Efficacy and safety of spleen aminopeptide oral lyophilized powder in ameliorating liver injury in infants and children with human cytomegalovirus infection: a single-center study in China

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Abstract

Background

Liver injury is both very common in infants and children and associated with low immune function. This study aimed to investigate the effect of spleen aminopeptide oral lyophilized powder (SAOLP) on liver injury in infants and children with human cytomegalovirus (HCMV) infection.

Methods

In this prospective observational study, 217 infants and children with both liver damage and HCMV infection who were admitted to the Department of Pediatric Gastroenterology, Children’s Hospital of Nanjing Medical University between July 2018 and May 2020 were investigated. The median age of patients was 0.75 years (0.36–3.77 years), with 105 male and 112 female participants. All 217 patients received ursodeoxycholic acid (UDCA) and/or reduced glutathione (GDC) therapy. Of these 217 patients, 114 also received SAOLP. Liver function, cellular immunity levels, HCMV antibody titer, and HCMV-DNA load values were measured 1 day before treatment, and on the second and fourth week after treatment.

Results

After 4 weeks, patients treated with SAOLP showed median levels of serum alanine aminotransferase (ALT), total bilirubin (TB), and direct bilirubin (DB) which were significantly lower than those seen in patients who did not receive it. In addition, the percentage of CD4+ cells was significantly higher in those treated with SAOLP in comparison to those treated with UDCA and/or GDC alone. The number of positive HCMV-immunoglobin M (IgM) patients was also sharply decreased in the group receiving SAOLP.

Conclusions

The addition of SAOLP to UDCA and/or GDC therapy may significantly relieve liver injury and reduce the jaundice index by enhancing immune function and anti-HCMV infection ability in infants and children.

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Most cited references 24

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Liver injury during highly pathogenic human coronavirus infections

Ling Xu, Jia Liu, Mengji Lu … (2020)

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐Cov‐2), the pathogen of 2019 novel coronavirus disease (COVID‐19), has posed a serious threat to global public health. The WHO has declared the outbreak of SARS‐CoV‐2 infection an international public health emergency. Lung lesions have been considered as the major damage caused by SARS‐CoV‐2 infection. However, liver injury has also been reported to occur during the course of the disease in severe cases. Similarly, previous studies have shown that liver damage was common in the patients infected by the other two highly pathogenic coronavirus – severe acute respiratory syndrome coronavirus (SARS‐CoV) and the Middle East respiratory syndrome coronavirus (MERS‐CoV), and associated with the severity of diseases. In this review, the characteristics and mechanism of liver injury caused by SARS‐CoV, MERS‐CoV as well as SARS‐CoV‐2 infection were summarized, which may provide help for further studies on the liver injury of COVID‐19.

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Is Open Access

Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy

Huanhuan Lv, Chenxiao Zhen, Junyu Liu … (2019)

Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells in order to meet the enhanced metabolism and vicious proliferation; meanwhile, they also have to develop an increased antioxidant defense system to cope with the higher oxidant state. Growing numbers of studies have implicated that altering the glutathione antioxidant system is associated with multiple forms of programmed cell death in cancer cells. In this review, we firstly focus on glutathione homeostasis from the perspectives of glutathione synthesis, distribution, transportation, and metabolism. Then, we discuss the function of glutathione in the antioxidant process. Afterwards, we also summarize the recent advance in the understanding of the mechanism by which glutathione plays a key role in multiple forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, and autophagy. Finally, we highlight the glutathione-targeting therapeutic approaches toward cancers. A comprehensive review on the glutathione homeostasis and the role of glutathione depletion in programmed cell death provide insight into the redox-based research concerning cancer therapeutics.

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Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited.

G Paumgartner, Ulrich Beuers (2002)

Ursodeoxycholic acid (UCDA) is increasingly used for the treatment of cholestatic liver diseases. Experimental evidence suggests three major mechanisms of action: (1) protection of cholangiocytes against cytotoxicity of hydrophobic bile acids, resulting from modulation of the composition of mixed phospholipid-rich micelles, reduction of bile acid cytotoxicity of bile and, possibly, decrease of the concentration of hydrophobic bile acids in the cholangiocytes; (2) stimulation of hepatobiliary secretion, putatively via Ca(2+)- and protein kinase C-alpha-dependent mechanisms and/or activation of p38(MAPK) and extracellular signal-regulated kinases (Erk) resulting in insertion of transporter molecules (e.g., bile salt export pump, BSEP, and conjugate export pump, MRP2) into the canalicular membrane of the hepatocyte and, possibly, activation of inserted carriers; (3) protection of hepatocytes against bile acid-induced apoptosis, involving inhibition of mitochondrial membrane permeability transition (MMPT), and possibly, stimulation of a survival pathway. In primary biliary cirrhosis, UDCA (13-15 mg/kg/d) improves serum liver chemistries, may delay disease progression to severe fibrosis or cirrhosis, and may prolong transplant-free survival. In primary sclerosing cholangitis, UDCA (13-20 mg/kg/d) improves serum liver chemistries and surrogate markers of prognosis, but effects on disease progression must be further evaluated. Anticholestatic effects of UDCA have also been reported in intrahepatic cholestasis of pregnancy, liver disease of cystic fibrosis, progressive familial intrahepatic cholestasis, and chronic graft-versus-host disease. Future efforts will focus on definition of additional clinical uses of UDCA, on optimized dosage regimens, as well as on further elucidation of mechanisms of action of UDCA at the molecular level.

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Author and article information

Journal

Journal ID (nlm-ta): Transl Pediatr

Journal ID (iso-abbrev): Transl Pediatr

Journal ID (publisher-id): TP

Title: Translational Pediatrics

Publisher: AME Publishing Company

ISSN (Print): 2224-4336

ISSN (Electronic): 2224-4344

Publication date (Print and electronic): January 2021

Publication date (Print): January 2021

Volume: 10

Issue: 1

Pages: 136-145

Affiliations

[1]Department of Pediatric Gastroenterology, Children’s Hospital of Nanjing Medical University , Nanjing, China

Author notes

Contributions: (I) Conception and design: H Yang; (II) Administrative support: Y Jin; (III) Provision of study materials or patients: Y Wu, X Dong, R Wu, X Zheng; (IV) Data analysis and interpretation: Y Jin, H Yang; (V) Manuscript writing: H Yang; (VI) Final approval of manuscript: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Hui Yang. Department of Pediatric Gastroenterology, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, China. Email: xinghui7325@ 123456sina.com .

[^]

ORCID: 0000-0002-6870-9740.

Article

Publisher ID: tp-10-01-136

DOI: 10.21037/tp-20-173

PMC ID: 7882289

PubMed ID: 33633945

SO-VID: 0067de01-87f0-4fb7-93e7-8f89183206f3

License:

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

History

Date received : 03 July 2020

Date accepted : 22 October 2020

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Efficacy and safety of spleen aminopeptide oral lyophilized powder in ameliorating liver injury in infants and children with human cytomegalovirus infection: a single-center study in China

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Most cited references 24

Liver injury during highly pathogenic human coronavirus infections

Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy

Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited.

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