SummaryMechanisms associated with the progression of simple steatosis to nonalcoholic fatty liver disease (NAFLD) remain undefined. Regulatory T cells (Tregs) play a critical role in regulating inflammatory processes in nonalcoholic steatohepatitis (NASH) and because T helper type 17 (Th17) functionally oppose Treg-mediated responses, this study focused on characterizing the role of Th17 cells using a NAFLD mouse model. C57BL/6 mice were fed either a normal diet (ND) or high fat (

OBJECTIVE:To investigate the efficacy of fenofibrate combination therapy in Chinese patients with primary biliary cirrhosis (PBC) who had a partial response to standard dose of ursodeoxycholic acid (UDCA) for at least one year. METHODS:PBC patients were treated with UDCA (13-15 mg/kg/day) for more than one year. The biochemical response to UDCA treatment was evaluated after treatment. Fenofibrate (200 mg/day) was added to 22 patients with partial response to UDCA. RESULTS:In patients with partial response to UDCA, serum alkaline phosphatase (ALP) and g-glutamyl transpeptidase levels significantly decreased after 3-month combination therapy of UDCA and fenofibrate, 68% of these patients even reached normal ALP level. Serum triglyceride (TG) and cholesterol levels were improved, and alanine transaminase (ALT) and aspartate transaminase (AST) were also decreased during the combination therapy. However, fenofibrate had no significant effect on serum bilirubin levels. The improvement of liver biochemical tests was maintained in some patients with long-term therapy (at least 6 months). No obvious adverse effects were observed in patients taking fenofibrate. CONCLUSIONS:Fenofibrate is effective for improving liver biochemical tests in patients who have partial response to UDCA monotherapy. It is worth exploring the efficacy of fenofibrate on histological changes in PBC patients.

OBJECTIVE:Although hepatitis B recurrence after liver transplantation has been reduced to 0%-10% since the application of the combination therapy of hepatitis B immunoglobulin (HBIG) and lamivudine, the viral mutation resistance of lamivudine is still an obstacle to the outcome of liver transplantation. Here we evaluate the role of entecavir in preventing hepatitis B recurrence after liver transplantation. METHODS:Patients who received a liver transplantation for hepatitis B virus (HBV)-related end-stage liver disease in our center from March 2006 to December 2008 were enrolled in this study. All patients received entecavir (0.5 mg orally, daily) or lamivudine (100 mg orally, daily) together with a long-term low dosage of HBIG to prevent hepatitis B recurrence after transplantation. Serum viral markers (HBsAg, antiHBs, HBeAg, anti-HBc and anti-HBe) and HBV-DNA level were determined. RESULTS:Thirty patients receiving entecavir and 90 patients receiving lamivudine were matched with the same age and sex in both groups. No reinfection of hepatitis B was detected in the entecavir group. The hepatitis B surface antigen of patients in the entecavir group became negative within one week and no patient had any adverse effect relating to entecavir. There was no difference in the cumulative survival rate between the entecavir group and the lamivudine group (P > 0.05). CONCLUSION:This study shows that entecavir combined with low dosages of HBIG is effective and safe in preventing hepatitis B recurrence after liver transplantation, but its long-term effect is still under investigation and a large-sample study will be carried out in the future.

T helper cells that produce interleukin-17 (IL-17) (Th17 cells) have recently been identified as the third distinct subset of effector T cells, the differentiation of which depends on specific transcription nuclear factor retinoic acid-related orphan nuclear receptor-gammat. Emerging data have suggested that Th17 cells play an important role in innate immunity, adaptive immunity and autoimmunity. Interestingly, there is a reciprocal relationship between Th17 cells and regulatory T cells (Treg), not only in development, but also in their effector function. Transforming growth factor (TGF)-beta induces Treg-specific transcription factor Forkhead box P3(FOXP3), while the addition of IL-6 to TGF-beta inhibits the generation of Treg cells and induces Th17 cells. It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis. In addition to IL-6, other factors such as retinoic acid, rapamycin, or cytokines (e.g., IL-2 and IL-27) could dictate the balance between Th17 and Treg cells. Since Treg cells play an important role in hepatic immunity with overregulation in chronic viral hepatitis and hepatic carcinoma, and inadequate inhibition in autoimmune liver diseases, graft rejection and acute liver failure, it is reasonable to assume that Th17 cells may play a reciprocal role in these diseases. Thus, future research on the Treg/Th17 balance may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune-related liver diseases.

Histone acetylation regulates p21WAF1 expression in human colon cancer cell lines, Colo-320 and SW1116.

Liver X receptors (LXRs) are members of the superfamily of metabolic nuclear receptors, which play central roles in the regulation of cholesterol absorption, efflux, transportation and excretion and many other processes correlating with lipid metabolism. LXRs can also regulate inflammation in vitro and in vivo. Accumulating evidence demonstrates that LXR are involved in the metabolism and inflammation in human diseases. Nonalcoholic fatty liver disease (NAFLD) is classically associated with lipid metabolic disorders and inflammatory responses, especially in the nonalcoholic steatohepatitis (NASH) phase. The effects of LXRs on cholesterol metabolism and inflammation make them attractive as a potential target for the treatment of NAFLD. Since the ability to synthesize triglycerides may be protective in obesity and fatty liver, the hepatic lipogenesis by LXRs should not rule out the possibility of the use of LXRs in NAFLD.KEY WORDS: cholesterol metabolism, inflammatory response, liver X receptor, macrophage, nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is characterized by an accumulation of excess triglycerides in hepatocytes, and insulin resistance is now considered the fundamental operative mechanism throughout the prevalence and progression of the disease. Besides their role in dietary lipid absorption and cholesterol homeostasis, evidence has accumulated that bile acids are also signaling molecules that play two important roles in glucose and lipid metabolism: in the nuclear hormone receptors as farnesoid X receptors (FXR), as well as ligands for G‐protein‐coupled receptors TGR5. The activated FXR‐SHP pathway regulates the enterohepatic recycling and biosynthesis of bile acids and underlies the down‐regulation of hepatic fatty acid and triglyceride biosynthesis and very low density lipoprotein production mediated by sterol‐regulatory element‐binding protein‐1c. The bile acid‐TGR5‐cAMP‐D2 signaling pathway in human skeletal muscle in the fasting–feeding cycle increases energy expenditure and prevents obesity. Therefore, a molecular basis has been provided for a link between bile acids, lipid metabolism and glucose homeostasis, which can open novel pharmacological approaches against insulin resistance and nonalcoholic fatty liver disease.

Anti-HBc-positive donors can significantly increase the incidence of de novo HBV infection in HBsAg-negative recipients. Administration with adefovir in patients who are resistant to lamivudine seems to be an effective and safe way for de novo HBV infection.