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Liu F.,Shandong University | Liu F.,Shanghai JiaoTong University | Wang L.,Shandong University | Li X.Y.,Jinan Infectious Disease Hospital | And 4 more authors.
Journal of Gastroenterology and Hepatology (Australia)

Background and Aims: Lamivudine, a nucleoside analog, is commonly used for treatment of chronic hepatitis B (CHB) but its durability of effectiveness after withdrawal is still uncertain. This study was designed to assess the durability of lamivudine treatment with stringent cessation criteria in hepatitis B e antigen (HBeAg)-negative patients and to explore potential predictive factors. Methods: Sixty one HBeAg-negative CHB patients who had received lamivudine for at least 24months and had maintained undetectable serum hepatitis B virus (HBV) DNA plus normal alanine aminotransferase for ≥18months before withdrawal were included. They were followed up monthly during the first 4months and at 3-month or 6-month intervals thereafter. Relapse was defined as serum HBV DNA≥104 copies/mL. Results: Thirty one of 61 patients relapsed during follow-up, over 90% occurred within 18months after lamivudine withdrawal. Cumulative relapse rates at months 6, 12, 24, 36, 48 and 60 were 26.2%, 43.6%, 49.7%, 52.1%, 56.1% and 56.1%, respectively. Cox regression revealed that age was the only predictive factor for relapse, with lower relapse rates found in younger patients. Hepatitis B surface antigen (HBsAg) turned negative in eight patients, and none of them relapsed during follow-up. Conclusion: Effectiveness of lamivudine treatment is not durable in HBeAg-negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged ≤20years. The ideal end point of lamivudine treatment is clearance of serum HBsAg. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd. Source

Wang L.,Shandong University | Liu F.,Shanghai JiaoTong University | Liu Y.-D.,Yantai Infectious Disease Hospital | Li X.-Y.,Jinan Infectious Disease Hospital | And 3 more authors.
Journal of Viral Hepatitis

The cessation criteria for lamivudine treatment vary in published articles and their results are contradictory, especially factors predicting relapse. To clarify these contradictions, this long-term follow-up study of 125 Chinese hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients was designed with stringent cessation criterion. All patients received lamivudine and achieved HBeAg seroconversion (group A, n = 82) or loss (group B, n = 43) with undetectable hepatitis B virus (HBV) DNA by PCR assay during the treatment. Lamivudine was withdrawn ≥6 months after HBeAg seroconversion/loss occurred. The median treatment durations were 24 (12-54) months and 36 (18-89) months in group A and group B, respectively. Patients were followed up for median 24 (2-84) months. The cumulative relapse (defined as serum HBV DNA ≥10 4 copies/mL) rates in the two groups at months 12, 24, 36 and 48 were 23.4%vs 35.0%, 25.0%vs 37.7%, 25.0%vs 41.1% and 29.4%vs 41.1%, respectively (log-rank test, P = 0.119). For patients whose total treatment duration ≥18 months in group A, the cumulative relapse rates at months 12, 24, 36 and 48 were 18.3%, 20.1%, 20.1% and 25.1%, which was significantly lower than those with a shorter duration (log-rank test, P = 0.002). The mean age and median total duration were statistically different between relapsers and nonrelapsers in group A (33.9 ± 13.6 vs 23.1 ± 11.0 years, P < 0.001 and 24 vs 26 months, P = 0.003). Cox regression revealed that age was the only predictive factor for relapse (RR, 1.069; 95% CI, 1.032-1.106, P < 0.001). Patients aged <30 years relapsed less frequently in 5 years (12.3%vs 53.5%, P = 0.001). In conclusion, for patients who maintained HBeAg seroconversion for ≥6 months and total duration for ≥18 months, lamivudine withdrawal is a reasonable option. Prolonged treatment may be required for patients aged greater than 30 years to reduce relapse. © 2009 Blackwell Publishing Ltd. Source

Yu J.G.,Yantai Infectious Disease Hospital
Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology

To discuss the epidemiological and clinical characteristics of the hospitalized children with hand foot and mouth disease (HFMD) in Yantai area. Epidemiological and clinical data of HFMD children from 2009 to 2010 were summarized and analyzed retrospectively. Most of the infected (94.6%) were under 5 years old and the ratio between male and female was 1.5: 1. Oral mucosal pox or ulcer as well as hand and foot rashes were observed in all 931 patients. Fever and neurological disorders occurred in 840 (90.2%) and 121 (13.0%) patients respectively. The incidence was positively correlated with air temperature (r = 0.887, P < 0.001), with a peak in April to September (88.9%). The ratio of children from countryside, total duration of fever, serum concentration of c-reacting protein (CRP) and fasting blood glucose (FBG) were significantly higher in severe cases than in those mild ones. Multivariate analysis showed longer mean duration of fever( Odds ratio [OR], 1.491; 95% confidence interval [ CI] 1.170-1.901; P = 0.001) and hyperglycemia (OR, 1.124; 95% CI 1.016-1.245; P = 0.024) were independent risk factors of severity. Children younger than 5 years old are susceptible to HFMD and most cases occur in April to September. The monthly incidence is positively correlated with temperature of that month. Longer duration of fever and hyperglycemia are independent risk factors for severity. Most cases could have a favorable prognosis after timely diagnosis and proper intervention. Source

Wang L.-Y.,Shandong University | Meng Q.-H.,Capital Medical University | Zou Z.-Q.,Yantai Infectious Disease Hospital | Fan Y.-C.,Shandong University | And 6 more authors.
Digestive Diseases and Sciences

Background T helper (Th) 17 cells participate in the pathogenesis of liver diseases but their exact role in acuteon- chronic hepatitis B liver failure (ACHBLF) still remains obscure. Aims This present study was aimed to characterize the circulating Th17 cells and to analyze their association with disease progression in ACHBLF. Methods This retrospective study consisted of 40 ACHBLF patients, 40 chronic hepatitis B (CHB) patients and 20 healthy controls. The frequency of peripheral Th17 cells and IL-17 mRNA level in peripheral blood mononuclear cells (PBMCs) were estimated by flow cytometry and relative quantitative real-time polymerase chain reaction. Results We found that the frequency of peripheral Th17 cells, as well as the level of IL-17 mRNA in PBMCs, was significantly increased in ACHBLF patients compared with CHB patients and healthy controls. In ACHBLF patients, the frequency of Th17 cells was positively correlated with serum total bilirubin (r = 0.392, P = 0.012) and model for end-stage liver disease scores (r = 0.383, P = 0.015), but negatively correlated with prothrombin activity (r = -0.317, P = 0.046). The same trend was observed as for relative expression of IL-17. Furthermore, the frequency of Th17 cells and IL-17 mRNA level were significantly elevated in non-survivors compared with survivors in ACHBLF patients. Conclusions These results suggested that Th17 cells as well as IL-17 might be related with disease severity and prognosis in ACHBLF patients. © Springer Science+Business Media, LLC 2011. Source

Wang C.,Capital Medical University | Cao B.,Capital Medical University | Liu Q.-Q.,Beijing University of Chinese Medicine | Zou Z.-Q.,Yantai Infectious Disease Hospital | And 16 more authors.
Annals of Internal Medicine

Background: Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. Objective: To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. Design: Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) Setting: Eleven hospitals from 4 provinces in China. Patients: 410 young adults aged 15 to 59 years with laboratoryconfirmed H1N1 influenza. Intervention: Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. Measurements: Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. Results: Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. Limitations: Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. Conclusion: Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. © 2011 American College of Physicians. Source

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