Meta-Analysis
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Jun 28, 2022; 10(3): 186-194
Published online Jun 28, 2022. doi: 10.13105/wjma.v10.i3.186
Difference in incidence of developing hepatocellular carcinoma between hepatitis B virus-and hepatitis C virus-infected patients
Kazuo Tarao, Akito Nozaki, Hirokazu Komatsu, Naomi Ideno, Tatsuji Komatsu, Takaaki Ikeda, Masataka Taguri, Shin Maeda
Kazuo Tarao, Department of Gastroenterology, Tarao's Gastroenterological Clinic, Yokohama City 241-0821, Japan
Akito Nozaki, Naomi Ideno, Gastroenterological Center, Yokohama City University Medical Center, Yokohama City 232-0024, Japan
Hirokazu Komatsu, Department of Gastroenterology, Yokohama Municipal Citizen’s Hospital, Yokohama City 2211-0855, Japan
Tatsuji Komatsu, Department of Clinical Research, National Hospital Organization, Yokohama Medical Center, Yokohama City 2458575, Japan
Takaaki Ikeda, Department of Gastroenterology, Yokosuka General Hospital Uwamachi, Yokosuka City 238-8567, Japan
Masataka Taguri, Department of Data Science, Yokohama City University, Yokohama, Yokohama City 236-0004, Japan
Shin Maeda, Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama City 236-0004, Japan
Author contributions: Tarao K summarized the data and wrote the paper; Nozaki A, Komatsu H, Ideno N, Komatsu T, Ikeda T, Maeda S were involved in the interpretation of data, and the development and critical revision of the manuscript for important intellectual content; Taguri M conducted statistical analysis.
Conflict-of-interest statement: All the authors declare no conflicts of interest associated with this manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kazuo Tarao, MD, PhD, Director, Department of Gastroenterology, Tarao's Gastroenterological Clinic, 3rd Floor, Taiyo-Building, 2-58-6, Futamatagawa, Asahi-ku, Yokohama City 241-0821, Japan. duoluoweih7@gmail.com
Received: April 13, 2022
Peer-review started: April 13, 2022
First decision: May 31, 2022
Revised: June 14, 2022
Accepted: June 27, 2022
Article in press: June 27, 2022
Published online: June 28, 2022
Processing time: 83 Days and 3.6 Hours
Abstract
BACKGROUND

It is generally accepted that the incidence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-associated patients is higher than that in hepatitis B virus (HBV)-associated patients. The reason why this difference in the incidence of HCC occurs in patients with HBV and HCV infections remains unclear. We report the possibility that the contributing power of inflammation, which is the main risk factor for developing HCC, may be different with HBV and HCV infections.

AIM

To investigate this, we surveyed the hazard ratio of inflammation for HCC development which was identified by serum alanine aminotransferase (ALT) levels between patients with HBV and HCV infections.

METHODS

The PubMed database was searched (2001-2021) for studies published in English regarding the incidence of HCC identifying 8924 HBV-and 7376 HCV- infected patients. From these studies, interferon-treated patients with both HBV and HCV infections were excluded. Furthermore, in HBV patients, those administered nucleos(t)ide analogues were excluded, and in HCV patients, those administered direct acting antivirals were also excluded. Studies citing hazard ratios of HCC regarding inflammation (serum elevated alanine aminotransferase levels) were selected. Finally, there were 14 studies of HBV- infected patients and 8 studies of HCV-infected patients. We calculated the hazard ratio in patients in an inflammatory state (serum ALT levels were above the normal range).

RESULTS

In the 14 studies of HBV patients, the average hazard ratio (HR) of elevated ALT for developing HCC was 2.74 [1.98-3.77] and that in the 8 studies of HCV-infected patients was 5.51 [3.08-9.83]. The HR of inflammation for HCC development in HCV-associated liver diseases is about twice that in HBV-associated liver diseases. HR in HCV-infected patients was significantly (P = 0.0391) higher than that in HBV-infected patients. In hepatitis B patients, the abnormal range adopted was 28-45 IU/L, and in hepatitis C patients, it was 20-50 IU/L. It was demonstrated that the abnormal ALT levels adopted in hepatitis B and C patients were very similar in this series.

CONCLUSION

The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT between HBV and HCV infections.

Keywords: Hazard ratio of alanine aminotransferase; Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma; Elevated alanine aminotransferase

Core Tip: It is generally accepted that the incidence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-associated of patients is higher than that in hepatitis B virus (HBV)-associated patients. We demonstrated that the incidence of HCC in HCV-associated cirrhotic patients was 4.81%/year as compared with 3.23% in HBV-associated patients based on analytic assessment of already published papers. In HBV infection, alanine aminotransferase (ALT) is the second highest risk factor, and in HCV infection, ALT is the highest risk factor, for HCC development. The hazard ratio (HR) for developing HCC in the inflammatory state (serum ALT levels exceeded the normal range) was compared between HBV and HCV patients. In the 14 studies of HBV patients, the average HR was 2.74 as compared with 5.51 in the 8 studies of HCV patients (P = 0.0391). The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT for HCC development between HBV and HCV infections.