Human leukocyte antigen alleles and haplotypes associated with chronicity of hepatitis B virus infection in Koreans.

CONTEXT: Chronic hepatitis B infection is the leading cause of cirrhosis and hepatocellular carcinoma. Human leukocyte antigen may be involved in the chronicity of hepatitis B virus (HBV) infection. OBJECTIVE: To analyze the association between HBV chronicity and human leukocyte antigen alleles and haplotypes of 636 organ donors and recipients. DESIGN: Subjects were categorized into 2 groups according to their clinical and serologic profiles, specifically, an HBV natural convalescent group and an HBV chronic carrier (CC) group. RESULTS: Hepatitis B chronicity was positively associated with A33 (P = .004, odds ratio [OR] = 1.59) and DR7 (P < .001, OR = 2.58), and negatively associated with HLA-DR13 (P < .001, OR = 0.40). Coexpression of A33 and DR7 was significantly higher in the CC group (OR = 3.63), compared with that of either allele alone (OR = 1.76 in A33; OR = 2.53 in DR7). The statistically significant haplotypes were B44-DR7 (P < .001, OR = 5.44), A33-DR7 (P < .001, OR = 4.47), and A33-B44-DR7 (P < .001, OR = 7.31) in the CC group. CONCLUSIONS: Our results indicate that alleles of A33, DR7, and haplotypes containing DR7 are associated with HBV chronicity among Koreans. Moreover, the 2 antigens had an additive effect on chronicity. These findings support the theory that human leukocyte antigen class I-restricted cytotoxic T cells and human leukocyte antigen class II-restricted helper T cells play an important role in HBV chronicity.

Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets.

Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and anticarcinogenic activities. However, the effect of curcumin on the maturation and immunostimulatory function of dendritic cells (DC) largely remains unknown. In this study, we examined whether curcumin can influence surface molecule expression, cytokine production, and their underlying signaling pathways in murine bone marrow-derived DC. DC were derived from murine bone marrow cells and used as immature or LPS-stimulated mature cells. The DC were tested for surface molecule expression, cytokine production, dextran uptake, the capacity to induce T cell differentiation, and their underlying signaling pathways. Curcumin significantly suppressed CD80, CD86, and MHC class II expression, but not MHC class I expression, in the DC. The DC also exhibited impaired IL-12 expression and proinflammatory cytokine production (IL-1beta, IL-6, and TNF-alpha). The curcumin-treated DC were highly efficient at Ag capture, via mannose receptor-mediated endocytosis. Curcumin inhibited LPS-induced MAPK activation and the translocation of NF-kappaB p65. In addition, the curcumin-treated DC showed an impaired induction of Th1 responses and a normal cell-mediated immune response. These novel findings provide new insight into the immunopharmacological role of curcumin in impacting on the DC. These novel findings open perspectives for the understanding of the immunopharmacological role of curcumin and therapeutic adjuvants for DC-related acute and chronic diseases.

[HBV DNA levels, aminotransferase and histological activity in young male patients with HBeAg positive chronic hepatitis B].

BACKGROUND/AIMS: A significant correlation between HBV DNA and liver damage was found in precore mutant strains but there was no significant association between viral replication and liver damage in HBeAg positive patients. Laboratory tests are often requested to predict hepatitis activity (grade) and fibrosis (stage) in HBeAg positive chronic hepatitis B. We assessed ALT, AST, and HBV-branched DNA to find which is the best for predicting hepatitis activity and fibrosis. METHODS: Routine biochemical liver function tests and HBV DNA in sera were assessed in 119 young patients positive with HBsAg and HBeAg. The mean age of patients was 21+/-2 years. All patients were male. By logistic regression analysis the relationships between laboratory data, hepatitis activity, fibrosis, or risk of chronic active hepatitis were analyzed. RESULTS: There was a significant correlation between aminotransferase (AST, ALT) and hepatitis activity/ fibrosis. A significant inverse relationship between the HBV bDNA and hepatitis activity was demonstrated (Pearson's correlation coefficient: lobular activity,-0.305; porto-periportal activity, -0.410). But HBV bDNA was not correlated with severity of fibrosis. AST and HBV bDNA was the important test for predicting the more severe hepatitis activity (lobular activity and porto-periportal activity: score>/=3, respectively) CONCLUSION: The higher AST, but the lower HBV bDNA, in sera shows the more severe hepatitis activity. AST and HBV bDNA could be helpful for assessing the hepatitis activity in young male patients with HBeAg positive chronic hepatitis B if proper reference values are used.

[A case of fulminant hepatic failure in Wilson's disease combined with systemic lupus erythematosus].

Patients with systemic lupus erythematosus (SLE) have a chance of developing liver involvement in their lifetime. The main cause of liver involvement in SLE patients is previous treatment with hepatotoxic drugs or hepatotropic viral hepatitis. Wilson's disease is a hereditary disorder and is usually diagnosed in patients presenting either neuropsychiatric disorders or manifestations related to chronic liver disease. Fulminant hepatic failure as the initial manifestation of Wilson's disease is rare. The relationship between systemic lupus erythematosus and Wilson's disease has not been established. We report a case of a 12-year-old girl with SLE who presented fulminant hepatic failure as an initial manifestation of Wilson's disease. The diagnosis was established with decreased serum ceruloplasmin level and the presence of Kayser-Fleischer ring. We treated with repeated plasma exchange. Despite repeated plasma exchange she died of multi-organ failure on the 16th hospital day. Considering this case, Wilson's disease should be considered as a cause of fulminant hepatic failure, especially in juvenile age cases.