Alcoholic and non-alcoholic acute pancreatitis mortality in the United States, 2006–2023: A nationwide trend analysis

Abstract

We analyzed national mortality from Acute pancreatitis (AP) in United States (US) adults from 2006–2023 using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database to compare alcoholic AP (AAP) and non-alcoholic AP (non-AAP) across demographic and geographic groups. During this period, there were 52,904 AP deaths, including 6,759 AAP deaths and 46,145 non-AAP deaths. Overall, AP age-adjusted mortality rate (AAMR) declined from 1.54 to 1.19 per 100,000, and non-AAP AAMR declined from 1.38 to 0.99 per 100,000. In contrast, AAP AAMR increased from 0.13 to 0.23 per 100,000, and AAP deaths rose by more than 60 percent. Crude mortality fell in adults aged 75 years and older but increased in adults aged 25 to 44 years, especially for AAP. AAP deaths increased in both males and females and in both metropolitan and nonmetropolitan areas. These findings show that while non-AAP mortality continues to decline, AAP mortality is increasing and represents a growing, largely preventable source of premature death that warrants targeted prevention, improved access to alcohol use treatment, and community-level policies addressing harmful drinking behaviors, with particular concern for younger adults entering their peak working years.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-026-37268-6.

Introduction

AP is an acute inflammatory condition of the pancreas that ranges from transient abdominal pain to multiorgan failure and death¹. Clinical severity is standardized by the revised Atlanta Classification, which defines mild, moderately severe, and severe AP based on organ failure and local or systemic complications; severe AP is marked by persistent organ failure and drives most fatal cases¹. AP is also a major cause of emergency hospitalization and healthcare spending in the US, contributing substantial direct costs and productivity loss². Because fatal AP is closely linked to irreversible organ dysfunction, national AP mortality trends can serve as a population-level indicator of severe disease burden^1,2.

Etiology is central to AP risk. In the US, most AP is attributed to gallstone-related obstruction or alcohol-associated pancreatic injury³. These pathways affect different populations: gallstone-related AP is more common in older adults and in women, while AAP disproportionately affects working-age men with high-risk alcohol use³. Alcohol exposure itself has shifted. During the COVID-19 pandemic, US adults reported higher drinking frequency, more heavy episodic drinking, and more alcohol-related harm at home⁴. These changes raise concern that AAP incidence and severity may be increasing in younger and middle-aged adults, potentially slowing prior gains in survival.

Access to timely critical care may further influence AP outcomes. The National Center for Health Statistics (NCHS) 2013 urban-rural county classification is widely used to study health gaps between metropolitan and nonmetropolitan areas in the US⁵. Nonmetropolitan hospitals face persistent constraints, including shortages of specialty clinicians, fewer intensive care unit beds, and, in some cases, ICU downsizing or closure, which can delay escalation of organ support for time-sensitive critical illness⁶. These structural limitations are directly relevant to severe AP, which often requires rapid hemodynamic stabilization, respiratory support, and interfacility transfer. Racial and ethnic inequities are also well described: Black patients with AP have been shown to present with greater physiological derangement, including more severe kidney injury, and to encounter barriers to advanced care⁷. Recent national hospitalization analyses continue to report differences in complications, ICU use, and in-hospital mortality across racial and ethnic groups⁸. Together, these observations suggest that AP mortality may vary by etiology, geography, and race and ethnicity, and that these disparities may persist or widen over time⁹.

Despite these concerns, there has not been a recent national mortality analysis that (1) separates AAP from non-AAP, (2) spans contemporary data through 2023, including the COVID-19 period, and (3) characterizes differences by sex, age, race and ethnicity, US Census region, and urbanization. Using nationally representative mortality data from the CDC WONDER system, we describe trends in deaths and AAMRs from AP overall, AAP, and non-AAP in the US from 2006 to 2023. We quantify percent changes in deaths, changes in AAMR, and average annual percent change (AAPC) estimates using Joinpoint regression, and we identify which populations currently carry the greatest mortality burden.

Materials and methods

Study design and data source

We conducted a nationwide ecological time-trend analysis of AP mortality in the US from 2006 through 2023. Mortality data were obtained from the CDC WONDER Underlying Cause of Death database (https://wonder.cdc.gov/)^10,11, which compiles and harmonizes death certificate data for essentially all US residents through the National Vital Statistics System maintained by the NCHS. Each record includes an underlying cause of death coded by the International Classification of Diseases, Tenth Revision (ICD-10), along with demographic and geographic information. Because CDC WONDER provides only de-identified, aggregate data, institutional review board approval and informed consent were not required.

We restricted analyses to adults, since pancreatitis-related death in children is rare and often reflects distinct etiologies. Age was grouped in 10-year categories from 25–34 years through 85+ years. CDC WONDER suppresses cells with fewer than 10 deaths and flags unstable estimates in small strata to protect confidentiality, and we did not attempt to recover or impute suppressed values.

Case definitions and stratification variables

Deaths were included if AP (ICD-10 code K85) was listed as the underlying cause of death. We further classified AP into AAP (ICD-10 code K85.2), attributed to alcohol-related pancreatic injury, and non-AAP (ICD-10 code K85.0, K85.1, K85.3, K85.8, and K85.9), which includes biliary idiopathic acute pancreatitis, biliary acute pancreatitis, drug-induced acute pancreatitis, and other acute pancreatitis⁹. These designations reflect the certifying physician’s judgment of the primary precipitating cause. We explored further etiologic sub-classification within nonalcoholic acute pancreatitis, but partial subgroup counts were frequently suppressed under CDC WONDER privacy rules, limiting the reliability of age-adjusted estimates. Accordingly, we did not conduct additional subtype-specific analyses.

For each year, we extracted mortality counts and mortality rates overall and by sex (female, male); age group (25–34, 35–44, 45–54, 55–64, 65–74, 75–84, and ≥85 years); and race and ethnicity (Hispanic, non-Hispanic (NH) White, NH Black, NH Other). Consistent with national surveillance practice, NH Other combines smaller groups, including American Indian or Alaska Native, Asian, Pacific Islander, Native Hawaiian or Other Pacific Islander, and multiracial individuals¹².

We also summarized mortality by US Census region (Northeast, Midwest, South, West) and by county urbanization. Urbanization was defined using the 2013 NCHS Urban–Rural Classification Scheme for Counties. For analysis, we collapsed the six NCHS categories into metropolitan (large central metro, large fringe metro, medium metro, small metro) and nonmetropolitan (micropolitan, noncore). Because CDC WONDER does not provide AAMR by urbanization after 2020¹³, AAMR by urbanization was analyzed for 2006–2020, and death counts by urbanization were summarized through 2023.

Outcomes and measures

For each subgroup and year, we obtained: (1) the number of deaths; (2) the crude mortality rate per 100,000 persons with 95 percent confidence intervals (CI); and (3) the AAMR per 100,000 persons with 95 percent CI. AAMR is standardized to the 2000 US standard population¹⁴, which permits comparisons over time and across groups with different age structures.

To describe long-term change, we calculated the percent change in deaths from 2006 to 2023 as [(deaths in 2023 − deaths in 2006) / deaths in 2006] × 100 percent¹⁵. We then quantified temporal patterns using the AAPC, which summarizes the mean yearly change in mortality over the study interval on the log scale. For age-stratified analyses, crude mortality rates were used instead of AAMR because CDC WONDER does not generate age-adjusted rates for 10-year age bands.

Statistical analysis

We modeled trends in AAMR (or crude mortality rate for age-band analyses) using the Joinpoint Regression Program (version 5.2.0.0, National Cancer Institute). Joinpoint fits piecewise log-linear segments to annual rates and uses permutation tests to identify statistically supported inflection points (“joinpoints”), then reports the annual percent change (APC) for each segment and the overall AAPC with parametric 95 percent CIs^16,17. We used default permutation-based model selection and default confidence interval settings. Analyses of urbanization were restricted to 2006–2020 for AAMR because of post-2020 data limitations. All other data processing and quality checks were performed in R version 4.4.3. We did not impute any suppressed cells (<10 deaths), consistent with the CDC WONDER confidentiality policy.

Ethical considerations

The study utilized publicly available, de-identified aggregate data. CDC WONDER data comply with federal confidentiality standards and contain no individual identifiers. Therefore, the analysis was exempt from institutional review board review and did not require informed consent.

Results

National mortality trends in acute pancreatitis

From 2006 to 2023, there were 52,904 deaths attributed to AP in the US (Table 1). Annual AP deaths were similar in 2006 (3,040 deaths) and 2023 (3,018 deaths), a −0.72 percent change. However, the national AAMR for AP declined from 1.54 per 100,000 (95% CI: 1.48 to 1.59) in 2006 to 1.19 per 100,000 (95% CI: 1.15 to 1.24) in 2023, with an AAPC of −1.43 percent (95% CI: −3.20 to 0.37) (Figure 1). When separated by etiology, AAP and non-AAP followed opposite trends. AAP deaths rose 63.3 percent (297 to 485) and its AAMR increased from 0.13 to 0.23 per 100,000, whereas non-AAP deaths fell 7.66 percent (2,743 to 2,533) and its AAMR declined from 1.38 to 0.99 per 100,000 (Figure 2).

Table 1.

Acute pancreatitis deaths and AAMR in the United States in 2006 and 2023, and their temporal trends.

Characteristic	Deaths				AAMR
	2006-2023	2006	2023	Percent change	2006 (95% CI)	2023 (95% CI)	AAPC (95% CI)
Both	52904	3040	3018	-0.72	1.54 (1.48 to 1.59)	1.19 (1.15 to 1.24)	-1.43 (-3.20 to 0.37)
Female	21829	1350	1179	-12.67	1.17 (1.11 to 1.23)	0.82 (0.77 to 0.87)	-2.06 (-4.13 to 0.06)
Male	31075	1690	1839	8.82	1.94 (1.85 to 2.03)	1.56 (1.49 to 1.64)	-1.17 (-3.50 to 1.22)
Census region
Northeast	8527	547	500	-8.59	1.38 (1.26 to 1.50)	1.09 (0.99 to 1.18)	-0.63 (-1.80 to 0.56)
Midwest	12122	678	698	2.95	1.49 (1.38 to 1.61)	1.32 (1.22 to 1.42)	-0.44 (-1.94 to 1.09)
South	21967	1285	1214	-5.53	1.81 (1.71 to 1.91)	1.25 (1.17 to 1.32)	-1.69 (-2.71 to -0.66)
West	10288	530	606	14.34	1.25 (1.14 to 1.36)	1.03 (0.95 to 1.12)	-1.44 (-3.85 to 1.04)
Race
Hispanic	4073	191	265	38.74	1.30 (1.10 to 1.50)	0.78 (0.68 to 0.88)	-2.39 (-4.52 to -0.21)
NH Black	6413	374	364	-2.67	1.89 (1.69 to 2.08)	1.30 (1.17 to 1.44)	-1.75 (-3.46 to -0.02)
NH White	40567	2396	2254	-5.93	1.54 (1.48 to 1.60)	1.32 (1.26 to 1.38)	-0.86 (-2.80 to 1.11)
NH Other	1714	71	133	87.32	0.88 (0.68 to 1.13)	0.65 (0.54 to 0.76)	-1.49 (-2.72 to -0.26)
2013 urbanization level*
Metropolitan	42058	2426	2433	0.29	1.49 (1.43 to 1.55)	1.23 (1.18 to 1.28)	-1.31 (-2.69 to 0.08)
Nonmetropolitan	10846	614	585	-4.72	1.76 (1.62 to 1.90)	1.61 (1.47 to 1.74)	-1.81 (-2.59 to -1.02)
Age group#
25-34	2524	102	174	70.59	0.26 (0.21 to 0.31)	0.38 (0.33 to 0.44)	2.17 (-1.77 to 6.28)
35-44	4594	246	320	30.08	0.57 (0.50 to 0.64)	0.72 (0.64 to 0.80)	1.18 (-3.07 to 5.62)
45-54	7328	404	390	-3.47	0.93 (0.84 to 1.02)	0.96 (0.87 to 1.06)	-0.08 (-3.69 to 3.66)
55-64	9898	488	573	17.42	1.53 (1.39 to 1.66)	1.37 (1.26 to 1.48)	-0.21 (-1.25 to 0.83)
65-74	10482	553	657	18.81	2.88 (2.64 to 3.12)	1.89 (1.75 to 2.04)	-1.94 (-2.97 to -0.90)
75-84	10077	686	539	-21.43	5.24 (4.85 to 5.63)	2.93 (2.69 to 3.18)	-3.49 (-3.92 to -3.05)
85+	8001	561	365	-34.94	11.53 (10.58 to 12.48)	5.89 (5.29 to 6.50)	-4.12 (-4.89 to -3.36)

AAMR, age-adjusted mortality rate; CI, confidence interval; AAPC, average annual percent change; NH, non-Hispanic.

^*AAMR in 2023 is based on data in 2020.

^#AAMR was replaced by crude mortality.

Fig. 1.

Temporal trends in AAMRs for acute pancreatitis in the United States, overall and by sex, 2006–2023. Abbreviations: AAMR, age-adjusted mortality rate; APC, annual percent change.

Fig. 2.

Temporal trends in AAMRs for acute pancreatitis subtypes, 2006–2023. Abbreviations: AAMR, age-adjusted mortality rate; APC, annual percent change; AAPC, average annual percent change.

Notably, the national decline was not monotonic. Across etiologies, AAMR showed a clear pandemic-era inflection, with a transient increase between 2019 and 2021 that was visible in both AAP and non-AAP trends, before rates resumed their longer-term decline toward 2023.

Sex differences

Over the study period, males accounted for 31,075 AP deaths and females for 21,829 (Table 1). In females, AP deaths fell from 1,350 in 2006 to 1,179 in 2023 (−12.67 percent), and the female AP AAMR declined from 1.17 to 0.82 per 100,000 (AAPC −2.06 percent). In males, AP deaths increased from 1,690 to 1,839 (+8.82 percent), although the male AP AAMR still decreased from 1.94 to 1.56 per 100,000 (Figure 1). The sex gap was most pronounced for AAP. AAP deaths were predominantly male (5,191 male vs 1,568 female), and increased in both sexes (male: 230 to 371; female: 67 to 114) (Table 2 and Figure S1). By contrast, in non-AAP, female deaths declined (−16.99 percent) and male deaths were essentially stable (+0.55 percent), while AAMR fell in both sexes (Table 3 and Figure S2).

Table 2.

Acute alcoholic pancreatitis deaths and AAMR in the United States in 2006 and 2023, and their temporal trends.

Characteristic	Deaths				AAMR
	2006-2023	2006	2023	Percent change	2006 (95% CI)	2023 (95% CI)	AAPC (95% CI)
Both	6759	297	485	63.3	0.13 (0.12 to 0.15)	0.23 (0.21 to 0.25)	2.00 (-2.04 to 6.21)
Female	1568	67	114	70.15	0.07 (0.05 to 0.09)	0.09 (0.07 to 0.11)	1.97 (-12.18 to 18.40)
Male	5191	230	371	61.3	0.23 (0.20 to 0.26)	0.34 (0.30 to 0.38)	1.17 (-2.29 to 4.76)
Census region
Northeast	861	44	43	-2.27	0.12 (0.09 to 0.17)	0.13 (0.09 to 0.17)	0.14 (-2.59 to 2.94)
Midwest	1413	57	126	121.05	0.11 (0.09 to 0.15)	0.28 (0.23 to 0.33)	5.32 (-3.30 to 14.71)
South	2271	100	179	79	0.11 (0.09 to 0.13)	0.20 (0.17 to 0.23)	2.23 (-3.01 to 7.76)
West	2214	96	137	42.71	0.21 (0.17 to 0.26)	0.25 (0.21 to 0.29)	0.55 (-5.39 to 6.86)
Race
Hispanic	653	33	54	63.64	0.19 (0.13 to 0.27)	0.15 (0.11 to 0.20)	-0.18 (-3.73 to 3.49)
NH Black	1009	44	80	81.82	0.19 (0.14 to 0.26)	0.30 (0.23 to 0.37)	0.96 (-4.72 to 6.97)
NH White	4812	214	331	54.67	0.13 (0.11 to 0.15)	0.23 (0.20 to 0.26)	2.43 (-2.03 to 7.09)
NH Other	226	NA	19	NA	NA	NA	NA
2013 urbanization level*
Metropolitan	5629	251	401	59.76	0.16 (0.14 to 0.18)	0.26 (0.24 to 0.29)	2.15 (-3.33 to 7.94)
Nonmetropolitan	1130	46	84	82.61	0.13 (0.09 to 0.17)	0.27 (0.21 to 0.33)	2.22 (-1.48 to 6.06)
Age group#
25-34	764	24	53	120.83	0.06 (0.04 to 0.09)	0.12 (0.09 to 0.15)	NA
35-44	1358	64	115	79.69	0.15 (0.11 to 0.19)	0.26 (0.21 to 0.31)	2.50 (-2.46 to 7.71)
45-54	1897	104	119	14.42	0.24 (0.19 to 0.29)	0.29 (0.24 to 0.35)	0.07 (-3.08 to 3.33)
55-64	1699	68	112	64.71	0.21 (0.17 to 0.27)	0.27 (0.22 to 0.32)	1.45 (-1.91 to 4.92)
65-74	750	20	65	225	0.10 (0.06 to 0.16)	0.19 (0.14 to 0.24)	NA
75-84	242	14	18	28.57	NA (0.06 to 0.18)	NA (0.06 to 0.15)	NA
85+	49	NA	NA	NA	NA	NA	NA

AAMR, age-adjusted mortality rate; CI, confidence interval; AAPC, average annual percent change; NH, non-Hispanic.

^*AAMR in 2023 is based on data in 2020.

^#AAMR was replaced by crude mortality.

Table 3.

Non-alcoholic acute pancreatitis deaths and AAMR in the United States in 2006 and 2023, and their temporal trends.

Characteristic	Deaths				AAMR
	2006-2023	2006	2023	Percent change	2006 (95% CI)	2023 (95% CI)	AAPC (95% CI)
Both	46145	2743	2533	-7.66	1.38 (1.33 to 1.43)	0.99 (0.95 to 1.03)	-1.90 (-3.95 to 0.20)
Female	20261	1283	1065	-16.99	1.10 (1.04 to 1.16)	0.73 (0.68 to 0.77)	-1.96 (-3.27 to -0.62)
Male	25884	1460	1468	0.55	1.67 (1.58 to 1.75)	1.22 (1.15 to 1.28)	-1.68 (-3.73 to 0.42)
Census region
Northeast	7666	503	457	-9.15	1.27 (1.16 to 1.39)	0.96 (0.87 to 1.05)	-0.79 (-2.12 to 0.56)
Midwest	10709	621	572	-7.89	1.35 (1.24 to 1.45)	1.08 (0.99 to 1.17)	-1.23 (-2.00 to -0.45)
South	19696	1185	1035	-12.66	1.67 (1.57 to 1.76)	1.04 (0.97 to 1.10)	-2.36 (-3.00 to -1.72)
West	8074	434	469	8.06	1.04 (0.94 to 1.14)	0.79 (0.72 to 0.87)	-1.81 (-4.93 to 1.42)
Race
Hispanic	3420	158	211	33.54	1.13 (0.94 to 1.32)	0.66 (0.57 to 0.75)	-2.59 (-3.73 to -1.45)
NH Black	5404	330	284	-13.94	1.70 (1.52 to 1.89)	1.02 (0.90 to 1.14)	-2.26 (-3.96 to -0.54)
NH White	35755	2182	1923	-11.87	1.41 (1.35 to 1.47)	1.07 (1.02 to 1.12)	-1.07 (-2.07 to -0.05)
NH Other	1452	67	114	70.15	0.88 (0.67 to 1.13)	0.54 (0.44 to 0.64)	-2.19 (-3.42 to -0.95)
2013 urbanization level*
Metropolitan	36429	2175	2032	-6.57	1.31 (1.26 to 1.37)	1.01 (0.97 to 1.06)	-2.39 (-3.04 to -1.72)
Nonmetropolitan	9716	568	501	-11.80	1.63 (1.50 to 1.77)	1.36 (1.23 to 1.48)	-2.26 (-2.99 to -1.53)
Age group#
25-34	1760	78	121	55.13	0.20 (0.16 to 0.25)	0.27 (0.22 to 0.31)	1.72 (-3.78 to 7.53)
35-44	3236	182	205	12.64	0.42 (0.36 to 0.48)	0.46 (0.40 to 0.52)	1.72 (0.39 to 3.06)
45-54	5431	300	271	-9.67	0.69 (0.61 to 0.77)	0.67 (0.59 to 0.75)	0.43 (-2.64 to 3.59)
55-64	8199	420	461	9.76	1.32 (1.19 to 1.44)	1.10 (1.00 to 1.20)	-0.64 (-1.55 to 0.27)
65-74	9732	533	592	11.07	2.78 (2.54 to 3.01)	1.71 (1.57 to 1.84)	-2.31 (-3.32 to -1.30)
75-84	9835	672	521	-22.47	5.13 (4.74 to 5.52)	2.84 (2.59 to 3.08)	-3.61 (-4.02 to -3.19)
85+	7952	558	362	-35.13	11.47 (10.52 to 12.42)	5.84 (5.24 to 6.45)	-4.15 (-4.94 to -3.36)

AAMR, age-adjusted mortality rate; CI, confidence interval; AAPC, average annual percent change; NH, non-Hispanic.

^*AAMR in 2023 is based on data in 2020.

^#AAMR was replaced by crude mortality.

Consistent with the national pattern, AP AAMR in both sexes exhibited a brief increase during 2019 to 2021, which was apparent in the sex-stratified curves prior to the subsequent return toward longer-term declines.

Age-specific patterns

Age patterns showed a shift toward relatively younger adults (Tables 1–3). In AP overall, deaths rose in younger groups: ages 25 to 34 years increased from 102 to 174 deaths (+70.59 percent), and ages 35 to 44 years increased from 246 to 320 deaths (+30.08 percent). At the same time, mortality in the oldest groups declined sharply. AP deaths in those aged 75 to 84 years fell from 686 to 539 (−21.43 percent), and in those aged 85 years and older fell from 561 to 365 (−34.94 percent), with crude mortality rates in the 85+ group dropping from 11.53 to 5.89 per 100,000 (AAPC −4.12 percent) (Figure 3). AAP in particular increased in both younger and older adults, including ages 25 to 34 years (24 to 53 deaths, +120.83 percent) and ages 65 to 74 years (20 to 65 deaths, +225 percent), although some estimates in the oldest age strata were suppressed (Figure S3 and S4).

Fig. 3.

Temporal trends in crude death rates for acute pancreatitis by age group, 2006–2023. Abbreviations: APC, annual percent change.

Racial and ethnic differences

From 2006 to 2023, most AP deaths occurred in NH White decedents (40,567 deaths), followed by NH Black (6,413 deaths), Hispanic (4,073 deaths), and NH Other (1,714 deaths) (Table 1). AP deaths increased in Hispanic (+38.74 percent, 191 to 265) and NH Other (+87.32 percent, 71 to 133) groups, and were more stable or slightly lower in NH White (−5.93 percent) and NH Black (−2.67 percent) groups. Despite these differences in absolute counts, AP AAMR declined in all racial and ethnic groups. For example, AP AAMR fell from 1.30 to 0.78 per 100,000 in Hispanic decedents and from 1.89 to 1.30 per 100,000 in NH Black decedents (Figure 4). AAP deaths rose across multiple racial and ethnic groups, including NH Black (44 to 80 deaths, +81.82 percent) and NH White (214 to 331 deaths, +54.67 percent) (Table 2 and Figure S5). In contrast, non-AAP deaths fell in NH White and NH Black groups but increased in Hispanic and NH Other groups, even though non-AAP AAMR decreased in all groups (Table 3 and Figure S6). The race/ethnicity-stratified AAMR curves also showed a consistent pandemic-era reversal, with AAMR increasing between 2019 and 2021 across groups before resuming decline thereafter.

Fig. 4.

Temporal trends in AAMRs for acute pancreatitis by race/ethnicity, 2006–2023. Abbreviations: AAMR, age-adjusted mortality rate; APC, annual percent change; NH, non-Hispanic.

Geographic variation by Census region

Geographic patterns differed by US Census region (Tables 1–3). The South had the highest cumulative AP mortality burden (21,967 deaths from 2006 to 2023), followed by the Midwest (12,122), West (10,288), and Northeast (8,527). From 2006 to 2023, AP deaths decreased in the South (−5.53 percent) and Northeast (−8.59 percent), rose modestly in the Midwest (+2.95 percent), and rose in the West (+14.34 percent). Age-adjusted mortality declined in all regions, including a drop in AP AAMR in the South from 1.81 to 1.25 per 100,000 (AAPC −1.69 percent) (Figure 5). AAP deaths increased sharply in the Midwest (+121.05 percent, 57 to 126) and the South (+79 percent, 100 to 179), whereas non-AAP deaths declined across most regions (Figure 6). Across regions, AAMR similarly showed a temporary increase during 2019 to 2021.

Fig. 5.

Temporal trends in AAMRs for acute pancreatitis by United States census region (Northeast, Midwest, South, West), 2006–2023. Abbreviations: AAMR, age-adjusted mortality rate; APC, annual percent change.

Fig. 6.

Temporal trends in AAMRs for acute pancreatitis subtypes by United States Census region (Northeast, Midwest, South, West), 2006–2023. (A) alcoholic acute pancreatitis; (B) non-alcoholic acute pancreatitis

Urbanization

Urbanization was associated with differences in both levels and trends (Tables 1–3). Most AP deaths occurred in metropolitan counties (42,058 deaths) rather than nonmetropolitan counties (10,846 deaths). In metropolitan areas, AP deaths were 2,426 in 2006 and 2,433 in 2023 (+0.29 percent); in nonmetropolitan areas, AP deaths were 614 and 585 (−4.72 percent). The AP AAMR declined in both settings (metropolitan 1.49 to 1.23 per 100,000; nonmetropolitan 1.76 to 1.61 per 100,000), although age-adjusted rates by urbanization were only available through 2020 (Figure 7). AAP deaths increased in both metropolitan (251 to 401, +59.76 percent) and nonmetropolitan (46 to 84, +82.61 percent) counties, and AAP AAMR rose in both settings. By contrast, non-AAP AAMR fell in both metropolitan (1.31 to 1.01 per 100,000) and nonmetropolitan (1.63 to 1.36 per 100,000) areas (Figure 8). Within the available years for urbanization-stratified AAMR, both metropolitan and nonmetropolitan areas showed a pandemic-era uptick around 2019–2020, and the pandemic-era increase in AAP AAMR was more pronounced in metropolitan areas (Figure 7 and Figure 8).

Fig. 7.

Temporal trends in AAMRs for acute pancreatitis by urbanization level, 2006–2020. Abbreviations: AAMR, age-adjusted mortality rate; APC, annual percent change.

Fig. 8.

Temporal trends in AAMRs for acute pancreatitis subtypes by urbanization level, 2006–2020. (A) alcoholic acute pancreatitis; (B) non-alcoholic acute pancreatitis. Abbreviations: AAMR, age-adjusted mortality rate; APC, annual percent change.

Discussion

This national analysis of U.S. mortality from AP between 2006 and 2023 shows a modest decline in AAMR, despite AP remaining a common gastrointestinal emergency. This decline aligns with improvements in early resuscitation, high-acuity triage, and stepwise management of pancreatic necrosis, which likely reduced per-population mortality risk, even as absolute deaths remained stable or increased in some subgroups. Advances in the management of non-AAP have become increasingly standardized. In addition to improvements in supportive care and early risk stratification, etiology-directed pathways for biliary, metabolic, drug-related, and post-procedural pancreatitis have matured over time, including timely diagnostic imaging, selective endoscopic intervention when indicated, prevention of procedure-related pancreatitis, and definitive source control to reduce recurrence in appropriate patients¹⁸. These combined practice improvements provide a plausible clinical context for the long-term decline in non-AAP mortality observed in our study.

In contrast, deaths attributed specifically to AAP increased substantially. Nationally, AAP deaths rose by more than 60 percent between 2006 and 2023, and the AAMR for AAP nearly doubled, from 0.13 to 0.23 per 100,000. This increase was not confined to one demographic group. Both men and women experienced large relative increases in AAP deaths, and AAP mortality climbed across metropolitan and nonmetropolitan areas and across Census regions. Alcohol is a direct pancreatic toxin, and repeated heavy drinking can trigger severe necroinflammatory injury, recurrent flares, and eventual organ failure¹⁹. Historically, alcohol related pancreatitis has been concentrated in working age adults and has shown a strong male predominance^20,21. Our findings confirm that men still account for most AAP deaths, but the proportional increase in fatal AAP was similar in women, suggesting that alcohol associated pancreatic injury is no longer limited to stereotypical high risk male drinkers. The observed rise in AAP mortality is consistent with broader vital statistics showing that US mortality from alcohol related causes accelerated in recent years^22–24.

Sex and age patterns in our results provide additional warning signals. Overall, AP AAMR declined faster in women than in men, and female non-AAP AAMR fell substantially. Sex differences in nonalcoholic acute pancreatitis mortality are likely multifactorial. In a large U.S. nationwide inpatient analysis, females had lower in-hospital mortality and fewer severe complications than males²⁵, and a comprehensive review further suggests that sex-related differences in risk-factor profiles and etiologic distribution may contribute to disparate outcomes²⁶. However, female AAP deaths still increased by about 70 percent, nearly matching the increase in men, and AAP AAMR rose in both sexes. This mirrors national data showing rising high intensity alcohol use and alcohol related harms in the US during and after the COVID-19 pandemic, with particularly rapid increases among women^4,23. Age gradients were similarly concerning. Crude mortality from overall AP and from non-AAP fell steeply in those aged 85 years and older. The decline in crude death rates among adults aged 85 years and older may partly reflect denominator expansion, because rapid growth of the “oldest old” population can make the aggregated 85+ category less comparable over time²⁷. In addition, hospitalization-based analyses report decreasing acute pancreatitis case fatality over time, consistent with improvements in supportive care and complication management²⁸, which may also contribute to this pattern. However, deaths increased in younger adults. Among adults aged 25 to 34 years, AP deaths rose by more than 70 percent, and AAP deaths more than doubled, consistent with a shift toward premature, alcohol driven pancreatic failure. Population level studies of alcohol associated liver disease report the same pattern: since 2018, mortality has accelerated fastest in adults aged 25 to 44 years and in women, suggesting a syndemic of hazardous drinking, metabolic stress, and delayed care that intensified during the pandemic^23,24. We also observed a transient rise in AP mortality, including non-AAP, during 2020 to 2022, which may reflect pandemic-related disruptions in urgent care. During early COVID-19, emergency department admissions declined substantially and AP cohorts reported delayed hospital presentation; delayed evaluation together with strained inpatient capacity could plausibly worsen outcomes even if overall incidence did not rise^29,30.

These pandemic-era dynamics also provide a useful context for cross-country comparison. The 2021 nationwide Japanese survey reported improved in-hospital outcomes³¹, and Japan’s recurrent national surveys within a universal health coverage system support coordinated practice evaluation and broad access to care^32–34. A nationwide inpatient database study further reported unchanged ICU/HDU bed capacity but lower ICU/HDU occupancy during the pandemic, suggesting a distinct critical care utilization pattern³⁵. In contrast, U.S. adults experienced increases in alcohol use and alcohol-related adverse consequences during early COVID-19⁴, and U.S. hospitals faced substantial crowding and resource strain. Although these mechanisms cannot be tested directly in death-certificate data, they offer a plausible explanation for why worsening AP mortality in the United States could coexist with improving in-hospital outcomes reported in Japan during the pandemic.

Disparities by race/ethnicity and geography underscore the structural nature of AP mortality. Although AAMR declined in every racial/ethnic group, absolute deaths fell in NH White and NH Black groups but rose in Hispanic and NH Other groups, which can occur when population size and exposure patterns shift even as per-population risk decreases. Lower non-AAP AAMR among Hispanic individuals may partly align with the broader Hispanic mortality advantage described in longitudinal evidence³⁶. Higher AAMR among NH White and NH Black populations may reflect comorbidity burden and structural differences in timely access to high-acuity rescue care, given documented variation in geographic ICU access by income, race/ethnicity, and urbanicity, and evidence that racial/ethnic minority patients with AP disproportionately live in higher social vulnerability neighborhoods^37,38. Because race/Hispanic origin can be misclassified on death certificates, estimates for heterogeneous groups such as NH Other should be interpreted cautiously³⁹. Ultimately, clarifying the true drivers of these disparities will require patient-level studies that capture severity, timing, and care pathways. Geographic structure compounds these disparities. Nonmetropolitan counties, particularly in the South and Midwest, often have fewer ICU beds, longer transfer times to centers with surgical capacity, and chronic shortages of critical care clinicians⁶. Those same regions in our data showed pronounced increases in AP deaths. The intersection of rising alcohol toxicity, structural racism in access to specialty care, and longstanding rural workforce shortages likely contributes to the persistence of preventable pancreatitis deaths in marginalized populations. Our study also found that during the COVID-19 period, the increase in AAP mortality was more pronounced in metropolitan areas. This pattern may reflect urban-rural differences in alcohol exposure and psychosocial stressors. Pandemic-related disruptions in daily living and working conditions differed by urbanicity: national labor-force evidence suggests greater work disruption in urban areas and lower remote-work prevalence in rural settings⁴⁰, and telecommuting and mobility changes varied substantially across U.S. geographies during the first pandemic year⁴¹. Consistent with these contextual differences, surveys during the pandemic reported that self-reported increases in alcohol consumption were more common in urban or suburban respondents than in rural respondents^42,43. Together, these urbanicity-linked shifts could plausibly amplify alcohol exposure and stress in metropolitan communities, helping to explain the more rapid rise in AAP mortality observed in our urban-stratified trends.

These findings have several implications. First, the steady decline in non-AAP mortality, especially among the oldest adults, suggests real progress in preventing deaths from biliary and other non-alcohol etiologies. Maintaining timely biliary decompression, appropriate early endoscopy, and same admission cholecystectomy, even in frail elders, remains essential^18,44. Second, the surge in AAP mortality signals an urgent, largely preventable threat. The pandemic period was marked by increased stress, social isolation, and loosening of alcohol access policies such as expanded home delivery, alongside disruptions in addiction treatment and primary care. National surveillance shows that alcohol attributable deaths jumped by nearly 30 percent from 2016 to 2021, with a disproportionately steep increase among women, and that alcohol associated liver disease mortality accelerated after 2018, especially in younger adults^4,23. Integrating rapid addiction assessment, brief intervention, and linkage to treatment into emergency, gastroenterology, and critical care pathways is likely to be lifesaving. Third, rural and small town hospitals, which already operate with thin margins, limited ICU capacity, and long transfer distances, need targeted investment in critical care infrastructure, advanced endoscopy access, and telecritical care if the US is to avoid widening urban-rural gaps in severe AP survival^6,45.

This study has limitations. First, all analyses rely on death certificates, and attribution of AP, AAP, or non-AAP as the underlying cause of death reflects the certifying clinician’s judgment. Misclassification is possible in complex critical illness where pancreatitis coexists with sepsis, cirrhosis, trauma, or multiorgan failure. Second, CDC mortality data suppress cells with fewer than 10 deaths to protect privacy, which prevents detailed analysis of very small strata, such as AAP, in those aged 85 years or older, in some NH Other categories, and some typing data of non-AAP. We did not attempt to back calculate suppressed values. Third, our rate comparisons use AAMR standardized to the year 2000 US population, which is necessary for fair comparison across groups of different age structure, but can diverge from age specific crude rates. Fourth, temporal trends were summarized using Joinpoint regression. Joinpoint uses permutation tests to locate inflection points and then reports an AAPC, which may obscure sharp pandemic era surges followed by stabilization. In addition, CDC WONDER does not include symptom onset, time to presentation, ICU admission, or time from onset to death. Thus, we cannot separate early deaths from later complications or evaluate ICU access as a mediator, even though mortality in acute pancreatitis is driven largely by early persistent organ failure. Finally, this is an ecological analysis. We cannot link individual drinking patterns, comorbidities, procedure timing, or transfer delays to individual outcomes, limiting causal inference.

Our study focuses on fatal acute pancreatitis and cannot capture nonfatal severe disease, which is clinically substantial. CDC WONDER does not provide severity markers such as organ failure, pancreatic necrosis, ICU admission, or procedure level interventions, precluding direct comparison of severity distributions between alcohol associated and nonalcoholic etiologies. Nevertheless, prior clinical cohorts suggest that etiology influences severity: Alcoholic etiology has been associated with increased risk of organ failure and pancreatic necrosis in sentinel acute pancreatitis⁴⁶, and systematic reviews indicate differing risks of nonmild disease and complications across biliary, alcohol related, hypertriglyceridemic, and post ERCP pancreatitis⁴⁷. Future work linking mortality trends with hospitalization based severity metrics will be important to fully characterize the evolving burden of both fatal and nonfatal severe acute pancreatitis.

Conclusions

From 2006 to 2023, the overall AAMR from AP in the US declined, driven largely by improvements in non-alcoholic etiologies. At the same time, alcoholic AP mortality increased sharply in both men and women, across a broad adult age range, and in metropolitan and nonmetropolitan settings. Pancreatitis mortality is therefore becoming more alcohol-driven and more demographically diverse. And despite declining AAMR across all racial/ethnic groups, population growth and changing exposure may be shifting the absolute burden of fatal AP toward Hispanic and NH Other communities.

These findings indicate that national strategies to further reduce pancreatitis mortality must address high-risk alcohol use, integrate addiction services into AP care, and ensure equitable access to advanced pancreatobiliary and critical care across regions and populations. Without such steps, rising alcoholic pancreatitis mortality could erode or reverse the overall gains achieved in pancreatitis survival.

Abbreviations

AP

Acute pancreatitis

AAP

Alcoholic acute pancreatitis

non-AAP

Non-alcoholic acute pancreatitis

AAMR

Age-adjusted mortality rate

AAPC

Average annual percent change

APC

Annual percent change

CDC Wonder

Centers for disease control and prevention wide-ranging online data for epidemiologic research

NCHS

National center for health statistics

NH

Non-Hispanic

CI

Confidence interval

US

United States

Author contributions

Dongliang Yang: Writing-original draft, Methodology, Investigation, Formal analysis. Fei Zhang: Writing-original draft, Methodology, Formal analysis. Lishan Bai: Validation, Investigation, Formal analysis. Xiaoyong Wang: Writing-original draft, Supervision, Resources, Project administration, Methodology, Investigation, Funding acquisition, Conceptualization.

Data availability

The data used in this paper were obtained from free database downloads and have been described explicitly in the text. Further inquiries can be directed to the corresponding author.

Declarations

Conflict of interest

The authors declare no competing interests.

Ethics

There was no need to get informed consent or ethical approval for this study again because all of the data were taken from published sources, and the informed consent and approval were received.