Hepatitis Monthly
Volume:21 Issue: 7, Jul 2021

 There is limited research on the effects of physical activity with moderate intensity on βklotho (BKL) and fibroblast growth factor-21 (FGF-21) proteins expression in diabetic patients with non-alcoholic fatty liver disease (NAFLD).

 This study was aimed to determine the effects of eight weeks of endurance and resistance training on BKL and FGF-21 proteins expression in diabetic women with NAFLD.

 Forty-five diabetic women (age: 51 ± 8 years, height: 158 ± 2 cm, weight: 75 ± 8 kg) with NAFLD participated. The subjects were randomly divided into three groups, including control (n = 15), endurance training (n = 15), and resistance training (n = 15). The enzyme-linked immunosorbent assay (ELISA) was used to measure BKL and FGF-21 proteins. Two-way ANOVA with repeated measures was applied to determine differences at a significant level of P < 0.05.

 Eight weeks of endurance and resistance training reduced AST, ALT, and FGF-21 (25, 26, 19% and 13, 16, 13%, respectively) and increased BKL (16% and 18, respectively). However, in the variables of HDL, insulin, AST, ALT, FGF-21, and BKL, a significant difference was observed in the control group (P < 0.05). Also, there was a significant difference between the control and training groups in BKL and FGF21 proteins expression (P < 0.05), but no significant difference was observed between the two training groups (P > 0.05).

 The results suggest that both moderate-intensity endurance and resistance training can modulate the destructive effects of type 2 diabetes and NAFLD on BKL and FGF-21 proteins expression, and there is no difference between the two training methods.

Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma, but the understanding of the regulatory mechanisms driving NASH is not comprehensive.

We aimed to identify the potential markers of NASH and explore their relationship with immune cell populations.

Five gene expression datasets for NASH were downloaded from the Gene Expression Omnibus and European Bioinformatics Institute Array Express databases. Differentially expressed genes (DEGs) between NASH and controls were screened. Gene Ontology-Biological Process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for functional enrichment analysis of DEGs. Among the candidate genes selected from the protein-protein interaction (PPI) network and module analysis, DEG signatures were further identified using least absolute shrinkage and selection operator regression analysis. The Spearman correlation coefficient was calculated to assess the correlation between DEG signatures and immune cell abundance based on the CIBERSORT algorithm.

We screened 403 upregulated, and 158 downregulated DEGs for NASH, and they were mainly enriched in GO-BP, including the inflammatory response, innate immune response, signal transduction, and KEGG pathways, such as the pathways involved in cancer (e.g., the PI3K-Akt signaling pathway), and focal adhesion. We then screened 73 candidate genes from the PPI network and module analysis and finally identified 17 DEG signatures. By evaluating their relationship with immune cell populations, 12 DEG signatures were found to correlate with activated dendritic cells, resting dendritic cells, M2 macrophages, monocytes, neutrophils, and resting memory CD4 T cells, which were significantly different between the NASH and control tissues.

We identified a 17-DEG-signature as a candidate biomarker for NASH and analyzed its relationship with immune infiltration in NASH.

 Hepatitis C virus (HCV) may remain asymptomatic or cause liver fibrosis and cirrhosis.

 We aimed to assess the relationship between serum peptidyl-prolyl cis-trans isomerase NIMA-interacted 1 (Pin1) levels and liver fibrosis due to HCV.

 Serum samples of successive patients with HCV genotype 1b and healthy volunteers were collected, and Pin1 levels were measured using ELISA kits. Liver fibrosis stages were calculated by the Ishak Scoring System and subdivided into two groups; stage < 3 (mild fibrosis) and ≥ 3 (advanced fibrosis). Correlation and area under receiver operating characteristics (AUROC) analysis were used to investigate the relationship between Pin1 and clinical and histopathological properties of HCV infection.

 Ninety-four patients with HCV and 47 age- and sex-matched volunteers were included. The median age of the participants was 52, and 55% of whom were females. The mean (SD) of Pin1 serum level was significantly higher in the HCV group compared with healthy volunteers (33.94 (21.15) vs. 26.82 (8.85) pg/mL, respectively, P = 0.007). Seventy-seven (82%) and 17 (18%) of the participants showed mild and advanced fibrosis, respectively. Pin1 serum levels were significantly lower in the mild compared with advanced fibrosis group (29 (17.88) vs. 43.59 (7.98) pg/mL, respectively, P < 0.001). We found a significantly positive correlation between Pin1 serum level and liver fibrosis stage (r = 0.71, P < 0.001). The cut off of 33.04 pg/mL of Pin1 serum level showed the best sensitivity (100%) and specificity (68.4%) (AUROC = 0.81 [95% confidence interval: 0.72 - 0.90], P < 0.001) for distinguishing advanced from mild liver fibrosis.

 Serum Pin1 level may be a relevant marker for predicting liver fibrosis in HCV infected patients.

 Secreted frizzled-related protein 4 (sFRP4) is elevated in hepatocellular carcinoma (HCC) patients, suggesting that it can be served as a candidate marker for diagnosing HCC. However, little is known about its role in the different stages of chronic hepatitis B virus (HBV) infection.

 This study was conducted to explore the clinical value of plasma sFRP4 in the different stages of chronic HBV infection.

 A total of 303 patients with chronic HBV infection were enrolled in this cross-sectional study. They were classified into the chronic hepatitis B (CHB), liver cirrhosis (LC), HCC, and acute-on-chronic liver failure (ACLF) groups on admission. Additionally, 30 healthy subjects were included in the healthy control (HC) group. The clinical value of plasma sFRP4 in the different stages of chronic HBV infection was analyzed.

 There were 54, 85, 105, 59, and 30 cases in the CHB, LC, HCC, ACLF, and HC groups, respectively. ACLF group had the highest plasma sFRP4 levels compared to the CHB, LC, and HCC groups (all P < 0.001), followed by the HCC and LC groups. LC and HCC groups were found with up-regulated sFRP4 than the CHB group (all P < 0.05). High levels of plasma sFRP4 were recognized as an independent risk factor for distinguishing patients with ACLF from patients with CHB and LC [adjusted odds ratio (OR):1.005, 95% confidence interval (CI): 1.000 - 1.010, P = 0.043], with the area under the receiver operating characteristic curve (AUC) of 0.790 (95% CI: 0.726 - 0.844, P < 0.001). However, in patients with ACLF, plasma sFRP4 levels in the deteriorated group were higher than in the improved group, with a marginally significant difference (P = 0.071). The AUC for predicting the 90 days prognosis in patients with ACLF was 0.640 (P = 0.064).

 Plasma sFRP4 might be a biomarker to reflect the progression of chronic HBV infection. However, it was not significantly related to the prognosis in patients with ACLF; we did not find this, which may be due to the small sample size.

Context: 

Hepatitis C Virus (HCV) infection is a major cause of chronic cirrhosis and hepatocellular carcinoma. Approximately 30% of infected persons with HCV spontaneously clear the viral infection; but, some of the remaining patients develop chronic HCV. Studies show that HLA molecules play an important role in the outcome of HCV infection by influencing the efficiency of the antiviral immune response to HCV infection. It is now known that polymorphisms in HLA loci are associated with HCV susceptibility or clearance. The purpose of the present study was to systematically review the studies that reported the association of HLA class II alleles (HLA-DQ and HLA-DR) with the outcome of HCV infection.

Evidence Acquisition: 

Studies were identified by searching electronic databases, including PubMed and Scopus. A total of 12,265 relevant studies were identified by the electronic search, of which a total of 19 eligible papers were identified that were meta-analyzed for the association between HLA class II alleles and the outcome of HCV infection.

 Subjects carrying HLA-DQB1*0301, HLA-DQB1*0501, HLA-DRB1*1303, HLA-DRB1*1201, HLA-DRB1*0401, HLA-DRB1*0101, and HLA-DRB1*1101 alleles were significantly associated with higher spontaneous clearance of HCV infection.

 The data from the current study confirm that several polymorphisms in HLA-DQ and HLA-DR loci are correlated with the clearance of HCV infection. Identifying these polymorphisms may contribute to a better understanding of immune mechanisms of HCV clearance or persistence.