본문 바로가기
KERD
논문KCI 등재

Subclinical versus advanced forms of alcohol-related liver disease: Need for early detection

Ramón Bataller|Concepción Gómez-Medina|Luma Melo|David Martí-Aguado
대한간학회 (The korean Association for the Study of the Liver)|2023.02|Clinical and Molecular Hepatology|제29권 제1호|pp. 1-15

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

HepatitisAlcoholicLiver diseases

초록

Alcohol-related liver disease (ALD) consists of a wide spectrum of clinical manifestations and pathological features, ranging from asymptomatic patients to decompensated cirrhosis and hepatocellular carcinoma. Patients with heavy alcohol intake and advanced fibrosis often develop a subacute form of liver failure called alcohol-induced hepatitis (AH). Globally, most patients with ALD are identified at late stages of the disease, limiting therapeutic interventions. Thus, there is a need for early detection of ALD patients, which is lacking in most countries. The identification of alcohol misuse is hampered by the existence of alcohol underreporting by many patients. There are useful biomarkers that can detect recent alcohol use. Moreover, there are several non-invasive techniques to assess the presence of advanced fibrosis among patients with alcohol misuse, which could identify patients at high risk of liver related events or early death. In this review, we discuss differences between early stages of ALD and AH as the cornerstone of advanced forms. A global overview of epidemiological, anthropometric, clinical, analytical, histological, and molecular differences is summarized in this article. We propose that campaigns aimed at identifying patients with subclinical forms can prevent the development of life-threatening forms.

Abstract

Alcohol-related liver disease (ALD) consists of a wide spectrum of clinical manifestations and pathological features, ranging from asymptomatic patients to decompensated cirrhosis and hepatocellular carcinoma. Patients with heavy alcohol intake and advanced fibrosis often develop a subacute form of liver failure called alcohol-induced hepatitis (AH). Globally, most patients with ALD are identified at late stages of the disease, limiting therapeutic interventions. Thus, there is a need for early detection of ALD patients, which is lacking in most countries. The identification of alcohol misuse is hampered by the existence of alcohol underreporting by many patients. There are useful biomarkers that can detect recent alcohol use. Moreover, there are several non-invasive techniques to assess the presence of advanced fibrosis among patients with alcohol misuse, which could identify patients at high risk of liver related events or early death. In this review, we discuss differences between early stages of ALD and AH as the cornerstone of advanced forms. A global overview of epidemiological, anthropometric, clinical, analytical, histological, and molecular differences is summarized in this article. We propose that campaigns aimed at identifying patients with subclinical forms can prevent the development of life-threatening forms.

참고문헌 (115)

  1. Global status report on alcohol and health 2018, "World Health Organization", World Health Organization, ~ (2019)
  2. Argemi J, "Alcoholicrelated liver disease : pathogenesis, management and future therapeutic developments", Rev Esp Enferm Dig, 112, pp.869~878 (2020)
  3. Bataller R, "Liver fibrosis in alcoholic liver disease", Semin Liver Dis, 35, pp.146~156 (2015)
  4. Lackner C, "Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease", J Hepatol, 66, pp.610~618 (2017)
  5. Seitz HK, "Alcoholic liver disease", Nat Rev Dis Primers, 4, pp.16~ (2018)
  6. Gao B, "Alcoholic liver disease : pathogenesis and new therapeutic targets", Gastroenterology, 141, pp.1572~1585 (2011)
  7. Mathurin P, "Trends in the management and burden of alcoholic liver disease", J Hepatol, 62(1 Suppl), pp.S38~S46 (2015)
  8. Felix Stickel, "Pathophysiology and Management of Alcoholic Liver Disease: Update 2016", Gut and Liver, 11(2), pp.173~188 (2017), 거트앤리버 소화기연관학회협의회
  9. Seitz HK, "The history of alcoholic liver disease : from an unrecognized disease to one of the most frequent diseases in hepatology", J Clin Med, 10, pp.858~ (2021)
  10. Shah ND, "Alcohol-related liver disease is rarely detected at early stages compared with liver diseases of other etiologies worldwide", Clin Gastroenterol Hepatol, 17, pp.2320~2329 (2019)
  11. Parker R, "Natural history of histologically proven alcohol-related liver disease : a systematic review", J Hepatol, 71, pp.586~593 (2019)
  12. Simon TG, "Mortality in biopsy-confirmed nonalcoholic fatty liver disease : results from a nationwide cohort", Gut, 70, pp.1375~1382 (2021)
  13. Singal AK, "ACG clinical guideline : alcoholic liver disease", Am J Gastroenterol, 113, pp.175~194 (2018)
  14. Crabb DW, "Diagnosis and treatment of alcohol-associated liver diseases : 2019 practice guidance from the American Association for the Study of Liver Diseases", Hepatology, 71, pp.306~333 (2020)
  15. Bruha R, "Alcoholic liver disease", World J Hepatol, 4, pp.81~90 (2012)
  16. Marti-Aguado D, "Digital pathology : accurate technique for quantitative assessment of histological features in metabolic-associated fatty liver disease", Aliment Pharmacol Ther, 53, pp.160~171 (2021)
  17. Israelsen M, "Collagen proportionate area predicts clinical outcomes in patients with alcohol-related liver disease", Aliment Pharmacol Ther, 52, pp.1728~1739 (2020)
  18. Shah ND, "Worldwide lack of early referral of patients with alcoholic liver disease : results of the global alcoholic liver disease survey(GLADIS)", J Hepatol, 66(Supplement 1), pp.S107~S108 (2017)
  19. Ventura-Cots M, "Clinical, histological and molecular profiling of different stages of alcohol-related liver disease", Gut, 71, pp.1856~1866 (2022)
  20. Cortez-Pinto H, "Nonalcoholic steatohepatitis--a long-term follow-up study : comparison with alcoholic hepatitis in ambulatory and hospitalized patients", Dig Dis Sci, 48, pp.1909~1913 (2003)
  21. Bouchier IA, "A prospective study of alcoholic liver disease and mortality", J Hepatol, 16, pp.290~297 (1992)
  22. Chedid A, "Prognostic factors in alcoholic liver disease. VA Cooperative Study Group", Am J Gastroenterol, 86, pp.210~216 (1991)
  23. Altamirano J, "A histologic scoring system for prognosis of patients with alcoholic hepatitis", Gastroenterology, 146, pp.1231~1239 (2014)
  24. Dominguez M, "Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis", Gastroenterology, 136, pp.1639~1650 (2009)
  25. Affò S, "Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis", Gut, 62, pp.452~460 (2013)
  26. Lanthier N, "Hepatic cell proliferation plays a pivotal role in the prognosis of alcoholic hepatitis", J Hepatol, 63, pp.609~621 (2015)
  27. Lackner C, "Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease", J Hepatol, 75, pp.810~819 (2021)
  28. Crabb DW, "Standard definitions and common data elements for clinical trials in patients with alcoholic hepatitis : recommendation from the NIAAA alcoholic hepatitis consortia", Gastroenterology, 150, pp.785~790 (2016)
  29. American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders" (2013), American Psychiatric Association
  30. Saunders JB, "Development of the alcohol use disorders identification test(AUDIT) : WHO collaborative project on early detection of persons with harmful alcohol consumption--II", Addiction, 88, pp.791~804 (1993)
  31. Bush K, "The AUDIT alcohol consumption questions(AUDIT-C) : an effective brief screening test for problem drinking. Ambulatory care quality improvement project(ACQUIP). Alcohol use disorders identification test", Arch Intern Med, 158, pp.1789~1795 (1998)
  32. Fiellin DA, "Screening for alcohol problems in primary care : a systematic review", Arch Intern Med, 160, pp.1977~1989 (2000)
  33. Saitz R, "Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial", JAMA, 272, pp.519~523 (1994)
  34. Baraona E, "Alcoholic hepatomegaly : accumulation of protein in the liver", Science, 190, pp.794~795 (1975)
  35. Mendenhall CL, "Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans administration cooperative study group on alcoholic hepatitis", Am J Med, 76, pp.211~222 (1984)
  36. Litten RZ, "Alcohol biomarkers in applied settings : recent advances and future research opportunities", Alcohol Clin Exp Res, 34, pp.955~967 (2010)
  37. Cabezas J, "Biomarkers for monitoring alcohol use", Clin Liver Dis(Hoboken), 8, pp.59~63 (2016)
  38. Sterneck M, "Determination of ethyl glucuronide in hair improves evaluation of long-term alcohol abstention in liver transplant candidates", Liver Int, 34, pp.469~476 (2014)
  39. Stewart SH, "Validation of blood phosphatidylethanol as an alcohol consumption biomarker in patients with chronic liver disease", Alcohol Clin Exp Res, 38, pp.1706~1711 (2014)
  40. Fleming MF, "A review of genetic, biological, pharmacological, and clinical factors that affect carbohydratedeficient transferrin levels", Alcohol Clin Exp Res, 28, pp.1347~1355 (2004)
  41. Hrubec Z, "Evidence of genetic predisposition to alcoholic cirrhosis and psychosis : twin concordances for alcoholism and its biological end points by zygosity among male veterans", Alcohol Clin Exp Res, 5, pp.207~215 (1981)
  42. Reed T, "Genetic predisposition to organ-specific endpoints of alcoholism", Alcohol Clin Exp Res, 20, pp.1528~1533 (1996)
  43. Whitfield JB, "Brief report : genetics of alcoholic cirrhosis-GenomALC multinational study", Alcohol Clin Exp Res, 39, pp.836~842 (2015)
  44. Poynard T, "Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups", Lancet, 349, pp.825~832 (1997)
  45. Bedogni G, "Natural course of chronic HCV and HBV infection and role of alcohol in the general population : the Dionysos study", Am J Gastroenterol, 103, pp.2248~2253 (2008)
  46. Novo-Veleiro I, "Alcoholic liver disease and hepatitis C virus infection", World J Gastroenterol, 22, pp.1411~1420 (2016)
  47. Iida-Ueno A, "Hepatitis B virus infection and alcohol consumption", World J Gastroenterol, 23, pp.2651~2659 (2017)
  48. Åberg F, "Binge drinking and the risk of liver events : a population-based cohort study", Liver Int, 37, pp.1373~1381 (2017)
  49. Pose E, "Interaction between metabolic syndrome and alcohol consumption, risk factors of liver fibrosis : a population-based study", Liver Int, 41, pp.1556~1564 (2021)
  50. Thiele M, "Accuracy of the enhanced liver fibrosis test vs fibrotest, elastography, and indirect markers in detection of advanced fibrosis in patients with alcoholic liver disease", Gastroenterology, 154, pp.1369~1379 (2018)
  51. Chrostek L, "Liver fibrosis markers in alcoholic liver disease", World J Gastroenterol, 20, pp.8018~8023 (2014)
  52. Mueller S, "Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease", Liver Int, 35, pp.2514~2521 (2015)
  53. Pavlov CS, "Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease", Cochrane Database Syst Rev, 1, pp.CD010542~ (2015)
  54. Thiele M, "Controlled attenuation parameter and alcoholic hepatic steatosis : diagnostic accuracy and role of alcohol detoxification", J Hepatol, 68, pp.1025~1032 (2018)
  55. Rasmussen DN, "Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease", J Hepatol, 75, pp.1017~1025 (2021)
  56. Ferraioli G, "Point shear wave elastography method for assessing liver stiffness", World J Gastroenterol, 20, pp.4787~4796 (2014)
  57. Cho Y, "Point shear wave elastography predicts fibrosis severity and steatohepatitis in alcohol-related liver disease", Hepatol Int, 14, pp.270~280 (2020)
  58. Trebicka J, "Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease", Gut, 71, pp.402~414 (2022)
  59. Marti-Aguado D, "Magnetic resonance imaging analysis of liver fibrosis and inflammation: overwhelming gray zones restrict clinical use", Abdom Radiol (NY), 45, pp.3557~3568 (2020)
  60. Selvaraj EA, "Diagnostic accuracy of elastography and magnetic resonance imaging in patients with NAFLD : a systematic review and meta-analysis", J Hepatol, 75, pp.770~785 (2021)
  61. Chen HW, "Computed tomography-based radiomics identifies novel prognostic factors in alcohol associated hepatitis", AASLD The Liver Meeting; (2020)
  62. European Association for the Study of Liver, "EASL clinical practical guidelines : management of alcoholic liver disease", J Hepatol, 57, pp.399~420 (2012)
  63. Ventura-Cots M, "Histological and molecular profiling reveals ductular reaction as a driver of portal hypertension in patients with alcohol-associated hepatitis", AASLD The Liver Meeting; (2020)
  64. Dubois M, "Histologic parameter score does not predict short-term survival in severe alcoholic hepatitis", United European Gastroenterol J, 8, pp.1003~1012 (2020)
  65. Arab JP, "Alcohol-related liver disease : clinical practice guidelines by the Latin American Association for the study of the liver(ALEH)", Ann Hepatol, 18, pp.518~535 (2019)
  66. Maddrey WC, "Corticosteroid therapy of alcoholic hepatitis", Gastroenterology, 75, pp.193~199 (1978)
  67. Kamath PS, "The model for end-stage liver disease(MELD)", Hepatology, 45, pp.797~805 (2007)
  68. Forrest EH, "Analysis of factors predictive of mortality in alcoholic hepatitis and derivation and validation of the Glasgow alcoholic hepatitis score", Gut, 54, pp.1174~1179 (2005)
  69. Gholam PM, "Prognosis and prognostic scoring models for alcoholic liver disease and acute alcoholic hepatitis", Clin Liver Dis, 20, pp.491~497 (2016)
  70. Dominguez M, "A new scoring system for prognostic stratification of patients with alcoholic hepatitis", Am J Gastroenterol, 103, pp.2747~2756 (2008)
  71. Dunn W, "MELD accurately predicts mortality in patients with alcoholic hepatitis", Hepatology, 41, pp.353~358 (2005)
  72. Arraez DM, "A large worldwide study shows that meld is the best scoring system to predict mortality in alcoholassociated hepatitis", AASLD The Liver Meeting; (2020)
  73. Louvet A, "The Lille model : a new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids", Hepatology, 45, pp.1348~1354 (2007)
  74. Altamirano J, "Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis", Clin Gastroenterol Hepatol, 10, pp.65~71 (2012)
  75. Sujan R, "A validated score predicts acute kidney injury and survival in patients with alcoholic hepatitis", Liver Transpl, 24, pp.1655~1664 (2018)
  76. Fernandez-Carrillo C, "Identification of interleukin-18 as a specific urine biomarler of acute kidney injury in patients with alcohol-associated hepatitis", AASLD The Liver Meeting; (2020)
  77. Degré D, "Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey’s discriminant function <32", J Hepatol, 72, pp.636~642 (2020)
  78. Clemente A, "Early alcohol relapse after an episode of alcohol-induced hepatitis (AH): prevalence, impact on liver function, genetic and non-genetic factors and identification of distinct risk profiles", AASLD The Liver Meeting (2020)
  79. Arab JP, "Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis : a worldwide study", J Hepatol, 75, pp.1026~1033 (2021)
  80. Louvet A, "Corticosteroids reduce risk of death within 28 days for patients with severe alcoholic hepatitis, compared with pentoxifylline or placebo-a meta-analysis of individual data from controlled trials", Gastroenterology, 155, pp.458~468 (2018)
  81. Cho Y, "Efficacy of granulocyte colony stimulating factor in patients with severe alcoholic hepatitis with partial or null response to steroid(GRACIAH trial) : study protocol for a randomized controlled trial", Trials, 19, pp.696~ (2018)
  82. Shasthry SM, "Efficacy of granulocyte colony-stimulating factor in the management of steroid-nonresponsive severe alcoholic hepatitis : a double-blind randomized controlled trial", Hepatology, 70, pp.802~811 (2019)
  83. Louvet A, "Combination of amoxicillin", clavulanate and prednisolone in severe alcoholic hepatitis : results of the randomized controlled trial Antibiocor, 2021, pp.2021, S201~S202
  84. Bajaj JS, "A randomized clinical trial of fecal microbiota transplant for alcohol use disorder", Hepatology, 73, pp.1688~1700 (2021)
  85. McClain CJ, "DUR-928 therapy for acute alcoholic hepatitis : a pilot study", Hepatology, 70, pp.1483~1484 (2019)
  86. Arab JP, "An open-label, dose-escalation study to assess the safety and efficacy of il-22 agonist f-652 in patients with alcoholassociated hepatitis", Hepatology, 72, pp.441~453 (2020)
  87. Mathurin P, "Early liver transplantation for severe alcoholic hepatitis", N Engl J Med, 365, pp.1790~1800 (2011)
  88. Singal AK, "Outcomes after liver transplantation for alcoholic hepatitis are similar to alcoholic cirrhosis : exploratory analysis from the UNOS database", Hepatology, 55, pp.1398~1405 (2012)
  89. Im GY, "Early liver transplantation for severe alcoholic hepatitis in the United States--a single-center experience", Am J Transplant, 16, pp.841~849 (2016)
  90. Lee BP, "Three-year results of a pilot program in early liver transplantation for severe alcoholic hepatitis", Ann Surg, 265, pp.20~29 (2017)
  91. Ronis MJ, "The role of ethanol metabolism in development of alcoholic steatohepatitis in the rat", Alcohol, 44, pp.157~169 (2010)
  92. Jiang Y, "Alcohol metabolizing enzymes, microsomal ethanol oxidizing system, cytochrome P450 2E1, catalase, and aldehyde dehydrogenase in alcohol-associated liver disease", Biomedicines, 8, pp.50~ (2020)
  93. Crabb DW, "Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology", Proc Nutr Soc, 63, pp.49~63 (2004)
  94. Arab JP, "Gut-liver axis, cirrhosis and portal hypertension : the chicken and the egg", Hepatol Int, 12(Suppl 1), pp.24~33 (2018)
  95. Petrasek J, "IL-1 receptor antagonist ameliorates inflammasomedependent alcoholic steatohepatitis in mice", J Clin Invest, 122, pp.3476~3489 (2012)
  96. Idalsoaga F, "Nonalcoholic fatty liver disease and alcohol-related liver disease:two intertwined entities", Front Med(Lausanne), 7, pp.448~ (2020)
  97. Chedid A, "The immunology of fibrogenesis in alcoholic liver disease", Arch Pathol Lab Med, 128, pp.1230~1238 (2004)
  98. Lackner C, "Fibrosis and alcohol-related liver disease", J Hepatol, 70, pp.294~304 (2019)
  99. Bataller R, "Liver fibrosis", J Clin Invest, 115, pp.209~218 (2005)
  100. Setshedi M, "Acetaldehyde adducts in alcoholic liver disease", Oxid Med Cell Longev, 3, pp.178~185 (2010)
  101. Zhu H, "Oxidative stress and redox signaling mechanisms of alcoholic liver disease : updated experimental and clinical evidence", J Dig Dis, 13, pp.133~142 (2012)
  102. Yi HS, "Alcohol dehydrogenase III exacerbates liver fibrosis by enhancing stellate cell activation and suppressing natural killer cells in mice", Hepatology, 60, pp.1044~1053 (2014)
  103. Notas G, "NK and NKT cells in liver injury and fibrosis", Clin Immunol, 130, pp.16~26 (2009)
  104. Argemi J, "Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis", Nat Commun, 10, pp.3126~ (2019)
  105. European Association for Study of Liver, "EASL-ALEH clinical practice guidelines : non-invasive tests for evaluation of liver disease severity and prognosis", J Hepatol, 63, pp.237~264 (2015)
  106. Madsen BS, "Prediction of liver fibrosis severity in alcoholic liver disease by human microfibrillar-associated protein 4", Liver Int, 40, pp.1701~1712 (2020)
  107. Prystupa A, "Analysis of novel serum markers of fibrosis and angiogenesis in patients with alcoholic liver cirrhosis", Ann Agric Environ Med, 27, pp.568~573 (2020)
  108. Bianco C, "Genetic predisposition similarities between NASH and ASH : identification of new therapeutic targets", JHEP Rep, 3, pp.100284~ (2021)
  109. Whitfield JB, "A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers", J Hepatol, 76, pp.275~282 (2022)
  110. Vatsalya V, "Keratin 18 is a diagnostic and prognostic factor for acute alcoholic hepatitis", Clin Gastroenterol Hepatol, 18, pp.2046~2054 (2020)
  111. Hu K, "Lipoprotein Z, a hepatotoxic lipoprotein, predicts outcome in alcohol-associated hepatitis", Hepatology, 75, pp.968~982 (2022)
  112. Duan Y, "Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease", Nature, 575, pp.505~511 (2019)
  113. Guldiken N, "Serum transferrin as a biomarker of hepatocyte nuclear factor 4 alpha activity and hepatocyte function in liver diseases", BMC Med, 19, pp.39~ (2021)
  114. Michelena J, "Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis", Hepatology, 62, pp.762~772 (2015)
  115. Momen-Heravi F, "Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis", J Transl Med, 13, pp.261~ (2015)

관련 논문AI추천

Alcohol-associated liver disease: Natural history, management and novel targeted therapiesAna Clemente-Sánchez, Edilmar Alvarado-Tapias, Elisa Pose, Hugo López-Pelayo, Jordi Gratacós-Ginès, Ramón Bataller대한간학회 · Clinical and Molecular Hepatology2025 · 제31권 제2호Pathophysiology and Management of Alcoholic Liver Disease: Update 2016Christian Datz, Felix Stickel, Jochen Hampe, Ramon Bataller거트앤리버 소화기연관학회협의회 · Gut and Liver2017 · 제11권 제2호Misclassification of Alcohol Use Disorder in MASLD and MetALD: Prevalence, Clinical Characteristics, and OutcomesAhn Sung-Ho, Jeon So Young, Jun Dae Won, Lee Hye Sun, Lee Jun-Hyuk, Park Jimin, Yoon Eileen L.거트앤리버 소화기연관학회협의회 · Gut and Liver2025 · 제19권 제5호Plasma Levels of K18 Fragments Do Not Correlate with Alcoholic Liver FibrosisChristian Datz, Christina Kihm, Felix Stickel, Jochen Hampe, Mathias Worni, Matteo Montani, Viola Schlossberger거트앤리버 소화기연관학회협의회 · Gut and Liver2019 · 제13권 제1호Prognostic Value of the Alcoholic Hepatitis Histologic Score in Korean Patients with Biopsy-Proven Alcoholic HepatitisByeong Gwan Kim, Dong Hyeon Lee, Jeong Mo Bae, Kook Lae Lee, Mee Soo Chang, Sae Kyung Joo, Won Kim, Yong Jin Jung, Youn I Choi거트앤리버 소화기연관학회협의회 · Gut and Liver2020 · 제14권 제5호Programmed cell death in alcohol-associated liver diseaseLaura E. Nagy, Tatsunori Miyata대한간학회 · Clinical and Molecular Hepatology2020 · 제26권 제4호

이 간행물의 다른 논문 (46건)

PrefaceYoon Jun Kimpp. 2-2PrefaceSeung Up Kimpp. 3-3Non-alcoholic fatty liver disease: Definition and subtypesSeul Ki Han, 김문영, 백순구pp. 5-16Management of refractory ascitesFlorence Wongpp. 16-32Wnt signaling in liver regeneration, disease, and cancerJae-Il Park, Gengyi Zoupp. 33-50
원문 보기