Gastroenterology 2022;162:621–644
SPECIAL ARTICLE
Burden and Cost of Gastrointestinal, Liver, and Pancreatic
Diseases in the United States: Update 2021
Anne F. Peery,1 Seth D. Crockett,1 Caitlin C. Murphy,2 Elizabeth T. Jensen,3 Hannah P. Kim,1
Matthew D. Egberg,1 Jennifer L. Lund,4 Andrew M. Moon,1 Virginia Pate,4 Edward L. Barnes,1
Courtney L. Schlusser,4 Todd H. Baron,1 Nicholas J. Shaheen,1 and Robert S. Sandler1
1
Center for Gastrointestinal Biology and Disease, University of North Carolina School of Medicine, Chapel Hill, North Carolina;
2
University of Texas Health Science Center at Houston, Houston, Texas; 3Wake Forest School of Medicine, Winston-Salem,
North Carolina; and 4Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel
Hill, North Carolina.
BACKGROUND & AIMS: Gastrointestinal diseases account for
considerable health care use and expenditures. We estimated
the annual burden, costs, and research funding associated with
gastrointestinal, liver, and pancreatic diseases in the United
States. METHODS: We generated estimates using data from the
National Ambulatory Medical Care Survey; National Hospital
Ambulatory Medical Care Survey; Nationwide Emergency
Department Sample; National Inpatient Sample; Kids’ Inpatient
Database; Nationwide Readmissions Database; Surveillance,
Epidemiology, and End Results program; National Vital Statis-
tics System; Centers for Disease Control and Prevention Wide-
Ranging Online Data for Epidemiologic Research; MarketScan
Commercial Claims and Encounters data; MarketScan Medicare
Supplemental data; United Network for Organ Sharing registry;
Medical Expenditure Panel Survey; and National Institutes of
Health (NIH). RESULTS: Gastrointestinal health care expendi-
tures totaled $119.6 billion in 2018. Annually, there were more
than 36.8 million ambulatory visits for gastrointestinal symp-
toms and 43.4 million ambulatory visits with a primary
gastrointestinal diagnosis. Hospitalizations for a principal
gastrointestinal diagnosis accounted for more than 3.8 million
admissions, with 403,699 readmissions. A total of 22.2 million
gastrointestinal endoscopies were performed, and 284,844 new
gastrointestinal cancers were diagnosed. Gastrointestinal dis-
eases and cancers caused 255,407 deaths. The NIH supported
$3.1 billion (7.5% of the NIH budget) for gastrointestinal
research in 2020. CONCLUSIONS: Gastrointestinal diseases are
responsible for millions of health care encounters and hun-
dreds of thousands of deaths that annually costs billions of
dollars in the United States. To reduce the high burden of
gastrointestinal diseases, focused clinical and public health ef-
forts, supported by additional research funding, are warranted.
Keywords: Health Care Costs; Endoscopy; Digestive System
Diseases; Neoplasms.
G astrointestinal (GI) diseases are common, cause
considerable suffering, and can be fatal. GI diseases
account for substantial health care use and expenditures.1–3
Reports detailing the burden of GI diseases are necessary
for clinical research, decision making, and priority setting.
Our aim was to describe health care use, expenditures, and
research funding across GI, liver, and pancreatic diseases in
the United States. To that end, we used multiple data
sources to produce GI-specific summary statistics on office-
based and emergency department (ED) visits, adult and
pediatric hospitalizations, readmissions, and mortality. We
report statistics and temporal trends in GI endoscopy, can-
cers, and organ transplants. We estimated GI-specific health
care expenditures and summarized National Institutes of
Health (NIH) funding for GI research.
Methods
Symptoms and Diagnoses Across Ambulatory
Settings
We used the 2016 National Ambulatory Medical Care Sur-
vey (NAMCS) and the National Hospital Ambulatory Medical
Care Survey (NHAMCS) to tabulate the leading GI symptoms
and diagnoses in the United States for outpatient office-based
and ED visits. The NAMCS and NHAMCS are national surveys
conducted annually by the US Centers for Disease Control and
Prevention (CDC).4 The NAMCS surveys nonfederal employed
office-based physicians or nonphysician clinicians primarily
engaged in direct patient care. The NHAMCS collects data on ED
visits exclusive of federal, military, and Veterans Administra-
tion hospitals. We downloaded public use data files from the
CDC website to perform our analyses. Patient-reported symp-
toms are available in both the NAMCS and NHAMCS. We used
Abbreviations used in this paper: AHRQ, Agency for Healthcare Research
and Quality; CCSR, Clinical Classifications Software Refined; CDC, US
Centers for Disease Control and Prevention; CDC WONDER, Centers for
Disease Control and Prevention Wide-Ranging Online Data for Epidemi-
ologic Research; ED, emergency department; GI, gastrointestinal; ERCP,
SPECIAL ARTICLE
endoscopic retrograde cholangiopancreatography; EUS, endoscopic ul-
trasonography; HCUP, Healthcare Cost and Utilization Project; ICD-9,
International Classification of Diseases, Ninth Revision; ICD-10-CM, In-
ternational Classification of Diseases, 10th Revision, Clinical Modification;
KID, Kids’ Inpatient Database; MEPS, Medical Expenditure Panel Survey;
NAMCS, National Ambulatory Medical Care Survey; NEDS, Nationwide
Emergency Department Sample; NHAMCS, National Hospital Ambulatory
Medical Care Survey; NIH, National Institutes of Health; NIS, National
Inpatient Sample; NRD, Nationwide Readmissions Database; SEER, Sur-
veillance, Epidemiology, and End Results; UNOS, United Network for Or-
gan Sharing.
Most current article
© 2022 by the AGA Institute
0016-5085/$36.00
https://doi.org/10.1053/j.gastro.2021.10.017
 622 Peery et al Gastroenterology Vol. 162, No. 2

Table 1.Leading GI Symptoms Prompting an Ambulatory Visit, 2016

Estimated number of annual visits

Rank Symptoms Office visits ED visits Total

1 Abdominal pain 6,893,881 12,524,768 19,418,649

a
2 Vomiting 2,596,369 2,768,558 5,364,928
a
3 Nausea 1,636,346 2,304,775 3,941,121
a
4 Diarrhea 1,915,475 667,584 2,583,060
a
5 GI bleeding 659,135 874,612 1,533,747
a
6 Constipation 864,103 378,331 1,242,434
a,b
7 Anorectal symptoms 786,668 94,993 881,661
8 Heartburn and indigestiona,b 680,031 43,432 723,463
a,b
9 Decreased appetite 511,705 59,662 571,367
a,b
10 Dysphagia 412,870 154,853 567,723
Total 36,828,153

NOTE. Sources: The 2016 NAMCS and NHAMCS, ED only.4

a
Categories reported from the NAMCS with <30 observations, which should be interpreted with caution.
b
Categories reported from the NHAMCS (ED only) with <30 observations, which should be interpreted with caution.

the most important complaint (variable RFV1) for our analyses.
We combined related symptoms and totaled data from office
visits and ED visits to present the top 10 most common
symptoms. We categorized physician and nonphysician di-
agnoses into relevant disease categories based on clinical
expertise using the International Classification of Diseases, 10th
Revision, Clinical Modification (ICD-10-CM) (see
Supplementary Tables 1 and 2). We used the primary diagnosis
code only. After combining the related diagnoses, we created a
rank order list. The NAMCS and NHAMCS are based on prob-
ability samples. Therefore, sampling weights were applied to all
analyses to generate national estimates. When there were
fewer than 30 observations for a specific condition, the esti-
mates are unreliable and should be interpreted with caution.
Both analyses include children and adults.
Emergency Department Visits
The most common GI diagnoses in the ED were compiled
using discharge data from the Nationwide Emergency Depart-
ment Sample (NEDS), part of the Agency for Healthcare
Research and Quality (AHRQ) Healthcare Cost and Utilization
Project (HCUP). The NEDS is the largest, publicly available, all-
payer ED database in the United States. The 2018 NEDS con-
SPECIAL ARTICLE
combining related codes (see Supplementary Table 3), and
present the top 20 GI diagnoses and symptoms. Diagnosis
categories and associated codes were determined using previ-
ously published GI coding categories mapped to ICD-10
codes.2,5–8 Weighted national estimates for ED visits in 2018
were generated, including estimates of the total number of
visits and rate of visits per 100,000 persons for each individual
ICD-10 code (or group of codes). We included the number of
secondary diagnoses for each GI category. Secondary diagnoses
are additional diagnoses that appear on the discharge record
with the first-listed or principal diagnosis.
Additional information on the most common GI diagnoses
among patients seen in the ED according to Clinical Classifica-
tions Software Refined (CCSR) categories is provided in
Supplementary Table 4, including mean age, numbers admitted
to the hospital, and deaths. CCSR is a tool developed by the
AHRQ for clustering diagnoses into a manageable number of
clinically meaningful, policy-relevant categories. A complete list
of GI-related CCSR diagnoses is also included in Supplementary
Table 4 and was used to estimate the total number of ED visits
in the United States with a principal diagnosis code for a GI
disease or symptom.

tains information from 990 hospitals participating in the HCUP Hospitalizations

across 36 states and the District of Columbia, approximating a
20% stratified sample of US hospital-owned EDs. The NEDS
sampling frame includes discharge information on patients
admitted to the hospital from an ED, patients treated and dis-
charged from an ED, and patients transferred to another hos-
pital from an ED.
We queried the database for the rank order of the principal
visit diagnosis (ie, ICD-10 codes) from the ED for children and
adults in all hospitals. We identified all GI diagnoses and
symptoms, which were subsequently rank ordered after
The most common GI diagnoses from hospital admissions
were compiled using discharge data from the National Inpatient
Sample (NIS), part of the HCUP. The NIS approximates a 20%
stratified sample of all discharges from US community hospi-
tals, excluding rehabilitation and long-term acute care hospi-
tals. The NIS contains information on all hospital stays,
regardless of expected payer, including persons covered by
Medicare, Medicaid, private insurance, and the uninsured. The
sampling frame for the 2018 NIS comprises more than 97% of
the United States across 47 states and the District of Columbia.
February 2022 Burden of Gastrointestinal Diseases 623

Table 2.Leading Physician Diagnoses for GI Disorders in the United States, 2016

Estimated number of annual visits

Diagnosis Office visitsa ED visitsa Total

Abdominal pain 7,979,815 7,693,205 15,673,020

Nausea and vomiting 2,569,377 2,469,273 5,038,650
GERD and reflux esophagitis 4,345,680 317,964 4,663,644
Constipation 2,226,455 854,399 3,080,854
Abdominal wall and inguinal hernia 2,468,048 289,434 2,757,482
Diarrheab 1,362,383 626,030 1,988,413
b,c
Hemorrhoids 1,803,032 86,514 1,889,546
b
Gastritis and dyspepsia 1,128,641 490,448 1,619,089
b
Cholelithiasis 863,398 326,985 1,190,383
b,c
Dysphagia 1,049,240 89,325 1,138,565
b
Diverticular disease of the colon 783,928 288,183 1,072,111
b,c
Malignant neoplasm of the colon or rectum 1,046,452 13,806 1,060,258
b,c
Chronic liver disease and cirrhosis 330,201 129,724 459,925
Hepatitis C infection b,c
383,650 — 383,650
b,c
Rectal bleeding 235,322 139,448 374,770
b,c
Pancreatitis—acute and chronic 70,201 194,468 264,669
Crohn’s diseaseb,c 230,770 18,874 249,644
b,c
Irritable bowel syndrome 245,673 1531 247,204
b,c
Appendicitis 119,691 54,302 173,993
b,c
Benign neoplasm of colon and rectum 43,720 3145 46,865
Total 43,381,926

NOTE. Source: The 2016 NAMCS and the 2016 NHAMCS, ED only.4
GERD, gastroesophageal reflux disease.
a
Gray shading denotes categories that decreased in visits by 50% or more compared to 2014 data.
b
Categories reported from the NAMCS with <30 observations, which should be interpreted with caution.
c
Categories reported from the NHAMCS (ED only) with <30 observations, which should be interpreted with caution.

We queried the database for the rank order of the principal
discharge diagnosis (ie, ICD-10) for all patients in all hospitals.
For inpatient stays, the principal diagnosis is that condition
thought to be chiefly responsible for the patient’s admission to
the hospital. We identified the top 15 GI diagnoses and symp-
toms, which were subsequently rank ordered after combining
related diagnosis codes. Diagnosis categories and associated
codes were determined using previously published GI coding
categories mapped to ICD-10 codes.2,5–8 Specific groupings of
associated with each CCSR category. Information on the most
common GI procedure categories related to GI hospital admis-
sions are also provided in Supplementary Table 6.
Pediatric Hospitalizations
We performed a cross-sectional analysis of the 2016 data
contained within the Kids’ Inpatient Database (KID), a nation-
SPECIAL ARTICLE

ICD-10 codes for each category are detailed in Supplementary
Table 3. Weighted national estimates for visits in 2018 were
generated. We also included the number of secondary di-
agnoses for each GI category. Secondary diagnoses are addi-
tional diagnoses that appear on the discharge record with the
first-listed or principal diagnosis.
A complete list of GI-related CCSR diagnoses is included in
Supplementary Table 5 and was used to estimate the total
number of admissions with a principal diagnosis code for GI
diseases or symptoms. The list includes median length of stay,
median charges and costs, and number of inpatient deaths
ally representative sample of pediatric (aged <21 years at
admission) hospitalizations from the HCUP.9 KID is the largest
publicly available, all-payer pediatric inpatient database and is
designed to be representative of pediatric hospital care across
the United States. In 2016, the KID data set included pediatric
hospitalization data from 44 states including the District of
Columbia and represented nearly 4,200 participating commu-
nity hospitals (defined as short-term, nonfederal, general, and
specialty), excluding rehabilitation hospitals.
We queried the 2016 KID database and analyzed the principal
discharge diagnosis (ie, ICD-10) for all hospitalizations from
 624 Peery et al Gastroenterology Vol. 162, No. 2

Table 3.Most Common GI, Liver, and Pancreatic Principal Diagnoses From US ED Visits, 2018

Annual number of Rate of visits Annual number of

visits (principal per 100,000 visits (all listed
Rank Diagnosis/symptom diagnosis) persons diagnoses)

1 Abdominal pain 5,755,363 1762 12,017,501

2 Nausea and vomiting 2,160,754 661 8,487,667
3 Noninfectious gastroenteritis/colitis 1,261,948 386 1,835,848
4 Constipation 1,084,724 332 3,448,680
5 GI bleeding 941,658 288 1,707,704
Upper GI bleeding 431,141 132 1,009,733
Lower GI bleeding 271,575 83 459,028
GI bleeding not otherwise specified 238,942 73 238,943
6 Cholelithiasis and cholecystitis 726,636 222 1,453,137
7 Gastritis/duodenitis/ulcers (nonbleeding) 645,327 198 1,653,652
a
8 GI infection 618,243 189 1,003,089
b
9 Diarrhea 595,133 182 3,162,456
10 Diverticulitis 462,954 142 629,139
11 Pancreatitis 419,344 128 890,382
Acute pancreatitis 381,741 117 626,769
Chronic pancreatitis 37,603 12 263,613
12 Liver disease and viral hepatitis 400,567 123 4,471,214
Alcoholic liver disease 130,154 40 613,948
Hepatic encephalopathy 54,589 17 196,699
Ascites or SBP 53,873 16 431,043
Viral hepatitis 25,594 8 1,005,812
Acute liver failure 25,089 8 131,755
13 Appendicitis 379,197 116 417,028
14 Gastroesophageal reflux 354,698 109 9,279,382
15 Intestinal obstruction and ileus 350,045 107 703,280
Obstruction 300,267 92 431,722
Ileus 49,778 15 271,558
16 GI disorders during pregnancy 308,898 95 440,810
17 Foreign body in GI tract 201,613 62 236,204
c
18 Hemorrhoids 193,353 59 645,928
19 Inflammatory bowel disease 148,923 46 548,217
Crohn’s disease 94,711 29 381,856
Ulcerative colitis 54,212 17 166,361
20 Abdominal abscess/peritonitisd 97,780 30 251,409

NOTE. Total ED visits in 2018 with a principal diagnosis code for a GI diagnosis or symptom (see Supplementary Table 4 for
complete list) ¼ 17,943,067. Source: HCUP NEDS.9
SBP, spontaneous bacterial peritonitis.
SPECIAL ARTICLE

a
Includes C difficile infection.
b
Does not include diarrhea coded as gastroenteritis, C difficile infection, or GI infection.
c
Excludes hemorrhoids of pregnancy (included with GI disorders during pregnancy).
d
Excludes liver abscess and SBP.

participating hospitals. We identified GI diagnoses, which were
subsequently rank ordered in frequency after combining related
diagnosis codes (see Supplementary Table 7). Weighted national
estimates for diagnosis frequency estimates were generated using
2016 KID weighting coefficients provided by the HCUP/AHRQ.
Median length of stay in days and interquartile range (25%–75%)
were analyzed in addition to median hospital charges (dollars)
per hospitalization and interquartile range. Hospital charges
represent hospital billing for covered hospital services but do not
include professional fees or noncovered charges.
February 2022 Burden of Gastrointestinal Diseases 625

Table 4.Most Common GI, Liver, and Pancreatic Principal Diagnoses From US Hospitals, 2018

Annual number of admissions Rate of visits per Annual number of admissions

Rank Diagnosis/symptom (principal diagnosis) 100,000 persons (all listed diagnoses)

1 GI bleeding 530,855 166.6 1,275,025

Upper GI bleeding 311,015 97.6 786,470
Lower GI bleeding 113,020 35.5 211,350
GI bleeding NOS 110,030 34.5 277,205
2 Cholelithiasis and cholecystitis 316,020 99.2 741,060
3 Pancreatitis 299,150 93.9 685,880
Acute pancreatitis 288,220 90.4 492,555
Chronic pancreatitis 10,930 3.4 193,325
4 Liver disease 280,645 88.1 3,682,015
Alcoholic liver disease 104,920 32.9 548,940
Hepatic encephalopathy 48,765 15.3 189,945
Acute liver failure 26,480 8.3 169,700
Viral hepatitis 15,600 4.9 722,920
Ascites or spontaneous bacterial 12,025 3.8 395,410
peritonitis
5 Intestinal obstruction 275,355 82.1 417,890
6 Diverticulitis 207,150 65.0 323,760
7 Obesity 193,840 60.8 5,172,209
8 Appendicitis 158,265 49.7 190,770
a
9 Functional/motility disorders 137,495 43.1 3,970,930
10 Colorectal cancer 125,805 39.5 259,235
11 Noninfectious gastroenteritis/colitis 123,235 38.7 508,760
b
12 GI infection 105,095 33.0 248,385
13 Inflammatory bowel disease 99,165 31.1 346,710
Crohn’s disease 60,880 19.1 216,695
Ulcerative colitis 38,285 12.0 130,015
14 C difficile infection 88,815 27.9 307,075
15 Abdominal pain 58,990 18.5 450,790

NOTE. Total admissions in 2018 with a principal diagnosis code for a GI diagnosis or symptom (see Supplementary Table 5 for
complete list) ¼ 3,873,354. Source: HCUP NIS.9
NOS, NOS, not otherwise specified.
a
Includes esophageal (eg, achalasia), gastric (eg, dyspepsia), and intestinal (eg, irritable bowel syndrome) functional/motility
syndromes, as well as constipation and diarrhea.
b
Includes Salmonella; Shigella; Escherichia coli; and other viral, bacterial, and parasitic GI infections. Does not include C
difficile infection (reported separately).

Readmissions code as a primary diagnosis on the index admission was eligible

Using the 2018 Nationwide Readmissions Database (NRD), for inclusion in this study. Diagnosis categories and associated
a resource of the HCUP State Inpatient Databases, we compiled codes (see Supplementary Table 3) were determined using
previously published GI coding categories.2,5–8
SPECIAL ARTICLE

30-day all-cause readmission rates after an index stay for a GI

indication. The NRD is a publicly available, all-payer, inpatient
database from the United States that is designed to be nation-
ally representative of readmission rates for all payers and the
uninsured. The NRD includes data from 17,686,511 admissions
across 28 states and uses individual linkage identifiers within a
state to allow for the assessment of readmissions. This linkage
allows the identification of readmissions to hospitals where the
index admission did not occur. We identified all patients with
an ICD-10 code for the most common inpatient GI discharge
diagnoses in the NRD. Any patient with an ICD-10 diagnosis
We included patients aged 18 years and older. Patients
were required to have a full 30 days between the date of
discharge from their index admission and December 31, 2018.
Patients with an index hospitalization that ended in death or
transfer to another acute care faculty were excluded. The pri-
mary outcome was the first all-cause readmission within 30
days of the index hospitalization. We calculated weighted na-
tional estimates for index stays and first readmissions. We
estimated the total charges associated with both index admis-
sions and the first readmission.
 626 Peery et al Gastroenterology Vol. 162, No. 2

Table 5.Most Common Pediatric GI, Liver, and Pancreatic Principal Diagnoses in US Hospitals, 2016

Annual number Total charges per

of admissions Length of stay, days, hospitalization, US$,
Rank Principal diagnosis (principal diagnosis) median (IQR) median (IQR)

1 Appendicitis 58,017 1.7 (0.7–3.7) 34,710 (24,043–51,060)

2 Intestinal infection 25,550 1.7 (0.8–3.0) 14,179 (8537–24,709)
Viral 13,932 1.4 (0.6–2.4) 12,381 (7669–20,838)
Bacterial 9322 2.4 (1.4–4.0) 17,709 (10,481–31,672)
Protozoan 347 2.4 (1.3–4.3) 17,012 (8958–31,846)
Unspecified 1949 1.5 (0.7–2.5) 14,313 (8871–23,513)
3 Inflammatory bowel disease 24,238 2.3 (1.0–4.6) 22,090 (11,066–45,074)
Crohn’s disease 7604 3.5 (2.0–6.2) 35,570 (20,239–62,460)
Ulcerative colitis 5243 3.9 (2.2–6.7) 37,277 (20,131–69,160)
Other noninfective gastroenteritisa 11,391 1.3 (0.5–2.4) 12,904 (7494–22,539)
4 Pancreaticobiliary diseases 22,813 2.3 (1.2–3.9) 31,484 (18,265–52,208)
Cholelithiasis/cholecystitis 10,948 1.9 (1.0–3.2) 37,607 (24,557–56.575)
Acute pancreatitis 9134 2.7 (1.4–4.4) 22,817 (12,969–42,226)
Otherb 2731 2.9 (1.4–5.8) 33,325 (19,216–59,794)
5 Upper alimentary tract diseases 17,930 2.0 (1.0–4.0) 21,896 (11,380–40,211)
GERD 8151 1.8 (0.8–3.8) 16,701 (8776–35,224)
Esophagitis/gastritis/duodenitis 4456 1.9 (0.8–3.4) 21,496 (11,834–35,230)
Other diseases of the upper tract 3498 2.5 (1.1–5.3) 29,136 (16,518–52,902)
Ulceration of the upper tract 1480 2.6 (1.4–4.4) 31,439 (20,228–50,436)
Functional dyspepsia 345 3.6 (1.9–6.9) 30,709 (17,167–60,881)
6 Congenital malformations 15,922 2.5 (1.3–6.4) 33,670 (20,951–75,388)
Upper alimentary tract 8513 1.6 (1.0–2.7) 24,423 (17,831–36,389)
Otherc 4193 4.6 (2.4–8.9) 53,767 (31,286–101,317)
Large intestine malformation 1646 3.8 (2.0–8.4) 53,211 (31,516–97,567)
Biliary malformation 947 6.6 (3.3–12.2) 84,066 (39,537–167,355)
Small intestine malformation 623 23.0 (13.6–44.1) 217,392 (124,347–413,120)
7 Paralytic ileus 14,060 2.2 (1.0–4.6) 20,259 (10,509–44,482)
8 Functional intestinal disorder 11,169 1.5 (1.0–2.7) 12,922 (7356–23,700)
9 Abdomen and/or pelvic pain 8482 1.1 (0.4–2.3) 16,190 (9508–26,623)
10 Nausea and vomiting 4466 1.5 (0.6–2.9) 14,261 (8234–24,973)
Total 202,647

NOTE. Source: HCUP KID.

a
Includes allergic and dietetic gastroenteritis and colitis; food protein–induced enteropathy; indeterminate colitis; eosinophilic
gastritis; gastroenteritis or colitis; other specified noninfective gastroenteritis and colitis; and noninfective gastroenteritis and
colitis, unspecified.
b
Includes other diseases of the gallbladder, biliary tract, and pancreas.
c
Includes other congenital malformations of digestive system.

Cancer Incidence and Mortality death certificates filed in all 50 US states and the District of
We estimated the incidence and mortality rates of GI can- Columbia.
cers in adults (aged 20 years) during 1992–2018 using data We estimated age-adjusted (to the 2000 US standard pop-
SPECIAL ARTICLE

from the National Cancer Institute’s Surveillance, Epidemiology,
and End Results (SEER) program of cancer registries and the
National Center for Health Statistics. SEER routinely collects
data on patient demographics, primary tumor site, tumor
morphology, and stage for all cancers diagnosed in defined
geographic regions. The SEER 13 registries cover approxi-
mately 14% of the US population and include Alaska, Atlanta,
Connecticut, Detroit, rural Georgia, Hawaii, Iowa, Los Angeles,
New Mexico, San Francisco–Oakland, San Jose–Monterey,
Seattle–Puget Sound, and Utah. Mortality data are collected
and compiled by the National Center for Health Statistics from
ulation) incidence and mortality rates of esophageal, colorectal,
gastric, liver, pancreas, gallbladder, and small intestine cancer
as rates per 100,000 persons using SEER*Stat, version 8.3.9,
overall and by year and race/ethnicity.10 Race/ethnicity
included non-Hispanic White, non-Hispanic Black, Hispanic
(any race), non-Hispanic Asian/Pacific Islander, and non-
Hispanic Alaska Native/American Indian.
Noncancer Mortality
We determined the most common causes of non–cancer-
related GI deaths in the United States from the CDC’s Wide-
February 2022 Burden of Gastrointestinal Diseases 627

Table 6.All-Cause 30-Day Readmissions Ranked by Most Frequently Readmitted GI, Liver, or Pancreatic Conditions in US
Hospitals, 2018

Number of 30-day
Principal diagnosis for index Number of all-cause Readmitted, Median charge per Median charge per
Rank hospital stay index stays readmissions % index stay, US$ readmission, US$

1 GI bleedinga 486,447 84,533 17.4 32,450 36,546

Upper 286,676 50,519 17.6 33,340 36,590
Lower 103,361 15,619 15.1 30,933 36,252
2 Liver disease 200,633 63,072 31.4 34,792 36,120
3 Pancreatitis 269,247 42,727 15.9 26,471 28,944
Acute 259,284 40,036 15.4 26,434 29,024
Chronic 9963 2691 27.0 27,816 27,416
4 Intestinal obstruction 279,871 40,144 14.3 27,680 35,788
5 Cholelithiasis and cholecystitis 286,711 27,098 9.5 46,734 39,041
6 Diverticulitis 204,805 24,874 12.1 30,552 38,740
b
7 Functional/motility disorders 101,699 19,876 19.5 27,625 35,785
8 C difficile infection 80,842 18,438 22.8 27,734 33,686
9 Colorectal cancer 113,519 17,955 15.8 68,727 39,639
10 Inflammatory bowel disease 88,113 16,285 18.5 31,770 36,206
Ulcerative colitis 32,667 5686 17.4 34,276 38,684
Crohn’s disease 55,446 10,599 19.1 30,312 34,633
11 Noninfectious gastroenteritis/colitis 112,408 16,224 14.4 24,894 34,556
12 Abdominal pain 54,246 9101 16.8 24,523 33,220
c
13 GI infection 80,525 9097 11.3 22,224 32,740
14 Obesity 175,528 6830 3.9 43,259 31,061
15 Appendicitis 108,454 6676 6.2 40,826 32,105
16 Gastritis 37,985 6287 16.5 27,493 29,912
17 Gastroesophageal reflux disease 29,217 3574 12.2 30,213 36,638
Total 403,699

NOTE. Source: HCUP NRD.9

a
The code “Gastrointestinal hemorrhage NOS” (578.9) was included in the overall GI bleeding category but was not included in
subcategories of upper and lower GI bleeding because it is nonspecific.
b
Includes esophageal (eg, achalasia), gastric (eg, dyspepsia), and intestinal (eg, irritable bowel syndrome) functional/motility
syndromes, as well as constipation and diarrhea.
c
Includes Salmonella; Shigella; E coli; and other viral, bacterial, and parasitic GI infections. Does not include C difficile
infection.

Ranging Online Data for Epidemiologic Research (CDC of death. Diagnoses were combined to create clinically mean-
WONDER),11 a publicly available online database developed by ingful categories. The crude rate per 100,000 deaths was
SPECIAL ARTICLE

the CDC. Causes of death are derived from physician-completed
death certificates and are classified in accordance with ICD-10.
The underlying cause of death is defined as the disease that
initiated the train of events leading to death. A disease listed as
a contributing cause of death is classified on the death certifi-
cate as the underlying cause or any of 20 additional diseases
leading to death. For this analysis, we used the 2019 public use
data files from CDC WONDER for underlying cause of death and
multiple cause of death. The 15 most common nonmalignant GI
causes of death were identified using ICD-10 codes (see
Supplementary Table 22) and were ranked by underlying cause
calculated by dividing the number of deaths listed as an un-
derlying cause by the total US population of children and adults
in the United States in 2019 (328,239,523 from the US Census
Bureau) and multiplying by 100,000. We also calculated
numbers of deaths and mortality rates stratified by ethnicity
and race (Supplementary Tables 23 and 24).
Endoscopy Use and Trends
Using the IBM MarketScan Commercial Claims and En-
counters database and IBM MarketScan Medicare
 628 Peery et al Gastroenterology Vol. 162, No. 2

Table 7.New Diagnoses and Deaths From GI, Pancreatic, Supplemental database, we examined patterns of endoscopy
and Liver Cancers in the United States, 2018 use in adults (aged 18 years) during 2002–2019. We
examined temporal trends in upper endoscopy, colonoscopy,
Number of new Number of flexible sigmoidoscopy, endoscopic retrograde chol-
Cancer site diagnoses deaths angiopancreatography (ERCP), and upper and lower
endoscopic ultrasonography (EUS). MarketScan is an
Colon and rectum 141,074 52,163
employer-based claims database that includes 77 contributing
Pancreas 52,546 44,914 employers and 12 contributing health plans, with 126 unique
Liver and intrahepatic bile ducts 34,638 27,685 carriers and 8 Medicaid states representing approximately
165 million covered lives. The Medicare Supplemental data-
Stomach 24,101 11,043 base includes beneficiaries aged 65 years with an employer-
Esophagus 18,364 15,419 sponsored Medicare Supplemental plan. We summed the total
number of months persons aged 18–64 years (MarketScan)
Small intestine 9810 1686 and 65 years (Medicare Supplemental) were enrolled in
Gallbladder 4311 2180 their insurance plan in each calendar year as standardized
denominators of enrollee-time. We then depicted time trends
Total 284,844 155,090
by calculating a rate of the procedure per 1000 enrollee-years
in each calendar year, assuming constant rates within each
NOTE. Sources: National Program of Cancer Registries and calendar year. We examined rates by age group (18–29, 30–
National Center for Health Statistics, 2018. 39, 40–49, 50–64, 65–74 and 75 years). We estimated the
SPECIAL ARTICLE

Figure 1. (A) Age-adjusted

incidence of esophageal
cancer by race/ethnicity,
National Cancer Institute’s
SEER program of cancer
registries, 1992–2018. (B)
Age-adjusted mortality of
esophageal cancer, National
Center of Health Statistics,
1992–2018. NH, Non-
Hispanic.
February 2022
Figure 2. (A) Age-adjusted
incidence of colon and
rectal cancer by race/
ethnicity, National Cancer
Institute’s SEER program of
cancer registries, 1992–
2018. (B) Age-adjusted
mortality of colon and rectal
cancer, National Center of
Health Statistics, 1992–
2018.
number of procedures performed in 2019 by standardizing
the number of procedures in each database to 2018 US
Census Bureau data (within age categories).
Organ Transplant
We used information available through the United
Network for Organ Sharing (UNOS) registry to tabulate data
related to liver, intestine, and pancreas organ transplants.
UNOS is a nonprofit scientific and educational organization
that administers the Organ Procurement and Trans-
plantation Network in the United States. An online database
system, UNetSM, was developed to collect, store, analyze,
and publish all Organ Procurement and Transplantation
Network data. Data are collected through an online appli-
cation from transplant professionals in hospitals, histocom-
patibility laboratories, and organ procurement organizations
across the country. The data we included are publicly
available as deidentified data at optn.transplant.hrsa.gov/
data/. We included patients with a history of liver, intestine,
or pancreas transplant during 1988–2020. Data extracted
included number of patients on the wait list, type of
transplant, patient demographics at the time of transplant,
Burden of Gastrointestinal Diseases 629
recipient’s primary disease, and donor characteristics. We
report frequencies and proportions for these data.
Expenditures
Using data from the 2018 Medical Expenditure Panel Sur-
vey (MEPS),12 we estimated total expenditures (not charges)
for GI diseases and symptoms. The MEPS is a set of large-scale
surveys of families and individuals, their medical providers
(including doctors, hospitals, and pharmacies), and employers
across the United States. MEPS collects data on the use of
specific health services, how frequently they are used, and the
SPECIAL ARTICLE
cost of these services. These surveys are designed to collect
data from a nationally representative sample of households in
the United States. In the 2018 MEPS Household Component,
29,415 persons were surveyed. This survey represents the
civilian noninstitutionalized population. Expenditures are
available only for CCSR categories. All GI-related categories
available in MEPS were pulled for this analysis. The full-year
consolidated data file for 2018 was used to estimate expendi-
tures. All estimates were weighted by the MEPS person-level
weight (PERWT18F) to produce national estimates of
expenditures.
 630 Peery et al
National Institutes of Health Categorical
Spending
We gathered estimates of annual GI-specific and all-cancer
funding from the NIH between 2011 and 2022.13 Estimates
were selected from NIH-determined research areas. Actual ex-
penditures are reported when available; otherwise, the values
were estimated. Individual research projects could be included
in multiple categories. We also report the total NIH budget
between 2011 and 2022 from the NIH Office of Budget.14 We
SPECIAL ARTICLE
calculated the percentage of the NIH budget spent on digestive
and liver diseases and the percentage of NIH cancer funding
spent on GI cancer research.
Results
Symptoms and Diagnoses Across Ambulatory
Settings
The leading GI symptoms prompting a visit are shown in
Table 1. Abdominal pain was responsible for more than 19.0
Gastroenterology Vol. 162, No. 2
Figure 3. (A) Age-adjusted
incidence of stomach can-
cer by race/ethnicity, Na-
tional Cancer Institute’s
SEER program of cancer
registries, 1992–2018. (B)
Age-adjusted mortality of
stomach cancer, National
Center of Health Statistics,
1992–2018.
million visits, followed by vomiting (5.4 million visits),
nausea (3.9 million visits), diarrhea (2.6 million visits), and
GI bleeding (1.5 million visits). Constipation, anorectal
symptoms, heartburn, decreased appetite, and dysphagia
accounted for an additional 4.0 million visits. Abdominal
pain is also the most frequent diagnosis (vs symptom), with
15.7 million annual visits (Table 2). There were more than
4.7 million visits with GERD and reflux esophagitis di-
agnoses, and hemorrhoid diagnoses accounted for nearly 1.9
million visits.
Emergency Department Visits
In 2018, there were 17.9 million ED visits with a prin-
cipal diagnosis code for a GI diagnosis or symptom (for a
comprehensive list, see Supplementary Table 4). The most
common GI diagnoses are detailed in Table 3. Abdominal
pain was the most common principal diagnosis, with 5.8
million visits. Nausea/vomiting (2.2 million visits),
February 2022 Burden of Gastrointestinal Diseases 631

Figure 4. (A) Age-adjusted

incidence of liver and intra-
hepatic bile duct cancer by
race/ethnicity, National
Cancer Institute’s SEER
program of cancer regis-
tries, 1992–2018. (B) Age-
adjusted mortality of liver
and intrahepatic bile duct
cancer, National Center of
Health Statistics, 1992–
2018.

constipation (1.1 million visits), and GI bleeding (941,658
visits) were also high-frequency primary diagnoses. A
foreign body in the GI tract accounted for 201,613 visits.
Abdominal pain (12.0 million visits), gastroesophageal
reflux disease (9.3 million visits), and nausea/vomiting (8.5
million visits) were common secondary diagnoses that
appear on the discharge record with the principal diagnosis.
Additional details on the most common GI diagnoses and
symptoms among patients seen in the ED are available in
are detailed in Table 4. GI bleeding (530,855 visits), chole-
lithiasis and cholecystitis (316,020 visits), pancreatitis
(299,150 visits), and liver disease (280,645 visits) were the
most common principal GI discharge diagnoses. Gastro-
esophageal reflux disease (6.0 million visits), liver disease
(3.7 million visits), functional/motility disorders (4.0
million visits), and GI bleeding (1.3 million visits) were
common secondary diagnoses that appear on the discharge
record with the principal diagnosis. Length of stay, median
SPECIAL ARTICLE

Supplementary Table 4.
Hospitalizations
In 2018, there were 3.9 million adult hospital admissions
with a principal diagnosis code for a GI diagnosis or
symptom (for a comprehensive list, see Supplementary
Table 5). The estimated aggregate charges (“the national
bill”) and costs for GI hospitalizations in 2018 were more
than $200 billion and $47 billion, respectively. The most
common GI diagnoses associated with hospital admissions
charges and costs, and deaths by category are detailed in
Supplementary Table 5. The most common GI procedures
related to a hospital admission were esophagogas-
troduodenoscopy, cholecystectomy, colectomy, para-
centesis, and appendectomy (Supplementary Table 6).
Pediatric Hospitalizations
In 2016, there were an estimated 202,647 pediatric
hospital admissions with a principal diagnosis code for a GI
 632 Peery et al
disease or symptom. The most common GI diagnoses are
detailed in Table 5. Appendicitis was the most frequent
discharge diagnosis (58,017 visits) and was associated with
a median charge of nearly $35,000. Intestinal infection
(25,550 visits) was the second leading discharge diagnosis
among pediatric hospitalizations. Of those infectious hospi-
talizations, viral gastroenteritis was the most frequent, with
nearly 14,000 hospitalizations. Congenital malformations
were the sixth leading discharge diagnosis but the second
highest median total cost per hospitalization, driven pre-
dominately by small bowel malformations.
SPECIAL ARTICLE
Readmissions
In 2018, there were an estimated 403,699 readmissions
within 30 days of an index admission for a GI condition. The
most common readmissions are detailed in Table 6. GI
bleeding, liver disease, and pancreatitis had the highest
number of all-cause readmissions within 30 days. Liver
disease (31.4%), chronic pancreatitis (27.0%), and Clos-
tridioides difficile infection (22.8) had the highest rates of
Gastroenterology Vol. 162, No. 2
Figure 5. (A) Age-adjusted
incidence of pancreas
cancer by race/ethnicity,
National Cancer Institute’s
SEER program of cancer
registries, 1992–2018. (B)
Age-adjusted mortality of
pancreas cancer, National
Center of Health Statistics,
1992–2018.
all-cause readmissions. Median charges for readmissions
were higher than median charges for an index admission for
most disease categories.
Cancer Incidence and Mortality
In 2018, there were 284,844 new diagnoses and 155,090
deaths from GI cancers (Table 7). Between 1992 and 2018,
the incidence and mortality of esophageal cancer (Figure 1A
and B) decreased among non-Hispanic Blacks, Asians, and
Hispanics. Over the same time, esophageal cancer incidence
and mortality increased in non-Hispanic Whites. The inci-
dence and mortality of colorectal cancer (Figure 2A and B)
decreased among all races/ethnicities but remained higher
among non-Hispanic Blacks compared to other racial/ethnic
groups. The incidence and mortality of gastric cancer
(Figure 3A and B) decreased among all race/ethnicities, and
incidence rates are now highest among Hispanics. Liver
cancer incidence (Figure 4A) began decreasing among all
races/ethnicities between 2007 and 2015, but mortality
increased (Figure 4B) between 1992 and 2018 for all races/
 February 2022
Table 8.Causes of Death From Nonmalignant GI, Pancreatic, and Liver Diseases in the United States, 2019

Rank Disease Women Men Total

Deaths Deaths Crude mortality Deaths Deaths Crude mortality Deaths Deaths Crude mortality
underlyinga contributingb rate per 100,000c underlyinga contributingb rate per 100,000c underlyinga contributingb rate per 100,000c
1 Alcohol-associated liver 7460 9294 4.5 16,650 22,339 10.3 24,110 31,633 7.3
disease
2 Hepatic fibrosis/cirrhosis 8763 18,473 5.3 11,421 26,381 7.1 20,184 44,854 6.1
(all-cause)d
3 GI bleeding, unspecified 4642 16,184 2.8 4906 19,662 3.0 9548 35,846 2.9
4 Vascular disorders of the 4781 9082 2.9 2976 6395 1.8 7757 15,477 2.4
intestine
5 Paralytic ileus and 3934 10,225 2.4 3009 8314 1.9 6943 18,539 2.1
intestinal obstruction
6 Hepatic failure (acute and 2095 12,173 1.3 2516 15,746 1.6 4611 27,919 1.4
chronic)d
7 C difficile 2644 4569 1.6 1889 3557 1.2 4533 8126 1.4
8 Ulcers (gastric/duodenal/ 1746 3328 1.0 1798 3708 1.1 3544 7036 1.1
peptic)
9 Chronic hepatitis C 1252 4008 0.8 2245 10,223 1.4 3497 14,231 1.1
10 Fatty change of liver—not 2158 3667 1.3 1315 2987 0.8 3473 6654 1.1
elsewhere specified
11 Diverticular disease 1931 3042 1.2 983 1738 0.6 2914 4780 0.9
12 Acute pancreatitis 1118 2311 0.7 1693 3367 1.0 2811 5678 0.9
13 Perforation of intestine 1676 4369 1.0 1021 3131 0.6 2697 7500 0.8
(nontraumatic)

Burden of Gastrointestinal Diseases

14 Cholecystitis 1290 1950 0.8 1305 2098 0.8 2595 4048 0.8
15 Cholangitis 536 1144 0.3 564 1249 0.3 1100 2393 0.3
Totals 100,317 234,714

NOTE. Source: CDC WONDER.11 See Supplementary Table 22 for specific groupings of ICD-10-CM codes for each category.
a
The underlying cause of death is defined as the disease that initiated the train of events leading to death.
b
A contributing cause of death is classified on the death certificate as the underlying cause or any of 20 additional diseases leading to death.
c
Crude rate per 100,000 deaths was calculated by dividing the number of deaths listed as an underlying cause by the total population in the United States in 2019 then
multiplying by 100,000.
d
Does not include deaths from liver disease, unspecified (K76.9), which accounted for 3711 deaths in 2019.

633
SPECIAL ARTICLE
 634 Peery et al
Table 9.Estimated Annual Number of Endoscopic
Procedures in the United States, 2019
Procedures Number
Colonoscopy 13,837,748
Upper endoscopy 7,459,419
Flexible sigmoidoscopy 379,883
Upper EUS 290,655
ERCP 177,508
Lower EUS 17,428
Total 22,162,641
NOTE. Source: MarketScan Commercial Claims and En-
counters and Medicare Supplemental database.
ethnicities except non-Hispanic Asians. The incidence of
pancreatic cancer (Figure 5A) increased among non-
Hispanic Whites, Asians, and Hispanics between 1992 and
2018 and remained highest among non-Hispanic Blacks.
Pancreatic cancer mortality has changed little over this time
(Figure 5B). Given the small population size, cancer rates for
Alaska Native/American Indian were not stable and are
included in Supplementary Tables 8 to 21. We observed
increasing incidence and mortality for almost all GI cancers
in this population between 1992 and 2018. Because gall-
bladder and small intestine cancers are rare, temporal
trends of these cancers are included in Supplementary
Tables 16, 17, 20 and 21 only.
Noncancer Mortality
Among the top 15 causes of death from nonmalignant GI
diseases in 2019, there were a total of 100,317 total deaths
(Table 8). The most common causes of nonmalignant GI-
related mortality were alcohol-associated liver disease, un-
derlying 24,110 deaths and serving as a contributing factor
for more than twice that number; hepatic fibrosis/cirrhosis
of any etiology (20,184 deaths); GI bleeding (9548 deaths);
vascular disorders of the intestine (7757 deaths); and
paralytic ileus and intestinal obstruction (6943 thousand
deaths). More than half (56%) of deaths from all nonma-
lignant GI diseases were attributable to liver disease. When
stratified by race/ethnicity, a similar distribution of causes
of death was observed (see Supplementary Tables 23
and 24).
SPECIAL ARTICLE
Endoscopy Use and Trends
In 2019, an estimated 13,837,748 colonoscopies;
7,459,419 upper endoscopies; 379,883 flexible sigmoidos-
copies; 290,655 upper EUSs; 177,508 ERCPs; and 17,428
lower EUSs were performed in adults (Table 9). Colonos-
copy use in adults aged 50–74 years increased every year
between 2011 and 2019, whereas rates in adults aged 75
years decreased and then plateaued (Figure 6A). Since 2002,
Gastroenterology Vol. 162, No. 2
rates of upper endoscopies increased slightly in adults aged
18–74 years and decreased in the oldest age group
(Figure 6B). Rates of flexible sigmoidoscopies decreased
across all age groups between 2002 and 2010 and then
plateaued (Figure 6C). The rates of ERCPs have remained
stable across all age groups between 2002 and 2019
(Figure 6D), while upper EUS use increased each year
(Figure 6E). The rates of lower EUSs have declined since
2012 (Figure 6F).
Organ Transplant
In 2020, there were 12,610 persons added to the liver
transplant wait list, as well as 138 intestine, 446 pancreas,
and 1275 kidney/pancreas candidates added to their
respective wait lists. The number of liver transplants per-
formed has steadily increased over the past 3 decades, with
a total of 8906 liver transplants performed in 2020
(Figure 7A). Alcohol-associated cirrhosis is the leading
indication for liver transplantation, accounting for 25.9% of
liver transplants in 2020, followed by cirrhosis from
nonalcoholic steatohepatitis (14.7%) and hepatocellular
carcinoma (14.1%). In contrast to liver transplants, there
has been a decrease in the number of intestine and pancreas
single-organ transplants throughout the past decade,
whereas the number of combined kidney/pancreas trans-
plants has remained stable (Figure 7B–D). A total of 91 in-
testine and 962 pancreas (135 pancreas only, 827
simultaneous kidney/pancreas) transplants were per-
formed in 2020. Short gut syndrome accounted for 45.1% of
all intestine transplants, and 13.2% were related to intestine
graft failure and need for retransplant. A primary diagnosis
of diabetes accounted for 82.7% of pancreas transplants.
The characteristics of the transplant recipients and donors
are described in Table 10.
Expenditures
Health care expenditures for GI conditions totaled
$119.6 billion annually (Table 11). Among the 23 condition
categories available, the 5 most expensive categories were
biliary tract disease ($16.9 billion), esophageal disorders
($12.1 billion), abdominal pain ($9.5 billion), abdominal
hernias ($9.0 billion), and diverticular disease ($9.0 billion).
Prescription medications accounted for 53% of expendi-
tures for esophageal disorders and 71% of expenditures for
inflammatory bowel diseases.
National Institutes of Health Categorical
Spending
The NIH supported $2.3 billion in digestive diseases
research and $845 million in liver disease research in 2020
(Table 12). The total NIH budget increased from $30.6
billion in 2011 to $41.5 billion in 2020. Funding for GI
research has kept pace with increases in the NIH budget. In
2020, $319 million financed colorectal cancer research, and
$130 million was allocated for liver cancer research, $230
million for pancreatic cancer research, $24 million
for stomach cancer research, and $37 for esophageal cancer
February 2022 Burden of Gastrointestinal Diseases 635

Figure 6. (A) Colonoscopies

performed per 1000 enrollee-
years, by age group, Market-
Scan Commercial Claims and
Encounters and Medicare
Supplemental database,
2002–2019. (B) Upper endos-
copies performed per 1000
enrollee-years, by age group,
MarketScan Commercial
Claims and Encounters and
Medicare Supplemental data-
base, 2002–2019.

research (Table 13). Of the $7.0 billion in funded cancer some GI conditions. For example, the MEPS estimate asso-
research at the NIH in 2020, 10.5% supported GI cancer ciated with GI bleeding was $300 million. In comparison, the
SPECIAL ARTICLE

research. aggregate cost of GI bleeding was more realistically $3.7

Discussion
GI, liver, and pancreatic diseases account for a substan-
tial burden of health care in the United States. Expenditures
total at least $119.6 billion annually using data from the
MEPS. This conservative estimate did not include most GI
cancers and likely underestimated the costs associated with
billion, as estimated using inpatient data from the NIS. The
NIH supported $3.1 billion for GI-specific research in 2020,
with GI research continuing to capture roughly 7% of the
NIH budget.
Using discharge data from the NIS, we determined the
most common primary GI diagnoses leading to hospitaliza-
tions.15,16 We also reported the total number of secondary
diagnoses for each GI category because GI conditions may
 636 Peery et al Gastroenterology Vol. 162, No. 2

Figure 6. Continued. (C)

Flexible sigmoidoscopies
performed per 1000
enrollee-years, by age
group, MarketScan Com-
mercial Claims and En-
counters and Medicare
Supplemental database,
2002–2019. (D) Endo-
scopic retrograde chol-
angiopancreatographies
performed per 1000
enrollee-years, by age
group, MarketScan Com-
mercial Claims and En-
counters and Medicare
Supplemental database,
2002–2019.
SPECIAL ARTICLE

develop after admission to the hospital (eg, GI bleeding) or
may be an underlying condition for hospitalized patients
(eg, liver disease). We found substantial numbers of GI
conditions and symptoms listed in secondary positions on
the discharge record. For example, liver disease accounted
for 280,645 discharges with a primary diagnosis; however,
there were 13-fold as many discharges (3.6 million in 2018)
with liver disease as a secondary diagnosis.17 Including all
diagnoses captures a burden of GI disease not previously
reported.
We used data from the KID database to specifically es-
timate the most common primary GI diagnoses among
children. Compared with a similar report using data from
1997, the total number of admissions for pediatric intestinal
infections has decreased by more than 50% over the last 20
years.18 This decline may be attributable to the introduction
of the rotavirus vaccine in 2006, which is now a routine
immunization for all US infants.19 Admissions for abdominal
pain have also declined, whereas those for acute pancrea-
titis increased. This change is potentially due to an
February 2022 Burden of Gastrointestinal Diseases 637

Figure 6. Continued. (E)

Upper EUS performed per
1000 enrollee-years, by age
group, MarketScan Com-
mercial Claims and En-
counters and Medicare
Supplemental database,
2002–2019. (F) Lower EUS
performed per 1000
enrollee-years, by age
group, MarketScan Com-
mercial Claims and En-
counters and Medicare
Supplemental database,
2002–2019.

increased awareness of pediatric pancreatitis and recate- demonstrated the highest total number of 30-day all-cause
SPECIAL ARTICLE

gorization from abdominal pain to pancreatitis.20,21 Admis-
sions for inflammatory bowel disease have increased, which
is likely due to increased disease incidence.22,23 Similar to
1997, appendicitis remains the most common primary GI
diagnosis among children in the United States.24
Readmissions represent a significant burden for pa-
tients admitted with a primary diagnosis of a GI condition.
In our evaluation of readmissions using the NRD, patients
with a primary admission for GI bleeding or liver disease
readmissions. The burden of readmissions among patients
with liver disease is noteworthy and markedly higher
compared to our last report.3 We suspect that the high
burden of readmissions in the liver disease population is
accurate given that a similarly high proportion of 30-day
readmissions has been noted in other recent evaluations
of patients with a primary diagnosis of a liver disease
(particularly those with complications of cirrhosis).25–29 In
comparison to readmission data from the 2015 NRD,
 638 Peery et al
Figure 7. (A) Numbers of persons added to the waiting list and liver transplants performed, UNOS registry, 1988–2020. (B)
Numbers of persons added to the waiting list and intestine transplants performed, UNOS registry, 1988–2020.
readmissions for a primary diagnosis of obesity and
appendicitis have decreased. However, it should be noted
that there were significant changes in coding from the ICD-
Ninth Revision (ICD-9) to ICD-10 within the 2015 data.
Additionally, there is a high likelihood that patients
admitted with a primary diagnosis of obesity or appendi-
citis may have undergone a surgical procedure during the
primary admission, potentially leading to anomalies in
readmission counts in prior evaluations using a different
ICD coding system.
GI cancers account for a large number of diagnoses and
deaths annually, with persistent disparities in incidence and
SPECIAL ARTICLE
mortality rates by race/ethnicity. Despite an uptake in
colorectal cancer screening and surveillance, colorectal
cancer remains the leading cause of mortality among GI
cancers. Pancreas cancer mortality rates in 2018 are
approaching rates for colorectal cancer mortality. If that
trend continues, we may soon see pancreas cancer become
the leading cause of GI cancer–related death. Liver cancer
mortality continues to increase over time. We found that of
the $7.0 billion in cancer research funded at the NIH in
2020, 10.5% supported GI cancer research.
Gastroenterology Vol. 162, No. 2
We determined the most common causes of non–cancer-
related GI deaths in the United States using data from the
CDC. A substantial proportion of deaths from all nonmalig-
nant GI diseases were attributable to liver disease. Mortality
from alcohol-associated liver disease and nonalcoholic fatty
liver disease continue to increase over time.30 Hepatitis C–
related mortality is declining (rate per 100,000: 2.3 in
2012, 1.8 in 2016, and 1.1 in 2019), likely as a result of the
availability of effective hepatitis C therapy.31–33 Mortality
from C difficile infection has declined since 2011, likely as a
result of a true decline in C difficile infection and potentially
from more effective therapy.34
Using data from commercial claims, we estimated the
annual number of GI endoscopies in the United States and
described patterns of use between 2002 and 2019. Colo-
noscopy use in adults aged 50–74 years has increased every
year since 2011. This trend is likely driven by an uptake in
colorectal cancer screening and surveillance.35 Rates of
ERCP have remained stable, which is expected given that
indications for this procedure have not changed in the last
20 years.36 Compared to ERCP, upper EUS is relatively new,
with growing and evolving utility beyond the staging of
February 2022
Figure 7. Continued. (C) Numbers of persons added to the waiting list and pancreas transplants performed, UNOS registry,
1988–2020. (D) Numbers of persons added to the waiting list and of kidney-pancreas transplants performed, UNOS registry,
1988–2020.
malignancy. Rates of upper EUS have increased over time as
EUS becomes a standard approach to tissue acquisition in
pancreatic cancer, and a tissue diagnose is required in these
patients for the delivery of neoadjuvant therapy.37,38
Additionally, therapeutic endoscopy is increasingly being
performed for drainage of pancreatic pseudocysts and
walled-off necrosis, biliary drainage, and the creation of
enteric anastomoses, among other procedures. Racial,
ethnic, and regional disparities in access to most GI endos-
copy procedures exist, which suggests an unmet need for GI
procedures across the United States.39–41
We gathered information available through the UNOS
registry to examine national characteristics and temporal
trends related to liver, intestine, and pancreas organ
transplants. Liver transplants account for a vast majority of
all GI-related solid organ transplants. Over the past 3 de-
cades, we have seen a steady increase in the number of liver
transplants performed each year. This growth is, in part, due
to an increase in living donor transplants and the use of
organs from donations after circulatory death and from
donors with positive hepatitis C virus status. Liver
Burden of Gastrointestinal Diseases 639
transplants from living donors began in 1989 and have
grown from 0.1% to 5.5% in 2020. Additionally, livers from
donations after circulatory death accounted for 1.1% of all
liver transplants in 1993 and have increased to 9.3% of
transplants in 2020, and liver donations from hepatitis C
virus–positive donors began in 1994 and have increased
from 1.2% to 9.0%. Remarkably, the number of liver
transplants in 2020 (8906 transplants) did not decline
during the COVID-19 pandemic compared to 2019 (8896
transplants).42
This work has limitations. We relied on data collected
SPECIAL ARTICLE
by the CDC on leading GI symptoms prompting an ambu-
latory visit and leading physician diagnoses in the ambu-
latory setting. The number of sampled visits in the 2016
data set was substantially reduced, and as a consequence,
some diagnoses from the prior report (eg, ulcerative coli-
tis) had too few visits in 2016 to generate estimates.
Compared with our last report, the numbers of ambulatory
visits reported in Tables 1 and 2 have decreased. The
decreased number of visits may be related to changes in
sampling or may be due to a downward trend in outpatient
 640 Peery et al Gastroenterology Vol. 162, No. 2

Table 10.Recipient and Donor Characteristics of Liver, Pancreas, and Intestine Transplants in the United States, 2020

Characteristics Liver Pancreas ± Kidney Intestine

Transplants performed, n 8906 962 91

Age, y, n (%)
<1 139 (1.6) 5 (0.5) 5 (5.5)
1–5 166 (1.9) 8 (0.8) 16 (17.6)
6–10 64 (0.7) 4 (0.4) 7 (7.7)
11–17 133 (1.5) 6 (0.6) 6 (6.6)
18–34 606 (6.8) 226 (23.5) 23 (25.3)
35–49 1751 (19.7) 477 (49.6) 18 (19.8)
50–64 4054 (45.5) 228 (23.7) 13 (14.3)
>65 1993 (22.4) 8 (0.9) 3 (3.3)
Sex, n (%)
Male 5562 (62.5) 559 (58.1) 52 (57.1)
Female 3344 (37.5) 403 (41.9) 39 (42.9)
Race/ethnicity, n (%)
White 6118 (68.7) 495 (51.5) 53 (58.2)
Black 705 (7.9) 269 (28.0) 25 (27.5)
Hispanic 1539 (17.3) 151 (15.7) 9 (9.9)
Asian 381 (4.3) 35 (3.6) 3 (3.3)
American Indian/Alaska Native 71 (0.8) 4 (0.4) 0 (0.0)
Pacific Islander 19 (0.2) 2 (0.2) 0 (0.0)
Multiracial 73 (0.8) 6 (0.6) 1 (1.1)
Hepatitis C virus–positive donors, n (%) 805 (9.0) 39 (4.1) 3 (3.3)
Hepatitis B virus core–positive antibody donors, n (%) 413 (4.6) 10 (1.0) 0 (0.0)
High-risk donors, n (%) 2,54 (27.6) 241 (25.1) 14 (15.4)
All donation after circulatory death þ nondonation after
circulatory death, n (%)
Brain death donor 7587 (85.2) 943 (98.0) 91 (100.0)
Donation after circulatory death donors 831 (9.3) 28 (2.9) 0 (0.0)
Living donors 491 (5.5) 0 (0.0) 0 (0.0)

NOTE. Source: UNOS registry.

visits in the primary care setting.3,43 Since our last report,
diagnosis coding has transitioned from ICD-9 to ICD-10. We
mapped the codes from the last report. In addition to
mapping, we consulted available lists of ICD-10 codes for
specific GI conditions to ensure that important diseases
were not overlooked. Because of differences between the
ICD-9 and ICD-10 codes, caution should be used when
comparing our results in this report to prior estimates. We
may have overestimated the number of GI procedures
performed annually because we do not have data from
uninsured individuals and those covered by Medicaid. Our
SPECIAL ARTICLE
Classifications Software codes to CCSR codes. Given these
changes, the AHRQ recommend extreme caution when
comparing data expenditures before and after this transi-
tion. The limitations of each data source are described in
Supplementary Table 25.
It is essential that we understand the basic epidemiology
of digestive and liver diseases in the United States and
identify changes in this epidemiology over time. Carefully
examining the data in this report can help generate areas for
future investigation, prioritize research funding, identify
areas of unmet need or disparities, and provide an impor-

estimates appear to be conservative compared with
others.44,45 Using data from the MEPS, total expenditures
for GI diseases fell from $135.9 billion in 2015 to $119.6
billion in 2018. A decrease in hepatitis expenditures ($23.2
billion to $3.1 billion) accounted for most of this difference.
There is evidence that drug expenditures for hepatitis C
medications peaked in 2015 in the United States and have
decreased over time.46 It is also important to note that
between 2015 and 2018, diagnosis coding transitioned
from ICD-9 to ICD-10, and the MEPS switched from Clinical
tant overview of the impact of digestive and liver conditions.
By periodically updating the data, we can map trends and
identify gaps. During the COVID-19 pandemic, elective
endoscopy stopped, and patients delayed or lost access to
health care. In the future, we expect to find a greater burden
of mortality from GI diseases and cancers because of the
impact of COVID-19 on health care. Finally, we hope that
others will use this report as motivation to take a deeper
dive into individual diseases. There is much to learn from
carefully studying existing data sources.
Table 11.Total Expenses for GI, Pancreatic, and Liver Diseases in the United States, 2018

February 2022
Distribution of total expenditures by type of service

Total expenditure Office-based Outpatient department Hospital inpatient Prescribed Home

Condition categorya in millions provider visits, % visits, % stays, % ED visits, % medicines, % health, %

Biliary tract diseases $16,912.6 21 13 61 4 1 1

Esophageal disorders $12,119.0 21 10 13 3 53 2
Abdominal pain and other digestive/ $9511.1 14 9 38 20 20 7
abdomen signs and symptoms
Abdominal hernias $9018.8 27 32 34 6 2 6
Diverticulosis and diverticulitis $8984.8 4 3 82 10 1 1
Other GI disorders $8706.4 11 13 31 10 36 5
Regional enteritis and ulcerative colitis $8520.7 9 1 18 2 71 1
Other liver diseases $5756.6 4 8 50 2 37 5
Intestinal obstruction and ileus $5325.1 2 1 94 4 0 1
Pancreatic disorders (excluding diabetes) $4974.7 26 2 44 3 26 1
Appendicitis/appendiceal conditions $4769.4 2 4 80 14 0 1
Anal and rectal conditions $3823.5 3 0 94 2 0 1
Other disorders of stomach and duodenum $3231.5 20 8 9 9 54 11
b b b
Hepatitis $3050.9 6 6 88
Noninfectious gastroenteritis $2905.8 20 5 39 9 28 0
b
Gastritis and duodenitis $2811.9 9 6 22 46 18
b
Intestinal infections $2425.8 9 5 53 29 4
Nausea and vomiting $2155.5 13 3 39 15 29 1

Burden of Gastrointestinal Diseases

Colorectal cancers $1349.3 51 26 18 0 6 36
b
Hemorrhoids $1324.6 26 45 21 3 6
b
Dysphagia $840.8 30 38 28 3 1
b
Gastroduodenal ulcers $819.8 8 9 72 2 10
Gastrointestinal bleeding $301.7 19 15 8 39 19 21
Total $119,640.30

NOTE. Source: MEPS data, Household Component 2018 survey.12

a
The condition categories were defined using the CCRS, which is a tool developed by the AHRQ for clustering diagnoses into a manageable number of clinically
meaningful, policy-relevant categories.

641
b
No survey participants reported services from which expenditures can be extrapolated.

SPECIAL ARTICLE
 642 Peery et al Gastroenterology Vol. 162, No. 2

Table 12.NIH Estimates of Funding for Select GI Disease Categories and Total Budget, 2011–2022

2021 2022
GI disease category 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 estimated estimated

Digestive diseases $1698 $1719 $1575 $1607 $1684 $1745 $1881 $2242 $2173 $2273 $2316 $2390
Inflammatory bowel $113 $121 $114 $125 $128 $126 $134 $144 $163 $177 $180 $186
disease
Liver diseases $623 $632 $594 $605 $616 $635 $691 $802 $851 $845 $860 $892
Chronic liver disease $303 $288 $282 $293 $295 $293 $285 $324 $351 $368 $373 $388
and cirrhosis
Hepatitis $208 $210 $195 $251 $262 $267 $306 $349 $378 $362 $371 $385
Hepatitis A $4 $2 $2 $3 $4 $3 $4 $5 $3 $5 $5 $5
Hepatitis B $58 $51 $48 $48 $42 $47 $42 $55 $67 $70 $72 $74
Hepatitis C $114 $112 $101 $111 $96 $107 $114 $129 $150 $120 $123 $128
NIH total budget $30,630 $30,802 $29,129 $30,019 $30,293 $32,258 $34,147 $36,642 $39,420 $41,525 — —
NIH budget spent on 7.6 7.6 7.4 7.4 7.6 7.4 7.5 8.3 7.7 7.5 — —
digestive and
liver diseases, %

NOTE. Dollar values are in millions and rounded. Sources: NIH Research Portfolio Online Reporting Tools Categorical
Spending and NIH Office of Budget.

Supplementary Material
Note: To access the supplementary material accompanying
this article, visit the online version of Gastroenterology at
www.gastrojournal.org, and at https://doi.org/10.1053/
j.gastro.2021.10.017.
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SPECIAL ARTICLE
Gastroenterology Vol. 162, No. 2
Received June 30, 2021. Accepted October 15, 2021.
Correspondence
Address correspondence to: Anne F. Peery, MD, MSCR, University of North
Carolina School of Medicine, Bioinformatics Building CB # 7080, 130 Mason
Farm Road, Chapel Hill, North Carolina 27599-7555. e-mail:
anne_peery@med.unc.edu.
CRediT Authorship Contributions
Anne F. Peery, MD, MSCR (Conceptualization: Equal; Data curation: Lead;
Formal analysis: Supporting; Writing – original draft, review, and editing: Lead).
Seth D. Crockett, MD, MPH (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Caitlin C. Murphy, PhD (Data curation: Lead; Formal analysis: Lead; Writing –
original draft, review, and editing: Supporting).
Elizabeth T. Jensen, MPH, PhD (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Hannah P. Kim, MD, MSCR (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Matthew D. Egberg, MD, MPH (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Jennifer L. Lund, PhD, MSPH (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Andrew M. Moon, MD, MPH (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Virginia Pate, MS (Data curation: Lead; Formal analysis: Lead; Writing –
original draft, review, and editing: Supporting).
Edward L. Barnes, MD, MPH (Data curation: Supporting; Formal analysis:
Supporting; Writing – original draft, review, and editing: Supporting).
Courtney L. Schlusser, MPH (Data curation: Lead; Formal analysis: Lead;
Writing – original draft, review, and editing: Supporting).
Todd H. Baron, MD (Writing – review and editing: Supporting).
Nicholas J. Shaheen, MD, MPH (Conceptualization: supporting; Writing –
original draft, review, and editing: Supporting).
Robert S. Sandler, MD, MPH (Conceptualization: Equal; Data curation:
Supporting; Formal analysis: Supporting; Writing – original draft, review, and
editing: Supporting).
Conflicts of interest
The authors disclose no conflicts.
Funding
Supported by the National Center for Advancing Translational Sciences,
National Institutes of Health, through grant award numbers P30 DK034987
(to Robert S. Sandler), R01 DK094738 (to Robert S. Sandler) and
T32DK007634 (to Hannah P. Kim, Andrew M. Moon, and Courtney L.
Schlusser). The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes of Health.