Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy

Vetriselvan Subramaniyan; Srikumar Chakravarthi; Ravindran Jegasothy; Wu Yuan Seng; Neeraj Kumar Fuloria; Shivkanya Fuloria; Iswar Hazarika; Anju Das

doi:10.1016/j.toxrep.2021.02.010

Alcohol-associated liver disease: A review on its pathophysiology, diagnosis and drug therapy

Toxicol Rep. 2021 Feb 19:8:376-385. doi: 10.1016/j.toxrep.2021.02.010. eCollection 2021.

Authors

Vetriselvan Subramaniyan¹, Srikumar Chakravarthi², Ravindran Jegasothy³, Wu Yuan Seng⁴, Neeraj Kumar Fuloria⁵, Shivkanya Fuloria⁵, Iswar Hazarika⁶, Anju Das⁷

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia.
² Department of Pathology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia.
³ Department of Obstetrics and Gynecology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia.
⁴ Department of Biochemistry, Faculty of Medicine, Bioscience and Nursing, MAHSA University, SP 2, Bandar Saujana Putra, 42610, Malaysia.
⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy AIMST University, Jalan Bedong-Semeling, 08100, Malaysia.
⁶ Department of Pharmacology, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, 781017, India.
⁷ Department of Pharmacology, Royal School of Pharmacy, Royal Global University, Guwahati, 781035, India.

Abstract

One of the global burdens of health care is an alcohol-associated liver disease (ALD) and liver-related death which is caused due to acute or chronic consumption of alcohol. Chronic consumption of alcohol damage the normal defense mechanism of the liver and likely to disturb the gut barrier system, mucosal immune cells, which leads to decreased nutrient absorption. Therapy of ALD depends upon the spectrum of liver injury that causes fatty liver, hepatitis, and cirrhosis. The foundation of therapy starts with abstinence from alcohol. Corticosteroids are used for the treatment of ALD but due to poor acceptance, continuing mortality, and identification of tumor necrosis factor-alpha as an integral component in pathogenesis, recent studies focus on pentoxifylline and, antitumor necrosis factor antibody to neutralize cytokines in the therapy of severe alcoholic hepatitis. Antioxidants also play a significant role in the treatment but till today there is no universally accepted therapy available for any stage of ALD. The treatment aspects need to restore the gut functions and require nutrient-based treatments to regulate the functions of the gut system and prevent liver injury. The vital action of saturated fatty acids greatly controls the gut barrier. Overall, this review mainly focuses on the mechanism of alcohol-induced metabolic dysfunction, contribution to liver pathogenesis, the effect of pregnancy, and targeted therapy of ALD.

Keywords: ALD, alcohol associated liver disease; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Alcohol; CD14, cluster of differentiation14; CHD, congenital heart disease; ECM, extracellualr matrix; FASD, fetal alcohol spectrum disorders; FDA, food and drug administration; GGTP, gamma-glutamyl transpeptidase; GSH, Glutathione; H2O2, hydrogen peroxide; HCV, chronic hepatitis C; HSC, hepatic stellate cells; IGR, intrauterine growth retardation; IL, interleukin; Immune modulation; JECH, Japan Environment and Children's Study; Liver pathogenesis; MDF, maddrey’s discriminant function; NA, nutritional assessment; NAC, N-acetylcysteine; NADPH, Nicotinamide adenine dinucleotide phosphate; OLT, Orthotopic liver transplantation; Pregnancy; ROS, reactive oxygen species; TLR4, toll-like receptor 4; TNF, Tumor necrosis factor; Targeted therapy.

Publication types

Review