Alcohol-associated liver disease (ALD) is a leading cause of preventable cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality, yet current laboratory and imaging tools detect only late-stage disease. This narrative review synthesizes emerging evidence on novel biomarkers that capture the multidimensional pathophysiology of ALD and discusses their utility for routine clinical practice. Traditional serum-based liver fibrosis markers (e.g., cytokeratin-18 fragments, Pro-C3, the enhanced liver fibrosis test) improve non-invasive staging risk beyond aminotransferases, while elastography techniques, such as vibration-controlled transient elastography and magnetic resonance elastography, can also quantify liver stiffness with high precision. Among novel mechanistic biomarkers, genetic polymorphisms in PNPLA3, TM6SF2, MBOAT7, HSD17B13, and polygenic risk scores define lifetime risk, whereas sex-specific hormonal milieus also modify susceptibility and progression. Moreover, gut dysbiosis signatures, including reduced Faecalibacterium prausnitzii, Akkermansia muciniphila, and a lower Firmicutes/Bacteroidetes ratio, and their metabolites (short-chain fatty acids, and bile acids, trimethylamine N-oxide) correlate with liver inflammation and fibrosis. Endocrine imbalances of cortisol, testosterone, and thyroid hormones further stratify metabolic vulnerability. Ultimately, multi-omics platforms (i.e., transcriptomics, lipidomics, proteomics, metabolomics, and epigenomics) can reveal distinct molecular signatures that predict steatohepatitis, fibrogenesis, and early HCC. Integrating these biomarkers enables phase-specific enrichment strategies, earlier intervention windows, adaptive dose-finding, and mechanismbased endpoints in ALD trials. Remaining challenges include assay standardization, validation across diverse cohorts, and incorporation into regulatory frameworks. Future work could evaluate cost-effectiveness and feasibility in routine clinical practice. Widespread adoption promises earlier diagnosis, personalized risk reduction, and more efficient drug development for this globally prevalent disorder.
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Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Only 20% of heavy alcohol consumers develop alcoholic liver cirrhosis. The intestinal microbiota (IM) has been recently identified as a key player in the severity of liver injury in ALD. Common features of ALD include a decrease of gut epithelial tight junction protein expression, mucin production, and antimicrobial peptide levels. This disruption of the gut barrier, which is a prerequisite for ALD, leads to the passage of bacterial products into the blood stream (endotoxemia). Moreover, metabolites produced by bacteria, such as short chain fatty acids, volatile organic compounds (VOS), and bile acids (BA), are involved in ALD pathology. Probiotic treatment, IM transplantation, or the consumption of dietary fiber, such as pectin, which all alter the ratio of bacterial species, have been shown to improve liver injury in animal models of ALD and to be associated with an improvement in gut barrier function. Although the connections between the microbiota and the host in ALD are well established, the underlying mechanisms are still an active area of research. Targeting the microbiome through the use of prebiotic, probiotic, and postbiotic modalities could be an attractive new approach to manage ALD.
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Anemia appears frequently in patients with alcoholic liver disease (ALD) but has never been linked to bilateral nonarteritic anterior ischemic optic neuropathy (NAION). A 65-year-old woman with a medical history of alcoholic cirrhosis was admitted for bilateral NAION. On admission, she was found to have a low arterial pressure and severe normocytic anemia (48 g/L). The anemia was related to chronic bleeding due to antral gastritis along with other factors associated with ALD. The applied treatment consisted of urgent transfusion followed by high doses of proton-pump inhibitors, iron and vitamin supplementation, and support in lifestyle measures. Her hemoglobin levels remained stable after 2 years but the patient still suffered from visual loss. This case highlights the link between anemia and bilateral NAION in ALD patients. The optic nerve head is prone to infarction in this context due to the vascularization characteristics of ALD. Hemoglobin levels should be monitored in ALD patients to avoid the severe complication of NAION.
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The Role of Long Non-Coding RNAs (lncRNAs) in the Development and Progression of Fibrosis Associated with Nonalcoholic Fatty Liver Disease (NAFLD) Amanda Hanson, Danielle Wilhelmsen, Johanna K. DiStefano Non-Coding RNA.2018; 4(3): 18. CrossRef
Prebiotic and probiotic treatment of nonalcoholic fatty liver disease: a systematic review and meta-analysis Brett R Loman, Diego Hernández-Saavedra, Ruopeng An, R Scott Rector Nutrition Reviews.2018; 76(11): 822. CrossRef
Science, serendipity, and the single degree Helen H. Hobbs Journal of Clinical Investigation.2018; 128(10): 4218. CrossRef
Modulation of gut microbiome in nonalcoholic fatty liver disease: pro-, pre-, syn-, and antibiotics Min Seok Cho, Sang Yeol Kim, Ki Tae Suk, Byung-Yong Kim Journal of Microbiology.2018; 56(12): 855. CrossRef
Promoting genetics in non-alcoholic fatty liver disease: Combined risk score through polymorphisms and clinical variables Umberto Vespasiani-Gentilucci, Paolo Gallo, Chiara Dell’Unto, Mara Volpentesta, Raffaele Antonelli-Incalzi, Antonio Picardi World Journal of Gastroenterology.2018; 24(43): 4835. CrossRef
Nonalcoholic Fatty Liver Disease Progresses into Severe NASH when Physiological Mechanisms of Tissue Homeostasis Collapse Silvia Sookoian, Carlos J. Pirola Annals of Hepatology.2018; 17(2): 182. CrossRef
A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease Paola Dongiovanni, Luca Valenti International Journal of Molecular Sciences.2017; 18(7): 1534. CrossRef
Hígado graso no alcohólico: una pandemia poco conocida Salvador Augustin, Isabel Graupera, Juan Caballeria Medicina Clínica.2017; 149(12): 542. CrossRef
Isocaloric Dietary Changes and Non-Alcoholic Fatty Liver Disease in High Cardiometabolic Risk Individuals Giuseppe Della Pepa, Claudia Vetrani, Gianluca Lombardi, Lutgarda Bozzetto, Giovanni Annuzzi, Angela Rivellese Nutrients.2017; 9(10): 1065. CrossRef
What Is the Optimal Dietary Composition for NAFLD? Elena S. George, Audrey C. Tierney, Katrina L. Campbell, Graeme A. Macdonald, Ingrid J. Hickman Current Hepatology Reports.2017; 16(4): 346. CrossRef
Non-alcoholic fatty liver disease: A poorly known pandemic Salvador Augustin, Isabel Graupera, Juan Caballeria Medicina Clínica (English Edition).2017; 149(12): 542. CrossRef
Recompensation following first decompensation in patients with alcohol-related cirrhosis Ji Yoon Kwak, Hankyu Jeon, Hyeon Uk Kwon, Jae Eun Kim, Ji Hee Han, Jung Woo Choi, Ra Ri Cha, Jae Min Lee, Sang Soo Lee BMC Gastroenterology.2026;[Epub] CrossRef
Aetiology of chronic liver disease is a valuable factor for stratifying adverse outcomes of acute decompensation: prospective observational study Jung Hee Kim, Sung-Eun Kim, Do Seon Song, Hee Yeon Kim, Eileen L. Yoon, Ji Won Park, Tae Hyung Kim, Young-Kul Jung, Ki Tae Suk, Hyung Joon Yim, Jung Hyun Kwon, Sung Won Lee, Seong Hee Kang, Moon Young Kim, Soung Won Jeong, Jae-Young Jang, Jeong Ju Yoo, Sa Annals of Medicine.2025;[Epub] CrossRef
Factors influencing active participation in cardiac rehabilitation among patients with cardiovascular disease: A nationwide cohort study Chul Kim, Jung Hwa Hong, Jang Woo Lee PM&R.2025; 17(10): 1140. CrossRef
New prognostic model for hospitalized patients with alcoholic cirrhosis and Maddrey’s discriminant function <32 Tae Hyung Kim, Hyung Joon Yim, Young Kul Jung, Do Seon Song, Eileen L. Yoon, Hee Yeon Kim, Seong Hee Kang, Young Chang, Jeong-Ju Yoo, Baek Gyu Jun, Sung Won Lee, Jung Gil Park, Ji Won Park, Sung-Eun Kim, Tae Yeob Kim, Soung Won Jeong, Ki Tae Suk, Moon You Hepatology International.2024; 18(2): 500. CrossRef
Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B Tae Hyung Kim, Ji Hoon Kim, Hyung Joon Yim, Yeon Seok Seo, Sun Young Yim, Young-Sun Lee, Young Kul Jung, Jong Eun Yeon, Soon Ho Um, Kwan Soo Byun Gut and Liver.2024; 18(2): 305. CrossRef
Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort Jihye Lim, Jung Hee Kim, Sung‐Eun Kim, Seul Ki Han, Tae Hyung Kim, Hyung Joon Yim, Young Kul Jung, Do Seon Song, Eileen L. Yoon, Hee Yeon Kim, Seong Hee Kang, Young Chang, Jeong‐Ju Yoo, Sung Won Lee, Jung Gil Park, Ji Won Park, Soung Won Jeong, Ki Tae Suk Journal of Gastroenterology and Hepatology.2024; 39(9): 1932. CrossRef
Effect of diabetes on mortality and liver transplantation in alcoholic liver cirrhotic patients with acute decompensation Jihye Lim, Sung-Eun Kim, Ae Jeong Jo, Jung Hee Kim, Seul Ki Han, Tae Hyung Kim, Hyung Joon Yim, Young Kul Jung, Do Seon Song, Eileen L. Yoon, Hee Yeon Kim, Seong Hee Kang, Young Chang, Jeong-Ju Yoo, Sung Won Lee, Jung Gil Park, Ji Won Park, Soung Won Jeon Hepatology International.2024; 18(5): 1579. CrossRef
The Role of Cardiac Rehabilitation in Promoting Lifestyle Modification Among Cardiovascular Patients: A Nationwide Cohort Study Chul Kim, Jung Hwa Hong, Jang Woo Lee Healthcare.2024; 12(24): 2553. CrossRef
Comparison of decline in renal function between patients with chronic hepatitis B with or without antiviral therapy Jae Seung Lee, Chan‐Young Jung, Jung Il Lee, Sang Hoon Ahn, Beom Seok Kim, Seung Up Kim Alimentary Pharmacology & Therapeutics.2023; 58(1): 99. CrossRef
Association of the etiology and peak level of markedly elevated aminotransferases with mortality: a multicenter study Ji Yoon Kwak, Hyun-gyu Kim, Ji Hee Han, Hankyu Jeon, Ra Ri Cha, Sang Soo Lee Hepatology Communications.2023;[Epub] CrossRef
Liver Imaging Reporting and Data System version 2018 for diagnosing hepatocellular carcinoma in alcoholic liver cirrhosis and virus-related cirrhosis Ji Young Choi, Sang Hyun Choi, Jae Ho Byun, So Jung Lee, So Yeon Kim, Hyung Jin Won, Yong Moon Shin European Journal of Radiology.2023; 168: 111139. CrossRef
The Clinical Courses and Prognosis of Cirrhotic Patients after First Acute Decompensation: Prospective Cohort Study Jung Kim, Sung-Eun Kim, Do Song, Hee Kim, Eileen Yoon, Seong Kang, Young-Kul Jung, Jung Kwon, Sung Lee, Seul Han, Young Chang, Soung Jeong, Jeong Yoo, Young-Joo Jin, Gab Cheon, Byung Kim, Yeon Seo, Hyoungsu Kim, Ji Park, Tae Kim, Dong Sinn, Woo Chung, Hwi Diagnostics.2023; 14(1): 14. CrossRef
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Feasibility and Reproducibility of Multifrequency Magnetic Resonance Elastography in Healthy and Diseased Pancreases Qike Song, Yu Shi, Feng Gao, Meng Yin, Rui Yang, Yuanyuan Liu, Shiling Zhong, Yang Hong Journal of Magnetic Resonance Imaging.2022; 56(6): 1769. CrossRef
Association between the dietary inflammatory index and bone markers in postmenopausal women Daeun Song, Jieun Kim, Minji Kang, Jungwon Park, Haelim Lee, Deog-Yoon Kim, So Young Park, Hyunjung Lim, Masaki Mogi PLOS ONE.2022; 17(3): e0265630. CrossRef
Long-Term Prediction Model for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Antiviral Therapy: Based on Data from Korean Patients Ji Hun Lee, Seung Kak Shin, Seong Hee Kang, Tae Hyung Kim, Hyung Joon Yim, Sun Young Yim, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Jong Eun Yeon, Oh Sang Kwon, Soon Ho Um, Kwan Soo Byun Journal of Clinical Medicine.2022; 11(22): 6613. CrossRef
Correlation between shift work and non-alcoholic fatty liver disease among male workers in the steel manufacturing company of Korea: a cross-sectional study Kiseok Kim, Yong-Jin Lee, Soon-Chan Kwon, Young-Sun Min, Hyun Kyo Lee, Gwangin Baek, Sang Hyeon Kim, Eun-Chul Jang Annals of Occupational and Environmental Medicine.2022;[Epub] CrossRef
Different Performance of Liver Stiffness Measurement According to Etiology and Outcome for the Prediction of Liver-Related Events Joo Hyun Oh, Myung Ji Goh, Yewan Park, Jihye Kim, Wonseok Kang, Dong Hyun Sinn, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Yong-Han Paik Digestive Diseases and Sciences.2021; 66(8): 2816. CrossRef
Current Status of Deceased Donor Liver Transplantation for Alcoholic Liver Disease in Korea in MELD Era Dong Jin Joo The Korean Journal of Gastroenterology.2021; 77(1): 4. CrossRef
Outcome of patients with severe alcoholic hepatitis after Model for End-Stage Liver Disease-based allocation system implementation in Korea Tae Jin Kwon, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Dong Hyun Sinn, Seung Woon Paik Korean Journal of Transplantation.2021; 35(1): 24. CrossRef
Normative Pancreatic Stiffness Levels and Related Influences Established by Magnetic Resonance Elastography in Volunteers Youli Xu, Xiaoli Cai, Yu Shi, Meng Yin, Gongyu Lan, Xianyi Zhang, Ruoyun Ji, Chang Liu Journal of Magnetic Resonance Imaging.2020; 52(2): 448. CrossRef
Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea Won Young Jang, Woo Jin Chung, Byoung Kuk Jang, Jae Seok Hwang, Heon Ju Lee, Moon Joo Hwang, Young Oh Kweon, Won Young Tak, Soo Young Park, Su Hyun Lee, Chang Hyeong Lee, Byung Seok Kim, Si Hye Kim, Jeong Ill Suh, Jun Gi Park Journal of Korean Medical Science.2020;[Epub] CrossRef
Diagnosis and Severity Assessment of Alcohol-Related Liver Disease Eunju Kim, Seung Ha Park The Korean Journal of Gastroenterology.2020; 76(2): 60. CrossRef
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 Yuri Cho, Youn Su Park, Hwi Young Kim, Won Kim, Heon Ju Lee, Dong Joon Kim Trials.2018;[Epub] CrossRef
Alcoholic Liver Disease Is Associated with an Increased Risk of Gastric Cancer Tae Hoon Ha, Byeong Gwan Kim, Donghyong Jeong, Sohee Oh, Won Kim, Yong Jin Jung, Dong Won Ahn, Ji Bong Jeong, Ji Won Kim, Kook Lae Lee, Seong-Joon Koh Digestive Diseases and Sciences.2017; 62(1): 273. CrossRef
Korean Patients Undergoing Deceased Donor Liver Transplantation for Alcoholic Liver Disease Have Non-Inferior Survival Outcomes than for Hepatitis B Virus: a Real-World Experience without Minimum Abstinence before Transplantation Suk Kyun Hong, Nam-Joon Yi, Hyo-Sin Kim, Sung Woo Ahn, Kyung Chul Yoon, Hyeyoung Kim, Kwang-Woong Lee, Kyung-Suk Suh Journal of Korean Medical Science.2017; 32(6): 919. CrossRef
The Association between Vitamin D Insufficiency and Nonalcoholic Fatty Liver Disease: A Population-Based Study Yeonjung Ha, Seong Hwang, Kyu Rim Nutrients.2017; 9(8): 806. CrossRef
Prediction of virologic response to tenofovir mono‐rescue therapy for multidrug resistant chronic hepatitis B Sangheun Lee, Jun Yong Park, Do Young Kim, Beom Kyung Kim, Seung Up Kim, Kijun Song, Hye Jin Ku, Kwang‐Hyub Han, Sang Hoon Ahn Journal of Medical Virology.2016; 88(6): 1027. CrossRef
Relationship between 25-Hydroxyvitamin D Levels and Liver Fibrosis as Assessed by Transient Elastography in Patients with Chronic Liver Disease Bong Jin Ko, Young Seok Kim, Sang Gyune Kim, Jung Hwan Park, Sae Hwan Lee, Soung Won Jeong, Jae Young Jang, Hong Soo Kim, Boo Sung Kim, Sun Mi Kim, Young Don Kim, Gab Jin Cheon, Bo Ra Lee Gut and Liver.2016; 10(5): 818. CrossRef
Clinical Characteristics and Prognostic Impact of Bacterial Infection in Hospitalized Patients with Alcoholic Liver Disease Jin Kyoung Park, Chang Hun Lee, In Hee Kim, Seon Min Kim, Ji Won Jang, Seong Hun Kim, Sang Wook Kim, Seung Ok Lee, Soo Teik Lee, Dae-Ghon Kim Journal of Korean Medical Science.2015; 30(5): 598. CrossRef
Effects of Korean Red Ginseng (Panax ginseng), urushiol (Rhus vernicifera Stokes), and probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) on the gut–liver axis of alcoholic liver disease Chang Seok Bang, So Hyung Hong, Ki Tae Suk, Jin Bong Kim, Sang Hak Han, Hotaik Sung, Eun Ji Kim, Myoung Jo Kim, Moon Young Kim, Soon Koo Baik, Dong Joon Kim Journal of Ginseng Research.2014; 38(3): 167. CrossRef
An effective integrated method for comprehensive identification of eighty-five compounds in Zhi-Zi-Da-Huang decoction by HPLC-DAD-ESI-MS (TOF) and HPLC-DAD-ESI-MS/MS (QqQ) without the help of reference standards Lingling Zou, Xixi Li, Qingshui Shi, Fang Feng Anal. Methods.2014; 6(12): 4312. CrossRef
Alcoholic liver disease: Treatment Ki Tae Suk World Journal of Gastroenterology.2014; 20(36): 12934. CrossRef
Background/Aims Although alcohol withdrawal syndrome (AWS) is often developed in the patients with alcoholic liver disease, the studies about which clinical factors are associated with the development of AWS have been rarely studied. The aim of this study was to reveal clinical factors indicating a higher risk for the development of AWS at admission. Methods: The retrospective case-controlled study was conducted among patients with alcoholic liver disease. The cases were divided into two groups according to whether AWS was developed or not. We compared their past medical history, physical examination and laboratory data at admission. Results: AWS was significantly developed in patients who had experienced AWS in the past, increased serum chloride concentration at admission. Conclusions: It is possible to predict the patients who are more likely develop to AWS by means of past medical history and a serum biochemical test at admission. We suggest more intensive therapy will be required to prevent the development of AWS in these patients. These results are preliminary and need further prospective development and validation, particularly regarding the variety of variables.
Background/Aims Alcoholic liver disease with metabolic acidosis may have possible causes such as alcoholic ketoacidosis, diabetic ketoacidosis, lactic acidosis. Salicylate, methanol, and ethylene glycol intoxication should also be considered. The aim of this study was to investigate the short-term prognostic factors in patients with alcoholic liver disease with metabolic acidosis. Methods: Clinical data related to twenty-nine patients with alcoholic liver disease and metabolic acidosis was analysed retrospectively. Patients were divided into two groups according to the outcome (survival or death). Past medical history, and physical, laboratory and radiologic data at admission were compared. Results: The amount of daily alcohol intake differed significantly between the two groups (P=0.034), but duration and total amount of alcohol intake did not differ significantly between the two groups (P=0.128; P=0.360). The presence of ascites differed significantly between two the groups (P=0.019). On laboratory testing, the following differed significantly: base excess (P=0.038), hemoglobin (P=0.019), platelet (P=0.040), total bilirubin (P=0.007), albumin (P=0.012), creatinine (P=0.014), phosphorus (P=0.021), chloride (P=0.010), ammonia (P=0.003), prothrombin time (P=0.033), fibrinogen (P=0.011) and D-dimer (P=0.024). Review of the medical history of the patients showed diabetes (10/29), cirrhosis (10/29), and hepatocellular carcinoma (1/29). Combined conditions at admission were sepsis (8/29), pneumonia (7/29), acute renal failure (6/29), rhabdomyolysis (5/29), gastrointestinal hemorrhage (4/29), acute pancreatitis (3/29), acute respiratory distress syndrome (2/29), and acute myocardial infarction (1/29). Conclusions: The amount of daily alcohol intake, base excess, hemoglobin, platelet, total bilirubin, albumin, creatinine, phosphorus, chloride, ammonia, prothrombin time, fibrinogen and D-dimer seemed to be useful parameters in predicting short-term prognosis of patients with alcoholic liver disease with metabolic acidosis. Further study is needed to define the significance of these factors. (Korean J Hepatol 2004;10:117-124)
Background/Aims The liver function tests (LFTs), such as aspartate aminotransferase (AST), alanine
aminotransferase (ALT), and γ-glutamyltranspeptidase (γ-GT), have been widely used as screening tests but
their low positive predictive value can cause many false positive results. To evaluate the clinical usefulness of
these tests, we analyzed the serial LFT results for factory workers, and we compared the risk factors for the
groups that were divided according to the serial LFT results. Methods: From June 2001 to October 2001, 1223
consecutive healthy workers in a single factory were enrolled in our study; a questionnaire, LFT and liver
ultrasonography were done for all the subjects. The previous LFT results were collected from the Annual
health examination survey. According to the abnormalities on the serial LFT, the participants were classified
into three groups (abnormal-in-both, alternating or, normal-in-both) and the risk factors were compared
among these groups using multiple logistic regression analysis. Results: The prevalence of LFT abnormality
on a single test was 16.8%, but on the serial LFT, only 5% of the study participants showed consistent
abnormality. The risk factors for the abnormal-in-both group, compared with the alternating group, were
liver ultrasonography abnormality such as a fatty liver (odds ratio, 2.2; P=0.026) and a heavy alcohol intake
(more than 210 g/week) (odds ratio, 7.2; P=0.064). HBsAg was not a significant risk factor for any of the three
groups. Conclusions: In factory workers having serial LFT abnormalities, alcoholic liver disease could be the
principal cause of abnormal LFT. Even if the HBsAg were positive in patients with abnormal LFT, there is
the possibility of another causes for LFT abnormalities such as alcoholic liver disease and non-alcoholic
steatosis or steatohepatitis. (Korean J Hepatol 2005;11:144-156)
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