Cirrhosis epidemiology and demographics: Difference between revisions

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{{Cirrhosis}}
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==Overview==
==Overview==
The most common cause of cirrhosis in the United States is chronic and heavy [[alcohol]] use, while the most common cause of cirrhosis worldwide is the [[hepatitis]] virus. Cirrhosis and [[chronic liver disease]] is the 12th leading cause of death in United States.
The most common cause of cirrhosis in the United States is chronic and heavy [[alcohol]] use, while the most common cause of cirrhosis worldwide and in Asian countries is the [[hepatitis]] virus. The gender that is most commonly affected by cirrhosis varies, depending upon the [[etiology]]. The [[incidence]] of cirrhosis increases with age; the median age of diagnosis of cirrhosis due to [[alcoholic liver disease]] is 52 years. The median age of diagnosis of cryptogenic/[[Non-alcoholic fatty liver disease|NAFLD]]/[[Non-alcoholic fatty liver disease|NASH]] cirrhosis is 60 years.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
===Incidence===
*The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
*In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
===Prevalence===
===Prevalence===
*The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
* In 2015, the [[prevalence]] of cirrhosis was approximately 270 per 100,000 individuals in the United States.<ref name="pmid25291348">{{cite journal |vauthors=Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, Volk ML |title=The Epidemiology of Cirrhosis in the United States: A Population-based Study |journal=J. Clin. Gastroenterol. |volume=49 |issue=8 |pages=690–6 |year=2015 |pmid=25291348 |doi=10.1097/MCG.0000000000000208 |url=}}</ref>  
*In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
*Currently, approximately seventy percent of cirrhotic individuals are unaware of having [[liver]] disease and go undiagnosed.
*The prevalence of [disease/malignancy] is estimated to be [number] cases annually.
*The [[prevalence]] of cirrhosis is higher in:
 
**Non-Hispanic blacks
* In 2001, cirrhosis was the tenth leading cause of death for men and the twelfth leading cause for women in the United States.<ref>Anderson RN, Smith BL. Deaths: leading causes for 2001. ''Natl Vital Stat Rep''2003;52:1-85. PMID 14626726.</ref>  
**Individuals below the poverty line
* The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.
**Mexican Americans
* In 2006, cirrhosis was the twelfth leading cause of deaths in United States.<ref>Heron MP, Hoyert DL, Murphy SL, Xu JQ, Kochanek KD, Tejada-Vera B. Deaths: Final data for 2006. National vital statistics reports; vol 57 no 14. Hyattsville, MD: National Center for Health Statistics. 2009.</ref>
**Areas with high illiteracy rates
* Established cirrhosis has a 10-year mortality of 34-66%, largely dependent on the cause of the cirrhosis.
*Chronic and heavy [[alcohol]] use is responsible for more than half of the cases of cirrhosis in the United States.<ref name="pmid25291348">{{cite journal |vauthors=Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, Volk ML |title=The Epidemiology of Cirrhosis in the United States: A Population-based Study |journal=J. Clin. Gastroenterol. |volume=49 |issue=8 |pages=690–6 |year=2015 |pmid=25291348 |doi=10.1097/MCG.0000000000000208 |url=}}</ref>
* Alcoholic cirrhosis has a worse prognosis than [[primary biliary cirrhosis]] and cirrhosis due to [[hepatitis]]. <ref>Sorensen HT, Thulstrup AM, Mellemkjar L, Jepsen P, Christensen E, Olsen JH, Vilstrup H. Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: a nationwide cohort study in Denmark. ''J Clin Epidemiol''2003;56:88-93. PMID 12589875.</ref>
*The cost of [[cirrhosis]] in terms of human suffering, hospital costs, and lost [[productivity]] is high.
* Hospital Inpatient Care: Number of discharges with chronic liver disease or cirrhosis as the first-listed diagnosis: 101,000[http://www.cdc.gov/nchs/fastats/liverdis.htm]
*The rate of developing [[hepatocellular carcinoma]] in cirrhotic patients is approximately 1%-4% per year.<ref name=":0">{{cite journal |author=Yu ML, Chuang WL |title=Treatment of chronic hepatitis C in Asia: when East meets West |journal=J. Gastroenterol. Hepatol. |volume=24 |issue=3 |pages=336–45 |year=2009 |pmid=19335784 |doi=10.1111/j.1440-1746.2009.05789.x |url=}},</ref>
* Mortality due to cirrhosis and chronic liver disease in US: 
'''Alcoholic cirrhosis:'''  
** Number of deaths: 30,558
* [[Cirrhosis|Alcoholic cirrhosis]] develops in 15% of individuals who drink heavily for more than a decade.   
** Deaths per 100,000 population: 10.0[http://www.cdc.gov/nchs/fastats/liverdis.htm]
* There is great variability in the amount of [[alcohol]] needed to cause cirrhosis (as little as 3-4 drinks a day in some men and 2-3 in some women).<ref name="urlIncidence rates of liver cirrhosis and related diseases in Baltimore and selected areas of the United States - ScienceDirect">{{cite web |url=https://www.sciencedirect.com/science/article/pii/0021968179901176 |title=Incidence rates of liver cirrhosis and related diseases in Baltimore and selected areas of the United States - ScienceDirect |format= |work= |accessdate=}}</ref>
* '''Alcoholic cirrhosis:''' Alcoholic cirrhosis develops in 15% of individuals who drink heavily for more than a decade.  There is great variability in the amount of [[alcohol]] needed to cause cirrhosis (as little as 3-4 drinks a day in some men and 2-3 in some women).
'''Chronic hepatitis B:'''  
* '''Chronic hepatitis B:''' The [[hepatitis B virus]] is probably the most common cause of cirrhosis worldwide, especially South-East Asia, but it is less common in the United States and the Western world.
* Chronic [[hepatitis B]] is the most common cause of cirrhosis worldwide, especially South-East Asia, but is less common in the United States.
* '''Primary biliary cirrhosis:''' In some areas of the US and UK the prevalence is estimated to be as high as 1 in 4000.
'''Primary biliary cirrhosis:'''
* '''Non alcoholic fatty liver disease:'''  [[Non alcoholic fatty liver disease]], in turn, may progress to [[fibrosis]] and, later, [[cirrhosis]]. Studies of serial [[liver biopsy|liver biopsies]] estimate a 26-37% rate of hepatic fibrosis and 2-15% rate of cirrhosis in less than 6 years. <ref>Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42(1):132–8.</ref><ref>Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease:a clinical histopathological study. Am J Gastroenterol 2003;98(9):2042–7.</ref><ref>Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73.</ref>
* In some areas of the US and UK, the [[prevalence]] is as high as 1 in 4000.
* '''[[Alpha 1-antitrypsin deficiency]]''':  Approximately 40 percent of adults with PI*ZZ have histologically significant liver injury and cirrhosis <ref>{{cite journal |author=Bals R |title=Alpha-1-antitrypsin deficiency |journal=Best Pract Res Clin Gastroenterol |volume=24 |issue=5 |pages=629–33 |year=2010 |pmid=20955965 |doi=10.1016/j.bpg.2010.08.006 |url=}}</ref>
'''Non alcoholic fatty liver disease (NAFLD):'''  <ref>Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42(1):132–8.</ref><ref>Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease:a clinical histopathological study. Am J Gastroenterol 2003;98(9):2042–7.</ref><ref>Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73.</ref>
Hepatopulmonary syndrome: has a prevalence of 4-47%.
* [[Non-alcoholic fatty liver disease|NAFLD]] has a 30 percent risk of [[fibrosis]]
 
* [[Non-alcoholic fatty liver disease|NAFLD]] has a 2-15% rate of cirrhosis in less than 6 years
Portopulmonary hypertension The prevalence is 2% in patients with cirrhosis.
'''Alpha 1-antitrypsin deficiency''':   
 
* Approximately 40 percent of adults with [[Zygosity|homozygosity]] of PIZZ have histologically significant [[liver]] injury and cirrhosis.<ref>{{cite journal |author=Bals R |title=Alpha-1-antitrypsin deficiency |journal=Best Pract Res Clin Gastroenterol |volume=24 |issue=5 |pages=629–33 |year=2010 |pmid=20955965 |doi=10.1016/j.bpg.2010.08.006 |url=}}</ref>  
Cirrhotic cardiomyopathy has 50% prevalence in cirrhotic patients.
'''Hepatopulmonary syndrom'''<nowiki/>e:
 
* [[Hepatopulmonary syndrome]] has a prevalence of 4-47% in cirrhotic patients.
'''Portopulmonary hypertension''':
* The prevalence of [[portopulmonary hypertension]] is 2% in patients with cirrhosis.  
'''Cirrhotic cardiomyopathy:'''
* The prevalence of cirrhotic [[cardiomyopathy]] is 50% in cirrhotic patients.
===Case-fatality rate/Mortality rate===
===Case-fatality rate/Mortality rate===
*In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate/mortality rate of [number range]%.
*The 10 year-[[mortality rate]] of cirrhosis is approximately 34- 66 percent, largely dependent on the cause of cirrhosis.
*The case-fatality rate/mortality rate of [disease name] is approximately [number range].
In 2001, cirrhosis was the tenth leading cause of death among men and the twelfth leading cause of death among women in the United States.<ref>Anderson RN, Smith BL. Deaths: leading causes for 2001. ''Natl Vital Stat Rep''2003;52:1-85. PMID 14626726.</ref>
 
* In 2006, cirrhosis was the twelfth leading cause of all deaths in United States.<ref>Heron MP, Hoyert DL, Murphy SL, Xu JQ, Kochanek KD, Tejada-Vera B. Deaths: Final data for 2006. National vital statistics reports; vol 57 no 14. Hyattsville, MD: National Center for Health Statistics. 2009.</ref>
===Age===
===Age===
*Patients of all age groups may develop [disease name].
*Cirrhosis is infrequently seen in young adults.
*The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
*The incidence of cirrhosis increases with age; the median age at diagnosis of cirrhosis due to [[alcoholic liver disease]] is 52 years.<ref name="pmid25203153">{{cite journal |vauthors=Sajja KC, Mohan DP, Rockey DC |title=Age and ethnicity in cirrhosis |journal=J. Investig. Med. |volume=62 |issue=7 |pages=920–6 |year=2014 |pmid=25203153 |pmc=4172494 |doi=10.1097/JIM.0000000000000106 |url=}}</ref>
*[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
*The median age of diagnosis of cryptogenic/[[Non-alcoholic fatty liver disease|NAFLD]]/[[Non-alcoholic fatty liver disease|NASH]] cirrhosis is 60 years.  
*[Chronic disease name] is usually first diagnosed among [age group].
*The median age of diagnosis of [[Autoimmune hepatitis|autoimmune]] cirrhosis is 43 years.  
*[Acute disease name] commonly affects [age group].


===Race===
===Race===
*There is no racial predilection to [disease name].
*The [[prevalence]] of cirrhosis is higher in: [http://www.natap.org/2005/AASLD/aasld_29.htm]<ref name="pmid25203153">{{cite journal |vauthors=Sajja KC, Mohan DP, Rockey DC |title=Age and ethnicity in cirrhosis |journal=J. Investig. Med. |volume=62 |issue=7 |pages=920–6 |year=2014 |pmid=25203153 |pmc=4172494 |doi=10.1097/JIM.0000000000000106 |url=}}</ref>
*[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
**Non-Hispanic blacks
**Mexican Americans
**Hispanics with [[hepatitis C]] infection
===Gender===
===Gender===
*[Disease name] affects men and women equally.
*The gender that is most commonly affected by cirrhosis varies, depending on the underlying [[etiology]].
*[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
'''Primary biliary cirrhosis''':
===Region===
*[[Primary biliary cirrhosis]] is more common in women.
*The majority of [disease name] cases are reported in [geographical region].
'''Chronic [[Hepatitis C]]''':
 
* The risk of cirrhosis after 20 years is estimated to be approximately 10%-15% for men and 1-5% for women.<ref name=":0" />
*[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
'''Non alcoholic fatty liver disease''':
 
* [[Non-alcoholic fatty liver disease]] is more common among men than women in all age groups until age 60.
* At 60 years of age, the prevalence of cirrhosis in males and females equalizes, due to absence of the protective nature of [[estrogen]].<ref name="Lobanova2009">{{cite journal|author=Lobanova YS, Scherbakov AM, Shatskaya VA, Evteev VA, Krasil’nikov MA|title=NF- kappaB suppression provokes the sensitization of hormone-resistant breast cancer cells to estrogen apoptosis|journal=Mol Cell Biochem|volume=324|year=2009}}</ref>
'''Autoimmune hepatitis''':
* [[Autoimmune hepatitis]] usually occurs in women in seventy percent of cases between the ages of 15 and 40.
'''Alpha1 antitrypsin deficiency''':
* Male gender and [[obesity]] may be risk factors for progression to advanced [[liver]] disease in adulthood among patients with severe [[Alpha 1-antitrypsin deficiency|AAT]] deficiency.<ref>{{cite journal |author=Bowlus CL, Willner I, Zern MA, ''et al.'' |title=Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=4 |pages=390–6 |year=2005 |pmid=15822045 |doi= |url=}}</ref>
===Developed Countries===
===Developed Countries===
* Chronic and heavy [[alcohol]] use is responsible for more than half of the cases of cirrhosis in the United States.


===Developing Countries===
===Developing Countries===
 
* Chronic [[hepatitis B]] is the most common cause of cirrhosis worldwide, especially South-East Asia, but is less common in the United States.
 
===Age===
* Cirrhosis is infrequently seen in young adults.
 
===Gender===
* '''Primary biliary cirrhosis''' :  [[Primary biliary cirrhosis]] is more common in women.
* '''Chronic [[Hepatitis C]]''':  Among those chronically infected, the risk of cirrhosis after 20 years varies between studies but has been estimated at ~10%-15% for men and ~1-5% for women. The reason for this difference is not known. Once cirrhosis is established, the rate of developing  [[hepatocellular carcinoma]] is ~1%-4% per year<ref>{{cite journal |author=Yu ML, Chuang WL |title=Treatment of chronic hepatitis C in Asia: when East meets West |journal=J. Gastroenterol. Hepatol. |volume=24 |issue=3 |pages=336–45 |year=2009 |month=March |pmid=19335784 |doi=10.1111/j.1440-1746.2009.05789.x |url=}},</ref>
* '''Non alcoholic fatty liver disease''':  [[Non-alcoholic fatty liver disease]] is also more common among men than women in all age groups until age 60, where the prevalence between sex equalize. This is due to the protective nature of [[estrogen]].<ref name="Lobanova2009">{{cite journal|author=Lobanova YS, Scherbakov AM, Shatskaya VA, Evteev VA, Krasil’nikov MA|title=NF- kappaB suppression provokes the sensitization of hormone-resistant breast cancer cells to estrogen apoptosis|journal=Mol Cell Biochem|volume=324|year=2009}}</ref>
* '''Autoimmune hepatitis''':  [[Autoimmune hepatitis]] usually occurs in women (70 %) between the ages of 15 and 40.
* '''[[Alpha1 antitrypsin deficiency]]''':  Male gender and obesity may be risk factors for progression to advanced liver disease in adulthood among patients with severe AAT deficiency.<ref>{{cite journal |author=Bowlus CL, Willner I, Zern MA, ''et al.'' |title=Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency |journal=Clin. Gastroenterol. Hepatol. |volume=3 |issue=4 |pages=390–6 |year=2005 |month=April |pmid=15822045 |doi= |url=}}</ref>
 
===Race===
* There is greater prevalence of cirrhosis in hispanics with [[hepatitis C]] infection than in caucasian or african american.[http://www.natap.org/2005/AASLD/aasld_29.htm]


==References==
==References==

Latest revision as of 18:24, 27 December 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2] Sudarshana Datta, MD [3]

Overview

The most common cause of cirrhosis in the United States is chronic and heavy alcohol use, while the most common cause of cirrhosis worldwide and in Asian countries is the hepatitis virus. The gender that is most commonly affected by cirrhosis varies, depending upon the etiology. The incidence of cirrhosis increases with age; the median age of diagnosis of cirrhosis due to alcoholic liver disease is 52 years. The median age of diagnosis of cryptogenic/NAFLD/NASH cirrhosis is 60 years.

Epidemiology and Demographics

Prevalence

  • In 2015, the prevalence of cirrhosis was approximately 270 per 100,000 individuals in the United States.[1]
  • Currently, approximately seventy percent of cirrhotic individuals are unaware of having liver disease and go undiagnosed.
  • The prevalence of cirrhosis is higher in:
    • Non-Hispanic blacks
    • Individuals below the poverty line
    • Mexican Americans
    • Areas with high illiteracy rates
  • Chronic and heavy alcohol use is responsible for more than half of the cases of cirrhosis in the United States.[1]
  • The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.
  • The rate of developing hepatocellular carcinoma in cirrhotic patients is approximately 1%-4% per year.[2]

Alcoholic cirrhosis:

  • Alcoholic cirrhosis develops in 15% of individuals who drink heavily for more than a decade.
  • There is great variability in the amount of alcohol needed to cause cirrhosis (as little as 3-4 drinks a day in some men and 2-3 in some women).[3]

Chronic hepatitis B:

  • Chronic hepatitis B is the most common cause of cirrhosis worldwide, especially South-East Asia, but is less common in the United States.

Primary biliary cirrhosis:

  • In some areas of the US and UK, the prevalence is as high as 1 in 4000.

Non alcoholic fatty liver disease (NAFLD): [4][5][6]

  • NAFLD has a 30 percent risk of fibrosis
  • NAFLD has a 2-15% rate of cirrhosis in less than 6 years

Alpha 1-antitrypsin deficiency:

  • Approximately 40 percent of adults with homozygosity of PIZZ have histologically significant liver injury and cirrhosis.[7]

Hepatopulmonary syndrome:

Portopulmonary hypertension:

Cirrhotic cardiomyopathy:

  • The prevalence of cirrhotic cardiomyopathy is 50% in cirrhotic patients.

Case-fatality rate/Mortality rate

  • The 10 year-mortality rate of cirrhosis is approximately 34- 66 percent, largely dependent on the cause of cirrhosis.

In 2001, cirrhosis was the tenth leading cause of death among men and the twelfth leading cause of death among women in the United States.[8]

  • In 2006, cirrhosis was the twelfth leading cause of all deaths in United States.[9]

Age

  • Cirrhosis is infrequently seen in young adults.
  • The incidence of cirrhosis increases with age; the median age at diagnosis of cirrhosis due to alcoholic liver disease is 52 years.[10]
  • The median age of diagnosis of cryptogenic/NAFLD/NASH cirrhosis is 60 years.
  • The median age of diagnosis of autoimmune cirrhosis is 43 years.

Race

Gender

  • The gender that is most commonly affected by cirrhosis varies, depending on the underlying etiology.

Primary biliary cirrhosis:

Chronic Hepatitis C:

  • The risk of cirrhosis after 20 years is estimated to be approximately 10%-15% for men and 1-5% for women.[2]

Non alcoholic fatty liver disease:

  • Non-alcoholic fatty liver disease is more common among men than women in all age groups until age 60.
  • At 60 years of age, the prevalence of cirrhosis in males and females equalizes, due to absence of the protective nature of estrogen.[11]

Autoimmune hepatitis:

  • Autoimmune hepatitis usually occurs in women in seventy percent of cases between the ages of 15 and 40.

Alpha1 antitrypsin deficiency:

  • Male gender and obesity may be risk factors for progression to advanced liver disease in adulthood among patients with severe AAT deficiency.[12]

Developed Countries

  • Chronic and heavy alcohol use is responsible for more than half of the cases of cirrhosis in the United States.

Developing Countries

  • Chronic hepatitis B is the most common cause of cirrhosis worldwide, especially South-East Asia, but is less common in the United States.

References

  1. ↑ 1.0 1.1 Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, Volk ML (2015). "The Epidemiology of Cirrhosis in the United States: A Population-based Study". J. Clin. Gastroenterol. 49 (8): 690–6. doi:10.1097/MCG.0000000000000208. PMID 25291348.
  2. ↑ 2.0 2.1 Yu ML, Chuang WL (2009). "Treatment of chronic hepatitis C in Asia: when East meets West". J. Gastroenterol. Hepatol. 24 (3): 336–45. doi:10.1111/j.1440-1746.2009.05789.x. PMID 19335784.,
  3. ↑ "Incidence rates of liver cirrhosis and related diseases in Baltimore and selected areas of the United States - ScienceDirect".
  4. ↑ Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42(1):132–8.
  5. ↑ Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease:a clinical histopathological study. Am J Gastroenterol 2003;98(9):2042–7.
  6. ↑ Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73.
  7. ↑ Bals R (2010). "Alpha-1-antitrypsin deficiency". Best Pract Res Clin Gastroenterol. 24 (5): 629–33. doi:10.1016/j.bpg.2010.08.006. PMID 20955965.
  8. ↑ Anderson RN, Smith BL. Deaths: leading causes for 2001. Natl Vital Stat Rep2003;52:1-85. PMID 14626726.
  9. ↑ Heron MP, Hoyert DL, Murphy SL, Xu JQ, Kochanek KD, Tejada-Vera B. Deaths: Final data for 2006. National vital statistics reports; vol 57 no 14. Hyattsville, MD: National Center for Health Statistics. 2009.
  10. ↑ 10.0 10.1 Sajja KC, Mohan DP, Rockey DC (2014). "Age and ethnicity in cirrhosis". J. Investig. Med. 62 (7): 920–6. doi:10.1097/JIM.0000000000000106. PMC 4172494. PMID 25203153.
  11. ↑ Lobanova YS, Scherbakov AM, Shatskaya VA, Evteev VA, Krasil’nikov MA (2009). "NF- kappaB suppression provokes the sensitization of hormone-resistant breast cancer cells to estrogen apoptosis". Mol Cell Biochem. 324.
  12. ↑ Bowlus CL, Willner I, Zern MA; et al. (2005). "Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency". Clin. Gastroenterol. Hepatol. 3 (4): 390–6. PMID 15822045.

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