Thrsp is reported to be involved in liver steatosis induced by PXR,[23] which is another receptor for TO901317.[24] However, whether PXR-mediated Thrsp expression is involved in the steatotic effects induced by other PXR activators, such as rifampicin, nifedipine, and carbamazepine, remains uncharacterized.[38] In contrast to LXR-α, which induces Thrsp expression by the SREBP-1c–dependent

pathway, PXR can up-regulate Thrsp expression by directly binding to TRE in the Thrsp promoter.[23] Because LXR-α/β double-KO mice exhibited a complete abrogation of TO901317-induced Thrsp expression, it is unlikely that PXR is responsible ATM/ATR inhibitor drugs for this process. Although SREBP-1c gene deficiency significantly reduced basal and TO901317-induced Thrsp expression, Thrsp levels in TO901317-treated, SREBP-1c–null mouse livers tended to increase, indicating that minor regulatory mechanism(s) other than LXR and PXR pathways may be involved. In conclusion, the present study provides direct evidence that Thrsp is a lipogenic gene in the liver. LXR activation promotes Thrsp expression through an LXR-α–mediated, SREBP-1c–dependent mechanism (Fig. 7). Thrsp may represent a potential therapeutic target for the treatment of NAFLD. The authors

thank T. Guan for his assistance in editing the manuscript. Additional Supporting Information may be found in the online version of this article. “
“Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, Hydroxychloroquine which ranges from click here 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates. We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated

for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion—loss of HBeAg and antibody to HBeAg (anti-HBe) development. The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26–52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10 IU/mL (hazard ratio [HR] = 2.59 [1.04–6.44]), P = 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05–7.81], P = 0.040), but not the choice of nucleos(t)ides. The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels.