Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B / 中南大学学报(医学版)

OBJECTIVES@#Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).@*METHODS@#This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.@*RESULTS@#Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).@*CONCLUSIONS@#The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.

Comparison of tenofovir alafenamide and entecavir for hepatitis B virus-related acute-on-chronic liver failure / 中南大学学报(医学版)

OBJECTIVES@#Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF.@*METHODS@#The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．.@*RESULTS@#After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group.@*CONCLUSIONS@#TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.

Construction of the overexpressed lentiviral vector for targeting human TNFAIP1 gene / 中国医师杂志

Objective To construct a lentivirus vector over-expressing Tumor necrosis factor alpha induced protein 1 (TNFAIP1) gene and detect its expression level in vitro.Methods The full length of TNFAIP1 gene fragments were amplified by polymerase chain reaction (PCR).The pEZ-Lv105 vectors were digested by restriction endonuclease which was then linked to the full length of TNFAIP1 gene fragments by using T4DNA ligase.The plasmids were transfected into E.coli stbl3 and then we obtained the highly expressing positive clones by screening and identifying.The lentivirus vectors containing TNFAIP1 gene were transfected into 293T cells for package according to the packing kit manual.Results TNFAIP1 gene was amplified and successfully bound to the pEZ-Lv105 lentivirus vectors.The sequences of the recombinant plasmids were confirmed correctly by PCR and DNA sequence.The enhanced green fluorescent protein (eGFP) could be observed after recombinant lentiviruses were cotransfected into 293T cells.Conclusions The TNFAIP1 overexpressed lentivirus vector is successfully constructed,which provides a molecular tool for further study of TNFAIP1 gene in optic nerve glioma.

Research progress in regulation roles of G protein-coupled receptors in hepatocellular carcinoma / 中国药理学与毒理学杂志

G protein- coupled receptors (GPCRs), also known as seven- transmembrane domain receptors, constitute the largest superfamily of cell surface receptors. By coupling to heterotrimeric G proteins, arrestins and other signaling molecules, GPCRs modulate diverse signal transduction pathways under physiological and pathological conditions. Recent studies have revealed crucial roles of GPCRs in tumorigenesis and development of cancer metastasis. This review summarizes roles of GPCRs, particularly the roles of those coupled to chemokines, prostaglandin, lysophosphatidic acid, endothelin, catecholamine and angiotensin in proliferation, invasion, metastasis and angiogenesis of hepatoma cells and development of hepatocellular carcinoma. The potential of GPCRs- based therapeutics being used for hepatocellular carcinoma is also highlighted.

Type Ⅲ TGF-βreceptor mediated signaling pathway and its role in fibrotic diseases / 中国药理学通报

Transforming growth factor β(TGF-β)superfamily ligands play an important role in regulating cellular homeostasis including proliferation,differentiation,apoptosis,immune sur-veillance and angiogenesis.Type Ⅲ TGF-βreceptor (TβRⅢ) is considered to be the coreceptor of TGF-βsuperfamily.TβRⅢnot only has an effect on classical Smad signaling pathway,but also on non-Smad signaling pathway.TβRⅢplays a crucial role in fibrosis,tumor,cardiovascular diseases via mediating kinds of signaling pathways.This paper reviews TβRⅢ mediated sig-naling pathway and its role in fibrotic diseases.