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Objective: To compare the efficacy and safety of the common antivirals, including adefovir dipivoxil (ADV), pegylated-interferon alpha-2a (peg-IFN) and lamivudine (LAM), used as combination therapies to treat chronic hepatitis B (CHB) patients with positivity for the hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) harboring the ADV-resistance mutation, rtN236T, and to explore the factors associated with curative outcome., Methods: Sixty-five adult CHB patients (age range: 20-60 years) who were unresponsive to ADV therapy (HBeAg-positive; HBV DNA >or= 10(5) copies/ml), LAM-naive, and tested positive for the rtN236T HBV mutation were enrolled in the study and randomly divided into two treatment groups: Group A (n = 33), who were administered ADV (10 mg/day, orally) plus peg-IFN (180 microg/week, subcutaneous injection) for 48 weeks; and Group B (n = 32 patients), who received the ADV plus LAM (100 mg/day, orally) for 48 weeks followed by continued LAM treatment for an additional 24 weeks. Pre- (baseline), during and post-treatment measurements of HBV viral loads and hepatitis B markers were made by quantitative PCR and electrochemiluminescence assays, respectively. All patients underwent liver biopsies to determine the histological activity index (HAI) and treatment response regarding inflammation and fibrosis stage. The rates of virological response (VR), HBeAg-negativity, HBeAg seroconversion, and alanine aminotransferase (ALT) normalization were calculated, and the significance of differences between groups were assessed by Student's t-test and Chi2 test., Results: There were no significant differences between the two groups in regards to sex, age, or baseline levels of HBV DNA, ALT, and total bilirubin (P > 0.05). At weeks 24 and 48 of treatment and 24 after treatment end, group A showed significantly higher (vs. group B, P < 0.05) rates of reduced HBV DNA viral loads (81.8%, 90.9%, and 75.8% vs. 53.1%, 56.2%, and 59.4%), VR (48.5%, 60.6%, and 42.4% vs. 31.3%, 34.4%, and 31.3%), HBeAg-negativity (39.4%, 60.6%, and 54.5% vs. 12.5%, 37.5%, and 37.5%), HBeAg seroconversion (27.3%, 54.5%, and 48.5% vs. 6.3%, 15.6%, and 18.8%), and ALT normalization (72.7%, 84.8%, and 78.8% vs. 46.9%, 56.3%, and 46.9%). After 48 weeks of treatment, group A showed significantly improved HAI (vs. group B, P < 0.05). With the exception of treatment-related increased creatinine (P < 0.05), group A showed significantly higher rates of adverse reactions; although, none was serious enough to threaten patient safety or necessitate early termination of the treatment regimen. Twenty-four weeks after treatment completion, five patients had HBV viral loads of >or= 2log10 copies/ml and four had < or= 500 copies/ml, and ALT was normalized in 28 patients. The four patients in group A with HBV DNA < or= 500 copies/ml and elevated ALT during treatment did not show HBeAg seroconversion., Conclusion: Peg-IFN plus ADV combination therapy produced better outcomes than the ADV plus LAM combination therapy in regards to HBV viral loads, VR rate, HBeAg-negative rate, HBeAg seroconversion rate, ALT normalization rate, and HAI, but was associated with a higher rate of adverse reactions (none of which were severe). Lack of HBeAg seroconversion was associated with higher virus load and ALT levels.

Objective: To clinically study the antiviral effects of lamivudine and entecavir on patients with early-to-mid stage Hepatitis B related acute on chronic liver failure (HBV-ACLF). METHODS; A prospective, randomized, open and parallel controlled clinical trial was designed to observe the antiviral effects of nucleoside analogues on patients with early-to-mid stage HBV-ACLF. Three groups were set for controlled study, i. e. basic treatment group, lamivudine plus basic treatment group and entecavir plus basic treatment group., Results: One month after treatment, the improvement rates of lamivudine group and entecavir group were 58.85% and 59.15% respectively, significantly higher than that of basic treatment group which was 34.84% (Chi(2) = 9.8323, P = 0.043). By the end of six months, the cumulative survival rates of patients with the antiviral treatments, i.e., lamivudine, entecavir, were 65.8%, 60.1%, significantly higher than that (42%) without the antiviral treatment (P = 0.045, P = 0.04 respectively). The cumulative survival rate in patients with a MELD score < 30 was higher than that with a MELD score over 30 (Chi(2) = 3.920, P = 0.048). For the patients with pretreatment HBV DNA > or = 10(7), the cumulative survival rate in patients with entecavir treatments group was higher than that of patients in basic treatment group (Chi(2) = 5. 014 P= 0.025). According to the Ordinal Regression analysis, antiviral therapy by using either lamivudine or entecavia could significantly increase the improvement rate of patients with early-to-mid stage HBV-ACLF. But severe complications, including hepatorenal syndrome, electrolyte imbalance and hepatic encephalopathy, medical history of liver cirrhosis, and pretreatment HBV DNA > or = 10(7) had significant impacts on prognosis of this group patients., Conclusions: Antiviral therapy by using either lamivudine or entecavia could significantly increase the survival rate of patients with early-to-mid stage HBV-ACLF.

Objective: To explore the key points of nursing HBeAg negative cirrhotic patients with nucleot(s) ide analogues antiviral therapy., Method: Patients enrolled into this study were divided into antiviral group (58 cases) and control group (53 cases). Patients from control group only received the supportive and symptomatic treatment and those from antiviral group received the additional nucleot (s) ide analogues treatment. All patients were observed during hospitalization and were followed up in clinic. Finally, we would make a nursing assessment., Results: All patients finished the 96-week treatment and follow-up, except 6 patients died. Alanine transferase normalization rate and HBV DNA decline were more remarkable in antiviral group than that in control group. HBV DNA negative( <500 copies/ml) after 96-week treatment were 88.7% in antiviral group and 32. 5% in control group respectively(Chi(2) = 31.427, P = 0.001)., Conclusion: Nucleot(s) ide analogues are significantly effective to inhibit HBV DNA replication in HBeAg negative cirrhotic patients and improve liver function. The key points of nursing these patients including appropriate patients' educating, benign nurse-patient relationship building, medical compliance emphasizing, and attentive complication observing and dealing.

Objective: To evaluate the efficacy and safety of 96 weeks adefovir dipivoxil (ADV) treatment for chronic hepatitis patients with cirrhosis in their decompensation period., Methods: Chronic hepatitis patients with cirrhosis in their decompensation period were randomly divided into two groups. An ADV group: patients treated with 10 mg ADV per day; a lamivudine (LMV) group: patients treated with 100mg LMV per day. The course of treatment lasted 96 weeks. Serum levels of ALT, AST, Alb, Tbil, HbeAg, HBV DNA, PCIII, IVC, LN and HA, renal function, Child-Pugh scores, drug adverse reactions and complication during the treatment of the two groups were analyzed., Results: During the two-year treatment, the proportions of patients with a return to normal liver function were similar in both groups. With the treatment prolonged, serum HBV DNA levels of the patients in adefovir dipivoxil group decreased gradually. The HBV DNA level in some lamivudine-treated patients was increased. The sero-conversion rate of HBeAg/HBeAb of the patients in the two groups was increased with the prolongation of the treatment. At 96 weeks, the ratio of emerging virus-resistant strains was lower in the adefovir dipivoxil group than in the lamivudine group. The levels of the serum markers of hepatic fibrosis of the patients in the two groups remained low. Child-Pugh scores of the patients in the two groups were significantly improved. No significant difference in the total incidence of complications between the two groups was noticed. Each of the two groups had a patient with liver-kidney syndrome and other serious complications., Conclusion: The efficacy and safety of adefovir dipivoxil and lamivudine treatment for the above patients are similar, but the ratio of emerging virus-resistant strains of the adefovir dipivoxil treatment group is lower than that of lamivudine treatment group.

Objective: To investigate the incidence of HBV reactivation and its clinical characteristics in the non-active HBsAg carriers receiving chemotherapy or immunosuppressant treatment, and to evaluate the role of nucleos(t)ide analogues against HBV reactivation., Methods: Non-active HBsAg carriers suffering from cancer, autoimmune diseases recieving immunosuppression therapy or cytotoxic chemotherapy were enrolled in the study. The in-patients from June 2002 to April 2007 in the Second Affiliated Hospital of Chongqing Medical University were assigned in the control group. The outpatients or in-patients with the similar disease condition from April 2007 to July 2008 were enrolled in the preventive group. The characteristics of HBV replication, liver damage, clinical symptoms and effectiveness of nucleos(t)ide analogues as prophylaxis for HBV reactivation were observed. The nucleos(t)ide analogues were used before chemotheraphy or immunosuppressive agents. The characheristics and clinical manifestations about HBV reactivation were investigated., Results: Of the 32 patients in preventive group, the amount of HBV DNA was detected in the 1rst, 3rd, 6th and 12th month after nucleos(t)ide analogues treatment. After chemotherapy or immunosuppressant treatment, only 9.4% (3/32) of them suffered from HBV reactivation, as indicated by positive HBV DNA in the serum and abnormal liver function. Ot the 77 patients in control group without nucleos(t)ide analogues treatment before chemotherapy or immunosuppression therapy, 58.4% (45/77) shown HBV reactivation, 4 patients in the control group died of liver failure, and one liver failure patient recieved liver transplantation., Conclusion: HBV can be activated in immunosuppressed patients, nucleos(t)ide analogues should be used in early phase to prevent HBV reactivation.

Objective: To evaluate the efficacy and safety of 48 weeks adefovir dipivoxil (ADV) treatment for chronic hepatitis patients with cirrhosis in their decompensation period., Methods: Sixty-two chronic hepatitis patients with cirrhosis in their decompensation period were randomly put into two groups. An adefovir dipivoxil (ADV) group: 32 patients treated with 10 mg of ADV a day; and a lamivudine (LMV) group: 30 patients treated with 100 mg of LMV a day. The course of treatment lasted 48 weeks. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alb, TBil, HBeAg, HBV DNA, PCIII, IVC, LN, and HA, renal function, Child-Pugh scores and drug adverse reactions during the treatment of the two groups were checked, compared and analyzed., Results: The ratios of recovery for liver functions and the negativity rate of HBV DNA, HBeAg, including sero-conversion rate of HBeAg/HBeAb, were increased with prolongation of the treatment period; however, the differences between the two groups were not statistically significant (P > 0.05). Two patients treated with lamivudine suffered from YMDD variation at the 48th week; the ratio of variation was 6.7%. No YMDD variation happened in the ADV group. On the 24th week of the treatment, the levels of the serum markers of hepatic fibrosis declined obviously, compared with those prior to the treatment (P < 0.01). There were no significant statistical differences of those levels between the two groups (P > 0.05). No significant differences of Child-Pugh scores were noticed between the two groups (P > 0.05). No drug related renal function impairment was found during the treatment. Two patients of each group had adverse drug reactions but all were mild., Conclusion: The efficacy and safety of adefovir dipivoxil and lamivudine treatment for the above patients were similar, but the ratio of emerging virus-resistant strains was lower in the adefovir dipivoxil treatment group.

Objective: To observe the efficacy and safety of lamivudine and interferon-alpha (IFN-alpha) therapy on decrease of serum hepatitis B virus (HBV) loading of HBV transgenic mice during pregnancy., Methods: Thirty-five transgenic mice replicating high levels of hepatitis B virus were randomly allocated into 5 groups, each of seven. Pregnant HBV transgenic mice in experimental groups 1 and 2 were given orally lamivudine [100 mg/(kg x d)] from pregnancy day 5 or 10 to delivery, mice in experimental groups 3 and 4 were given intramuscular (im) injection of IFN-alpha [5MU/(m(2) x 2d)], and mice in experimental group 5 were given normal saline at the same times. The changes of serum HBsAg, HBV DNA before and after the treatment were detected. At the same time, eighteen C57BL/6J female mice (clean level) were randomly allocated into control groups 1, 2 and 3 (each group of six), which were given lamivudine, IFN-alpha and saline respectively (the dosage was the same as that of experimental groups). The safety indexes of pregnant mice, fetus and newborns in experimental groups and control groups were observed., Results: (1) The changes of serum HBsAg titers: The average serum HBsAg titers from mice in experimental group 1 were lowered significantly from (166 +/- 98) ng/ml to (82 +/- 59) ng/ml after drug treatment (P < 0.05). Those from mice in experimental group 2 were also reduced from (159 +/- 49) ng/ml to (82 +/- 60) ng/ml after drug treatment, but there was no significant difference between before and after the treatment (P > 0.05). There was no significant difference in serum HBsAg between before and after the treatment in other groups (P > 0.05). (2) The changes of HBV DNA titers: The serum HBV DNA titers from mice in experimental groups 1 and 2 were significantly decreased, from (5.50 +/- 0.86) copies/ml to (2.58 +/- 2.01) copies/ml, with significant difference between before and after the treatment (P < 0.01). Those from mice in experimental groups 3 and 4 were reduced from (5.55 +/- 0.24) copies/ml to (5.46 +/- 0.45) copies/ml, without significant difference between before and after the treatment (P > 0.05). The serum HBV DNA titer from mice in experimental group 5 was not different between before and after the treatment (P > 0.05). (3) Observation of safety indexes: no evidence in toxicity were observed in mice from experimental groups and control groups. No significant abnormalities of live fetus were observed. The postnatal survival and weight of live pups were not different between the groups (P > 0.05). (4) Comparison of the rate of dead fetus and the rate of maternal dead fetus: The rate of dead fetus and the rate of maternal dead fetus from mice in experimental groups 1 and 2 were 8.3% and 50.0% respectively, those from mice in experimental groups 3 and 4 were 8.2% and 66.7% respectively, and those from mice in experimental group 5 were 9.7% and 66.7%. There was no significant difference in the rate of dead fetus and the rate of maternal dead fetus from mice between the groups (P > 0.05)., Conclusions: Effective lamivudine treatment during gestation can reduce hepatitis B viremia in pregnant HBV transgenic mice, thus lowering the risk of intrauterine infection. It has no significant adverse effect on safety of pregnant mice and their offspring.

Objective: To analysis the efficacy and safety of lamivudine (made in China) therapy for 52 weeks in adolescent patients with chronic hepatitis B (CHB)., Methods: One hundred and five teenage CHB patients were treated with lamivudine 100 mg once daily for 52 weeks. Patients with elevated ALT at baseline were in group 1 and those with normal ALT were in group 2. The changes of HBV DNA, HBV seromarkers and ALT at the end of 12, 24 and 52 weeks after lamivudine therapy were compared with those at baseline. Adverse events were recorded and evaluated., Results: At the end of 52 weeks of lamivudine therapy, HBV DNA-ve, HBeAg loss and anti-HBe seroconversion were observed in 92.0%, 24.4% and 22.0% in group 1 patients and 76.1%, 14.2% and 14.2% in group 2 patients respectively. No significant differences were found between two groups. At 12, 24 and 52 weeks, normalization rates of ALT were 59.0%, 66.7% and 76.0%, normal ALT with undetectable HBV DNA were 44.9%, 64.1% and 70.7% at the same time. During 52 weeks lamivudine treatment 26 mild adverse events were observed in 18 patients., Conclusion: Lamivudine can inhibit HBV replication rapidly and normalize ALT in majority adolescent CHB patients. HBeAg loss or seroconversion of anti-HBe was observed in some of these patients. All patients in this study were safety and well tolerated.

Objective: To investigate clinical effect, liver pathohistological changes (including pathology, HBV markers in liver tissue) in patients with chronic hepatitis B., Methods: 70 patients of chronic hepatitis B were administered 100 mg Lamivudine orally daily for 1 year. The serum HBV-DNA, HBeAg/anti-HBe, hepatic chemistry and the hepatic fibrosis markers were studied. The needle biopsy of liver were performed in 35 patients before and after treatment and Knodell pathological score were done, HBsAg, HBcAg, alpha-SMA in liver tissue were examined by immunohistochemistry method., Results: After 1 year treatment the full response rate, partial response rate and no response rate were 23.72%, 69.49% and 6.78%, the patients in whom HBeAg seroconversion had higher base-line Alanine aminotransferase levels than the patients without seroconversion. Activity index of hepatic histology in 41.18% patients had a significant decrease. Histological assessment revealed that necrosis in portal area, pylenphlebitis and fibrosis were obviously alleviated. The liver immunohistochemistry examination showed HBcAg and alpha-SMA in liver decreased significantly in the patients with HBeAg seroconversion, no obvious alteration was observed in HBsAg expression. Lamivudine seems an effective compound with high safety and low side effect., Conclusion: These results suggested that lamivudine (100mg/d) could suppress HBV-DNA replication, promote ALT normalization, accelerate HBeAg/anti-HBe seroconversion, improve the liver pathological changes, slow down the development of liver fibrosis

Objective: To further verify the efficacy and safety of locally manufactured lamivudine on patients with chronic hepatitis B (CHB)., Methods: 2200 patients with CHB were recruited and received lamivudine orally 100 mg once daily for 12 months. The efficacy assessments included virologic response rate (defined by the absence of serum HBV DNA, HBeAg loss and HBeAg/HBeAb seroconversion), percentage of patients with normalization of alanine aminotransferase (ALT). Meanwhile improvement of quality of life (QOL) measured by mos SF-36 QOL questionnaire and liver histology evaluation were conducted in some patients. The safety assessments included adverse events, serious adverse events and laboratory abnormalities. All 2200 patients received at least one dose of medication and were all included in the safety population., Results: Ninety seven percent of patients (2137/2200) recruited were HBV DNA positive by dot blot (sensitivity GRT or equal to 1.0 pg/ml) at baseline. At the end of 12 months treatment, HBV DNA was undetectable in 80% patients (1538/1920) with HBV DNA positive before treatment. Among the 79%(1744/2200) of the patients recruited had positive HBV DNA accompanied abnormal ALT levels at baseline, 72% patients became ALT normal. And among the 84% (1843/2200) of the patients recruited were HBV DNA and HBeAg positive, anti-HBe negative, 16% (269/1650) patients achieved HBeAg/HBeAb seroconversion after 12 months of lamivudine treatment. The HBeAg/HBeAb seroconversion rate was positive correlation to the ALT level before treatment. A total of 304 patients completed the health-related QOL questionnaire. After 12 months treatment, lamivudine improved both their physical and mental health, especially for their mental health. 133 evaluable, paired liver biopsies were obtained for histological assessment, among whom 115 patients had abnormal ALT levels at baseline. Compared with pre-treatment most of their liver injury got alleviated (51.9%) or no further deterioration (36%), only 12% worsening. During the 12 months treatment, 9% patients withdrew from the study and 17% patients showed at least one adverse event, mild or moderate. There were no obvious difference between this study and the previously reported lamivudine Phase II or III study with regard to the kinds, incidence and severity of adverse events., Conclusion: The efficacy and safety profile of the locally manufactured lamivudine 100 mg tablets are similar with those of the previously reported available lamivudine tablets imported in treating Chinese chronic hepatitis B patients.

Objective: To evaluate the long-term effect of lamivudine on the loss of serum HBV DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis B patients and its safety profile and tolerance with multi-center, randomized, double blind and placebo controlled trial., Method: 429 patients with chronic HBV infection as defined by positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine and placebo groups. 322 patients received lamivudine 100 mg daily and 107 patients received placebo treatment for 12 weeks. Then, all patients were offered a further 40 weeks of open label lamivudine treatment. The efficacy and safety were evaluated with clinical, biochemical, hematological and virological parameters., Results: After 12 weeks treatment, HBV DNA response (serum HBV DNA < 1.6 ng/L) rate in lamivudine group was higher than in placebo group (92.2% VS 14.1%, P < 0.01); but at week 52, there was no difference between lamivudine and placebo/lamivudine groups (71.0% VS 77.7%, P > 0.05). Rate of HBV DNA breakthrough in lamivudine group was higher than in placebo/lamivudine group (24.4% VS 8.5%, P < 0.01). Proportion of HBeAg/anti-HBe seroconversion had no difference in two groups (7.5% VS 5.2%, P > 0.05). By week 12, ALT normalization rate in lamivudine group was higher than in placebo group (60.3% VS 27.5%, P < 0.01); but after 52 weeks treatment, there was no difference between two groups (70.9% VS 74.5%, P > 0.05). At week 48, HBV YMDD mutation rate in lamivudine group was higher than in placebo/lamivudine group (14.6% VS 5.0%, P < 0.05). The incidence of adverse events was similar for both lamivudine and placebo/lamivudine group up to week 12 and 52. There was few severe drug-related adverse event., Conclusion: Sustained HBV replication suppression could be obtained from long-term treatment with lamivudine 100 mg daily accompanied with good tolerance and safety.