Abstract
Background:
Cirrhosis and other chronic liver diseases are the 12th leading cause of death globally and impose a substantial economic burden. Estimating the macroeconomic burden and distribution can provide a policy rationale for the prevention and treatment of these issues. We aimed to estimate and project the macroeconomic burden of cirrhosis and other chronic liver diseases in 190 countries and territories, as well as their distribution across world regions.
Methods:
We calculated the macroeconomic burden of cirrhosis and other chronic liver diseases in 190 countries using a health-augmented macroeconomic model that accounts for the impact of morbidity and mortality on labor supply, age differences in education and experience among those affected by cirrhosis and other chronic liver diseases, and reduced investment due to the shifting of costs of these disease-related treatments from savings.
Results:
Our findings suggest that cirrhosis and other chronic liver diseases will cost the world economy INT$ 2.649 trillion (2.502–2.827) in 2021–2050. The United States has the largest economic burden of cirrhosis and other chronic liver diseases, followed by China and India. Although low- and middle-income countries have the highest health burdens (91.4% of the global disability-adjusted life years), their share of the economic burden of cirrhosis is only 57.1% of the global loss.
Conclusions:
The macroeconomic burden of cirrhosis and other chronic liver diseases is sizeable and distributed unequally across countries and world regions. Our study emphasizes the need for greater investment globally in controlling cirrhosis and other chronic liver diseases and their associated health and economic burdens.
Keywords: global burden of disease, global economic burdens, global health, gross domestic product, health-augmented macroeconomic model
INTRODUCTION
Cirrhosis and other chronic liver diseases represent a public health challenge worldwide.1 Cirrhosis and other chronic liver diseases are the 12th leading cause of death globally and the 18th leading cause of disability-adjusted life years (DALYs) globally.2,3 Since 1990, the global number of cases and deaths from cirrhosis and other chronic liver diseases has been increasing annually. Specifically, the number of deaths attributable to compensated cirrhosis worldwide has doubled during this period.4 In 2021, cirrhosis and other chronic liver diseases caused 1.43 million deaths, with India accounting for the highest number of deaths, followed by China, Indonesia, the United States of America, and Russia. The incidence rate, prevalence, and mortality for cirrhosis and other chronic liver diseases are shown in detail in Supplemental Appendix 1, http://links.lww.com/HC9/C222 Viral hepatitis, alcohol-associated liver disease (ALD), and metabolic dysfunction–associated steatotic liver disease (MASLD) are the leading causes of cirrhosis and other chronic liver diseases globally.5 In addition, the prevalence of MASLD and the mortality of ALD are increasing rapidly in several regions of the world due to factors such as high alcohol consumption, obesity or overweight, and population aging.6 Without comprehensive interventions, these health burdens will rise dramatically in the coming decades.
Beyond the health burden, cirrhosis and other chronic liver diseases also inflict a large economic toll through reduced productivity, unemployment, loss of labor, and capital investment. The economic burden of cirrhosis and other chronic liver diseases includes both direct and indirect costs.7 Direct costs include all expenditures related to the treatment of cirrhosis and other chronic liver diseases, such as liver transplantation, medications, hospitalization, and treatment of complications.8,9 Indirect costs refer to the loss of productivity or earnings associated with morbidity and premature mortality. Estimating the economic burden of cirrhosis and other chronic liver diseases and its distribution across regions and countries of the world enables policymakers to: (1) formulate appropriate interventions to curb the increase in mortality and morbidity associated with cirrhosis and other chronic liver diseases, (2) rationalize the allocation of resources, and (3) strengthen healthcare systems that can effectively cope with the projected increase in the prevalence of cirrhosis and other chronic liver diseases.
Previous studies assessed the economic burden in only one or a few countries.7,10,11,12,13,14,15,16,17,18 For example, 1 study showed that total healthcare expenditures for cirrhosis and other chronic liver diseases in the United States reached $32.5 billion in 2016, an annual increase of ~4.3% over the past 2 decades.16 Studies have also evaluated the economic burden of MASLD, which showed that the direct medical costs of MASLD are ~$103 billion per year in the United States, at an average of $1613 per patient, and $35 billion per year in 4 European countries (Germany, France, Italy, and the United Kingdom).17
In conclusion, the lack of information on the economic burden of cirrhosis and other chronic liver diseases hinders the assessment of cirrhosis prevention and treatment, as well as the development of health policies. Moreover, most studies assessing the economic burden of cirrhosis and other chronic liver diseases have simply summed the direct and indirect costs (cost-of-illness approach) without considering the impact of economic adjustment mechanisms.19 On the other hand, this approach does not take into account changes in physical capital due to the impact of cirrhosis on treatment costs and savings, nor does it take into account changes in population dynamics associated with morbidity and mortality. The health-augmented macroeconomic model constructed by Chen et al. effectively addresses these issues and has been used to assess the global economic burdens of cancer, chronic obstructive pulmonary disease (COPD), Alzheimer’s disease (AD), and road injuries.20,21,22,23
Using a health-augmented macroeconomic model, this study estimates the macroeconomic costs of cirrhosis and other chronic liver diseases in 190 countries and territories around the world from 2021 to 2050 to provide data support for promoting global cirrhosis and other chronic liver diseases management.
METHODS
Model description
This study adheres to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022. We estimated the macroeconomic burden of cirrhosis and other chronic liver diseases in 190 countries and territories with the health-augmented macroeconomic model, which has been described in detail in previous studies19,21,22,23 and Supplemental Appendix S2, http://links.lww.com/HC9/C222. In the Global Burden of Disease (GBD) Study, cirrhosis and other chronic liver diseases were divided into 5 main aetiologies. This included cirrhosis and other chronic liver diseases due to alcohol use, chronic hepatitis B, chronic hepatitis C, non-alcoholic fatty liver diseases, and cirrhosis related to other causes.
The model elucidates 2 pathways by which diseases contribute to the macroeconomic burden. On the one hand, both morbidity and mortality associated with cirrhosis and other chronic liver diseases reduce the effective labor supply. The morbidity of cirrhosis and other chronic liver diseases increases labor absenteeism and thus reduces productivity, while mortality due to cirrhosis and other chronic liver diseases directly reduces the size of the working-age population. On the other hand, any costs associated with cirrhosis and other chronic liver diseases treatment reduce total savings and investment, thus hindering physical capital accumulation in society. Households affected by cirrhosis and other chronic liver diseases need to divert resources from savings to cover out-of-pocket expenses or increase premiums to pay for treatment through insurance companies. Notably, a shift in consumption from other goods or services to health care does not constitute an economic loss, but simply a reallocation of resources across different sectors of the economy. This is because a shift in consumption to healthcare expenditure does not reduce the productive capacity of the economy. Conversely, shifting funds from physical capital investment to healthcare consumption reduces the prospects for future growth of physical capital.
To quantify the macroeconomic costs of cirrhosis and other chronic liver diseases, we compared total annual output in the form of gross domestic product (GDP) over the period 2021–2050 under 2 scenarios: (1) a status quo scenario, in which no further interventions are implemented to reduce mortality and morbidity associated with cirrhosis and other chronic liver diseases relative to current and projected rates; and (2) a counterfactual scenario, in which cirrhosis and other chronic liver diseases are assumed to be completely eliminated at zero cost. The macroeconomic burden of cirrhosis and other chronic liver diseases was defined as the cumulative difference in projected annual GDP between the 2 scenarios.
Data sources
This study used publicly accessible data (Supplemental Appendix S3, http://links.lww.com/HC9/C222) that did not meet the regulatory definition of human participant research and were exempt from Institutional Review Board review under the Common Rule. Data on cirrhosis and other chronic liver diseases incidence, prevalence, mortality, years of life lost due to premature mortality (YLL), and years lost due to disability (YLD) were from GBD 2021 by the Institute for Health Metrics and Evaluation.1 Data on educational attainment, labor force participation, population, and physical capital were from the Barro-Lee Education Database,24 the International Labor Organization,25 the United Nations Department of Economic and Social Affairs (DESA),26 and the Penn World Table projections,27 respectively. Cirrhosis and other chronic liver diseases treatment costs were from Dieleman et al.28 GDP projections for the status quo scenario and savings rate data were from the World Bank World Development Indicators database and the World Economic Outlook database.29,30,31 More details on data sources and parameter values are provided in Supplemental Appendix S3, http://links.lww.com/HC9/C222. To make estimates comparable across countries, economic data and estimations were converted to 2017 international dollars (INT$).
We estimated the economic burden of cirrhosis and other chronic liver diseases for 190 countries and territories globally and for a set of World Bank regions. Of the 190 countries and territories, 126 had all the data inputs we needed, and their economic burden of cirrhosis and other chronic liver diseases was calculated directly through the health-augmented macroeconomic model; the remaining 64 countries and territories lacked the necessary data, and we referred to previous studies that used linear projections to infer their economic burden of cirrhosis and other chronic liver diseases (Supplemental Appendix 4, http://links.lww.com/HC9/C222). We further stratified the model by etiology, including chronic hepatitis B, chronic hepatitis C, cirrhosis due to alcohol, metabolic dysfunction–associated fatty liver disease (MAFLD), including cirrhosis, and cirrhosis due to other causes, to capture the differential economic and health implications of each etiology.
Sensitivity analysis
Confidence intervals for the economic burden of cirrhosis and other chronic liver diseases were provided by varying mortality and morbidity rates according to the lower and upper bounds (95% uncertainty intervals) of the GBD mortality and morbidity data. In addition, we provided estimates with a discount rate of 3% in the main analysis and estimates with discount rates of 0%, 2%, and 5% in Supplemental Appendix 5, http://links.lww.com/HC9/C222. Analyses were conducted using R 4.3.3 software.
RESULT
We calculated the global macroeconomic burden of cirrhosis and other chronic liver diseases as the sum of the GDP differences between the status quo and the counterfactual scenario of eliminating cirrhosis and other chronic liver diseases for 2021–2050. Table 1 shows the economic burden for the 126 countries/areas with complete data and the 64 countries/areas with missing data. The former accounted for a total of 86.0% of the global population and 95.3% of GDP. The United States has the largest economic burden of cirrhosis and other chronic liver diseases at INT$ 496 billion, followed by China and India at INT$ 436 billion and INT$ 340 billion, respectively. In terms of percentage of GDP, Kuwait had the largest share (0.18%), followed by Saudi Arabia (0.16%) and Iraq (0.13%). Guyana, Qatar, and Kuwait have the highest economic burden per capita at INT$ 1989, INT$ 1773, and INT$ 1707, respectively. Figures 1 and 2 show the total macroeconomic burden and the economic burden as a share of GDP for each country.
TABLE 1.
Total macroeconomic burden, economic burden as a proportion of GDP in 2021–2050 adjusted for projected economic growth rate, and per capita economic burden attributable to cirrhosis and other chronic liver diseases mortality and morbidity in 2021–2050, by country and World Bank region
| Economic loss, millions of 2017 INT$ (uncertainty intervala) | Proportion of total GDP in 2021–2050, × 10−3% (uncertainty intervala) | Per capita loss, 2017 INT$ (uncertainty intervala) | |
|---|---|---|---|
| North America | |||
| Bermudab | 69 (62–77) | 55 (49–61) | 1135 (1012–1259) |
| Canada | 24,529 (23,559–25,630) | 52 (50–54) | 577 (554–603) |
| United States of America | 495,643 (489,635–501,698) | 91 (89–92) | 1377 (1360–1394) |
| East Asia and the Pacific | |||
| Australia | 20,687 (20,388–21,024) | 61 (60–62) | 705 (695–717) |
| Brunei Darussalam | 119 (101–143) | 20 (17–24) | 246 (209–294) |
| Cambodia | 4259 (3501–5252) | 116 (95–142) | 227 (186–280) |
| China | 436,356 (413,217–466,148) | 41 (39–44) | 310 (294–331) |
| Fiji | 142 (128–162) | 42 (38–48) | 140 (126–159) |
| Indonesia | 90,169 (78,454–106,310) | 70 (61–83) | 300 (261–353) |
| Japan | 64,439 (64,104–64,765) | 58 (58–58) | 561 (558–564) |
| Kiribatib | 4 (4–5) | 72 (66–78) | 27 (25–29) |
| Lao People’s Democratic Republic | 904 (794–1099) | 37 (33–45) | 103 (91–126) |
| Malaysia | 5835 (4563–7356) | 17 (13–22) | 153 (120–193) |
| Marshall Islandsb | 5 (5–6) | 65 (59–71) | 112 (101–122) |
| Micronesia (Federated States of)b | 6 (5–6) | 64 (58–70) | 45 (40–49) |
| Mongolia | 922 (852–1009) | 63 (58–69) | 235 (217–257) |
| Myanmarb | 5882 (5377–6386) | 70 (64–76) | 102 (93–111) |
| Naurub | 2 (2–3) | 59 (53–65) | 177 (159–195) |
| New Zealand | 2681 (2654–2710) | 43 (42–43) | 475 (470–480) |
| Palaub | 4 (4–4) | 69 (63–75) | 235 (215–256) |
| Papua New Guineab | 582 (515–649) | 52 (46–58) | 47 (41–52) |
| Philippines | 28,878 (27,754–30,728) | 63 (61–68) | 210 (202–223) |
| Republic of Korea | 47,498 (45,946–49,515) | 76 (74–79) | 940 (909–980) |
| Samoab | 20 (18–22) | 57 (51–63) | 74 (66–82) |
| Singapore | 10,542 (10,508–10,580) | 62 (62–63) | 1660 (1655–1666) |
| Solomon Islandsb | 29 (26–31) | 61 (55–67) | 30 (27–33) |
| Taiwan (Province of China)b | 28,088 (25,801–30,375) | 73 (67–79) | 1188 (1091–1285) |
| Thailand | 34,080 (29,668–39,621) | 93 (81–108) | 476 (414–553) |
| Timor-Lesteb | 127 (113–141) | 54 (48–60) | 81 (72–90) |
| Tongab | 11 (10–12) | 64 (58–69) | 89 (81–98) |
| Tuvalub | 1 (1–1) | 64 (58–70) | 97 (88–106) |
| Vanuatub | 19 (17–21) | 67 (61–73) | 43 (39–47) |
| Vietnam | 27,208 (21,684–35,076) | 50 (40–64) | 260 (207–335) |
| Europe and Central Asia | |||
| Albania | 483 (457–517) | 38 (36–41) | 176 (167–189) |
| Andorrab | 45 (39–51) | 43 (37–49) | 555 (478–631) |
| Armenia | 1985 (1966–2005) | 119 (118–120) | 728 (721–735) |
| Austria | 5160 (5050–5280) | 43 (42–44) | 571 (559–585) |
| Azerbaijanb | 2666 (2460–2871) | 77 (71–83) | 247 (228–266) |
| Belarusb | 2123 (1886–2359) | 54 (48–60) | 236 (209–262) |
| Belgium | 6166 (6061–6281) | 42 (42–43) | 515 (506–524) |
| Bosnia and Herzegovinab | 938 (845–1031) | 60 (54–66) | 311 (280–341) |
| Bulgaria | 5654 (5240–6091) | 115 (107–124) | 941 (872–1014) |
| Croatia | 1299 (1246–1357) | 34 (33–36) | 348 (334–364) |
| Cyprus | 556 (536–582) | 37 (36–39) | 415 (401–434) |
| Czech Republic | 7996 (7585–8418) | 65 (61–68) | 761 (722–801) |
| Denmark | 2737 (2662–2822) | 31 (30–32) | 440 (428–454) |
| Estonia | 1096 (1009–1189) | 73 (67–79) | 870 (801–944) |
| Finland | 3212 (3133–3300) | 49 (48–50) | 579 (565–595) |
| France | 30,986 (30,302–31,734) | 42 (41–43) | 470 (460–482) |
| Georgiab | 1730 (1595–1865) | 77 (71–83) | 482 (445–520) |
| Germany | 59,859 (57,839–62,075) | 57 (55–59) | 729 (705–756) |
| Greece | 1409 (1367–1457) | 19 (18–19) | 143 (139–148) |
| Hungary | 5206 (4922–5510) | 50 (47–53) | 550 (520–583) |
| Iceland | 166 (160–173) | 26 (25–27) | 416 (401–435) |
| Ireland | 8178 (8086–8278) | 39 (38–39) | 1514 (1497–1532) |
| Italy | 25,679 (25,575–25,783) | 45 (44–45) | 455 (453–457) |
| Kazakhstan | 9069 (8422–10,132) | 59 (54–65) | 409 (380–457) |
| Kyrgyzstan | 786 (717–860) | 67 (61–73) | 99 (90–108) |
| Latvia | 887 (807–971) | 54 (49–59) | 547 (498–598) |
| Lithuania | 2507 (2365–2653) | 77 (73–82) | 1020 (962–1080) |
| Luxembourg | 442 (429–458) | 22 (22–23) | 612 (594–633) |
| Montenegrob | 206 (180–232) | 47 (41–53) | 336 (293–378) |
| Netherlands | 10,801 (10,631–10,991) | 41 (41–42) | 600 (591–611) |
| North Macedoniab | 498 (439–556) | 51 (45–57) | 245 (216–274) |
| Norway | 4796 (4775–4818) | 56 (56–56) | 809 (806–813) |
| Poland | 38,791 (37,565–40,044) | 88 (85–90) | 1022 (989–1055) |
| Portugal | 3285 (3228–3346) | 34 (33–34) | 332 (326–338) |
| Republic of Moldova | 1386 (1295–1484) | 123 (115–132) | 445 (416–477) |
| Romania | 23,341 (22,140–24,636) | 107 (101–113) | 1249 (1185–1319) |
| Russian Federation | 83,698 (81,326–86,063) | 88 (86–91) | 601 (584–618) |
| San Marinob | 24 (21–27) | 48 (42–54) | 735 (643–827) |
| Serbia | 2633 (2479–2828) | 63 (59–68) | 400 (377–430) |
| Slovakia | 3345 (3020–3752) | 68 (61–76) | 613 (553–687) |
| Slovenia | 1011 (989–1038) | 39 (38–40) | 485 (474–497) |
| Spain | 22,244 (22,001–22,511) | 45 (44–46) | 477 (472–483) |
| Sweden | 8311 (8250–8379) | 59 (58–59) | 739 (734–746) |
| Switzerland | 4938 (4869–5014) | 32 (32–33) | 529 (522–537) |
| Tajikistan | 1805 (1543–2238) | 95 (81–118) | 146 (125–181) |
| Turkmenistanb | 3397 (3193–3602) | 99 (93–105) | 463 (435–490) |
| Türkiye | 40,044 (39,375–40,942) | 47 (46–48) | 439 (432–449) |
| Ukraine | 7464 (6097–9215) | 66 (54–81) | 203 (166–251) |
| United Kingdom | 33,369 (33,088–33,649) | 44 (43–44) | 477 (473–481) |
| Uzbekistanb | 8818 (8124–9512) | 76 (70–82) | 220 (203–237) |
| Middle East and North Africa | |||
| Algeria | 9483 (9275–9802) | 76 (74–78) | 181 (177–187) |
| Bahrain | 1194 (1170–1224) | 55 (54–57) | 729 (715–748) |
| Djiboutib | 141 (128–154) | 63 (57–69) | 107 (97–118) |
| Egypt | 39,013 (37,202–41,269) | 76 (72–80) | 291 (277–308) |
| Iran (Islamic Republic of)b | 26,434 (24,452–28,417) | 80 (74–86) | 280 (259–301) |
| Iraq | 17,466 (17,313–17,680) | 133 (132–135) | 300 (297–303) |
| Israel | 6610 (6533–6693) | 48 (48–49) | 610 (603–618) |
| Jordan | 1453 (1431–1483) | 52 (51–53) | 115 (113–117) |
| Kuwait | 8098 (8082–8115) | 176 (176–176) | 1707 (1704–1711) |
| Lebanonb | 1239 (1145–1332) | 79 (73–85) | 253 (234–273) |
| Libyab | 4600 (4286–4914) | 87 (82–93) | 598 (557–639) |
| Malta | 808 (798–819) | 74 (73–75) | 1502 (1483–1523) |
| Morocco | 6840 (6643–7195) | 78 (76–82) | 164 (159–173) |
| Omanb | 2990 (2754–3226) | 76 (70–82) | 555 (511–598) |
| Qatar | 5251 (5226–5290) | 82 (81–82) | 1773 (1764–1786) |
| Saudi Arabia | 71,822 (70,215–73,976) | 158 (154–162) | 1680 (1642–1730) |
| Tunisia | 3206 (3129–3325) | 98 (96–102) | 238 (233–247) |
| United Arab Emiratesb | 13,868 (12,692–15,044) | 70 (64–76) | 1340 (1227–1454) |
| Yemenb | 720 (653–788) | 64 (58–70) | 16 (15–18) |
| South Asia | |||
| Afghanistanb | 1169 (1064–1274) | 67 (61–73) | 21 (19–23) |
| Bangladesh | 5217 (594–12,108) | 10 (1–23) | 27 (3–63) |
| Bhutanb | 235 (213–256) | 66 (60–72) | 280 (255–306) |
| India | 339,844 (304,857–379,243) | 75 (67–83) | 217 (194–242) |
| Maldives | 264 (256–275) | 48 (47–50) | 502 (486–523) |
| Nepal | 3152 (2585–3886) | 66 (54–82) | 92 (75–113) |
| Pakistan | 20,496 (15,578–25,957) | 48 (36–60) | 69 (52–87) |
| Sri Lanka | 4112 (3511–4857) | 45 (38–53) | 186 (158–219) |
| Latin America and the Caribbean | |||
| Antigua and Barbudab | 38 (34–42) | 57 (51–63) | 392 (351–433) |
| Argentina | 4613 (4346–4911) | 22 (21–24) | 94 (89–100) |
| Bahamasb | 196 (177–216) | 60 (54–66) | 450 (405–495) |
| Barbados | 16 (13–19) | 16 (13–19) | 56 (47–66) |
| Belize | 62 (57–67) | 66 (61–71) | 130 (120–141) |
| Bolivia (Plurinational State of) | 2136 (1951–2388) | 75 (68–84) | 148 (135–165) |
| Brazil | 34,516 (34,175–34,853) | 48 (48–49) | 152 (150–153) |
| Chile | 7703 (7499–7935) | 62 (61–64) | 379 (369–391) |
| Colombia | 17,096 (16,935–17,277) | 80 (80–81) | 309 (306–312) |
| Costa Rica | 2295 (2213–2389) | 68 (65–71) | 413 (398–430) |
| Dominican Republic | 4455 (3284–5741) | 52 (38–67) | 360 (265–464) |
| Dominicab | 13 (11–14) | 60 (54–66) | 169 (152–186) |
| Ecuador | 2486 (2399–2586) | 56 (54–58) | 122 (118–127) |
| El Salvador | 1187 (1045–1355) | 78 (68–89) | 179 (157–204) |
| Grenadab | 31 (28–34) | 59 (53–64) | 237 (213–261) |
| Guatemala | 3662 (3410–3934) | 76 (71–82) | 172 (160–185) |
| Guyanab | 1701 (1558–1844) | 71 (65–77) | 1989 (1822–2156) |
| Haiti | 232 (159–334) | 32 (22–47) | 17 (12–25) |
| Honduras | 830 (666–1069) | 45 (36–58) | 67 (53–86) |
| Jamaica | 185 (174–198) | 28 (26–30) | 67 (63–72) |
| Mexico | 56,683 (54,786–58,733) | 92 (89–96) | 410 (396–425) |
| Nicaragua | 808 (769–852) | 83 (79–88) | 100 (95–105) |
| Panama | 4303 (4246–4368) | 86 (85–88) | 840 (829–853) |
| Paraguay | 1545 (1464–1647) | 57 (54–61) | 199 (188–212) |
| Peru | 5072 (4419–5922) | 42 (36–48) | 132 (115–155) |
| Puerto Ricob | 1378 (1262–1494) | 71 (65–77) | 445 (408–483) |
| Saint Kitts and Nevisb | 25 (22–27) | 65 (59–71) | 516 (469–563) |
| Saint Luciab | 42 (37–46) | 60 (54–66) | 228 (206–251) |
| Saint Vincent and the Grenadinesb | 25 (23–28) | 59 (53–65) | 244 (219–269) |
| Surinameb | 136 (123–149) | 63 (57–69) | 201 (182–220) |
| Trinidad and Tobagob | 341 (303–378) | 54 (48–60) | 222 (198–247) |
| Uruguay | 912 (893–933) | 46 (45–47) | 267 (261–273) |
| Venezuela (Bolivarian Republic of)b | 1066 (956–1176) | 58 (52–64) | 32 (29–36) |
| Sub-Saharan Africa | |||
| Angolab | 2815 (2552–3078) | 64 (58–70) | 54 (49–59) |
| Benin | 696 (486–1049) | 37 (26–55) | 38 (26–57) |
| Botswana | 1048 (1008–1109) | 75 (72–79) | 331 (318–350) |
| Burkina Fasob | 1093 (970–1216) | 53 (47–59) | 35 (31–39) |
| Burundi | 127 (104–160) | 52 (42–66) | 7 (6–9) |
| Cabo Verdeb | 107 (98–116) | 68 (62–74) | 162 (147–176) |
| Cameroon | 1312 (915–1822) | 39 (27–54) | 34 (24–48) |
| Central African Republicb | 107 (98–115) | 75 (69–81) | 13 (12–14) |
| Chadb | 349 (317–382) | 64 (58–70) | 13 (12–15) |
| Comorosb | 56 (51–61) | 69 (63–75) | 55 (50–59) |
| Congo | 245 (177–347) | 60 (44–85) | 31 (22–44) |
| Côte d’Ivoire | 1924 (1350–2733) | 27 (19–38) | 50 (35–71) |
| Democratic Republic of the Congo | 2498 (1981–3248) | 64 (50–83) | 17 (13–22) |
| Equatorial Guineab | 155 (138–173) | 54 (48–59) | 71 (63–78) |
| Eswatini | 177 (150–213) | 60 (51–73) | 127 (107–153) |
| Ethiopiab | 9276 (8257–10,296) | 54 (48–60) | 56 (50–62) |
| Gabon | 488 (395–632) | 58 (47–75) | 162 (131–209) |
| Gambia | 84 (50–130) | 38 (23–59) | 23 (14–36) |
| Ghana | 2972 (2273–3943) | 41 (32–55) | 70 (54–94) |
| Guinea-Bissaub | 89 (80–97) | 64 (58–70) | 32 (29–35) |
| Guineab | 1278 (1160–1395) | 65 (59–71) | 69 (63–76) |
| Kenya | 3758 (2853–5320) | 39 (30–55) | 54 (41–77) |
| Lesotho | 72 (58–93) | 67 (53–86) | 28 (22–35) |
| Liberiab | 130 (118–142) | 65 (59–71) | 19 (17–20) |
| Madagascarb | 793 (706–881) | 54 (48–60) | 20 (18–22) |
| Malawib | 588 (531–645) | 61 (56–67) | 21 (19–23) |
| Mali | 874 (689–1145) | 48 (38–63) | 26 (21–35) |
| Mauritania | 452 (397–546) | 54 (47–65) | 69 (60–83) |
| Mauritius | 692 (670–717) | 77 (75–80) | 533 (516–552) |
| Mozambique | 1443 (1344–1587) | 97 (91–107) | 31 (29–34) |
| Namibia | 264 (221–336) | 50 (41–63) | 85 (71–107) |
| Niger | 1139 (963–1500) | 77 (65–101) | 27 (23–36) |
| Nigeriab | 17,111 (15,567–18,655) | 66 (60–72) | 59 (53–64) |
| Rwanda | 588 (398–931) | 36 (25–58) | 33 (22–52) |
| Sao Tome and Principeb | 18 (16–19) | 74 (68–80) | 60 (55–65) |
| Senegal | 1599 (1325–1994) | 58 (48–73) | 67 (56–84) |
| Seychellesb | 70 (64–76) | 71 (65–77) | 619 (568–671) |
| Sierra Leone | 290 (239–372) | 59 (48–75) | 26 (22–34) |
| Somaliab | 717 (661–773) | 76 (70–82) | 28 (26–30) |
| South Africa | 9423 (8989–9933) | 52 (50–55) | 140 (134–148) |
| South Sudanb | 41 (37–45) | 65 (59–71) | 3 (3–3) |
| Sudan | 859 (710–1162) | 28 (23–37) | 14 (11–18) |
| Togo | 325 (216–470) | 46 (31–67) | 28 (18–40) |
| Uganda | 2473 (2054–3050) | 56 (47–69) | 38 (31–46) |
| United Republic of Tanzania | 2015 (1315–3096) | 27 (18–42) | 22 (14–33) |
| Zambia | 1351 (1055–1749) | 65 (51–84) | 49 (38–63) |
| Zimbabwe | 89 (30–168) | 10 (3–19) | 4 (1–8) |
Uncertainty intervals in parentheses were calculated in the sensitivity analysis based on the lower and upper bounds of 95% uncertainty intervals for Global Burden of Disease Study 2021 mortality and morbidity data.
Results imputed due to missing data.
Abbreviations: GDP, gross domestic product; INT$, international dollars.
FIGURE 1.
Macroeconomic burden due to cirrhosis and other chronic liver diseases from 2021 to 2050. Abbreviation: INT$, international dollars.
FIGURE 2.
Economic burden of cirrhosis and other chronic liver diseases as a proportion of total GDP in 2021–2050. Abbreviation: GDP, gross domestic product.
Table 2 presents the results of the World Bank study for each region and country income group. We estimate the global macroeconomic burden of cirrhosis and other chronic liver diseases to be INT$ 2.649 trillion (2.502–2.827) in 2021–2050, with a discount rate of 3% in the main analysis. Without discounting, this estimate would be INT$ 4.843 trillion (4.585–5.157); with a discount rate of 2%, it would be INT$ 3.216 trillion (confidence interval 3.041–3.43); and with a discount rate of 5%, it would be INT$ 1.834 trillion (1.729–1.961) (Supplemental Appendix 5, http://links.lww.com/HC9/C222). Our main results suggest that the burden due to cirrhosis and other chronic liver diseases is equivalent to 0.062% (confidence interval 0.058–0.066) of the total global cumulative GDP in 2021–2050, or a per capita burden of INT$ 303 (286–323).
TABLE 2.
Total macroeconomic burden, economic burden as a proportion of total GDP, and per capita economic burden attributable to cirrhosis and other chronic liver diseases mortality and morbidity in 2021–2050 by World Bank region, by World Bank income group, and globally
| Economic loss, billions of 2017 INT$ (uncertainty intervala) | Proportion of total GDP in 2021–2050, × 10−3% (uncertainty intervala) | Per capita loss, 2017 INT$ (uncertainty intervala) | |
|---|---|---|---|
| By World Bank region | |||
| North America | 520 (513–527) | 87 (86–89) | 1299 (1281–1316) |
| East Asia and the Pacific | 809 (756–879) | 49 (46–53) | 340 (317–369) |
| Europe and central Asia | 493 (477–511) | 57 (55–59) | 533 (516–553) |
| Middle East and North Africa | 221 (213–231) | 96 (93–100) | 407 (392–425) |
| South Asia | 374 (329–428) | 66 (58–75) | 174 (152–198) |
| Latin America and the Caribbean | 156 (149–163) | 63 (61–66) | 223 (214–233) |
| Sub-Saharan Africa | 74 (64–88) | 52 (45–62) | 45 (39–53) |
| By World Bank country income group | |||
| High income | 1139 (1116–1165) | 71 (70–73) | 903 (884–923) |
| Upper-middle income | 892 (839–958) | 51 (48–55) | 313 (295–337) |
| Lower-middle income | 591 (523–673) | 65 (58–74) | 160 (141–182) |
| Low income | 26 (22–30) | 56 (48–66) | 28 (24–33) |
| Global (190 countries and territories) | 2649 (2502–2827) | 62 (58–66) | 303 (286–323) |
Uncertainty intervals in parentheses are calculated based on the lower and upper bounds of 95% uncertainty intervals for Global Burden of Disease Study 2021 mortality and morbidity data.
Abbreviations: GDP, gross domestic product; INT$, international dollars.
Among the World Bank regions, East Asia and the Pacific had the highest macroeconomic burden of cirrhosis and other chronic liver diseases, followed by North America (Table 2). The Middle East and North Africa have the largest economic loss as a proportion of output, equivalent to 0.096% of cumulative GDP in 2021–2050 (uncertainty interval 0.093–0.1). As expected, the economic burden of cirrhosis and other chronic liver diseases was positively correlated with country income groups, as well as with total GDP and the proportion of economic losses per capita; the highest burden is found in high-income countries, with total economic losses of INT$ 1.139 trillion (1.116–1.165) and per capita economic losses of INT$ 903 (884–923). In comparison, the total cost of cirrhosis to low-income countries is estimated at INT$ 2.6 billion (2.2–3.0) with a per capita loss of INT$ 28 (24–33). Supplemental Appendix S5, http://links.lww.com/HC9/C222, presents the estimates at different discount rates by World Bank region and World Bank income group.
Cirrhosis and other chronic liver diseases resulted in 41.8 million disability-adjusted life-years (DALYs) globally in 2021. The distribution of the economic burden was not proportional to population size and DALYs. For example, North America accounts for only 0.2% of global DALYs but 19.6% of the global economic burden, while sub-Saharan Africa accounts for 15.3% of global DALYs but only 2.8% of the economic burden. Notably, while the economic burden of cirrhosis and other chronic liver diseases is relatively low in low- and middle-income countries (56.0% and 1% of the global economic burden, respectively), the burden of disease as measured by DALYs is very high (82.8% and 8.6% of global DALYs, respectively; Table 3). Table 4 presents the economic burden stratified by etiology, detailing the losses attributable to each major cause in terms of total GDP loss, per capita loss, and share of global economic impact. The economic burden and per capita impact of chronic liver disease vary substantially across etiologies. For example, MAFLD, including cirrhosis, contributes substantially to both total economic burden and per capita losses, whereas cirrhosis due to other causes has a comparatively smaller impact.
TABLE 3.
Comparison of macroeconomic burden and lifetime health burden of cirrhosis and other chronic liver diseases, by World Bank region and country income group
| Economic burden in 2021–2050, billions of 2017 INT$ (global %) | DALYs in 2021, millions (global %) | Total GDP in 2021, billions of 2017 INT$ (global %) | Population in 2021, millions (global %) | |
|---|---|---|---|---|
| By World Bank region | ||||
| North America | 520 (19.6%) | 0.1 (0.2%) | 22,945 (17.2%) | 375 (4.8%) |
| East Asia and the Pacific | 809 (30.6%) | 10.5 (25.1%) | 43,588 (32.6%) | 2346 (30.1%) |
| Europe and Central Asia | 493 (18.6%) | 5.9 (14.1%) | 32,889 (24.6%) | 921 (11.8%) |
| Middle East and North Africa | 221 (8.3%) | 2.1 (5%) | 7757 (5.8%) | 456 (5.8%) |
| South Asia | 374 (14.1%) | 13.1 (31.3%) | 12,100 (9.1%) | 1893 (24.3%) |
| Latin America and the Caribbean | 156 (5.9%) | 3.8 (9.1%) | 9942 (7.4%) | 641 (8.2%) |
| Sub-Saharan Africa | 74 (2.8%) | 6.4 (15.3%) | 4369 (3.3%) | 1163 (14.9%) |
| By World Bank country income group | ||||
| High income | 1139 (43%) | 3.6 (8.6%) | 61,915 (46.3%) | 1233 (15.8%) |
| Upper-middle income | 892 (33.7%) | 14.8 (35.3%) | 48,683 (36.4%) | 2771 (35.5%) |
| Lower-middle income | 591 (22.3%) | 19.9 (47.5%) | 21,679 (16.2%) | 3137 (40.2%) |
| Low income | 26 (1%) | 3.6 (8.6%) | 1154 (0.9%) | 626 (8.0%) |
| Global (190 countries and territories) | 2649 (100%) | 41.8 (100%) | 133,589 (100%) | 7795 (100%) |
Abbreviations: DALY, disability-adjusted life-year; GDP, gross domestic product; INT$, international dollars.
TABLE 4.
The economic burden, proportion, and per capita loss of global cirrhosis and other chronic liver diseases by etiology
| Economic loss, millions of 2017 INT$ (uncertainty interval*) | Proportion of total GDP in 2020–2050, ×10−3% (uncertainty interval*) | Per capita loss, 2017 INT$ (uncertainty interval*) | |
|---|---|---|---|
| Chronic hepatitis B including cirrhosis | 1.863 (1.675–2.107) | 0.04 (0.04–0.05) | 0.21 (0.19–0.24) |
| Chronic hepatitis C including cirrhosis | 1.793 (1.487–2.128) | 0.04 (0.03–0.05) | 0.21 (0.17–0.24) |
| Cirrhosis due to alcohol | 1.735 (1.461–2.004) | 0.04 (0.03–0.05) | 0.20 (0.17–0.23) |
| MAFLD including cirrhosis | 2642.742 (2496.779–2819.574) | 61.854 (57.88–65.83) | 302.284 (285.40–322.15) |
| Cirrhosis due to other causes | 0.867 (0.598–1.187) | 0.02 (0.01–0.03) | 0.10 (0.07–0.14) |
| Cirrhosis and other chronic liver diseases | 2649 (2502–2827) | 62 (58–66) | 303 (286–323) |
Uncertainty intervals in parentheses are calculated based on the lower and upper bounds of 95% uncertainty intervals for Global Burden of Disease Study 2021 mortality and morbidity data.
Abbreviations: INT$, international dollars; MAFLD, metabolic dysfunction–associated fatty liver disease.
DISCUSSION
This study comprehensively estimated the macroeconomic burden of cirrhosis and other chronic liver diseases in 190 countries worldwide using macroeconomic modeling. To the best of our knowledge, this study is the first to analyze the economic burden of cirrhosis and other chronic liver diseases by considering productivity losses in populations with different levels of education and experience. Our results suggest that cirrhosis and other chronic liver diseases will cost a total of INT$ 2.6 trillion between 2021 and 2050, which exceeds the total GDP of Italy (the world’s eighth-largest economy in constant 2017 international dollars) in 2021.
Although low- and middle-income countries account for 91.4% of the global burden of DALYs for cirrhosis and other chronic liver diseases and 85% of the global population, they contribute only 57.1% of the global economic costs of cirrhosis and other chronic liver diseases. This phenomenon is particularly evident in low-income countries, which account for only 1% of the global economic cost of cirrhosis and other chronic liver diseases but 8.6% of the global burden of cirrhosis and other chronic liver diseases DALYs. Disparities in economic development may help explain the differences in the magnitude of the economic burden across income groups. First, the labor force in high-income countries is typically more educated than in low- and middle-income countries, implying that the loss of human capital from an equivalent loss of DALY would be greater. Second, health systems are more advanced in high-income countries, which means that treatment costs are much higher. Our findings suggest that the reduction in physical capital accumulation due to the diversion of savings to pay for treatment plays a more important role in high-income countries than in low-income countries. Overall, high-income countries bear the highest economic costs of cirrhosis and other chronic liver diseases, while low- and middle-income countries bear the greatest absolute health burden due to their larger populations.
In terms of global regions, the greatest economic burden of cirrhosis and other chronic liver diseases is in East Asia and the Pacific, followed by North America and Europe, and Central Asia, which 3 regions account for 68.8% of the global economic burden of cirrhosis and other chronic liver diseases. These regions may face such a high economic burden in part because they are home to the 2 countries with the largest economic burden of cirrhosis and other chronic liver diseases: the United States and China. The high economic burden of cirrhosis and other chronic liver diseases in China is largely attributable to the substantial health burden it faces, with China having the highest number of cases of cirrhosis. In contrast, the United States is typically a high-income country with a highly educated labor force, and high per capita human capital losses are a contributing factor to high economic costs. In addition, the United States faces a heavy burden of treatment costs, which can lead to significant physical capital losses.
Given the significant impact of cirrhosis and other chronic liver diseases on the global economy and the health of populations, our findings highlight the critical importance of investing in effective public health interventions to mitigate the burden of cirrhosis and other chronic liver diseases. Firstly, we should strengthen primary health care by integrating chronic liver disease screening programs into health insurance coverage. Countries should implement educational campaigns in clinical, workplace, and community settings to increase knowledge and awareness of chronic liver diseases. This ensures that socially vulnerable populations have equal access to the management of chronic liver disease to prevent progression to cirrhosis.32
Secondly, chronic liver disease is often underdiagnosed, leading to many patients developing decompensated cirrhosis at advanced stages.33 According to a report from the United Kingdom, 75% of patients with cirrhosis are unaware of their condition before presenting with an emergency.34 At the same time, medical interventions for cirrhosis have limited prognostic benefit while requiring resource-intensive treatments such as liver transplantation. Therefore, the focus of care should shift from complication management to upstream prevention,35 screening, and early treatment. Strengthening the prevention and management of viral hepatitis, promoting universal screening of HBV and HCV, and vaccination are crucial. MASLD screening is recommended for individuals with metabolic risk factors or type 2 diabetes mellitus. Screening for HCC in cirrhotic patients and high-risk groups is also recommended to reduce mortality from cirrhosis.36
Thirdly, active implementation of public health policies targeting risk factors for cirrhosis and other chronic liver diseases is essential. Controlling alcohol consumption is particularly critical.37 As early as 1967, a study found a strong correlation between population-level alcohol consumption and cirrhosis mortality.38 The dose relationship between alcohol and liver disease is exponential, with heavy and extreme drinkers comprising a significant proportion of those with alcohol-associated cirrhosis.39 The most effective and cost-effective intervention for alcohol is to increase its price.40 A systematic review suggests that a 10% increase in alcohol prices leads to a reduction in alcohol consumption of about 5%.41 Promoting MUP (Minimum Unit Pricing) legislation, which sets a minimum price for a unit of alcohol, can prevent extreme drinkers from purchasing large quantities of cheap alcohol.42,43 In addition, regulating the marketing of alcoholic beverages, 1 of the 10 policy action areas in the World Health Organization’s global strategy to reduce harmful use of alcohol, is crucial. This includes reducing the digital marketing of alcohol.44 In addition, it is necessary to implement public health policies to promote healthy lifestyles. Obesity and type 2 diabetes are major risk factors for MASLD,37 while MASLD accounts for approximately three-quarters of cirrhosis and other chronic liver disease cases, a proportion that continues to rise.
Our study has several limitations (Supplemental Appendix S6, http://links.lww.com/HC9/C222). First, due to missing data, we estimated certain inputs (eg, health expenditures, labor participation, mortality, morbidity) for 64 countries by interpolation and projection based on available data. Countries with complete data cover more than 85% of the global population and more than 95% of global GDP, which supports the robustness of our global patterns. While this necessary imputation introduces additional uncertainty for a subset of countries, results for those settings should be interpreted with appropriate caution. Second, we primarily relied on estimates from the GBD 2021 data. However, the availability and quality of the underlying data used in our modeling limited the accuracy of these estimates, especially for countries with weaker health surveillance systems. To reflect this variability, we have provided the 95% uncertainty interval for each country’s estimated economic loss to aid interpretation. Third, we used US data in this study to extrapolate cirrhosis and other chronic liver diseases' health expenditures across all countries, assuming that the cost of disease per capita is directly proportional to healthcare expenditures per capita, which may have affected the results, but this approach is widely used in other similar studies. Fourth, our projections assume that current treatment patterns and effectiveness remain constant over time. We did not incorporate the introduction of potential future therapies for chronic liver diseases that could substantially improve survival (as well as increase costs). If significantly more effective and costly treatments (eg, for MASLD or viral hepatitis) become available, the actual economic burden could differ from our estimates. Fifth, our model did not incorporate the impact of metabolic comorbidities that often accompany MASLD. The exclusion of these co-occurring conditions means our estimates may underestimate the full health and economic burden of chronic liver disease.
Supplementary Material
Footnotes
The global economic burden of cirrhosis and other chronic liver diseases for 190 countries and territories in 2021–2050.
Co-first authorship: Ruxu Zhang and Jinxi Li contributed equally to this work and are joint first authors.
Abbreviations: AD, Alzheimer’s disease; ALD, alcohol-associated liver disease; CHEERS, Consolidated Health Economic Evaluation Reporting Standards; COPD, chronic obstructive pulmonary disease; DALYs, disability-adjusted life years; DESA, United Nations Department of Economic and Social Affairs; GBD, global burden of disease; GDP, gross domestic product; HBV, viral hepatitis type B; HCC, hepatocellular carcinoma; HCV, viral hepatitis type C; INT$, international dollars; MAFLD, metabolic dysfunction–associated fatty liver disease; MASLD, metabolic dysfunction–associated steatotic liver disease; MUP, Minimum Unit Pricing; YLD, years lost due to disability; YLL, years of life lost due to premature mortality.
Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, www.hepcommjournal.com.
Contributor Information
Ruxu Zhang, Email: 18733005084@163.com.
Jinxi Li, Email: 740010895@qq.com.
Yanhong Gong, Email: gongyanhong@hust.edu.cn.
Ketao Mu, Email: muketao@tjh.tjmu.edu.cn.
Jianwei Zheng, Email: zhengjianweitjh@163.com.
Xiaoxv Yin, Email: yxx@hust.edu.cn.
FUNDING INFORMATION
This work was supported by grants from the National Natural Science Foundation of China-Youth Science Fund (grant number 81901713). The funders were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
CONFLICTS OF INTEREST
The authors have no conflicts to report.
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