Durability of efficacy after telbivudine off-treatment in chronic hepatitis B patients.

BACKGROUND/AIMS: Current international guidelines indicate that finite therapy with nucleos(t)ide analogues (NAs) is possible in chronic hepatitis B (CHB) patients. Here we evaluate the durability of efficacy after telbivudine (LdT) off-treatment. METHODS: 39 CHB patients with normalized ALT, undetectable HBV-DNA and HBeAg seroconversion for at least 48 weeks were observed after telbivudine discontinuation. We analyzed the follow-up clinical condition of off-treatment, calculated the cumulative clinical relapse rate, and explored the predictive factors for clinical relapse. RESULTS: Totally 8 patients encountered clinical relapse in the first 60 weeks after telbivudine discontinuation. The cumulative clinical relapse rates at week 24, 48, 60 and 204 were respectively 2.6%, 7.7%, 16.3% and 23.3%. No significant difference was found between cumulative clinical relapse rates of HBeAg(+) and HBeAg(-). No significant baseline or on-treatment factors for clinical relapse were found. CONCLUSION: The present study demonstrated that most CHB patients maintained sustained response and HBeAg seroconversion following telbivudine off-treatment. Clinical relapses may often occur in the early period, with low clinical relapse rate. More follow-up data will be on-going and complemented in the further studies.

Effect of fluoride exposure on bone metabolism indicators ALP, BALP, and BGP.

OBJECTIVE: To analyze the changes in serum alkaline phosphatase (ALP) and bone alkaline phosphatase (BALP) activity and changes in osteocalcin (BGP) content following fluoride exposure and, thereby, determine the reference indications of fluoride-induced changes in bone metabolism. METHODS: In the animal study, rats were allowed free access to drinking water containing different concentrations (10, 150, or 400 mg/L) of sodium fluoride. Serum ALP and BALP activity and serum BGP content were assessed at three exposure time-points. In the spot study, serum ALP and BALP activity and serum BGP content were assessed in workers exposed to fluoride in their working environment for different periods of time. RESULTS: Compared with the control group, on days 15 and 30, the activity of serum ALP in the low- and medium-dose group was significantly higher (p < 0.05), while in the high-dose group it was significantly lower (p < 0.05). Only on day 30 was the activity of serum BALP in the medium-dose group significantly higher than that of the control group (p < 0.05). BGP content was lower in the high-dose group than in the control group (p < 0.05) on days 30 and 90, but it was higher in the medium-dose group on day 90. Compared with the control group, BGP content in the fluoride-exposed group was higher (p < 0.05). In the spot study, serum ALP activity and serum BGP content in the medium working-age group were higher than that in the short working-age group (p < 0.05). However, serum ALP activity and serum BGP content were lower in the long working-age group than in the medium working-age group (p < 0.05). CONCLUSIONS: Our results suggest that serum fluoride and urinary fluoride can be used as reference indications to provide an overall reflection of the body's fluoride-load and fluoride exposure level. Serum ALP activity and serum BGP content can be used as important reference indications for diagnosing bone metabolism changes resulting from fluoride exposure.

Interactive effect of fluoride burden with calcitonin receptor gene polymorphisms on the risk of F bone injury.

PURPOSE: This study aims to examine the interactive effect of fluoride burden with calcitonin receptor (CTR) gene polymorphisms on the risk of fluoride (F) bone injury and provide the basis for determination of F bone injury risk factors. METHODS: In this case-control study, a total of 119 cases and 126 controls were enrolled from 2 aluminum plants in Hubei province. F burden (UF) was measured by F ion-selective electrode method. The CTR gene polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios, 95% confidence intervals (CI). RESULTS: The odds of developing F bone injury for participants in the moderate F burden group versus the mild F burden group were 4.1 (95% CI: 1.9, 8.7); the heavy F burden group versus the mild F burden group were 14.1 (95% CI: 6.5, 30.6). The odds of developing F bone injury for participants with the TC & TT genotypes versus the CC genotype were 2.6 (95% CI: 1.4, 4.7). The interactions between TC & TT genotypes and moderate, heavy F burden were significant (OR = 14.4; OR = 40.3). CONCLUSION: The interactive effect of F burden and CTR genotype was significant, which increased the F bone injury risk.

[A pilot study of peginterferon alfa-2a combined with short-term lamivudine therapy in HBeAg-positive chronic hepatitis B patients].

OBJECTIVES: To investigate the efficacy of by combining a 12-week course of lamivudine in those HBeAg-positive hepatitis B patients receiving peginterferon alfa-2a (peg-IFN alpha-2a) therapy. METHODS: A total of 58 patients initiated a 52-week course of peginterferon alfa-2a were enrolled and divided into 3 groups. The patients with HBV DNA undetectable or HBeAg negative at week 12 were divided into group A, in this group treatment continued to week 52 with peg-IFN alpha-2a alone; The rest patients were divided into group B1 and B2, in group B1, lamivudine was combined at a course of 12 weeks, while in group B2 treatment continued to week 52 with peg-IFN alpha-2a alone. Clinical responses were assessed at week 52. RESULTS: 8 out of 58 patients achieved undetectable HBV DNA or HBeAg loss at week 12 and divide into group A. In this group the HBV DNA loss rate, HBeAg seroconversion rate, HBsAg loss rate and ALT normalization rate were 100% (8/8), 75% (6/8), 0% (0/8) and 100% (8/8) respectively at the end of treatment. In this group the HBV DNA loss rate, HBeAg seroconversion rate, HBsAg loss rate and ALT normalization rate were 100% (8/8), 75% (6/8), 0% (0/8) and 100%(8/8) respectively at the end of treatment. The rest 50 patients without early response to peg-IFN alpha-2a at week 12 were divided into group B1 (24 patients enrolled) and B2 (26 patients). At the end of treatment, the HBV DNA loss rate, HBeAg seroconversion rate, HBsAg loss rate and ALT normalization rate in Group B1 were 50% (12/24), 38% (9/24), 4% (1/24) and 63% (15/24) respectively, and 31% (8/26), 27% (7/26), 0% (0/26) and 35% (9/26) respectively in group B2. CONCLUSION: Those patients with early responses to peg-IFN alpha-2a therapy can achieve high clinical responses at the end of 52-week treatment. The combining therapy of lamivudine for a course of 12-weeks can improve the clinical responses for the patients without early responses to peg-IFN alpha-2a.

[Toxic effects of ammonium perchlorate on thyroid of rats].

OBJECTIVE: To study the effects of toxicity of ammonium perchlorate (AP) on thyroid of rats. METHODS: Eighty-eight Wistar rats were treated orally with different dosages of AP. Three treated groups received 129, 257, 514 mg.kg(-1).d(-1) of AP respectively and one control group drunk water for 13 weeks. Another 3 groups received 1.2, 46.5, 465.0 mg.kg(-1).d(-1) of AP respectively and one control group drunk water for 36 weeks. The behavior and change of body weight in rats were observed. The levels of thyroid hormones in serum were measured and the pathological changes of thyroid tissue were observed as well. RESULTS: There were no differences in behavior and change of body weight between different AP exposure time. When the rats were treated with AP 514 mg for 13 weeks, free triiodothyronine (FT3, 2.48 pmol/L), free thyroxin (FT4, 13.33 pmol/L) were lower than those in control group (3.24, 20.92 pmol/L respectively, P<0.05). Thyroid-stimulating hormone (TSH, 0.375 mIU/L), thyroglobulin (TG, 3.37 microg/L) were higher than those in control group (0.29 mIU/L, 2.00 microg/L respectively, P<0.05). When the rats were treated with AP 465 mg for 36 weeks, FT3 (2.65 pmol/L) was lower than that in control group (4.97 pmol/L, P<0.01). FT4 in 46.5, 465 mg groups (10.63, 2.17 pmol/L respectively) were lower than that in control group (15.74 pmol/L, P<0.05, P<0.01). TSH in 465 mg group (0.34 mIU/L) was higher than that in control group (0.14 mIU/L, P<0.05). Histopathologic examination showed that follicle proliferation, no colloid in follicle, gore, follicular diminishing or atresia were found in 46.5, 465 mg groups with a dose-effect relationship. CONCLUSIONS: The toxic effects of AP on the growth of rats were not found, but those on the thyroid of rats were found significantly. Thyroid is the target organ of AP. It is considered that none effect dose of AP for rat thyroid may be 1.2 mg.kg(-1).d(-1), its threshold dose may be 46.5 mg.kg(-1).d(-1).

[Study on metabolism of preventive anti-fluorine agent on rats].

In order to study the metabolism of preventive anti-fluorine agent, 30 rats are randomly divided into high-dose, low-dose and a control groups. The high dose (400 mg/kg.d) and low dose (16 mg/kg.d) are orally administrated respectively, and the content of boron and/or zinc in urine, dung, serum, bone, liver, muscles, brain tissues is determined. The results showed that during the administration of this agent, the content of boron in urine and the content of zinc in dung increases obviously in both high-dose and low-dose groups and their discharge rate is consistent with the dose given. The content of boron and zinc in bone, liver, and zinc in serum, muscles, brain tissues increases evidently compared to that in control group but decreases rapidly after administration of the agent. The findings revealed that there is a rapid metabolism of boron and zinc in the body of rats. The highest content of the agent is observed in bones. The content ranks second in liver and muscles but no accumulative effects are observed.