Adenine ; analogs & derivatives ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Nucleosides ; therapeutic use ; Organophosphonates ; therapeutic use

Adenine ; analogs & derivatives ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Nucleosides ; therapeutic use ; Organophosphonates ; therapeutic use

OBJECTIVETo investigate the efficacy profile of entecavir capsule (ETV) as a chronic hepatitis B therapy, as compared to lamivudine (LAM).

METHODSIn 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).

RESULTSAfter 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).

CONCLUSIONETV 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.

Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Male ; Young Adult

OBJECTIVETo 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.

METHODSThe 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.

RESULTSAt 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.

CONCLUSIONFor 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.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Drug Therapy, Combination ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferons ; therapeutic use ; Organophosphonates ; therapeutic use

OBJECTIVETo evaluate antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B.

METHODS92 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.

RESULTSPatients 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.

CONCLUSIONIndividualizing 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.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Treatment Outcome

Objective: To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment. Methods: Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months. Results: In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) ( Conclusion During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.
Adult ; Antiviral Agents/therapeutic use* ; Cytokines/blood* ; Female ; Guanine/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Interferon-alpha/therapeutic use* ; Male ; Polyethylene Glycols/therapeutic use* ; Prospective Studies ; Recombinant Proteins/therapeutic use*

Chronic hepatitis B (CHB) is a serious health problem in Korea. The natural history of chronic HBV infection has been divided into 4 phases: immune tolerance, immune clearance, inactive HBsAg carrier state and reactivation. During the phases of immune tolerance and inactive HBsAg carrier state, no treatment is required. Patients in the immune clearance or reactivation phases are candidates for therapy. In the last years, treatment effects of CHB have considerably improved. Several agents are currently approved for the treatment of CHB: interferon alpha, pegylated interferon alpha, lamivudine, adefovir, entecavir, telbivudine and clevudine in Korea. The treatment recommendations from the 2004 Korean Association for the Study of the Liver guideline on the management of CHB have been updated to incorporate new therapeutic options. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Issues for consideration include efficacy, safety and incidences of resistance, and method of administration of antiviral therapy in treatment-naive patients.
Adenine/analogs & derivatives/therapeutic use ; Antiviral Agents/*therapeutic use ; Arabinofuranosyluracil/analogs & derivatives/therapeutic use ; Guanine/analogs & derivatives/therapeutic use ; Hepatitis B, Chronic/*drug therapy ; Humans ; Interferon Alfa-2a/therapeutic use ; Interferon Alfa-2b/therapeutic use ; Korea ; Lamivudine/therapeutic use ; Phosphonic Acids/therapeutic use ; Polyethylene Glycols/therapeutic use ; Practice Guidelines as Topic

No abstract available.
Antiviral Agents/*therapeutic use ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/*genetics ; Hepatitis B, Chronic/*drug therapy ; Humans ; Liver Cirrhosis/*etiology ; Male

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.
Antiviral Agents/therapeutic use* ; Carcinoma, Hepatocellular/surgery* ; Guanine/analogs & derivatives* ; Hepatectomy ; Hepatitis B virus ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Neoplasms/surgery* ; Retrospective Studies ; Tenofovir/therapeutic use*

OBJECTIVETo investigate the expression of thymidylate synthase (TS) in patients with advanced lung adenocarcinoma and its relation with the therapeutic effect of pemetrexed.

METHODSThe clinicopathological data of 38 patients with stage IIIIB/IV lung adenocarcinoma receiving pemetrexed treatment were retrospectively analyzed. The tumor samples of the patients were collected for detecting TS expression using RT-PCR, and the therapeutic effect of the treatment was analyzed.

RESULTSTS positivity was found in 26.32 (10/38) of the patients. TS positivity was not correlated to gender, TNM stage or PS score. The total response rate of pemetrexed treatment (CR+PR) was 34.21 (13/38) in these patients, and the rate was 39.29% (11/28) in TS-negative patients, as compared to 20.00% (2/10) in the positive patients (P=0.087). Patients with low TS expression had significantly higher control rate by pemetrexed treatment than those with TS overexpression [89.29% (25/28) vs 40.00% (4/10), P=0.002].

CONCLUSIONTS expression may serve as a potential indicator of chemosensitivity to pemetrexed in patients with advanced lung adenocarcinoma.

Adenocarcinoma ; drug therapy ; enzymology ; Antineoplastic Agents ; therapeutic use ; Female ; Folic Acid Antagonists ; therapeutic use ; Glutamates ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; Male ; Middle Aged ; Pemetrexed ; Retrospective Studies ; Thymidylate Synthase ; metabolism