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Objective: To study the effect of entecavir on the reproductive function of male patients with chronic hepatitis B (CHB)., Methods: This study included 56 CHB male patients (aged 18－45 ［33.14 ± 5.38］ years) initially treated with entecavir at 0.5 mg/d for 24 weeks from 2015 to 2018 and another 24 healthy fertile male volunteers (aged 21－45 ［32.62 ± 5.94］ years) as normal controls. We obtained the body mass index (BMI), reproductive hormone levels, semen parameters and IIEF-5 scores from the subjects and compared them between the two groups before and after treatment., Results: There were no statistically significant differences between the CHB and normal control groups in age, BMI, lifestyle and baseline reproductive hormone levels except in the levels of FSH (［3.92 ± 1.29］ vs ［3.08 ± 0.85］ mIU/ml, P = 0.003) and E2 (［35.79 ± 7.49］ vs ［28.25 ± 7.09］ pg/ml, P < 0.01). The semen parameters were significantly lower in the CHB patients than in the normal controls, including total sperm motility (［37.75 ± 13.33］% vs ［49.58 ± 9.27］%, P = 0.004), the percentage of progressively motile sperm (PMS) (［30.70 ± 10.03］% vs ［42.46 ± 8.90］%, P < 0.01), sperm concentration (［51.51 ± 19.50］ vs 70.33 ± 30.62) ×10⁶/ml, P = 0.007), and total sperm count (［160.2 ± 51.8］ vs ［225.91 ± 97.97］ ×106, P = 0.002), and so were the IIEF-5 scores (19.32 ± 2.34 vs 21.25 ± 2.35, P = 0.0006). After 24 weeks of entecavir treatment, the CHB patients showed no significant difference from the baseline in the semen volume, semen pH and days of abstinence, but remarkable improvement in total motility (［37.75 ± 13.33］ vs ［44.1 ± 11.89］%, P = 0.004), PMS (［30.70 ± 10.03］ vs ［38.30 ± 7.42］%, P < 0.01), sperm concentration (［51.51 ± 19.50］ vs ［62.00 ± 24.64］ ×10⁶/ml, P = 0.007), total sperm count (［160.21 ± 51.8］ vs ［207.65 ± 81.69］ ×106, P = 0.0002), and IIEF-5 score (20.13 ± 1.82 vs 19.32 ± 2.34, P = 0.02)., Conclusions: CHB patients have lower sexual function and semen quality than normal males. Entecavir can significantly improve the liver function, sexual function and semen quality of the CHB patients, but whether it directly improves the sexual function and semen quality of the patients or indirectly through liver function improvement needs to be further studied.

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman's rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods ( P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion: Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.

Objective: To evaluate the therapeutic effects of entecavir (ETV) and interferon- α (IFN- α ) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels., Methods: We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- α treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- α treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and &gt; 10× ULN (subgroup 3)]., Results: In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- α treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( P &lt; 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- α treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( P &lt; 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( P &lt; 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- α group, the rates were also similar between subgroups 1 and 2 (30.6% vs 33.3%, P &gt; 0.05); but the rates differed significantly between the same subgroups with different treatments ( P &lt; 0.05)., Conclusions: In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- α treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- α can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- α more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (&gt; 5 × ULN) show better responses to both ETV and IFN- α treatment than those with ALT level below 5×ULN. We thus recommend IFN- α for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.

Objective: To determine the timing and efficacy of entecavir (ETV) therapy in hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) using a new simple scoring system. Methods: A total of 212 patients with HBV-ACLF were treated with ETV 0.5 mg daily besides the routine treatment. The severity of illness was scored by the HBV-ACLF prognostic scoring system. Hepatic failure severity scores, hepatitis B virus DNA (HBV DNA) load, and length of hospital stay were recorded at the time of initiation of treatment, and the time of survival to hospital discharge/end of life. Results: Patiens were divided into four groups by the admission severity scores according to the percentile table: low score group (score≤ 4), medium-low score group (score: 5-7), medium-high score group (score: 8-11), and high score group (score ≥12). As the scores increased, the mortality rate increased. There were significant differences among different groups (χ(2)=310.662, P< 0.001). There were significant difference of the admission and discharge/death severity scores in the low score group ( P= 0.003). There were significant differences of the comparison of HBV DNA load at admission and death/discharge using ETV in low-, medium-low, and medium-high score groups ( P< 0.001). There were no significant differences of HBV DNA load at admission and death/discharge using ETV for dead and survival patients in the medium-low, and medium-high score groups. Conclusions: The efficacy of ETV in the rescue treatment of HBV-ACLF is related to the severity of ACLF when starting medication. The HBV-ACLF prognostic scoring system can clearly determine the timing and efficacy of ETV treatment of HBV-ACLF.

Objective: To observe continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B. Methods: Data of patients with active stage of chronic hepatitis B over the past 6 years were collected and analyzed retrospectively. The incidence of drug resistance mutation and related factors between patients taking LAM or ETV continuously and intermittently were compared with those taking LAM or ETV. Data comparison was performed using χ (2) test. Results: Patients with HBV DNA≥10(5) copies / ml at the time of initial treatment had higher resistance mutation rates than those with HBV DNA < 10(5) copies / ml at either continuous or intermittent treatment, and patients with intermittent treatment had higher resistance mutation rates than those with continuous treatment. Simultaneously, the incidence of drug resistance mutation in LAM and ETV in the first, second and third years were significantly higher in intermittent treatment than that of continuous treatment ( P < 0.05). There was a positive correlation between the frequency of drug withdrawal and the rate of drug resistance mutation. There were no individual difference and drug difference between LAM and ETV. Conclusion: In the treatment of chronic hepatitis B with oral nucleoside analogues, drug resistance may occur in either continuous or intermittent treatment. When comparing continuous with intermittent treatment, it suggests that intermittent is more likely to cause viral resistance mutation.

Objective: To observe the efficacy and safety of de novo combination of Lamivudine(LAM) and Adefovir Dipivoxil (ADV) therapy counter to Entecavir (ETV) monotherapy in patients with chronic hepatitis B (CHB)- related compensated liver cirrhosis. Methods: Patients with chronic hepatitis B-related compensated cirrhosis who were initially treated with LAM and ADV for more than 1 year were randomly assigned to two groups, one half replaced with ETV monotherapy, and the other half continued LAM and ADV co-therapy. Liver biochemistry, renal biochemistry, estimated glomerular filtration rate, alpha-fetoprotein, HBV serology markers and serum HBV DNA were measured every 3 months. Urine β2-microglobulin was measured every 6 months And retinol binding protein, followed up for 3 years. The mean values of the two groups were compared with t-test, and the rate of comparison was analyzed by x2 test. Results: A total of 580 cases were collected, 290 cases were replaced with ETV monotherapy, the other 290 patients continued to LAM and ADV combination therapy. In the ETV group, the rates of HBV DNA negative conversion at 1 year, 2 years and 3 years were 77.6%, 84.5% and 94.5% respectively, while the HBV DNA negative conversion rates at 1, 2 and 3 years in the LAM and ADV combination groups were 69.3%, 73.4% and 80.3% respectively. Among them, the negative rates of HBV DNA in the second year and the third year were P < 0.05, the difference was statistically significant. The 3-year cumulative gene-resistant rate in the ETV group was 1.4%, while the combined treatment was as high as 8.6%, and the difference was statistically significant in the two groups. The estimated value of serum creatinine and glomerular filtration rate in ETV group was followed by 3 years, and the baseline level was maintained, in the same group, the serum creatinine was higher than baseline, and the estimated value of glomerular filtration rate decreased. The results showed that there were 6.2%, 12.1%, 22.1% and 0, 0.3%, 1%, respectively, in 1, 2 and 3 years for the group of consecutive treatment and the replacement of ETV Group. The estimated glomerular filtration rate decreased by more than 30% compared with the baseline. The difference was statistically significant; the proportion of serum creatinine in the 1 year, 2 years and 3 years of the combined treatment group was 1.7%, 4.5% and 6.6%, compared with the baseline rise of > 50 μmol/l, and the ETV group was replaced in the 1 year, The values of 2 and 3 years were 0,0,0.7%, of which the 2nd and 3rd years were statistically significant; the proportion of microalbuminuria and retinol-binding protein in patients with combined treatment group was also significantly higher than that of Β2-m ETV Group. Conclusion: The initial combination of LAM and ADV therapy is inferior in terms of ETV monotherapy. Single therapy with ETV increase the rate of viral response, reduce the incidence of drug resistance, and also reduce the incidence of renal impairment in patients with chronic hepatitis B -related compensated liver cirrhosis.

Objective: To investigate the clinical effect and safety of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in the treatment of previously untreated HBeAg-positive chronic hepatitis B (CHB) patients with a high viral load. Methods: A retrospective analysis was performed for the clinical data of 152 HBeAg-positive CHB patients with a high viral load (HBV DNA≥10(6) IU/ml) who were firstly treated with ETV (ETV group) or TDF (TDF group), with 76 patients in each group. The serum levels of alanine aminotransferase (ALT), HBV DNA, HBeAg, anti-HBe, creatinine, and creatine kinase were measured at baseline, and the patients were followed up and evaluated at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 of treatment. The Kaplan-Meier survival curves were used to analyze cumulative complete virologic response, HBeAg seroconversion, and ALT normalization rate. The Cox proportional hazards regression model was used to identify the influencing factors for virologic response. P < 0.05 was considered statistically significant. Results: There were no significant differences in ALT normalization rate between the ETV group and the TDF group at weeks 4, 12, 24, 48, 72, and 96 of treatment (18.1%/55.6%/83.3%/90.3%/93.1%/97.2% vs 16.0%/53.6%/75.4%/94.2%/100%/100%, P > 0.05). There were also no significant differences in virologic response rate between the ETV group and the TDF group at weeks 48 and 96 of treatment (89.5%/97.3% vs 93.4%/98.7%, P > 0.05). The multivariate analysis showed that the baseline parameters were not predictive factors for virologic response. At week 48 of treatment, the TDF group had a significantly higher HBeAg seroconversion rate than the ETV group (14.5% vs 3.9%, P = 0.048); at week 96 of treatment, there was no significant difference in HBeAg seroconversion rate between the two groups (15.8% vs 7.9%, P = 0.132). The Kaplan-Meier survival analysis showed that there were no significant differences between the two groups in cumulative ALT normalization rate, cumulative HBV DNA undetectable rate, and cumulative seroconversion rate. Only one patient in the ETV group experienced virologic breakthrough from weeks 60 to 72 of treatment, and there were no serious adverse reactions. Conclusion: TDF and ETV had similar clinical effects, HBeAg seroconversion rate, and safety in previously untreated HBeAg-positive CHB patients with a high viral load.

Objective: To explore the expression level of peripheral blood Th1/Th2 type cytokines of chronic hepatitis b (CHB) patients in the entecavir (ETV) antiviral treatment, analyze the relationship between various cytokines, and the correlation among of cytokines and HBV DNA loads. Methods: Luminex Liquid Chip Technology was applied to detect the peripheral blood Th1/Th2 type cytokines expression level of CHB patients; At the same time, liver function was detected by Fully Automatic Biochemical Analyzer; HBV DNA loads were detected by PCR Method; Hepatitis b virology markers were detected by Chemiluminescence Method. F-test and Pearson correlation analysis were used for statistical analysis. Results: Before ETV antiviral treatment, peripheral blood Th1 cytokines IFN gamma expression level in patients with CHB increased significantly ( P = 0.010) compared with the healthy control group while TNF alpha expression level having no statistically significant difference ( P = 0.095); Th2 type cytokines IL-4, IL-6, IL-10 levels decreased obviously ( P = 0.039, P = 0.014, P = 0.026) compared with those in the control group. After 48 weeks of treatment, Th1 cytokines IFN gamma and TNF alpha expression levels were reduced significantly (19.2±5.03 pg/ml vs 24.69±6.51 pg/ml, and 6.09±4.99 pg/ml vs 9.50±7.34 pg/ml, P < 0.001, and P = 0.016) compared with that before treatment; Th2 type cytokines IL-4, IL-6 expression level increased significantly (33.86±22.47 pg/ml vs 21.32±12.84 pg/ml, and 11.65±6.91 pg/ml vs 8.51±4.94 pg/ml, P = 0.004, and P = 0.029) compared with that before treatment while IL-10 expression level having no statistical significance ( P = 0.081). There was disorder and irregularity in the correlation between the levels of Th1/Th2 type cytokines. And there was no correlation between the various cytokines and HBV DNA loads in patients with CHB. Conclusion: ETV can not only inhibit HBV DNA replication, reducing HBV DNA loads, but also contribute to regulate Th1/Th2 type cytokines expression level in patients with CHB, but there was no correlation between the levels of various cytokines, various cytokines and HBV DNA loads.

Objective: To investigate the clinical effect and safety of entecavir capsules in the treatment of treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). Methods: A total of 158 HBeAg-positive CHB patients were given oral entecavir capsules at a dose of 0.5 mg/time once a day for 144 weeks. Clinical outcome and safety were evaluated at baseline and at 24, 48, 72, 96, 120, and 144 weeks of treatment respectively. The Fisher's exact test was used for the analysis of categorical data. Results: After 144 weeks of treatment, 90.91% of all patients achieved virologic response (< 69 IU/ml), the normalization rate of alanine aminotransferase was 88.18%, the clearance rate of HBeAg was 33.33%, and the seroconversion rate of HBeAg was 24.07%. Of all patients, 2 dropped out due to adverse events and 5 experienced serious adverse reactions. Conclusion: Entecavir capsules can inhibit viral replication and have good safety in treatment-naïve HBeAg-positive CHB patients.

Objective: To analyze the relationship between baseline liver pathologic changes and the effectiveness of entecavir(ETV) and investigate the predictive value of baseline liver pathologic changes in determining the effectiveness of ETV, to provide reliable basis for precision medicine in patients with chronic hepatitis B(CHB). Methods: A total of 1 366 cases with CHB were retrospectively recruited who underwent liver biopsy between January 2006 to June 2016 and were treated with ETV over 96 weeks.The relationship between baseline liver pathologic changes and the antiviral responses to ETV at 48, 96 weeks were compared. Results: Liver pathology was employed to make the definite inflammation grade and the fibrosis stage.According to the liver inflammation and fibrosis, patients were divided into 4 groups(G1, G2, G3, G4 and S1, S2, S3, S4 respectively). The complete response rate of G1, G2, G3 and G4 after 48 weeks ETV treatment was 26.3%(10/38), 30.9%(121/391), 35.3%(101/286), 44.4%(52/117) respectively in HBeAg positive patients and was 61.5%(24/39), 80.4%(148/184), 82.4%(201/244), 88.1%(59/67) respectively in HBeAg negative patients.There was statistical difference in the complete response rates among liver inflammation grades both in HBeAg positive patients(χ(2)=8.510, P <0.05) and in HBeAg negative patients(χ(2)=12.054, P <0.05)respectively.The differences were still statistical significant after 96 weeks ETV treatment ( P <0.05). The complete response rates of S1, S2, S3 and S4 after 48 weeks ETV treatment were 39.0%(41/105), 37.8%(127/336), 30.9%(97/314), 24.7%(19/77), respectively in HBeAg positive patients and was 85.7%(30/35), 84.4%(92/109), 83.9%(162/193), 75.1%(148/197) respectively in HBeAg negative patients. Whether HBeAg was positive or not, the rates were in decline but there was no statistical difference in the complete response rates among liver fibrosis stages(χ(2)=7.765, P >0.05; χ(2)=6.729, P >0.05). The differences were still not statistical significant after 96 weeks ETV treatment ( P >0.05). But after further grouping, whether HBeAg was positive or not, as the degree of fibrosis stage was aggravating, the complete response rate of G2, G3 and G4 after 48 weeks ETV treatment decreased at the same degree of inflammation grade and the differences were statistically significant ( P <0.05). The differences were still statistical significant after 96 weeks ETV treatment ( P <0.05). Conclusions: The responses to ETV treatment are closely related with baseline liver pathology.The CHB patients with higher score of inflammation and lower score of fibrosis will have a good response to ETV treatment.The degree of inflammation grades and fibrosis stages can be used as early predictors of ETV treatment for CHB.

Objective: To investigate the dynamic changes in serum β2-microglobulin, retinol-binding protein, and cystatin C in chronic hepatitis B(CHB)patients treated with tenofovir or entecavir alone as the anti-HBV therapy, as well as their value in identifying early renal dysfunction. Methods: A total of 61 previously untreated CHB patients who were diagnosed and treated in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to August 2015 were enrolled and divided into tenofovir group and entecavir group. The serum levels of β2-microglobulin, retinol-binding protein, cystatin C, and creatinine and estimated glomerular filtration rate(eGFR)were compared between the two groups at baseline and 4, 8, 39, 52, 78, and 104 weeks after antiviral therapy. The independent samples t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. P < 0.05 was considered statistically significant. Results: A total of 61 CHB patients were enrolled, with 31 in the tenofovir group and 30 in the entecavir group. The two groups had comparable serum levels of β2-microglobulin, retinol-binding protein, and cystatin C at baseline, but there were significant differences in β2-microglobulin and retinol-binding protein over time(both P < 0.05). There was a significant difference in cystatin C at 78 weeks( t = -2.062, P = 0.044), but there was no significant difference at 104 weeks( t = -1.544, P = 0.128). There were no significant differences in serum creatinine or eGFR at any time point between the two groups( P > 0.05). At 104 weeks, there were no significant differences in HBV-DNA clearance rate or the level of virologic breakthrough between the two groups( P > 0.05). Conclusion: Serum β2-microglobulin, retinol binding protein, and cystatin C are more sensitive than eGFR in the monitoring of early renal dysfunction during the anti-HBV therapy with tenofovir or entecavir alone.

We report a rare case of HBsAg seroconversion after 7 years of entecavir therapy in a 48-year-old HBeAg-negative CHB male patient with chronic hepatitis B (CHB). After a poor response to a 48-week interferon-α 2b therapy, the patient received long-term entecavir therapy. Serum ALT levels became normal and HBV DNA viral load was undetectable at the 10th week after commencement of entecavir treatment, and seroconversion of HBsAg was detected after 7 years of entecavir therapy.

Objective: To evaluate the effect of long-term therapy with entecavir and Fufang Biejia Ruangan tablet in patients with chronic hepatitis B (CHB)-associated fibrosis and explore the synergistic therapy that accelerates the reversion of liver fibrosis., Methods: A total of 197 patients with CHB-associated fibrosis were recruited from Nanfang Hospital between June, 2010 and June, 2015. The patients were divided into two groups after matching for age, gender and liver stiffness measurement (LSM), namely group A (n=98) treated with Fufang Biejia Ruangan Tablet plus entecavir, and group B (n=99) to receive entecavir only. HBV DNA quantification, HBV serological indicators, blood biochemical indexes, and results of abdominal ultrasound and FibroScan were recorded every 12 weeks. FibroScan values were converted to Metavir staging., Results: Both groups showed significant decreases in serum levels of HBV DNA, alanine aminotransferase (ALT), and LSM value from baseline (all P<0.05). The median time to achieve Metavir fibrosis staging improvement were 72 weeks in group A and 96 weeks in group B (P<0.05), and the median time to achieve ALT and AST normalization were 12 and 24 weeks in Group A, respectively, significantly shorter than the time in group B (P<0.05). No significant difference was found between the two groups in HBV DNA undetectable rate and HBeAg seroconversion rate., Conclusion: The combination therapy with Fufang Biejia Ruangan tablet and entecavir produces a stronger efficacy than entecavir alone in the treatment of chronic hepatitis B patients with liver fibrosis, and Fufang Biejia Ruangan tablet shows an obvious hepatoprotective effect in these patients.

Objective: To investigate HBsAg clearance rate in previously untreated patients with HBeAg-positive chronic hepatitis B (CHB) treated with nucleos(t)ides and interferons and its influencing factors based on the clinical diagnosis and treatment dat., Methods: A retrospective cohort study was conducted in 1 767 previously untreated HBeAg-positive CHB patients who visited Beijing You'an Hospital from February 14, 2008 to December 31, 2012. HBsAg clearance rates were calculated for patients with different characteristics, and the Cox regression model was used to investigate the influencing factors for HBsAg clearance., Results: The overall annual HBsAg clearance rate was 0.46% in 1767 patients, and in the patients treated with adefovir, entecavir, telbivudine, and common interferon, the annual HBsAg clearance rate was 0.52%, 0.47%, 0.45%, and 1.18%, respectively. No patients in the lamivudine and pegylated interferon-α groups experienced HBsAg clearance, which might be due to the small sample size. The univariate analysis showed that HBsAg clearance rate was associated with the patient's age when he/she visited the hospital and baseline HBsAg titer level. After adjustment for other factors, the patients treated with common interferon had a significantly higher possibility of HBsAg clearance than those treated with entecavir (HR = 8.33, 95% CI: 1.19-58.50, P = 0.0329), but the possibility of HBsAg clearance showed no significant difference between patients treated with other nucleos(t)ides and entecavir. The patients aged≥50 years had a probability of HBsAg clearance 4.92 times that of those aged < 50 years (HR = 4.92, 95% CI: 1.38-17.50, P = 0.0139) and the patients with baseline HBsAg titer level < 3 log10 IU/ml had a probability of HBsAg clearance 22.77 times higher than that of those with baseline HBsAg titer level≥3 log10 IU/ml (HR = 23.77, 95% CI: 6.17-91.51, P < 0.0001)., Conclusion: The previously untreated CHB patients achieve a low annual HBsAg clearance rate under current antiviral therapeutic regimens, especially nucleos(t)ides. Baseline HBsAg titer level is closely associated with HBsAg clearance.

Objective: To investigate the efficacy and safety of 104-week sequential therapy with telbivudine or entecavir in HBeAg-positive chronic hepatitis B (CHB) patients with suboptimal responses to 24-week pegylated interferon-α-2a (PEG-IFN-α-2a) therapy., Methods: A total of 130 HBeAg-positive CHB patients with HBV DNA≥5.0 lg IU/ml and a reduction in HBsAg quantitation < 1 lg IU/ml compared with baseline who received PEG-IFN-α-2a therapy for 24 weeks were enrolled and randomly divided into telbivudine group and entecavir group, and 5 of them were lost. HBeAg clearance rate and seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate at week 104 were observed. The t-test, chi-square test, or multivariate Cox regression analysis were used for statistical analysis of different types of data., Results: At week 104 of treatment, HBV DNA clearance rate showed no significant difference between the telbivudine group and entecavir group (P = 0.363), and the telbivudine group had significantly higher HBeAg clearance rate and HBeAg seroconversion rate than the entecavir group (HBeAg clearance rate: 61.29% vs 23.81%, P < 0.01; HBeAg seroconversion rate: 51.61% vs 19.05%, P < 0.01). Male sex and telbivudine therapy were baseline predictors of HBeAg seroconversion. The multivariate Cox regression analysis (Forward LR, a = 0.05) showed that the presence or absence of HBeAg seroconversion at week 104 was significantly associated with male sex (HR = 4.917), a reduction in HBsAg > 0.5 lg IU/ml at week 12 of treatment compared baseline (HR = 3.514), and a reduction in HBeAg > 1 lg COI at week 12 of treatment compared baseline (HR = 8.651)., Conclusion: In HBeAg-positive CHB patients with suboptimal responses to 24-week PEG-IFNα-2a therapy, the sequential therapy with telbivudine helps achieve better HBeAg clearance rate and seroconversion rate compared with the sequential therapy with entecavir and can be used as a therapeutic regimen for such patients. A reduction in HBeAg > 1 lg COI at week 12 of treatment compared baseline can be used as a predictive factor for HBeAg seroconversion at week 104.

Objective: To investigate the regulatory roles of cytokines expressed on peripheral blood T cells in chronic hepatitis B virus (HBV) infection., Methods: Sixty patients with chronic HBV infection were categorized into immune tolerance phase (IT), immune clearance phase (IC), and inactive carrier phase (IA) groups. Twenty healthy individuals were enrolled as healthy controls. Another 21 HBeAg-positive chronic hepatitis (CHB) patients were administrated with entecavir (0.5 mg/d) for 6 months. Serum alanine transaminase (ALT) levels were tested by automatic biochemistry analyzer, and HBV DNA loads were tested by PCR, and cytokines expressed on T cells were examined by flow cytometry., Results: There were negative correlations between IFN-γ levels expressed by peripheral blood CD4(+)T cells and CD8(+)T cells and serum HBV DNA loads in patients with chronic HBV infection, and there were negative correlations between the ratio of IFN-γ/IL-4 in peripheral blood CD4(+)T cells and CD8(+)T cells and serum HBV DNA loads. In addition, the expression levels of IFN-γ were gradually elevated and the expression levels of IL-4 were gradually lowered from IT to IA. In IT, the level of IFN-γ expressed by T cells in patients was lower than that in healthy controls and the level of IL-4 was higher than that in healthy controls. In IA, the levels of IFN-γ and IL-4 were recovered to the normal. Anti-virus therapy reduced serum HBV DNA load and ALT levels in patients, which was accompanied with the increase of IFN-γ level and IFN-γ/IL-4 ratio in CD8(+)T cells., Conclusion: During chronic HBV infection, IFN-γ and IL-4 expressed by peripheral blood T cells play dual immunoregulatory roles, which are correlated with the efficacy of entecavir.

Objective: To evaluate the efficacy and safety of 4 treatment options for HBeAg-positive chronic hepatitis B (CHB) patients following a suboptimal response to 24-week interferon monotherapy., Methods: The data of 193 HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy were collected from Nanfang Hospital between September, 2010 and January, 2013. According to the subsequent treatments, the patients were divided into group A with additional entecavir or adefovir, group B with further interferon monotherapy, group C with conversion to NAs therapy, and group D with direct therapy withdrawal, and the biochemical and virological results at weeks 24, 48 and 72 were analyzed in the 4 groups., Results: At week 48, the HBV DNA negative rates and serum alanine aminotransferase (ALT) normalization rates were both significantly higher in group A and C than in group B (P<0.05); in group A, ETV therapy subgroup had a significantly higher HBV DNA negative rate than ADV therapy subgroup at week 48 (90.3% vs 59.5%, Χ=8.255, P=0.004). At week 72, 39.7%(27/68) of the patients in group A achieved HBeAg seroconversion, a rate significantly higher than those in groups B (Χ=4.238, P=0.040) and C (Χ=7.681, P=0.006); the HBV DNA negative rate and ALT normalization rate in group A were 85.3%(58/68) and 86.8%(59/68), respectively, both significantly higher than those in group B (Χ=23.018, P<0.001; Χ=5.987, P=0.014) but comparable to those in group C (P>0.05). In the two subgroups in group A, the HBV DNA negative rate and HBeAg seroconversion rate were both significantly higher in ETV subgroup (Χ=9.823, P=0.002; Χ=5.450, P=0.020). In group D, all the patients remained HBeAg-positive with abnormal ALT levels and high level of HBV DNA., Conclusion: For HBeAg-positive CHB patients with suboptimal response to 24-week interferon monotherapy, combined treatment with NAs (especially ETV) and extension of the treatment course can significantly improve the HBeAg seroconversion rates, HBV DNA negative rates, and ALT normalization rates.

Objective: To investigate the clinical effect of combination therapy with Fufang Biejia Ruangan tablet and entecavir in patients with hepatitis B virus (HBV)-related cirrhosis., Methods: A total of 163 patients with HBV-related cirrhosis were recruited for treatment between March 2010 and August 2012, and divided into the following three groups:group A (n =56) received Fufang Biejia Ruangan Tablet plus entecavir; group B (n =52) received entecavir only; and group C (n =55) received Fufang Biejia Ruangan tablet only. Enzyme-linked immunoassay methods were used to measure serum levels of hyaluronic acid (HA), laminin (LN), collagen (PCIV) and prolyl endopeptidase (PLD). The grade of liver fibrosis was determined upon liver biopsy, and score of liver stiffness was measured by FibroScan., Results: All three treatment groups showed significant decreases from baseline in serum levels of alanine aminotransferase, aspartate aminotransferase, HBV DNA, HA, LN, PCIV and PLD (all P < 0.05). However, the changes in HA, LN, PCIV and PLD levels were significantly greater in group A than in either group B or C (P < 0.05). All three treatment groups showed significant improvements from baseline in liver fibrosis grade and liver stiffness score (P < 0.05). The total effective rate of group A was 82.14%, which was significantly higher than that of groups B and C (P < 0.05)., Conclusion: Combination therapy of Fufang Biejia Ruangan tablet plus entecavir is effective for treating HBV-related cirrhosis.

Objective: To prospectively evaluate the efficacy of a traditional Chinese medicine (TCM)-based therapy for treating liver fibrosis in patients with chronic hepatitis B (CHB), and to investigate the patients' perception of the treatment's effects on quality of life (QoL)., Methods: A total of 430 patients with CHB-related liver fibrosis were randomly assigned to treatment groups for receipt of a 12-month course of the antiviral drug entecavir alone (control group) or in combination with the TCM Liuweiwuling tablets. Patients were assessed before (pre-treatment) and after therapy and the treatment-related differences in clinical manifestations, levels of liver function markers and liver fibrosis indexes, color ultrasound images, and hepatitis B virus (HBV) DNA load were compared between the two groups by statistical analysis. The generic QoL scale developed by the World Health Organization (WHOQOL-BREF) was used to score the patients' perceptions of treatment outcome., Results: After treatment, the patients in both groups showed significant improvement in the majority of clinical manifestations (both P less than 0.05), with the exception of bloating. In addition, both groups showed significant improvements of liver function markers and in signs of liver fibrosis (both P less than 0.05). Both groups also showed significant reductions in the diameters of the portal and splenic (both P less than 0.05), as well as increases in the rate of undetectable HBV DNA (with a statistically similar outcome achieved in the two groups). Finally, both groups had higher QoL scores after treatment, with all assessed parameters except environment showing a significant improvement (all P less than 0.05)., Conclusion: When used in combination with entecavir, the TCM Liuweiwuling tablet is a safe therapy for CHB and its related liver fibrosis and may help to improve the QoL of these patients.

Objective: To evaluate the impact of histology on efficacy of pemetrexed in Chinese non-small cell lung cancer (NSCLC) patients. This report summarized the results of two clinical trials of pemetrexed in Chinese patients with advanced NSCLC in 2nd line setting and maintenance setting after 1st line (JMID study and Chinese subgroup from JMEN study) treatment., Methods: For the Chinese JMID study (second-line), Chinese patients with locally advanced or metastatic (stage IIIA, IIIB or IV) NSCLC who had prior chemotherapy were enrolled. The study was designed to investigate the noninferiority of pemetrexed (500 mg/m(2), day 1 of each 21-day cycle) to docetaxel (75 mg/m(2), day 1 of each 21-day cycle) in terms of overall survival (OS). For the global JMEN study (maintenance), patients initially diagnosed with IIIB or IV NSCLC, those who had not progressed after completing at least four cycles of platinum-based chemotherapy were enrolled to test for the superiority of pemetrexed (500 mg/m(2), day 1 of each 21-day cycle) over placebo with progression free survival (PFS) as primary endpoint., Results: In JMID study, the OS was similar between the pemetrexed group (Pem group) and docetaxel group (Doc group). Retrospective histological subtype analysis showed survival benefits (both OS and PFS) numerically of non-squamous patients over squamous patients in the Pem group (OS: HR 0.74, 95% CI 0.45-1.21, P = 0.2267, median 11.7 vs. 9.7 months; PFS: HR 0.77, 95% CI 0.44-1.34, P = 0.3585, median 3.0 vs. 1.7 months). In the Chinese subgroup of JMEN study, the median PFS in the Pem group for squamous and nonsquamous patients was 4.2 and 1.5 months for squamous patients, the median OS in the Pem group for squamous and nonsquamous patients was 22.5 and 6.2 months for squamous patients. In JMEN China subgroup analysis, the HR on histology was not analyzed due to the small sample size. In terms of safety profile, drug-related grade 3 or 4 hematological toxicities (leukocytopenia and neutropenia) events occurring after second-line treatment were significantly lower in the Pem group than in the Doc group (both P < 0.001). Similarly in patients receiving pemetrexed maintenance after first-line treatment, incidences of toxicity events were low., Conclusions: Consistent with global results, in Chinese NSCLC patients, histology has an impact on the efficacy of pemetrexed, in which non-squamous histology predicts a positive outcome for patients treated with pemetrexed. In terms of overall safety, pemetrexed is better than docetaxel with a lower incidence of adverse events and anticipates manageable safety profile in NSCLC patients. Based on consistent Chinese data from the two studies, pemetrexed is recommended as a standard chemotherapy regime in both second-line and maintenance setting after first-line treatment for Chinese non-squamous NSCLC patients.

Objective: To explore the efficacy and safety of pemetrexed in the treatment of relapsed primary central nervous system lymphoma (PCNSL)., Methods: Seven cases with relapsed PCNSL admitted in our hospital between August 2012 and August 2013 were retrospectively reviewed., Results: Of the 7 relapsed cases, ectopic recurrence occurred in 3, in situ recurrence in 3 and leptomeningeal metastasis in 1. Patients with relapsed PCNSL were administered with high-dose pemetrexed (900 mg/m²) once for every 3 weeks and supplemented with folic acid and vitamin B₁₂. Complete remission was obtained in 2 patients, partial remission in 3 patients and progressive disease in 2. The overall response rate was 71.4% (5/7). The main adverse reactions were myelosuppression and gastrointestinal reaction., Conclusion: Treatment of relapsed PCNSL is difficult, and its prognosis is very poor. Pemetrexed therapy is a meaningful trial.

Objective: To compare the efficacy and safety of recombinant human interferon α-2b (INFα-2b) monotherapy and combined therapy with entecavir (ETV) plus adefovir dipivoxil (ADV) in chronic hepatitis B patients with poor response to combined therapy with lamivudine and ADV., Methods: A total of 161 patients with chronic hepatitis B refractory to to combined therapy with lamivudine (LAM) and ADV were randomized to receive INFα-2b monotherapy (5×10(6), three times a week) (group A) or combined therapy with entecavir (0.5 mg/day) plus adefovir (10 mg/day) (group B). Serum levels of HBsAg, HBeAg and HBV viral load were analyzed at 48 weeks using chemiluminescence assay and by real-time PCR as appropriate. The drug resistance genes in HBV was tested by direct DNA sequencing., Results: At 48 weeks of treatment, HBV DNA decreased significantly in groups A and B to 2.06∓1.15log10 copies/ml and 1.77∓1.28log10 copies/ml, respectively. The rates of viral response, serological response, and biochemical response in groups A and B were 48.15% (39/81) vs 53.75% (43/80), 61.70% (50/81) vs 53.75% (43/80), and 49.38% (40/81) vs 60.00% (48/80), showing no significant differences between the two groups (P>0.05). The drug resistance gene mutation rate was significanty higher in group B (64.86%, 24/37) than in group A (30.95%, 13/42, P<0.05)., Conclusion: Chronic hepatitis B patients refractory to lamivudine combined with ADV have a good response to INFα-2b monotherapy and combined therapy with entecavir and ADV , and interferon treatment is preferred to reduce potential drug resistance gene mutations.

Objective: To investigate the efficacy profile of entecavir capsule (ETV) as a chronic hepatitis B therapy, as compared to lamivudine (LAM)., Methods: In this multicenter, randomized, double-blind, parallel group evaluation of ETV, 232 subjects were administered a 96-week course of 0.5 mg/day ETV or 100 mg/day LAM. PCR measurement of hepatitis B virus (HBV) was conducted throughout the treatment course to determine achievement of complete virologic response (CVR; defined as less than 500 copies/ml of HBV DNA) or experience of virology rebound ( more than 500 copies/ml of HBV DNA after achievement of CVR)., Results: After week-48 of treatment, the ETV group showed a higher CVR rate (90.3% vs. LAM: 59.4%) and lower virology rebound rate (1.9% vs. LAM: 13.9%). After week-96 of treatment, the ETV group continued to have a higher CVR rate (86.0% vs. LAM: 71.4%), and virology rebound was experienced by significantly less subjects in the ETV group (1.2% vs. LAM: 11.9%, P = 0.005)., Conclusion: ETV therapy can quickly and continuously suppress HBV replication in chronic hepatitis B patients, and has a lower resistance rate than LAM. Compared to LAM, ETV may be a superior long-term treatment choice for chronic hepatitis B.

Objective: To evaluate the efficacy and safety of entecavir (ETV) as a long-term treatment in patients with lamivudine (LAM)-refractory chronic hepatitis B (CHB)., Methods: In this phase II study of ETV-056, 32 CHB patients with resistance to LAM monotherapy were administered ETV at 1.0 mg/day and monitored over a period of 8 years. The virologic, serologic and biochemical responses were measured throughout the treatment course. Outcomes analysis was conducted according to intention-to-treat principles., Results: At baseline and treatment weeks 8, 12, 24, 48, 96, 144, 192, 240, and 420, the proportion of patients with HBV DNA less than 300 copies/ml was 0, 6.3% (2/32), 9.4% (3/32), 18.8% (6/32), 18.8%(6/32), 46.9% (15/32), 43.8% (14/32), 50.0% (16/32), 50.0% (16/32), and 62.5% (20/32). At treatment weeks 48, 96, 168, 192, 240, and 420, the proportion of patients experiencing virological breakthrough was 6.1% (2/32), 9.4% (3/32), 12.5% (4/32), 18.8%(6/32), 25.0%(8/32), and 28.1% (9/32). In the 8 year study period, 32.3% (10/31) of patients achieved HBs seroconversion and four patients achieved HBe seroconversion., Conclusion: While treatment with 1.0 mg/day ETV for up to 8 years resulted in mild HBV DNA suppression and increase of HBeAg seroconversion, the safety profile of this therapy was good but the economic cost was high and virological breakthrough rates were high.

Objective: To evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB)., Methods: The patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded., Results: As in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05)., Conclusion: Performing analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.

Background and Objective: Subsequent chemotherapy were needed in patients with advanced pulmonary adenocarcinoma experiencing disease progression after epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. The study is to explore factors potentially influencing efficacy of subsequent chemotherapy., Methods: One hundred and ninety-one patients with advanced lung adenocarcinoma, who were resistant from EGFR-TKIs and then received subsequent chemotherapy, were identified. Data of patient's characteristics, responses to chemotherapy and survival time were analyzed retrospectively., Results: The overall response rate of the pemetrexed-based chemotherapy (9.3%) was higher than non-pemetrexed-based regimen (1.1%), P=0.011. Furthermore, the response in the second-line was more obvisous [objective response rate (ORR) 14.3% vs 3.7%, P=0.041]. The patients who achieved response of partial response (PR) showed longer progression-free survival (PFS) than those who achieved non-PR (PFS 10.1 months and 2.3 months, P=0.012). The patients treated with platinum-based chemotherapy had longer PFS and OS than those with non-platinum-based chemotherapy, therefore platinum-based regimen was independent prognosis factors for PFS and OS (PFS: RR=0.634, 95%CI: 0.466-0.832, P=0.004; OS: RR=0.666, 95%CI: 0.460-0.960, P=0.030), especially the pateients who were aquired EGFR-TKIs resistance and who got drmatic progression from EGFR-TKIs treatment might got more benefits from platinum-based chemotherapy. However there was no significant difference in ORR, PFS or OS between patients with TKIs primary resistance and acquired resistance, or between dramtic progression and gradual/local progression., Conclusion: The patients with advanced lung adenocarcinoma might get benefits from pemetrexed-based or platinum-based chemotherapy after they were EGFR-TKIs resistace.

Background and Objective: Gefitinib and Pemetrexed are drugs used as second-line therapy for advanced non-small cell lung cancer (NSCLC), although studies comparing the two drugs are limited. The aim of this study is to explore the effects, safety, and quality of life (QoL) of Gefitinib and Pemetrexed on patients with advanced non-squamous NSCLC., Methods: Forty-six advanced non-squamous NSCLC patients who failed to first-line therapy were randomly divided into two groups with 23 patients each, one using oral Gefitinib (Gefitinib group) and the other using intravenous injection Pemetrexed (Pemetrexed group). The effects, safety, and QoL were determined and analyzed., Results: For the Pemetrexed group, objective response rate (ORR) was 13.0% (3/23), disease control rate (DCR) was 30.4% (7/23), and median progression-free survival (mPFS) was 3.1 months. In the Gefitinib group, ORR was 17.3% (4/23), DCR was 39.1% (9/23), and mPFS was 4.4 months. Compared with the Pemetrexed group, the ORR, DCR, and mPFS in the Gefitinib group exhibited no statistical significance (P>0.05). Furthermore, the most common toxicities in the Pemetrexed group were neutropenia (n=9, 39.13%) and fatigue (n=8, 34.78%), whereas those in the in Gefitinib group were skin rash (n=8, 34.78%) and diarrhea (n=4, 17.39%). Compared with baseline, the QoL improved in both groups but to different degrees. Likewise, emotional, functional well-being, and QoL aspects specifically related to lung cancer were better improved in the Gefitinib group than in the Pemetrexed group (P<0.05)., Conclusions: The effects of Pemetrexed and Gefitinib as second line therapy were similar, although with different AEs. Both drugs could improve the QoL, but Gefitinib showed better overall results than Pemetrexed.

Objective: To investigate the dynamic quantitative changes in expression of hepatitis B virus (HBV) surface antigen (HBsAg) that occurs during the natural recovery course and the short-term antivirus treatment period of patients suffering from flares in chronic hepatitis B (CHB)., Methods: CHB patients presenting for treatment of flare-ups were randomly assigned to receive treatment with Entecavir antiviral (group A, n = 39) or to naturally resolve the acute condition (group B, n = 22). All patients MELD scores were calculated and HBsAg levels and HBV DNA loads were measured upon admission (baseline), at worst-condition stage, and end of treatment/flare-up (discharge). Pairwise comparisons of intergroup differences were made to evaluate the change in the three disease parameters over time in response to the management approach., Results: The levels of HBsAg were not significantly different between the two groups at baseline, worst-condition stage and discharge (group A: (3.68+/-0.45), (3.84+/-0.19) and (3.69+/-0.58) log10 cut-off index (COI) respectively; group B: (3.59+/-0.54), (3.47+/-0.76) and (3.43+/-0.68) log10 COI respectively; all P more than 0.05). However, the HBV DNA loads were significantly lower in group A than in group B at the worst-condition stage and at discharge (all P less than 0.05). In group A, the MELD scores were significantly higher at baseline and at worst-condition stage than at discharge (all P = 0.000), but the difference between baseline and worst-condition stage was not significant. Also in group A, the HBV DNA load showed a gradually decreasing trend over time (baseline more than worst-condition stage more than discharge, all P less than 0.05). No significant differences were observed over time in the HBsAg levels of group A. In group B, the MELD scores were significantly higher at baseline and at worst-condition stage than at discharge (all P = 0.000), but the difference between baseline and worst-condition stage was not significant (P = 0.619). Also in group B, the HBV DNA loads were significantly higher at baseline and worst-condition stage than at discharge (P = 0.000 and P = 0.003 respectively), but the difference between baseline and worst-condition stage was not significant. Finally, no significant differences were observed over time in the HBsAg levels of group B., Conclusion: Natural recovery from an acute flare-up of CHB is not accompanied by a change in HBsAg levels. In addition, short-term antiviral treatment to resolve the flare-up has no influence on HBsAg level.

Objective: To investigate the drug-resistant genes at hepatitis B virus (HBV) polymerase region during entecavir (ETV) treatment., Methods: Serum samples from chronic hepatitis B patients with virologic breakthrough during enticavir therapy were studied. The resistant mutation patterns in the polymerase gene of hepatitis B virus were analyzed using the polymerase chain reaction (PCR)-sequencing method., Results: ETV resistance was detected from 19 out of 29 ETV-refractory patients, among whom 16 (84.2%) had a history of lamivudine-refractory. The mutation patterns were diverse, while rtL180 + rtM204 + rtT184 (58.6%, 17/29) was most common in patients with ETV genotype resistance. Four of 7 patients (7/29, 24.1%) with genotype B were detected to have ETV genotype resistance, while 15 of 22 patients (22/29, 75.9%) with genotype C were detected to have ETV genotype resistance. The rate of ETV genotype resistance was 57.1% (4/7) and 68.2% (15/22) in patients with genotype B and genotype C,while no statistical difference was found(P = 0.665)., Conclusions: ETV genotype resistance is more common in patients who have been refractory to ETV and lamivudine sequential treatment. rtM204+rtL180+rtT184 mutation is common in genotype B and C ETV resistance patients.

Objective: To explore relations between the opportunities and effects of internal general treatment added Entecavir on acute-on-chronic liver failure (ACLF) of HBeAg-negative chronic hepatitis B in different score ranges of acute-on-chronic liver failure severity., Methods: A total of 108 ACLF of HBeAg-negative chronic hepatitis B patients with different ACLF severity score were treated with internal general treatment added Entecavir. The liver failure severity scores, HBV-DNA loads during the initiation of therapy, recovery phase and in deathbed phase, courses of Entecavir administration and mortalities were studied., Results: For 19 patients with high ACLF score (> or = 12), the difference in ACLF score between pre and post-treatment was not significant. The difference in HBV-DNA load between pre and post-treatment was not significant and the mortality was 18/19. For 30 patients with higher intermediate ACLF score (8-11), the difference in ACLF score between pre and post-treatment was not significant. The difference in HBV-DNA load between pre and post-treatment was significant, and the mortality was 66.67% (20/30). For 36 patients with lower intermediate ACLF score (5-7), the difference in ACLF score between pre and posttreatment was not significant. The difference in HBV-DNA load between pre and post-treatment was significant, and the mortality was 30.56% (11/36). For 23 patients with low ACLF score (< or = 4), the difference in ACLF score between pre and post-treatment was significant. The difference in HBV-DNA load between pre and post-treatment was significant, and the mortality was 8.70% (2/23)., Conclusions: A novel acute-on-chronic liver failure scoring system can syllabify differentiate the relations between the opportunities and efficacies on the Entecavir treatment for HBeAg-negative ACLF.

Objective: To investigate the efficacy and safety of peginterferon alfa-2a (Peg-IFNa-2a) therapy for treating chronic hepatitis B (CHB) in patients who failed to achieve a satisfactory end point with entecavir (ETV) treatment., Methods: Fifty-seven CHB patients with positivity for hepatitis B e antigen (HBeAg) who had completed a standard ETV monotherapy course, of at least 96 weeks, and who had achieved a virological response (defined as HBV DNA less than 500 copies/ml) but without HBeAg seroconversion (defined as 0.227 PEI U/ml less than HBeAg less than or equal to 50 PEI U/ml) were enrolled in the study. The patients were randomly assigned to receive a 48-week treatment with Peg -IFNa-2a (experimental group, n = 27) or continued ETV therapy (control group, n = 30). Serum samples were collected from all patients for assessment of biochemical, virological and serological responses to treatment. Inter-group differences were statistically evaluated by t-test or Chi-squared test., Results: The baseline levels of alanine aminotransferase, hepatitis B surface antigen (HBsAg), and HBeAg were similar between the patients comprising the experimental and controls groups. At treatment week 48, the experimental group showed significantly higher rates of HBeAg clearance (Peg-IFNa-2a: 40.7% vs. ETV: 16.7%, x2 = 4.079, P less than 0.05) and seroconversion (37.0% vs. 13.3%, x2 = 5.110, P less than 0.05). The experimental group also showed higher rates of HBsAg clearance (7.4% vs. 0%) and HBV DNA relapse (11.1% vs. 0%), but the differences did not reach statistical significance (x2 = 2.307 and 3.519, both P more than 0.05). However, the level of HBsAg was significantly lower in the experimental group (2866.0+2580.4 vs. 4335.8+2650.0 IU/ml, t = 5.11, P less than 0.05)., Conclusion: HBeAg-positive CHB patients with unsatisfactory response to initial ETV monotherapy achieved HBeAg seroconversion and clearance following sequential Peg-IFN a-2a treatment.

Objective: To analyze the predictive factors of the therapeutic effects of interferons (IFNs) and entecavir (ETV) treatments for 48 weeks in patients with chronic hepatitis B (CHB) positive for HBeAg., Methods: This retrospective analysis compared the treatment efficacy of IFNs and ETV in 129 CHB patients positive for HBeAg. Twenty-seven of the patients were treated with PEG-IFNα-2a (180 µg once a week, PEG-IFN group), 51 patients with conventional IFNα (5 MIU three times a week, IFN group), and 51 with ETV (0.5 mg once daily, ETV group) for 48 weeks., Results: After completion of the treatment cycles, the patients in ETV group showed a significantly higher HBV DNA undetectable rate and a significantly lower HBeAg seroconversion rate than those in PEG-IFN and IFN groups (P<0.05); HBeAg seroconversion rates were similar between PEG-IFN group and IFN group (Χ(2)=0.709, P=0.400). In PEG-IFN and ETV groups, HBeAg seroconversion rates were not associated with age, gender, baseline HBeAg, baseline HBV DNA and baseline ALT. In IFN group, HBeAg seroconversion rates were associated with baseline HBeAg (P=0.048) but not with age, gender, baseline HBV DNA and baseline ALT. In PEG-IFNα-2a group, ROC analysis showed that the sensitivity and specificity of HBeAg seroconversion at 48 weeks were 0.778 and 0.889, respectively, when the decline rate of HBeAg between baseline and week 24 exceeded 97.81%, with the corresponding positive and negative predictive values (PPV and NPV) of 0.778 and 0.889, respectively; the sensitivity and specificity of HBeAg seroconversion at 48 weeks were 0.889 and 0.722, respectively, when the decline rate of HBeAg between week 12 and week 24 was over 42.75%, with the corresponding PPV and NPV of 0.615 and 0.929, respectively., Conclusion: Treatments with PEG-IFNα-2a and conventional IFNα for 48 weeks can achieve a higher HBeAg seroconversion rate than ETV, but the latter produces a higher HBV DNA undetectable rate. For PEG-IFNα-2a treatment, the decline rate of HBeAg between baseline and week 24 over 97.81% is the best predicting factor for HBeAg seroconversion at week 48 in CHB patients positive for HBeAg.

Objective: To compare the efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs in the second-line treatment for patients with advanced non-small cell lung cancer., Methods: The clinical data of 170 patients with advanced non-small cell lung cancer who failed standard first-line chemotherapy were reviewed. Those who received docetaxol as second-line therapy were designated as group A (n = 60), those who received pemetrexed as second-line therapy were designated as group B (n = 49), and those who received EGFR-TKIs as second-line therapy were designated as group C (n = 61). PFS and MST were estimated by Kaplan-Meier method and the differences between groups were compared by log-rank test., Results: The response rate in the groups A, B and C group was 15.0% (9/60), 24.5% (12/49) and 36.1% (22/61), respectively. The PFS after second-line therapy in the groups A, B and C was 5.49 months (95%CI: 4.03 - 6.95 months), 5.42 months (95%CI: 4.23 - 6.60 months) and 9.31 months (95%CI: 6.88 - 11.73 months), respectively (P = 0.045). The MST after second-line therapy in the groups A, B and C was 14.89 months (95%CI: 11.23 - 18.55 months), 15.81 months (95%CI: 12.11 - 19.52 months) and 17.47 months (95%CI: 13.38 - 21.56 months), respectively (P = 0.574). Regression analysis showed that the performance status score (PS) and response for second-line treatment are independent prognostic factors in each sub-group, and pathological type is an independent prognostic factor in the group C (P = 0.003)., Conclusions: The safety of the three drugs used as second-line treatment for patients with advanced non-small-cell lung cancer, who failed standard first-line chemotherapy, is comparable, but the EGFR-TKIs group has the highest response rate, and the EGFR-TKIs group has the longest PFS with a statistically significant difference, while there is no significant difference in MST among the three groups. When patients receive second-line treatment, the performance status < 2 and the response rate for second-line treatment are independent prognostic factors. Furthermore, pathological type (adenocarcinoma) is also an independent prognostic factor for EGFR-TKIs as second-line treatment.

Background and Objective: Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC). Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment., Methods: The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1) to receive cisplatin plus pemetrexed chemotherapy (PC group) or gemcitabine plus cisplatin (GC group) every 3 weeks. The primary end point was progression free survival (PFS) and the secondary end points included 1 year survival rate, objective response rate (ORR), survival without grade 3/4 toxicity (SWT3/4) and safety profile., Results: A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS), the PFS was 168 days (5.6 months) vs 140 days (4.7 months) (P=0.16), one year survival rate was 50.0% vs 54.9% (P=0.47), ORR was 24.4% vs 14.2% (P=0.06) in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23). In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003). The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia., Conclusions: The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

Background and Objective: Due to the various inter-individual differences in the biological characteristics of tumor cells, as well as issues on the efficacy, adverse reactions, and defects of existing drugs, we compared the clinical efficacy and toxicity of pemetrexed and gemcitabine combined with cisplatin for the treatment of previously untreated advanced non-small cell lung cancer (NSCLC)., Methods: 251 patients were randomly divided into pemetrexed combined with cisplatin group (PP group) with 127 cases and gemcitabine combined with cisplatin group (GP group) with 124 cases. PP group received pemetrexed 500 mg/m² iv infusion d1 and cisplatin 75 mg/m² iv infusion d1, whereas GP group received gemcitabine 1,000 mg/m² iv infusion d1,8 and cisplatin 75 mg/m² iv infusion d1. The treatment cycle was once every three weeks. In addition, folic acid, vitamin B12, and dexamethasone were administered in both groups., Results: The total clinical effective rates in PP group and GP group were 25.20% and 17.74%, respectively. The total efficiencies of non-squamous cell carcinoma were 27.62% and 16.00%. The tumor progression duration in these two groups was 6.5 and 5.6 months, respectively. The median survival time in the two groups was 16.9 and 17.0 months, respectively, with 59.62% and 65.87% survival rates of 1 year and 27.28% and 27.93% survival rates of 2 years, respectively. The total efficacy of non-squamous cell carcinoma in the PP group was significantly higher than that in GP group. The results were statistically significant. However, there were no significant differences in total response rates, tumor progression duration, and median survival rates of 1 and 2 years. The rate of adverse reactions, including white blood cell reduction, lower platelet count, lower hemoglobin, and hair loss in the PP group was significantly lower than that in the GP group. The results were statistically significant., Conclusion: The clinical efficacy of pemetrexed and gemcitabine combined with cisplatin for the treatment of previously untreated advanced NSCLC was roughly the same, but the adverse reactions decreased significantly in the PP group compared with those in the GP group. Therefore, pemetrexed combined with cisplatin can be used as a safe and effective drug for clinical first-line treatment for previously untreated NSCLC.

Objective: To evaluate the efficacy and safety of entecavir (ETV) maleate versus ETV in Chinese patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB)., Methods: This was a randomized, double-blind, double-dummy, controlled, multicenter study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A; n = 26) or 0.5 mg/day ETV maleate (n = 31). Hepatitis B virus (HBV) DNA levels were measured at weeks 12, 24, and 48 by the Roche Cobas Ampliprep/Taqman PCR assay. Adverse events (AE) were recorded., Results: Baseline characteristics were similar between the two groups. At weeks 12, 24, and 48, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 4.24, 4.61 and 4.88 log10 IU/mL vs. B: 4.01, 4.50 and 4.99 log10 IU/mL, respectively; all P more than 0.05). Patients who achieved undetectable levels of serum HBV DNA (less than 20 IU/mL) at week 48 were similar in the two groups (A: 69.23% vs. B: 80.65%; P more than 0.05). Both groups achieved similar normalization of ALT at week 48 (A: 96.00% vs. B: 83.87%; P more than 0.05). The overall AE incidence was similar for the two groups (A: 22.22% vs. B: 9.38%; P more than 0.05)., Conclusion: Entecavir maleate and entecavir showed similar efficacy and safety in patients with HBeAg-negative CHB.

Objective: To investigate the changes in serum hepatitis B viral load (HBV DNA) and transformer growth factor-β(1)(TGF-β1) in patients with chronic hepatitis B after entecavir treatment and evaluates the therapeutic effect of entecavir., Methods: Sixty-three patients with chronic hepatitis B were randomly assigned into entecavir group (n=33) and control group (n=30). The entecavir group consisted of 9 mild, 17 moderate, and 7 severe cases, all treated with oral entecavir (0.5 mg daily) and general hepatoprotective drugs; the control group, consisting of 13 mild, 12 moderate and 5 severe cases, was treated with the hepatoprotective drugs only. Serum HBV DNA and TGF-β(1)were determined before and at 3 and 6 months during the treatment., Results: Entecavir treatment reduced serum HBV DNA load in all the cases in entecavir group, and the difference was statistically significant between the levels measured at 3 and 6 months (P<0.05). The treatment also resulted in decreased serum TGF-β(1)levels in moderate and severe cases, and the severe cases showed a significant TGF-β(1)reduction after a 6-month treatment (P<0.05)., Conclusion: Entecavir can lower serum HBV DNA load levels in patients with chronic hepatitis B. Entecavir is also effective to reduce serum TGF-β(1)levels in moderate and severe cases, especially in the latter.

Background and Objective: The immune function disorder relates closely to the occurrence, metastasis, and prognosis of cancer. T lymphocyte subsets take an important role in immune function. We identified the dynamic changes of the immune system by investigating the levels of T lymphocyte subsets in peripheral blood of lung cancer patients with advanced stage adenocarcinoma undergoing first line chemotherapy. The results aided the search for rational chemo-immunotherapy strategies in lung cancer treatment., Methods: Samples from 49 patients with pathologically demonstrated advanced stage adenocarcinoma cell lung cancer were compared with those from 33 healthy donors. Subsequently, the patients were separately treated with Docetaxol-based or Pemetrexed-based therapy. Peripheral blood samples at different time points after therapy were analyzed by flowcytometry. The lymphocyte subsets of the total lymphocytes were compared. Independent sample t test was used for the quantitative data analysis., Results: The percentage of CD3+, CD3+CD4+, CD4+CD25+ cells of the lung cancer patients significantly varied from those of the healthy donors, the P values are 0.012, 0.034 and 0.006 separately. The CD3+ and CD3+CD4+ levels increased significantly on the 4th and 7th-10th day post-chemotherapy, which return to normal levels on the 21th day. The CD3+ level increased significantly both in the treatment group on all time points, while the CD3+, CD3+CD4+, CD4+/CD8+ levels significantly increased and the CD3+CD8+, CD8+CD28- levels significantly decreased on the 4th day in Pemetrexed group. The CD3+CD4+ levels increased significantly on the 4th and 7th-10th day and the CD3+CD8+, CD8+CD28- levels decreased on the 4th day in partial response group., Conclusions: The immune function of advanced stage adenocarcinoma cell lung cancer patients was evidently suppressed, and was restored at the 4th day, followed by a reduction at the 21st day after chemotherapy. On the 4th day, Pemetrexed showed better effect on the immune system. The change of immune system post-chemotherapy could be related with the prognosis.

Background and Objective: Pemetrexed is a standard second-line therapy in advanced non-small cell lung cancer (NSCLC). Currently, cytotoxic treatments beyond second-line therapy are not available. This study evaluated the efficacy and safety of pemetrexed as a salvage regimen in heavily pretreated patients with NSCLC., Methods: Clinical data on 37 patients with advanced NSCLC who received pemetrexed as second-line therapy or beyond in Cancer Hospital of Peking Union Medical College from Feb 2005 to Sep 2009 were reviewed and analyzed retrospectively., Results: Thirteen patients (35.1%) received pemetrexed as second-line treatment, whereas 24 (64.9%) received it as third-line treatment or beyond. Complete response, partial response, stable disease and progressive disease were noted in 1 (2.7%), 2 (5.4%), 17 (45.9%) and 12 (32.4%) of the patients, respectively, with the disease control rate being 54.1%. The median duration of progression free survival was 8.05 months, whereas that of overall survival was 19.29 months., Conclusions: Pemetrexed is efficacious and tolerable as second-line therapy or beyond for advanced NSCLC and should thus be recommended for patients with this disease.

Objective: To evaluate of the efficacy and safety of entecavir (ETV) combined with Shenxian Yiganling (SY) versus ETV therapy on patients with HBeAg-positive chronic hepatitis B (CHB) for 48 weeks., Methods: One hundred and sixty-four CHB patients were assigned to two groups with the cohort study: the ETV combined with SY treatment group and the ETV control group. The alanine aminotransferase (ALT), the undetectable HBV DNA level, and HBeAg negative conversion rate, and HBeAg serological negative conversion rate were observed before and after treatment., Results: At week 48, there was no significant difference in the normalization of ALT levels (70.00% vs 67.61%, P > 0.05) and undetectable HBV DNA levels (72.50% vs 73.24%, P > 0.05) between the two groups. There was significant difference in the HBeAg negative conversion rate (39.44% vs 23.75%) and HBeAg serological negative conversion rate (32.39% vs 15.00%) (both P < 0.05)., Conclusion: ETV combined with SY promoted the HBeAg serological negative conversion rate possibly through the recovery of the immune functions.

Background and Objective: Pemetrexed in combination with platinum or a single-agent has been approved for the first- and second-line treatment of non-small cell lung cancer (NSCLC). However, the role of pemetrexed therapy in the third-line and beyond treatment of NSCLC has yet to be generally accepted. The present retrospective study reports the efficacy and safety of pemetrexed in the third-line and beyond treatment of advanced non-squamous NSCLC., Methods: A total of 46 patients with advanced non-squamous NSCLC received a combination of pemetrexed plus platinum or a single-agent after multi-line treatment failed to yield positive results., Results: Of the 46 patients who participated in the study, 7 achieved partial responses, 20 reached a stage of stable disease, and 19 reached a stage of progressive disease. The over-all object response rate was 15.2% and the disease control rate (DCR) was 58.7%. The median progression-free survival time was 3.0 months. Pemetrexed in combination with platinum yielded a higher DCR than the pemetrexed plus single-agent treatment (P=0.043). Common adverse events included nausea, vomiting and myelosuppression., Conclusions: Administration of pemetrexed after failure of multi-line treatment is clinically beneficial to patients with advanced non-squamous NSCLC. The toxic effects of the treatment appear to be tolerable.

Objective: To compare the efficacy of second-line EGFR-TKIs followed by third-line pemetrexed with second-line pemetrexed followed by third-line EGFR-TKIs in patients with advanced lung adenocarcinoma., Methods: From March 2007 to August 2008, 83 patients with advanced lung adenocarcinoma who failed standard first-line chemotherapy were included in this study. The patients who received EGFR-TKIs as second-line therapy followed by third-line pemetrexed were designated as group A (n = 45). The patients who received pemetrexed as second-line therapy followed by third-line EGFR-TKIs were designated as group B (n = 38). PFS and MST were estimated with Kaplan-Meier analysis and the difference between groups were compared with Log-rank test., Results: The progression-free survival (PFS) after second-line therapy in the groups A and B was 8.05 months (95% CI, 5.90 to 10.20) and 4.20 months (95% CI, 3.33 to 5.06), respectively (P = 0.001). The PFS after second-line therapy in smokers and non-smokers was 3.69 months (95% CI, 5.00 to 7.59) and 7.12 months (95% CI, 5.51 to 8.38), respectively (P = 0.007). The PFS of male and female patients was 5.56 months (95% CI, 4.02 to 7.10) and 6.85 months (95% CI, 4.98 to 7.58), respectively (P = 0.279). The PFS after third-line therapy in groups A and B was 6.88 months (95% CI, 5.07 to 8.69) and 7.60 months (95% CI, 5.59 to 9.12) respectively, (P = 0.899). The PFS after third-line therapy in smokers and non-smokers was 4.95 months (95% CI, 2.83 to 7.05) and 8.49 months (95% CI, 6.27 to 10.76), respectively (P = 0.050). The PFS after third-line therapy in male and female patients was 5. 96 months (95% CI, 4.02 to 7.91) amd 8.38 months (95% CI, 5.68 to 11.07), respectively (P = 0.176). The MST in groups A and B was 23.60 months (95% CI, 19.23 to 28.00) and 15.58 months (95% CI, 11.85 to 19.32), respectively (P = 0.021). The MST in smokers and non-smokers was 11.99 months (95% CI, 8.55 to 15.49) and 23.18 months (95% CI, 19.33 to 27.02), respectively (P = 0.001). The MST in male and female patients was 17.40 months (95% CI, 13. 19 to 21.61) and 22.74 months (95% CI, 18.29 to 27.19), respectively (P = 0.111)., Conclusions: Second line EGFR TKIs followed by third line pemetrexed regimen improves the PFS and MST compared with the regimen second line pemetrexed followed by third line EGFR TKIs in patients with advanced lung adenocarcinoma. Smoking status is an independent prognostic factor. Survival is not influenced by gender. Prospective clinical trials are needed to confirm these findings.

Objective: To explore the opportunity and effect of internal general treatment added entecavir on acute-on-chronic liver failure (ACLF) of HBeAg-negative chronic hepatitis B patients in different ranges of MELD score., Methods: A total of 101 ACLF of HBeAg-negative chronic hepatitis B patients treated with internal general treatment added entecavir were divided into three groups according to the MELD score. The mortalities and HBV DNA loads during the initiation of therapy, recovery phase and in deathbed phase were studied., Results: 20 of patients with high MELD score (> or = 30) received (14.6 +/- 14.1) days treatment. The difference in MELD score between pre-(36.03 +/- 5.01) and post-treatment (39.86 +/- 5.95) was significant (t = - 2.994, P = 0.007). There was no significant difference in HBV DNA load between pre-[(4.454 +/- 1.714) copies log10/ml] and post-treatment [(3.979 +/- 1.947) copies log10/ml] (t = 2.212, P = 0.051), the mortality was 100% (20/20). 47 of patients with moderate MELD score (22-30) received (51.5 +/- 41.6) days treatment. There was no significant difference in MELD score between pre-(25.71 +/- 2.47) and post-treatment (26.18 +/- 13.32) (t = - 0.263, P = 0.794). The difference in MELD score between pre-[(6.084 +/- 1.795) copies log10/ml] and post-treatment [(3.378 +/- 2.156) copies log10/ml] was significant (t =7.148, P = 0.000), the mortality was 53.19% (25/47). 34 of patients with low MELD score (< or = 22) received (67.2 +/- 40.9) days treatment. The difference in MELD score was significant between pre-(< or = 18.85 +/- 2.72) and post-treatment (11.68 +/- 7.23) (t = 5.983, P = 0.000). There was significant difference in HBV DNA load between pre-[(5. 945 +/- 1.635) copies log10/ml] and post-treatment [(2.725 +/- 1.194) copies log10/ml] (t = 9.962, P = 0.000), the mortality was 2.94% (1/34)., Conclusions: The ACLF of HBeAg-negative chronic hepatitis B patients with a low score of MELD score (< or = 22) mostly survive with internal general treatment added entecavir. The mortality of the patients with a MELD score (22-30) is 53.19% (25/47). The patients with high MELD score (> or = 30) which almost lack the opportunity of treatment, is associated with fatal liver failure and need for emergency liver transplantation.

Objective: To evaluate the efficacy of entecavir (ETV) 1.0 mg/d or ETV plus adefovir dipivoxil (ADV) in adults with chronic hepatitis B virus (HBV) infection who had previously resisted lamivudine (LAM) and failed with rescue treatment of LAM + ADV., Methods: 40 patients were enrolled. 14 patients were treated with ETV 1.0 mg/d monotherapy while 26 patients were treated with ETV 1.0 mg/d + ADV 10 mg/d. The HBV DNA level, liver function, HBV serology and renal function were observed., Results: There was no statistically significant difference with baseline situation between group ETV 1.0 mg and group ETV + ADV. HBV DNA level in group ETV 1.0 mg was (5.768 ± 0.709) log10 copies/ml on baseline, and it declined to (4.712 ± 0.846) log10 copies/ml, (3.914 ± 0.996) log10 copies/ml, (3.702 ± 0.934) log10 copies/ml, (3.879 ± 0.913) log10 copies/ml and (3.855 ± 1.070) log10 copies/ml at 4, 8, 12, 24 and 48 weeks. HBV DNA level in group ETV + ADV was (5.703 ± 0.845) log10 copies/ml on baseline, and it declined to (4.476 ± 0.905) log10 copies/ml, (3.590 ± 0.884) log10 copies/ml, (2.987 ± 0.673) log10 copies/ml and (2.933 ± 0.535) log10 copies/ml at 4, 8, 12 and 24 weeks. At 24 weeks, there were 28.6% patients achieved HBV DNA < 500 copies/ml in group ETV 1.0 mg, but there were 80.8% patients in group ETV + ADV achieved this level. Statistically significant difference existed between (x(2) = 8.469, P = 0.004 ). At 48 weeks, there were still 4 patients achieved HBV DNA < 500 copies/ml in group ETV 1.0 mg, but patients in group ETV + ADV all achieved it. At 24 weeks, ALT levels of 42.9% patients in group ETV 1.0 mg were back to normal, but there were 92.3% patients' ALT levels back to normal in group ETV + ADV. There was statistically significant difference (x(2) = 9.337, P = 0.002). At 48 weeks, ALT levels of 57.1% patients in group ETV 1.0 mg were back to normal, but all patients' ALT levels were back to normal in group ETV + ADV. At 48 weeks, there was 1 patient with HBeAg seroconversion in group ETV 1.0 mg while there were 4 patients in group ETV + ADV., Conclusion: As rescue treatment for patients with chronic hepatitis B who had previously resisted LAM and failed with treatment of LAM + ADV, ETV + ADV was more efficient than ETV 1.0 mg monotherapy, and it can achieve better virological and biochemical response.

Objective: To evaluate antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B., Methods: 92 chronic hepatitis B patients were enrolled to receive the treatment with Peg-IFNa-2a 180 μg subcutaneous injection once weekly. The patients who did not get early response were divided into 3 groups: group 1, extend the treatment to 72 weeks; group 2, combined with nucleus(s)ide analogue (entecavir or adefovir) treatment; group 3, continue the treatment until 48 weeks. HBV DNA and quantitative HBsAg were assessed at baseline, week 12, 24, 36 and after 24 weeks follow-up., Results: Patients in group 1 had significantly higher SVR rate (78.3%) than patients in group 3 (38.1%, X2=7.33, P<0.05). The mean reduction of HBsAg in group 1 at 24 weeks of post-treatment follow up was higher than that in group 3 (t=2.11, P<0.05). In group 2 the mean reductions of HBV DNA at 24 weeks of post-treatment follow up were (3.9+/-1.1) log10 copy/ml and (3.7+/-1.3) log10 copy/ml respectively with combination of entecavir or adefovir, both of which were significantly higher than that in group 3(t=8.45 and 6.31, P<0.05); the SVR rates in the entecavir group and the adefovir group (83.3% and 85.7%, respectively) were significantly higher than that in group 3 (X2=8.20 and 7.78, P<0.05); the mean reductions of HBsAg in the entecavir group and the adefovir group [(0.8+/-0.5) log10 IU/ml and (0.9+/-0.3) log10 IU/ml, respectively ] were significantly greater than group 3[(0.4+/-0.3) log10 IU/ml, t=3.05 and 4.58, P<0.05]. The level of HBV DNA and C genotype were the main predictors of response., Conclusion: Individualizing therapy by prolonging the duration of Peg-IFNa-2a treatment to 72 weeks or adding nucleoside analogues such as entecavir and adefovir in patients without early response may substantially increase the SVR rate and lead to the decrease of HBsAg.

Background and Objective: At present, there is no standard salvage treatment strategies for lung cancer. The aim of this study is to compare the efficacies and safeties of pemetrexed alone with pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma to provide evidences for combination therapy., Methods: From January 2009 to February 2011, 83 patients with stage IV lung adenocarcinoma received pemetrexed alone (single agent arm, n=47) or pemetrexed combined with oxaliplatin (combination arm, n=36) as salvage therapy. All 83 patients had performance status (PS) scores of 0-2., Results: Eighty-one patients were included in the final analysis. The median progression-free survival (PFS) in the single agent arm was 3.6 months versus 4.1 months in the combination arm (P=0.268). The objective response rate (ORR) was 6.5% versus 20% (P=0.092), and the disease control rate (DCR) was 56.5% versus 65.7% (P=0.493), respectively. The response rates of the hematological and gastrointestinal toxicities in the single agent and combination arms were 33.9% versus 47.2% (P=0.460) and 21.2% versus 25.0% (P=0.213), respectively., Conclusions: For salvage therapy, pemetrexed combined with oxaliplatin is tolerable in stage IV lung adenocarcinoma patients with good PS scores. Compared with pemetrexed alone, pemetrexed combined with oxaliplatin therapy showed higher response rate, but did not significantly prolong the PFS.