Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2020; 12(12): 1258-1167
Published online Dec 27, 2020. doi: 10.4254/wjh.v12.i12.1258
Effects of proprotein convertase subtilisin/kexin type-9 inhibitors on fatty liver
Muhammad Shafiq, Timothy Walmann, Venkat Nutalapati, Cheryl Gibson, Yousaf Zafar
Muhammad Shafiq, Cheryl Gibson, General and Geriatric Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
Timothy Walmann, Department of Diagnostic Radiology, University of Kansas Medical Center, Kansas City, KS 66160, United States
Venkat Nutalapati, Department of Gastroenterology, University of Kansas Medical Center, Kansas City, KS 66160, United States
Yousaf Zafar, Internal Medicine, NCH Health Care System, Naples, FL 34102, United States
Author contributions: Shafiq M was involved in all aspects of this study, including but not limited to study design, data collection, and writing of the abstract and manuscript; Walmann T read all the pre- and post-treatment liver imaging scans; Nutalapati V and Zafar Y provided assistance in abstract and manuscript preparation; Gibson C assisted with data analysis.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of University of Kansas Medical Center (Kansas City, KS, United States).
Informed consent statement: In accordance with the retrospective design of the study, based upon chart reviews, no informed consent was required.
Conflict-of-interest statement: The authors declare having no financial relationships to disclose.
Data sharing statement: All relevant data has been provided in this article. No additional data is available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Muhammad Shafiq, MD, Assistant Professor, General and Geriatric Medicine, University of Kansas Medical Center, 4000 Cambridge Street, 6040 Delp & Mail Stop 1020, Kansas City, KS 66160, United States. mshafiq@kumc.edu
Received: June 9, 2020
Peer-review started: June 9, 2020
First decision: September 18, 2020
Revised: October 7, 2020
Accepted: November 12, 2020
Article in press: November 12, 2020
Published online: December 27, 2020
Processing time: 192 Days and 2.8 Hours
Abstract
BACKGROUND

Many studies have investigated the progression of nonalcoholic fatty liver disease (NAFLD) and its predisposing risk factors, but the conclusions from these studies have been conflicting. More challenging is the fact that no effective treatment is currently available for NAFLD.

AIM

To determine the effects of proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors on fatty infiltration of the liver.

METHODS

This retrospective, chart review-based study was conducted on patients, 18-year-old and above, who were currently on PCSK9 inhibitor drug therapy. Patients were excluded from the study according to missing pre- or post-treatment imaging or laboratory values, presence of cirrhosis or rhabdomyolysis, or development of acute liver injury during the PCSK9 inhibitor treatment period; the latter being due to false elevation of liver function markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Radiographic improvement was assessed by a single radiologist, who read both the pre- and post-treatment images to minimize reading bias. Fatty infiltration of the liver was also assessed by changes in ALT and AST, with pre- and post-treatment levels compared by paired t-test (alpha criterion: 0.05).

RESULTS

Of the 29 patients included in the study, 8 were male (27.6%) and 21 were female (72.4%). Essential hypertension was present in 25 (86.2%) of the patients, diabetes mellitus in 18 (62.1%) and obesity in 15 (51.7%). In all, patients were on PCSK9 inhibitors for a mean duration of 23.69 ± 11.18 mo until the most recent ALT and AST measures were obtained. Of the 11 patients who received the radiologic diagnosis of hepatic steatosis, 8 (72.73%) achieved complete radiologic resolution upon use of PCSK9 inhibitors (mean duration of 17.6 mo). On average, the ALT level (IU/L) decreased from 21.83 ± 11.89 at pretreatment to 17.69 ± 8.00 at post-treatment (2-tailed P = 0.042) and AST level (IU/L) decreased from 22.48 ± 9.00 pretreatment to 20.59 ± 5.47 post-treatment (2-tailed P = 0.201).

CONCLUSION

PCSK9 inhibitors can slow down or even completely resolve NAFLD.

Keywords: Proprotein convertase subtilisin/kexin type-9 inhibitor; Fatty liver; Nonalcoholic fatty liver disease; Alanine aminotransferase; Aspartate aminotransferase; Imaging

Core Tip: This retrospective study evaluated the effects of proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors on fatty infiltration of the liver. Among the 29 selected patients, 11 were found to have radiologic diagnosis of hepatic steatosis and 8 of those (72.73%) achieved complete radiologic resolution of the condition upon use of PCSK9 inhibitors for mean duration of 17.6 mo. Both alanine aminotransferase and aspartate aminotransferase levels showed a downward trend after PCSK9 inhibitors for mean duration of 23.69 ± 11.18 mo. These results highlight the potential benefit of PCSK9 inhibitors use for patients with nonalcoholic fatty liver disease.