Despite significant advancements in the management of chronic liver disease (CLD), CLD persists as a significant public health concern in the United States [1,2]. The coronavirus disease 2019 (COVID-19) pandemic further exacerbated this challenge, increasing risks for individuals with CLD [3]. In the early stages of the pandemic, healthcare priorities shifted towards COVID-19 management, adversely affecting the care of those with CLD [4]. As a result, there was a notable increase in all-cause mortality associated with alcohol-related liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), while mortality related to hepatitis C virus (HCV) remained relatively stable [5]. With improved access to healthcare, widespread COVID-19 vaccination, and the easing of lockdown measures, these mortality trends may change in the pandemic’s later stages. Recent research indicates that excess deaths unrelated to COVID-19 in the US were 2 to 4 times more prevalent among non-Hispanic Black individuals, non-Hispanic Asian, and Hispanic individuals compared to non-Hispanic White individuals [6]. This suggests that the impact of the COVID-19 pandemic on mortality from CLD may vary across different racial and ethnic groups. This study aims to assess the evolving landscape of CLD mortality trends by race, ethnicity, and sex in the US from 2018 to 2023, encompassing the periods before, during, and after the COVID-19 pandemic.

To analyze trends in quarterly mortality related to CLD from the first quarter (Q1) of 2018 to the fourth quarter (Q4) of 2023, our analysis utilizes a de-identified National Vital Statistics System (NVSS) dataset of adults aged 25 and older, employing previously validated methodologies [5,7]. We used the International Classification of Diseases, Tenth Revision codes to identify ALD (K70: K70.0, K70.1, K70.2, K70.3, K70.4, and K70.9), HCV (B17.1, B18.2, B19.2), and MASLD (K76.0, K75.81). Individuals diagnosed with both HCV and ALD were categorized under HCV.

Race and ethnicity were classified into five mutually exclusive groups: Hispanic (of any race), non-Hispanic White, non-Hispanic Black, non-Hispanic Asian or Pacific Islander, and non-Hispanic American Indian or Alaska Native individuals. Due to the limited number of events, data for the non-Hispanic American Indian or Alaska Native group were deemed unreliable and were excluded from the final mortality analysis by race and ethnicity.

We have defined the pre-pandemic period as January 2018 to December 2019, the pandemic period as January 2020 to May 2023, and the post-pandemic period as May 2023 to December 2023. For our study on the COVID-19 pandemic, we have further categorized the early pandemic phase as January 2020 to December 2020 and the late pandemic phase as January 2021 (marking the start of universal COVID-19 vaccination) through May 2023.

We calculated quarterly age-standardized mortality due to CLD, adjusting for the age distribution of the 2010 US standard population. We analyzed temporal trends using the National Cancer Institute’s Joinpoint Regression Program (version 5.3.0.0). The quarterly percentage change (QPC) for each segment was reported, along with the average QPC, to summarize the trends and transitions [8]. Joinpoint regression was utilized to identify significant change points in mortality trends and to calculate the quarter-toquarter percentage change in quarterly age-standardized mortality, including the 95% confidence interval (CI) and Pvalue [8].

This study examined a total of 18,573,415 deaths among US adults aged 25 and older from 2018 to 2023. Within this population, there were 208,152 deaths attributed to ALD, 82,938 deaths related to HCV, and 47,988 deaths associated with MASLD.

Supplementary Table 1 and Figure 1 show the racial and ethnic differences in age-standardized mortality related to CLD. In the first quarter of 2018, non-Hispanic Black individuals exhibited the highest mortality due to HCV at 3.07 per 100,000 individuals, followed by Hispanic individuals at 2.19, non-Hispanic White individuals at 1.61, and non-Hispanic Asian individuals at 0.62. Although quarterly HCV-related mortality continued to decline, the rate of decrease was slower, particularly among Hispanic and non-Hispanic White individuals during the pandemic. Before the pandemic, quarterly age-standardized HCV-related mortality showed a steady decline, remained relatively stable during the early pandemic, and further decreased in the late pandemic among Hispanic individuals. The downward trend in HCV-related mortality varied by race and ethnicity, with Hispanic individuals experiencing the steepest decline (QPC -3.1%, 95% CI –4.9% to –3.2%), followed by non-Hispanic Black (QPC -2.3%, 95% CI –2.9% to –1.7%), non-Hispanic Asian (QPC –2.0%, 95% CI –2.9% to –1.1%), and non-Hispanic White individuals (QPC –1.9%, 95% CI –2.3% to –1.4%). During the study period, the average quarterly age-standardized mortality related to ALD increased (average QPC 0.8% to 1.3%). Mortality remained stable before the COVID-19 pandemic but saw a sharp rise during the early COVID-19 pandemic across all racial and ethnic groups except non-Hispanic Asian individuals, followed by a decline in the late pandemic. In 2018, Hispanic individuals had the highest mortality at 3.71 per 100,000, compared to 3.24 for non-Hispanic White and 2.02 for non-Hispanic Black individuals. Quarterly age-standardized mortality related to MASLD remained stable before the pandemic but accelerated during the early COVID-19 pandemic, with QPCs ranging from 7.4% for non-Hispanic White to 17.7% for non-Hispanic Black, except for non-Hispanic Asian individuals. In 2023, non-Hispanic White individuals had the highest mortality for MASLD at 1.03 per 100,000, compared to 0.94 for Hispanic individuals and 0.29 for non-Hispanic Asian individuals. The increasing trend in MASLD-related mortality (average QPC 1.4% to 1.9%) was more pronounced than that of ALD-related mortality (average QPC 0.8% to 1.3%).

When examining mortality by sex, we found that HCVand ALD-related mortality were higher in males compared to females (Supplementary Table 1 and Fig. 1). For females, quarterly age-standardized HCV-related mortality showed a steady decline before the pandemic, remained relatively stable during the early pandemic, and decreased further in the late pandemic. In contrast, males experienced a consistent decrease in HCV-related mortality throughout the same periods. ALD-related mortality remained stable for both sexes before the pandemic, saw a sharp increase during the early COVID-19 pandemic, and then declined in the late pandemic. Although MASLD-related mortality was slightly higher in females than in males, the upward trends in MASLD-related mortality were similar for both sexes.

Using the most recent US national mortality data, we identified distinct trends in etiology-based mortality related to CLD across different races, ethnicities, and sexes before, during, and after the COVID-19 pandemic. We noted that the racial and ethnic minority groups in the US bear a disproportionately higher burden of CLD-related mortality. In particular, non-Hispanic Black individuals experienced higher HCV-related mortality, while Hispanic individuals had higher mortality related to ALD and MASLD. Conversely, we observed a more pronounced decline in HCV-related mortality trends among Hispanic and non-Hispanic Black individuals compared to non-Hispanic White individuals. ALD-related mortality remained stable before the pandemic, surged during the early pandemic, and then slightly decreased, returning to pre-COVID levels. Additionally, quarterly age-standardized MASLD-related mortality remained stable before the pandemic but accelerated during the early COVID-19 pandemic.

A recent study indicated that all-cause mortality for ALD and MASLD has risen, with a sharp rise during the early COVID-19 pandemic [9]. During this period, it became challenging to monitor diseases, screen for cirrhosis and hepatocellular carcinoma, and access treatment or liver transplantation for patients with CLD [10]. The increase in ALDrelated mortality before the pandemic was worsened by a rise in harmful drinking during lockdowns and restricted access to support and treatment [3,5,11]. Additionally, the pandemic has led to unhealthy lifestyles, including poor diet and reduced physical activity, which may propagate the surge in the risk of MASLD. However, following the early pandemic, enhanced healthcare access, widespread vaccination, and decreased social isolation likely helped reduce the surge in ALD and MASLD-related deaths. These factors may also have played a role in the continued decline in HCV-related mortality, which decreased after the introduction of potent antiviral agents.

This study benefits from providing updated CLD-related mortality trends, encompassing the COVID-19 pandemic. However, several limitations should be considered. First, the use of multiple causes of death on death certificates may lead to underestimation or misclassification despite coding methods are applied consistently. Second, NVSS 2018-2023 mortality data uses six race categories for racespecific rates, while data from 1999–2019 uses four bridgedrace categories. This difference prevents us from combining the datasets. Finally, data for the non-Hispanic American Indian or Alaska Native population was not included due to concerns about reliability stemming from a small number of events.

A previous study reported that all-cause mortality from ALD and MASLD steadily increased from 2007 to 2016 [1]. During the early COVID-19 pandemic, mortality for ALD and MASLD rapidly accelerated compared to the pre-COVID-19 era [5]. Although mortality from ALD slightly decreased during the late pandemic, returning to pre-COVID levels, increasing trends in mortality from ALD and MASLD have continued in the US [9].

In summary, racial and ethnic minority individuals experience a disproportionately high burden of CLD-related mortality. Future research should focus on formally studying the reasons for these disparities in mortality among racial and ethnic minority individuals with CLD. This may provide insights into key mechanistic pathways and/or gaps in healthcare access.