The predictive value of core antigen testing for the management of hepatitis C patients receiving pegylated interferon/ribavirin treatment

A new quantitative marker of HCV viremia based on the detection of the core antigen of the virus has recently become commercially available in Europe. The usefulness of this test was examined for the management of patients treated with pegylated interferon/ribavirin. One hundred twenty-eight pegylated interferon/ribavirin treated patients were studied. Serum samples were available at baseline, week 4 and week 12 time-points, respectively. Core antigen was quantified using the trak-C assay (Ortho Clinical Diagnostics, Raritan, NJ). For all genotypes at week 4, the positive and negative predictive values of HCV core antigen were 81.4 and 92.9%, respectively, while at week 12 they were 67.9 and 100%, respectively. These predictive values varied substantially according to viral genotype. Among patients with a negative core antigen level (<1.5 pg/ml) at week 12, only 33% of those who were positive at week 4 achieved a sustained virological response whereas 85% of those who were already negative did (P < 0.001). The core antigen assay may be used at week 4 and week 12 to distinguish patients who will achieve a sustained virological response from those who will relapse/breakthrough. This assay is a new reliable alternative for early prediction of virological non-response in patients treated with pegylated interferon/ribavirin.     

Toward tissue-selective pancreatic B-cells KATP channel openers belonging to 3-alkylamino-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides

3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the K(ATP) channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position. Thus, 3-(ethylamino)-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide (11) expressed a marked inhibitory activity on pancreatic B-cells (IC(50) = 1 microM) associated with a weak vasorelaxant effect (ED(50) > 300 microM), whereas 7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide (27), which was only slightly active on insulin-secreting cells (IC(50) > 10 microM), was found to be very potent on vascular smooth muscle cells (ED(50) = 0.29 microM). Radioisotopic and electrophysiological investigations performed with 7-chlorinated, 7-iodinated, and 7-fluorinated 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides confirmed that the drugs activated K(ATP) channels. The present data revealed that subtle structural modifications of 3-(alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides can generate original compounds activating K(ATP) channels and exhibiting different in vitro tissue selectivity profiles.     

What is your diagnosis? Hypochromic microcytic anemia with Evans syndrome or autoimmune thrombocytopenic purpura?

We report a case of Evans syndrome associated with scleroderma in a 50-year-old woman admitted to the department of internal medicine of Yalgado Ouedraogo National Teaching Hospital in Burkina Faso. The interest of this case lies in on its mode of revelation: chronic bleeding that led to hypochromic microcytic anemia. The indirect antiglobulin test was positive. Corticosteroid treatment has been successful. Nonetheless, because autoimmune cytopenia may indicate underlying disorders, particularly lymphoid tissue malignancies, rigorous monitoring of this patient is essential.     

Pharmacokinetic/pharmacodynamic and time-to-event models of ribavirin-induced anaemia in chronic hepatitis C

BACKGROUND: Interferon (IFN)-alpha and ribavirin combination therapy is the standard treatment for patients with chronic hepatitis C. However, ribavirin induces anaemia, especially by haemolysis, an adverse effect that is dose-limiting. OBJECTIVES: The aim of this study was to determine the relationships between ribavirin exposure and haemoglobin time-course, the time-to-anaemia and the covariates influencing these relationships in a population of patients treated for chronic hepatitis C. In addition, we also intended to establish a simple rule defining the need for dosage adjustment, using data obtained during the first month of treatment. METHODS: A retrospective analysis of 99 patients treated with IFNalpha plus ribavirin, with known dosage administration history, liver biopsy, demographic data, red blood cell counts, haemoglobin level (1037 measurements, median 10 per patient, range 2-31) and serum creatinine during the entire treatment period (178 days, range 53-382 days) was conducted. The data were analysed by a pharmacokinetic/pharmacodynamic population model and Weibull time-to-anaemia model. The rule defining the need for dosage adjustment was as follows: adjustment was needed if haemoglobin at steady state (H(ss)), estimated by the Bayesian method based on data obtained during the first month of treatment, was <12 g/dL for men or <11 g/dL for women. RESULTS: In both models, anaemia was related to the exposure of erythrocytes to ribavirin at time t (RT in mg/kg/day) by a maximum effect model, with RT(50) (dosage administration rate at which half the maximal effect is reached) approximately 12 mg/kg/day, and the significant covariates were initial haemoglobin level and bodyweight. Performances of a Bayesian prediction of H(ss) based on two early haemoglobin level measurements were encouraging (mean prediction error 0.12 g/dL, precision 0.85 g/dL). The proposed rule for the need of dosage adjustment was able to predict the actual evolution of the dosage regimen in 76% of non-adapted patients and 69% of adapted patients. CONCLUSION: The current guidelines for ribavirin dosage administration, based on bodyweight, are adequate, at least in the 45-105 kg range. Results indicate that Bayesian therapeutic monitoring could be helpful in controlling ribavirin-induced anaemia.     

Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis

Our aims were to measure the kinetics of serum tumour necrosis alpha (TNF-α) and transforming growth factor beta (TGF-β) levels as markers of progression of disease in nontreated chronic hepatitis C virus (HCV)-infected patients with minimal or no fibrosis and minimal histology activity index (HAI) scores. Our study group consisted of 56 patients diagnosed with minimal (1) or no fibrosis (0) and minimal HAI (0–1) on their first biopsy as defined by Knodell and METAVIR scores. We compared their initial (entry of study) cytokine levels with a group of 103 HCV controls with minimal (0–1) to mild fibrosis (0–3) and mild HAI (5.5). Serum TNF-α and TGF-β levels were measured by enzyme-linked-immunosorbent-assay. A significant difference was seen in TNF-α levels at baseline in the study group vs. controls. Regardless of their HAI, there was a correlation between TGF-β and degree of fibrosis. As shown by their biopsies, during the 3 years (from entry to follow up), many of the patients that initially had minimal fibrosis progressed to higher degree of fibrosis. This progression is paralleled by an increase in TGF-β levels when comparing initial and follow-up levels. In conclusion, serum TNF-α reflects the progression of inflammation as seen in liver biopsies and TGF-β reflects the degree of fibrosis in HCV patients.     

Perihepatitis and HIV/AIDS infection. Apropos of 13 cases at the National Hospital of Bobo-Dioulasso

Perihepatitis or Fitz-Hugh syndrome, peritonitis located in the right hypochondriasis (RH), is a relatively rare affectation. However, the HIV-AIDS pandemic has brought about the emergence and re-emergence of disease-states either uncommon or formerly on the decline as well as the appearance of opportunistic illness. We report the results of a retrospective study conducted in the National Hospital of Bobo-Dioulasso (Burkina-Faso) between 1 June 1997 and 31 December 1999 in an effort to contribute to a wider vision of diseases associated with HIV-AIDS. We based our study on 130 laparoscopies carried out for unexplained pain linked to RH (with or without fever), as well as abdominal-pelvian or diffuse abdominal pain. Thirteen cases (11 women, 2 men) of perihepatitis were diagnosed. The mean age for women and men was respectively 31.4 and 39.5. HIV serology was systematically carried out for all patients and, in case of perihepatitis, cultures were taken. All patients were infected with HIV and some presented signs of AIDS according to the WHO classification. In clinical terms, a shalking pain for RH was noted for 5 patients, abdominal sensitivity in 8 cases as well as gynaecological anomalies: cul-de-sac moving pain (4 cases), leuchorrea (3 cases) and mucosic vulvovaginitis (1 case). Paraclinical tests revealed a slight hepatic cytolysis for only 3 patients (1.5 N). 6 patients tested positive for Chlamydia trachomatis; the 7 others could not be tested, but this aetiology was assumed for evaluating the efficacy of the treatment under study. The high frequency of perihepatitis in these patients, all of whom were suffering from HIV-AIDS, and its presence in the 2 male cases, suggest that immunodepression is conducive to the appearance of this disease.     

Medical history of Teflon

The different stages in the medical use of Teflon are recalled. After animal experimentation which started in 1949, Teflon has been used in humans since 1962 in otorhinolaryngology, since 1973 in urology and, more recently, since 1984 in the treatment of vesicorenal reflux. The long-term future is still uncertain, especially with regard to children, for whom life expectancy is long.