Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease

Sasaki, Reina; Masuzaki, Ryota; Takahashi, Hiroshi; Mizutani, Taku; Matsumoto, Naoki; Nirei, Kazushige; Moriyama, Mitsuhiko

doi:10.3390/ijms21176384

Cited by 9 publications

(10 citation statements)

References 151 publications

(234 reference statements)

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“…Zinc chloride affects inflammasome associated signaling pathways in Huh7 cells infected with HAV. It has been reported that nucleotide organization domain (NOD)-like receptors (NLRs) can play a role in the host response to HAV infection (15,16). Therefore, we examined the effects of 5 μM zinc chloride on the replication of HAV genotype IIIA HA11-1299.…”

Section: Suppression Of Hav Replication Was Stronger With the Combination Of Interferon Plus Zinc Compounds Than With Interferon Alonementioning

confidence: 99%

Additive Effects of Zinc Chloride on the Suppression of Hepatitis A Virus Replication by Interferon in Human Hepatoma Huh7 Cells

Kanda

Sasaki

Masuzaki

et al. 2020

In Vivo

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Background/Aim: Hepatitis A virus (HAV) infection is still one of the serious health problems worldwide, despite the existence of effective vaccines for HAV. Zinc compounds have antiviral activities against various DNA and RNA viruses. Therefore, we investigated the effects of zinc compounds on the antiviral activity of interferon against HAV. Materials and Methods: The effects of zinc compounds with or without interferon on HAV genotype IIIA HA11-1299 replication were examined in human hepatoma Huh7 cells. Cell viability was examined by the MTS assay. Inflammasome associated gene expression was examined by real-time reverse transcription-polymerase chain reaction. Results: Both zinc sulfate and zinc chloride had an inhibitory effect on HAV replication. Zinc sulfate tended to enhance while zinc chloride significantly enhanced the anti-HAV effect induced by interferon-alpha-2a. Zinc chloride significantly up-regulated mitogen-activated protein kinase 12 (MAPK12) and downregulated 6 related genes [baculoviral IAP repeat containing 3 (BIRC3), interleukin 1 beta (IL1B), proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1), prostaglandinendoperoxide synthase 2 (PTGS2), PYD and CARD domain containing (PYCARD), and tumor necrosis factor (TNF)]. Conclusion: Zinc chloride inhibits HAV replication and has additive effects on the anti-HAV activities of interferon.

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Section: Suppression Of Hav Replication Was Stronger With the Combination Of Interferon Plus Zinc Compounds Than With Interferon Alonementioning

confidence: 99%

Additive Effects of Zinc Chloride on the Suppression of Hepatitis A Virus Replication by Interferon in Human Hepatoma Huh7 Cells

Kanda

Sasaki

Masuzaki

et al. 2020

In Vivo

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“…HAV occasionally causes acute liver failure, and HAV infection is one of the important insults in acute-on-chronic liver failure (ACLF). The severity of the ACLF caused by acute hepatitis A may be associated with severe underlying chronic liver diseases, such as advanced liver fibrosis and cirrhosis [ 4 , 38 ]. Some countries, such as Japan, have no universal vaccination program for HAV infection, and drug development for hepatitis A could be useful for controlling HAV infection and preventing severe hepatitis A.…”

Section: Discussionmentioning

confidence: 99%

“…The hepatitis A virus (HAV) is one of the major causes of acute hepatitis [ 1 , 2 , 3 ], sometimes resulting in acute liver failure, leading to a transplant or even death [ 3 , 4 ]. Although a vaccine for HAV infection has been achieved, gaining access to vaccinations may be difficult in low- and middle-income countries due to the associated high costs or ethical problems [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication

Sasaki

Masuzaki

Matsumoto

et al. 2021

IJMS

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Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) and its triggering of interferon-β production. Because MAP2K3 seems to play a role in antiviral immunity against HAV infection, it is a promising target for drug development. The inhibition of MAP2K3 may also prevent HAV patients from developing a severe hepatitis A infection.

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“…Considering any potential direct impact on HCC, HAV lacks chronicity and progression to cirrhosis, which are thought to be prerequisites of hepatocellular oncogenesis [19] and HAV past infection is not associated with the development of HCC [20,21]. Nevertheless, the pathophysiological background of HAV-mediated tissue damage implies a potential indirect contribution to HCC, at least in specific sub-populations [18].…”

Section: Hepatitis Amentioning

confidence: 99%

“…Additionally, the impact of acute HAV infection in patients' outcome is strongly dependent on the health of the liver at the time of infection. Thus, in patients with CLD, the addition of HAV infection predisposes to acute liver failure and/or cirrhosis decompensation and progress [19].…”

Section: Hepatitis Amentioning

confidence: 99%

Viral Hepatitis and Hepatocellular Carcinoma: State of the Art

et al. 2021

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Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.

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Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease

Cited by 9 publications

References 151 publications

Additive Effects of Zinc Chloride on the Suppression of Hepatitis A Virus Replication by Interferon in Human Hepatoma Huh7 Cells

Additive Effects of Zinc Chloride on the Suppression of Hepatitis A Virus Replication by Interferon in Human Hepatoma Huh7 Cells

Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication

Viral Hepatitis and Hepatocellular Carcinoma: State of the Art

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