with immunomodulators., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Mucopolysaccharidosis II (MPS II, Hunter syndrome) is a rare, X-linked lysosomal storage disease caused by reduced activity of iduronate-2-sulfatase (I2S), with subsequent cellular accumulation of the glycosaminoglycans (GAGs), heparan sulfate, and dermatan sulfate (DS). DS is a major component of the extracellular matrix of heart valves, which can be affected in MPS II. We investigated the natural history of valve disease in MPS II and the impact of long-term intravenous enzyme replacement therapy (ERT) with recombinant I2S (idursulfase). In total, 604 cardiac examinations were assessed from serial follow-up of 80 male patients (49 neuronopathic). Valve disease was classified according to standard practice from hemodynamic features evident from echocardiography. The natural history group comprised 48 patients (up to 14.8 years of follow-up; median, 2.6 years; 24 patients started ERT during the study); 56 patients were treated (up to 14.2 years of follow-up; median, 6.2 years). Lifetime GAG burden (calculated from urinary GAG measurements) correlated significantly with the degree of valve disease. Onset of moderate-to-severe valve disease was significantly delayed in treated (median age at onset, 29.1 ± 2 [95% CI: 25.2-32.9] years; Kaplan-Meier estimation) versus untreated patients (17.6 ± 1 [95% Cl: 15.8-19.4] years; p < 0.0001). Cox regression modeling found that long-term ERT reduced the probability of developing severe valve disease (χ 2 , 32.736; significant after 5 years of ERT). Overall, this study found that valve disease severity in MPS II correlates with GAG burden and that progression is delayed by long-term ERT., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: Bacteremia with species in the genus Campylobacter is rare, and knowledge of the disease course in comparison with Campylobacter enteritis is limited., Methods: This is a retrospective population-based study. Episodes of Campylobacter bacteremia and Campylobacter enteritis with a concurrent negative blood culture result that occurred between 2015 and 2022 in southern Sweden were identified through the laboratory database. Medical records were reviewed, and clinical features between patients with bacteremic Campylobacter infections were compared with patients with Campylobacter spp found in feces., Results: The study included 29 bacteremic infections with Campylobacter and 119 cases of Campylobacter spp found in feces. Patients with Campylobacter bacteremia were significantly older than those with enteritis (72 years [IQR, 58-62] vs 58 years [IQR, 33-67], P < .0001). Eleven patients with bacteremia developed sepsis within 48 hours from blood culturing, and no patient died within 30 days from hospital admission., Conclusions: Campylobacter bacteremia is rare and occurs mainly in the elderly with comorbidities. In comparison with Campylobacter infections limited to the gastrointestinal tract, patients with bacteremic Campylobacter infections are older and seem more prone to develop sepsis. Classical gastroenteritis symptoms in bacteremic cases with Campylobacter may be absent., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Effective direct-acting antiviral treatment against hepatitis C virus infection is available in many countries worldwide. Despite good treatment results, a proportion of patients does not respond to treatment. The aim of this study was to investigate the long-term prognosis and the outcome of salvage therapy, after an initial treatment failure, in a nation-wide real-life setting., Method: Data from all adult patients registered in the national Swedish hepatitis C treatment register who did not achieve sustained virological response after initial antiviral treatment, was retrieved from 2014 through 2018., Results: In total, 288 patients with primary treatment failure were included, of whom 236 underwent a second treatment course as salvage therapy after a median delay of 353 (IQR: 215-650) days. Fifteen patients received a third treatment course as second salvage treatment after a further median delay of 193 (IQR: 160-378) days. One-hundred-eleven out of 124 (90%) non-cirrhotic and 62/79 (78%) cirrhotic patients achieved sustained virological response following the first salvage treatment. Sustained virological response was achieved by 108/112 (96%) patients who received a triple antiviral regimen. In total 69 patients were lost to follow-up or died waiting for salvage treatment. Baseline cirrhosis was associated with poor long-term survival., Conclusion: Our study indicates that salvage therapy was effective in most patients with primary treatment failure, in particular when a triple direct acting antiviral regimen was given. To avoid the risk of death or complications, patients with primary treatment failure should be offered salvage therapy with a triple regimen, as soon as possible.