The Experts below are selected from a list of 3468 Experts worldwide ranked by ideXlab platform
Beth Kaminski - One of the best experts on this subject based on the ideXlab platform.
-
lumacaftor ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Rose Gubitosiklug, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Mary Ann Oriordan, Beth KaminskiAbstract:BACKGROUND: Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. AIM: To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. METHODS: Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. RESULTS: Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. CONCLUSION: Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
-
Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Rose Gubitosi-klug, Maryann O’riordan, Beth KaminskiAbstract:Background Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. Aim To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. Methods Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. Results Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. Conclusion Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
Katherine Kutney - One of the best experts on this subject based on the ideXlab platform.
-
lumacaftor ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Rose Gubitosiklug, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Mary Ann Oriordan, Beth KaminskiAbstract:BACKGROUND: Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. AIM: To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. METHODS: Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. RESULTS: Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. CONCLUSION: Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
-
Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Rose Gubitosi-klug, Maryann O’riordan, Beth KaminskiAbstract:Background Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. Aim To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. Methods Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. Results Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. Conclusion Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
Antoinette Moran - One of the best experts on this subject based on the ideXlab platform.
-
Diabetes related mortality in adults with Cystic fibrosis role of genotype and sex
American Journal of Respiratory and Critical Care Medicine, 2015Co-Authors: Connor Lewis, Scott M Blackman, Amanda Nelson, Ewa Oberdorfer, Daniel Wells, Jordan M Dunitz, William Thomas, Antoinette MoranAbstract:Rationale: Diabetes is associated with increased mortality in Cystic fibrosis. Aggressive screening and early institution of insulin treatment significantly reduced this risk over the period of 1992–2008.Objectives: To determine if progressive improvement in Cystic fibrosis–related Diabetes (CFRD) mortality has continued since 2008, and examine associations with CFTR genotypes linked to pancreatic insufficiency and to sex.Methods: Chart review was performed on 664 patients followed from 2008 to 2012.Measurements and Main Results: Overall mortality for patients with CFRD was 1.8 per 100 person-years, compared with 0.5 in patients with CF without Diabetes (P = 0.0002); neither rate changed significantly from mortality reported for 2003–2008. Genotype impacted both mortality and Diabetes risk: adults with severe CFTR genotypes experienced greater mortality at every age older than 32 years than those with mild genotypes (P = 0.002), and the risk of developing CFRD was also greatly increased in those with seve...
-
insulin secretion improves in Cystic fibrosis following ivacaftor correction of cftr a small pilot study
Pediatric Diabetes, 2013Co-Authors: Melena D Bellin, Joanne L Billings, Jordan M Dunitz, Terri Laguna, Janice Leschyshyn, Warren E Regelmann, Antoinette MoranAbstract:Cystic fibrosis related Diabetes (CFRD) is characterized by progressive insulin insufficiency. It is extraordinarily prevalent in the Cystic fibrosis (CF) population, occurring in 15–20% of adolescents and, eventually, more than half of adults (1). Few of the remaining patients have completely normal glucose metabolism; even those with normal fasting and 2-hour oral glucose tolerance test (OGTT) glucose levels typically have mid-OGTT glucose elevation and have defective acute insulin secretion in response to intravenous glucose (2). While CFRD does not usually develop before puberty, it has its roots in childhood and glucose intolerance is common in 6–9 year old children with CF (3). It has not been studied in younger children, but ferret models of CF demonstrate insulin secretory abnormalities in the newborn period (4), suggesting that there may be an intrinsic defect in beta-cell function in CF. CF is caused by abnormalities in the CF transmembrane conductance regulator (CFTR), an ATP-binding cassette transporter-class ion channel involved in chloride, sodium and water transport and absorption across cell membranes. CFTR defects lead to thick, viscous secretions with well-known chronic complications including obstructive lung disease associated with infection and inflammation, sinusitis, intestinal obstruction, liver disease and infertility. Pancreatic exocrine insufficiency develops as plugged ductules prevent digestive enzymes from reaching the gut; autodigestion of the pancreas by these trapped enzymes leads to fibrosis. It has long been debated whether insulin insufficiency in CF is merely a physical, “by-stander” consequence of this fibrotic destruction of the pancreatic architecture, or if CFTR defects per se impact insulin secretion (5). CFTR is expressed in human and mouse pancreatic alpha- and beta-cells (6; 7), but it is not known whether it is involved in hormone secretion. There has previously been no way to directly test this in a human model. Ivacaftor (VX-770, Kalydeco™, Vertex Pharmaceuticals, Cambridge, MA) is the first of a group of “potentiator” molecules being developed to correct the CFTR defect. CFTR is made in the endoplasmic reticulum, processed in the Golgi apparatus, and secreted in vesicles which chaperone proteins carry to the cell membrane, where it must be inserted and then must function normally. Defects leading to CF may occur at any of these steps. In patients with the G551D mutation (about 4% of the CF population), CFTR is found in the cell membrane but is dysfunctional. Ivacaftor corrects this defect by restoring channel gating, through an as-yet unidentified mechanism (8). In clinical Phase 2 and 3 trials, ivacaftor produced dramatic improvements in skin sweat chloride levels and in lung function within just 3 weeks (9; 10), and the drug has recently been approved by the FDA in children down to age 6. The initiation of ivacaftor therapy offers a unique opportunity to test the role of CFTR in human insulin secretion, potentially opening the way for novel Diabetes therapies and for prevention or at least amelioration of Diabetes in CF.
-
Diagnosis, screening, and management of Cystic fibrosis–related Diabetes
Current Diabetes Reports, 2002Co-Authors: Antoinette MoranAbstract:Diabetes is a common complication of Cystic fibrosis (CF), occurring in approximately 40% of adult patients. It is clinically distinct from type 1 or type 2 Diabetes, and requires a unique approach. Because of evidence that it is associated with increased morbidity and mortality, prompt diagnosis and aggressive management of CF-related Diabetes (CFRD) is important. The Cystic Fibrosis Foundation held a consensus conference in 1998 to define the current standards for the diagnosis and care of this disease. This article reviews those recommendations, and presents a practical approach to the management of CFRD.
Kimberly Mcbennett - One of the best experts on this subject based on the ideXlab platform.
-
lumacaftor ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Rose Gubitosiklug, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Mary Ann Oriordan, Beth KaminskiAbstract:BACKGROUND: Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. AIM: To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. METHODS: Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. RESULTS: Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. CONCLUSION: Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
-
Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Rose Gubitosi-klug, Maryann O’riordan, Beth KaminskiAbstract:Background Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. Aim To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. Methods Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. Results Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. Conclusion Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
Christopher A Flask - One of the best experts on this subject based on the ideXlab platform.
-
lumacaftor ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Rose Gubitosiklug, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Mary Ann Oriordan, Beth KaminskiAbstract:BACKGROUND: Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. AIM: To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. METHODS: Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. RESULTS: Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. CONCLUSION: Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
-
Lumacaftor/ivacaftor therapy is associated with reduced hepatic steatosis in Cystic fibrosis patients
World Journal of Hepatology, 2019Co-Authors: Katherine Kutney, Shannon B Donnola, Kimberly Mcbennett, Thomas Joseph Sferra, Christopher A Flask, Rose Gubitosi-klug, Maryann O’riordan, Beth KaminskiAbstract:Background Hepatic steatosis is a common form of Cystic fibrosis associated liver disease (CFLD) seen in an estimated 15%-60% of patients with Cystic fibrosis (CF). The pathophysiology and health implications of hepatic steatosis in Cystic fibrosis remain largely unknown. In the general population, hepatic steatosis is strongly associated with insulin resistance and type 2 Diabetes. Cystic fibrosis related Diabetes (CFRD) impacts 40%-50% of CF adults and is characterized by both insulin insufficiency and insulin resistance. We hypothesized that patients with CFRD would have higher levels of hepatic steatosis than Cystic fibrosis patients without Diabetes. Aim To determine whether CFRD is associated with hepatic steatosis and to explore the impact of lumacaftor/ivacaftor therapy on hepatic steatosis in CF. Methods Thirty patients with CF were recruited from a tertiary care medical center for this cross-sectional study. Only pancreatic insufficient patients with CFRD or normal glucose tolerance (NGT) were included. Patients with established CFLD, end stage lung disease, or persistently elevated liver enzymes were excluded. Mean magnetic resonance imaging (MRI) proton density fat fraction (PDFF) was obtained for all participants. Clinical characteristics [age, sex, body mass index, percent predicted forced expiratory volume at 1 s (FEV1), lumacaftor/ivacaftor use] and blood chemistries were assessed for possible association with hepatic steatosis. Hepatic steatosis was defined as a mean MRI PDFF > 5%. Patients were grouped by Diabetes status (CFRD, NGT) and Cystic fibrosis transmembrane conductance regulator (CFTR) modulator use (lumacaftor/ivacaftor, no lumacaftor/ivacaftor) to determine between group differences. Continuous variables were analyzed with a Wilcoxon rank sum test and discrete variables with a Chi square test or Fisher's exact test. Results Twenty subjects were included in the final analysis. The median age was 22.3 years (11.3-39.0) and median FEV1 was 77% (33%-105%). Twelve subjects had CFRD and 8 had NGT. Nine subjects were receiving lumacaftor/ivacaftor. The median PDFF was 3.0% (0.0%-21.0%). Six subjects (30%) had hepatic steatosis defined as PDFF > 5%. Hepatic fat fraction was significantly lower in patients receiving lumacaftor/ivacaftor (median, range) (2.0%, 0.0%-6.4%) than in patients not receiving lumacaftor/ivacaftor (4.1%, 2.7-21.0%), P = 0.002. Though patients with CFRD had lower PDFF (2.2%, 0.0%-14.5%) than patients with NGT (4.9%, 2.4-21.0%) this did not reach statistical significance, P = 0.06. No other clinical characteristic was strongly associated with hepatic steatosis. Conclusion Use of the CFTR modulator lumacaftor/ivacaftor was associated with significantly lower hepatic steatosis. No association between CFRD and hepatic steatosis was found in this cohort.
