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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 28, 2016; 22(24): 5459-5466
Published online Jun 28, 2016. doi: 10.3748/wjg.v22.i24.5459
Natural regression of fibrosis in chronic hepatitis B
Shogo Ohkoshi, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa, Kenya Kamimura, Masahiko Yano
Shogo Ohkoshi, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa, Department of Internal Medicine, School of Life Dentistry at Niigata, The Nippon Dental University, Niigata 951-8580, Japan
Kenya Kamimura, Masahiko Yano, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University, Niigata 951-8520, Japan
Author contributions: Ohkoshi S wrote the paper; Yano M and Kamimura K collected the data; Hirono H, Watanabe K and Hasegawa K had critical discussions regarding the study and manuscript with Ohkoshi S.
Supported by A Grant-in-Aid for Scientific Research (C) (25461012 to Ohkoshi S) from the Japan Society for the Promotion of Science.
Conflict-of-interest statement: The authors do not have any commercial affiliation or consultancy that could be construed as a conflict of interest.
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: Shogo Ohkoshi, MD, PhD, Department of Internal Medicine, School of Life Dentistry at Niigata, The Nippon Dental University, 1-8 Hamaura-Cho, Chuo-ku, Niigata 951-8580, Japan. okoshi@ngt.ndu.ac.jp
Telephone: +81-25-2118243 Fax: +81-25-2671582
Received: March 5, 2016
Peer-review started: March 7, 2016
First decision: April 14, 2016
Revised: April 20, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 28, 2016
Processing time: 108 Days and 1.1 Hours
Abstract

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B (CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBeAg seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma (HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been (pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosis-induced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue.

Keywords: Chronic hepatitis B; Cirrhosis; Spontaneous remission; Regression of fibrosis; Occult hepatitis B infection; Hepatocellular carcinoma surveillance of hepatitis B virus

Core tip: The fibrosis of liver cirrhosis may be reversible. Regression of fibrosis in hepatitis B virus (HBV) patients with (pre)cirrhosis might be a more common phenomenon than generally considered. This might cause the underestimation of fibrosis levels in chronic hepatitis B, suggesting a difficulty with the surveillance system of HBV-hepatocellular carcinoma (HCC). That is, some HCC patients with non-cirrhotic liver might have been cirrhotic in the past, after which spontaneous regression of fibrosis occurred. Cirrhosis-HCC mechanisms, compared to the direct action of the viral genome, might be more prevalent than generally considered in HBV patients.