Prospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2018; 24(11): 1269-1277
Published online Mar 21, 2018. doi: 10.3748/wjg.v24.i11.1269
Fatty liver in hepatitis C patients post-sustained virological response with direct-acting antivirals
Mazen Noureddin, Micaela M Wong, Tsuyoshi Todo, Shelly C Lu, Arun J Sanyal, Edward A Mena
Mazen Noureddin, Fatty Liver Program, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Mazen Noureddin, Shelly C Lu, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Micaela M Wong, Edward A Mena, California Liver Research Institute, Pasadena, CA 91105, United States
Tsuyoshi Todo, Comprehensive Transplant Center, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
Arun J Sanyal, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States
Author contributions: Noureddin M provided the study concept and design; Noureddin M, Wong MM and Mena EA contributed to acquisition of data; Noureddin M, Wong MM, Todo T, Lu SC and Sanyal AJ contributed to analysis and interpretation of data; Noureddin M drafted the manuscript; Noureddin M, Wong MM, Todo T, Lu SC, Sanyal AJ and Mena EA contributed to critical revision of the manuscript for important intellectual content; Noureddin M contributed to the statistical analysis; Noureddin M and Mena EA provided administrative and technical support and study supervision; Wong MM provided support for carrying out the study; all authors gave final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Institutional review board statement: This study was approved by the Central Institutional Review Board.
Informed consent statement: Informed voluntary consent was acquired from all the study participants.
Conflict-of-interest statement: Noureddin M has been on the advisory board or a speaker for EchoSens North America, OWL, Intercept and Abbott; Noureddin M has received research support from Gilead, Galmed, Galectin, Conatus, Zydus and Shire; Noureddin M is a minor shareholder of Anaetos; Sanyal AJ has been a consultant to Intercept, Galectin, BMS, Nitto Denko, Nimbus, Aredlyx, Vivelyx, and Tandeva; Sanyal AJ has received grants from Gilead, Intercept, Novartis, Merck, BMS, and Tobira; Sanyal AJ has stock or stock options in Genfit, Akarna, Tiziana, Natural Shield, Durect, and Exhalenz. Mena EA has received research support from Galmed, Conatus, Shire, Merck and Gilead; Mena EA has been a consultant and advisor to Gilead, Abbvie, Merck, Bayer, and Grifalos; Mena EA is a member of the speakers’ bureaus for Gilead, Abbvie, Merck, Bayer, Echosens North America and Grifalos; Mena EA owns stocks in Gilead and Galectin; The other authors report no conflicts of interest.
Data sharing statement: The statistical code and dataset are available from the corresponding author at mazen.noureddin@cshs.org. Consent for data sharing was not obtained but the presented data are anonymized and risk of identification is low.
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/
Correspondence to: Mazen Noureddin, MD, MHSc, Associate Professor, Division of Digestive and Liver Diseases, Comprehensive Transplant Program, Cedars-Sinai Medical Center, 8900 Beverly Blvd, Suite 250, Los Angeles, CA 90048 United States. mazen.noureddin@cshs.org
Telephone: +1-310-4237088 Fax: +1-310-2488197
Received: December 3, 2017
Peer-review started: December 5, 2017
First decision: December 14, 2017
Revised: January 27, 2018
Accepted: March 3, 2018
Article in press: March 3, 2018
Published online: March 21, 2018
Processing time: 102 Days and 13.3 Hours
ARTICLE HIGHLIGHTS
Research background

It is known that the hepatic steatosis prevalence in hepatitis C patients who have achieved a sustained virological response with interferon is approximately 50%. However, the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals has not previously been studied. Knowledge of this is important in order to direct appropriate long-term follow up for patients.

Research motivation

Post-sustained virological response (SVR), hepatitis C patients, many of whom have normal liver enzymes, are too often being discharged from their hepatologists’ care with no further plans for follow up. The current European and United States guidelines only recommend long-term follow up in patients with elevated enzymes. In addition, many hepatitis C patients who have achieved an SVR are excluded from nonalcoholic fatty liver disease (NAFLD) clinical trials. We think it is important to determine the prevalence of NAFLD post-SVR and assess the severity of liver disease in these patients. Determining these things can provide a basis for future research aimed at determining the long-term natural history of the disease in these patients, and may prompt changes in both liver society guidelines for follow up and in clinical trial exclusion criteria.

Research objectives

The main objective, to determine the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals, was achieved. This knowledge provides a basis for future research aimed at determining the long-term natural history of the disease in these patients.

Research methods

In this study we used transient elastography with controlled attenuation parameter to measure steatosis and fibrosis in hepatitis C patients post-SVR. This was the first study to measure both fibrosis and steatosis in hepatitis C patients using the FibroScan technology.

Research results

Our findings have added knowledge previously unknown in this field that may help to guide the need for long-term monitoring of hepatitis C patients post-SVR, with a particular focus on the possible occurrence of NAFLD in these patients, whether or not there are elevated liver enzymes. The most important future research will be to carry out long-term follow up on hepatitis C patients post-SVR to determine the prevalence of fatty liver over time.

Research conclusions

This is the first prospective study to assess the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals. The study’s findings that fatty liver is present in 47.5% of these patients and that some steatotic patients have clinically significant fibrosis despite normal liver enzymes should raise awareness of the high post-SVR prevalence of fatty liver and the importance of post-SVR assessment of steatosis and fibrosis and long-term follow up with these patients. The study’s findings raise concern that the recommendations found in the current U.S. and European guidelines for follow up of patients post-SVR could result in a lack of adequate long-term monitoring of these patients. In particular, the very high prevalence of fatty liver (47.5%) with continuing clinically significant fibrosis in the steatotic patients despite normal liver enzymes should be of concern to clinicians. Therefore, we recommend post-SVR assessment of steatosis and fibrosis in those with abnormal BMI or other risk factors typical of NAFLD. In patients found to have hepatic steatosis long-term follow up is clearly warranted.

Research perspectives

Our study’s assessment of steatosis and fibrosis in hepatitis C patients at almost a year post-SVR has shown that long-term monitoring of these patients to assess the possibility of fatty liver and fibrosis is important. With this study, we have provided a foundation upon which lengthier and larger studies should expand, using regularly scheduled transient elastography with controlled attenuation parameter assessments in order to determine whether this high level of steatosis is still present multiple years post-SVR and the clinical ramifications for patients.