Long-term hepatitis B virus surface antigen decay in HIV-1/hepatitis B virus-coinfected adults initiating a tenofovir-containing regimen.

Hepatitis B virus (HBV) surface antigen (HBsAg) decay was explored in HIV-1- and HBV-coinfected patients beginning antiretroviral (ARV) therapy containing tenofovir disoproxil fumarate (TDF). The mean HBsAg decay was 0.38 log(10) IU/ml/year (95% confidence interval [CI], 0.71 to 0.05) in 18 patients with sustained plasma HIV-1 RNA suppression and 0.15 log(10) IU/ml/year (0.21 to 0.09) in 12 patients experiencing HIV-1 virologic failure due to suboptimal adherence to ARV (P = 0.17). We estimated that six of these 18 patients will attain HBsAg values below 10 IU/ml after 10 years of treatment.

High rates of active hepatitis B and C co-infections in HIV-1 infected Cameroonian adults initiating antiretroviral therapy.

OBJECTIVES: To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV-infected patients initiating antiretroviral therapy in Cameroon. METHODS: Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti-hepatitis B core (anti-HBc), anti-HCV and - if HBsAg or anti-HCV result was positive or indeterminate - for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6-13.5]. The median HBV viral load was 2.47 x 10(7) IU/mL [interquartile range (IQR) 3680-1.59 x 10(8); range 270 to >2.2 x 10(8)]. Twenty-one patients (12.4%, 95% CI 7.9-18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400-2.06 x 10(6); range 640-5.5 x 10(6)). No patient was co-infected with HBV and HCV. In multivariate analysis, HCV co-infection was associated with greater age [>or=45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49-40.55, P<0.001] and abnormal serum alanine aminotransferase level [>or=1.25 x upper limit of normal (ULN) vs. <1.25 x ULN, OR 7.81, 95% CI 1.54-39.66, P=0.01]; HBV co-infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32-14.17, P=0.02). CONCLUSIONS: These high rates of active HBV and HCV co-infections in HIV-positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV-endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.

Lymphocytotoxic antibodies and antiglobulins in renal allograft recipients. Correlative study with acute rejection.

In 45 patients who received kidney transplants, both homologous and heterologous human antiglobulins (anti-Ig) and HLA cytotoxic antibodies have been studied before and after transplantation and in some cases after nephrectomy. A similar study has been performed in a control group of 1,019 healthy blood donors and in 130 patients with acute or chronic glomerulonephritis. After transplantation, homologous anti-IgG were found in 60% of the patients, as compared with 3.5% in the healthy blood donors and 21% in patients with various forms of glomerulonephritis. This difference is particularly striking in sera obtained prior to nephrectomy; the presence of anti-IgG and cytotoxic antibodies in the same patient being significantly associated with early transplant failure. Anti-IgA were found in 75% of the patients with transplants and in 37% of the patients with glomerulonephritis. There was no relationship between the anti-IgA and the outcome of the graft. On the other hand, heterologous anti-Ig were unchanged in the three groups investigated. The mechanism of formation of the anti-IgG is not clear. They are probably antibodies against antigenic structures of the patient's own antibodies, previously combined with a soluble antigen or an antigen on the transplant that has undergone molecular transformation in the course of this reaction. Their pathogenic role, although not demonstrated, can be strongly suspected, and, in a practical way, screening for the anti-Ig in kidney transplant recipients could be of value as a prognostic test.

Hepatitis C in a ward for cystic fibrosis and diabetic patients: possible transmission by spring-loaded finger-stick devices for self-monitoring of capillary blood glucose.

OBJECTIVE: To identify the routes of transmission in a nosocomial outbreak of hepatitis C virus (HCV) infection. DESIGN: Epidemiological investigation, including screening for HCV of hospitalized patients, and a retrospective cohort study, review of hygiene and medical practices, and molecular comparison of HCV isolates. SETTING: A specialized care unit for cystic fibrosis (CF) and diabetic patients at an acute-care facility in the south of France. RESULTS: Of the 57 CF patients (age in 1995: 2-28 years), 38 (66.7%) were tested and 22 (57.9%) were anti-HCV positive. Eight (50%) of 16 patients with anti-HCV antibody tested by polymerase chain reaction were viremic. No patients had received blood products or had any history of intravenous drug use. All 18 (100%) patients with CF who had ever undergone self-monitoring of capillary blood glucose in the unit were anti-HCV positive, compared to 4 (20%) of 20 who had not (relative risk, 5.0; 95% confidence interval, 2.1-12.0). Seventy (39.5%) of the patients with diabetes were screened for anti-HCV; 12 (18.8%) tested positive, with 3 (25%) positive for HCV-RNA. Patients with diabetes had routine capillary blood glucose monitoring while hospitalized and shared with CF patients the same spring-triggered devices for capillary blood glucose monitoring. The disposable platform of the devices was not changed between patient use. All HCV isolates belonged to the type 1, subtype b, and phylogenetic analysis showed a close homology by sequencing of NS5b and E2/HVR regions. CONCLUSION: As reported earlier for the hepatitis B virus, shared spring-triggered devices for capillary blood glucose monitoring by finger puncture may transmit HCV. Strict application of Standard Precautions procedures is warranted in any healthcare setting.

Hepatitis C virus genotypes and quantification of serum hepatitis C RNA in liver transplant recipients. Relationship with histologic outcome of recurrent hepatitis C.

The reasons for wide variations in the severity of recurrent hepatitis C after liver transplantation are unclear. We studied liver transplant recipients to assess the effect of hepatitis C virus (HCV) genotype and HCV RNA quantification on histologic progression of recurrent hepatitis C after transplantation. Twenty-five patients underwent transplantation for HCV cirrhosis and were followed up with virologic and histologic assessments for a mean of 51 months. HCV genotype was determined by line probe assay. HCV RNA was quantitated in serum samples by nested polymerase chain reaction. The HCV genotype 1 was detected in 17 patients and other genotypes in 8. Acute lobular hepatitis developed in 17 patients 162 days posttransplantation on average. Long-term biopsy specimens (mean, 51 months after the date of liver transplantation; range, 24-86 months) showed chronic hepatitis in 19 patients (mild, 5; moderate, 9; and severe, 5, 2 with extensive scarring). The serum alanine aminotransferase level was correlated with hepatocyte necrosis (piecemeal and lobular) but not with portal inflammation or fibrosis. Patients infected with genotype 1 had a higher Knodell score, and the 5 patients with severe hepatitis C all were infected with genotype 1. HCV RNA levels were significantly higher in patients with genotype 1 than in patients with other genotypes, as were the severity of histologic recurrence and levels of viral replication.

Local immunotherapy of recurrent glioblastoma multiforme by intracerebral perfusion of interleukin-2 and LAK cells.

A non randomized pilot study has been undertaken to evaluate the feasibility of local immunotherapy (IT) of recurrent glioblastoma multiforme (GM) by continuous intracerebral perfusion of recombinant interleukin-2 (rIL-2, Eurocetus) with and without lymphokine activated killer (LAK) cells. At time of surgical removal of the tumor, a catheter was implanted in the cavity left by tumor debulking allowing continuous perfusion of rIL-2. Five patients received 18 x 10(6) IU/day or rIL-2 for five days. At days 1, 3, and 5 after surgery, rIL-2 perfusion was briefly interrupted for the injection of LAK cells. Eight other patients received rIL-2 alone, either 24 x 10(6) IU/day (five patients) or 54 x 10(6) IU/day (three patients). Capillary leak syndrome, which is the main side effect of systemic infusion of rIL-2, was never observed, but local immunotherapy induced fever, confusion, and cerebral edema in all patients. Despite local IT, tumor progression was diagnosed by CT scan 4 to 12 weeks after the treatment.

[Post-transfusional hepatitis]. / Les hépatites post-transfusionnelles.

Viral hepatitis has become a major complication of transfusion. Its frequency depends upon the number of blood units injected (packed cells, platelets, fresh frozen plasma), the origin of blood donors and the quality of controls performed after blood donation. Several reports estimate that this transmitted disease affects 2.3 to 26.5% of recipients (average: 10%). Among 100 cases of post-transfusion hepatitis, 10 are due to the hepatitis B virus (despite systematic search for HBs Ag), 89 are due to one of the non-A non-B viruses (not detectable by specific serological tests) and 1 to several viruses, specially CMV. The systematic exclusion of prospective blood donors with a hig level of aminotransferase (above twice the normal value) and/or with an anti-HBc antibody prevents the transmission of all hepatitis B and of two-thirds of non-A non-B hepatitis. About 5% of all blood donors are thus excluded. This practice has been made legal in France in October, 1988.

[Transfusion and transmission of infectious and parasitic diseases excluding AIDS and viral hepatitis]. / Transfusion et transmission des maladies infectieuses et parasitaires à l'exclusion du SIDA et des hépatites virales.

Many viruses, bacteria or parasites can survive in stored blood for varying lengths of time. Recipients are therefore exposed to a risk which depends on the prevalence of pathogens in blood donor populations, the clinical and laboratory controls performed in blood transfusion centres and the efficiency of the patient's immune system. Beside the HIV and hepatitis viruses, transfusions may transmit the HTL virus in endemic areas or if the blood donor comes from one of these areas (e.g. the French West Indies), the CMV virus (but only in patients with weak immune defences) and some exotic viruses in specific regions. As regards bacterial agents, syphilis is prevented by blood storage at 4 degrees C for 72 hours and brucellosis remains a minor risk, but the very rare endotoxinic shock is severe and lethal in two-thirds of the cases. Infestation by parasites is common in certain areas, but it may occur in France after transfusion from blood donors coming from these areas; malaria transmitted by blood perfusion is a real problem. Drastic procedures of rejection of blood donors at risk, including examination and laboratory screening, must be applied and are effective in preventing these dangers. These procedures are well-known and are compulsory in France.

Combining rapid diagnostic tests and dried blood spot assays for point-of-care testing of human immunodeficiency virus, hepatitis B and hepatitis C infections in Burkina Faso, West Africa.

People screened for human immunodeficiency virus (HIV) using rapid diagnostic tests (RDTs) in Africa remain generally unaware of their status for hepatitis B (HBV) and hepatitis C (HCV) infections. We evaluated a two-step screening strategy in Burkina Faso, using both HIV RDTs and Dried Blood Spot (DBS) assays to confirm an HIV-positive test, and to test for HBV and HCV infections. HIV counselling and point-of-care testing were performed at a voluntary counselling and testing centre with HBV, HCV status and HIV confirmation using DBS specimens, being assessed at a central laboratory. Serological testing on plasma was used as the reference standard assay to control for the performance of DBS assays. Nineteen out of 218 participants included in the study were positive for HIV using RDTs. A fourth-generation HIV ELISA and immunoblot assays on DBS confirmed HIV status. Twenty-four out of 25 participants infected with HBV were found positive for hepatitis B surface antigen (HBsAg) using DBS. One sample with a low HBsAg concentration on plasma was not detected on DBS. Five participants tested positive for HCV antibodies were confirmed positive with an immunoblot assay using DBS specimens. Laboratory results were communicated within 7 days to participants with no loss to follow up of participants between the first and second post-test counselling sessions. In conclusion, DBS collection during HIV point-of-care testing enables screening and confirmation of HBV, HCV and HIV infections. Diagnosis using DBS may assist with implementation of national programmes for HBV, HCV and HIV screening and clinical care in middle- to low-income countries.

Investigation of memory B cell responses to hepatitis B surface antigen in health care workers considered as non-responders to vaccination.

Up to 20% of health care workers are considered as non-responders to hepatitis B vaccination (anti-HBs<10 m UI/ml in serum). We have explored memory B cells differentiated in vitro into anti-HBs antibody-secreting cells (anti-HBs-SCs) by ELISPOT assay. Anti-HBs-SCs were detected in vaccinated responders (n = 11) and non-responders (n = 10) but IgG anti-HBs-SCs were significantly lower in the non-responder group (p<0.001). Low amounts of HBs antibodies were also quantified by ELISA in non-responders' sera. These results indicate that a suboptimal B cell response exists in non-responders to HBV vaccination. This B cell response may mediate a protection against clinically significant breakthrough hepatitis B infection.