Qinglong Jin

Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population

Background: Recent genome‐wide association studies found that genetic polymorphisms near the IL28B gene is strongly associated with sustained viral response and spontaneous viral clearance in chronically infected hepatitis C patients.

Immunologic Characterization of Posthepatitis Cirrhosis Caused by HBV and HCV Infection

No specific treatment can reverse the liver injury in cirrhosis. This study aims to characterize immune status and correlations between cirrhosis induced by HBV and HCV. Phenotypes of peripheral blood lymphocyte subsets (T, NK, regulatory T cells) and Th cytokine secretion were analyzed using flow cytometry in 42 HBV-cirrhotic and 40 HCV-cirrhotic patients. Cirrhotic patients had a lower proportion of CD3+CD8+T cells and NK cells, while the proportion of CD3+CD4+T cells and Treg cells were higher than those of healthy controls. The levels of Th2 cytokine (IL-6) in cirrhotic patients were increased, while only the Th1 cytokine (IFN-γ) increased in HBV-cirrhotic patients. These findings show that there is no difference between the cirrhotic groups except in the IFN-γ level. In cirrhosis, defects in innate, adaptive immune cells are likely regardless of which virus is involved. A cytokine imbalance may play a role in the development of posthepatitic cirrhosis.

Red Blood Cell Distribution Width to Platelet Ratio is Related to Histologic Severity of Primary Biliary Cirrhosis.

AbstractWe aimed to investigate whether red blood cell distribution width (RDW) and RDW to platelet ratio (RPR) were related to the histologic severity of primary biliary cirrhosis (PBC).Seventy-three treatment-naïve PBC patients who had undergone a liver biopsy between January 2010 and January 2015 were enrolled in our study. The patients’ histological stages were based on the classifications of Ludwig and Scheuer. The patients were divided into early stage (Stage I) and advanced stage (Stage II, III, and IV) hepatic fibrosis according to their histological stage. All common patient demographics, clinical characteristics, hematological parameters, liver biochemistry, and antimitochondrial M2 antibody levels (AMA-M2) were retrospectively analyzed, and RDW, RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were calculated.A total of 28 (38.4%) patients had early stage PBC, whereas 45 (62.6%) were classified as advanced stage. Regarding age, no significant differences between the early and advanced stages were observed. Patients with advanced stage PBC had significantly higher RDW (13.6 vs 14.4; P = 0.019), conjugated bilirubin (10.1 vs 23.4; P = 0.029), and significantly lower cholinesterase (7901.1 vs 6060.8; P = 0.001) and platelets (212.6 vs 167.0; P = 0.006). However, no significant differences (P > 0.05) in other routine parameters previously evaluated in PBC, including aspartate aminotransferase (AST) and mean platelet volume, were found between the groups. The sensitivity and specificity of RDW were 33.3% and 92.9%, respectively, and the area under the receiver-operating characteristic curve (AUROC) was 0.66. However, the sensitivity and specificity of RPR were 46.7% and 96.4%, respectively, and the corresponding AUROC was 0.74 (P < 0.001). Hence, compared with preexisting indicators, RPR showed a higher AUROC than APRI (0.648; P = 0.035) and FIB-4 (0.682; P = 0.009).RDW and RPR may be a new noninvasive marker for predicting histologic severity of PBC.

Red blood cell distribution width and globulin, noninvasive indicators of fibrosis and inflammation in chronic hepatitis patients.

Aims We aimed to develop new simple predictive models for significant fibrosis and inflammation in chronic hepatitis patients using routine laboratory parameters. Methods A total of 218 patients who had undergone liver biopsy were enrolled in our study. Among these, 116 had chronic hepatitis B, 65 had primary biliary cirrhosis, and 37 had autoimmune hepatitis. Patients were divided into two groups: absent–mild (S0–S1, G0–G1) and moderate–severe (S2–S4, G2–G4) according to the histologic severity of liver fibrosis and inflammation. All common demographics and routine laboratory parameters were analyzed. Results Red blood cell distribution width (RDW) and globulin values increased with progressive liver fibrosis and inflammation. After adjustment for other potent predictors, liver fibrosis was associated independently with RDW and platelet (odds ratio=0.976 and 1.487, respectively), whereas significant inflammation was associated independently with globulin, alanine aminotransferase, red blood cell, and platelet (odds ratio=1.153, 1.017, 0.392, and 1.487, respectively). The sensitivity and specificity of model A were 73.4 and 79.1% for the detection of significant liver fibrosis [area under the receiver-operating characteristic curve (AUROC)=0.81, P<0.001]. The sensitivity and specificity of model B were 75.9 and 88.9% for predicting advanced liver inflammation (AUROC=0.89, P<0.001). Compared with pre-existing indicators, model A achieved the highest AUROC (0.81, P<0.001) for liver fibrosis, whereas model B showed the highest AUROC (0.89, P<0.001) for liver inflammation. Conclusion RDW may provide a useful clinical value for predicting liver fibrosis; meanwhile, globulin may provide a useful clinical value for predicting liver inflammation in chronic hepatitis patients with other markers.

Antiviral treatment alters the frequency of activating and inhibitory receptor-expressing natural killer cells in chronic hepatitis B virus infected patients.

Natural killer (NK) cells play a critical role in innate antiviral immunity, but little is known about the impact of antiviral therapy on the frequency of NK cell subsets. To this aim, we performed this longitudinal study to examine the dynamic changes of the frequency of different subsets of NK cells in CHB patients after initiation of tenofovir or adefovir therapy. We found that NK cell numbers and subset distribution differ between CHB patients and normal subjects; furthermore, the association was found between ALT level and CD158b+ NK cell in HBV patients. In tenofovir group, the frequency of NK cells increased during the treatment accompanied by downregulated expression of NKG2A and KIR2DL3. In adefovir group, NK cell numbers did not differ during the treatment, but also accompanied by downregulated expression of NKG2A and KIR2DL3. Our results demonstrate that treatment with tenofovir leads to viral load reduction, and correlated with NK cell frequencies in peripheral blood of chronic hepatitis B virus infection. In addition, treatments with both tenofovir and adefovir in chronic HBV infected patients induce a decrease of the frequency of inhibitory receptor+ NK cells, which may account for the partial restoration of the function of NK cells in peripheral blood following treatment.

Dyslipidemia in northeastern China

Dyslipidemia, is a major risk factor for premature coronary artery disease. Our aim was to estimate the prevalence of dyslipidemia (blood lipid abnormalities) and other risk factors associated with coronary artery diseases among an adult population in northeastern China. Throughout the months of September and October of 2007,a population-based cross-sectional study was conducted and a total of 3,815 individuals were included. Total cholesterol (TC), high-density cholesterol (HDL-C), low-density cholesterol (LDL-C), and triglycerides (TG) were measured. A binary logistic regression analysis was conducted to determine risk factors associated with dyslipidemia. The prevalence of hypercholesterolemia, high LDL-C, low HDL-C, and hypertriglyceridemia were 17.3%, 27.8%, 11.66% and 29.85%, respectively. The prevalence of hypertension, central obesity, alcoholic liver disease (ALD), non-ALD, diabetes and metabolic syndrome was higher in serum lipid abnormality groups than in the non-dyslipidemia group (p < 0.001). In a binary logistic regression, hyperlipidemia was positively correlated with age, male, hypertension, high body mass index, etc. There were negative correlations with being female and the level of education a subject had attained. Dyslipidemia is a major risk factor for premature coronary artery diseases and an important public health issue in the northeastern part of China. Dyslipidemia is more frequent than expected based on previous studies. To control dyslipidemia, routine evaluations in clinics and community centers are needed, as well as effective public health education.

Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population: A Case-Control Study

Background:Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance. The aim of this study was to identify associations between estrogen receptor (ESR) gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population. Methods:Thirty-six patients with PBC (case group) and 35 healthy individuals (control group) from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms (rs2234693, rs2228480, and rs3798577) from ESR1 and two (rs1256030 and rs1048315) from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected. Results:Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele (odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872–4.5517). Haplotypes TGC of ESR1 rs2234693, rs2228480, and rs3798577 were risk factors for having PBC. The C allele at ESR1 rs2234693 was associated with abnormal alkaline phosphatase (OR = 5.2469, 95% CI = 1.3704–20.0895) and gamma-glutamyl transferase (OR = 3.4286, 95% CI = 1.0083–13.6578) levels in PBC patients. Conclusions:ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.

MicroRNA-223 and microRNA-21 in peripheral blood B cells associated with progression of primary biliary cholangitis patients

Recently, there is ample evidence suggesting the important role of microRNAs (miRNAs) in autoimmune diseases via modulating B cells function. Primary biliary cholangitis (PBC) is a progressive immune-mediated liver disease with unclear pathogenic mechanism. Whether the miRNA in peripheral B cells of PBC involve the mechanisms of pathology and progression is not known. The present study explores miRNA deregulation in peripheral B-cell of PBC from stage I to IV and healthy controls. Peripheral B cells were obtained from 72 PBC patients (stage I, n = 17; stage II, n = 23; stage III, n = 16; stage IV, n = 16) and 15 healthy controls. Initially, in a discovery study, miRNA array analysis was performed, subsequently, in a validation study, quantitative PCR was used to investigate miRNA expression profile in B cells of PBS patients compared to healthy controls. Based on bioinformatics analysis, we identified the potential biological processes and significant signaling pathways affected by these microRNAs, and generated the microRNA–gene network. The discovery study identified 558 miRNAs differentially expressed in B cells of PBC patients compared to controls. Interestingly, among all differentially expressed miRNAs, hsa-miR-223-3p and hsa-miR-21-5p were the only miRNAs that showed consistent and significant down-regulation from stage I to stage III of PBC. Bioinformatics showed that potential target genes of both miRNAs involved in migration, cell differentiation, apoptosis, and signal transduction pathways. In conclusion, our results suggest that the expression profiles of miRNA in peripheral B cells of PBC patients are closely associated with the disease progression, especially the down-regulation of hsa-miR-223-3p and hsa-miR-21-5p. Taken together, our study offers novel perspectives on the role of miRNAs in PBC pathogenesis.

Changes in liver stiffness and its associated factors during oral antiviral therapy in Chinese patients with chronic hepatitis B

The present study aimed to assess improvements in liver stiffness determined by transient elastography and associated factors in Chinese patients with chronic hepatitis B (CHB) during long-term treatment with oral antiviral drugs. A total of 334 consecutive Chinese patients with CHB who underwent oral antiviral therapy and received at least two liver stiffness measurements (LSMs) at the First Hospital of Jilin University (Changchun, China) from December 2012 to February 2015 were enrolled in the present study. The cohort included 201 patients without liver cirrhosis (group 0) and 133 patients with liver cirrhosis (group 1). Each patient was subjected to LSM twice with an interval of 6 months. The mean initial liver stiffness values were 14.01±9.37 and 21.59±10.25 kPa for patients in group 0 and group 1, respectively (P<0.001). Multivariate analysis revealed that higher aspartate aminotransferase and lower alanine aminotransferase levels at baseline as well as higher α-fetoprotein levels at follow-up (24 weeks) were associated with a greater decline of liver stiffness in group 0. Furthermore, a higher liver stiffness at baseline and a longer course of antiviral therapy prior to the initial LSM were significantly correlated with a reduction of liver stiffness, whereas higher total bilirubin levels at follow-up contributed to increased liver stiffness in group 1. In conclusion, LSM at the beginning and the end of a 24-week observation period showed that antiviral drug therapy significantly improved in group 1, while a marked decreasing trend was also observed in group 0. In group 0, the reduction of liver stiffness was correlated with liver inflammation, whereas in group 1, it was correlated with the treatment duration prior to the initial LSM and serum levels of hepatitis B virus DNA. Furthermore, a higher liver stiffness at baseline was associated with a greater reduction of liver stiffness in each group.

Association between ABO blood group and HCV-related hepatocellular carcinoma risk in China.

Abstract The ABO blood group has previously been reported to be associated with risk for certain malignancies; however, data about the risks for hepatocellular carcinoma (HCC) according to blood type are limited. Thus, we conducted a retrospective case–control study to investigate whether the ABO blood group contributes to hepatitis C virus (HCV) infection–induced HCC. From January 2010 to June 2016, 447 consecutive patients with chronic HCV infection were recruited. Of these patients, 217 had HCV-related HCC, and 230 had chronic hepatitis C (CHC) without HCC. We performed multivariate logistic regression to probe the association between the ABO blood group and HCC risk. Compared with subjects with blood type O, patients with blood type A had an adjusted odds ratio (AOR) of 3.301 (95% confidence interval [CI], 1.927–5.653) for HCC after adjusting for age and gender. We found statistically significant associations between blood type A and HCC risk for both men (AOR [95% CI] = 4.192 [1.959–8.973]) and women (AOR [95% CI] = 2.594 [1.231–5.466]), and for patients aged below 70 years (<60 years: AOR [95% CI] = 3.418 [1.338–8.734]; 60–69 years: AOR [95% CI] = 3.917 [1.730–8.867]). Thus, HCC risk is associated with ABO blood type in Chinese CHC patients, and CHC patients with blood type A are more susceptible to HCV-related HCC than patients with other blood types.