Establishment of male rat models for fertility after liver transplantation / 器官移植

Objective To establish male rat models for fertility following liver transplantation. Methods Male Sprague-Dawley (SD) rats were used as the donors and recipients of liver transplantation. The donor liver was transplanted with two-cuff technique. Liver transplantation was performed in 15 male SD rats. At 3 weeks after liver transplantation, 5 rats were randomly sacrificed for detection of sperm deformity rate. The remaining male rats were mixed bred and mated with healthy female SD rats at a ratio of 1︰2. General conditions of the rats undergoing liver transplantation were recorded. Liver function parameters were detected after liver transplantation. Postoperative sperm deformity rate was observed. The pregnant status of female rats and health situation of their offsprings was monitored. Results All 15 rats (100%) underwent liver transplantation successfully. Nine rats (9/10) survived longer than 8 weeks. Liver function parameters were normal in male rats following liver transplantation. The sperm deformity rate was ranged from 0.5% to 1.3%. Ten male rats undergoing liver transplantation were mixed bred with female rats at a ratio of 1︰2 for 1 week. All female rats were successfully mated and delivered their offsprings after 3 weeks. The offsprings had no evident physiological deformity. Conclusions Male rat models for fertility are successfully established after liver transplantation, which serve as an animal model to evaluate the fertility performance in male patients undergoing liver transplantation.

Osteopontin Promoter Polymorphism at Locus-156 is Associated with HCC in Patients with HBV Infection in Chinese Population / 中山大学学报(医学科学版)

[Objective]To study the association between the polymorphisms in the promoter region of Osteopontin(OPN)with hepatitis B virus(HBV)-related HCC.[Methods]A total of 225 cases diagnosed with hepatitis B virus(HBV)-related HCC and 200 age-matched patients with HBV infection without HCC were collected. Three polymorphisms(-156delG/G,-443T/C and-616T/G)in the Osteopontin promoter were genotyped using direct sequencing.[Results]The frequency of-156delG/delG genotype in the HCC group was higher than that of in the control group (P = 0.003). There was a significantly increased frequency of the allele-156delG(P<0.001)in HCC patients. Logistic regression analysis was performed to show an increase HCC risk associated with the delG variant genotype(OR1.64;95%CI 1.25~2.16). There were no differences between the groups in the genotype distributions and allele frequencies of SNP-443T/C and-616T/G.[Conclusion]Our findings suggest that allele-156delG in the Osteopontin promoter may be a marker for risk of HCC with HBV infection in Chinese Han population.

Efficacy of 48-week tenofovir disoproxil fumarate therapy in patients who were unresponsive to nucleoside-analogue treatments / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).</p><p><b>METHODS</b>A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.</p><p><b>RESULTS</b>Over the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.</p><p><b>CONCLUSION</b>For CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.</p>

Risk factors of hepatocellular carcinoma in patients with HBV-related liver cirrhosis receiving nucleos (t) ide analogues treatment / 中华临床感染病杂志

Objective To survey the incidence of hepatocellular carcinoma (HCC) in patients with HBV-related cirrhosis receiving nucleos(t)ide analogues treatment and to assess its risk factors.Methods A total of 141 patients with HBV-related liver cirrhosis receiving nucleos(t) ide therapy from April 2008 to June 2011 were enrolled.The clinical data including virological and biochemical tests were retrospectively analyzed.Univariate and multivariate Cox proportional hazards regression model was used to identify the risk factors of HCC occurrence.Results Patients were followed up for 6.4 to 87.6 months with a median followup time of 32.5 months.During the follow-up period,15 out of 141 patients developed HCC with an average annual incidence rate of 3.8％.HCC incidence was higher in HBeAg positive cirrhosis and in those with family history of liver cancer ( RR =4.524 and 3.858,P ＜ 0.05 ).Conclusions Patients with HBV-related cirrhosis have a high incidence rate of HCC even they recieve nucleos (t) ide analogues treatment.HBeAg positive cirrhosis and family history of liver cancer are independent risk factors for HCC.