Showing papers by "Raffaele Bruno published in 2004"

Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome.

Abstract: OBJECTIVE Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-seropositive individuals. The aim of the study was to compare the main features of HCC in HIV-seropositive individuals with those in to HIV-negative patients. PATIENTS AND METHODS All HIV-infected subjects with a diagnosis of HCC included in three cancer registry databases were enrolled in the study as cases. HCC cases that occurred in the province of Brescia, North Italy, in the period 1995-1998 and all cases reported at the Italian Liver Cancer Project were enrolled as controls. All data were collected using a standardized case report form. The main clinical and epidemiological characteristics of patients with HCC and their survival were compared between HIV-positive and uninfected subjects. RESULTS Forty-one HIV-infected subjects with HCC were identified. Multivariate analysis adjusted for age and sex identified an association between HIV infection and HCV infection [odds ratio (OR), 11; P = 0.005], and infiltrating tumours and/or extranodal metastasis at presentation (OR = 11.8; P < 0.001). HIV infection was independently associated with shorter survival (hazard ratio, 1.63; P = 0.015). CONCLUSIONS HCC in HIV-infected patients is mainly associated with underlying chronic hepatitis C and has a more aggressive clinical course. Thus, preventative strategies (including the treatment of hepatitis C) should be implemented in the management of HIV/HCV-coinfected patients.

Viral dynamics and pharmacokinetics of peginterferon alpha-2a and peginterferon alpha-2b in naive patients with chronic hepatitis c: a randomized, controlled study.

Abstract: The two available pegylated interferon formulations, peginterferon alpha-2a and peginterferon alpha-2b, have different pharmacokinetic profiles; as a result they may have differing abilities to suppress the hepatitis C virus. A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving peginterferon alpha-2b either once or twice weekly suggests that once-weekly administration of peginterferon alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period. The objective of this study was to compare viral dynamics and pharmacokinetics between peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive chronic hepatitis C patients. Patients were randomized to receive peginterferon alpha-2a 180 microg (n=10) or peginterferon alpha-2b 1.0 microg/kg (n=12) once weekly. Serum peginterferon concentrations were measured at baseline, 24, 48, 120 and 168h. Hepatitis C virus (HCV) RNA was measured at baseline, 24, 48, 120 and 168 h during week 1 and then at 4 and 12 weeks. Peginterferon alpha-2b achieved maximal serum levels at 24 h, and then decreased rapidly. Of the 12 patients who received peginterferon alpha-2b, no drug was detectable in seven (58%) patients at 120 h and in 11 (92%) at 168 h. In contrast, peginterferon alpha-2a concentrations increased continuously over time, reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups. However, at week 12, mean HCV RNA was significantly lower in the peginterferon alpha-2a group versus the peginterferon alpha-2b group (2.8126 vs 3.8726; P<0.01). The differences in mean HCV RNA values at 12 weeks may be related to the different absorption and distribution profiles of the two drugs. In conclusion, once-weekly administration of peginterferon alpha-2b (1.0 microg/kg/wk) may be insufficient for continuous interferon exposure; twice-weekly administration may help avoid increases in viral replication as interferon levels decline. Larger-scale studies assessing both viral kinetics and sustained virological responses are needed to confirm these observations.

The management of hepatitis B virus/HIV-1 co-infected patients starting their first HAART regimen. Treating two infections for the price of one drug?

Abstract: We examined the impact of a lamivudine-containing highly active antiretroviral therapy (HAART) regimen on 164 hepatitis B virus/HIV co-infected individuals starting their first HAART. Lamivudine-treated patients (accounting for 73% of the study population) showed a significantly lower level of alanine aminotransferase over follow-up [-81.1 mU/ml mean difference; 95% confidence intervals (95% CI): -30.3; -131.7, P=0.003] and a significantly reduced risk of liver-related morbidity/mortality [Relative hazard (RH)=0.07; 95% CI: 0.01-0.38, P=0.002] than those starting a lamivudine sparing-regimen.

Host factors affecting the outcome of treatment of hepatitis C.

Abstract: The development of peginterferon and ribavirin combination therapy has significantly improved the sustained virologic response (SVR) rates in patients with chronic hepatitis C. However, poor patient adherence to therapy negatively influences drug levels and drug exposure, often preventing the development of an inhibitory drug level. To optimize patient adherence, the clinician must recognize factors predicting low adherence and negotiate a treatment plan that the patient understands and to which he or she commits. If adverse effects become intolerable, continuing patients on a reduced dose rather than withdrawing treatment seems to confer considerable advantage in preserving the chance for attaining an SVR. Results of a head-to-head comparison have demonstrated the possibility that, in cases of dose reduction, levels of peginterferon alfa-2a could remain above the limit of detection, whereas those of peginterferon alfa-2b might not.

Dissociation of Serum and Liver Hepatitis C Virus RNA Levels in Patients Coinfected with Human Immunodeficiency Virus and Treated with Antiretroviral Drugs

Abstract: We examined hepatitis C virus (HCV) RNA levels in serum, peripheral blood mononuclear cells (PBMC), and the liver for 135 patients with chronic HCV infections, 44 of whom were human immunodeficiency virus (HIV) positive and treated with highly active antiretroviral therapy (group A), 66 of whom were HIV negative (group B), with abnormal serum alanine aminotransferase (ALT) values, and 25 of whom were HIV negative, with ALT values of ≤15 times the normal value (group C) Patients had not been treated with interferon, with or without ribavirin, at the time of the study A statistically significant correlation between HCV RNA levels in the liver and serum was reproducibly documented, whereas this was inconsistent for serum and PBMC A comparative evaluation of HCV RNA levels in the liver and PBMC showed significantly lower values for group A than for groups B and C (P < 001 and P < 00001, respectively) In contrast, HCV RNA levels in serum were significantly higher for group A than for group B (P < 0001) A dissociation between HCV RNA levels in serum and the liver was found for patients with HIV-HCV coinfections Although the relative contribution of extrahepatic reservoirs, including lymphoid cells, to HCV RNA levels in serum is unclear, it may be speculated that a low intrahepatic HCV burden is caused by restored immunocompetence after successful antiretroviral therapy in coinfected patients