Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023
Article information
See the commentary-article "Revealing the importance of a multidisciplinary approach to reducing the global burden of SLD through the COVID-19 pandemic: Editorial on “Current burden of steatotic liver disease and fibrosis among adults in the United States, 2017–2023”" on page 625.
Abstract
Background/Aims
Multi-society experts proposed the adoption of new terminology, metabolic dysfunction-associated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.
Methods
Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.
Results
The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4–36.7). Within this category, the age-adjusted prevalence for MASLD was 31.9% (95% CI 30.4–33.4), MetALD 2.2% (95% CI 1.8–2.6), and ALD 0.8% (95% CI 0.6–1.1). The prevalence of SLD and MASLD showed a statistically insignificant decrease during COVID-19, while ALD increased without significance. In contrast, the prevalence of advanced fibrosis in SLD was significantly higher during the COVID-19 era, at 9.8% for 285 dB/m and 7.8% for 263 dB/m, compared to 7.4% (P=0.039) and 6% (P=0.041) in the pre-COVID-19 era. The proportion of advanced fibrosis and cirrhosis in individuals with ALD was two-fold higher than MASLD and MetALD, largely due to increases during the COVID-19 era.
Conclusions
While the prevalence of SLD and its subcategories remained stable, there was a significant increase in advanced fibrosis among SLD individuals during the COVID-19 era, with ALD having a proportion of advanced fibrosis and cirrhosis that was twice as high as MASLD and MetALD.
Graphical Abstract
INTRODUCTION
Previously, the burden of nonalcoholic fatty liver disease (NAFLD) was projected to increase due to rising rates of type 2 diabetes and obesity, and it was identified as the most rapidly increasing cause of chronic liver disease both in the United States (US) and worldwide [1,2]. Recently, a panel of multi-society experts proposed a new terminology and recommended the adoption of a disease spectrum for steatotic liver disease (SLD) that is inclusive of metabolic dysfunction-associated SLD (MASLD), metabolic dysfunction and alcohol-related SLD (MetALD), alcohol-related liver disease (ALD), and cryptogenic SLD [3,4]. The central focus of this classification is to distinctly categorize the SLD based on the impact of cardiometabolic risk factors and alcohol consumption while acknowledging the overlap between the two in individuals with MetALD [3,4]. Therefore, the paradigm shift from NAFLD to MASLD entails not only a change in terminology but also risk-stratified adjustments to the definition. The upper limit for alcohol consumption for MASLD is set at 140 g/week for women and 210 g/week for men. The new terminology also introduces the concept of MetALD, which encompasses individuals with MASLD who consume alcohol between 140–210 g/week, extending up to a maximum of 350–420 g/week. Beyond this threshold of alcohol consumption, individuals are classified as strictly ALD. The new classification impacts the prevalence of disease burden estimates. It attempts to define risk-stratified patient phenotypes that are fundamental to understanding the variation in pathogenesis, facilitate future drug development programs, and provide each individual a pathway to risk-based precision management.
During the global pandemic of coronavirus disease-2019 (COVID-19), individuals with SLD were considered a vulnerable population at increased risk for complications [5]. Hospital resources were largely focused on managing COVID-19, adversely affecting the care of individuals with SLD and other metabolic complications at the primary care level [6]. The COVID-19 pandemic has led to a significant increase in alcohol consumption in the US, with rising alcohol-related complications, including hospitalizations that are likely to have lasting repercussions [7]. The pandemic has fostered unhealthy lifestyles, including unhealthy diets and sedentary behavior, which contribute to MASLD and hepatic fibrosis. A US-based study found that 50% of individuals were noted to have an increase in body weight during the COVID-19 pandemic, with 65% of those who were overweight before the pandemic gaining more weight, compared to 40% of those who were normal weight [8]. However, no studies have examined the national burden of SLD and subcategories using the new terminology, SLD, and comparing pre-COVID-19 and COVID-19 eras. This study investigated the contemporary prevalence of SLD, MASLD, MetALD, and ALD, as assessed by controlled attenuation parameter (CAP) score and fibrosis stage using transient elastography in a nationally representative sample of adults in the US. Additionally, we compared the prevalence of MASLD, MetALD, ALD, and SLD-related fibrosis and cirrhosis between the pre-COVID-19 era (2017–2020 pre-pandemic) and the COVID-19 era (2021–2023).
MATERIALS AND METHODS
Study population
This study analyzes data from the National Health and Nutrition Examination Survey (NHANES) covering the period from 2017 until March 2020 (pre-pandemic data) and from August 2021 to August 2023. The NHANES dataset is a national survey employing a complex, clustered, stratified, multi-stage probability sampling design to represent the US national population accurately. This dataset includes demographic and socioeconomic information, health-related questionnaires and examinations, laboratory tests, and transient elastography.
Of the adults (≥18 years) who underwent examination at a mobile examination center (n=15,300), we excluded 3,101 individuals with missing alcohol consumption questionnaires, cardiometabolic variables, and those for whom transient elastography data were ineligible and incomplete. Consequently, the final study sample was comprised of 12,199 adults with complete data. Upon comparing the overall population that underwent examination at the mobile examination center (n=15,300), populations with transient elastography results (n=13,294), and the final sample with complete data (n=12,199) to evaluate our selection process, we observed that the three groups exhibited comparable demographic and anthropometric traits (Supplementary Table 1). The availability of transient elastography, alcohol consumption questionnaires, and cardiometabolic variables has been characterized as random. Furthermore, our analysis indicated that the demographic characteristics of the larger NHANES sample and the final sample with complete data were similar, thereby mitigating concerns of selection bias.
The NHANES was approved by the National Center for Health Statistics Institutional Review Board. All participants provided written informed consent for their involvement in this survey.
Clinical and laboratory evaluations
The detailed methods for clinical and laboratory data have been previously described [9-11]. In brief, we defined race/ethnicity as non-Hispanic white, non-Hispanic black, Hispanic, non-Hispanic Asians, and others. Marital status was dichotomized as married/living with a partner vs. not. Current smoker was defined as ongoing smoking among individuals who had smoked at least 100 cigarettes in their lifetime. Alcohol consumption was calculated using the previously published method [12].
Definition of steatotic liver disease and advanced fibrosis
The detailed methods for defining SLD and fibrosis stage using transient elastography have been previously described [9-11]. The NHANES examined transient elastography assessment for all participants aged 12 years and older. However, individuals were deemed ineligible for liver transient elastography if they (1) were unable to lie flat on the examination table, (2) were currently pregnant, (3) had an implanted electronic medical device, (4) had a bandage or lesions on the right side of their abdomen near the ribs, or (5) refused to undergo the procedure or had limited time during examination visit [13]. Participants were examined for CAP score and liver stiffness measurements using the Fibroscan model 502 V2 Touch (Echosens, Waltham, MA, USA). Results from transient elastography were considered incomplete if there were fewer than 10 valid liver stiffness measurements, if the interquartile range to median ratio of liver stiffness was 30% or greater, or if participants fasted for less than 3 hours. The inter-observer reliability was 0.94 for CAP and 0.86 for liver stiffness. We defined SLD as CAP scores of 285 dB/m or higher (cut-off optimizing sensitivity and specificity) [14]. For the sensitivity analysis, we defined SLD as CAP scores of 263 dB/m or more (the cut-off of sensitivity fixed at 90%) [14].
Among individuals with SLD, 1) MASLD was defined as the presence of SLD with one or more cardiometabolic criteria and no other discernible cause, such as ALD, MetALD, or other etiology; 2) MetALD was defined as individuals who met both SLD with one or more cardiometabolic criteria and consumption of alcohol between 140–350 g/week if women and 210–420 g/week if men; 3) ALD was defined as a) SLD+alcohol consumption >350 g/week (women)/>420 g/week (men)+cardiometabolic risk factor, or b) SLD+alcohol consumption >140 g/week (women)/>210 g/week (men)+no cardiometabolic risk factors [15]; 4) cryptogenic SLD was defined as SLD with no identifiable cause [3].
Transient elastography values of 8 kPa or higher (≥F2) [16-18], 11.6 kPa or higher (≥F3) [15], and 13.1 kPa or higher (≥F4) [18] were considered to have significant fibrosis, advanced fibrosis, and cirrhosis among individuals with SLD and subcategories of SLD.
Statistical analysis
Due to the complex sample design employed by NHANES, we used appropriate sample weights to reconstitute population-level data for the entire US. Among comparison groups, we present the means ± standard errors of continuous variables and proportions with 95% confidence intervals (CIs) of categorical variables and compare baseline characteristics using the linear regression for continuous variables and the chi-square test for categorical variables. We calculated age-adjusted prevalence estimates using direct standardization with age-based proportions based on the 2020 US Census population. All data analyses were completed using STATA 17.0 (StataCorp, College Station, TX, USA) with Taylor series linearization.
RESULTS
The mean age of the population was 47.2 years (95% CI 46.3–48.1), with 50.0% of the participants identifying as men. The racial and ethnic composition of the NHANES 2017–2023 population closely mirrors that of the US, comprising 62.8% non-Hispanic whites, 10.7% non-Hispanic blacks, 16.3% Hispanics, and 5.4% non-Hispanic Asians.
Prevalence of SLD and SLD subcategories and fibrosis stage among Individuals with SLD
The weighted age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% CI 33.4–36.7, Supplementary Fig. 1), corresponding to approximately 72 million out of a representative 205 million US adults. Within the umbrella term of SLD, the weighted age-adjusted prevalence was 31.9% (95% CI 30.4–33.4) for MASLD, 2.2% (95% CI 1.8–2.6) for MetALD, and 0.8% (95% CI 0.6–1.1) for ALD. As expected, the prevalence of SLD increased to 47.7% (95% CI 46.1–49.3) in a sensitivity analysis where the CAP threshold for SLD was adjusted to ≥263 dB/m (Supplementary Fig. 1). The baseline characteristics of the study population are shown in Table 1. Individuals with SLD were older and had a higher representation of men and Hispanics than those without SLD, while the proportion of non-Hispanic blacks was lower. Additionally, individuals with SLD exhibited higher BMI and waist circumference. Those with MetALD and ALD also had a higher proportion of men, non-Hispanic whites, and current smokers than those without SLD.
Baseline characteristics of the study population based on steatotic liver disease (n=12,199)
As shown in Figure 1A, the prevalence of MASLD was notably higher in Hispanics (38.7%, 95% CI 35.9–41.5), followed by non-Hispanic Asians (32.7%, 95% CI 28.2–37.1), non-Hispanic whites (31.0%, 95% CI 29.0–33.1) and non-Hispanic blacks (25.9%, 95% CI 23.3–28.6). In terms of MetALD, the prevalence was substantially higher in non-Hispanic whites (2.5%, 95% CI 1.9–3.2), followed by Hispanics (1.7%, 95% CI 1.1–2.3), non-Hispanic blacks (1.4%, 95% CI 0.8–2.0) and non-Hispanic Asians (0.4%, 95% CI 0–0.8) as shown in Figure 1C. The prevalence of ALD among different races and ethnicities mimicked the trends in MetALD (Fig. 1E). Although MASLD, MetALD, and ALD were more prevalent among men than women, this disparity is particularly pronounced for ALD with statistical significance. The age-adjusted prevalence was 43.1% (95% CI 41.7–44.6) for MASLD, 3.2% (95% CI 2.8–3.5) for MetALD, and 1.0% (95% CI 0.8–1.3) for ALD, based on a cut-off value of 263 dB/m. The prevalence was comparable across various races/ethnicities and sexes when comparing results based on a cut-off of 285 dB/m (Fig. 1B, 1D, 1F).
Age-adjusted prevalence of SLD subcategories by sex and race/ethnicity in the United States, 2017–2023. (A) Age-adjusted prevalence of MASLD defined as CAP score ≥285 dB/m. (B) Age-adjusted prevalence of MASLD defined as CAP score ≥263 dB/m. (C) Age-adjusted prevalence of MetALD defined as CAP score ≥285 dB/m. (D) Age-adjusted prevalence of MetALD defined as CAP score ≥263 dB/m. (E) Age-adjusted prevalence of ALD defined as CAP score ≥285 dB/m. (F) Age-adjusted prevalence of ALD defined as CAP score ≥263 dB/m. ALD, alcohol-related liver disease; CAP, controlled attenuation parameter; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-related steatotic liver disease; SLD, steatotic liver disease.
Among individuals with MASLD (≥285 dB/m, Fig. 2), the age-adjusted prevalence of significant fibrosis, advanced fibrosis, and cirrhosis was 20.0% (95% CI 17.8–22.3), 8.1% (95% CI 7.0–9.4) and 6.2% (95% CI 5.1–7.5), respectively. The age-adjusted prevalence of advanced fibrosis (20.2%) among individuals with ALD was significantly higher than that of those with MASLD (8.1%) and MetALD (6.3%; P=0.005).
Age-adjusted prevalence of fibrosis and cirrhosis among individuals with SLD subcategories in the United States, 2017–2023. (A) Age-adjusted prevalence of fibrosis and cirrhosis among individuals with SLD subcategories defined as CAP score ≥285 dB/m. (B) Age-adjusted prevalence of fibrosis and cirrhosis among individuals with SLD subcategories defined as CAP score ≥263 dB/m. Transient elastography values of 8 kPa or higher (≥F2), 11.6 kPa or higher (≥F3), and 13.1 kPa or higher (≥F4) were considered to have significant fibrosis, advanced fibrosis, and cirrhosis among individuals with subcategories of SLD. P-value for comparison between MASLD vs. MetALD vs. ALD. ALD, alcohol-related liver disease; CAP, controlled attenuation parameter; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-related steatotic liver disease; SLD, steatotic liver disease.
Comparison of prevalence of SLD and fibrosis between the pre-COVID-19 era (2017–2020 pre-pandemic) and the COVID-19 era (2021–2023)
When comparing the two NHANES cycles (pre-COVID-19 era [2017–March 2020] vs. COVID-19 era [Aug 2021–Aug 2023]), most demographic and clinical characteristics showed no differences. However, alcohol consumption increased during the COVID-19 era, while the number of current smokers declined (Supplementary Table 2).
As shown in Figure 3A, 3B, the prevalence of SLD and MASLD showed a slight decrease during the COVID-19 era, although this change was not statistically significant. In contrast, ALD appeared to increase, but without statistical significance. However, the prevalence of advanced fibrosis among individuals with SLD was significantly higher during the COVID-19 era (9.8% at 285 dB/m and 7.8% at 263 dB/m) compared to the pre-COVID-19 era (7.4% at 285 dB/m [P=0.039] and 6% at 263 dB/m [P=0.041]; Fig. 3C, 3D). Among individuals with SLD (≥263 dB/m), we observed a statistically significant increase in the proportion of significant fibrosis during the COVID-19 era compared to the pre-COVID-19 era. However, there was no difference in the proportion of cirrhosis between the two eras.
Comparison between the Pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) Regarding the Prevalence of SLD and SLD Subcategories and Fibrosis and Cirrhosis among Individuals with SLD in the United States, 2017–2023. (A) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of SLD and SLD subcategories defined as CAP score ≥ 285 dB/m. (B) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of SLD and SLD subcategories defined as CAP score ≥263 dB/m. (C) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of fibrosis and cirrhosis among individuals with SLD defined as CAP score ≥285 dB/m. (D) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of fibrosis and cirrhosis among individuals with SLD defined as CAP score ≥263 dB/m. Transient elastography values of 8 kPa or higher (≥F2), 11.6 kPa or higher (≥F3), and 13.1 kPa or higher (≥F4) were considered to have significant fibrosis, advanced fibrosis, and cirrhosis among individuals with SLD and subcategories of SLD. CAP, controlled attenuation parameter; SLD, steatotic liver disease.
When we disaggregated SLD into subcategories (Fig. 4A–4F), the proportion of significant fibrosis and advanced fibrosis among individuals with MASLD was higher during the COVID-19 era compared to the pre-COVID-19 era; however, these differences did not reach statistical significance (P=0.067 and 0.081 for advanced fibrosis; P=0.083 and 0.125 for significant fibrosis). The proportion of each fibrosis stage among individuals with ALD was nearly two-fold higher during the COVID-19 era compared to the pre-COVID-19 era, but this difference also did not reach statistical significance due to a wide CI stemming from a small sample size of ALD.
Comparison between the Pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) Regarding the prevalence of fibrosis and cirrhosis among individuals with MASLD, MetALD, ALD in the United States, 2017–2023. (A) Comparison between the preCOVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of Fibrosis and Cirrhosis among Individuals with MASLD defined as CAP score ≥285 dB/m. (B) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of Fibrosis and Cirrhosis among Individuals with MASLD defined as CAP score ≥263 dB/m. (C) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of Fibrosis and Cirrhosis among Individuals with MetALD defined as CAP score ≥285 dB/m. (D) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of Fibrosis and Cirrhosis among Individuals with MetALD defined as CAP score ≥263 dB/m. (E) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of Fibrosis and Cirrhosis among Individuals with ALD defined as CAP score ≥285 dB/m. (F) Comparison between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023) regarding the prevalence of Fibrosis and Cirrhosis among Individuals with ALD defined as CAP score ≥263 dB/m. Transient elastography values of 8 kPa or higher (≥F2), 11.6 kPa or higher (≥F3), and 13.1 kPa or higher (≥F4) were considered to have significant fibrosis, advanced fibrosis, and cirrhosis among individuals with SLD and subcategories of SLD. ALD, alcohol-related liver disease; CAP, controlled attenuation parameter; MASLD, metabolic dysfunction-associated steatotic liver disease; MetALD, metabolic dysfunction and alcohol-related steatotic liver disease; SLD, steatotic liver disease.
DISCUSSION
In this population-based study involving a nationally representative sample of American adults, the prevalence of SLD was found to be 35.0%, with 31.9% having MASLD, 2.2% having MetALD, and 0.8% having ALD. Although the prevalence of SLD and its subcategories did not differ between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023), there was a significant increase in the proportion of significant or advanced fibrosis among individuals with SLD during the COVID-19 era compared to the pre-COVID-19 era. Additionally, the proportion of advanced fibrosis and cirrhosis among individuals with ALD was two-fold higher than that of MASLD and MetALD, primarily due to increases during the COVID-19 era.
Although the introduction of the new classification for SLD has led to several national studies examining the prevalence of MASLD, MetALD, and ALD using the NHANES 2017–2020 [15,19,20], none have provided contemporary national estimates, including the recent cycles that included data from the COVID-19 era (August 2021 to August 2023). In the third US NHANES (1988–1994), the prevalence of ultrasonography-diagnosed NAFLD was 34.0%, with advanced fibrosis at 3.2% [21]. A recent study based on the NHANES dataset found that the prevalence of NAFLD, defined by the US Fatty Liver Index, stabilized from 28.3% (1999–2004) to 33.2% (2009–2012) and 31.9% (2013–2016) [22]. However, the prevalence of NAFLD-related advanced fibrosis increased from 3.3% (2005–2008) to 6.4% (2009–2012), and 6.8% (2013–2016) in the US [23]. In accordance with these findings, the prevalence of SLD and its subcategories did not differ between the pre-COVID-19 era (2017–2020) and the COVID-19 era (2021–2023). Instead, we noted a higher proportion of significant (20.4%) or advanced fibrosis (8.5%) among individuals with SLD from 2017 to 2023, along with an upward trend in significant or advanced fibrosis during the recent cycle (2021–2023).
Three studies based on the NHANES 2017–2020 reported SLD prevalence at 37.8% (263 dB/m; n=9,698) [20], 34.6% (288 dB/m; n=7,367) [15], and 42.1% (274 dB/m; n=3,173) [19]. The prevalence for MASLD, MetALD, and ALD was 32.5%, 2.6%, 1.2% at 263 dB/m [20], 31.1%, 2%, 0.7% at 288 dB/m [15], and 37.6%, 3.2%, 1.7% at 274 dB/m, respectively [19]. The reported prevalence of fibrosis in MASLD varied across studies, with findings of 15.2% (8.0 kPa) [19], 20.9% (8.6 kPa) [20], and 7.6% (11.7 kPa) [15]. In individuals with MetALD, the proportion of fibrosis was found to be 9.5% (8.0 kPa) [19], 13.3% (8.6 kPa) [20], and 5.9% (11.7 kPa) [15]. For ALD, the prevalence of fibrosis was reported as 0% (8.0 kPa) [19], and 12% (8.6 kPa) [20]. Although these studies based on the previous NHANES cycle (2017–2020) used various cut-offs of CAP and liver stiffness measurement, their general prevalence for SLD subcategories aligns with our findings, as indicated by a slightly lower prevalence of MASLD in our study. However, our study revealed significantly higher fibrosis in MetALD and ALD than those reported in the previous studies. A recent US community-based study reported SLD prevalence, as defined by MRI proton density fat fraction, to be 75%, with MASLD at 67.3%, MetALD at 4.8%, and ALD at 2.6% [24]. Advanced fibrosis, defined by MR elastography, was reported at 14.9% for MASLD, 7.7% for MetALD, and 14.3% for ALD [24]. The higher prevalence of SLD observed in this study is likely attributable to its focus exclusively on overweight and obese participants, in contrast to our study.
We found that the proportion of advanced fibrosis and cirrhosis among individuals with ALD was two-fold higher than that in those with MASLD and MetALD, largely due to increases during the COVID-19 era. Although several studies noted that there was no significant difference in advanced fibrosis and cirrhosis among the subcategories [15,19,20,24], a previous study showed that the prevalence of advanced fibrosis was higher in metabolic dysfunction-associated fatty liver disease (MAFLD) with significant alcohol consumption than those without, consistent with our findings [25]. A recent meta-analysis showed that moderate alcohol intake increased the risk for advanced fibrosis in individuals with NAFLD [26]. The COVID-19 pandemic has resulted in significant changes in alcohol consumption in the US, marked by increased alcohol consumption and related complications leading to hospitalizations that are likely to have long-lasting repercussions [7]. The pandemic has fostered unhealthy lifestyles, including unhealthy diets and sedentary behavior, both of which contribute to the rapid progression of hepatic fibrosis [8]. All-cause mortality from ALD increased significantly during the COVID-19 era, following a period of stability before the pandemic in the US [27]. Factors contributing to this dramatic rise in mortality, which is linked to ALD rather than COVID-19, may include the inability to seek and attend routine standard-of-care outpatient visits, social isolation leading to mental health illnesses, an increase in harmful drinking and relapse, and barriers to utilize cessation services [28]. A recent study from Denmark indicated that the risk of decompensation and overall mortality increased stepwise from MASLD to MetALD and then to ALD [29]. Another study showed that Individuals with MetALD demonstrated a higher risk of all-cause and cancer-related mortality [30]. The crucial question is whether the required period of abstinence for transitioning a patient from ALD or MetALD to MASLD needs to be determined by their history of excessive alcohol use or if it should also take into account the severity of fibrosis and the presence of cardiometabolic risk factors that may affect the progression of disease post-abstinence. To optimize patient care in the post-COVID-19 era, rising alcohol consumption in the general population must be addressed and curtailed at the societal and policymaking levels.
Hispanics and non-Hispanic Asians exhibit a higher prevalence of MASLD, whereas non-Hispanic whites face a greater risk of MetALD and ALD. Regarding MASLD, the higher prevalence of MASLD in Hispanic populations is partly linked to the PNPLA3 (patatin-like phospholipase domain-containing protein 3) gene polymorphism, rs738409 [31,32]. This variant leads to greater hepatic fat accumulation and inflammation, heightening MASLD risk, and is more common in those of Hispanic descent [31]. Additionally, lifestyle and social factors influence health outcomes, contributing to the observed racial and ethnic disparities in MASLD prevalence [31]. In addition, healthcare disruptions during the COVID-19 pandemic may have exacerbated existing gaps in healthcare inequalities [33]. Implementing multifaceted strategies, such as equitable access, community engagement, and improved access to services with a focus on linkage-to-care, can improve the healthcare system and help reduce disparities among individuals with SLD.
Although this is the first study to investigate the contemporary prevalence of SLD and its subcategories, as well as fibrosis by transient elastography, in a representative sample of the US general population during both the pre-COVID-19 and COVID-19 eras, it does have several limitations. First, the NHANES data lacks histology data, which are considered the gold standard for diagnosing MASLD and fibrosis/cirrhosis. Recently, studies have reported sufficient accuracy of the CAP and liver stiffness measurement compared to biopsy [14,16]. Second, alcohol consumption was assessed through self-reporting of alcohol consumption over the past year rather than by using longitudinal high-sensitivity alcohol metabolites that are available at this time. Third, no universally accepted cut-off guidelines exist for CAP score and liver stiffness. However, we used the most validated cut-off point for CAP score and liver stiffness in several studies [14-18]. Fourth, in comparing individuals with and without available transient elastography data, we found that a higher proportion of obese and older individuals were either ineligible or had incomplete test results (Supplementary Table 3). These results were influenced by the ineligibility criteria and limitations associated with transient elastography beyond the XL probe. Such discrepancies may introduce selection bias, prompting us to interpret our findings cautiously. Finally, as a cross-sectional analysis, this study was unable to assess whether the newly proposed criteria effectively predict future hepatic or extrahepatic complications of SLD.
In conclusion, we report the contemporary national burden of SLD and its subcategories, revealing that one-third of US adults have MASLD. Additionally, there was a significant rise in the proportion of individuals with advanced fibrosis during the COVID-19 era compared to the pre-COVID-19 era. Despite the recent approval of pharmacological agent to treat MASLD, the mainstay for the management of MASLD, MetALD, and ALD involves lifestyle modifications, including regular physical activity, dietary changes, and moderation in alcohol consumption [34,35]. Furthermore, a multidisciplinary effort to integrate lifestyle modifications to control blood pressure, blood glucose, and hyperlipidemia may serve as the foundation for therapeutic strategies for individuals with MASLD and MetALD [36]. An emerging concept of conducting multidisciplinary clinics with the inclusion of clinical pharmacists, dieticians, and physical therapists will provide a comprehensive platform to address both preventative and management needs in this patient population.
Notes
Authors’ contribution
Donghee Kim was involved in study concept and design, analysis, and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content, study supervision, and approval of the final draft manuscript. Pojsakorn Danpanichkul, Karn Wijarnpreecha, and George Cholankeril were involved in interpretation of data, critical revision of the manuscript for important intellectual content, and approval of the final draft manuscript. Aijaz Ahmed and Rohit Loomba were involved in study concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content, study supervision, and approval of the final draft manuscript.
Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
ALD
alcohol-related liver disease
CI
confidence interval
MASLD
metabolic dysfunction-associated steatotic liver disease
MetALD
metabolic dysfunction and alcohol-related steatotic liver disease
NAFLD
non-alcoholic fatty liver disease
NHANES
National Health and Nutrition Examination Survey
SLD
steatotic liver disease
SUPPLEMENTAL MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (http://www.e-cmh.org).
Comparison of demographic and anthropometric characteristics between population examined at the mobile examination center (MEC), population with available transient elastography examination, and final sample
Characteristics of study populations based on the NHANES cycles (2017–2020 vs. 2021–2023, n=12,201)
Comparison of demographic and anthropometric characteristics between individuals with and without available transient elastography data
Age-adjusted Prevalence of SLD by Sex in the United States, 2017–2023. SLD, steatotic liver disease.
References
Article information Continued
Notes
Study Highlights
• This research investigates the prevalence of SLD and its subtypes in the US using NHANES (2017–2023). The findings reveal a weighted age-adjusted prevalence of SLD at 35.0%, impacting around 72 million adults. Among these, 31.9% were diagnosed with MASLD, 2.2% with MetALD, and 0.8% with ALD. Higher rates of MASLD were observed in Hispanics and non-Hispanic Asians, while non-Hispanic whites showed increased risks for MetALD and ALD. The study highlights a rise in advanced fibrosis during the COVID-19 pandemic. These findings emphasize the necessity for enhanced healthcare access and community involvement to tackle disparities in the management of SLD.