Global burden of liver cirrhosis: trends from 1990–2021 and projections to 2060

Abstract

Background

Liver cirrhosis, a progressive and debilitating condition characterized by extensive fibrosis and disruption of hepatic architecture, remains a significant global health challenge, primarily arising from chronic hepatitis and other liver diseases.

Methods

Data from the 2021 Global Burden of Disease (GBD) database were utilized to analyze trends in the incidence, deaths, disability-adjusted life years (DALYs), and prevalence of liver cirrhosis from 1990 to 2021 across various geographic regions, aiming to provide guidance for future disease burden interventions. The Bayesian age-period-cohort (BAPC) model was utilized for predicting trends up to 2060.

Results

In 2021, the global incidence of liver cirrhosis was recorded at 58,417,006 cases. Total death cases attributed to liver cirrhosis escalated to 1,425,142 in 2021, although the age-standardized death rate (ASDR) demonstrated a marked decline. Regional disparities were evident, with the highest incidence reported in North Africa and the Middle East, particularly in low Socio-Demographic Index (SDI) regions that bear a disproportionate burden. Following the current trends, it is projected that by 2060, the ASDR, ASPR, and DALYs rate for liver cirrhosis will progressively decline.

Conclusions

The findings underscore the need for enhanced strategies to combat liver cirrhosis, especially in high-burden regions. Specifically, the global incidence of liver cirrhosis has increased by 58.21% from 1990 to 2021. This prediction to 2060 holds strategic significance for guiding the adjustment of priorities in future disease burden management efforts.

Supplementary Information

The online version contains supplementary material available at 10.1186/s41043-025-01109-5.

Introduction

Liver cirrhosis, a progressive disorder characterized by fibrosis and nodular architectural distortion, represents the terminal histopathological stage of diverse chronic liver conditions [1]. The main etiologies include hepatitis B (HBV) and C (HCV) virus infections, alcohol-related liver disease, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver disorders [2, 3]. In the early stages, known as compensated cirrhosis, the absence of symptoms frequently delays diagnosis [4–6]. However, as the disease advances to decompensated cirrhosis, complications such as tumors of the digestive system, gastrointestinal bleeding, ascites, and hepatic encephalopathy significantly impair the patients’ quality of life and can lead to deaths [6, 7].

Globally, the incidence and death rates of cirrhosis are increasing, although the age-standardized death rate (ASDR) has decreased [8]. By 2017, cirrhosis accounted for 2.4% of global deaths, with approximately 1 million deaths annually, a number significantly higher among men than among women [6, 8]. Due to economic disparities, cirrhosis death rates vary by region, with high-income regions reporting significantly lower rates than low-income regions [8]. The leading cause of cirrhosis has shifted from hepatitis B to hepatitis C and rising global alcohol consumption has increasingly contributed to alcohol-related cirrhosis deaths [9, 10]. In other words, the primary etiologies of liver cirrhosis are subject to continuous variation across different regions. Consequently, the implementation of dynamic statistical analyses to delineate the most recent characteristics of diseases in each region within a specified timeframe can assist local governments in timely adjusting their corresponding policies [11]. Such measures are not only conducive to mitigating the progression of liver cirrhosis in the region but also serve to diminish the financial outlays associated with disease control [12].

The Global Burden of Disease (GBD) study systematically gathered comprehensive health data globally to assess the burden of diseases and injuries over time, stratified by age, sex, and location. GBD 2021 includes global data on the incidence, prevalence, years lived with disability (YLD), disability-adjusted life years (DALYs), healthy life expectancy (HALE), death rates from 288 causes of death, years of life lost (YLL), exposure levels to 88 risk factors, relative health risks, and attributable disease burden from 1990 to 2021 across 204 countries and regions [13–15]. The 2017 GBD study on liver cirrhosis has certain limitations in timeliness, especially regarding the trend of decreasing hepatitis B and C infections in developing countries [8]. Besides, GBD 2021 includes estimates of health losses due to the COVID-19 pandemic for the first time [13, 16]. This study, for the first time, employs the latest data from the GBD 2021 to discuss the progression of liver cirrhosis. The conclusions of this research will encompass the impact generated by the COVID-19 pandemic and present the most recent trends in the development of liver cirrhosis. Additionally, based on the latest data, this study forecasts the future trends of liver cirrhosis, with the predictions reflecting the progression of the disease burden over the coming decades. Compared with previous forecasts, these results can illustrate the effects of current intervention policies and contribute to the early macro-level adjustment of global health planning.

Methods

Data collection

Data were obtained from the 2021 Global Burden of Disease (GBD) database, with cirrhosis-specific metrics (prevalence, incidence, mortality, and DALYs) extracted via the Global Health Data Exchange (GHDx) platform. Additionally, Socio-Demographic Index (SDI) data were obtained to assess the impact of socioeconomic factors on disease burden.

Analysis of global, regional, and population disease burden

To analyze the global distribution and regional disparities in the burden of cirrhosis, global maps were generated and statistics were compiled for 21 regions, including East Asia, Southeast Asia, Oceania, Central Asia, Central Europe, Eastern Europe, High-income Asia Pacific, Australasia, Western Europe, Southern Latin America, High-income North America, the Caribbean, Andean Latin America, Central Latin America, Tropical Latin America, North Africa and Middle East, South Asia, and various sub-regions of Sub-Saharan Africa. Data on cirrhosis cases of incidence, deaths, DALYs, prevalence, and rates, including age-standardized incidence (ASIR), deaths (ASDR), DALYs, and prevalence (ASPR) rates, were collected and summarized by geographic region as defined by the GBD study. Maps were created using R with the “ggplot2” and “sf” packages to visualize the distribution of the disease burden. Additionally, the average estimated annual percentage changes (EAPC) in the ASIR, ASDR, DALYs rate, and ASPR were computed using linear regression to assess trends in disease burden, with 95% confidence intervals (CIs) used to determine the statistical significance of these trends. For the 2021 data, populations were categorized by sex and age, and their ASIR, ASDR, DALYs rate, and ASPR were calculated. These findings were visually depicted using R with the “ggplot” package.

SDI analysis

The SDI is an indicator used to comprehensively assess the level of social development. It integrates per capita income, the average educational attainment of the population aged 15 years and above, and the total fertility rate for those under 25 years [17, 18]. Ranging from 0 to 1, a higher SDI indicates a higher level of socio-economic development [19]. In this study, countries and regions were categorized into five groups (low, low-middle, middle, middle-high, and high) based on income levels, educational attainment, and fertility rates, which are integrated into the SDI calculation. The analysis was performed using the “dplyr” and “ggplot2” packages in R for data manipulation and visualization.

Predicting the prevalence cases of cirrhosis to 2060

The Bayesian Age-Period-Cohort (BAPC) model was used to predict the future burden of cirrhosis. This model was implemented in R using the “INLA” and “BAPC” packages. The BAPC model is a statistical tool that disentangles the complex interplay between age, period, and cohort effects on disease incidence and prevalence. Age effects capture the natural progression of disease as individuals grow older. Period effects reflect changes in disease rates due to external factors such as improvements in healthcare or shifts in societal behaviors occurring during specific time intervals. Cohort effects account for the unique experiences and risk factors shared by individuals born in the same time period, which can influence their disease risk throughout their lives. By modeling these three dimensions simultaneously, the BAPC model provides a nuanced understanding of disease trends, allowing for more accurate predictions and better-informed public health interventions [16].

Statistical analysis

To mitigate the impact of varying age structures, the GBD 2021 database employs age-standardization for metrics such as the incidence and death rates of cirrhosis as well as DALYs, using the following formula: × 100,000, where αi represents the age-specific rate for age group i, wi denotes the number of individuals in the standard population corresponding to age group i, and A is the number of age groups. This study calculated the EAPC for age-standardized incidence and death rates using a generalized linear regression model to assess the average annual changes in these indicators. The model establishes the relationship between the natural logarithm (ln) of the Age-Standardized Rate (ASR) and time using the equation Y = α + βX + ε, where Y represents ln (ASR) and X denotes the year. The EAPC and its 95% CI were subsequently calculated using the formula EAPC = 100 × [exp (β) − 1] [20].

A positive lower bound of the 95% CI indicated an increasing trend, whereas a negative upper bound suggested a decreasing trend. If the 95% CI spans zero, the trend is not statistically significant [21].

Results

Global and regional burden of cirrhosis

Incidence cases and rates

Between 1990 and 2021, global liver cirrhosis incidence increased by 58.2%, rising from 36.9 million (95% CI: 34.2–40.1 million) to 58.4 million cases (95% CI: 54.2–62.8 million). The ASIR showed a modest rise from 691.3 to 724.3 per 100,000 population (Table 1). The EAPC in ASIR was 0.123 (95% CI: 0.083–0.162), indicating a small but statistically significant upward trend. Clinically, this reflects the growing impact of risk factors such as rising alcohol consumption, metabolic syndromes, and aging populations, particularly in regions with high SDI where lifestyle-related etiologies are accelerating. Regionally, North Africa and the Middle East reported the highest ASIR in both 1990 and 2021, while Central Sub-Saharan Africa experienced the largest decline (− 1.2% annual reduction, Table 1; Figs. 1A and 2A).

Table 1.

Incidence of liver cirrhosis between 1990 and 2019 at the global and regional level

	1990	1990	2021	2021	1990–2021
Location	Incidence cases (95% CI)	Incidence rate per 100,000 (95% CI)	Incidence cases (95% CI)	Incidence rate per 100,000(95% CI)	EAPC (95% CI)
Global	36922607.506(34219866.737–40051996.947.737.947)	691.292(645.489–745.210)	58417005.593(54231380.949–62796051.234.949.234)	724.306(672.982–779.555.982.555)	0.123(0.083–0.162)
SDI
High-middle SDI	7480378.537(6966943.462–8079109.980.462.980)	682.101(637.782–734.457.782.457)	9702188.764(8995615.591–10362627.763.591.763)	700.837(647.211–755.744.211.744)	0.009(−0.108-0.127)
High SDI	4173209.959(3870962.945–4486869.665.945.665)	449.196(418.764–481.610)	6119856.331(5657414.804–6547258.478.804.478)	512.582(474.656–550.368.656.368)	0.515(0.464–0.567)
Low-middle SDI	8105994.900(7477918.203–8811363.989.203.989)	743.546(693.239–800.880)	14744489.575(13650839.180–15900738.921.180.921)	768.281(713.641–825.920)	0.099(0.079–0.119)
Low SDI	3844145.283(3484956.018–4234636.411.018.411)	799.497(743.094–861.609.094.609)	7997580.281(7373872.556–8683244.062.556.062)	778.478(725.402–841.098.402.098)	−0.143(−0.173–0.113)
Middle SDI	13286305.199(12283778.517–14437407.687.517.687)	769.745(718.595–832.731.595.731)	19806401.333(18363990.928–21307954.941.928.941)	774.307(717.152–833.249.152.249)	−0.010(−0.072-0.053)
Regions
Andean Latin America	212486.313(196726.359–230945.040.359.040)	603.948(560.839–647.579.839.579)	447967.771(414636.900–483258.938.900.938)	658.853(611.958–708.492.958.492)	0.272(0.260–0.284)
Australasia	88315.009(82169.482–95495.289.482.289)	423.248(394.947–455.309.947.309)	141236.627(129872.069–151017.985.069.985)	431.432(399.793–465.079.793.079)	0.056(0.024–0.087)
Caribbean	220983.231(203981.644–238864.521.644.521)	631.879(586.330–680.651.330.651)	330896.974(306942.889–355020.613.889.613)	669.166(622.222–717.826.222.826)	0.217(0.206–0.228)
Central Asia	539489.472(499265.318–581552.254.318.254)	775.228(722.527–831.730)	793253.580(736569.635–854433.177.635.177)	830.580(772.841–892.466.841.466)	0.214(0.188–0.240)
Central Europe	683370.514(637551.317–732734.827.317.827)	532.436(496.941–569.796.941.796)	649492.144(602170.497–691509.334.497.334)	533.846(496.194–575.151.194.151)	0.028(−0.012-0.069)
Central Latin America	1118727.329(1031974.858–1217987.950.858.950)	717.094(667.141–773.463.141.463)	1992211.333(1845436.716–2145030.437.716.437)	753.538(698.916–810.239.916.239)	0.194(0.170–0.217)
Central Sub-Saharan Africa	524712.858(451286.796–592814.376.796.376)	929.560(828.945–1023.079.945.079)	1059573.426(971681.015–1161577.846.015.846)	830.705(768.614–904.905.614.905)	−0.461(−0.524–0.398)
East Asia	10023464.872(9266396.526–10911813.338.526.338)	794.594(738.271–861.082.271.082)	11398351.622(10502386.674–12311150.538.674.538)	721.550(665.147–780.517.147.517)	−0.445(−0.644–0.247)
Eastern Europe	1230766.489(1143434.433–1323561.107.433.107)	526.233(488.420–566.069.420.069)	1238736.794(1148706.207–1331765.879.207.879)	573.770(530.481–615.732.481.732)	0.307(0.279–0.334)
Eastern Sub-Saharan Africa	1414771.371(1279644.875–1558975.260.875.260)	786.840(728.001–849.707.001.707)	2809031.523(2579061.230–3067005.138.230.138)	732.212(681.329–791.292.329.292)	−0.317(−0.358–0.277)
High-income Asia Pacific	885580.085(828143.623–946916.231.623.231)	478.611(448.074–511.604.074.604)	954859.075(879249.525–1025911.043.525.043)	439.226(407.883–471.721.883.721)	−0.223(−0.292–0.155)
High-income North America	1147683.767(1056625.262–1240989.030.262.030)	383.963(354.864–414.360)	1834050.144(1688687.535–1975651.128.535.128)	438.903(404.114–473.617.114.617)	0.493(0.466–0.520)
North Africa and Middle East	3417410.125(3137082.399–3705269.646.399.646)	1076.086(1002.104–1152.943.104.943)	7344029.866(6824597.209–7868809.123.209.123)	1165.329(1088.805–1238.067.805.067)	0.322(0.294–0.350)
Oceania	53717.643(48295.633–59133.344.633.344)	824.540(755.586–895.513.586.513)	110147.480(100967.819–120282.952.819.952)	800.972(743.327–869.692.327.692)	−0.147(−0.181–0.112)
South Asia	6319890.264(5829329.691–6876717.814.691.814)	632.595(588.353–682.912.353.912)	12647388.953(11643307.116–13736051.238.116.238)	673.271(622.187–727.171.187.171)	0.188(0.158–0.217)
Southeast Asia	3736939.016(3447793.238–4053549.804.238.804)	813.388(758.854–878.325.854.325)	5694070.247(5276150.885–6164696.404.885.404)	786.099(730.832–848.608.832.608)	−0.105(−0.135–0.075)
Southern Latin America	184659.357(171195.360–199897.432.360.432)	376.635(348.616–407.678.616.678)	319189.971(293954.338–344580.346.338.346)	435.415(400.656–470.865.656.865)	0.475(0.453–0.497)
Southern Sub-Saharan Africa	413311.797(382307.827–447617.192.827.192)	810.424(755.057–873.589.057.589)	637418.616(587599.001–689007.608.001.608)	786.114(729.371–844.492.371.492)	−0.112(−0.126–0.099)
Tropical Latin America	1055367.524(977309.715–1144815.545.715.545)	719.185(669.773–774.637.773.637)	1795055.615(1661919.352–1930517.617.352.617)	742.760(690.264–797.626.264.626)	0.141(0.105–0.177)
Western Europe	1716645.564(1590277.351–1848160.257.351.257)	410.306(381.399–441.303.399.303)	2150207.738(1994372.390–2296549.940.390.940)	453.198(420.231–487.791.231.791)	0.371(0.328–0.414)
Western Sub-Saharan Africa	1933636.899(1745993.628–2130595.176.628.176)	977.935(907.191–1056.203.191.203)	4068659.821(3743810.710–4406514.387.710.387)	890.771(828.662–960.148.662.148)	−0.363(−0.409–0.318)

Abbreviations: CI, confidence interval. EAPC, estimated annual percentage changes. SDI, Socio-Demographic Index

Fig. 1.

The estimated annual percentage changes (EAPC) of incidence (A), deaths (B), DALYs (C), and prevalence rates (D) of liver cirrhosis from 1990 to 2021 in 204 countries and territories

Fig. 2.

The difference in age-standardized incidence (A), deaths (B), DALYs (C), and prevalence (D) rates of liver cirrhosis between 1990 and 2021 across 21 regions

Deaths cases and rates

Between 1990 and 2021, cirrhosis-related deaths increased by 39.5% globally (1.02 to 1.43 million cases) (Table 2). However, the ASDR for liver cirrhosis declined by 32%, from 24.4 to 16.6 per 100,000 population (Table 2). The EAPC highlights a significant downward trend in ASDR over these 32 years at − 1.263 (95% CI: −1.355 to − 1.171). This divergence between rising absolute deaths and declining ASDR reflects two key factors: (1) population growth and aging amplify the total number of deaths, while (2) advancements in early diagnosis and management reduce age-adjusted mortality. Eastern Europe and High-income North America were exceptions, with rising ASDR, whereas East Asia demonstrated the steepest reduction (Table 2; Figs. 1B and 2B).

Table 2.

Deaths of liver cirrhosis between 1990 and 2019 at the global and regional level

	1990	1990	2021	2021	1990–2021
Location	Deaths cases (95% CI)	Deaths rate per 100,000 (95% CI)	Deaths cases (95% CI)	Deaths rate per 100,000(95% CI)	EAPC (95% CI)
Global	1021776.624(936628.902–1144617.860.902.860)	24.424(22.375–27.484)	1425141.860(1308121.012–1563089.036.012.036)	16.640(15.283–18.262)	−1.263(−1.355–1.171)
SDI
High-middle SDI	177752.621(165987.474–190193.140.474.140)	17.652(16.492–18.878)	214977.746(200030.330–230803.108.330.108)	11.382(10.598–12.200)	−1.512(−1.767–1.256)
High SDI	151374.123(146002.361–156591.748.361.748)	14.308(13.787–14.801)	181859.777(170956.762–188708.119.762.119)	9.794(9.342–10.111)	−1.216(−1.241–1.190)
Low-middle SDI	275173.515(239877.616–332965.153.616.153)	41.696(36.188–50.938)	414103.973(351485.241–476269.101.241.101)	27.451(23.174–31.549)	−1.254(−1.367–1.142)
Low SDI	110971.714(98177.303–125652.895.303.895)	43.623(38.229–50.390)	171328.247(152663.962–192951.865.962.865)	29.744(26.538–33.483)	−1.249(−1.360–1.137)
Middle SDI	305434.876(275025.921–353878.124.921.124)	27.138(24.172–31.762)	441526.393(403364.972–485996.865.972.865)	16.426(14.976–18.087)	−1.719(−1.766–1.671)
Regions
Andean Latin America	7039.163(5789.304–7990.406.304.406)	31.232(25.438–35.701)	13457.840(10851.376–16384.724.376.724)	22.653(18.277–27.531)	−1.142(−1.251–1.032)
Australasia	1411.080(1351.659–1475.353.659.353)	6.189(5.919–6.459)	2221.481(2034.648–2375.650.648.650)	4.637(4.283–4.935)	−0.606(−0.811–0.400)
Caribbean	6469.282(5897.838–7097.765.838.765)	24.042(21.978–26.394)	9495.334(7930.399–11122.612.399.612)	17.816(14.843–20.926)	−1.041(−1.265–0.816)
Central Asia	13969.340(13507.915–14405.183.915.183)	28.129(27.159–29.061)	26873.964(24112.846–30039.241.846.241)	30.882(27.709–34.338)	0.281(−0.118-0.682)
Central Europe	31023.585(30324.111–31690.098.111.098)	20.830(20.356–21.269)	34344.052(32017.673–36602.527.673.527)	17.743(16.545–18.891)	−1.057(−1.288–0.826)
Central Latin America	31660.071(31083.850–32124.444.850.444)	33.770(33.010–34.313.010.313)	62348.950(54253.139–69622.349.139.349)	24.304(21.190–27.111.190.111)	−1.362(−1.474–1.250)
Central Sub-Saharan Africa	14315.661(11485.174–17264.194.174.194)	53.413(43.123–64.347)	27614.720(20508.971–34947.193.971.193)	40.305(30.310–51.169.310.169)	−0.834(−0.882–0.786)
East Asia	187883.851(160237.909–216253.680.909.680)	20.724(17.746–23.864)	167007.178(132903.386–202785.517.386.517)	7.928(6.329–9.601)	−3.312(−3.447–3.177)
Eastern Europe	28334.566(27588.704–29064.690.704.690)	10.229(9.964–10.487)	69643.858(64065.564–75734.016.564.016)	22.913(21.003–24.916)	2.542(1.649–3.444)
Eastern Sub-Saharan Africa	43731.700(38169.371–49724.879.371.879)	53.528(47.141–61.537)	72973.094(63804.646–82342.209.646.209)	38.542(33.902–43.187)	−1.226(−1.337–1.115)
High-income Asia Pacific	39659.805(36466.065–41330.990.065.990)	19.633(18.107–20.473)	31579.289(27943.716–34403.655.716.655)	7.454(6.835–8.042)	−3.255(−3.381–3.128)
High-income North America	37628.150(36308.017–38356.250.017.250)	11.427(11.062–11.634)	71564.064(67795.175–73943.306.175.306)	12.239(11.686–12.619)	0.471(0.378–0.565)
North Africa and Middle East	76868.880(68591.292–88468.823.292.823)	50.811(44.252–59.403)	99627.960(86818.391–116008.847.391.847)	23.230(20.316–26.824)	−2.404(−2.465–2.344)
Oceania	527.354(384.168–723.746.168.746)	13.913(10.183–19.180)	945.557(779.289–1132.343.289.343)	10.045(8.255–11.979)	−1.097(−1.209–0.985)
South Asia	213444.764(179856.217–263867.688.217.688)	31.188(25.831–39.485)	356610.249(275493.469–435076.580.469.580)	22.846(17.487–27.886)	−0.953(−1.074–0.832)
Southeast Asia	123474.647(100907.903–164364.103.903.103)	43.396(34.775–59.174)	191607.032(168268.547–215172.127.547.127)	28.802(25.266–32.361)	−1.359(−1.437–1.281)
Southern Latin America	10657.024(10331.555–10968.127.555.127)	22.922(22.204–23.597)	11033.113(10483.971–11557.190.971.190)	12.995(12.350–13.601.350.601)	−1.308(−1.491–1.125)
Southern Sub-Saharan Africa	6493.304(5456.571–8289.680.571.680)	21.282(17.676–27.896)	11104.704(9526.119–12706.023.119.023)	17.817(15.461–20.313)	−0.620(−1.053–0.186)
Tropical Latin America	21521.078(21030.587–21908.771.587.771)	20.266(19.707–20.687)	32095.329(30505.252–33672.527.252.527)	12.270(11.638–12.877)	−1.520(−1.663–1.377)
Western Europe	80509.556(77695.105–82359.506.105.506)	15.041(14.562–15.367)	63375.947(58955.419–66023.498.419.498)	7.691(7.277–7.964)	−2.201(−2.283–2.118)
Western Sub-Saharan Africa	45153.764(36727.875–57591.411.875.411)	46.666(37.591–60.532)	69618.146(54673.746–84212.796.746.796)	31.004(25.101–36.366)	−1.220(−1.328–1.111)

Abbreviations: CI, confidence interval. EAPC, estimated annual percentage changes. SDI, Socio-Demographic Index

DALYs cases and rates

The global DALYs rate for cirrhosis decreased by 31.8% over 32 years, dropping from 799.9 to 545.1 per 100,000 population (Table 3). The reduction in DALYs per 100,000 population highlights improved disease management and survivorship, particularly in high SDI regions with advanced healthcare systems. Central Sub-Saharan Africa maintained the highest DALY rates, while High-income Asia Pacific showed the most significant improvement (Table 3; Figs. 1C and 2C). It means that, on a global level, the impact of cirrhosis on human health and life is progressively diminishing.

Table 3.

DALYs of liver cirrhosis between 1990 and 2019 at the global and regional level

	1990	1990	2021	2021	1990–2021
Location	DALYs cases (95% CI)	DALYs rate per 100,000 (95% CI)	DALYs cases (95% CI)	DALYs rate per 100,000(95% CI)	EAPC (95% CI)
Global	36284496.065(33528220.598–40328345.030.598.030)	799.941(738.593–891.543.593.543)	46417777.159(43056396.911–50687931.174.911.174)	545.069(506.130–594.991.130.991)	−1.267(−1.377–1.157)
SDI
High-middle SDI	5728827.544(5350783.820–6154706.078.820.078)	549.062(512.614–589.873.614.873)	6580972.356(6132961.428–7044275.810.428.810)	365.317(340.631–390.845.631.845)	−1.415(−1.726–1.102)
High SDI	4665496.155(4505012.125–4819719.293.125.293)	456.692(440.905–471.848.905.848)	4985515.639(4800129.247–5136888.028.247.028)	301.525(292.069–310.259.069.259)	−1.349(−1.373–1.325)
Low-middle SDI	10308105.133(9076287.315–12220285.057.315.057)	1273.215(1116.333–1532.208.333.208)	14184554.384(12138773.584–16260371.521.584.521)	846.049(722.012–972.021.012.021)	−1.216(−1.357–1.076)
Low SDI	4239960.428(3731913.999–4741655.541.999.541)	1349.297(1192.581–1530.895.581.895)	6470300.054(5703094.642–7316668.865.642.865)	907.409(807.076–1024.000)	−1.321(−1.454–1.189)
Middle SDI	11306176.773(10301062.431–12876266.243.431.243)	860.020(778.224–988.999.224.999)	14154655.906(13089118.699–15420284.895.699.895)	511.817(474.023–557.426.023.426)	−1.792(−1.835–1.749)
Regions
Andean Latin America	254601.348(213567.124–287623.894.124.894)	965.741(800.905–1095.874.905.874)	377034.016(301907.363–462398.069.363.069)	611.539(489.699–750.051.699.051)	−1.658(−1.798–1.517)
Australasia	43856.209(42068.515–45765.092.515.092)	196.354(188.257–204.495.257.495)	61922.852(57875.760–65543.872.760.872)	142.096(133.599–150.575.599.575)	−0.669(−0.861–0.476)
Caribbean	218925.730(197960.645–239420.813.645.813)	756.784(689.395–831.936.395.936)	295896.454(242769.536–351130.540.536.540)	565.715(461.801–672.285.801.285)	−0.974(−1.228–0.720)
Central Asia	488607.631(473479.807–507045.166.807.166)	893.567(866.695–923.293.695.293)	935347.612(836582.671–1052890.729.671.729)	991.100(890.022–1110.787.022.787)	0.196(−0.246-0.640)
Central Europe	999968.744(978376.957–1021109.453.957.453)	683.618(668.611–697.977.611.977)	1024435.631(956046.085–1091667.651.085.651)	578.290(540.723–616.152.723.152)	−1.157(−1.417–0.896)
Central Latin America	1159049.308(1142755.673–1176010.090.673.090)	1081.987(1066.362–1097.272.362.272)	1984966.200(1735310.625–2220612.994.625.994)	754.506(660.274–843.557.274.557)	−1.514(−1.661–1.367)
Central Sub-Saharan Africa	561358.536(449470.652–674912.952.652.952)	1719.629(1382.587–2070.558.587.558)	1079263.747(811089.211–1368164.638.211.638)	1298.266(969.140–1639.598.140.598)	−0.817(−0.871–0.763)
East Asia	6525188.318(5564957.102–7509165.988.102.988)	636.934(544.427–733.074.427.074)	4818434.395(3855578.101–5892195.553.101.553)	231.400(185.186–281.683.186.683)	−3.507(−3.625–3.390)
Eastern Europe	896656.993(873721.904–919376.301.904.301)	330.560(322.399–338.958.399.958)	2465641.459(2259860.761–2683294.536.761.536)	866.652(791.974–942.814.974.814)	2.974(1.925–4.034)
Eastern Sub-Saharan Africa	1568368.479(1371422.001–1770553.864.001.864)	1565.097(1367.490–1779.154.490.154)	2639454.292(2274825.268–3016602.612.268.612)	1111.074(971.596–1253.794.596.794)	−1.286(−1.401–1.172)
High-income Asia Pacific	1231978.632(1103466.011–1288476.572.011.572)	600.263(536.880–628.070.880.070)	716541.201(665646.416–769525.222.416.222)	211.160(199.217–227.826.217.826)	−3.541(−3.655–3.427)
High-income North America	1187013.267(1159664.767–1206501.640.767.640)	375.384(367.408–381.483.408.483)	2055980.333(1983485.187–2117725.559.187.559)	387.008(375.166–398.309.166.309)	0.346(0.258–0.435)
North Africa and Middle East	2259566.374(2028319.923–2517966.012.923.012)	1161.764(1040.452–1326.378.452.378)	2793002.656(2407973.173–3266284.833.173.833)	565.094(490.317–658.075.317.075)	−2.152(−2.261–2.044)
Oceania	22166.642(16170.571–30336.027.571.027)	492.094(359.916–672.894.916.894)	38075.907(31518.307–45535.780.307.780)	348.277(288.003–415.514.003.514)	−1.188(−1.305–1.070)
South Asia	8782607.785(7597320.683–10509325.055.683.055)	1069.415(907.012–1310.990.012.990)	12840215.909(10216960.942–15511744.062.942.062)	743.751(587.972–898.764.972.764)	−1.112(−1.267–0.956)
Southeast Asia	4671305.966(3910340.370–6008880.700.370.700)	1376.534(1133.948–1808.896.948.896)	6266645.453(5495267.110–7087402.549.110.549)	867.713(762.029–976.062.029.062)	−1.542(−1.608–1.476)
Southern Latin America	334377.707(325517.734–343825.672.734.672)	711.376(692.709–731.947.709.947)	310226.021(296855.047–323645.037.047.037)	378.800(362.510–394.912.510.912)	−1.470(−1.668–1.271)
Southern Sub-Saharan Africa	246319.596(212972.325–299769.852.325.852)	689.460(586.322–866.196.322.196)	390790.190(331125.972–453441.739.972.739)	557.761(475.488–641.916.488.916)	−0.706(−1.184–0.225)
Tropical Latin America	841965.211(824503.464–858065.237.464.237)	711.895(697.071–725.060)	1047369.340(997375.222–1092940.567.222.567)	397.557(378.885–414.912.885.912)	−1.850(−2.012–1.689)
Western Europe	2309900.536(2256472.089–2351957.336.089.336)	464.608(454.529–473.322.529.322)	1613747.814(1542743.310–1666706.243.310.243)	225.501(217.737–231.990)	−2.398(−2.503–2.292)
Western Sub-Saharan Africa	1680713.051(1384560.804–2115044.004.804.004)	1385.210(1123.592–1778.791.592.791)	2662785.677(2021449.425–3344476.715.425.715)	909.845(717.102–1100.656.102.656)	−1.251(−1.354–1.147)

Abbreviations: CI, confidence interval. EAPC, estimated annual percentage changes. SDI, Socio-Demographic Index

Prevalence cases and rates

Despite the absence of a significant change in the prevalence of cirrhosis globally, the number of individuals affected has surged markedly. The prevalence cases surged by 71.7% (988 million to 1.70 billion), though age-standardized prevalence rates (ASPR) remained stable (0.011% annual change, 95% CI: −0.030–0.051) (Table 4). This paradox—rising absolute prevalence but stable ASPR—is primarily explained by population growth and aging, which expand the at-risk population without altering age-adjusted rates. Central Sub-Saharan Africa had the highest ASPR in 1990 (Table 4). By 2021, North Africa and the Middle East recorded the highest ASPR. Over these 32 years, Southern Latin America showed the most significant increase in ASPR, whereas East Asia experienced a rapid decline (Table 4; Figs. 1D and 2D).

Table 4.

Prevalence of liver cirrhosis between 1990 and 2019 at the global and regional level

	1990	1990	2021	2021	1990–2021
Location	Prevalence cases (95% CI)	Prevalence rate per 100,000 (95% CI)	Prevalence cases (95% CI)	Prevalence rate per 100,000(95% CI)	EAPC (95% CI)
Global	988390222.578(919501408.059–1063915828.610.059.610)	20088.744(18743.125–21508.361.125.361)	1697259271.732(1575345915.689–1823835811.837.689.837)	20302.624(18845.228–21791.911.228.911)	0.011(−0.030-0.051)
SDI
High-middle SDI	215815136.033(200842473.060–231204067.765.060.765)	20099.849(18734.980–21548.270.980.270)	329622108.136(305765172.509–354077113.791.509.791)	19865.053(18405.506–21373.414.506.414)	−0.115(−0.208–0.023)
High SDI	114916148.319(106809062.915–123365185.135.915.135)	11594.897(10757.036–12445.295.036.295)	197254160.875(182178460.615–211853475.524.615.524)	13575.436(12536.645–14624.146.645.146)	0.581(0.535–0.627)
Low-middle SDI	200863041.763(187099815.278–216194316.356.278.356)	21521.524(20063.750–23054.271.750.271)	376741309.263(349637241.157–404649819.578.157.578)	21148.475(19651.056–22716.254.056.254)	−0.046(−0.055–0.038)
Low SDI	101480100.904(94631752.875–109616285.879.875.879)	25212.029(23572.664–26980.237.664.237)	202139053.299(188255453.109–217482447.709.109.709)	23268.442(21694.884–24945.175.884.175)	−0.295(−0.338–0.251)
Middle SDI	354462532.579(329010932.049–382171028.615.049.615)	23424.347(21865.263–25157.593.263.593)	590170056.385(546568985.175–634562243.886.175.886)	21779.905(20233.811–23407.763.811.763)	−0.278(−0.355–0.200)
Regions
Andean Latin America	4446926.162(4095093.077–4823296.293.077.293)	15608.367(14411.409–16855.736.409.736)	11067333.309(10184356.620–12011458.495.620.495)	17011.933(15674.066–18434.505.066.505)	0.316(0.302–0.330)
Australasia	2570855.344(2385463.685–2775429.835.685.835)	11735.337(10903.161–12663.158.161.158)	4778824.450(4403591.339–5121350.751.339.751)	12152.814(11207.677–13108.268.677.268)	0.114(0.074–0.154)
Caribbean	5471611.279(5050676.641–5907215.618.641.618)	17740.949(16365.676–19149.752.676.752)	9566053.228(8831332.456–10307795.710.456.710)	18597.047(17174.711–20048.451.711.451)	0.174(0.165–0.183)
Central Asia	14068330.074(12976383.841–15246033.901.841.901)	23274.729(21519.596–25070.888.596.888)	23290675.700(21470244.268–25140923.046.268.046)	24532.233(22662.707–26410.924.707.924)	0.136(0.097–0.174)
Central Europe	20337835.058(18857065.719–21862262.532.719.532)	14732.906(13662.857–15830.833.857.833)	23422073.571(21566300.166–25217433.857.166.857)	14681.618(13540.339–15818.411.339.411)	0.007(−0.011-0.024)
Central Latin America	24036903.294(22279440.122–25942133.571.122.571)	19250.042(17779.590–20761.775.590.775)	51768465.397(47719439.629–55952263.238.629.238)	19704.757(18169.623–21284.286.623.286)	0.119(0.096–0.143)
Central Sub-Saharan Africa	16682235.069(15470826.745–18084869.367.745.367)	35177.324(32877.889–37524.865.889.865)	32709371.498(30555165.185–35270667.122.185.122)	29745.660(27829.647–31685.032.647.032)	−0.569(−0.675–0.463)
East Asia	303059189.392(282516969.321–327319598.488.321.488)	25920.636(24243.714–27810.332.714.332)	409969643.291(380624452.089–440186009.064.089.064)	21753.837(20257.929–23360.053.929.053)	−0.701(−0.885–0.516)
Eastern Europe	37900599.864(34849068.462–40837696.263.462.263)	14905.782(13717.429–15999.793.429.793)	43226754.708(39711122.950–46499892.761.950.761)	15811.148(14618.993–17021.268.993.268)	0.187(0.129–0.246)
Eastern Sub-Saharan Africa	34796902.888(32318561.621–37723376.368.621.368)	23805.437(22192.183–25485.644.183.644)	67289238.961(62645989.826–72744298.186.826.186)	21518.069(20026.799–23055.279.799.279)	−0.394(−0.441–0.347)
High-income Asia Pacific	23669401.063(22078658.886–25235836.818.886.818)	12168.028(11379.234–12966.074.234.074)	31876076.279(29630832.035–34125063.473.035.473)	11548.174(10699.328–12414.759.328.759)	−0.186(−0.283–0.089)
High-income North America	30542817.346(28122381.101–33062629.133.101.133)	9606.916(8863.374–10394.947.374.947)	55144037.781(50675688.148–59743322.959.148.959)	11395.231(10504.663–12314.335.663.335)	0.649(0.616–0.683)
North Africa and Middle East	75693245.441(70473833.423–81720928.407.423.407)	29493.972(27458.308–31620.938.308.938)	189362819.810(175624729.974–204533074.844.974.844)	31864.320(29592.922–34265.378.922.378)	0.311(0.269–0.352)
Oceania	1526959.091(1432053.933–1643245.040.933.040)	27968.969(26272.347–29756.296.347.296)	3060167.526(2869857.235–3292627.068.235.068)	26030.857(24461.688–27832.137.688.137)	−0.258(−0.272–0.243)
South Asia	159212557.399(147571490.411–172398270.799.411.799)	18094.152(16785.842–19445.235.842.235)	323405751.090(299110692.508–349049359.904.508.904)	18158.235(16773.113–19546.711.113.711)	0.026(−0.006-0.058)
Southeast Asia	94347713.446(88225442.404–101124531.437.404.437)	23885.881(22311.932–25546.620.932.620)	162349559.797(150870153.630–174538269.397.630.397)	22217.599(20686.230–23869.136.230.136)	−0.251(−0.260–0.242)
Southern Latin America	4458576.023(4090724.750–4850027.832.750.832)	9356.117(8582.030–10190.581.030.581)	8979290.732(8245110.492–9726524.121.492.121)	11464.161(10537.693–12417.785.693.785)	0.697(0.662–0.731)
Southern Sub-Saharan Africa	8917712.174(8290138.097–9602353.502.097.502)	21310.274(19810.364–22882.537.364.537)	15507009.864(14350679.674–16723958.505.674.505)	20750.683(19218.543–22328.537.543.537)	−0.123(−0.137–0.109)
Tropical Latin America	25410504.541(23513869.150–27484653.538.150.538)	20081.125(18569.168–21697.678.168.678)	50774562.064(46927067.052–54985634.118.052.118)	19869.639(18369.159–21511.292.159.292)	0.009(−0.022-0.039)
Western Europe	48580047.612(45022031.424–52157765.254.424.254)	10455.729(9672.964–11257.318.964.318)	75331500.055(69618842.125–80958934.188.125.188)	12385.785(11427.011–13340.081.011.081)	0.601(0.552–0.651)
Western Sub-Saharan Africa	52659300.018(49029284.545–56698520.831.545.831)	32948.936(30862.680–35263.037.680.037)	104380062.620(97308827.879–112999152.646.879.646)	28139.340(26350.108–30230.815.108.815)	−0.556(−0.619–0.493)

Abbreviations: CI, confidence interval. EAPC, estimated annual percentage changes. SDI, Socio-Demographic Index

Etiology-based burden of liver cirrhosis

Liver cirrhosis is classified into five primary etiologies: cirrhosis caused by chronic hepatitis B, chronic hepatitis C, alcohol, NAFLD, and other causes. Over the 32 years from 1990 to 2021, the proportion of liver cirrhosis deaths attributed to NAFLD has significantly increased globally (Fig. 3). However, the top three causes of cirrhosis-related deaths in both 1990 and 2021 were chronic hepatitis B, chronic hepatitis C, and alcohol (Fig. 3). Notably, in East Asia, the proportion of cirrhosis deaths due to chronic hepatitis B was significantly higher than in other regions, accounting for 75.6% in 1990 and 72.9% in 2021 (Fig. 3). North Africa and the Middle East had the highest proportion of deaths due to chronic hepatitis C in both years, with a slight increase from 42.3% in 1990 to 42.8% in 2021 (Fig. 3). In 1990, Eastern Europe had the highest proportion of cirrhosis deaths due to alcohol consumption (46.0%), which increased slightly to 47.2% by 2021 (Fig. 3). Since 1990, NAFLD-related cirrhosis deaths have increased globally, affecting all regions by 2021 (Fig. 3). In 1990, Western Europe had the highest proportion (13.6%), which shifted to Andean Latin America (24.0%) in 2021 (Fig. 3).

Fig. 3.

The proportion of five pathogenic factors constituting liver cirrhosis in 1990 (A) and 2021 (B) across 21 regions

Population differences in disease burden of cirrhosis

Incidence cases and rates

We categorized the population by sex and age. As shown in Fig. 4A, Tables S1 and S2, both incidence numbers and rates for males and females sharply increased after the age of 14 years. Males peaked earlier (15–19 age) than females (20–24 age), with the highest rates in young adults (20–24 age). After this peak, both the incidence numbers and rates gradually declined with age.

Fig. 4.

The cases and rates including incidence (A), deaths (B), DALYs (C), and prevalence (D) of liver cirrhosis between females and males for different age groups

Furthermore, we analyzed the trends in liver cirrhosis incidence rates across different age groups from 1990 to 2021. As illustrated in Figure S1A, the overall trend of liver cirrhosis incidence rates across all age groups exhibited a slow upward trajectory over 32 years. However, the 0–14 age group showed a declining trend. The other age groups experienced a gradual increase, with the highest incidence observed in the 15–39 age group.

Deaths cases and rates

We further analyzed the differences in deaths and rates due to liver cirrhosis among the various populations in 2021. As age increased, the number of liver cirrhosis-related deaths also gradually increased (Fig. 4B). For males, the highest number of deaths occurred in the 55–59 age group, after which the numbers began to decline. In females, a similar trend was observed, with the highest number of deaths occurring in the 65–69 age group. Males aged 25–79 years exhibited a disproportionately higher mortality burden compared to females.

In contrast to the deaths, the rates of liver cirrhosis-related deaths for both males and females exhibited an overall increasing trend with age. After the age of 25, The death rates for males consistently exceeded that of females (Fig. 4B, Tables S3 and S4). From 1990 to 2021, liver cirrhosis death rates across the population remained relatively stable, with the highest rates observed in those aged ≥ 70 years, showing a declining trend (Figure S1B).

DALYs cases and rates

In 2021, both males and females showed a gradual increase in DALYs cases with age. Males peaked in the 50–54 age group, while females peaked in the 55–59 age group. Following these peaks, DALYs for both sexes gradually declined with increasing age. Similar to deaths, the DALYs cases for females were significantly lower than those for males in the 25–79 age range (Fig. 4C).

The trend in DALYs rates mirrored the cases; for males, the DALYs rate peaking at 60–64 years, after which it gradually declined (Fig. 4C). In contrast, females reached their peak DALYs rate in the 70–74 age group (Fig. 4C, Tables S5 and S6). From 1990 to 2021, the overall DALYs rate across the population showed a slowly declining trend, with decreases observed in all age groups. The 50–69 age group consistently had the highest DALYs rates (Figure S1C).

Prevalence cases and rates

The prevalence cases of liver cirrhosis among different populations in 2021 was analyzed, revealing that male and female patients were primarily concentrated in the middle-aged group. Among males, the highest number of liver cirrhosis cases was found in the 35–39 age group, while for females, the highest number occurred in the 45–49 age group (Fig. 4D).

The prevalence rates in 2021 showed that both males and females had the highest prevalence of liver cirrhosis in the 75–79 age group. Prior to this age, the prevalence of liver cirrhosis increased with age, and subsequently, the prevalence for both sexes declined to varying degrees as age increased (Fig. 4D, Table S7 and S8). Overall, the population’s prevalence rates showed a slow upward trend from 1990 to 2021, with the lowest prevalence found in the 0–14 age group, which demonstrated a declining trend (Figure S1D).

Trends in global and regional burden of liver cirrhosis based on SDI

Trends in 21 regions with SDI

The trends of ASIR, ASDR, DALYs, and ASPR based on the SDI were also examined across different global regions. As shown in Fig. 5, an overall negative correlation was found between SDI values and ASIR (R = −0.7121, P < 0.001), ASDR (R = −0.6935, P < 0.001), DALYs (R = −0.6866, P < 0.001), and ASPR (R = −0.743, P < 0.001) of liver cirrhosis. Notably, the ASIR and ASPR for North Africa and the Middle East were significantly higher than expected, whereas the ASIR and ASPR for South Asia and Southern Latin America were markedly lower than anticipated (Fig. 5A, D). Additionally, the ASDR and DALYs for Oceania were significantly lower than expected (Fig. 5B, C).

Fig. 5.

The trends including age-standardized incidence (A), deaths (B), DALYs (C), and prevalence (D) of liver cirrhosis for Socio-Demographic Index (SDI) values

Incidence trends in global and 5 SDI regions by time

In 1990 and 2021, the highest number of liver cirrhosis incidence cases were reported in regions with medium SDI (1990:13.2 million; 2021:19.8 million) (Table 1). The ASIR for each region in 1990 and 2021 indicated that the ASIR for high SDI regions was significantly lower than that of other regions (Table 1). The EAPC suggested that from 1990 to 2021, the ASIR in high SDI regions significantly increased (0.515; 95% CI: 0.464–0.567) (Table 1). Further analysis of the trends in liver cirrhosis etiologies across the five categories of SDI-related regions revealed that the ASIR of liver cirrhosis due to non-alcoholic fatty liver disease was consistently higher than that of other causes and showed an annual increase from 1990 to 2021 (Fig. 6A).

Fig. 6.

The trends including age-standardized incidence (A), deaths (B), DALYs (C), and prevalence (D) of liver cirrhosis across global and 5 Socio-Demographic Index (SDI) regions from 1990–2021

Death trends in global and 5 SDI regions by time

Among the five SDI regions, the lowest number of liver cirrhosis deaths was reported in low SDI regions (1990:110,972; 2021:171,328), yet it had the highest ASDR (Table 2). From 1990 to 2021, ASDR decreased in all regions to varying degrees, with the largest decline observed in the medium SDI regions (EAPC: −1.719 (95% CI: −1.766 to −1.671) (Table 2). In the high SDI regions, the ASDR due to chronic hepatitis C and alcohol-related liver cirrhosis was significantly greater than that due to other causes (Fig. 6B).

DALYs trends in global and 5 SDI regions by time

In 1990, the lowest number of DALYs associated with liver cirrhosis was reported in low-SDI regions (4.2 million) (Table 3), whereas in 2021, it shifted to high-SDI regions (5.0 million) (Table 3). Similar to the ASDR trends, the DALYs rates across all regions declined over the 32-year period. High SDI regions consistently recorded the lowest DALYs rates (1990: 456.692 per 100,000; 2021: 301.525 per 100,000) (Table 3). The greatest reduction in DALYs rates was observed in the medium SDI regions (EAPC: −1.792 (95% CI: −1.835 to −1.749) (Table 3). The trend in the DALYs rates for various etiologies was similar to that of ASDR (Fig. 6C).

Prevalence trends in global and 5 SDI regions by time

In both 1990 and 2021, the medium SDI regions had the highest number of liver cirrhosis cases, which continued to increase (Table 4). Although the ASPR in high SDI regions has risen, it remained the lowest among all regions in 2021 (1990: 11,594.897 per 100,000; 2021: 13,575.436 per 100,000) (Table 4). The EAPC indicates that high SDI regions were the only regions where ASPR increased (0.581; 95% CI: 0.535–0.627), while ASPR in other regions remained stable or declined (Table 4). Except for low SDI regions, the ASPR for liver cirrhosis due to NAFLD was significantly higher than that for other causes. In the low SDI regions, the ASPR for liver cirrhosis due to chronic hepatitis B was greater than that for liver cirrhosis caused by NAFLD before 2008 (Fig. 6D).

Risk factors for cirrhosis

Research findings from the GBD database identified two primary risk factors for liver cirrhosis: drug use and high alcohol use, both classified as behavioral risks. The results indicated that, in 2021, the high SDI region had the highest rates of liver cirrhosis-related deaths due to drug use (22.97%) and excessive alcohol consumption (52.41%) among all regions (Fig. 7A, B). Compared with 1990, the proportion of liver cirrhosis deaths resulting from high alcohol use increased in all regions except the high SDI region, which saw a slight decrease. Conversely, the proportion of liver cirrhosis deaths attributed to drug use increased across all regions (Fig. 7A−C).

Fig. 7.

The proportion of Deaths attributable to risk factors in 1990 (A) and 2021 (B) and the trend of these proportions from 1990–2021 (C)

Prediction of the global burden of cirrhosis

According to the BAPC model, the predicted trends for the ASDR and DALYs rates are nearly identical, with both showing a continuous decline from 1990 to 2021, a trend anticipated to persist until 2060 (Fig. 8A, B). Prior to 2021, the ASPR for liver cirrhosis has fluctuated steadily; however, it is predicted that a gradual decline will begin after 2021, with the rate of decline expected to increase each year (Fig. 8C). In summary, the global burden of liver cirrhosis is expected to decrease gradually.

Fig. 8.

The trend of age-standardized deaths (A), DALYs (B), and prevalence (C) of liver cirrhosis from 1990–2021 and prediction to 2060 in global

Discussion

In 2021, the global number of liver cirrhosis prevalence cases and the rate have significantly increased compared to 1990, driven by several factors. The global incidence rate of liver cirrhosis has increased, while the death rate has declined (Tables 1 and 2). On the other hand, the global population continues to grow, projected to reach 9 to 10 billion by 2050 [22]. The large number of patients with liver cirrhosis imposes a serious economic burden on countries and regions, while also severely affecting the quality of life [23]. Additionally, ASIR for liver cirrhosis has increased over the past 32 years, likely linked to rising alcohol consumption, aging populations, and increasing obesity rates [12, 24]. Despite the decline in ASDR and DALYs due to economic development and advancements in medical technology [25], the only current cure for liver cirrhosis is liver transplantation [26]. Given the high cost and limited availability of donor organs, many patients with liver cirrhosis are unable to access this treatment. Therefore, a substantial number of patients with cirrhosis continue to rely solely on conservative medical management. Previous studies have indicated that, compared with other common chronic diseases, the healthcare costs associated with cirrhosis are relatively high [27].

This study revealed that Africa consistently has one of the highest ASIR for liver cirrhosis among global regions. This disparity is driven by inadequate healthcare infrastructure, a paucity of hepatology specialists, and insufficient governmental investment in hepatic disease prevention [28]. Additionally, the high prevalence of schistosomiasis and HBV infections, along with the widespread use of hepatotoxic traditional herbal medicines, further contributes to elevated rates of liver cirrhosis [29]. Recently, African governments have made strides by enhancing public awareness of chronic liver disease prevention and actively addressing HBV infections [30]. By 2021, these efforts have led to a significant decrease in the ASIR for liver cirrhosis in Africa.

From 1990 to 2021, the ASDR for liver cirrhosis worldwide has exhibited a declining trend; however, increases have been noted in Eastern Europe and High-Income North America. These changes are primarily driven by distinct regional etiological drivers and their underlying pathophysiological mechanisms. In Eastern Europe, alcohol abuse remains the dominant contributor, where chronic ethanol metabolism generates acetaldehyde adducts that promote oxidative stress, mitochondrial dysfunction, and hepatic stellate cell (HSC) activation, accelerating collagen deposition [31]. Concurrently, limited access to early interventions exacerbates progression to decompensated cirrhosis. In High-Income North America, rising metabolic dysfunction-associated steatotic liver disease drives fibrogenesis through lipotoxicity-induced hepatocyte apoptosis, TNF-α/IL-6-mediated inflammation, and TGF-β-dependent HSC activation [32]. This combines with persistent HCV transmission among people who inject drugs, where viral proteins directly activate profibrotic genes in HSCs. Evidence has shown that alcohol is a primary risk factor for liver cirrhosis [33], and there exists a pathological synergy between alcohol and obesity or fatty acid levels, impacting lipid accumulation and damage in liver cells and contributing to liver inflammation, fibrosis, and cancer development [34]. In contrast, East Asia experienced the most significant decline in ASDR for liver cirrhosis, likely due to rapid economic growth and advancements in medical technology in developing countries, particularly China. The widespread implementation of hepatitis B vaccination in this region has also played a crucial role in reducing the incidence of ASDR for liver cirrhosis [35]. So, the failure of alcohol policies in Eastern Europe and obesity control policies in North America are key drivers of the increase in ASDR in these regions. The success in East Asia is attributed to comprehensive public health strategies, including neonatal HBV immunization programs, subsidies for antiviral treatment, and grassroots cirrhosis surveillance networks, demonstrating the synergistic effect of vertical interventions and system strengthening.

The increase in global alcohol consumption has highlighted the issue of alcohol-related liver cirrhosis. A previous study indicated that between 1990 and 2019, deaths from alcohol-related liver cirrhosis increased by 59.68% worldwide [36]. According to the latest data from 2021, Eastern Europe has the highest proportion of deaths attributed to alcohol-related liver cirrhosis, which is closely linked to the region’s high levels of alcohol consumption. Consequently, regions with a significant prevalence of alcohol-related liver cirrhosis could prioritize alcohol control measures and implement relevant policies to prevent further increases in the number of cases. Notably, despite their moderate economic development, North Africa and the Middle East reported the lowest proportion of deaths due to alcohol-related liver cirrhosis. This is likely because many countries in the region predominantly have Muslim populations, where Islamic law prohibits the production, consumption, transport, and trade of alcohol [37]. All in all, the high burden of NAFLD in North America is directly related to policy failures, such as the lack of public funding for screening and lobbying by the food industry. In contrast, the low alcohol-related burden in North Africa and the Middle East highlights the role of strong cultural/religious norms as protective factors.

From 1990 to 2021, the proportion of deaths from liver cirrhosis due to NAFLD has increased rapidly in Andean Latin America, and the situation in Western Europe is similar. In fact, our research showed that all regions globally have experienced varying degrees of increase in deaths from liver cirrhosis related to NAFLD (Fig. 3). Based on existing data, it is reasonable to predict that cirrhosis caused by NAFLD will continue to increase globally [38–40], a trend that is widely accepted and aligns with our research findings (Fig. 6). However, currently no country in the world has formulated a written strategy for the prevention, management, and treatment of NAFLD [41]. Therefore, there is an urgent need to enhance the focus on this area. In fact, there is substantial overlap between the public health and health system approaches required for the prevention and management of NAFLD and those of other chronic diseases. For instance, medical education targeting overweight individuals and the customization of individualized dietary plans should be implemented. Meanwhile, incorporating NAFLD screening into routine health check-ups is essential to detect the disease at an early stage, thereby facilitating timely lifestyle modifications and delaying disease progression.

Our research revealed that the proportion of liver cirrhosis deaths caused by chronic hepatitis B in East Asia significantly surpasses those in other regions. In China, HBV infection accounts for approximately one-quarter of the global total [42]. Despite local government efforts to promote hepatitis B vaccination and antiviral treatments, the incidence of HBV infections has declined. However, East Asia continues to have the highest proportion of liver cirrhosis deaths attributable to chronic hepatitis B [43]. Conversely, High-income North America exhibits the lowest proportion of liver cirrhosis deaths related to chronic hepatitis B, yet it ranks among the highest globally for liver cirrhosis deaths due to chronic hepatitis C (Fig. 3). The drug-using population is particularly vulnerable to HCV infection, with injection drug use being the most common transmission route [44]. Reports indicate that High-income North America has one of the highest rates of dependence on marijuana, opioids, and cocaine [45]. Therefore, strengthening drug control measures is essential to effectively reduce HCV infection rates in North America.

The ASIR, ASDR, and age standardized DALYs rates for liver cirrhosis were higher in men than in women, with one major reason likely related to alcohol consumption. Traditionally, alcohol-related liver cirrhosis has been perceived as more severe in men. However, research has demonstrated that alcohol intake among women is gradually increasing, and that they are more susceptible to the harmful effects of alcohol, leading to a narrowing of this gap [46]. Additionally, over the past 40 years, prenatal sex-selective abortion has led to a global gender imbalance, resulting in a higher number of males than females [47], which also contributes to the higher incidence and death rates of liver cirrhosis in men.

Generally, a region’s level of economic development is positively correlated with advancements in medical technology [48]. Our study shows that the ASIR, ASDR, age standardized DALYs rate, and ASPR of liver cirrhosis are all negatively correlated with the SDI value, which aligns with previous studies [8, 10]. Higher levels of medical technology in a region are associated with better prevention and treatment outcomes for hepatitis viruses and liver cirrhosis, suggesting that SDI serves as a protective factor for liver cirrhosis. However, it is noteworthy that a high SDI is associated with increased rates of dyslipidemia and obesity [49]. In particular, the ASIR and ASPR in North Africa and the Middle East were significantly higher than expected, likely due to the region’s elevated rates of HCV and HBV infections [50].

The BAPC model predicts a gradual decline in the global ASPR, ASDR, and age standardized DALYs rates associated with liver cirrhosis, which is inconsistent with previous projections using GBD 2019 [10, 51]. This is probably driven by several key factors. First, improvements in the average global economic level and advancements in medical technology have increased per capita healthcare resources, resulting in extended survival of patients with decompensated liver cirrhosis. Second, as more countries transition to a developed status, there is likely to be a growing awareness among the public regarding chronic diseases such as liver cirrhosis, leading to lifestyle changes that further mitigate the global burden of the disease. Third, long-term investments made by governments in the widespread distribution of hepatitis virus vaccines and antiviral treatments are expected to gradually produce positive outcomes. The interplay between these factors may ultimately contribute to a decrease in the global burden of liver cirrhosis. In summary, the predicted downward trend relies on the continuation of current epidemiological trends and the sustainability of healthcare policies. Geopolitical turbulence may undermine progress, especially in rapidly transitioning regions with medium SDI.

The findings demand coordinated action across stakeholders. High SDI: Legislate mandatory NAFLD screening in primary care and adopt alcohol taxation models. Middle SDI: Integrate HBV vaccination with metabolic syndrome surveillance, as piloted in China’s 2023 liver disease guidelines. Low SDI: Subsidize HCV rapid diagnostics and regulate traditional medicine via WHO herbal safety standards. Meanwhile, researchers should also conduct cost-effectiveness analyses of alcohol taxes and NAFLD screening in high SDI regions and develop low-cost, non-invasive diagnostic methods in resource-limited settings. Here are the beneficial outcomes resulting from the policy changes brought about by previous studies: (1) High-alcohol-consumption regions: Ireland’s 2022 minimum unit pricing policy has successfully reduced alcohol - related emergency department visits and length of stay [52]. Lithuania’s 18-year control policy has also significantly reduced liver cirrhosis mortality [53]. (2) High-HBV/HCV prevalence regions: The World Health Organization has formulated several vaccine-related policies [54, 55], including the Immunization Agenda 2030. These aim to further reduce infection rates in areas with high HBV/HCV prevalence. (3) High-NAFLD prevalence regions: The Mediterranean diet policy launched by the American Heart Association has been proven to be beneficial for NAFLD patients [56].

The regional heterogeneity in cirrhosis burden demands tailored policy interventions. In high-burden North Africa and the Middle East, where HCV/HBV dominate, governments should accelerate national viral hepatitis elimination programs by integrating HBV birth-dose vaccination into primary care systems, subsidizing pan-genotypic DAAs for HCV, and regulating hepatotoxic traditional medicines through WHO safety certification. Eastern Europe’s alcohol-driven mortality necessitates fiscal and clinical reforms including implementing minimum unit pricing, mandating addiction screening in hepatology clinics, and redirecting alcohol tax revenues to liver transplantation infrastructure. High-income North America must confront its dual NAFLD/HCV epidemic through universal NAFLD screening in diabetes/obesity programs, establishing supervised injection sites with HCV point-of-care testing to interrupt transmission, and expanding Medicaid coverage for antifibrotics. Crucially, low-SDI regions require international support for task-shifting strategies coupled with Gavi/Global Fund financing for antiviral therapies. These interventions align with WHO liver health targets but require political commitment to resource redistribution.

This study has several limitations. Firstly, the BAPC model projects a gradual decline in cirrhosis burden by 2060; however, these predictions must be contextualized by key methodological constraints: (1) The model assumes linear continuity of current epidemiological trends, rendering projections vulnerable to disruptive innovations or systemic shocks; (2) Cohort effects may be miscalibrated for diseases with long latency periods like NAFLD-related cirrhosis, where early-life metabolic exposures manifest clinically decades later; (3) Unaccounted variables—such as future gene therapies or climate change impacts on liver disease vectors—could substantially alter trajectories. Secondly, while the 2021 GBD data is comprehensive, it shows varying degrees of reliability across different countries: (1) In low-SDI regions, passive surveillance underestimates true cirrhosis prevalence by 30–50% due to fragmented diagnostics; (2) High-SDI regions exhibit ascertainment bias through stringent histological criteria that inflate severity metrics while missing compensated cases; (3) COVID-19 disruptions created transient data valleys in 2020–2021. These factors may overstate improvements in high-SDI settings while masking stagnation in resource-limited areas, necessitating cautious interpretation of regional disparities. Finally, while we incorporated GBD 2021’s preliminary COVID-19 adjustments, the pandemic’s long-term impacts remain uncertain. For example, in India, the delay in hepatitis C screening has led to a significant drop in case detection rates. In Africa, the disruption of hepatitis B vaccination campaigns may increase the future incidence of cirrhosis. So longitudinal data beyond 2021 are needed to fully quantify these effects.

Conclusion

Although the incidence of cirrhosis is rising globally, death rates have declined, indicating improvements in its management. Continuous monitoring and targeted interventions are crucial, particularly in high-burden regions, to mitigate the ongoing impact of this disease.

Abbreviations

GBD

Global Burden of Disease

DALYs

Disability-adjusted life years

SDI

Socio-Demographic Index

HBV

Hepatitis B virus

HCV

Hepatitis C virus

NAFLD

Non-alcoholic fatty liver disease

YLD

Years lived with disability

ASIR

Age-standardized incidence

ASDR

Age-standardized deaths

ASPR

Age-standardized prevalence

EAPC

Estimated annual percentage changes

CI

Confidence intervals

Author contributions

Xuefeng Luo and Yinghao He contributed equally to this work. Xuefeng Luo: Conceptualized the study, wrote the methodology, provided project administration, data curation, carried out the formal analysis, writing and original draft. Yinghao He: Conceptualized the study, wrote the methodology, provided project administration, data curation, carried out the formal analysis, writing and original draft. Zheng Jiang: Conceptualized and supervised the study, carried out the investigation, wrote the methodology, writing, review, and editing. Junyi Liao: Conceptualized and supervised the study, carried out the investigation, wrote the methodology, writing, review, and editing. All authors have reviewed and endorsed the manuscript.

Funding

This was supported by CQMU Program for Youth Innovation in Future Medicine (W0154), Cultivating Program and Candidate of Tip-Top Talent of The First Affiliated Hospital of Chongqing Medical University (#BJRC2021-04). Funding sources were not involved in the study design, in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication.

Data availability

Data used for the analyses are publicly available from the Institute of Health Metrics and Evaluation (http://www.healthdata.org/; http://ghdx.healthdata.org/gbd-results-tool).

Declarations

Consent for publication

Our research is a secondary analysis of public data. Meanwhile, we have also obtained the approval of the ethics exemption from the local ethics committee.

Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

Our research involved a secondary evaluation of the publicly accessible GBD Study, without primary data collection. At the same time, we have also obtained the approval of the ethics exemption from the local ethics committee. The confidentiality of the participants was ensured during data collection, and informed consent was taken from the respondents during the NFHS survey.