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Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR

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A Correction to this article was published on 09 February 2023

This article has been updated

Abstract

Hepatitis C virus infection is characterized by chronic liver inflammation and fibrogenesis, leading to end-stage liver failure and hepatocellular carcinoma over the course of 20 to 30 years. It seems not only the chronicity of hepatitis C but also the presence of the virus in non-hepatic tissues creates a favorable environment for the potential development of pathogenic impacts on extrahepatic systems and organs. Numerous extra-hepatic manifestations have been reported in association with HCV infection, all of which can substantially affect morbidity, mortality, and quality of life. With the recent development of DAAs, antiviral treatment can cure almost all patients with HCV infection, even those intolerant of or unresponsive to IFN treatment, and several large multicenter studies have confirmed the association of DAA-induced SVR with reductions in liver-related and liver-unrelated complications, such as cardiovascular events, end stage renal disease, and so on. Because, in addition to liver-related diseases, extrahepatic lesions are threatening for patients, it is important to eradicate the virus before these progress and affect life prognosis; in other words, patients should be treated before reaching the point of no return. Tailored surveillance with biomarkers such as M2BPGi and Ang-2, which can be used to identify patients with an elevated risk of EHM, and early prevention or treatment for these patients could improve the morbidity, mortality and QOL. Advancement of both basic and clinical research in this field including the development of more precise biomarkers is highly anticipated.

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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Abbreviations

HCV:

Hepatitis C virus

EHM:

Extra-hepatic manifestations

CVD:

Cardiovascular diseases

NHL:

Non-Hodgkin’s lymphoma

MACE:

Major adverse cardiovascular events

ESRD:

End stage renal disease

DAAs:

Direct-acting antiviral agents

CHC:

Chronic hepatitis C

HCC:

Hepatocellular carcinoma

SVR:

Sustained virological response

QOL:

Quality of life

IFN-λ3:

The type III interferon

ROS:

Reactive oxygen species

SASP:

Senescence-associated secretory phenotype

IL-6:

Interleukin-6

IFN:

Interferon

TLR:

Toll-like receptors

TNF-α:

Tumor necrosis factor-α

CRP:

C-reactive protein

Mincle:

Macrophage-inducible C-type lectin

HRQL:

Health-related quality of life

PROs:

Patient-reported outcomes

LDL-C:

Low-density lipoprotein cholesterol

EV:

Esophageal varices

IP-10:

IFN-γ-induced protein 10

CXCL10:

Chemokine (C-X-C motif) ligand 10

M2BPGi:

Mac-2 binding protein glycosylation isomer

HVPG:

Hepatic venous pressure gradient

Ang-2:

Angiopoietin-2

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Acknowledgements

The authors thank many of the collaborative researchers and colleagues in the hospital who participated in the Ochanomizu Liver Conference Study Group. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Numbers 22fk0210106, 22fk0210104, 22fk0210067, 22fk0210072, 22ama221302, 22fk0210113, 22fk0210102, and Grant-in-Aid for Scientific Research (KAKENHI grant numbers 20K08303, 21H02896, 21K07939, 21K07977, 21K19476, 22H03054, and 22K08005).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan

    Mina Nakagawa, Yasuhiro Asahina, Sei Kakinuma & Ryuichi Okamoto

  2. Institute of Education, Tokyo Medical and Dental University, Tokyo, Japan

    Mina Nakagawa

  3. Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan

    Yasuhiro Asahina

  4. Department of Clinical and Diagnostic Laboratory Science, Tokyo Medical and Dental University, Tokyo, Japan

    Sei Kakinuma

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  1. Mina Nakagawa
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  2. Yasuhiro Asahina
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  4. Ryuichi Okamoto
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Correspondence to Yasuhiro Asahina.

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Conflict of interest

MN is an associate editor of the journal of gastroenterology. YA belongs to a donation-funded department funded by Gilead Sciences, AbbVie GK, Toray Industries, and Fujirebio Inc. SK belongs to a donation-funded department funded by Gilead Sciences, AbbVie GK, Toray Industries, and Fujirebio until May 2020. RO received a donation from Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co. Ltd and Mochida Pharmaceutical Co.

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Nakagawa, M., Asahina, Y., Kakinuma, S. et al. Impact of eradication of hepatitis C virus on liver-related and -unrelated diseases: morbidity and mortality of chronic hepatitis C after SVR. J Gastroenterol 58, 299–310 (2023). https://doi.org/10.1007/s00535-022-01940-1

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