Types of human leukocyte antigen and decrease in HCV core antigen in serum for predicting efficacy of interferon-Α in patients with chronic hepatitis C: analysis by a prospective study

Background A prospective study was conducted to evaluate the influence of host factors, including human leukocyte antigen (HLA), and viral factors, including hepatitis C virus (HCV) core antigen, on the response to interferon (IFN)-.Methods Natural IFN- was given to 66 patients with chronic hepatitis C at a dose of 9 million units per day for 2 weeks, followed by 9 million units three times a week for 22 weeks.Results Sustained virological response without detectable HCV RNA in serum 24 weeks after the end of IFN therapy was achieved in 21 patients, while it was not in 32 patients; the remaining 13 patients were not evaluated. HCV core antigen and HCV RNA started to decrease 1 and 4 weeks, respectively, after the commencement of IFN in responders (P = 0.02 and P = 0.05, respectively). On univariate analysis, age of 50 years or less (P < 0.001); lack of HLA DR6 (P = 0.018) or DR52 (P < 0.041); platelets more than 14 × 10⁴/mm³ (P = 0.031); HCV core antigen 500fmol/l or less (P = 0.001); and HCV RNA 100KIU/ml or less were predictive of response. On multivariate analysis, age 50 years or less (odds ratio [OR], 4.009; P = 0.039); lack of HLA DR6 (OR, 8.130; P = 0.027); IFN-naive (OR, 11.63; P = 0.016); HCV core antigen 500fmol/l or less (OR, 10.61; P = 0.007); and genotypes other than 1b (OR, 8.929; P = 0.010) were predictive of response.Conclusions Lack of HLA DR6 determined the response to IFN. HCV core antigen was useful in predicting and monitoring the response to IFN.     

Anxiolytic-like profiles of histamine H3 receptor agonists in animal models of anxiety: a comparative study with antidepressants and benzodiazepine anxiolytic

Rationale  Histamine H3 receptor functions as a presynaptic auto- and hetero-receptor on histaminergic and non-histaminergic neurons in the brain regulating the synaptic release of numerous neurotransmitters. Therefore, the ligands for this receptor have been proposed to be of therapeutic interest for the treatment of various neuropsychiatric disorders. At present, however, the psychopharmacological profiles of H3 ligands, particularly H3 agonists, have not been extensively studied. Objective  The present study investigated the anxiolytic-like profiles of H3-selective agonists in a variety of classical (benzodiazepine-sensitive) and atypical (antidepressant-effective) animal models of anxiety. Comparator drugs used were diazepam and both fluvoxamine and desipramine in the former and latter models, respectively. Results  H3 agonist R-α-methylhistamine and immepip were inactive in rat elevated plus maze test and Vogel type conflict test where diazepam (5 mg/kg) produced significant anxiolytic-like effects. Meanwhile, these H3 agonists (10–30 mg/kg) significantly reduced isolation-induced vocalizations in guinea pig pups and isolation-induced aggressive behavior in mouse resident–intruder test. Moreover, in rat conditioned fear stress test, R-α-methylhistamine (30 mg/kg) and immepip (10 mg/kg) significantly decreased freezing time, which were completely reversed by concomitant treatment with H3 antagonist, thioperamide (10 mg/kg). In contrast to the limited efficacy obtained with desipramine (30 mg/kg), fluvoxamine (20–60 mg/kg) exhibited anxiolytic-like effects in all the latter three atypical models. Conclusions  These data suggest that the H3 agonists may have anxiolytic-like effects similar to those of selective serotonin reuptake inhibitors but not benzodiazepine anxiolytics and represent a novel strategy for the treatment of some anxiety disorders in which selective serotonin reuptake inhibitors are prescribed.     

De novo autoimmune hepatitis following living-donor liver transplantation for primary biliary cirrhosis

Abstract:  Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33-yr-old woman who presented complaining of marked fatigue and jaundice four yr after living-donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome-specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.     

Vascular endothelial growth factor and interleukin 6 production by Hodgkin lymphoma

A 20-year-old man complained of fever, general lymphadenopathy, severe lumbago, and gynecomastia in January 2003. The diagnosis of Hodgkin lymphoma was confirmed by biopsy specimens of the right supraclavicular lymph node. The clinical stage was IIIB, and the prognostic score was 3. Plasma levels of interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) were elevated to 446 pg/mL, and 1,710 pg/mL,respectively. Six-course combination chemotherapy with the ABVD regimen was initiated,and a complete response (CR) was achieved. Clinical signs disappeared and plasma levels of IL-6 and VEGF decreased to 5.0 pg/mL and 100 pg/mL, respectively. The patient remained in CR as of December 2006.Elevated IL-6 and VEGF may be appropriate tumor markers for patients with Hodgkin lymphoma.