Background and Aims:Recently,the World Health Organization adopted the first-ever global hepatitis strategy with the dream of eliminating viral hepatitis as a public health threat by 2030.However,the epidemiology and treatment rates of hepatitis C virus(HCV)infection in Western China are still unknown.Methods:A total of 111,916 adult individuals(15-96 years)who underwent the HCV-antibody(HCV-Ab)test in the Second Affiliated Hospital of Chongqing Medical University between 2013 and 2015 were included in this study.We retrospectively analyzed the electronic medical records'data for each,and the positivity of HCV-Ab and the treatment of HCV RNA-positive patients were evaluated.Results:During 2013-2015,the crude prevalence of HCVAb was 1.4%(95%CI:1.4-1.5;1,611/111,916)and the adjusted prevalence of HCV-Ab was 1.7%(95%CI:1.6-1.8),which was higher than in the 2006 national study(0.43%).The prevalence was 2-times higher in males than females(2.0%vs.1.1%,p<0.01).Notably,only 46%(434/951)of the HCV RNA-positive patients received standard peginterferon plus ribavirin treatment,with 370(82%)that completed treatment,of whom 272(74%)achieved sustained virologic response(SVR).Particularly,11%(32/292)of HCV RNA-positive patients were HBsAg-positive,and the SVR rate for them was lower than for the HBsAg-negative patients,but no significant difference was observed.Conclusions:HCV infection may have increased since 2006 in Western China.The SVR rate of peg-interferon plus ribavirin treatment was high,but the proportion of untreated HCV patients was large.Thus,more efforts need to be made by the government to create a scientific-based policy for HCV treatment and prevention.
Zhi-Wei ChenZhao LiQiao-He WangXiao-Ling WuHu LiHong RenPeng Hu
Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.
Background and Aims:Few previous studies have reported on a combination response(hepatitis B virus(HBV)DNA undetected,alanine aminotransferase normalization and hepatitis B e antigen(HBeAg)seroconversion)following nucleos(t)ide analogue(NAs)long-term therapy in patients with chronic hepatitis B(CHB).This study aimed to investigate the combination response on long-term NAs therapy in patients with HBeAg-positive CHB and to determine whether prolonged therapy is beneficial for combination response,particularly in optimal patients(baseline alanine aminotransferase level≥5 upper limit of normal and HBV DNA level<10^(9) copies/mL).Methods:In total,280 HBeAg-positive CHB patients were enrolled in this study.Among them,190 were treated with entecavir and 90 were treated with telbivudine.Results:The cumulative rates of combination response in the total number of patients were 8.6%at 1 year,13.2%at 2 years,19.1%at 3 years,24.2%at 4 years and 26.0%at 5 years.In optimal patients,the cumulative rate of combination response was significantly higher than that in the non-optimal patients at 3 years(p=0.043);the trend of the cumulative rate was not strong at the later time.Interestingly,in optimal patients,combination response mainly occurred in the first 3 years.Multivariate analysis identified HBeAg/anti-HBe seroconversion at 1 year as the only factor for combination response in optimal patients(hazard ratio:16.321;p=0.000).During the 3 years,the proportion with aspartate aminotransaminase to platelet ratio index≤0.5 increased from 15.6%at baseline to 71.3%at year 3.Conclusions:Upgrading the rate of combination response is limited by prolonging the treatment duration of NAs from 3 years to 5 years in HBeAg-positive CHB patients;a new switch treatment strategy modification should be considered,particularly in optimal patients.
Qiaohe WangHu LiDaohai DingMingli PengHong RenPeng Hu
Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly understood.Using flow cytometry staining,we precisely characterized the frequency,phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy controls.Interestingly,we found a substantial proportion of liver-infiltrating CD11b−CD27−(DN)NK subsets in tumor tissue from HCC patients.Remarkably,these relatively expanded DN NK subsets exhibited an inactive and immature phenotype.By detecting the expression of CD107a and interferon-gamma(IFN-γ)on NK subsets and NK cells,we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γin comparison to the other three subsets,which contributed to the dysfunction of TINK cells in HCC patients.In addition,we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients,as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size.A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up period.In conclusion,a substantial proportion of CD11b−CD27−NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor progression.Our study may provide a novel therapeutic target for the treatment of patients with HCC.
