Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg‐negative and anti‐HBc antibodies‐positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer

Summary. We studied clinical outcome and clinico‐virological factors associated with hepatitis B virus reactivation (HBV‐R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)‐negative/anti‐hepatitis B core antibodies (anti‐HBcAb)‐positive patients. Between 11/2003 and 12/2005, HBV‐R occurred in 7/84 HBsAg‐negative/anti‐HBcAb‐positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV‐R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV‐R involved non‐A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV‐R is a concern in HBsAg‐negative/anti‐HBcAb‐positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti‐HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV‐R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.     

Hepatitis E virus infection in patients infected with the human immunodeficiency virus

Hepatitis E virus (HEV) is a newly-identified causative agent of acute and chronic hepatitis in severely immunocompromized patients. The present study sought to assess the prevalences of past, recent, on-going, and chronic HEV infections in patients infected with human immunodeficiency virus (HIV) in Marseille, South-eastern France, and to determine if they were correlated with the patients' immunological status or with cirrhosis. Anti-HEV IgG and IgM and HEV RNA testing were concurrently performed on the plasma from 184 patients infected with HIV, including 81 with a CD4+ T-lymphocyte count (CD4 count) <50 cells/mm(3) and 32 with a cirrhosis. Prevalence of anti-HEV IgG and IgM was 4.4% (8/184) and 1.6% (3/184), respectively. Past, recent, and on-going infections were observed in 3.3% (6/184), 1.6% (3/184), and 0.5% (1/184) of the patients, respectively. Anti-HEV antibodies prevalence did not differ significantly according to CD4 count, cirrhosis, sex, age, mode of HIV transmission, and infection with hepatitis B or C virus. Anti-HEV IgG seroreversion was observed in two patients. The patient whose plasma tested positive for HEV RNA had a CD4 count <50 cells/mm(3) ; HEV genotype was 3f. In this patient, longitudinal testing showed HEV RNA positivity during a 10-month period, indicating chronic HEV infection; in contrast, anti-HEV IgG never tested positive. Further studies are needed to evaluate the performance of commercial HEV serological assays in patients infected with HIV and to assess the actual incidence, prevalence, and outcome of HEV infection in this special group of patients. HEV RNA testing is necessary for such purposes.     

No association between MTHFR A1298C and MTRR A66G polymorphisms, and MS in an Australian cohort

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier between methylenetetrahydrofolate reductase (MTHFR) and Hcy. MTRR plays a critical role in maintaining cobalamin in an active form and is consequently an important determinant of total plasma Hcy (pHcy) concentrations. Elevated intracellular pHcy levels have been suggested to play a role in CNS dysfunction, neurodegenerative, and cerebrovascular diseases. Our investigation entailed the genotyping of a cohort of 140 cases and matched controls for MTRR and MTHFR, by restriction length polymorphism (RFLP) techniques. Two polymorphisms: MTRR A66G and MTHFR A1298C were investigated in an Australian age and gender matched case-control study. No significant allelic frequency difference was observed between cases and controls at the α = 0.05 level (MTRR χ² = 0.005, P = 0.95, MTHFR χ² = 1.15, P = 0.28). Our preliminary findings suggest no association between the MTRR A66G and MTHFR A1298C polymorphisms and MS.     

Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST Study)

IntroductionAddition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5‐Is) in patients with erectile dysfunction not responding to PDE5‐Is with low or low‐normal T levels.AimsTo confirm this add‐on effect of T in men optimally treated with PDE5‐Is and to specify the baseline T levels at which such an effect becomes significant.MethodsA multicenter, multinational, double‐blind, placebo‐controlled study of 173 men, 45–80 years, nonresponders to treatment with different PDE5‐Is, with baseline total T levels ≤4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double‐blind, placebo‐controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory.Main Outcomes MeasuresMean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question).ResultsErectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5‐Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤3 ng/mL.ConclusionsThe maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5‐I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤3 ng/mL. Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, Cuzin B, Moncada I, Martin‐Morales A, Yassin A, Meuleman E, Eardley I, Dean JD, and Shabsigh R. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).