World J Gastroenterol. 2023 Jan 7;29(1):61-74. doi: 10.3748/wjg.v29.i1.61.
Cirrhosis is a leading cause of morbidity and mortality, impacting more than 120 million people worldwide. Although geographic differences exist, etiologic factors such as alcohol use disorder, chronic viral hepatitis infections, and non-alcoholic fatty liver disease are prevalent in nearly every region. Historically, significant effort has been devoted to modifying these risks to prevent disease progression. Nevertheless, more than 11% of patients with compensated cirrhosis experience hepatic decompensation each year. This transition signifies the most important prognostic factor in the natural history of the disease, corresponding to a decline in median survival to below 2 years. Over the past decade, the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized, and non-selective beta-blockers have emerged as the most effective option to date. However, a critical therapeutic gap still exists, and additional therapies have been proposed, including statins, rifaximin, and sodium-glucose cotransporter-2 inhibitors. Based on the results of innovative retrospective analyses and small-scale prospective trials, these pharmacotherapies represent promising options, but further studies, including randomized controlled trials, are necessary before they can be incorporated into clinical use. This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.