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1.
Dig Dis Sci ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100160

RESUMO

BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality. METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay. RESULTS: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes. CONCLUSION: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31926338
3.
Artigo em Inglês | MEDLINE | ID: mdl-31734449

RESUMO

BACKGROUND & AIMS: Many individuals presumed to have nonalcoholic fatty liver disease (NAFLD) consume moderate amounts of alcohol. Little is known about patterns of alcohol use in patients with NAFLD or how drinking behaviors affect liver fat. METHODS: We conducted a cross-sectional study of 2475 participants of the Framingham Heart Study with hepatic steatosis, as determined by computed tomography. We performed multivariable-adjusted logistic regression models to evaluate the association between alcohol drinking patterns and hepatic steatosis. Models were adjusted for sociodemographic factors, diet, and the components of the metabolic syndrome. We excluded heavy alcohol users, defined as women who consume more than 14 alcohol drinks per week and men who consume more than 21 alcohol drinks per week. RESULTS: In our sample (mean age, 49.8 ± 10.2 y; 50.3% women), the prevalence of hepatic steatosis was 17.5%. The total number of alcohol drinks per week and the maximum drinks consumed per drinking day each were associated with hepatic steatosis (adjusted odds ratio [aOR], 1.15; 95% CI, 1.02-1.29 and aOR 1.15; 95% CI, 1.02-1.30). Binge drinking occurred in 25.4% of individuals with presumed NAFLD and was associated with an increased odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98) among alcohol users. In a beverage-specific analysis, alcohol use patterns were associated with hepatic steatosis among beer drinkers, but not among wine drinkers. CONCLUSIONS: In a cross-sectional study of participants of the Framingham Heart Study with hepatic steatosis, we observed an association between alcohol use and liver fat, even after excluding heavy alcohol users from our analysis. Alcohol use therefore appears to be a risk factor for NAFLD. Prospective studies are needed to validate these findings and determine if alcohol use should be a focus for research, prevention, and treatment of presumed NAFLD.

4.
Hepatol Commun ; 3(8): 1073-1084, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31388628

RESUMO

Up to 25% of patients with nonalcoholic fatty liver disease (NAFLD) are not obese but may have a fat or muscle composition that predisposes them to NAFLD. Our aim was to determine whether body composition parameters associate with NAFLD and to identify genetic contributors to this association. This study included two cohorts. The first included 2,249 participants from the Framingham Heart Study who underwent a computed tomography scan to evaluate hepatic steatosis, dual-energy x-ray absorptiometry testing to assess body composition, and clinical examination. Body composition parameters were normalized to total body weight. A subset of participants underwent genotyping with an Affymetrix 550K single-nucleotide polymorphism array. The second cohort, Michigan Genomics Initiative, included 19,239 individuals with genotyping on the Illumina HumanCoreExome v.12.1 array and full electronic health record data. Using sex-stratified multivariable linear regression, greater central body fat associated with increased hepatic steatosis while greater lower extremity body fat associated with decreased hepatic steatosis. Greater appendicular lean mass was associated with decreased hepatic steatosis in men but not in women. A polygenic risk score for lipodystrophy (regional or global loss of adipose tissue) was associated with increased hepatic steatosis, increased liver fibrosis, and decreased lower extremity fat mass. Conclusion: Greater central body fat associated with increased hepatic steatosis, while greater lower extremity body fat and, in men, greater appendicular lean mass were associated with decreased hepatic steatosis. A genetic risk score for lipodystrophy was associated with NAFLD and liver fibrosis. Our results suggest that buffering of excess energy by peripheral fat and muscle may protect against NAFLD and liver fibrosis in the general population.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31404666

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is associated with increased liver- and cardiovascular disease (CVD)-related morbidity and mortality. In cross-sectional analyses, NAFLD clusters with several cardiometabolic traits including obesity,1,2 hypertension,3 diabetes,1 and dyslipidemia.3 However, liver fat is dynamic and changes over time. Aside from limited prior studies evaluating diet or exercise interventions, little is known about the association between changes in liver fat and the incidence of CVD risk factors. Additionally, previous studies often have limited follow-up; evaluate only select populations, such as individuals with obesity4,5 or diabetes6-8; and may not account for changes in weight or body mass index (BMI). The aim of the present study was to examine, in a longitudinal cohort, the natural history of liver fat change and the association with the incidence of multiple CVD risk factors.

6.
Therap Adv Gastroenterol ; 12: 1756284819832237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984290

RESUMO

Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. A number of risk factors have been associated with AF, though few studies have explored the association between gastrointestinal and liver diseases and AF. Additionally, AF and treatment for AF may predispose to gastrointestinal and liver diseases. We review the current literature on the bidirectional associations between gastrointestinal and liver diseases and AF. We highlight the gaps in knowledge and areas requiring future investigation.

7.
Liver Int ; 39(8): 1535-1544, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31033142

RESUMO

BACKGROUND & AIMS: Prior studies demonstrated an association between non-alcoholic fatty liver disease and chronic kidney disease (CKD), though data are conflicting. We examined the association between liver fat and prevalent and incident CKD in the Framingham Heart Study (FHS). METHODS: We included FHS participants who underwent computed tomography (CT) from 2002 to 2005 (n = 1315). After excluding heavy alcohol use (n = 211) and missing covariates (n = 117), the final sample included 987 participants. For the incident CKD analysis, we excluded 73 participants with prevalent CKD. Liver fat was measured by the average liver attenuation on CT. Estimated glomerular filtration rate (eGFR) was obtained using the CKD Epidemiology Collaboration Creatinine-Cystatin C equation, and CKD was defined as eGFR < 60 ml/min/1.73 m2 . Microalbuminuria was defined by sex-specific urinary albumin-creatinine ratio cut-offs. Multivariable-adjusted regression models were performed to determine the association between liver fat and CKD. RESULTS: The prevalence of hepatic steatosis and CKD were 19% and 14% respectively (55.9% women, mean age 60 ± 9 years). After adjusting for covariates, we observed no significant associations between liver fat and CKD, microalbuminuria or eGFR in cross-sectional analyses. We observed positive associations between liver fat, incident microalbuminuria and reduced eGFR in age- and sex-adjusted models; these relationships were not significant in multivariable-adjusted models. CONCLUSIONS: In this community-based cohort study, we did not observe significant associations between liver fat and prevalent or incident CKD with a median follow-up time of 12.5 years. The association between NAFLD and CKD may be accounted for by shared risk factors; confirmatory studies are needed.

8.
Dig Dis Sci ; 64(7): 2031-2038, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30945037

RESUMO

BACKGROUND: Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion. METHODS: This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data. RESULTS: The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer). CONCLUSIONS: Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series.


Assuntos
Corticosteroides/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/administração & dosagem , Imunização , Imunogenicidade da Vacina , Imunossupressores/efeitos adversos , /efeitos adversos , Adulto , Biomarcadores/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/imunologia , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento
9.
Curr Obes Rep ; 8(3): 220-228, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30945129

RESUMO

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD), the most prevalent cause of chronic liver disease worldwide, is strongly associated with obesity and insulin resistance. RECENT FINDINGS: Significant weight loss can improve NAFLD and nonalcoholic steatohepatitis (NASH). Diet and exercise that result in a sustained body weight reduction of 7-10% can improve liver fat content, NASH, and fibrosis. Vitamin E can be considered in patients with biopsy-proven NASH without diabetes, though caution must be used in those with prostate cancer. Pioglitazone improves liver histology, including fibrosis, and can be considered in patients with or without diabetes. Glucagon-like peptide-1 (GLP-1) antagonists may be beneficial in NASH, but more studies are needed before they can be recommended. Bariatric surgery, with resultant weight loss, can result in improvement in liver fat and inflammation. NAFLD treatment includes diet and exercise with a target 7-10% weight reduction. Treatment goals include improvements in liver fat content, liver inflammation, and fibrosis.


Assuntos
Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/terapia , Cirurgia Bariátrica , Peso Corporal , Dieta , Exercício , Peptídeo 1 Semelhante ao Glucagon , Humanos , Inflamação , Resistência à Insulina , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/diagnóstico , Masculino , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Pioglitazona , Neoplasias da Próstata , Vitamina E , Perda de Peso
10.
Diabetes ; 68(5): 1073-1083, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30936141

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 × 10-6) with replication at Bonferroni-corrected P < 8.6 × 10-4 Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 × 10-4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood-derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat-associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.


Assuntos
Metilação de DNA/fisiologia , Gorduras/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Biomarcadores/metabolismo , Metilação de DNA/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
Obesity (Silver Spring) ; 27(4): 670-677, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30825267

RESUMO

OBJECTIVE: This study examined the longitudinal associations between genetic risk, change in diet quality, and change in visceral adipose tissue (ΔVAT), abdominal subcutaneous adipose tissue (ΔSAT), and pericardial adipose tissue (ΔPAT). METHODS: A total of 1,677 Framingham Heart Study participants who had ectopic fat depots measured using computed tomography were analyzed. Diet quality was quantified using a Mediterranean-style diet score (MDS) and genetic risk by depot-specific genetic risk scores (GRSs). RESULTS: Per SD improvement in MDS, there was 50 cm3 (95% CI: 14-86; P = 0.007) less fat accumulation in VAT, 52 cm3 (95% CI: 12-92; P = 0.01) less fat accumulation in SAT, and 1.3 cm3 (95% CI: 0.1-2.4; P = 0.04) less fat accumulation in PAT. No association was observed between GRSs and ΔVAT or ΔSAT. Each 1-SD increase in the PAT GRS was associated with a 1.2-cm3 (95% CI: 0.1-2.3; P = 0.03) increase in ΔPAT. In participants with higher PAT GRS, those with ΔMDS ≥ 0 had a favorable change in PAT compared with the counterparts with ΔMDS < 0 (P = 0.008). CONCLUSIONS: Longitudinal improvements in diet quality are associated with less ectopic fat accumulation. This study suggests that diet quality may play a critical role in improving ectopic adiposity profiles.


Assuntos
Adiposidade/fisiologia , Dieta/normas , Gordura Intra-Abdominal/patologia , Obesidade/dietoterapia , Pericárdio/patologia , Gordura Subcutânea Abdominal/patologia , Adulto , Dieta Mediterrânea , Regulação para Baixo , Feminino , Interação Gene-Ambiente , Humanos , Gordura Intra-Abdominal/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão , Pericárdio/metabolismo , Controle de Qualidade , Fatores de Risco , Gordura Subcutânea Abdominal/metabolismo
12.
PLoS One ; 14(3): e0211811, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840670

RESUMO

BACKGROUND: Safety-net hospitals provide care for racially/ethnically diverse and disadvantaged urban populations. Their hospitalized patients with cirrhosis are relatively understudied and may be vulnerable to poor outcomes and racial/ethnic disparities. AIMS: To examine the outcomes of patients with cirrhosis hospitalized at regionally diverse safety-net hospitals and the impact of race/ethnicity. METHODS: A study of patients with cirrhosis hospitalized at 4 safety-net hospitals in 2012 was conducted. Demographic, clinical factors, and outcomes were compared between centers and racial/ethnic groups. Study endpoints included mortality and 30-day readmission. RESULTS: In 2012, 733 of 1,212 patients with cirrhosis were hospitalized for liver-related indications (median age 55 years, 65% male). The cohort was racially diverse (43% White, 25% black, 22% Hispanic, 3% Asian) with cirrhosis related to alcohol and viral hepatitis in 635 (87%) patients. Patients were hospitalized mainly for ascites (35%), hepatic encephalopathy (20%) and gastrointestinal bleeding (GIB) (17%). Fifty-four (7%) patients died during hospitalization and 145 (21%) survivors were readmitted within 30 days. Mortality rates ranged from 4 to 15% by center (p = .007) and from 3 to 10% by race/ethnicity (p = .03), but 30-day readmission rates were similar. Mortality was associated with Model for End-stage Liver Disease (MELD), acute-on-chronic liver failure, hepatocellular carcinoma, sodium and white blood cell count. Thirty-day readmission was associated with MELD and Charlson Comorbidity Index >4, with lower risk for GIB. We did not observe geographic or racial/ethnic differences in hospital outcomes in the risk-adjusted analysis. CONCLUSIONS: Hospital mortality and 30-day readmission in patients with cirrhosis at safety-net hospitals are associated with disease severity and comorbidities, with lower readmissions in patients admitted for GIB. Despite geographic and racial/ethnic differences in hospital mortality, these factors were not independently associated with mortality.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Cirrose Hepática/patologia , Comorbidade , Feminino , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Provedores de Redes de Segurança/estatística & dados numéricos
13.
Liver Int ; 39(6): 1022-1026, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30597691

RESUMO

BACKGROUND & AIMS: Emerging data from paediatric populations suggest that variants in the autophagy-governing immunity-related GTPase M (IRGM) gene may contribute to nonalcoholic fatty liver disease (NAFLD) susceptibility. We examined the relationship between IRGM rs13361189 variants and NAFLD in a community-based cohort of adults. METHODS: We included all Framingham Heart Study participants with available data on the IRGM rs13361189 variant, undergoing study-directed computed tomography (CT) scans of the abdomen (2002-2005). Using multivariable linear and logistic regression modelling, we evaluated cross-sectional associations between rs13361189 genotype and hepatic steatosis (HS). Among the subset of participants without baseline HS and who underwent follow-up CT scan between 2008 and 2011, we used multivariable logistic regression modelling to assess the longitudinal relationship between IRGM rs13361189 genotype and risk for incident HS. RESULTS: Among 2070 participants (50% women; mean age 51 ± 11 years), 332 (16%) had one copy of the variant rs13361189 variant C allele, while 19 (1%) had the CC genotype. Compared to the TT genotype, there was no increased odds of prevalent HS with the CT or CC genotype (multivariable-adjusted odds ratio [OR] 0.93 [95% CI 0.68-128] and 0.86 [95% CI 0.46-1.63], respectively). Among individuals without baseline HS (n = 1052), 19.3% developed incident HS over median 6.1 years. Compared to the TT genotype, neither the CT nor the CC genotype were significantly associated with incident HS (all P > 0.05). CONCLUSION: In our community-based, longitudinal cohort of Caucasian adults, variants in the autophagy-governing IRGM gene at the rs13361189 locus were not associated with increased prevalent or incident HS.

14.
Liver Int ; 39(4): 740-747, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30179294

RESUMO

BACKGROUND & AIMS: Little is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography. METHODS: We performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ≥30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included. RESULTS: Approximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78). CONCLUSIONS: Individuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.

15.
Clin Gastroenterol Hepatol ; 17(6): 1157-1164.e4, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30476583

RESUMO

BACKGROUND & AIMS: Nonalcoholic fatty liver disease is an inflammatory condition that results in progressive liver disease. It is unknown if individuals with hepatic steatosis, but not known to have liver disease, have higher serum concentrations of markers of systemic inflammation and oxidative stress. METHODS: We collected data from 2482 participants from the Framingham Heart Study (mean age, 51 ± 11 y; 51% women) who underwent computed tomography and measurement of 14 serum markers of systemic inflammation. Heavy alcohol users were excluded. The liver:phantom ratio (a continuous parameter of liver attenuation relative to a calibration phantom) was used to identify individuals with radiographic evidence of liver fat. Primary covariates included age, sex, smoking, alcohol, aspirin use, hypertension, dyslipidemia, diabetes, and cardiovascular disease. Body mass index and visceral fat were secondary covariates. We used multivariable linear regression models to assess the association between liver fat and systemic inflammatory markers. RESULTS: In multivariable-adjusted models, liver fat was associated with the following inflammatory markers: high-sensitivity C-reactive protein (P < .001), urinary isoprostanes (P < .001), interleukin 6 (P < .001), intercellular adhesion molecule 1 (P < .001), and P-selectin (P = .002). Additional adjustment for body mass index or visceral fat attenuated the results slightly, although all associations remained statistically significant (P for all ≤ .01). CONCLUSIONS: In a community-based cohort, individuals with hepatic steatosis without known liver disease had higher mean serum concentrations of systemic markers of inflammation. Studies are needed to determine whether treatment of hepatic steatosis reduces systemic inflammation.

16.
Dig Dis Sci ; 63(12): 3241-3249, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30078116

RESUMO

BACKGROUND: Treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) regimens has resulted in high rates of sustained virologic response (SVR). Treatment of vulnerable populations may be improved by incorporating an on-site intensive specialty pharmacy (ON-ISP). AIMS: To describe outcomes of HCV treatment at a safety-net hospital and proportion of subjects achieving SVR for those using the ON-ISP compared to an off-site pharmacy (OFF-SP). METHODS: A retrospective cohort study of 219 subjects treated for HCV with DAA at Boston Medical Center was conducted. Subject characteristics, virologic response, and pharmacy services used were recorded. We used multivariable logistic regression to test the association between ON-ISP and SVR after adjusting for covariates. RESULTS: SVR occurred in 71% of subjects by intention-to-treat (73% among ON-ISP users vs 57% among OFF-SP users) and 95% completing treatment per-protocol (96% among ON-ISP users vs 87% among OFF-SP users). Adjustment for age, sex, ethnicity, insurance, fibrosis, prior treatment, and MELD revealed an increased likelihood of SVR among users of ON-ISP: OR 6.0 (95% CI 1.18-31.0). No significant difference in treatment delay or adverse events was seen among users of either pharmacy type. CONCLUSIONS: HCV treatment with DAA was well tolerated, but the rate of SVR was low (71%) compared to trials. This was due to loss to follow-up, as the per-protocol rate of SVR was much higher (95%). Use of ON-ISP was associated with an increase in SVR and may be valuable for improving care for vulnerable populations.


Assuntos
Antivirais/uso terapêutico , Hepacivirus , Hepatite C , Assistência Farmacêutica , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C/diagnóstico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Assistência Farmacêutica/estatística & dados numéricos , Assistência Farmacêutica/provisão & distribução , Melhoria de Qualidade/organização & administração , Estudos Retrospectivos , Resposta Viral Sustentada , Estados Unidos/epidemiologia , Populações Vulneráveis/estatística & dados numéricos
17.
Gastroenterology ; 155(1): 107-117, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29604292

RESUMO

BACKGROUND & AIMS: Dietary modification has been recommended for treatment of nonalcoholic fatty liver disease (NAFLD), although it is not clear whether improving diet quality can prevent its development. We performed a prospective study to examine the association between diet quality change and change in liver fat. We also examined the association between genetic risk score and liver fat change in individuals with different levels of diet quality change. METHODS: Our study included 1521 participants who attended the seventh and eighth examinations (1998-2001 and 2005-2008) of the second-generation cohort or attended the first and second examinations (2002-2005 and 2008-2011) of the third-generation cohort in the Framingham Heart Study. The self-administered semiquantitative 126-item Harvard food frequency questionnaire was used to determine dietary intake in the year leading up to an examination. We assessed levels of liver fat using liver-phantom ratio (LPR) on computed tomography images from 2002 through 2005 and again from 2008 through 2011. LPR values are inversely related to liver fat: increased LPR indicates decreased liver fat. We examined associations of changes in 2 diet scores, the Mediterranean-style diet score (MDS) and Alternative Healthy Eating Index (AHEI), with changes in liver fat and new-onset fatty liver. We evaluated interactions between diet score change and a weighted genetic risk score for NAFLD, determined based on multiple single-nucleotide polymorphisms identified in genome-wide association studies of NAFLD. The primary outcome was change in LPR between baseline and follow-up measurement. RESULTS: For each 1 standard deviation increase in MDS, the LPR increased (meaning liver fat decreased) by 0.57 (95% confidence interval [CI] 0.27-0.86; P < .001) and the odds for incident fatty liver decreased by 26% (95% CI 10%-39%; P = .002). For each 1 standard deviation increase in AHEI, LPR increased by 0.56 (95% CI 0.29-0.84; P < .001) and the odds for incident fatty liver decreased by 21% (95% CI 5%-35%; P = .02). Increased diet scores were also associated with reduced odds of developing more-advanced fatty liver. Higher genetic risk scores were associated with increased liver fat accumulation in participants who had decreased MDS (P < .001) or AHEI scores (P = .001), but not in those with stable or improved diet scores (P for gene-diet interaction <.001). CONCLUSIONS: In an analysis of participants in the Framingham Heart Study, increasing diet quality, determined based on MDS and AHEI scores, is associated with less liver fat accumulation and reduced risk for new-onset fatty liver. An improved diet is particularly important for individuals with a high genetic risk for NAFLD.


Assuntos
Dietoterapia , Gordura Intra-Abdominal/diagnóstico por imagem , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Adulto , Idoso , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Tomografia Computadorizada por Raios X
19.
Am J Med ; 131(6): 684-692.e12, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29518370

RESUMO

BACKGROUND: We examined the associations among 8 different fat depots accumulated in various anatomic regions and the relationship between these fat depots and multiple cardiometabolic risk factors. METHODS: Participants were from the Framingham Heart Study Offspring and Third Generation who also participated in the multidetector computed tomography substudy in 2002-2005. Exposures were multidetector computed tomography-derived fat depots, including abdominal subcutaneous adipose tissue, abdominal visceral adipose tissue, intramuscular fat, intrathoracic fat, pericardial fat, thoracic periaortic fat, intrahepatic fat, and renal sinus fat. Multivariable-adjusted regression analyses with a forward selection procedure were performed to identify the most predictive fat depots. RESULTS: Of 2529 participants, 51.9% were women (mean age, 51.1 years). Visceral adipose tissue had the strongest correlations with each of the other fat measures (range, 0.26-0.77) and with various cardiometabolic risk factors (range, -0.34 to 0.39). As determined by the selection models, visceral adipose tissue was the only fat depot that was associated with all cardiometabolic risk factors evaluated in this study (all P<.05). Selection models also showed that subcutaneous adipose tissue and intrahepatic fat were associated with cardiometabolic risk factors related to the traits of dysglycemia, dyslipidemia, and hypertension (all P<.05). However, only associations with visceral adipose tissue and intrahepatic fat persisted after further adjustment for body mass index and waist circumference. CONCLUSIONS: Visceral adipose tissue and intrahepatic fat were consistent correlates of cardiometabolic risk factors, above and beyond standard anthropometric indices. Our data provide important insights for understanding the associations between variations in fat distribution and cardiometabolic abnormalities.


Assuntos
Tecido Adiposo/fisiologia , Composição Corporal , Distribuição da Gordura Corporal , Doenças Cardiovasculares/etiologia , Estudos Longitudinais , Doenças Metabólicas/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
Neoplasia ; 20(3): 289-294, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29471289

RESUMO

The biological underpinnings for racial disparities in colorectal cancer (CRC) incidence remain to be elucidated. We have previously reported that the cohesin SA-1 down-regulation is an early event in colon carcinogenesis which is dramatically accentuated in African-Americans. In order to investigate the mechanism, we evaluated single nucleotide polymorphisms (SNPs) for association with SA-1-related outcomes followed by gene editing of candidate SNP. We observed that rs34149860 SNP was significantly associated with a lower colonic mucosal SA-1 expression and evaluation of public databases showed striking racial discordance. Given that the predicted SNP would alter miR-29b binding site, we used CRISPR knock-in in CRC cells and demonstrated that the SNP but not wild-type had profound alterations in SA-1 expression with miR-29b inhibitor. This is the first demonstration of high-order chromatin regulators as a modulator of racial differences, risk alteration with SNPs and finally specific modulation by microRNAs.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Neoplasias Colorretais/genética , Regulação para Baixo/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Sítios de Ligação/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Predisposição Genética para Doença/genética , Células HCT116 , Humanos , MicroRNAs/genética
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