Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions

Table 1 Recent local epidemiological data on liver cirrhosis in the general population

Ref.	Country	Study population	Study period	Diagnostic methods	Presented data
[9]	US	7297435 patients with a GI diagnosis in a commercial insurance database	2016-2018	ICD-10 code	Nonalcoholic cirrhosis prevalence: 0.389%; average inpatient cost: 43733 dollars; annualized total costs: 53214 dollars
[10]	Germany	All hospital admissions (248085936 patients)	2005-2018	ICD-10 code	Prevalence: 0.94%
[11]	Japan	488 randomly selected individuals underwent fatty liver and advanced fibrosis screening	From October to November 2020	Liver stiffness measurement	Prevalence: 1%
[12]	US	Adult patients in a commercial medical claims database	2018	ICD-9 or ICD-10 code	Prevalence: 0.21%
[28]	China	503993 participants prospectively included in China Kadoorie Biobank	2004-2008 (10 years of follow-up)	ICD-10 code	Incidence: 756.4 and 397.4 per 100000 among diabetic patients and nondiabetic patients, respectively
[30]	Korea	Adult patients in the HIRA-NPS database	2012-2016	ICD-9 code	Alcoholic cirrhosis incident cases: 7295 cases
[31]	Sweden	All patients at Halland Hospital	2011-2018	ICD-10 code and SNOMED code	Age-standardized incidence: 23.2 per 100000 person-years
[32]	Korea	Adult patients in the NHIS database	2011-2015	KCD-7 code	Primary biliary cirrhosis average annual cumulative incidence: 68.32 cases per 10000000
[33]	Canada	Adult patients in the ICES databases	1997-2016	ICD-10 code	Age-standardized incidence: 70.6 in 1997 and 89.6 per 100000 person-years in 2016
[34]	Canada	Children in the ICES databases	1997-2017	ICES-validated algorithm	Age- and sex-adjusted incidence: 2.7 in 1997 and 10.6 per 100000 person-years in 2017
[44]	US	NIS	2003-2017	ICD-10 code	Alcoholic cirrhosis deaths in women: 14330 cases
[45]	Mexico	National Institute of Statistics and Geography	2000-2017	ICD-10 code	Alcoholic cirrhosis mortality rate: From 20.55 to 10.62 per 100000
[54]	US	Adult patients in the NIS	2008-2014	ICD-9 code	Hospitalization costs: 7.37 billion dollars in 2014

US: United States; ICD: International classification of diseases; HIRA-NPS: Health insurance review and assessment-national patient samples; SNOMED: Systematized nomenclature of medicine; NHIS: National Health Insurance Service; KCD: Korean standard classification of diseases; ICES: Institute for clinical evaluative sciences; NIS: National inpatient sample.

Table 2 Epidemiology of cirrhosis in specific at-risk populations

Ref.	Country	Study population	Study period	Diagnostic methods	Presented data
[13]	US	825 adults with type 2 diabetes who had reliable TE results from the NHANES	2017-2018	TE	Prevalence: 7.7%
[14]	US	Patients with NAFLD from the NHANES	2017-2018	TE	Prevalence: 4.4%
[15]	US	3115 HBsAg-negative/HBcAb-positive subjects from the NHANES	2001-2018	FIB-4	Cirrhosis/advanced liver fibrosis prevalence: 3.76%
[16]	13 countries in sub-Saharan Africa	HBV-infected population	2012-2019	TE, APRI and Fibrotest	Prevalence: 4.1% in primary care or the general population and 12.7% in referral or tertiary care settings
[17]	Spain	501 biopsy-proven NASH patients with paired TE data from tertiary centers	2015-2020	TE	Prevalence: 0.70%
[18]	Korea	27629 adults with MHO or MUHO from the KNHANES	2015-2019	Self-report survey or by an AST level ≥ 23.5 IU/L	Prevalence: 0.5% and 0.4% in MHO and MUHO, respectively
[19]	US	3386 patients with NAFLD in the TARGET-NASH study	2016-2019	Pragmatic case definitions	Prevalence: 22.6% in lean patients
[21]	Italy	6193 older subjects admitted to acute medical wards and included in the REPOSI registry	2010-2018	ICD-9 code	Prevalence: 5%
[22]	10 countries in the world	320777 dialysis patients	1980-2019	TE, histopathology, radiology, and ICD codes	Prevalence: 5%
[36]	NR	902 patients with a Fontan circulation	NR	NR	Cumulative incidence: 27.5%
[39]	Japan	1260 patients who underwent the Fontan procedure and survived to discharge from 9 institutions	From before 2011 to 2021 (median10.2 of years follow-up)	Biopsy or imaging or extrahepatic features	Cumulative incidence at 10, 20, and 30 years after the Fontan procedure: 0.9%, 11.6%, and 25.7%, respectively
[41]	Italy	All adults aged 30 years or older without cirrhosis in Rome	From 2001 follow up to 2015	A validated algorithm	Crude incidence rate: 67 per 100000 person-years

US: United States; TE: Transient elastography; NHANES: National Health and Nutrition Examination Survey; NAFLD: Nonalcoholic fatty liver disease; HBsAg: Hepatitis B surface antigen; HBcAb: Hepatitis B core antibody; FIB-4: Fibrosis-4; HBV: Hepatitis B virus; APRI: Aspartate transferase-to-platelet ratio index; NASH: Nonalcoholic steatohepatitis; MHO: Metabolically healthy obesity; MUHO: Metabolically unhealthy obesity; KNHANES: Korea National Health and Nutrition Examination Survey; AST: Aspartate transferase; IU/L: International unit per liter; REPOSI: Registro Politerapia Società Italiana di Medicina Interna; NR: Not recorded.

Table 3 Epidemiology of hepatocellular carcinoma in patients with cirrhosis

Ref.	Country	Study population	Study period	Study design	Epidemiology
[119]	US	392800 NAFLD patients from 26 major integrated US healthcare systems	2015-2020	Retrospective cohort study	Prevalence: 374.4/10000 persons
[120]	Sweden	15215 individuals with cirrhosis in the National Outpatient Register	2001-2016	Nationwide population-based cohort study	Incidence rate: 23 per 1000 person-years; cumulative incidence: 8.3% at 5 years and 12.2% (4.3% in women with alcoholic cirrhosis and 26.6% in men with viral hepatitis) at 10 years
[121]	US	2733 patients with cirrhosis in two contemporary prospective multiethnic cohorts	2016-2020 (with follow-up until June 30, 2021)	Prospective multiethnic cohort study	Annual incidence: 1.82% (1.71%, 1.32%, and 1.24% in cured HCV, ALD and NAFLD, respectively)
[122]	NA	29444 patients with HCV cure	NA	Meta-analysis	Incidence: 2.1 per 100 person-years
[123]	China	937 treatment-naïve adults with compensated HBV-induced cirrhosis	2012-2015 (with follow-up until June 30, 2019)	Prospective cohort study	Cumulative incidence: 7.4% at 5 years
[124]	Korea	359 patients with HBV-associated cirrhosis who were treated with ETV for at least 2 years	2007-2012 (median follow-up of 82 mo)	Retrospective cohort study	Cumulative incidence: 4.7%, 15.9%, 21.8% and 32.9% at 3, 5, 7 and 9 years, respectively
[125]	US	501 veterans with PBC and compensated cirrhosis	2008-2016 (with follow-up until December 31, 2019)	Retrospective cohort study	Incidence: 0.6 and 0.7 person-years in UDCA responders and UDCA partial responders, respectively
[126]	US	532 patients with PBC and compensated cirrhosis	2008-2016 (with follow-up until June 30, 2020)	Retrospective cohort study	Incidence: 0.9 and 0.3 person-years in males and females, respectively
[129]	NA	148333 patients with alcoholic cirrhosis	NA	Meta-analysis	Cumulative incidence: 1%, 2%, 3%, and 9% at 1, 3, 5, and 10 years, respectively
[131]	China	1095 patients with decompensated cirrhosis	2014-2019	Retrospective cohort study	Incidence: 3.92% in alcoholic cirrhosis
[132]	China	1515 patients with cirrhosis with alcoholism or/and HBV infection	2005-2020 (with follow-up until June 30, 2021)	Retrospective cohort study	Annual incidence: 3.5% (5.9%, 3.6%, and 2.9% in HBV plus alcoholism, HBV only and alcoholism only patients, respectively)

HCC: Hepatocellular carcinoma; US: United States; NAFLD: Nonalcoholic fatty liver disease; HCV: Hepatitis C virus; ALD: Alcoholic liver disease; NA: Not available; HBV: Hepatitis B virus; ETV: Entecavir; PBC: Primary biliary cholangitis; UDCA: Ursodeoxycholic acid.

Table 4 Latest global epidemiological features of cirrhosis

Ref.	Epidemiological figures	Latest research	Type or etiology of cirrhosis	Reported data
Prevalence
[6]	Age-standardized prevalence	GBD 2017	Cirrhosis	Compensated cirrhosis: 1395.0 (1323.5-1470.5); decompensated cirrhosis: 132.5 (128.6-136.2) per 100000
[6]	Age-standardized prevalence	GBD 2017	HBV-related cirrhosis	Compensated cirrhosis: 451.9 (420.0-485.9); decompensated cirrhosis: 36.6 (34.7-38.4)
[6]	Age-standardized prevalence	GBD 2017	HCV-related cirrhosis	Compensated cirrhosis: 341.1 (314.1-368.7); decompensated cirrhosis: 32.5 (30.6-34.5)
[6]	Age-standardized prevalence	GBD 2017	Alcohol-related cirrhosis	Compensated cirrhosis: 288.1 (267.5-311.3); decompensated cirrhosis: 30.0 (28.2-31.8)
[6]	Age-standardized prevalence	GBD 2017	NASH-related cirrhosis	Compensated cirrhosis: 115.5 (105.0-126.5); decompensated cirrhosis: 11.3 (10.4-12.1)
Incidence
[24]	Age-standardized incidence	GBD 2017	NASH-related cirrhosis	4.81 (4.38-5.28)
[26]	Age-standardized incidence	GBD 2019	HBV-related cirrhosis	4.91 (3.50-6.50)
[26]	Age-standardized incidence	GBD 2019	HCV-related cirrhosis	6.7 (5.0-8.6)
Mortality
[26]	Age-standardized Mortality	GBD 2019	HBV-related cirrhosis	4.03 (3.39-4.76)
[26]	Age-standardized Mortality	GBD 2019	HCV-related cirrhosis	4.82 (4.09-5.57)
[25]	Age-standardized mortality	GBD 2017	NASH-related cirrhosis	1.5 (1.3-1.6)
Public health burden
[52]	DALYs	GBD 2019	HBV-related cirrhosis	129.8 (95%CI 108.3-153.0)
[52]	DALYs	GBD 2019	HCV-related cirrhosis	146.2 (124.4-169.8)

GBD: Global burden of diseases, injuries, and risk factors study; HBV: Hepatitis B virus; HCV: Hepatitis C virus; UI: Uncertainty interval; CI: Confidence interval; NASH: Nonalcoholic steatohepatitis; DALYs: Disability-adjusted life-years.