Chronic infection with hepatitis C virus (HCV) was previously the leading indication for liver transplant (LT) in the United States. However, since 2014 the use of direct-acting antivirals (DAAs) has ...decreased the chronic HCV burden, while the prevalence of nonalcoholic steatohepatitis (NASH) has risen substantially through the last decade. Both gender and ethnic disparities in indications for LT have been shown in the past but no data on this have been reported since the implementation of DAAs.
We assessed changes in etiologies for LT listing and in gender and ethnic differences in those listed for LT. Adult patients registered for LT in the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between January 1, 2004 and December 31, 2016 were included. Multinomial logistic regression modeling was used to test for changes in waitlist or liver transplant rates.
The study included 127,164 adult patients registered for LT. By 2016, alcoholic liver disease (ALD) was the leading etiology for waitlisting and LT; NASH was second; hepatocellular carcinoma (HCC) due to chronic HCV and chronic HCV alone were 3rd and 4th. NASH was the leading cause for LT for women and the 2nd leading cause for men (following ALD). NASH increased as the cause in all ethnic subgroups and was the leading cause in 2016 among Asian, Hispanic, and non-Hispanic white females. We also found that although the indication for liver transplant for hepatocellular carcinoma (HCC) due to HCV has increased over the years, this indication decreased for the first time between 2015 and 2016 in both males and females.
NASH is currently the second leading cause for LT waitlist registration/liver transplantation overall, and in females, the leading cause. Given the rate of increase, NASH will likely rise to become the leading indication for LT in males as well.
Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority ...populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee‐for‐service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%). Conclusions: We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969‐1977)
Abstract
To investigate the association of alcohol intake with colorectal cancer risk according to race/ethnicity as well as sex, lifestyle-related factors, alcoholic beverage type, and anatomical ...subsite, we analyzed data from 190,698 black, Native Hawaiian, Japanese-American, Latino, and white persons in Hawaii and California in the Multiethnic Cohort Study, with 4,923 incident cases during a 16.7-year follow-up period (1993–2013). In multivariate Cox regression models, the hazard ratio was 1.16 (95% confidence interval (CI): 1.01, 1.34) for 15.0–29.9 g/day of alcohol and 1.28 (95% CI: 1.12, 1.45) for ≥30.0 g/day among men, and 1.06 (95% CI: 0.85, 1.32) and 1.15 (95% CI: 0.92, 1.43), respectively, among women, compared with nondrinkers (P for heterogeneity according to sex = 0.74). An increased risk was apparent among Native Hawaiians, Japanese Americans, Latinos, and white persons and among individuals with body mass index <25.0 (calculated as weight (kg)/height (m)2), never-users of nonsteroidal antiinflammatory drugs, and those with lower intake of dietary fiber and folate. Beer and wine, but not liquor, consumption was positively related to colorectal cancer risk. The association was stronger for rectum and left-colon tumors than for right-colon tumors. Our findings suggest that the positive association between alcohol and colorectal cancer varies according to race/ethnicity, lifestyle factors, alcoholic beverage type, and anatomical subsite of tumors.
Gallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, ...reproductive and obesity-related factors and GBD in multiethnic populations.
We performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993-2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders.
After a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m
, diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07-1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06-1.42).
Overall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups.
Exposure to poly- and perfluoroalkyl substances (PFAS), a class of persistent organic pollutants, is ubiquitous. Animal studies suggest that PFAS may increase risk of fatty liver and hepatocellular ...carcinoma (HCC) via impacts on hepatic lipid, amino acid, and glucose metabolism, but human data is lacking. We examined associations between PFAS exposure, altered metabolic pathways, and risk of non-viral HCC.
In this nested case-control study, pre-diagnostic plasma PFAS and metabolomics were measured in 50 incident HCC cases and 50 individually matched controls from the Multiethnic Cohort (MEC) study. Cases/controls were matched by age, sex, race, and study area. PFAS exposure and risk of HCC were examined using conditional logistic regression. A metabolome-wide association study and pathway enrichment analysis was performed for PFAS exposure and HCC risk, and key metabolites/metabolic pathways were identified using a meet in the middle approach.
High perfluorooctane sulfonic acid (PFOS) levels (90th percentile from NHANES; >55 μg/L) were associated with 4.5-fold increased risk of HCC (odds ratio 4.5, 95% CI 1.2-16.0). Pathway enrichment analysis showed that PFOS exposure was associated with alterations in amino acid and glycan biosynthesis pathways, which were also associated with HCC risk. We identified 4 metabolites linking PFOS exposure with HCC, including glucose, butyric acid (a short-chain fatty acid), α-ketoisovaleric acid (a branched-chain α-keto acid), and 7α-hydroxy-3-oxo-4-cholestenoate (a bile acid), each of which was positively associated with PFOS exposure and risk of HCC.
This proof-of-concept analysis shows that exposure to high PFOS levels was associated with increased risk of non-viral HCC, likely via alterations in glucose, amino acid, and bile acid metabolism. Larger studies are needed to confirm these findings.
Per- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they are difficult to break down and stay in the human body for years, are extremely common and can cause liver damage. In a first of its kind study, we found that exposure to high levels of perfluorooctanesulfonic acid, one of the most common PFAS chemicals, was linked to increased risk of hepatocellular carcinoma in humans. Hepatocellular carcinoma is difficult to treat and is one of the most common forms of liver cancer, and these findings may provide new avenues for helping to prevent this disease.
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•Associations of PFAS and risk of hepatocellular carcinoma were tested in humans.•PFAS and untargeted metabolomics were assessed in pre-diagnostic samples.•Exposure to high PFOS levels was linked to increased hepatocellular carcinoma risk.•The likely mechanisms were via alterations in glucose, amino acid, and bile acid metabolism.
•We evaluated serum PFAS and RCC risk in a racially and ethnically diverse cohort.•Concentrations of several PFAS differed by race and ethnicity (e.g., higher PFOS and PFNA in African American vs. ...White participants)•PFOA was suggestively associated with increased RCC risk among White participants.•We found a strong positive PFNA-RCC association among African American participants.
Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993–2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall doubling in serum concentration, ORcontinuous = 0.89 (95 %CI = 0.67, 1.18). However, we observed suggestive positive associations among White participants 2.12 (0.87, 5.18) and among participants who had blood drawn before 2002 1.49 (0.77, 2.87). Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall fourth vs. first quartile, OR = 1.84 (0.97, 3.50), Ptrend = 0.04; ORcontinuous = 1.29 (0.97, 1.71), with the strongest association observed among African American participants ORcontinuous = 3.69 (1.33, 10.25), followed by Native Hawaiian 2.24 (0.70, 7.19) and White 1.98 (0.92, 4.25) participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.
HCC incidence varies by race/ethnicity. We characterized racial differences in underlying etiology, presentation, and survival in the linkage of Multiethnic Cohort Study with SEER and Medicare ...claims.
HCC characteristics, treatment, and underlying etiology in participants were obtained. Deaths were ascertained using state death certificates and the National Death Index. Risk factors were collected via questionnaires. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for death.
Among 359 cases, the average age at diagnosis was 75.1. The most common etiology was hepatitis C (HCV) (33%), followed by nonalcoholic fatty liver disease (NAFLD) (31%), and different by ethnicity (
< 0.0001). African Americans (AA) (59.5%) and Latinos (40.6%) were more likely to be diagnosed with HCV-related HCC. In Japanese Americans (33.1%), Native Hawaiians (39.1%), and whites (34.8%), NAFLD was the most common etiology. Receipt of treatment varied across ethnic groups (
= 0.0005); AA had the highest proportion of no treatment (50.0%), followed by Latinos (45.3%), vs. whites (15.2%). HCC (72.2%) was the most common cause of death. In a multivariate analysis, AA (HR = 1.87; 95% CI: 1.06-3.28) had significantly higher mortality compared to whites.
We found significant ethnic differences in HCC underlying etiology, receipt of treatment, and outcome. The findings are important for reducing disparities.
Abstract
Background
Meningioma is the most common intracranial tumor in the US and its etiology remains poorly understood. Meningioma has been predominantly studied among white populations. The aim ...of this study was to evaluate the associations of anthropometric, comorbidity, and hormonal factors with meningioma in an ethnically diverse population.
Methods
A nested case-control analysis was performed within the Multiethnic Cohort (MEC). Meningioma cases were identified via linkage with Medicare and the California Office of Statewide Health Planning and Development Hospital Discharge data and were matched to up to 10 controls. Anthropometric, comorbidities, physical activity level, and hormonal factors at baseline based on questionnaires were evaluated for association with meningioma.
Results
A total of 894 cases and 8918 matched controls were included in this study. Increasing body mass index (BMI) (P-trend = 0.041) and weight increases since age 21 (P-trend = 0.0052) were positively associated with meningioma. Hormonal factors including oral contraceptive use (odds ratio OR: 1.24; 95% CI: 1.01–1.51) and estrogen hormonal therapy use (per 5 years, OR: 1.07; 95% CI: 1.01–1.15) were associated with meningioma risk. Hypertension was positively associated with meningioma (OR: 1.26; 95% CI: 1.09–1.47), with individuals who reported a history of both hypertension and diabetes showing a stronger association (OR: 1.54; 95% CI: 1.17–2.03). The tests for heterogeneity across race/ethnicity were not statistically significant (P heterogeneity ≥ 0.17); however, the association of BMI with meningioma was mainly observed in Japanese Americans (P-trend = 0.0036) and hypertension in Japanese Americans (OR: 1.63; 95% CI: 1.17–2.27) and Native Hawaiians (OR: 1.86; 95% CI: 1.02–3.40).
Conclusion
Obesity, hormonal factors, and hypertension were associated with meningioma in an ethnically diverse population.
Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites. In this large and ethnically diverse cohort, we assessed the transportability of previously identified ...genetic variants for NAFLD, built a genetic risk score (GRS), and examined its association with NAFLD risk in multiple ethnic groups. Thirty previously identified genome‐wide association studies (GWAS) variants (P < 5 × 10−8) and 17 other variants associated with NAFLD were examined in a nested case‐control study of NAFLD (1,448 cases/8,444 controls) in this multi‐ethnic cohort study. We then built a GRS using 11 independent single‐nucleotide polymorphisms from these prior studies and examined its association with NAFLD by cirrhosis status across multiple ethnic groups. Of the 30 GWAS SNPs, 20 (67%) were replicated (P < 0.05) in the pooled multi‐ethnic population. The highest percentage of replication was seen in Latinos (43%), followed by Japanese Americans (37%), Whites (17%), and Native Hawaiians and African Americans (≤10%). Several genetic variants, including those in PNPLA3 (patatin‐like phospholipase domain containing 3), HSD17B13 (hydroxysteroid 17‐beta dehydrogenase 13), TM6SF2 (transmembrane 6 superfamily member 2), GATAD2A (GATA zinc finger domain containing 2A), GCKR (glucokinase regulator), SUGP1 (SURP and G‐patch domain containing 1), MBOAT7 (membrane bound O‐acyltransferase domain containing 7), TRIB1 (tribbles pseudokinase 1), SAMM50 (sorting and assembly machinery component), and ERLIN1 (ER lipid raft associated 1)–CHUK (component of inhibitor of nuclear factor kappa B kinase complex)–CWF19L1 (CWF19 like cell cycle control factor 1) gene cluster, were replicated in at least two ethnic groups. An 11‐SNP weighted GRS was associated with NAFLD risk in the multi‐ethnic population (odds ratio OR per SD increase = 1.41; 95% confidence interval CI = 1.32‐1.50), as well as in each ethnic group (OR ranged from 1.30 in African Americans to 1.52 in Latinos). The GRS–NAFLD association was stronger for NAFLD with cirrhosis (OR = 1.67; 95% CI = 1.46‐1.92) compared to NAFLD without cirrhosis (OR = 1.37; 95% CI = 1.28‐1.46) (P heterogeneity = 0.003). Conclusion: In this ethnically diverse cohort, we replicated several key genetic variants for NAFLD and showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.
In this large and ethnically diverse study, we assessed the transportability of previously identified genetic variants for NAFLD, built a genetic risk score (GRS) with independent SNPs, and examined its association with NAFLD risk in multiple ethnic groups. Several genetic variants were replicated in at least two ethnic groups. A 11‐SNP weighted GRS was associated with NAFLD risk in the multiethnic population with stronger association for NAFLD with cirrhosis. Our study showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.
The association of body size, lifestyle, and medical conditions with renal cell cancer risk was examined among 161,126 Hawaii–Los Angeles Multiethnic Cohort participants (1993–2002). After 8.3 years ...of follow-up, 347 renal cell cancer cases (220 men, 127 women) were identified. Renal cell cancer risk increased with increasing body mass index in men (multivariate relative risk (RR) = 1.06 per unit of body mass index, p = 0.001) and women (RR = 1.07, p < 0.0001). The relative risks associated with being obese compared with being lean were 1.76 (95% confidence interval (CI): 1.20, 2.58) for men and 2.27 (95% CI: 1.37, 3.74) for women. Hypertension was associated with renal cell cancer (RRmen = 1.42, 95% CI: 1.07, 1.87; RRwomen = 1.58, 95% CI: 1.09, 2.28). Smoking was confirmed to be a risk factor for both sexes. Among women, diuretic use was associated with increased risk (RR = 1.63, 95% CI: 1.04, 2.57), whereas physical activity was associated with reduced risk (ptrend = 0.027). Alcohol consumption was inversely associated with risk for men (ptrend = 0.045). Compared with nondrinkers, men who drank ≥1 drinks/day had a 31% lower risk (95% CI: 0.49, 0.96). Results show that body mass index, smoking, and hypertension are risk factors for renal cell cancer in both sexes.
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