Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

AIM: To investigate peripheral T-lymphocyte sub-population profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS: Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR). The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS: CHB patients had significantly decreased CD3+ and CD4+ cells and CD4+/CD8+ ratio, and increased CD8+ cells compared with uninfected controls (55.44 ± 12.39 vs 71.07 ± 4.76, 30.92 ± 7.48 vs 38.94 ± 3.39, 1.01 ± 0.49 vs 1.67 ± 0.33, and 34.39 ± 9.22 vs 24.02 ± 4.35; P < 0.001, respectively). Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load, presence of serum hepatitis B e antigen (HBeAg) expression, liver disease severity, history of maternal HBV infection, and young age at HBV infection, all with P < 0.01. There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P < 0.001). There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r = -0.68, -0.65 and -0.75, all P < 0.0001), and a positive correlation between CD8+ cells and viral load (r = 0.70, P < 0.0001). There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P < 0.01). In multiple regression (after adjustment for age at HBV infection, maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations, and was the strongest predictor of variation in CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio. However, the effect of HBeAg was not significant.CONCLUSION: T-lymphocyte failure was signifi-cantly associated with viral replication level. The substantial linear dose-response relationship and strong independent predictive effect of viral load on T-lymphocyte subpopulations suggests the possibility of a causal relationship between them, and indicates the importance of viral load in the pathogenesis of T cell hyporesponsiveness in these patients.

Sex-influenced association of non-alcoholic fatty liver disease with colorectal adenomatous and hyperplastic polyps

AIM To investigate the relationship between non-alcoholic fatty liver disease(NAFLD) and colorectal adenomatous and hyperplastic polyps.METHODS A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups(2430 males and 1256 females). All subjects underwent laboratory testing,abdominal ultrasonography,colonoscopy,and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps.Furthermore,the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number,size,and location of colorectal polyps.RESULTS The prevalence of colorectal polyps was 38.8% in males(16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females(8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables,NAFLD was significantly associated with the prevalence of adenomatous polyps(OR = 1.28,95%CI: 1.05-1.51,P < 0.05) and hyperplastic polyps(OR = 1.35,95%CI: 1.01-1.82,P < 0.05). However,upon analyzing adenomatous and hyperplastic polyps in different sex groups,the significant association remained in males(OR = 1.53,95%CI: 1.18-2.00,P < 0.05; OR = 1.42,95%CI: 1.04-1.95,P < 0.05) but not in females(OR = 0.44,95%CI: 0.18-1.04,P > 0.05; OR = 1.18,95%CI: 0.50-2.78,P > 0.05). CONCLUSION NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However,NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.

Hepatitis B virus DNA is more powerful than HBeAg in predicting peripheral T-lymphocyte subpopulations in chronic HBV-infected individuals with normal liver function tests

AIM:To investigate the peripheral T-lymphocyte subpopulation profile,and its correlations with hepatitis B virus(HBV) replication level in chronic HBV-infected(CHI) individuals with normal liver function tests(LFTs) . METHODS:Frequencies of T-lymphocyte subpopu-lations in peripheral blood were measured by flow cytometry in 216 CHI individuals. HBV markers were detected with ELISA. Serum HBV DNA load was assessed with quantitative real-time PCR. Information of age at HBV infection,and maternal HBV infection status was collected. ANOVA linear trend test and linear regression were used in statistical analysis. RESULTS:CHI individuals had significantly decreased relative frequencies of CD3+,CD4+ subpopulationsand CD4+/CD8+ ratio,and increased CD8+ subset percentage compared with uninfected individuals(all P < 0.001) . There was a significant linear relationship between the load of HBV DNA and the parameters of T-lymphocyte subpopulations(ANOVA linear trend test P < 0.01) . The parameters were also significantly worse among individuals whose mothers were known to be HBV carriers,and those having gained infection before the age of 8 years. In multiple regressions,after adjustment for age at HBV infection and status of maternal HBV infection,log copies of HBV DNA maintained its highly significant predictive coefficient on T-lymphocyte subpopulations,whereas the effect of HBeAg was not significant. CONCLUSION:HBV DNA correlates with modification in the relative T-lymphocyte subpopulation frequencies. High viral load is more powerful than HBeAg in predicting the impaired balance of T-cell subsets.

Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B:A randomized controlled study

AIM: To observe the efficiency and safety of thymosin-α1 treatment in patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis. METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week (T-α1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-α) each day for fifteen days, then three times weekly (IFN-α group) for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P > 0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters). RESULTS: At the end of treatment, complete response, which was defined as alanine aminotransferase (ALT) normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-α1 group and in 15 of 33 (45.5%) patients in the IFN-α group (c2 = 1.36, P >0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-α1 group and in 9 of 33 (27.3%) patients in the IFN-α group (c2 = 2.93, P > 0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-α which was followed up for 12 mo, the rate of complete response was significantly higher in IFN-α group at the end of therapy (1 of 30 vs 15 of 33, c2 = 14.72, P < 0.001) and in the T-α1 group at the end of follow-up (1 of 30 vs 14 of 29, c2 = 15.71, P < 0.001). In T-α1 and IFN-α treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the follow- up period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the IFN-α and HC groups. The odds of ALT normalization and negative HBV DNA at the end of the follow-up was three-fold higher in the T-α1 group than in the IFN-α group. Unlike IFN-α, T-α1 was well tolerated by all patients, and no side effects appeared in T-α1 group.CONCLUSION: The results suggest that a 6-mo course of T-α1 therapy is effective and safe in patients with chronic hepatitis B. T-α1 is able to reduce HBV replication in patients with chronic hepatitis B. Furthermore, T-α1 is better tolerated than IFN-α and can gradually induce more sustained ALT normalization and HBV DNA and HBeAg loss. However, a response rate of 48.3% is still less ideal. A more effective therapeutic approach warrants further study.

Elevated preoperative CA125 is associated with poor survival in patients with metastatic colorectal cancer undergoing primary tumor resection:a retrospective cohort study

Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.