Tracking of Stem Cells in Chronic Liver Diseases: Current Trends and Developments.

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described.

The high level of IL-1β in the serum of ACLF patients induces increased IL-8 expression in hUC-MSCs and reduces the efficacy of hUC-MSCs in liver failure.

Background: Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients' serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs.

Upregulation of microRNA-125b-5p alleviates acute liver failure by regulating the Keap1/Nrf2/HO-1 pathway.

Background: Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are the two most common subtypes of liver failure. They are both life-threatening clinical problems with high short-term mortality. Although liver transplantation is an effective therapeutic, its application is limited due to the shortage of donor organs.

Concomitant Diseases and Co-contribution on Progression of Liver Stiffness in Patients with Hepatitis B Virus Infection.

Background: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear.

Aim: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness.

Methods: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017.

Antiviral Therapy for Chronic HBV Infection With Persistently Normal Alanine Aminotransferase: Controversy and Consensus.

ALT is one of the most sensitive biochemical indexes to reflect liver injury. It is generally believed that hepatitis B virus (HBV) infected patients with normal ALT levels are in either immune tolerance or low replication stage of the natural history of hepatitis B, and there is no or only mild inflammation in liver tissue, so antiviral therapy is not recommended. However, chronic HBV-infected patients with normal ALT levels are not always in a stable state.

Retrospective Analysis of the Clinical Efficacy of N-Acetylcysteine in the Treatment of Hepatitis B Virus Related Acute-on-Chronic Liver Failure.

HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high mortality due to severe intrahepatic cholestasis and coagulation dysfunction, thus new treatment measures are urgently needed to improve the therapeutic effect. This study aimed to observe the efficacy of N-acetylcysteine (NAC) in the treatment of HBV-ACLF. The data of patients with HBV-ACLF admitted to West China Hospital from October 2019 to August 2020 were collected retrospectively, and they were divided into treatment group and control group according to whether they had received additional NAC treatment.

Cell heterogeneity, rather than the cell storage solution, affects the behavior of mesenchymal stem cells in vitro and in vivo.

Background: Mesenchymal stem cells (MSCs) have to be expanded in vitro to reach a sufficient cell dose for the treatment of various diseases. During the process of expansion, some obstacles remain to be overcome. The purpose of this study was to investigate the effects of storage solutions and heterogeneity on the behavior of MSCs in vitro and in vivo.

Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background And Aim: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease).

Methods: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data.

Efficacy and safety of sofosbuvir-based pangenotypic direct-acting antiviral agents for chronic hepatitis C patients without genotype determination: Real-world experience of a retrospective study.

Several new, pangenotypic direct-acting antiviral agents (DAAs) have been approved, may reduce the need for genotyping to guide therapy decisions for patients with chronic hepatitis C (CHC).This study aimed to investigate the efficacy and safety of Sofosbuvir (SOF)-based pangenotypic DAAs therapy for CHC patients without genotype (GT determination in the real-world practice.This retrospective cohort study included treatment-naïve CHC patients without GT determination, who received SOF-based DAAs therapy, including 400 mg SOF plus 60 mg daclatasvir (DCV) daily or 400 mg SOF plus 100 mg velpatasvir (VEL) daily for 12 or 24 weeks.

Distribution and factors associated with serum HBV pregenomic RNA levels in Chinese chronic hepatitis B patients.

Correlations between serum hepatitus B virus (HBV) pregenomic RNA (pgRNA), hepatitus B surface antigen (HBsAg), and hepatitus B core-related antigen (HBcrAg) levels, and influencing factors of serum HBV pgRNA levels in Chinese chronic hepatitis B (CHB) patients are rarely reported. This was a retrospective cohort study consisting of 204 outpatients with CHB. Serum levels of HBV pgRNA, HBsAg, and HBcrAg were quantitative measured in frozen blood samples.

TRAIL inhibits HBV replication and expression by down-regulating liver-enriched transcription factors.

Background And Study Aims: To investigate the role of low-concentration TRAIL on HBV replication and expression.

Material And Methods: MTT assay was performed to determine the minimum concentrations of TRAIL protein in HepG2 cell apoptosis. HepG2 cells were transfected by HBV replication plasmid pHBV4.

Optimal drug administration manner would rescue partial virological response in chronic hepatitis B patients with entecavir or tenofovir treatment.

Not all treatment-naïve patients receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy can achieve complete virological response, and many factors may be related with the outcome of partial virological response. This study aimed to determine whether the manner of drug administration affects the antiviral efficacy of ETV/TDF monotherapy. All eligible patients were divided into complete or partial response cohorts based on their virological response following 24-week therapy.

Tenofovir monotherapy versus tenofovir plus entecavir combination therapy in HBeAg-positive chronic hepatitis patients with partial virological response to entecavir.

Aims: The aim of this retrospective study was to compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy and TDF + entecavir (ETV) combination therapy for chronic hepatitis B (CHB) patients with the partial virological response (PVR) to ETV.

Methods: CHB patients with PVR to ETV were switched to TDF monotherapy or TDF + ETV combination therapy. The primary efficacy outcome was a virological response (VR), and the secondary efficacy outcomes were hepatitis B e antigen (HBeAg) seroconversion and alanine aminotransferase (ALT) normalization.

TIPS Is Not Associated with a Higher Risk of Developing HCC in Cirrhotic Patients: A Systematic Review and Meta-analysis.

The association between portal-systemic shunt and hepatocellular carcinoma (HCC) development in patients who have cirrhosis is still controversial. This systematic review with meta-analysis was performed to systematically clarify the potential role of portal-systemic shunt in the development of HCC. The PubMed, Embase, and Cochrane Library databases were searched for potentially eligible literature.

An epidemiology survey of vitamin D deficiency and its influencing factors.

Background: There is growing evidence that vitamin D is related to the development of a variety of diseases. The current study was performed to investigate the status of serum vitamin D distribution among adult Chinese people and reveal the influence of gender, age, seasonality and residential regions on serum vitamin D levels.

Method: This cross-sectional study included 14,302 participants aged from 18 years old to 65 years old from six major cities in China.

Apolipoprotein A5 alleviates LPS/D-GalN-induced fulminant liver failure in mice by inhibiting TLR4-mediated NF-κB pathway.

Background: Fulminant liver failure (FHF) is a serious clinical problem and liver transplantation is the major intervention. But the overall survival rate of FHF is low owing to the donated organ shortage. Apolipoprotein A-V (ApoA5) is a regulator of triglyceride metabolism and has been reported to act as a predictor for remnant liver growth after preoperative portal vein embolization and liver surgery.

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA.

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg-positive and HBeAg-negative CHB patients. In this study, 85 HBeAg-positive and 25 HBeAg-negative patients who have never received antiviral therapy were included.

Stem cell transplantation for the treatment of end-stage liver disease.

The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer, liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease.

Insight into the role of TRAIL in liver diseases.

TNF-related apoptosis inducing ligand (TRAIL) is a potential antitumor protein known for its ability to selectively eliminate various types of tumor cells without exerting toxic effects in normal cells and tissues. TRAIL has recently been suggested as a potential therapeutic target in hepatocellular carcinoma (HCC) because it promotes apoptosis in cancer cells. Furthermore, studies on the role of TRAIL in liver injury have reported that TRAIL plays an essential role in viral hepatitis, fatty liver diseases, etc.

A retrospective study of the efficacy of sofosbuvir plus NS5A inhibitors for patients with hepatitis C virus genotype-2 chronic infection.

Background: A combination of sofosbuvir (SOF)+NS5A inhibitor therapies is the main treatment for patients with hepatitis C virus (HCV) genotype-2 (GT-2) chronic infection, but the data are rarely reported in China. This study aimed to investigate the virological response and liver fibrosis improvement among GT-2 patients receiving SOF+NS5A inhibitors.

Patients And Methods: In this retrospective study, patients who received SOF+NS5A inhibitors between March 2016 and July 2017 were recruited.

Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotype 6 in Southwest China: Real-world experience of a retrospective study.

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017.

Progress in mesenchymal stem cell-based therapy for acute liver failure.

Acute liver failure is a life-threatening clinical syndrome characterized by rapid development of hepatocellular necrosis leading to high mortality and resource costs. Numerous treatment strategies for acute liver failure simply prevent complications and decelerate disease progression. The only curative treatment for acute liver failure is liver transplantation, but there are many restrictions on the application of liver transplantation.

Human mesenchymal stem cells for hepatitis B virus-related acute-on-chronic liver failure: a systematic review with meta-analysis.

Background And Aim: Acute-on-chronic liver failure (ACLF) is a condition with high mortality. New strategies are urgently required. The present review aims to provide a comprehensive understanding of the efficacy and safety of mesenchymal stem cells (MSC) treatment in patients with ACLF associated with hepatitis B virus infection.

The truncated mutant HBsAg expression increases the tumorigenesis of hepatitis B virus by regulating TGF-β/Smad signaling pathway.

Background: It has been reported that the emergence of HBV rtA181T/sW172* mutant could result in a dominant secretion defect of HBsAg and increase the risk of HCC development. This study was designed to reveal the role and possible pathogenic mechanism of truncated mutant HBsAg in tumorigenesis of HBV rtA181T/sW172* mutant.

Results: As compared to wide type or substituted mutant HBsAg, the ratio of cell clones was significant higher in L02 cells stable expressing truncated mutant HBsAg.

New insights into the role of vitamin D in hepatocellular carcinoma.

In addition to being crucial for host immune defense, vitamin D is involved in cell proliferation, apoptosis, differentiation, inflammation, invasion and metastasis, angiogenesis and micro-RNA modulation. To date, clinical studies have demonstrated that vitamin D deficiency is common not only in patients with chronic liver diseases but also in those with hepatocellular carcinoma (HCC). Experimental studies have also demonstrated that vitamin D and its receptors are related to the occurrence of HCC and the prognoses of patients with HCC.