Racial/ethnic disparities in hepatocellular carcinoma incidence and mortality rates in the United States, 1992-2018.

BACKGROUND AND AIMS: HCC is characterized by racial/ethnic disparities in rates. Recent USA reports suggest that incidence has begun to decline, but it is not clear whether the declines have occurred among all groups, nor whether mortality has declined. Thus, the current study examined USA incidence and mortality between 1992 and 2018. APPROACH & RESULTS: HCC incidence and incidence-based mortality data from the Surveillance, Epidemiology, and End Results program were used to calculate age-standardized rates by race/ethnicity, sex, and age. Trends were analyzed using joinpoint regression to estimate annual percent change (APC). Age-period-cohort models assessed the effects on trends of age, calendar period, and birth cohort. Overall, HCC incidence significantly declined between 2015 and 2018 (APC, -5.6%). Whereas most groups experienced incidence declines, the trends were most evident among Asians/Pacific Islanders, women, and persons <50 years old. Exceptions were the rates among non-Hispanic Black persons, which did not significantly decline (APC, -0.7), and among American Indians/Alaska Natives, which significantly increased (APC, +4.3%). Age-period-cohort modeling found that birth cohort had a greater effect on rates than calendar period. Among the baby boom cohorts, the 1950-1954 cohort had the highest rates. Similar to the overall incidence decline, HCC mortality rates declined between 2013 and 2018 (APC, -2.2%). CONCLUSIONS: HCC incidence and mortality rates began to decline for most groups in 2015, but persistent differences in rates continued to exist. Rates among non-Hispanic Black persons did not decline significantly, and rates among American Indians/Alaska Natives significantly increased, suggesting that greater effort is needed to reduce the HCC burden among these vulnerable groups.

The role of daughters in relation to their mother's cervical cancer diagnosis and treatment in Guatemala: a descriptive study.

PURPOSE: There is currently no information on how caregivers for women diagnosed with cervical cancer in Guatemala, particularly daughters, are affected by their supportive role. This study's objective was to describe the support role of caregivers in the country, with a focus on daughters with a mother diagnosed with cervical cancer. METHODS: This analysis utilizes data from a cross-sectional study which aimed to understand pathways to cervical cancer care. Women seeking cervical cancer treatment at the Instituto de Cancerologia (INCAN) in Guatemala City, Guatemala and their companions were surveyed. Descriptive statistics were calculated. RESULTS: One hundred forty-five women seeking treatment and 71 companions participated in the study. Patient's daughters were most frequently reported as the person who provided the most support (51%) and as the most reported to have encouraged the patient to seek care. Furthermore, daughters were noted as the person most reported to fulfill the major household and livelihood roles of the patient while they were seeking or receiving treatment (38.0%). Most daughters reported that they were missing housework (77%), childcare (63%), and income-earning activities (60%) to attend the appointment with their mothers. CONCLUSION: Our study suggests that in Guatemala cervical cancer patient's daughters have a significant support role in their mother's cancer diagnosis. Furthermore, we found that while caring for their mothers, daughters in Guatemala are often unable to participate in their primary labor activities. This highlights the additional burden that cervical cancer has on women in Latin America.

Disparities in breast cancer mortality among Latin American women: trends and predictions for 2030.

BACKGROUND: Breast cancer is among the leading cause of cancer-related mortality among Latin American and Caribbean (LAC) women, but a comprehensive and updated analysis of mortality trends is lacking. The objective of this study was to determine the breast cancer mortality rates between 1997 and 2017 for LAC countries and predict mortality until 2030. METHODS: We retrieved breast cancer deaths across 17 LAC countries from the World Health Organization mortality database. Age-standardized mortality rates per 100,000 women-years were estimated. Mortality trends were evaluated with Joinpoint regression analyses by country and age group (all ages, < 50 years, and ≥ 50 years). By 2030, we predict number of deaths, mortality rates, changes in population structure and size, and the risk of death from breast cancer. RESULTS: Argentina, Uruguay, and Venezuela reported the highest mortality rates throughout the study period. Guatemala, El Salvador, and Nicaragua reported the largest increases (from 2.4 to 2.8% annually), whereas Argentina, Chile, and Uruguay reported downward trends (from - 1.0 to - 1.6% annually). In women < 50y, six countries presented downward trends and five countries showed increasing trends. In women ≥ 50y, three countries had decreased trends and ten showed increased trends. In 2030, increases in mortality are expected in the LAC region, mainly in Guatemala (+ 63.0%), Nicaragua (+ 47.3), El Salvador (+ 46.2%), Ecuador (+ 38.5%) and Venezuela (+ 29.9%). CONCLUSION: Our findings suggest considerable differences in breast cancer mortality across LAC countries by age group. To achieve the 2030 sustainable developmental goals, LAC countries should implement public health strategies to reduce mortality by breast cancer.

Agreement Between the Prevalence of Nonalcoholic Fatty Liver Disease Determined by Transient Elastography and Fatty Liver Indices.

Nonalcoholic fatty liver disease (NAFLD) is a global public health problem linked to the rising prevalence of obesity and metabolic disorders.1 Accurate estimates of NAFLD in populations are challenging because the gold standard for detection is liver biopsy, an invasive procedure that precludes its use in research settings.2 NAFLD can also be detected via noninvasive imaging, such as ultrasound, magnetic resonance imaging-determined proton density fat fraction, magnetic resonance spectroscopy, and the controlled attenuation parameter derived via transient elastography (CAP-TE).2 Given the complexities of imaging in population studies, however, many estimates have been based on calculated indices, such as the Fatty Liver Index (FLI)3 and the Hepatic Steatosis Index (HSI).4 Concern has been raised that the indices underestimate the prevalence of NAFLD,5 thus downplaying the scope of the public health challenge. Ability to examine whether these concerns are substantive has been provided by a recent study of the US population. Using data from the study, it was reported that the US prevalence of CAP-TE-determined NAFLD was 47.8%.6 The current analysis used data from the same national study to examine how well the fatty liver indices corresponded to CAP-TE-determined NAFLD. Because most persons with NAFLD reportedly have elevated alanine aminotransferase (ALT) levels,7 the correspondence between elevated ALT and CAP-TE was also examined.

Cervical cancer knowledge and barriers and facilitators to screening among women in two rural communities in Guatemala: a qualitative study.

BACKGROUND: Approximately 80% of deaths due to cervical cancer occur in low- and middle-income countries. In Guatemala, limited access to effective screening and treatment has resulted in alarmingly high cervical cancer incidence and mortality rates. Despite access to free-of-cost screening, women continue to face significant barriers in obtaining screening for cervical cancer. METHODS: In-depth interviews (N = 21) were conducted among women in two rural communities in Guatemala. Interviews followed a semi-structured guide to explore knowledge related to cervical cancer and barriers and facilitators to cervical cancer screening. RESULTS: Cervical cancer knowledge was variable across sites and across women. Women reported barriers to screening including ancillary costs, control by male partners, poor provider communication and systems-level resource constraints. Facilitators to screening included a desire to know one's own health status, conversations with other women, including community health workers, and extra-governmental health campaigns. CONCLUSIONS: Findings speak to the many challenges women face in obtaining screening for cervical cancer in their communities as well as existing facilitators. Future interventions must focus on improving cervical cancer-related knowledge as well as mitigating barriers and leveraging facilitators to promote screening.

Cervical cancer mortality among young women in Latin America and the Caribbean: trend analysis from 1997 to 2030.

BACKGROUND: Cervical cancer continues to show a high burden among young women worldwide, particularly in low- and middle-income countries. Limited data is available describing cervical cancer mortality among young women in Latin America and the Caribbean (LAC). The purpose of this study was to examine the mortality trends of cervical cancer among young women in LAC and predict mortality rates to 2030. METHODS: Deaths from cervical cancer were obtained from the World Health Organization mortality database. Age-standardized mortality rates per 100,000 women-years were estimated in women aged 20-44 years using the world standard population for 16 countries (and territories) in LAC from 1997 to 2017. We estimated the average mortality rates for the last 4 years (2014-2017). Joinpoint regression models were used to identify significant changes in mortality trends. Nordpred method was used for the prediction of the mortality rates to 2030. RESULTS: Between 2014 and 2017, Paraguay and Venezuela had the highest mortality rates of cervical cancer, whereas Puerto Rico had the lowest rates. Overall, most of the LAC countries showed downward trends of cervical cancer mortality over the entire period. Significant decreases were observed in Chile (Average annual percent change [AAPC]: - 2.4%), Colombia (AAPC: - 2.0%), Cuba (AAPC: - 3.6%), El Salvador (AAPC: - 3.1%), Mexico (AAPC: - 3.9%), Nicaragua (AAPC: - 1.7%), Panama (AAPC: - 1.7%), and Peru (AAPC: - 2.2%). In contrast, Brazil (AAPC: + 0.8%) and Paraguay (AAPC: + 3.7%) showed significant upward trends. By 2030, mortality rates are not predicted to further decrease in some LAC countries, including Argentina, Paraguay, and Venezuela. CONCLUSIONS: Mortality trends of cervical cancer among young women have large variability in LAC countries. Cervical cancer screening programs have a high priority for the region. Primary and secondary prevention in the community are necessary to accelerate a reduction of cervical cancer mortality by 2030.

Liver cancer mortality in Mexico: trend analysis from 1998 to 2018.

OBJECTIVE: To examine overall, sex, and state-specific liver cancer mortality trends in Mexico. Materials and meth-ods. Joinpoint regression was used to examine the trends in age-standardized mortality rates of liver cancer between 1998-2018. Estimated annual percent change with 95% confi-dence intervals (95%CI) were computed. Age-period-cohort models were used to assess the effects of age, calendar year, and birth cohort. RESULTS: The state-specific mortality rates ranged from 3.34 (Aguascalientes) to 7.96 (Chiapas) per 100 000 person-years. Sex-specific rates were roughly equal, nationwide. Overall, we observed a statistically significant decrease in liver cancer mortality rates between 1998-2018 (annual percent change, -0.8%; 95%CI -1.0, -0.6). The overall age-period-cohort models suggest that birth cohort may be the most important factor driving the trends. CONCLUSIONS: While there was overall decline in liver cancer mortality, differences in rates by region were observed. The regional differences may inform future studies of liver cancer etiology across the country.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

OBJECTIVE: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. MATERIALS AND METHODS: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. RESULTS: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. CONCLUSION: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer.

PURPOSE: Mutations in hereditary breast cancer genes play an important role in the risk for cancer. METHODS: Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. RESULTS: A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM, BARD1, CHEK2, and MSH6. The high ratio of BRCA1/BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212 + 1G > A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P = 0.038) or breast cancer (33% vs 15%, P < 0.001). CONCLUSIONS: Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.

Attributable Fractions of Nonalcoholic Fatty Liver Disease for Mortality in the United States: Results From the Third National Health and Nutrition Examination Survey With 27 Years of Follow-up.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of conditions, from simple steatosis to nonalcoholic steatohepatitis. Studies in the United States have reported an increased mortality risk among individuals with NAFLD; therefore, the population attributable fractions (PAFs) for mortality were examined. APPROACH AND RESULTS: A total of 12,253 adult individuals with ultrasound assessment of NAFLD from the Third National Health and Nutrition Examination Survey and mortality follow-up through 2015 were included in the analysis. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD in association with all-cause and cause-specific mortality. Overall, sex- and race/ethnicity-specific PAFs and 95% CIs were estimated. In the current study, presence of NAFLD was associated with a 20% increased risk of all-cause mortality (HR, 1.20; 95% CI, 1.08, 1.34). The overall PAF for all-cause mortality associated with NAFLD was 7.5% (95% CI, 3.0, 12.0). The PAF for diabetes-specific mortality was 38.0% (95% CI, 13.1, 63.0) overall, 40.8% (95% CI, 2.1, 79.6) in men, and 36.8% (95% CI, 6.6, 67.0) in women. The PAF for liver disease (LD)-specific mortality was notably higher in men (68.3%; 95% CI, 36.3, 100.0) than women (3.5%; 95% CI, -39.7, 46.8). In the race-specific analysis, the PAFs of NAFLD for all-cause mortality (9.3%; 95% CI, 4.0, 14.6) and diabetes-specific mortality (44.4%; 95% CI, 10.8, 78.0) were significantly greater than zero only for whites. CONCLUSIONS: In the United States, approximately 8% of all-cause mortality and more than one-third of LD- and diabetes-specific deaths are associated with NAFLD. With these high percentages, efforts are needed to reduce the burden of NAFLD in the United States.

Cervical cancer mortality in Peru: regional trend analysis from 2008-2017.

BACKGROUND: Cervical cancer is the third leading cause of cancer-related death among Latin American women. Peru has the sixth highest mortality rate for cervical cancer in the region with regional variations. We aimed to determine overall and regional cervical cancer mortality rates and trends in Peru between 2008 and 2017. METHODS: We performed an ecological study on the number of deaths by cervical cancer in Peru. Deaths were extracted from the Peruvian Ministry of Health mortality database. Age-standardized mortality rates (ASMR) were estimated per 100,000 women-years using the world standard Segi population. We computed mortality trends using the Joinpoint regression program, estimating the annual percent change (APC). For spatial analysis, GeoDA software was used. RESULTS: Peru showed downward trends in the last decade (from 11.62 in 2008 to 9.69 in 2017 (APC = - 2.2, 95% CI: - 4.3, - 0.1, p < 0.05). According to regional-specific analysis, the highest ASMR was in the rainforest region, although this declined from 34.16 in 2008 to 17.98 in 2017 (APC = - 4.3, 95% CI: - 7.2, - 1.3, p < 0.01). Concerning spatial analysis and clustering, the mortality rates from 2008 to 2017 showed a positive spatial autocorrelation and significant clustering (Moran's I: 0.35, p < 0.001) predominantly in the neighboring North-East departments (Loreto, Ucayali, and San Martin). CONCLUSIONS: Although mortality trends in the entire population are decreasing, mortality rates remain very high, mainly in the rainforest region. Our results encourage a need for further development and improvement of the current health care delivery system in Peru.

International trends in hepatocellular carcinoma incidence, 1978-2012.

Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.

Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012.

BACKGROUND: Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database. METHODS: Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios. RESULTS: The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.80; ASR for ECC, 2.24), Thailand (ASR for ICC, 2.19; ASR for ECC, 0.71), and Japan (ASR for ICC, 0.95; ASR for ECC, 0.83). Between 1993 and 2012, incidence rates of both ICC and ECC increased in most countries. The largest ASR increases over the study period occurred in Latvia (AAPC, 20.1%) and China (AAPC, 11.1%) for ICC and in Thailand (AAPC, 8.8%) and Colombia (AAPC, 8.5%) for ECC. CONCLUSIONS: In the 20 years examined, ICC and ECC incidence increased in the majority of countries worldwide. ICC and ECC incidence may continue to increase because of metabolic and infectious etiologic factors. Efforts to further elucidate risk factors contributing to these increases in incidence are warranted.

Associations between Helicobacter pylori with nonalcoholic fatty liver disease and other metabolic conditions in Guatemala.

BACKGROUND: Previous studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions. MATERIALS & METHODS: The analysis included 424 participants from a cross-sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated. RESULTS: No overall associations between H pylori,H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions. CONCLUSIONS: While no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition.

Using self-collection HPV testing to increase engagement in cervical cancer screening programs in rural Guatemala: a longitudinal analysis.

BACKGROUND: Cervical cancer is a leading cause of death in low- and middle-income countries. Self-collection testing for human papillomavirus (HPV) is an alternative form of cervical cancer screening that can be completed privately and at home. Understanding how the use of HPV testing influences follow-up care in low-resourced settings is crucial before broad implementation. This study aimed to identify if access to self-collection HPV testing impacts participation in established cervical cancer screening programs among women in two rural communities in Guatemala. METHODS: A cohort of 956 women was recruited in 2016 and followed for 2 years for the HPV Multiethnic Study (HPV MES). At baseline, women answered a questionnaire assessing cervical cancer screening history and were offered self-collection HPV testing. Women were re-contacted yearly to determine receipt of additional screening. Statistical changes in screening behavior before and throughout study participation, stratified by self-collection status, were assessed using McNemar pair tests for proportions. Alluvial plots were constructed to depict changes in individual screening behavior. The odds of changes in Pap-compliance (screened in past 3 years), given collection status, were assessed using multivariate logistic regressions. RESULTS: Reported screening rates increased 2 years after enrollment compared to rates reported for the 3 years before study entry among women who collected a sample (19.1% increase, p < 0.05), received results of their test (22.1% increase, p < 0.05), and received positive (24.2% increase, p < 0.1) or negative results (21.7% increase, p < 0.05). However, most increases came from one community, with minimal changes in the other. The adjusted odds of becoming Pap compliant were higher for women who collected a sample vs. did not (OR: 1.48, 95% CI: 0.64, 3.40), received their result vs. did not (OR: 1.29, 95% CI: 0.52, 3.02), and received a positive result vs. negative (OR: 2.43, 95% CI: 0.63, 16.10). CONCLUSIONS: Participation in self-collection HPV testing campaigns may increase likelihood of involvement in screening programs. However, results varied between communities, and reporting of screening histories was inconsistent. Future work should identify what community-specific factors promote success in HPV testing programs and focus on improving education on existing cervical cancer interventions.

Differences in prostate tumor characteristics and survival among religious groups in Songkhla, Thailand.

BACKGROUND: The incidence and mortality from prostate cancer is expected to increase in the next decade in Thailand. Despite the perceived lower risk in this population vs. developed, western countries, it is becoming an important public health issue. Prostate cancer incidence varies between the most predominant religious groups in Thailand, Buddhists and Muslims. However limited data is available describing the prostate cancer survival in these two populations. Here we examine differences in prostate tumor characteristics and survival between Buddhists and Muslims in the province of Songkhla, Thailand. METHODS: 945 incident prostate cancer cases (1990-2014) from the population-based Songkhla Cancer Registry were used in this analysis. Age, grade, stage, and year at diagnosis were compared across religious groups, using Wilcoxon or Chi-square tests. Kaplan Meier methods were used to estimate the median survival time and 5-year survival probabilities. Cox proportional hazards models were used to estimate hazard ratios (HR) between religious groups and 95% confidence intervals (CI) for mortality in age-adjusted and fully-adjusted models. RESULTS: Prostate tumor characteristics, age, and year at diagnosis were similar across religious groups. The median survival time after diagnosis of prostate cancer was longer in Buddhists 3.8 years compared with Muslims 3.2 years (p = 0.08). The age-adjusted risk of death after prostate cancer diagnosis was higher in Muslims compared with Buddhists (HR: 1.31; 95%CI: 1.00, 1.72). After adjustment by stage and grade, results were slightly attenuated (HR: 1.27, 95%CI: 0.97, 1.67). CONCLUSION: Muslims have shorter survival after prostate cancer diagnosis than do Buddhists in Thailand. The reasons underlying this difference require additional investigation in order to design targeted interventions for both populations.

Associations of per- and polyfluoroalkyl substances and nonalcoholic fatty liver disease in the United States adult population, 2003-2018.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide and a leading cause of liver-related mortality. Prior studies have linked per- and polyfluoroalkyl substances (PFAS) exposure to liver dysfunction and alterations in metabolic pathways, but the extent of a PFAS-NAFLD relationship is unclear. Thus, the aim of the current study was to examine whether there were associations between PFAS exposures and NAFLD in the US adult population over a 16-year period. Methods: Data from 10,234 persons who participated in the National Health and Nutrition Examination Survey between 2003 and 2018 were analyzed. Odds ratios and 95% confidence intervals were calculated using multivariable logistic regression for the associations between PFAS and NAFLD, defined by the Hepatic Steatosis Index (NAFLD-HSI), the Fatty Liver Index (NAFLD-FLI), and by Transient Elastography with Controlled Attenuation Parameter (NAFLD-TE-CAP). Results: Overall, there was a significant inverse association between total PFAS and NAFLD-HSI (P-trend = 0.04). Significant inverse associations were also found between perfluorohexane sulfonic acid (PFHxS) and NAFLD-HSI (P-trend = 0.04), and NAFLD-FLI (P-trend = 0.03). Analysis by time period, 2003-2010 versus 2011-2018, found that while inverse associations were more apparent during the latter period when total PFAS (P-trend = 0.02), PFHxS (P-trend = 0.04), and perfluorooctanoic acid (PFOA) (P-trend = 0.03) were inversely associated with NAFLD-HSI and PFOA was inversely associated with NAFLD-FLI (P-trend = 0.05), there were no significant interaction effects. No significant associations between the PFAS and NAFLD-TE-CAP were found. Conclusions: The current study found no evidence of a positive association between the most common PFAS and NAFLD in the US population.