The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

GBD 2017 Cirrhosis Collaborators, Sadaf G Sepanlou, Saeid Safiri, Catherine Bisignano, Kevin S Ikuta, Shahin Merat, Mehdi Saberifiroozi, Hossein Poustchi, Derrick Tsoi, Danny V Colombara, Amir Abdoli, Rufus Adesoji Adedoyin, Mohsen Afarideh, Sutapa Agrawal, Sohail Ahmad, Elham Ahmadian, Ehsan Ahmadpour, Tomi Akinyemiju, Chisom Joyqueenet Akunna, Vahid Alipour, Amir Almasi-Hashiani, Abdulaziz M Almulhim, Rajaa M Al-Raddadi, Nelson Alvis-Guzman, Nahla Hamed Anber, Colin Angus, Amir Anoushiravani, Jalal Arabloo, Ephrem Mebrahtu Araya, Daniel Asmelash, Bahar Ataeinia, Zerihun Ataro, Maha Moh'd Wahbi Atout, Floriane Ausloos, Ashish Awasthi, Alaa Badawi, Maciej Banach, Diana Fernanda Bejarano Ramirez, Akshaya Srikanth Bhagavathula, Neeraj Bhala, Krittika Bhattacharyya, Antonio Biondi, Srinivasa Rao Bolla, Archith Boloor, Antonio M Borzì, Zahid A Butt, Luis LA Alberto Cámera, Ismael R Campos-Nonato, Félix Carvalho, Dinh-Toi Chu, Sheng-Chia Chung, Paolo Angelo Cortesi, Vera M Costa, Benjamin C Cowie, Ahmad Daryani, Barbora de Courten, Gebre Teklemariam Demoz, Rupak Desai, Samath Dhamminda Dharmaratne, Shirin Djalalinia, Hoa Thi Do, Fariba Dorostkar, Thomas M Drake, Manisha Dubey, Bruce B Duncan, Andem Effiong, Aziz Eftekhari, Aisha Elsharkawy, Arash Etemadi, Mohammad Farahmand, Farshad Farzadfar, Eduarda Fernandes, Irina Filip, Florian Fischer, Ketema Bizuwork Bizuwork Gebremedhin, Birhanu Geta, Syed Amir Gilani, Paramjit Singh Gill, Reyna Alma Gutirrez, Michael Tamene Haile, Arvin Haj-Mirzaian, Saeed S Hamid, Milad Hasankhani, Amir Hasanzadeh, Maryam Hashemian, Hamid Yimam Hassen, Simon I Hay, Khezar Hayat, Behnam Heidari, Andualem Henok, Chi Linh Hoang, Mihaela Hostiuc, Sorin Hostiuc, Vivian Chia-Rong Hsieh, Ehimario U Igumbor, Olayinka Stephen Ilesanmi, Seyed Sina Naghibi Irvani, Nader Jafari Balalami, Spencer L James, Panniyammakal Jeemon, Ravi Prakash Jha, Jost B Jonas, Jacek Jerzy Jozwiak, Ali Kabir, Amir Kasaeian, Hagazi Gebremedhin Kassaye, Adane Teshome Kefale, Rovshan Khalilov, Muhammad Ali Khan, Ejaz Ahmad Khan, Amir Khater, Yun Jin Kim, Ai Koyanagi, Carlo La Vecchia, Lee-Ling Lim, Alan D Lopez, Stefan Lorkowski, Paulo A Lotufo, Rafael Lozano, Muhammed Magdy Abd El Razek, Hue Thi Mai, Navid Manafi, Amir Manafi, Mohammad Ali Mansournia, Lorenzo Giovanni Mantovani, Giampiero Mazzaglia, Dhruv Mehta, Walter Mendoza, Ritesh G Menezes, Melkamu Merid Mengesha, Tuomo J Meretoja, Tomislav Mestrovic, Bartosz Miazgowski, Ted R Miller, Erkin M Mirrakhimov, Prasanna Mithra, Babak Moazen, Masoud Moghadaszadeh, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Ali H Mokdad, Pablo A Montero-Zamora, Ghobad Moradi, Mukhammad David Naimzada, Vinod Nayak, Ionut Negoi, Trang Huyen Nguyen, Richard Ofori-Asenso, In-Hwan Oh, Tinuke O Olagunju, Jagadish Rao Padubidri, Keyvan Pakshir, Adrian Pana, Mona Pathak, Akram Pourshams, Navid Rabiee, Amir Radfar, Alireza Rafiei, Kiana Ramezanzadeh, Saleem Muhammad M Rana, Salman Rawaf, David Laith Rawaf, Robert C Reiner Jr, Leonardo Roever, Robin Room, Gholamreza Roshandel, Saeed Safari, Abdallah M Samy, Juan Sanabria, Benn Sartorius, Maria Inês Schmidt, Subramanian Senthilkumaran, Masood Ali Shaikh, Mehdi Sharif, Amrollah Sharifi, Mika Shigematsu, Jasvinder A Singh, Amin Soheili, Hafiz Ansar Rasul Suleria, Berhane Fseha Teklehaimanot, Berhe Etsay Tesfay, Marco Vacante, Amir Vahedian-Azimi, Pascual R Valdez, Tommi Juhani Vasankari, Giang Thu Vu, Yasir Waheed, Kidu Gidey Weldegwergs, Andrea Werdecker, Ronny Westerman, Dawit Zewdu Wondafrash, Adam Belay Wondmieneh, Yordanos Gizachew Yeshitila, Naohiro Yonemoto, Chuanhua Yu, Zoubida Zaidi, Afshin Zarghi, Shira Zelber-Sagi, Kaleab Alemayehu Zewdie, Zhi-Jiang Zhang, Xiu-Ju Zhao, Mohsen Naghavi, Reza Malekzadeh, GBD 2017 Cirrhosis Collaborators, Sadaf G Sepanlou, Saeid Safiri, Catherine Bisignano, Kevin S Ikuta, Shahin Merat, Mehdi Saberifiroozi, Hossein Poustchi, Derrick Tsoi, Danny V Colombara, Amir Abdoli, Rufus Adesoji Adedoyin, Mohsen Afarideh, Sutapa Agrawal, Sohail Ahmad, Elham Ahmadian, Ehsan Ahmadpour, Tomi Akinyemiju, Chisom Joyqueenet Akunna, Vahid Alipour, Amir Almasi-Hashiani, Abdulaziz M Almulhim, Rajaa M Al-Raddadi, Nelson Alvis-Guzman, Nahla Hamed Anber, Colin Angus, Amir Anoushiravani, Jalal Arabloo, Ephrem Mebrahtu Araya, Daniel Asmelash, Bahar Ataeinia, Zerihun Ataro, Maha Moh'd Wahbi Atout, Floriane Ausloos, Ashish Awasthi, Alaa Badawi, Maciej Banach, Diana Fernanda Bejarano Ramirez, Akshaya Srikanth Bhagavathula, Neeraj Bhala, Krittika Bhattacharyya, Antonio Biondi, Srinivasa Rao Bolla, Archith Boloor, Antonio M Borzì, Zahid A Butt, Luis LA Alberto Cámera, Ismael R Campos-Nonato, Félix Carvalho, Dinh-Toi Chu, Sheng-Chia Chung, Paolo Angelo Cortesi, Vera M Costa, Benjamin C Cowie, Ahmad Daryani, Barbora de Courten, Gebre Teklemariam Demoz, Rupak Desai, Samath Dhamminda Dharmaratne, Shirin Djalalinia, Hoa Thi Do, Fariba Dorostkar, Thomas M Drake, Manisha Dubey, Bruce B Duncan, Andem Effiong, Aziz Eftekhari, Aisha Elsharkawy, Arash Etemadi, Mohammad Farahmand, Farshad Farzadfar, Eduarda Fernandes, Irina Filip, Florian Fischer, Ketema Bizuwork Bizuwork Gebremedhin, Birhanu Geta, Syed Amir Gilani, Paramjit Singh Gill, Reyna Alma Gutirrez, Michael Tamene Haile, Arvin Haj-Mirzaian, Saeed S Hamid, Milad Hasankhani, Amir Hasanzadeh, Maryam Hashemian, Hamid Yimam Hassen, Simon I Hay, Khezar Hayat, Behnam Heidari, Andualem Henok, Chi Linh Hoang, Mihaela Hostiuc, Sorin Hostiuc, Vivian Chia-Rong Hsieh, Ehimario U Igumbor, Olayinka Stephen Ilesanmi, Seyed Sina Naghibi Irvani, Nader Jafari Balalami, Spencer L James, Panniyammakal Jeemon, Ravi Prakash Jha, Jost B Jonas, Jacek Jerzy Jozwiak, Ali Kabir, Amir Kasaeian, Hagazi Gebremedhin Kassaye, Adane Teshome Kefale, Rovshan Khalilov, Muhammad Ali Khan, Ejaz Ahmad Khan, Amir Khater, Yun Jin Kim, Ai Koyanagi, Carlo La Vecchia, Lee-Ling Lim, Alan D Lopez, Stefan Lorkowski, Paulo A Lotufo, Rafael Lozano, Muhammed Magdy Abd El Razek, Hue Thi Mai, Navid Manafi, Amir Manafi, Mohammad Ali Mansournia, Lorenzo Giovanni Mantovani, Giampiero Mazzaglia, Dhruv Mehta, Walter Mendoza, Ritesh G Menezes, Melkamu Merid Mengesha, Tuomo J Meretoja, Tomislav Mestrovic, Bartosz Miazgowski, Ted R Miller, Erkin M Mirrakhimov, Prasanna Mithra, Babak Moazen, Masoud Moghadaszadeh, Abdollah Mohammadian-Hafshejani, Shafiu Mohammed, Ali H Mokdad, Pablo A Montero-Zamora, Ghobad Moradi, Mukhammad David Naimzada, Vinod Nayak, Ionut Negoi, Trang Huyen Nguyen, Richard Ofori-Asenso, In-Hwan Oh, Tinuke O Olagunju, Jagadish Rao Padubidri, Keyvan Pakshir, Adrian Pana, Mona Pathak, Akram Pourshams, Navid Rabiee, Amir Radfar, Alireza Rafiei, Kiana Ramezanzadeh, Saleem Muhammad M Rana, Salman Rawaf, David Laith Rawaf, Robert C Reiner Jr, Leonardo Roever, Robin Room, Gholamreza Roshandel, Saeed Safari, Abdallah M Samy, Juan Sanabria, Benn Sartorius, Maria Inês Schmidt, Subramanian Senthilkumaran, Masood Ali Shaikh, Mehdi Sharif, Amrollah Sharifi, Mika Shigematsu, Jasvinder A Singh, Amin Soheili, Hafiz Ansar Rasul Suleria, Berhane Fseha Teklehaimanot, Berhe Etsay Tesfay, Marco Vacante, Amir Vahedian-Azimi, Pascual R Valdez, Tommi Juhani Vasankari, Giang Thu Vu, Yasir Waheed, Kidu Gidey Weldegwergs, Andrea Werdecker, Ronny Westerman, Dawit Zewdu Wondafrash, Adam Belay Wondmieneh, Yordanos Gizachew Yeshitila, Naohiro Yonemoto, Chuanhua Yu, Zoubida Zaidi, Afshin Zarghi, Shira Zelber-Sagi, Kaleab Alemayehu Zewdie, Zhi-Jiang Zhang, Xiu-Ju Zhao, Mohsen Naghavi, Reza Malekzadeh

Abstract

Background: Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories.

Methods: We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries.

Findings: In 2017, cirrhosis caused more than 1·32 million (95% UI 1·27-1·45) deaths (440 000 [416 000-518 000; 33·3%] in females and 883 000 [838 000-967 000; 66·7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2·4% (2·3-2·6) of total deaths globally in 2017 compared with 1·9% (1·8-2·0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21·0 (19·2-22·3) per 100 000 population in 1990 to 16·5 (15·8-18·1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32·2 [25·8-38·6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10·1 [9·8-10·5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3·7 [3·3-4·0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103·3 [64·4-133·4] per 100 000 in 2017). There were 10·6 million (10·3-10·9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33·2% for compensated cirrhosis and 54·8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases more than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI.

Interpretation: Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.

Funding: Bill & Melinda Gates Foundation.

Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Counts and age-standardised rates of cirrhosis death at the global level by sex, 1990–2017 Error bars indicate 95% UIs for number of deaths. Shading indicates 95% UIs for age-standardised death rates. UI=uncertainty interval.
Figure 2
Figure 2
Age-standardised rates for cirrhosis by region and sex, 2017 (A) Age-standardised death rate. (B) Age-standardised prevalence rate of compensated and decompensated cirrhosis. Error bars indicate 95% uncertainty intervals for age-standardised rates.
Figure 3
Figure 3
Age-standardised death rate for cirrhosis in 2017 (A), age-standardised prevalence for decompensated cirrhosis (B), and age-standardised prevalence for compensated cirrhosis (C), 2017 ATG=Antigua and Barbuda. FSM=Federated States of Micronesia. Isl=Islands. LCA=Saint Lucia. TLS=Timor-Leste. TTO=Trinidad and Tobago. VCT=Saint Vincent and the Grenadines.
Figure 3
Figure 3
Age-standardised death rate for cirrhosis in 2017 (A), age-standardised prevalence for decompensated cirrhosis (B), and age-standardised prevalence for compensated cirrhosis (C), 2017 ATG=Antigua and Barbuda. FSM=Federated States of Micronesia. Isl=Islands. LCA=Saint Lucia. TLS=Timor-Leste. TTO=Trinidad and Tobago. VCT=Saint Vincent and the Grenadines.
Figure 4
Figure 4
Proportion of deaths due to five causes of cirrhosis at global and regional levels by sex, 2017
Figure 5
Figure 5
Number of deaths and age-standardised death rates at the global level by cause of cirrhosis, 1990–2017 Bars refer to number of deaths in each year. Lines refer to age-standardised death rate in each year. NASH=non-alcoholic steatohepatitis.
Figure 6
Figure 6
Age patterns of deaths, DALYs, and prevalence of cirrhosis by sex, 2017 (A) Number of deaths and age-specific death rate per 100 000 population. (B) Number of DALYs and age-specific DALY rate per 100 000 population. (C) Number of prevalent cases and age-specific prevalence rates per 100 000 population of decompensated and compensated cirrhosis. Error bars indicate 95% UIs for number of deaths, DALYs, and prevalent cases. Shading indicates 95% UIs for death rates, DALY rates, and prevalence rates. DALYs=disability-adjusted life-years. UI=uncertainty interval.
Figure 7
Figure 7
Age-standardised rates of cirrhosis globally and for 21 regions by SDI, 1990–2017 (A) Age-standardised death rate per 100 000 population. (B) Age-standardised DALY rate per 100 0000 population. (C) Age-standardised prevalence per 100 000 population of decompensated cirrhosis. (D) Age-standardised prevalence per 100 000 population of compensated cirrhosis. For each region, points from left to right depict estimates from each year from 1990 to 2017. Black lines show the expected death, DALY, or prevalence rates on the basis of SDI alone. DALYs=disability-adjusted life-years. SDI=Socio-demographic Index.
Figure 7
Figure 7
Age-standardised rates of cirrhosis globally and for 21 regions by SDI, 1990–2017 (A) Age-standardised death rate per 100 000 population. (B) Age-standardised DALY rate per 100 0000 population. (C) Age-standardised prevalence per 100 000 population of decompensated cirrhosis. (D) Age-standardised prevalence per 100 000 population of compensated cirrhosis. For each region, points from left to right depict estimates from each year from 1990 to 2017. Black lines show the expected death, DALY, or prevalence rates on the basis of SDI alone. DALYs=disability-adjusted life-years. SDI=Socio-demographic Index.

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