Abstract
The concept that alcoholic liver disease (ALD) is as a toxic disease does not mirror the exact nature of the disease. ALD should be defined as an alcohol-associated lifestyle disease, the predisposition to which is largely governed by gene–environment interactions, much like other chronic diseases such as diabetes, atherosclerosis, and neurodegenerative diseases. The epidemiology and pathogenesis of ALD need to be re-addressed from this viewpoint. Specifically, the interactions between alcohol and secondary risk factors (high-fat diet, iron, tobacco, medications, female gender) and comorbidities (viral hepatitis, diabetes) are of urgent epidemiological importance. Molecular characterization of the interfaces of these interactions is essential for revelation or acquisition of new pathogenetic, preventive, and therapeutic insights.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Division of Epidemiological Surveillance and Health Situation and Trend Assessment Global Estimates for Health Situation. Assessment and Project. Geneva: World Health Organization; 1990
S Bellentani G Saccoccio G Costa C Tiribelli F Manenti M Sodde et al. (1997) ArticleTitleDrinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group Gut 41 845–50 Occurrence Handle9462221 Occurrence Handle1:STN:280:DyaK1c7itlOksQ%3D%3D Occurrence Handle10.1136/gut.41.6.845
FS Stinson BF Grant MC Dufour (2001) ArticleTitleThe critical dimension of ethnicity in liver cirrhosis mortality statistics Alcohol Clin Exp Res 25 1181–7 Occurrence Handle11505049 Occurrence Handle10.1111/j.1530-0277.2001.tb02333.x Occurrence Handle1:STN:280:DC%2BD3MvlvVOgsQ%3D%3D
H Harwood (2000) Updating estimates of the economic costs of alcohol abuse in the United States: estimates, update methods and data National Institute on Alcohol Abuse and Alcoholism Bethesda, MD
N Tao S Sussman J Nieto H Tsukamoto JM Yuan (2003) ArticleTitleDemographic characteristics of hospitalized patients with alcoholic liver disease and pancreatitis in Los Angeles County Alcohol Clin Exp Res 27 1798–804 Occurrence Handle14634496 Occurrence Handle10.1097/01.ALC.0000095862.30777.D9
CS Lieber LM DeCarli (1991) ArticleTitleHepatotoxicity of ethanol J Hepatol 12 394–401 Occurrence Handle1845298 Occurrence Handle10.1016/0168-8278(91)90846-4 Occurrence Handle1:CAS:528:DyaK3MXkvVKrsbg%3D
CS Lieber (1991) ArticleTitleMetabolism of ethanol and associated hepatotoxicity Drug Alcohol Rev 10 175–202 Occurrence Handle16840049 Occurrence Handle10.1080/09595239100185231 Occurrence Handle1:STN:280:DC%2BD28vhsl2htw%3D%3D
W Lelbach (1975) Quantitative aspects of drinking in alcoholic liver cirrhosis H Khanna Y Israel H Kalant (Eds) Alcoholic liver pathology Addiction Research Foundation of Ontario Toronto 1–18
M Ramstedt (2001) ArticleTitlePer capita alcohol consumption and liver cirrhosis mortality in 14 European countries Addiction 96 IssueIDSuppl 1 S19–33 Occurrence Handle11228075 Occurrence Handle10.1080/09652140020021152
T Sorensen M Orholm K Bensen G Hoybye K Eghoje P Christoffersen (1984) ArticleTitleProspective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis Lancet 2 241–4 Occurrence Handle6146805 Occurrence Handle10.1016/S0140-6736(84)90295-2 Occurrence Handle1:STN:280:DyaL2c3mvFCktw%3D%3D
TI Sorensen (1989) ArticleTitleAlcohol and liver injury: dose-related or permissive effect? Liver 9 189–97 Occurrence Handle2671569 Occurrence Handle1:STN:280:DyaL1MzmsVSmtA%3D%3D
M Kamper-Jorgensen M Gronbaek J Tolstrup U Becker (2004) ArticleTitleAlcohol and cirrhosis: dose-response or threshold effect? J Hepatol 41 25–30 Occurrence Handle15246203 Occurrence Handle10.1016/j.jhep.2004.03.002 Occurrence Handle1:CAS:528:DC%2BD2cXls1Wns7c%3D
S Bellentani C Tiribelli G Saccoccio M Sodde N Fratti Demartin Ceal (1994) ArticleTitlePrevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study Hepatology 20 1442–9 Occurrence Handle7982643 Occurrence Handle1:STN:280:DyaK2M%2FntlKrtQ%3D%3D Occurrence Handle10.1002/hep.1840200611
AL Klatsky MA Armstrong (1992) ArticleTitleAlcohol, smoking, coffee, and cirrhosis Am J Epidemiol 136 1248–57 Occurrence Handle1476147 Occurrence Handle1:STN:280:DyaK3s7hvVKguw%3D%3D
M Mukaiya M Nishi H Miyake K Hirata (1998) ArticleTitleChronic liver diseases for the risk of hepatocellular carcinoma: a case–control study in Japan. Etiologic association of alcohol consumption, cigarette smoking and the development of chronic liver diseases Hepatogastroenterology 45 2328–32 Occurrence Handle9951917 Occurrence Handle1:STN:280:DyaK1M7jsFerug%3D%3D
H Kuper A Tzonou E Kaklamani CC Hsieh P Lagiou HO Adami et al. (2000) ArticleTitleTobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma Int J Cancer 85 498–502 Occurrence Handle10699921 Occurrence Handle10.1002/(SICI)1097-0215(20000215)85:4<498::AID-IJC9>3.0.CO;2-F Occurrence Handle1:STN:280:DC%2BD3c7msVGltw%3D%3D
M Rotily JP Durbec P Berthezene H Sarles (1990) ArticleTitleDiet and alcohol in liver cirrhosis: a case–control study Eur J Clin Nutr 44 595–603 Occurrence Handle2209515 Occurrence Handle1:STN:280:DyaK3M%2FgsF2ltQ%3D%3D
C Mendenhall S Anderson R Weesner S Goldberg K Crolic (1984) ArticleTitleProtein-calorie malnutrition associated with alcoholic hepatitis. Veterans Administration Cooperative Study Group on Alcoholic Hepatitis Am J Med 76 211–22 Occurrence Handle6421159 Occurrence Handle10.1016/0002-9343(84)90776-9 Occurrence Handle1:STN:280:DyaL2c7isFertA%3D%3D
L Seeff B Cuccherini H Zimmerman E Adler S Benjamin (1986) ArticleTitleAcetaminophen hepatotoxicity in alcoholics. A therapeutic misadventure Ann Intern Med 104 339–404
S Naveau V Giraud E Borotto A Aubert F Capron JC Chaput (1997) ArticleTitleExcess weight risk factor for alcoholic liver disease Hepatology 25 108–11 Occurrence Handle8985274 Occurrence Handle10.1002/hep.510250120 Occurrence Handle1:STN:280:DyaK2s7jvVanug%3D%3D
B Raynard A Balian D Fallik F Capron P Bedossa JC Chaput et al. (2002) ArticleTitleRisk factors of fibrosis in alcohol-induced liver disease Hepatology 35 635–8 Occurrence Handle11870378 Occurrence Handle10.1053/jhep.2002.31782
M Peters N Terrault (2002) ArticleTitleAlcohol use and hepatitis C Hepatology 36 S220–5 Occurrence Handle12407597 Occurrence Handle10.1002/hep.1840360728
MM Hassan LY Hwang CJ Hatten M Swaim D Li JL Abbruzzese et al. (2002) ArticleTitleRisk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus Hepatology 36 1206–13 Occurrence Handle12395331 Occurrence Handle10.1053/jhep.2002.36780 Occurrence Handle1:CAS:528:DC%2BD38XovFaktr4%3D
G N'Kontchou J Paries MT Htar N Ganne-Carrie L Costentin V Grando-Lemaire et al. (2006) ArticleTitleRisk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis Clin Gastroenterol Hepatol 4 1062–8 Occurrence Handle16844421 Occurrence Handle10.1016/j.cgh.2006.05.013
M Vidali SF Stewart R Rolla AK Daly Y Chen E Mottaran et al. (2003) ArticleTitleGenetic and epigenetic factors in autoimmune reactions toward cytochrome P4502E1 in alcoholic liver disease Hepatology 37 410–9 Occurrence Handle12540792 Occurrence Handle10.1053/jhep.2003.50049 Occurrence Handle1:CAS:528:DC%2BD3sXhsFeltro%3D
AS Tavill AM Qadri (2004) ArticleTitleAlcohol and iron Semin Liver Dis 24 317–25 Occurrence Handle15349808 Occurrence Handle10.1055/s-2004-832943 Occurrence Handle1:CAS:528:DC%2BD2cXosVKmurc%3D
MS Aldrich KJ Brower JM Hall (1999) ArticleTitleSleep-disordered breathing in alcoholics Alcohol Clin Exp Res 23 134–40 Occurrence Handle10029214 Occurrence Handle1:CAS:528:DyaK1MXhtlagtL8%3D
U Becker A Deis TI Sorensen M Gronbaek K Borch-Johnsen CF Muller et al. (1996) ArticleTitlePrediction of risk of liver disease by alcohol intake, sex, and age: a prospective population study Hepatology 23 1025–9 Occurrence Handle8621128 Occurrence Handle10.1002/hep.510230513 Occurrence Handle1:STN:280:DyaK283gs1GhtQ%3D%3D
NM Wilfred de Alwis C Day (2007) ArticleTitleGenetics of alcoholic liver disease and nonalcoholic fatty liver disease Semin Liver Dis 27 44–54 Occurrence Handle17295176 Occurrence Handle10.1055/s-2006-960170 Occurrence Handle1:CAS:528:DC%2BD2sXjtlWrsLo%3D
JM Yuan S Govindarajan K Arakawa MC Yu (2004) ArticleTitleSynergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer 101 1009–17 Occurrence Handle15329910 Occurrence Handle10.1002/cncr.20427
H Tsukamoto SC Lu (2001) ArticleTitleCurrent concepts in the pathogenesis of alcoholic liver injury FASEB J 15 1335–49 Occurrence Handle11387231 Occurrence Handle10.1096/fj.00-0650rev Occurrence Handle1:CAS:528:DC%2BD3MXlvVersrw%3D
SC Lu ML Martinez-Chantar JM Mato (2006) ArticleTitleMethionine adenosyltransferase and S-adenosylmethionine in alcoholic liver disease J Gastroenterol Hepatol 21 IssueIDSuppl 3 S61–4 Occurrence Handle16958675 Occurrence Handle10.1111/j.1440-1746.2006.04575.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt7rL
S Barve S Joshi-Barve Z Song D Hill P Hote I Deaciuc et al. (2006) ArticleTitleInteractions of cytokines, S-adenosylmethionine, and S-adenosylhomocysteine in alcohol-induced liver disease and immune suppression J Gastroenterol Hepatol 21 IssueIDSuppl 3 S38–42 Occurrence Handle16958670 Occurrence Handle10.1111/j.1440-1746.2006.04590.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt73F
N Kaplowitz C Ji (2006) ArticleTitleUnfolding new mechanisms of alcoholic liver disease in the endoplasmic reticulum J Gastroenterol Hepatol 21 IssueIDSuppl 3 S7–9 Occurrence Handle16958678 Occurrence Handle10.1111/j.1440-1746.2006.04581.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt7zI
C Garcia-Ruiz JC Fernandez-Checa (2006) ArticleTitleMitochondrial glutathione: hepatocellular survival-death switch J Gastroenterol Hepatol 21 IssueIDSuppl 3 S3–6 Occurrence Handle16958667 Occurrence Handle10.1111/j.1440-1746.2006.04570.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt7zO
PH Park V Thakur MT Pritchard MR McMullen LE Nagy (2006) ArticleTitleRegulation of Kupffer cell activity during chronic ethanol exposure: role of adiponectin J Gastroenterol Hepatol 21 IssueIDSuppl 3 S30–3 Occurrence Handle16958668 Occurrence Handle10.1111/j.1440-1746.2006.04580.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt73J
H Tsukamoto M Lin M Ohata C Giulivi SW French G Brittenham (1999) ArticleTitleIron primes hepatic macrophages for NF-kappaB activation in alcoholic liver injury Am J Physiol 277 IssueID6 Pt 1 G1240–50 Occurrence Handle10600822 Occurrence Handle1:CAS:528:DC%2BD3cXhs1ygsg%3D%3D
S Xiong H She H Takeuchi B Han JF Engelhardt CH Barton et al. (2003) ArticleTitleSignaling role of intracellular iron in NF-kappaB activation J Biol Chem 278 17646–54 Occurrence Handle12637578 Occurrence Handle10.1074/jbc.M210905200 Occurrence Handle1:CAS:528:DC%2BD3sXjs1KisbY%3D
L Chen S Xiong H She SW Lin J Wang H Tsukamoto (2007) ArticleTitleIron causes interactions of TAK1, p21ras, and phosphatidylinositol 3-kinase in caveolae to activate IkappaB kinase in hepatic macrophages J Biol Chem 282 5582–8 Occurrence Handle17172471 Occurrence Handle10.1074/jbc.M609273200 Occurrence Handle1:CAS:528:DC%2BD2sXhvVaisbc%3D
DW Crabb S Liangpunsakul (2006) ArticleTitleAlcohol and lipid metabolism J Gastroenterol Hepatol 21 IssueIDSuppl 3 S56–60 Occurrence Handle16958674 Occurrence Handle10.1111/j.1440-1746.2006.04582.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt7rJ
D Tuma G Thiele D Xu L Klassen M Sorrell (1996) ArticleTitleAcetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration Hepatology 23 872–80 Occurrence Handle8666344 Occurrence Handle10.1002/hep.510230431 Occurrence Handle1:CAS:528:DyaK28XisFygt7c%3D
DJ Tuma (2002) ArticleTitleRole of malondialdehyde–acetaldehyde adducts in liver injury Free Radic Biol Med 32 303–8 Occurrence Handle11841919 Occurrence Handle10.1016/S0891-5849(01)00742-0 Occurrence Handle1:CAS:528:DC%2BD38XhtF2jt7w%3D
E Foy K Li C Wang R Sumpter SuffixJr M Ikeda SM Lemon et al. (2003) ArticleTitleRegulation of interferon regulatory factor-3 by the hepatitis C virus serine protease Science 300 1145–8 Occurrence Handle12702807 Occurrence Handle10.1126/science.1082604 Occurrence Handle1:CAS:528:DC%2BD3sXjslGqtro%3D
K Machida KT Cheng VM Sung AM Levine S Foung MM Lai (2006) ArticleTitleHepatitis C virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon and interleukin-6 J Virol 80 866–74 Occurrence Handle16378988 Occurrence Handle10.1128/JVI.80.2.866-874.2006 Occurrence Handle1:CAS:528:DC%2BD28XivVOqsg%3D%3D
T Wang SA Weinman (2006) ArticleTitleCauses and consequences of mitochondrial reactive oxygen species generation in hepatitis C J Gastroenterol Hepatol 21 IssueIDSuppl 3 S34–7 Occurrence Handle16958669 Occurrence Handle10.1111/j.1440-1746.2006.04591.x Occurrence Handle1:CAS:528:DC%2BD28Xht1Sgt73L
K Machida KT Cheng CK Lai KS Jeng VM Sung MM Lai (2006) ArticleTitleHepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation J Virol 80 7199–207 Occurrence Handle16809325 Occurrence Handle10.1128/JVI.00321-06 Occurrence Handle1:CAS:528:DC%2BD28XmvVaitL4%3D
Y Shintani H Fujie H Miyoshi T Tsutsumi K Tsukamoto S Kimura et al. (2004) ArticleTitleHepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance Gastroenterology 126 840–8 Occurrence Handle14988838 Occurrence Handle10.1053/j.gastro.2003.11.056 Occurrence Handle1:CAS:528:DC%2BD2cXivFCisLw%3D
K Koike (2006) ArticleTitleHepatitis C virus infection can present with metabolic disease by inducing insulin resistance Intervirology 49 51–7 Occurrence Handle16166789 Occurrence Handle10.1159/000087263 Occurrence Handle1:CAS:528:DC%2BD2MXhtVWntr7F
H Miyamoto K Moriishi K Moriya S Murata K Tanaka T Suzuki et al. (2007) ArticleTitleInvolvement of the PA28gamma-dependent pathway in insulin resistance induced by hepatitis C virus core protein J Virol 81 1727–35 Occurrence Handle17135326 Occurrence Handle10.1128/JVI.01683-06 Occurrence Handle1:CAS:528:DC%2BD2sXhslKjs7Y%3D
K Moriishi R Mochizuki K Moriya H Miyamoto Y Mori T Abe et al. (2007) ArticleTitleCritical role of PA28gamma in hepatitis C virus-associated steatogenesis and hepatocarcinogenesis Proc Natl Acad Sci USA 104 1661–6 Occurrence Handle17234812 Occurrence Handle10.1073/pnas.0607312104 Occurrence Handle1:CAS:528:DC%2BD2sXhslCns7w%3D
T Tsutsumi T Suzuki K Moriya Y Shintani H Fujie H Miyoshi et al. (2003) ArticleTitleHepatitis C virus core protein activates ERK and p38 MAPK in cooperation with ethanol in transgenic mice Hepatology 38 820–8 Occurrence Handle14512869 Occurrence Handle1:CAS:528:DC%2BD3sXovFGhtLc%3D
RG Thurman SuffixII (1998) ArticleTitleAlcoholic liver injury involves activation of Kupffer cells by endotoxin Am J Physiol 275 IssueID4 Pt 1 G605–11 Occurrence Handle9756487 Occurrence Handle1:CAS:528:DyaK1cXmsl2it7w%3D
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsukamoto, H. Conceptual importance of identifying alcoholic liver disease as a lifestyle disease. J Gastroenterol 42, 603–609 (2007). https://doi.org/10.1007/s00535-007-2075-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-007-2075-3