- Email: [email protected]
P1243 SOFOSBUVIR PLUS RIBAVIRIN, AN INTERFERON-FREE REGIMEN, IN THE TREATMENT OF TREATMENT-NAIVE AND TREATMENT-EXPERIENCED PATIENTS WITH CHRONIC GENOTYPE 4 HCV INFECTION
POSTERS of HCV-PI resistance in liver but not in plasma compartment of 3 pts: 2 of these 3 pts harbored D168E amino acid (aa) substitution associated with macrocyclic PI resistance and one harbored V55A aa change associated with boceprevir resistance. The remaining 2 pts exhibited a wild-type sequence in both compartments. Conclusions: The detection of discordant G1 subtypes in liver and plasma may be consequent to a mixed infection and selection of a specific subtype with greater adaptability to different environmental condition. The presence of natural mutations associated with HCV-PI resistance in liver tissue may explain the early emergence of these strains during triple therapy including HCV-PI. P1241 A FULLY-AUTOMATED PIPELINE FOR SEQUENCING WHOLE VIRAL GENOMES WITHOUT VIRUS-SPECIFIC PCR AMPLIFICATION TO DETERMINE HCV RESISTANCE TO ANTIVIRAL THERAPY D.G. Bonsall1 , P. Piazza2 , A. Trebes2 , A. Brown1 , J. Iles1 , J. Halliday1 , J. Hurst1 , E. Batty2 , A. Ansari1 , C. Ip2 , R. Bowden2 , D. Crook3 , P. Klenerman1 , E. Barnes1 . 1 Peter Medawar Building for Pathogen Research, Oxford University, 2 Wellcome Trust Centre for Human Genetics, 3 Nuffield Department of Clinical Medicine, Oxford, United Kingdom E-mail: [email protected] Background and Aims: To address the issue of HCV sequence variation and drug-resistance in the era of DAA therapies we developed a novel high-throughput pipeline for whole genome sequencing (WGS) and detection of DAA-resistance. We reasoned that it would be possible to generate viral sequences directly ex vivo, without selecting or amplifying viral RNA with virus-specific oligonucleotides. Methods: Total RNA was extracted from the plasma of DAA-naive patients (n = 82) chronically infected with HCV genotypes-1 -2 or -3 using magnetized-silica beads and sequenced using viral RNAseq (Illumina). Bioinformatic strategies for positive enrichment of viral sequences, negative exclusion of non-viral sequences, short-read mapping to known reference sequences and de novo assembly were optimized. The terminal stage of the fully-automated pipeline identifies known DAA-resistance mutations within high and lowfrequency quasi-species variants. Accuracy of WGS was confirmed by comparison with capillary Sanger sequencing. Results: We show robust WGS can be achieved on diverse viral isolates with a depth of coverage of >500, sufficient to call minor population variants. High and low frequency polymorphisms were detected that have previously been shown to confer resistance to NS3 and NS5a inhibitors. Conclusions: We report a novel method for HCV sequencing which harnesses the power of next generation sequencing approaches to allow, for the first time, affordable, full-genome HCV sequencing ex vivo without the requirement for primer-based selection of viral sequences. We have developed the first fully automated system for the detection of both major and minor DAA-resistant variants that can be used to guide bespoke therapies for the treatment of HCV infection.
P1242 RESISTANCE ANALYSIS OF HCV GENOTYPE 1 INFECTED PATIENTS TREATED WITH SOFOSBUVIR IN COMBINATION WITH LEDIPASVIR OR THE NS5B NONNUCLEOSIDE INHIBITOR GS-9669: THE ELECTRON STUDY E.S. Svarovskaia1 , R. Martin1 , V. Gontcharova1 , R.H. Hyland1 , E.J. Gane2 , C.A. Stedman3 , W.T. Symonds1 , M.D. Miller1 , H. Mo1 . 1 Gilead Sciences, Inc., Foster City, CA, United States; 2 New Zealand Transplant Unit, Auckland City Hospital, Auckland, 3 Christchurch Hospital, and University of Otago, Gastroenterology Department, Christchurch, New Zealand E-mail: [email protected] Background and Aims: The combination of sofosbuvir (SOF) with ledipasvir (LDV) or GS-9669 provides high efficacy in HCV genotype-1 infected patients. In this study we evaluated the impact of preexisting resistant-associated variants (RAVs) on treatment outcome and emergence of RAVs at relapse in patients receiving SOF with LDV or GS-9669 in the ELECTRON study. Methods: SOF/LDV, SOF/LDV+RBV, SOF+LDV+RBV, or SOF+GS-9669+ RBV was given for 12 weeks to treatment-naïve (TN) patients or prior null responders (Nulls), and Nulls with cirrhosis. Additionally, a group of TN patients received SOF/LDV+RBV for 6 weeks. NS5A and/or NS5B sequencing was performed at baseline. Deep sequencing analysis was performed for all patients who did not achieve SVR12 at baseline and relapse timepoints (assay cut-off of 1%). Results: No S282T NS5B RAV for SOF was detected across all treatment groups at baseline or relapse. Among LDV-treated patients, 10/78 (13%) had detectable LDV RAVs at baseline with 9/10 patients achieving SVR12. NS5A LDV RAVs were detected posttreatment in 6/11 subjects who relapsed (see table). No LDV phenotypic shift was observed in 4/5 patients who relapsed without LDV RAVs. Among GS-9669-treated subjects, 2 of 25 TN patients experienced viral relapse after SOF+GS-9669+RBV treatment. One patient had reinfection with genotype 3a HCV; the other had no SOF or GS-9669 genotypic or phenotypic resistance at baseline or relapse. Conclusions: The presence of baseline NS5A RAVs did not preclude patients from achieving SVR12 when treatment included the combination of SOF and LDV (9/10 had SVR12). NS5A RAVs, but not the NS5B SOF RAV S282T, were detected in ~55% of relapse subjects.
Total, N With LDV RAVs at BL Relapse, N With LDV RAVs at relapse
SOF+LDV+RBV 12 weeks, TN
SOF+LDV+RBV 12 weeks, Nulls
SOF/LDV+RBV 12 weeks, Nulls F4
SOF/LDV, 12 weeks, Nulls F4
SOF/LDV+RBV 6 weeks, TN
25 3, all achieved SVR12 0 0
9 1, all achieved SVR12 0 0
9 3, all achieved SVR12 0 0
10 3, 2/3 achieved SVR12 3 3/3
25 0 8 3/8
P1243 SOFOSBUVIR PLUS RIBAVIRIN, AN INTERFERON-FREE REGIMEN, IN THE TREATMENT OF TREATMENT-NAIVE AND TREATMENT-EXPERIENCED PATIENTS WITH CHRONIC GENOTYPE 4 HCV INFECTION P.J. Ruane1 , D. Ain1 , R. Meshrekey1 , J. Riad1 , M. Soliman1 , S. Mikhail1 , P.R. Wolfe1 , K. Kersey2 , B. Doehle2 , D. Jiang2 , W.T. Symonds2 . 1 Ruane Medical and Clinical Research Institute, Los Angeles, 2 Gilead Sciences, Inc., Foster City, CA, United States E-mail: [email protected] Background and Aims: Current treatment for GT4 is pegylated interferon (PEG) + ribavirin (RBV) for up to 48 weeks. In the NEUTRINO trial, sofosbuvir (SOF) +PEG+RBV for 12 weeks resulted in a 96% (27/28) SVR12 rate. This study assessed the safety and efficacy of SOF+RBV without interferon in treating GT4 HCV infection.
Journal of Hepatology 2014 vol. 60 | S361–S522
S503
POSTERS Methods: Patients, born in Egypt and of Egyptian ancestry, with chronic HCV GT4 infection were randomized 1:1, stratified by prior treatment status and cirrhosis status, to receive 12 or 24 weeks SOF (400 mg/day) +RBV (1000–1200 mg/day). Approximately 20% could have compensated cirrhosis. HCV subtyping and viral resistance testing used NS5B population and deep sequencing, respectively. Results: 60 patients were enrolled, 28 treatment-naïve (TN) and 32 treatment-experienced (TE). 68% were male, 23% cirrhotic, 17% IL28B CC. TN SVR12 rates were 79% (11/14) with 12w and 100% (14/14) with 24w SOF+RBV. TE SVR12 rates were 59% (10/17) with 12w and 87% (13/15) with 24w SOF+RBV. Relapse accounted for all virologic failures except in 1 TN subject receiving 12 weeks treatment who had a partial response. Most AEs were mild or moderate in severity and consistent with RBV known side effects. Final SVR results by baseline characteristics, including GT4 subtype, and resistance data will be presented. Conclusions: SOF+RBV provided a simple, well-tolerated, interferon-free regimen for patients with HCV GT4, including those who were interferon-ineligible, -intolerant, and failures, where an unmet medical need exists. Extending treatment duration to 24 weeks resulted in higher SVR12 rates in both treatment-naïve and -experienced patients. P1244 FAVORABLE PRECLINICAL PROFILE OF IDX21437, A NOVEL URIDINE NUCLEOTIDE PRODRUG, FOR USE IN A DIRECT-ACTING ANTIVIRAL (DAA) REGIMEN FOR HCV K. Gupta, M. Seifer, I. Serra, H. Rashidzadeh, S. Luo, M. La Colla, X.-R. Pan-Zhou, C. Chapron, B. Hernandez-Santiago, B. Mayes, S. Bhadresa, A. Moussa, R. Rush. Idenix Pharmaceuticals, Inc., Cambridge, MA, United States E-mail: [email protected] Background and Aims: The preclinical pharmacology, safety and early PK profile of IDX21437, a novel oral pan-genotypic HCV nucleotide prodrug, are characterized here. Methods: Antiviral activity was determined against NS5B enzymes and in HCV cell assays. Cytotoxicity was evaluated in a panel of mammalian cells. In vitro experiments were conducted using bacteria, mammalian hepatocytes, subcellular fractions and transporters. In vivo studies were performed in mice, rats and monkeys. Results: The triphosphate (TP) of IDX21437 was active against HCV NS5B genotypes (GT) 1–6 (0.10 to 0.25 mM), but not against human polymerases. IDX21437 selectively inhibited HCV replicons in cell-based assays. IDX21437 showed minimal cytotoxicity to 19 mammalian cell types including cardiomyocytes. A high resistance barrier and no cross-resistance to other DAA drug classes were observed. Combination studies showed additivity with other HCV DAAs, including the NS5A inhibitor samatasvir. IDX21437 exhibited minimal inhibition of key enzymes and transporters. Favorable ADME properties included rapid absorption, rapid and complete elimination, liver-targeted delivery with high liver TP formation and a TP half-life of 24h. In vitro and in vivo genotoxicity testing was negative. IDX21437 was well tolerated and there was no cardiac safety concern in rats and monkeys following 28-day once-daily oral dosing. Conclusions: IDX21437 is an HCV uridine nucleotide prodrug with a favorable pharmacology, safety, resistance and PK profile, high liver TP and minimal drug-drug interaction risk. These data suggest the potential for low-dose, once-daily use with samatasvir, an NS5A inhibitor, as a potent, pan-genotypic combination regimen in future clinical studies.
S504
13. GENETIC AND PEDIATRIC LIVER DISEASES
P1245 THERAPEUTIC CHELATION EFFICACY OF TRIENTINE ENCAPSULATED ALGINATE NANOPARTICLES FOR COPPER TOXICITY INDUCED HEPATOCEREBRAL DISEASES: A PRELIMINARY STUDY A. Pal1 , R. Prasad1 , R.K. Vasishta2 , B.R. Thapa3 . 1 Biochemistry, 2 Histopathology, 3 Gastroenterology, PGIMER, Chandigarh, India E-mail: [email protected] Background and Aims: Trientine is unable to mitigate the brain copper overload and neurological manifestations in Wilson’s disease patients. The aim of this study was to assess the therapeutic efficacy of orally administered Trientine loaded nanoparticles (7.2 mg Trientine/200g body-weight/day) to that of conventional Trientine (14.4 mg Trientine/200g body-weight/day) for 90 days in Wistar rat model for non-Wilsonian brain copper toxicosis. Methods: High performance liquid chromatography, atomic absorption spectrophotometry, biochemical estimations, neurobehavioral and histopathological studies, and nanoparticles preparation and their physicochemical characterization were carried out. Results: Trientine nanoparticles exhibited mean 351 nm size and less than 34% of Trientine release. Pharmacokinetics studies showed augmented levels of Trientine in brain of nanoparticles based Trientine delivery group compared to conventional Trientine delivery group. Conventional and nanoparticles based Trientine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary Cu levels, and acetylcholinesterase activity in rat model of Cu toxicosis. Conventional Trientine therapy resulted in negative rhodanine staining of liver and brain sections corroborated by 63%, and16% reduction in hepatic and brain copper content, respectively compared to non-treated Cu-intoxicated group. However, liver and brain sections of nanoparticles based Trientine therapy group demonstrated grade 1 copper, and no copper depositions substantiated by 46% and 28% reduction in hepatic and brain copper content, respectively in comparison to non-treated copperintoxicated group. Conclusions: Taken together, the present study reveals the first in vivo evidence for therapeutic efficacy of Trientine nanoparticles in chelating more brain copper and alleviating neurological deficits even at half the dose as given in conventional Trientine therapy. P1246 PHLEBOTOMY FREQUENCY REDUCED BY PROTON PUMP INHIBITORS IN PATIENTS WITH HEREDITARY HEMOCHROMATOSIS R.M.M. van Aerts1 , C.T.B.M. van Deursen2 , G.H. Koek3 . 1 Internal Medicine and Gastroenterology, Maastricht University Medical Center, Maastricht, 2 Internal Medicine and Gastroenterology, Atrium Medical Center Parkstad, Heerlen, 3 Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, Netherlands E-mail: [email protected] Background and Aims: Patients with hereditary hemochromatosis (HH) need frequent phlebotomies to reduce iron overload. A recent study showed that administration of proton pump inhibitors (PPIs) reduces the need for phlebotomies in C282Y homozygous patients. Lower levels of gastric acid probably have an influence on the intestinal iron absorption. We aim to confirm the hypothesis that PPIs reduce the need for phlebotomies in C282Y homozygous patients.
Journal of Hepatology 2014 vol. 60 | S361–S522
P1242 RESISTANCE ANALYSIS OF HCV GENOTYPE 1 INFECTED PATIENTS TREATED WITH SOFOSBUVIR IN COMBINATION WITH LEDIPASVIR OR THE NS5B NONNUCLEOSIDE INHIBITOR GS-9669: THE ELECTRON STUDY E.S. Svarovskaia1 , R. Martin1 , V. Gontcharova1 , R.H. Hyland1 , E.J. Gane2 , C.A. Stedman3 , W.T. Symonds1 , M.D. Miller1 , H. Mo1 . 1 Gilead Sciences, Inc., Foster City, CA, United States; 2 New Zealand Transplant Unit, Auckland City Hospital, Auckland, 3 Christchurch Hospital, and University of Otago, Gastroenterology Department, Christchurch, New Zealand E-mail: [email protected] Background and Aims: The combination of sofosbuvir (SOF) with ledipasvir (LDV) or GS-9669 provides high efficacy in HCV genotype-1 infected patients. In this study we evaluated the impact of preexisting resistant-associated variants (RAVs) on treatment outcome and emergence of RAVs at relapse in patients receiving SOF with LDV or GS-9669 in the ELECTRON study. Methods: SOF/LDV, SOF/LDV+RBV, SOF+LDV+RBV, or SOF+GS-9669+ RBV was given for 12 weeks to treatment-naïve (TN) patients or prior null responders (Nulls), and Nulls with cirrhosis. Additionally, a group of TN patients received SOF/LDV+RBV for 6 weeks. NS5A and/or NS5B sequencing was performed at baseline. Deep sequencing analysis was performed for all patients who did not achieve SVR12 at baseline and relapse timepoints (assay cut-off of 1%). Results: No S282T NS5B RAV for SOF was detected across all treatment groups at baseline or relapse. Among LDV-treated patients, 10/78 (13%) had detectable LDV RAVs at baseline with 9/10 patients achieving SVR12. NS5A LDV RAVs were detected posttreatment in 6/11 subjects who relapsed (see table). No LDV phenotypic shift was observed in 4/5 patients who relapsed without LDV RAVs. Among GS-9669-treated subjects, 2 of 25 TN patients experienced viral relapse after SOF+GS-9669+RBV treatment. One patient had reinfection with genotype 3a HCV; the other had no SOF or GS-9669 genotypic or phenotypic resistance at baseline or relapse. Conclusions: The presence of baseline NS5A RAVs did not preclude patients from achieving SVR12 when treatment included the combination of SOF and LDV (9/10 had SVR12). NS5A RAVs, but not the NS5B SOF RAV S282T, were detected in ~55% of relapse subjects.
Total, N With LDV RAVs at BL Relapse, N With LDV RAVs at relapse
SOF+LDV+RBV 12 weeks, TN
SOF+LDV+RBV 12 weeks, Nulls
SOF/LDV+RBV 12 weeks, Nulls F4
SOF/LDV, 12 weeks, Nulls F4
SOF/LDV+RBV 6 weeks, TN
25 3, all achieved SVR12 0 0
9 1, all achieved SVR12 0 0
9 3, all achieved SVR12 0 0
10 3, 2/3 achieved SVR12 3 3/3
25 0 8 3/8
P1243 SOFOSBUVIR PLUS RIBAVIRIN, AN INTERFERON-FREE REGIMEN, IN THE TREATMENT OF TREATMENT-NAIVE AND TREATMENT-EXPERIENCED PATIENTS WITH CHRONIC GENOTYPE 4 HCV INFECTION P.J. Ruane1 , D. Ain1 , R. Meshrekey1 , J. Riad1 , M. Soliman1 , S. Mikhail1 , P.R. Wolfe1 , K. Kersey2 , B. Doehle2 , D. Jiang2 , W.T. Symonds2 . 1 Ruane Medical and Clinical Research Institute, Los Angeles, 2 Gilead Sciences, Inc., Foster City, CA, United States E-mail: [email protected] Background and Aims: Current treatment for GT4 is pegylated interferon (PEG) + ribavirin (RBV) for up to 48 weeks. In the NEUTRINO trial, sofosbuvir (SOF) +PEG+RBV for 12 weeks resulted in a 96% (27/28) SVR12 rate. This study assessed the safety and efficacy of SOF+RBV without interferon in treating GT4 HCV infection.
Journal of Hepatology 2014 vol. 60 | S361–S522
S503
POSTERS Methods: Patients, born in Egypt and of Egyptian ancestry, with chronic HCV GT4 infection were randomized 1:1, stratified by prior treatment status and cirrhosis status, to receive 12 or 24 weeks SOF (400 mg/day) +RBV (1000–1200 mg/day). Approximately 20% could have compensated cirrhosis. HCV subtyping and viral resistance testing used NS5B population and deep sequencing, respectively. Results: 60 patients were enrolled, 28 treatment-naïve (TN) and 32 treatment-experienced (TE). 68% were male, 23% cirrhotic, 17% IL28B CC. TN SVR12 rates were 79% (11/14) with 12w and 100% (14/14) with 24w SOF+RBV. TE SVR12 rates were 59% (10/17) with 12w and 87% (13/15) with 24w SOF+RBV. Relapse accounted for all virologic failures except in 1 TN subject receiving 12 weeks treatment who had a partial response. Most AEs were mild or moderate in severity and consistent with RBV known side effects. Final SVR results by baseline characteristics, including GT4 subtype, and resistance data will be presented. Conclusions: SOF+RBV provided a simple, well-tolerated, interferon-free regimen for patients with HCV GT4, including those who were interferon-ineligible, -intolerant, and failures, where an unmet medical need exists. Extending treatment duration to 24 weeks resulted in higher SVR12 rates in both treatment-naïve and -experienced patients. P1244 FAVORABLE PRECLINICAL PROFILE OF IDX21437, A NOVEL URIDINE NUCLEOTIDE PRODRUG, FOR USE IN A DIRECT-ACTING ANTIVIRAL (DAA) REGIMEN FOR HCV K. Gupta, M. Seifer, I. Serra, H. Rashidzadeh, S. Luo, M. La Colla, X.-R. Pan-Zhou, C. Chapron, B. Hernandez-Santiago, B. Mayes, S. Bhadresa, A. Moussa, R. Rush. Idenix Pharmaceuticals, Inc., Cambridge, MA, United States E-mail: [email protected] Background and Aims: The preclinical pharmacology, safety and early PK profile of IDX21437, a novel oral pan-genotypic HCV nucleotide prodrug, are characterized here. Methods: Antiviral activity was determined against NS5B enzymes and in HCV cell assays. Cytotoxicity was evaluated in a panel of mammalian cells. In vitro experiments were conducted using bacteria, mammalian hepatocytes, subcellular fractions and transporters. In vivo studies were performed in mice, rats and monkeys. Results: The triphosphate (TP) of IDX21437 was active against HCV NS5B genotypes (GT) 1–6 (0.10 to 0.25 mM), but not against human polymerases. IDX21437 selectively inhibited HCV replicons in cell-based assays. IDX21437 showed minimal cytotoxicity to 19 mammalian cell types including cardiomyocytes. A high resistance barrier and no cross-resistance to other DAA drug classes were observed. Combination studies showed additivity with other HCV DAAs, including the NS5A inhibitor samatasvir. IDX21437 exhibited minimal inhibition of key enzymes and transporters. Favorable ADME properties included rapid absorption, rapid and complete elimination, liver-targeted delivery with high liver TP formation and a TP half-life of 24h. In vitro and in vivo genotoxicity testing was negative. IDX21437 was well tolerated and there was no cardiac safety concern in rats and monkeys following 28-day once-daily oral dosing. Conclusions: IDX21437 is an HCV uridine nucleotide prodrug with a favorable pharmacology, safety, resistance and PK profile, high liver TP and minimal drug-drug interaction risk. These data suggest the potential for low-dose, once-daily use with samatasvir, an NS5A inhibitor, as a potent, pan-genotypic combination regimen in future clinical studies.
S504
13. GENETIC AND PEDIATRIC LIVER DISEASES
P1245 THERAPEUTIC CHELATION EFFICACY OF TRIENTINE ENCAPSULATED ALGINATE NANOPARTICLES FOR COPPER TOXICITY INDUCED HEPATOCEREBRAL DISEASES: A PRELIMINARY STUDY A. Pal1 , R. Prasad1 , R.K. Vasishta2 , B.R. Thapa3 . 1 Biochemistry, 2 Histopathology, 3 Gastroenterology, PGIMER, Chandigarh, India E-mail: [email protected] Background and Aims: Trientine is unable to mitigate the brain copper overload and neurological manifestations in Wilson’s disease patients. The aim of this study was to assess the therapeutic efficacy of orally administered Trientine loaded nanoparticles (7.2 mg Trientine/200g body-weight/day) to that of conventional Trientine (14.4 mg Trientine/200g body-weight/day) for 90 days in Wistar rat model for non-Wilsonian brain copper toxicosis. Methods: High performance liquid chromatography, atomic absorption spectrophotometry, biochemical estimations, neurobehavioral and histopathological studies, and nanoparticles preparation and their physicochemical characterization were carried out. Results: Trientine nanoparticles exhibited mean 351 nm size and less than 34% of Trientine release. Pharmacokinetics studies showed augmented levels of Trientine in brain of nanoparticles based Trientine delivery group compared to conventional Trientine delivery group. Conventional and nanoparticles based Trientine therapy resulted in significantly improved neuromuscular coordination and memory along with concomitant increase in urinary Cu levels, and acetylcholinesterase activity in rat model of Cu toxicosis. Conventional Trientine therapy resulted in negative rhodanine staining of liver and brain sections corroborated by 63%, and16% reduction in hepatic and brain copper content, respectively compared to non-treated Cu-intoxicated group. However, liver and brain sections of nanoparticles based Trientine therapy group demonstrated grade 1 copper, and no copper depositions substantiated by 46% and 28% reduction in hepatic and brain copper content, respectively in comparison to non-treated copperintoxicated group. Conclusions: Taken together, the present study reveals the first in vivo evidence for therapeutic efficacy of Trientine nanoparticles in chelating more brain copper and alleviating neurological deficits even at half the dose as given in conventional Trientine therapy. P1246 PHLEBOTOMY FREQUENCY REDUCED BY PROTON PUMP INHIBITORS IN PATIENTS WITH HEREDITARY HEMOCHROMATOSIS R.M.M. van Aerts1 , C.T.B.M. van Deursen2 , G.H. Koek3 . 1 Internal Medicine and Gastroenterology, Maastricht University Medical Center, Maastricht, 2 Internal Medicine and Gastroenterology, Atrium Medical Center Parkstad, Heerlen, 3 Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, Netherlands E-mail: [email protected] Background and Aims: Patients with hereditary hemochromatosis (HH) need frequent phlebotomies to reduce iron overload. A recent study showed that administration of proton pump inhibitors (PPIs) reduces the need for phlebotomies in C282Y homozygous patients. Lower levels of gastric acid probably have an influence on the intestinal iron absorption. We aim to confirm the hypothesis that PPIs reduce the need for phlebotomies in C282Y homozygous patients.
Journal of Hepatology 2014 vol. 60 | S361–S522