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1.
Am J Gastroenterol ; 114(12): 1870-1877, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31688024

RESUMO

OBJECTIVES: Adherence to a healthy diet has been associated with a reduced risk of type 2 diabetes (T2D). Hepatocellular carcinoma (HCC) may have overlapping mechanisms with T2D, such as inflammation and insulin resistance. Thus, we examined the association between a previously developed T2D prevention dietary pattern and HCC risk. METHODS: We followed 87,943 women in the Nurses' Health Study and 49,665 men in the Health Professionals Follow-up Study for up to 32 years. The dietary diabetes risk reduction score, which includes dietary glycemic index, cereal fiber, ratio of polyunsaturated to saturated fats, trans fat, sugar-sweetened beverages, nuts, coffee, and red and processed meats, was obtained using validated food frequency questionnaires and updated every 4 years. The Cox proportional hazards regression model was used to calculate multivariable hazard ratios and confidence intervals (95% CIs). RESULTS: During over 1.9 million person-years, a total of 160 incident HCC cases were identified. The dietary diabetes risk reduction score was associated with a lower risk of HCC (top vs bottom quartile; hazard ratio: 0.57, 95% CI: 0.34-0.95; Ptrend = 0.03). All the individual food and beverage items were associated with the risk of HCC in the expected direction, although the association was weaker than the overall dietary pattern. DISCUSSION: Greater adherence to the T2D prevention diet was associated with a lower risk of developing HCC among US men and women. Further studies are needed to confirm and extend our findings.

2.
Int J Cancer ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677159

RESUMO

Obesity is known to be associated with primary liver cancer (PLC), but the separate effects of excess abdominal and gluteofemoral size are unclear. Thus, we examined the association between waist and hip circumference with risk of PLC overall and by histologic type - hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The Liver Cancer Pooling Project is a consortium of prospective cohort studies that includes data from 1,167,244 individuals (PLC n=2,208, HCC n=1,154, ICC n=335). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Waist circumference, per 5 cm increase, was associated with an 11% increased PLC risk (HR=1.11, 95%CI: 1.09-1.14), including when adjusted for hip circumference (HR=1.12, 95%CI: 1.08-1.17) and also when restricted to individuals in a normal body mass index (BMI) range (18.5-<25 kg/m2 ; HR=1.14, 95%CI: 1.07-1.21). Hip circumference, per 5 cm increase, was associated with a 9% increased PLC risk (HR=1.09, 95%CI: 1.06-1.12), but no association remained after adjustment for waist circumference (HR=0.99, 95%CI: 0.94-1.03). HCC and ICC results were similar. These findings suggest that excess abdominal size is associated with an increased risk of liver cancer, even among individuals considered to have a normal BMI. However, excess gluteofemoral size alone confers no increased risk. Our findings extend prior analyses, which found an association between excess adiposity and risk of liver cancer, by disentangling the separate effects of excess abdominal and gluteofemoral size through utilization of both waist and hip circumference measurements. This article is protected by copyright. All rights reserved.

4.
Ann Intern Med ; 171(5): 318-327, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31426090

RESUMO

Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Design: Prospective propensity score (PS)-matched cohort. Setting: Swedish registers, 2005 to 2013. Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults. Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users. Limitation: Lack of lipid, fibrosis, or HCC surveillance data. Conclusion: In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. Primary Funding Source: None.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31352095
6.
Int J Epidemiol ; 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31302687

RESUMO

BACKGROUND: Epidemiological evidence on the associations between meat intake and risk of hepatocellular carcinoma (HCC) was limited and inconsistent. METHODS: We prospectively examined the association between consumption of meats and meat mutagens with HCC risk using data from the Nurses' Health Study and the Health Professionals Follow-up Study. Cox proportional-hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for known liver-cancer risk factors. RESULTS: During up to 32 years of follow-up, we documented 163 incident HCC cases. The HRs of HCC for the highest vs the lowest tertile intake levels were 1.84 (95% CI: 1.16-2.92, Ptrend = 0.04) for processed red meats and 0.61 (95% CI: 0.40-0.91, Ptrend = 0.02) for total white meats. There was a null association between unprocessed red meats and HCC risk (HR = 1.06, 95% CI: 0.68-1.63, Ptrend = 0.85). We found both poultry (HR = 0.60, 95% CI: 0.40-0.90, Ptrend = 0.01) and fish (HR = 0.70, 95% CI: 0.47-1.05, Ptrend = 0.10) were inversely associated with HCC risk. The HR for HCC risk was 0.79 (95% CI: 0.61-1.02) when 1 standard deviation of processed red meats was substituted with an equivalent amount of poultry or fish intake. We also found a suggestive positive association of intake of meat-derived mutagenicity or heterocyclic amines with risk of HCC. CONCLUSIONS: Processed red meat intake might be associated with higher, whereas poultry or possibly fish intake might be associated with lower, risk of HCC. Replacing processed red meat with poultry or fish might be associated with reduced HCC risk.

7.
Cancer Prev Res (Phila) ; 12(6): 367-374, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31040153

RESUMO

Although increasing evidence suggests a potential beneficial effect of nut consumption on various diseases, no epidemiologic study has yet examined the association between nut consumption and risk of hepatocellular carcinoma (HCC). We prospectively examined this association in 88,783 women from the Nurses' Health Study and 51,492 men from the Health Professionals Follow-up Study. Nut consumption was assessed every 4 years using validated food frequency questionnaires. Multivariable HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression models after adjusting for HCC risk factors. After an average of 27.9 years of follow-up, we identified a total of 162 incident HCC cases. Higher total nut consumption was not significantly associated with HCC risk (the highest vs. lowest tertile intake, HR, 0.84; 95% CI, 0.56-1.26). For the same comparison, higher tree nut consumption was associated with a lower HCC risk (HR, 0.64; 95% CI, 0.43-0.95). We found nonsignificant inverse associations with consumption of walnuts, peanuts, and peanut butter. Overall, nut consumption was not strongly associated with HCC risk. There was a suggestive inverse association with tree nut consumption. Future studies should carefully consider hepatitis B or C virus infections and examine these associations in other racial/ethnic groups.

8.
J Natl Cancer Inst ; 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127946

RESUMO

BACKGROUND: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear. METHODS: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random effects meta-analysis produced summary estimates. All statistical tests were two-sided. RESULTS: Over a period of 38,369,156 person-years of follow-up, 1,391 gallbladder, 758 intrahepatic bile duct, 1,208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (e.g., current versus never smokers hazard ratio [HR] = 1.69, 95% confidence interval [CI] = 1.34 to 2.13 and 2.22, 95%CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all P-trend<0.01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (e.g., >40 cigarettes/day versus never smokers HR = 2.15, 95%CI: 1.15 to 4.00; P-trend=0.001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming ≥5 versus 0 drinks/day (HR = 2.35, 95%CI = 1.46 to 3.78; P-trend=0.04). There was evidence of statistical heterogeneity between several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers. CONCLUSIONS: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract.

10.
JAMA Oncol ; 5(6): 913, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31046070
11.
Clin Gastroenterol Hepatol ; 17(13): 2776-2784.e4, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31077838

RESUMO

BACKGROUND & AIMS: There are few data from prospective studies on the effects of aspirin on fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We performed a prospective cohort study of 361 adults with biopsy-confirmed NAFLD, from 2006 through 2015, examined every 3-12 months for incident advanced fibrosis defined using serial measurements of validated indices (the Fibrosis-4, NAFLD fibrosis score, and aspartate aminotransferase to platelet ratio indices). Histologic analyses of liver biopsies collected at baseline were performed by a blinded pathologist. Information collected at baseline and at each examination included frequency and duration of aspirin and nonsteroidal anti-inflammatory drug (NSAID) use. Using multivariable-adjusted logistic regression, we estimated the association of aspirin use with prevalent steatohepatitis (NASH) and fibrosis. Using multivariable-adjusted Cox proportional hazards modeling, we estimated the association between aspirin use and risk for fibrosis progression. RESULTS: At enrollment, 151 subjects used aspirin daily. Compared with non-regular use, daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% CI, 0.37-0.89) and fibrosis (adjusted odds ratio, 0.54; 95% CI, 0.31-0.82). Among individuals with baseline F0-F2 fibrosis (n = 317), 86 developed advanced fibrosis over 3692 person-years. Daily aspirin users had significantly lower risk for developing incident advanced fibrosis vs non-regular users (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.43-0.85). This relationship appeared to be duration dependent (adjusted P trend=.026), with the greatest benefit found with at least 4 years or more of aspirin use (aHR, 0.50; 95% CI, 0.35-0.73). Conversely, use of nonaspirin NSAIDs was not associated with risk for advanced fibrosis (aHR, 0.93; 95% CI, 0.81-1.05). CONCLUSIONS: In a prospective study of patients with biopsy-proven NAFLD, daily aspirin use was associated with less severe histologic features of NAFLD and NASH, and lower risk for progression to advanced fibrosis with time.

12.
Cancer Res ; 79(15): 3973-3982, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31113819

RESUMO

Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m2 increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.

13.
Int J Cancer ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31116416

RESUMO

Although increasing dairy product intake has been associated with risk of several cancers, epidemiological studies on hepatocellular carcinoma are sparse and have yielded inconsistent results. We prospectively assessed the associations of dairy products (total, milk, butter, cheese and yogurt) and their major components (calcium, vitamin D, fats and protein) with the risk of hepatocellular carcinoma development among 51,418 men and 93,427 women in the Health Professionals Follow-Up Study and the Nurses' Health Study. Diets were collected at baseline and updated every 4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression model. During up to 32 years of follow-up, a total of 164 hepatocellular carcinoma cases were documented. After adjustment for most known hepatocellular carcinoma risk factors, higher total dairy product intake was associated with an increased risk of hepatocellular carcinoma (highest vs. lowest tertile, HR = 1.85, 95% CI: 1.19-2.88; ptrend = 0.009). For the same comparison, we observed significant positive associations of high-fat dairy (HR = 1.81, 95% CI: 1.19-2.76; ptrend = 0.008) and butter (HR = 1.58, 95% CI: 1.06-2.36; ptrend = 0.04) with hepatocellular carcinoma risk. There was a nonsignificant inverse association between yogurt intake and hepatocellular carcinoma risk (HR = 0.72, 95% CI: 0.49-1.05; ptrend = 0.26). Our data suggest that higher intake of high-fat dairy foods was associated with higher, whereas higher yogurt consumption might be associated with lower risk of developing hepatocellular carcinoma among U.S. men and women.

14.
JAMA Oncol ; 5(6): 879-886, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30789662

RESUMO

Importance: Increased intake of whole grain and dietary fiber has been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for hepatocellular carcinoma (HCC). Therefore, we hypothesized that long-term intake of whole grains and dietary fiber may be associated with lower risk of HCC. Objective: To assess the associations of whole grain and dietary fiber intake with the risk of HCC. Design, Setting, and Participants: Cohort study of the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) in 125 455 participants from 2 cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study. Exposures: Intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) were collected and updated almost every 4 years using validated food frequency questionnaires. Main Outcomes and Measures: Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression model after adjusting for most known HCC risk factors. Results: After an average follow-up of 24.2 years, we identified 141 patients with HCC among 125 455 participants (77 241 women and 48 214 men (mean [SD] age, 63.4 [10.7] years). Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC. Conclusions and Relevance: Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.

15.
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.

16.
Hepatology ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30506561

RESUMO

Although adherence to healthy dietary guidelines has been associated with a reduced risk of several health outcomes including cardiovascular diseases, type 2 diabetes, and some cancers, little is known about the role of dietary patterns in the development of hepatocellular carcinoma. We prospectively assessed the associations of 3 key commonly used a priori dietary patterns, the Alternative Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH) with risk of incident hepatocellular carcinoma in the Health Professionals Follow-up Study and the Nurses' Health Study, two large prospective cohort studies. Diet was assessed almost every 4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards regression. During up to 32 years of follow-up, 160 incident hepatocellular carcinoma cases were identified. After adjustment for most hepatocellular carcinoma risk factors, participants in the highest tertile of AHEI-2010 had a multivariable HR of 0.61 (95% CI: 0.39-0.95, Ptrend = 0.03), compared with those in the lowest tertile. There was a suggestive but non-significant inverse association for AMED (HR = 0.75, 95% CI: 0.49-1.15, Ptrend = 0.18), and a null association for DASH (HR = 0.90, 95% CI: 0.59-1.36, Ptrend = 0.61) in relation to the risk of hepatocellular carcinoma development. Our findings suggest that better adherence to the Alternative Healthy Eating Index-2010 may decrease the risk of developing hepatocellular carcinoma among US adults. Future studies are needed to replicate our results, to examine these associations in other populations, and to elucidate the underlying mechanisms. This article is protected by copyright. All rights reserved.

17.
JAMA Oncol ; 2018 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-30286235

RESUMO

Importance: Prospective data on the risk of hepatocellular carcinoma (HCC) according to dose and duration of aspirin therapy are limited. Objective: To examine the potential benefits of aspirin use for primary HCC prevention at a range of doses and durations of use within 2 prospective, nationwide populations. Design, Setting, and Participants: Pooled analysis of 2 prospective US cohort studies: the Nurses' Health Study and the Health Professionals Follow-up Study. Data were accessed from November 1, 2017, through March 7, 2018. A total of 133 371 health care professionals who reported data on aspirin use, frequency, dosage, and duration of use biennially since 1980 in women and 1986 in men were included. Individuals with a cancer diagnosis at baseline (except nonmelanoma skin cancer) were excluded. Main Outcomes and Measures: Cox proportional hazards regression models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for HCC. Results: Of the 133 371 participants, 87 507 were women and 45 864 were men; in 1996, the median time of follow-up, the mean (SD) age was 62 (8) years for women and 64 (8) years for men. Over more than 26 years of follow-up encompassing 4 232 188 person-years, 108 incident HCC cases (65 women, 43 men) were documented. Compared with nonregular use, regular aspirin use (≥2 standard-dose [325-mg] tablets per week) was associated with reduced HCC risk (adjusted HR, 0.51; 95% CI, 0.34-0.77). This benefit appeared to be dose related: compared with nonuse, the multivariable-adjusted HR for HCC was 0.87 (95% CI, 0.51-1.48) for up to 1.5 standard-dose tablets per week, 0.51 (95% CI, 0.30-0.86) for more than 1.5 to 5 tablets per week, and 0.49 (95% CI, 0.28-0.96) for more than 5 tablets per week (P for trend = .006). Significantly lower HCC risk was observed with increasing duration (P for trend = .03); this decrease was apparent with use of 1.5 or more standard-dose aspirin tablets per week for 5 or more years (adjusted HR, 0.41; 95% CI, 0.21-0.77). In contrast, use of nonaspirin nonsteroidal anti-inflammatory drugs was not significantly associated with HCC risk (adjusted HR, 1.09; 95% CI, 0.78-1.51). Conclusions and Relevance: This study suggests that regular, long-term aspirin use is associated with a dose-dependent reduction in HCC risk, which is apparent after 5 or more years of use. Similar associations were not found with nonaspirin NSAIDs. Further research appears to be needed to clarify whether aspirin use represents a feasible strategy for primary prevention against HCC.

18.
Int J Cardiol ; 270: 245-252, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29903515

RESUMO

OBJECTIVE: The nonalcoholic fatty liver disease fibrosis score (NFS) is comprised of unique metabolic risk indicators that may accurately predict residual cardiovascular (CV) risk in patients with established coronary disease and metabolic dysfunction. METHODS: We applied the NFS prospectively to 14,819 post-ACS patients randomized to ezetimibe/simvastatin (E/S) or placebo/simvastatin (P/S), in the IMPROVE-IT trial, using validated NFS cutoffs. The primary endpoint included CV death, myocardial infarction, unstable angina, revascularization or stroke. Outcomes were compared between NFS categories and treatment arms using frequency of events, KM rates and adjusted Cox proportional hazard models. The ability of the NFS to predict recurrent CV events was independently validated in 5395 placebo-treated patients enrolled in the SOLID-TIMI 52 trial. RESULTS: Among 14,819 patients enrolled in IMPROVE-IT, 14.2% (N = 2106) were high-risk (NFS > 0.67). The high-risk group had a 30% increased risk of recurrent major CV events, compared to the low-risk NFS group (HR 1.30 [1.19-1.43]; p < 0.001). Among high-risk patients, ezetimibe/simvastatin conferred a 3.7% absolute reduction in risk of recurrent CV events, compared to placebo/simvastatin (HR 0.85 [0.74-0.98]), translating to a number-needed-to-treat of 27. Similar benefit was not found in the low-risk group (HR ezetimibe/simvastatin vs. placebo/simvastatin, 1.01 [0.91-1.12]; p-interaction = 0.053). The relationship between NFS category and recurrent CV events was independently validated in patients enrolled in SOLID-TIMI 52 (HR for NFS > 0.67 vs. NFS < -1.455 = 1.55 [1.32-1.81]; p < 0.001). CONCLUSION: Stratification of cardiovascular risk by NFS identifies an independent population of patients who are at highest risk of recurrent events, and most likely to benefit from dual lipid-lowering therapy. Clinical trials.gov: NCT00202878.

19.
Inflamm Bowel Dis ; 24(10): 2247-2257, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29788077

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized comorbidity in Crohn's disease (CD), but the mechanisms are poorly understood. Autophagy is a highly conserved process regulating innate immunity that contributes to CD susceptibility. Emerging data suggest that variants in the autophagy-governing IRGM gene may contribute to the accumulation of visceral adipose tissue (VAT) and hepatic fat. Our objective was to characterize the relationship between VAT, IRGM gene variants, and NAFLD risk in patients with CD. Methods: We included all CD patients in the Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM) without history of alcohol abuse or liver disease. Hepatic fat was quantified by liver attenuation (LA) on computed tomography, with NAFLD defined by the validated liver:spleen (L:S) ratio. NAFLD severity was estimated by the FIB-4 Index and alanine aminotransferase (ALT). Using logistic regression modeling, we examined the relationship between VAT, autophagy gene variants, and NAFLD risk. Results: Among 462 patients, 52% had NAFLD. Increasing VAT quartile was associated with reduced LA (mean change, -7.43; 95% confidence interval [CI], -10.05 to -4.81; Ptrend < 0.0001). In the fully adjusted model, patients in the highest VAT quartile had a 2.2-fold increased NAFLD risk (95% CI, 1.21 to 4.14; Ptrend = 0.032) and a 4.2-fold increased risk of ALT>upper limit of normal (ULN) (95% CI, 1.19 to 14.76; Ptrend = 0.017). The relationship between VAT and NAFLD was modified by IRGM variants rs4958847 and rs13361189 (Pinteraction = 0.005 and Pinteraction < 0.001, respectively). Conclusions: In a large CD cohort, VAT was directly associated with prevalent NAFLD, and this relationship was augmented by functionally annotated IRGM variants associated with impaired autophagy.

20.
Int J Cardiol ; 259: 198-204, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29579601

RESUMO

BACKGROUND: Biomarkers to predict the presence and severity of subclinical cardiovascular disease (CVD) in nonalcoholic fatty liver disease (NAFLD) are lacking. METHODS: 3876 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), without known chronic liver disease underwent baseline non-contrast cardiac CT, with NAFLD defined by validated liver:spleen ratio (L:S) < 1.0, and subclinical CVD defined by coronary artery calcium (CAC) score > 0. Randomly-selected subgroups underwent detailed inflammatory marker testing, including LpPLA2 mass (N = 2951), activity (N = 3020), high-sensitivity C-reactive protein (hsCRP; N = 3849), and interleukin-6 (IL-6; N = 3764). Among those with NAFLD, we estimated the prevalence of CAC > 0 and CAC > 100 for each SD biomarker increase, using multivariable log-binomial regression models adjusted for cardiometabolic risk factors. RESULTS: Seventeen percent (N = 668) of participants met the criteria for NAFLD. NAFLD participants were younger (mean age 61 ±â€¯10 vs. 63 ±â€¯10 years, p < .0001) but more likely to have an elevated BMI (mean 31.1 ±â€¯5.5 vs. 28.0 ±â€¯5.2 kg/m2, p < .0001), diabetes (22% vs. 11%, p < .0001), and increased inflammatory biomarkers, including LpPLA2 activity, hsCRP and IL-6 (all p < .0001). Among NAFLD participants, IL-6 was the only biomarker independently associated with prevalent CAC > 0 (PR = 1.06 [1.00-1.11]), or CAC > 100 (PR = 1.09 [1.02-1.17]). In contrast, circulating LpPLA2 mass/activity and hsCRP were not associated with either the prevalence or severity of subclinical CVD (all p > .05). CONCLUSION: In a large, multi-ethnic population with NAFLD, IL-6 is independently associated with the prevalence and severity of subclinical atherosclerosis. Further research into the longitudinal effects of NAFLD on progressive CVD will determine whether IL-6 is a marker or mediator of NAFLD-related atherosclerosis.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etnologia , Interleucina-6/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etnologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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