New view on alcoholic liver disease - potential role of PD1/PDL-1 pathway in the disease pathogenesis

Katarzyna Adamczyk, Beata Kasztelan-Szczerbińska, Anna Rycyk, Halina Cichoż-Lach



Introduction: Exposure to chronic, excessive alcohol consumption, its breakdown metabolites, and gut-derived endotoxins dysregulate immune signaling leading to activation of inflammation. As a result, the non-resolving inflammatory response and development of alcoholic liver disease (ALD) may occur. There are still no pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Material and Methods: The information provided was collected as a result of various article’s analyses on the development, diagnosis, and treatment of patients with alcoholic liver disease using Google Scholar and PubMed databases. Results: The pathway consisting of the programmed cell death 1 (PD-1) receptor and its ligand PD-L1 may play a critical role in the inhibition of self-reactive and inflammatory effector cells and the protection against immune-mediated tissue damage. There is a possibility of the potential gender-related differences in PD1/PD-L1 signaling in ALD. Conclusion: The better understanding of ALD as a dynamic process and all aspects of immune dysregulation may be important for the development of novel therapies in alcoholic liver disease. Results from a further study on the PD1/PDL-1 pathway might be exploited to re-define therapeutic targets and create sex-tailored treatments according to individual patient needs.


alcohol liver disease (ALD); immune dysregulation; programmed cell death 1 (PD-1); gender difference

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World Health Organization (WHO) Global Status Report on Alcohol and Health. Geneva: WHO; 2018. 38-46.


Tsochatzis EA, Bosch J, Burroughs AK. (2014). Liver cirrhosis. Lancet, 17;383(9930):1749-61.

Rehm J, Gmel GE Sr, Gmel G, et al. (2017). The relationship between different dimensions of alcohol use and the burden of disease-an update. Addiction, 112(6):968-1001.

Natalia A Osna, Terrence M Donohue Jr, Kusum K Kharbanda. (2017). Alcoholic Liver Disease: Pathogenesis and Current Management. Alcohol Research:current reviews, 38(2): 147–161.

Gao B, Battaler R.(2011).Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets. Gastroenterology, 141(5): 1572–1585.

Stickel F, Datz C, Hampe H, Bataller R. Pathophysiology and Management of Alcoholic Liver Disease: Update 2016. Gut and Liver,11(2): 173–188.

Konishi M, Ishii H.(2007). Role of microsomal enzymes in development of alcoholic liver diseases. Journal of Gastroenterology and Hepatology, 22(Suppl 1):S7–S10.

Bradford BU, Kono H, Isayama F, et al.(2005). Cytochrome P450 CYP2E1, but not nicotinamide adenine dinucleotide phosphate oxidase, is required for ethanol-induced oxidative DNA damage in rodent liver. Hepatology : official journal of the American Association for the Study of Liver Diseases, 41:336–344.

Scoccianti C, Cecchini M, Anderson AS, et al.(2015). European Code against Cancer 4th Edition: alcohol drinking and cancer. Cancer Epidemiology, 39(Suppl 1):S67–S74.

Bode C, Bode JC. Effect of alcohol consumption on the gut.(2003). Best practice and research. Clinical gastroenterology, 17(4):575–592.

Suraweera DB, Weeratunga AN, Hu RW, et al. (2015). Alcoholic hepatitis: The pivotal role of Kupffer cells. World Journal of Gastrointestinal Pathophysiology, 6(4):90–98.

Mathurin P, Deng QG, Keshavarzian A, et al. (2000). Exacerbation of alcoholic liver injury by enteral endotoxin in rats. Hepatology : official journal of the American Association for the Study of Liver Diseases, 32(5):1008–1017.

Ambade A, Mandrekar P. (2012). Oxidative stress and inflammation: Essential partners in alcoholic liver disease. International Journal of Hepatology, 2012: 853175

Craig J McClain, Zhenyuan Song, Shirish S, Barve, et al. 2004). Recent Advances in Alcoholic Liver Disease IV. Dysregulated cytokine metabolism in alcoholic liver disease. AJP Gastrointestinal and Liver Physiology, 287: G497–G502.

McClain CJ, Cohen DA. (1989). Increased tumor necrosis factor production by monocytes in alcoholic hepatitis. Hepatology : official journal of the American Association for the Study of Liver Diseases, 9: 349–351.

Kamimura S and Tsukamoto H. (1995). Cytokine gene expression by Kupffer cells in experimental alcoholic liver disease. Hepatology : official journal of the American Association for the Study of Liver Diseases, 21: 1304–1309.

Kasztelan-Szczerbinska B, Surdacka A, Slomka M, et al. (2014). Angiogenesis-related biomarkers in patients with alcoholic liver disease: their association with liver disease complications and outcome. Mediators Inflammation, 2014:673032.

Gao B, Tsukamoto H. (2016). Inflammation in alcoholic and nonalcoholic fatty liver disease: friend or foe?.Gastroenterology, 150, 1704-1709.

Szabo, G, Saha B. (2015). Alcohol’s Effect on Host Defense. Alcohol research : current reviews, 37, 159 -170.

Yamazaki T, Akiba H, Iwai H. et al. (2002). Expression of programmed death 1 ligands by murine T cells and APC. Journal of Immunology, 169:5538–45.

Agata Y, Kawasaki A, Nishimura H, Ishida Y, et al. (1996). Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. International Immunology, 8:765–72.

Keir ME, Butte MJ, Freeman GJ, Sharpe AH. (2008). PD-1 and its ligands in tolerance and immunity. Annual review of immunology, 26:677–704.

Boussiotis, VA, Chatterjee P, Li, L. (2014). Biochemical signaling of PD-1 on T cells and its functional implications. The cancer journal. 20, 265-271

Bardhan K., Anagnostou T., Boussiotis, V.A. (2012).The PD1:PD-L1/2 Pathway from discovery to clinical implementation. Frontiers of immunology, 7:550.

Zamani, MR, Aslani S, Salmaninejad A, et al. (2016). PD-1/PD-L and autoimmunity: A growing relationship. Cellular immunology, 310, 27-41.

Dinesh, RK, Hahn BH, Singh RP.(2010). PD-1, gender, and autoimmunity. Autoimmunity Reviews, 9, 583-587.

Shimizu I, Yoshikawa H, Kamochi M, Nakayama Y. (2012). Gender difference in alcoholic liver disease. INTECH Open Access Publisher, 11:24–40.

Eriksson CJ, Fukunaga T, Sarkola T, Lindholm H & Ahola L. (1996). Estrogen-relatedacetaldehyde elevation in women during alcohol intoxication. Alcoholism, clinical and experimental research, 20:1192-1195.

Sherlock S & Dooley J.(2002). Diseases of the liver and biliary system. Blackwell Science,Oxford,494.

Frezza M, di PC, Pozzato G, Terpin M, Baraona E & Lieber CS. (1990). High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. The New England journal of medicine, 322:95-99.

Nolen-Hoeksema S. (2004). Gender differences in risk factors and consequences for alcohol use and problems. Clinical psychology review, 24:981-1010.

Whitacre CC. (2001).Sex differences in autoimmune disease. Nature immunology, 2, 777-780

Muñoz-Cruz S, Togno-Pierce C, Morales-Montor J. (2011). Non-reproductive effects of sex steroids: their immunoregulatory role. Current topics in medicinal chemistry, 11(13):1714–1727

Jong Seong Roh, Dong Hyun Sohn. (2018). Damage-Associated Molecular Patterns in Inflammatory Diseases. Immune Network, 18(4): e27

Mihm S. (2018). Danger-Associated Molecular Patterns (DAMPs): Molecular Triggers for Sterile Inflammation in the Liver. International journal of molecular sciences,19(10):3104.

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