Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV infection. However, replication of hepatitis C virus (HCV) is not inhibited by HAART, and treatment-related hepatotoxicity is common. To clarify the effect of HAART in HIV/HCV-coinfected patients, we studied liver-related mortality and overall mortality in 285 patients who were regularly treated during the period 1990-2002 at our department. METHODS: Survival was analysed retrospectively by Kaplan-Meier and Cox's regression analyses after patients (81% haemophiliacs) had been stratified into three groups according to their antiretroviral therapy (HAART n=93, available after 1995; treatment exclusively with nucleoside analogues n=55, available after 1992; or no treatment, n=137). FINDINGS: Liver-related mortality rates were 0.45, 0.69, and 1.70 per 100 person-years in the HAART, antiretroviral-treatment, and untreated groups. Kaplan-Meier analysis of liver-related mortality confirmed the significant survival benefit in patients with antiretroviral therapy (p=0.018), and regression analysis identified HAART (odds ratio 0.106 [95% CI 0.020-0.564]), antiretroviral treatment (0.283 [0.103-0.780]), CD4-positive T-cell count (0.746 [0.641-0.868] per 0.05x10(9) cells/L), serum cholinesterase (0.962 [0.938-0.986] per 100 U/L), and age (1.065 [1.027-1.105] per year) as independent predictors of liver-related survival. Severe drug-related hepatotoxicity was seen in five patients treated with nucleoside analogues alone and 13 treated with HAART. No patient died from drug-related hepatotoxicity. INTERPRETATION: In addition to improved overall survival, antiretroviral therapy significantly reduced long-term liver-related mortality in our patients. This survival benefit seems to outweigh by far the associated risks of severe hepatotoxicity.

Bleeding complications after percutaneous liver biopsy. An analysis of risk factors.

BACKGROUND AND AIMS: To assess the risk of bleeding after percutaneous liver biopsy, we retrospectively analyzed 629 procedures with particular respect to patients with an increased a priori bleeding risk. METHODS: Factors possibly related to the risk of bleeding were analyzed by univariate analysis. Those variables which were significant in the univariate analysis were then entered into a forward conditional logistic regression model. RESULTS: Biopsy-related bleeding events defined as clinically overt complication (n = 10; 1.6%), an otherwise unexplained drop in serum hemoglobin concentration of greater than 2 g/dl (n = 45; 7.1%) or intra- or extrahepatic hematoma assessed by ultrasound (n = 17; 2.7%) were identified in 72 patients. 58% of the bleeding events occurred in patients with particular risk factors for bleeding. Biopsy-related mortality in the study cohort was 0.48%. Logistic regression analysis indicated mycobacterial infection [odds ratio (OR) 24.0], pre-biopsy prophylactic platelet substitution (OR 9.9), acute liver failure (OR 9.1), heparin administration on the day of biopsy (OR 8.7), advanced liver cirrhosis (OR 5.1), therapy with corticosteroids (OR 3.5) or metamizole (OR 2.8) and leukemia or lymphoma (OR 2.8) as significant (p < or = 0.05) independent risk factors. Delayed bleeding (>24 h after biopsy) was identified in 70% of the bleeding events. CONCLUSIONS: In our study cohort which comprised a high proportion of patients with particular risk factors for bleeding, biopsy-related bleeding occurred more frequently and later than commonly observed and was associated with only a few prognostic factors. Considering these predictors before liver biopsy will aid to reduce the rate of bleeding complications.

Parvovirus B19 transmission by heat-treated clotting factor concentrates.

BACKGROUND: Human parvovirus B19 (B19) DNA can be frequently detected in plasma-derived coagulation factor concentrates. The production of some clotting factor products includes heat treatment steps for virus inactivation, but the effectiveness of such steps for B19 inactivation is unclear. Moreover, detailed transmission case reports including DNA sequence analysis and quantification of B19 DNA from contaminated heat-treated blood components have not been provided so far. Therefore, the correlation between B19 DNA in blood components and infectivity remains unclear. STUDY DESIGN AND METHODS: Asymptomatic B19 infections of two patients with hemophilia A were detected by anti-B19 seroconversion after administration of B19-contaminated heat-treated clotting factors. The suitability of nucleic acid sequence analysis for confirmation of B19 transmission was investigated. Furthermore, the B19 DNA level in blood components was determined and the drug administration was reviewed to calculate the amount of inoculated B19 DNA. RESULTS: Both B19 transmissions from clotting factor products could be confirmed by identical nucleic acid sequences of virus DNA from patients and blood components while sequences from unrelated controls could be differentiated. One patient received, for 4 days, a total of 180 mL vapor heat-treated prothrombin complex concentrate containing 8.6 x 10(6) genome equivalents per mL of B19 DNA. The other patient received 966 mL of low-contamination (4.0 x 10(3) genome equivalents/mL) dry heat-treated FVIII concentrate over a period of 52 days. CONCLUSION: B19 transmissions can be confirmed by nucleic acid sequencing. However, due to the low variability of the B19 genome, a large part of the B19 genome must be analyzed. The transmissions show that the applied heat treatment procedures were not sufficient to inactivate B19 completely.