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World J Gastroenterol. Jul 28, 2021; 27(28): 4639-4652
Published online Jul 28, 2021. doi: 10.3748/wjg.v27.i28.4639
Addition of statins to the standard treatment in patients with cirrhosis: Safety and efficacy
Alberto E Muñoz, Florencia D Pollarsky, Mónica Marino, Mariano Cartier, Horacio Vázquez, Pablo Salgado, Gustavo Romero
Alberto E Muñoz, Florencia D Pollarsky, Mónica Marino, Mariano Cartier, Gustavo Romero, Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
Alberto E Muñoz, Pablo Salgado, Instituto de Investigaciones en Salud Pública, Facultad de Odontología, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires 1122, Argentina
Horacio Vázquez, Unidad Clínica, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Investigador Asociado del Gobierno de la Ciudad Autónoma de Buenos Aires, Ciudad Autónoma de Buenos Aires 1264, Argentina
Author contributions: Muñoz AE contributed as guarantor of the article; Muñoz AE, Pollarsky FD, Marino M, Cartier M and Romero G contributed to acquisition of data; Muñoz AE, Pollarsky FD, Vázquez H and Romero G contributed to analysis and interpretation of data, and drafting of the manuscript; Muñoz AE, Pollarsky FD, Marino M, Cartier M, Vázquez H, Salgado P and Romero G contributed to critical revision of the manuscript for important intellectual content; All authors approved the final version of the manuscript.
Conflict-of-interest statement: There is no conflict of interest associated with the author or coauthors contributing to this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Alberto E Muñoz, MD, Assistant Professor, Associate Specialist, Attending Doctor, Medical Assistant, Staff Physician, Sección Hepatología, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Facultad de Medicina, Universidad de Buenos Aires, Av, Caseros 2061, Ciudad Autónoma de Buenos Aires 1264, Argentina. aemunoz@intramed.net
Received: December 23, 2020
Peer-review started: December 23, 2020
First decision: February 11, 2021
Revised: February 26, 2021
Accepted: July 5, 2021
Article in press: July 5, 2021
Published online: July 28, 2021
Abstract

This review summarizes the safety and efficacy of statins in patients with cirrhosis. Due to concerns about the safety of statins in patients with impaired liver function, they have recently been investigated as a potential treatment option in cirrhosis. The most clinically significant adverse event is statin-related myopathy, and this may be related to the high serum statin concentrations in the setting of severely impaired liver function. Rhabdomyolysis is the most serious and potentially life-threatening manifestation. It has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values, such as 40 mg/d, are associated with many adverse events, especially muscle injury. Likewise, simvastatin should not be administered to patients with Model for End-stage Liver Disease score > 12 and/or Child-Pugh class C because of the high risk of severe muscle injury. Due to the pleiotropic effects, the focus on statins has shifted from being considered harmful to something useful. Through these effects, statins could prevent liver-related morbidity and mortality in cirrhotic patients. Observational studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation, hepatocellular carcinoma development and death. The few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure, quite likely through a reduction in hepatic resistance. Another large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival rate. Despite these encouraging outcomes, the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies involved. Therefore, it is advisable to perform further randomized controlled trials on a large series of patients with hard clinical endpoints, using different statin types and varying doses. The objectives would be to prevent liver-related morbidity and mortality rather than treating cirrhosis complications to take additional information that makes it possible to add statins to the standard of care of these patients.

Keywords: Cirrhosis, Liver disease, Statins, Safety, Efficiency

Core Tip: Several observational studies of statins in patients with liver disease were published, but they were highly biased. On the other hand, only one randomized controlled trial improved survival in Child-Pugh class A/B patients but did not reduce variceal rebleeding. Finally, the dose and type of statin to be used should be defined. This review concludes that new randomized controlled trials are necessary before endorsing statin use in patients with chronic liver disease.