Savino F A Patruno

Performance of Real-Time Strain Elastography, Transient Elastography, and Aspartate-to-Platelet Ratio Index in the Assessment of Fibrosis in Chronic Hepatitis C

OBJECTIVE The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients with chronic hepatitis C by using histologic Metavir scores as reference standard. SUBJECTS AND METHODS Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis. RESULTS One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively. CONCLUSION Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.

Pharmacodynamics of peginterferon alfa‐2a and peginterferon alfa‐2b in interferon‐naïve patients with chronic hepatitis C: a randomized, controlled study

Background  Peginterferon alfa‐2a and alfa‐2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus.

Natural history of compensated viral cirrhosis in a cohort of patients with HIV infection

Background: The natural history of initially compensated cirrhosis in patients with HIV and concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection is poorly defined. This study was designed to investigate the incidence and type of liver-related complications and mortality in coinfected cirrhotic patients. Methods: We retrospectively identified a cohort of patients coinfected with HIV and HCV or HBV and initially compensated viral cirrhosis. Time to decompensation and mortality from liver-related causes were recorded. Results: Between 1999 and 2004, 392 HIV-infected patients underwent a follow-up of ≥6 months. Sixty-nine patients (17.6%) with initially compensated cirrhosis were identified (7 HBV positive, 59 HCV positive, and 3 positive for both HBV and HCV). The most frequent complication was ascites. The mortality was 71.3 per 1000 person-years (95% confidence interval [CI], 47 to 108) in HIV-infected patients with HBV and/or HCV compensated cirrhosis, 8 (95% CI, 4 to 16) in HIV/HCV-coinfected patients without cirrhosis, and 6.5 (95% CI, 2.7 to 15.5) in HIV-monoinfected patients. After the first event of decompensation, the survival rate was 48% at 1 year and 18.1% at 3 years. Treatment with HAART after the first event of decompensation was associated with an increased survival rate (61.1% and 26.2% at 1 and 3 years, respectively, vs. 26.7% and 0%; P < 0.0001). Conclusions: These results indicate significant morbidity and mortality during the 6 years after the diagnosis of compensated cirrhosis due to HBV and/or HCV in HIV-infected patients, identifying ascites as the most frequent complication.

Performance of liver stiffness measurements by transient elastography in chronic hepatitis

AIM To compare results of liver stiffness measurements by transient elastography (TE) obtained in our patients population with that used in a recently published meta-analysis. METHODS This was a single center cross-sectional study. Consecutive patients with chronic viral hepatitis scheduled for liver biopsy at the outpatient ward of our Infectious Diseases Department were enrolled. TE was carried out by using FibroScan™ (Echosens, Paris, France). Liver biopsy was performed on the same day as TE, as day case procedure. Fibrosis was staged according to the Metavir scoring system. The diagnostic performance of TE was assessed by using receiver operating characteristic (ROC) curves and the area under the ROC curve analysis. RESULTS Two hundred and fifty-two patients met the inclusion criteria. Six (2%) patients were excluded due to unreliable TE measurements. Thus, 246 (171 men and 75 women) patients were analyzed. One hundred and ninety-five (79.3%) patients had chronic hepatitis C, 41 (16.7%) had chronic hepatitis B, and 10 (4.0%) were coinfected with human immunodeficiency virus. ROC curve analysis identified optimal cut-off value of TE as high as 6.9 kPa for F ≥ 2; 7.9 kPa for F ≥ 3; 9.6 kPa for F = 4 in all patients (n = 246), and as high as 6.9 kPa for F ≥ 2; 7.3 kPa for F ≥ 3; 9.3 kPa for F = 4 in patients with hepatitis C (n = 195). Cut-off values of TE obtained by maximizing only the specificity were as high as 6.9 kPa for F ≥ 2; 9.6 kPa for F ≥ 3; 12.2 kPa for F = 4 in all patients (n = 246), and as high as 7.0 kPa for F ≥ 2; 9.3 kPa for F ≥ 3; 12.3 kPa for F = 4 in patients with hepatitis C (n = 195). CONCLUSION The cut-off values of TE obtained in this single center study are comparable to that obtained in a recently published meta-analysis that included up to 40 studies.

Correlation between FIB4, liver stiffness and metabolic parameters in patients with HIV and hepatitis C virus co-infection

BACKGROUND/AIMS Assessment of liver fibrosis is crucial in HIV/HCV coinfected patients, in whom metabolic disturbances are frequent. Aims of this study were to analyse the association of two non-invasive liver fibrosis evaluation methods, liver stiffness measurement and FIB4, and their correlation with metabolic parameters. METHODS This was a single centre cross-sectional study. All patients underwent biochemical and virological assessment, FIB4 score, HOMA and transient elastography. RESULTS Seventy-five patients were evaluated. Liver stiffness values positively correlated with FIB4 (R = 0.62; p < 0.0001). By ROC curve analysis the optimal cut-off for liver stiffness to identify high FIB4 was calculated as 10.1 kPa. The area under the ROC curve was 0.78 (95% CI 0.78-0.94, sensitivity 83.3%, specificity 80.7%). Liver stiffness values positively correlated with HOMA score (R = 0.31; p = 0.006). CONCLUSIONS The combination of two non invasive tools provide a useful system for the assessment of fibrosis evolution in patients with HIV-HCV coinfection.

Efficacy of a short-term amphotericin B + flucytosine combination therapy followed by itraconazole monotherapy in acute and chronic AIDS-associated cryptococcosis

Summary. The authors report the clinical and microbiological findings of a 6‐month follow‐up of nine AIDS patients affected with cryptococcosis. Among these, seven patients suffered from meningoencephalitis and two from disseminated infection. The antifungal therapy during acute illness included the administration of amphotericin B at doses of 0.6 mg kg‐1 day‐1 i.v. plus flucytosine at doses of 100 mg kg‐1 day‐1 i.v. during the first 15 days followed by itraconazole at doses of 400 mg day‐1 p.o. in the following 15 days. The maintenance treatment included itraconazole at doses of 200 mg day‐1 p.o. indefinitely. During the 6‐month follow‐up, one patient died of hepatic failure related to C virus (HCV) hepatitis reactivation and another patient died of polymicrobial pneumonia. In two patients, the presence of multiple nodular lesions in the cerebral computerized tomography (CT) scan, related to cryptococcal granulomas, was associated with the persistance of fungi in the cerebrospinal fluid. In three patients with meningoencephalitis the three‐drugs regimen was effective in eradicating the neurological infection, and relapses were not observed during the maintenance therapy with itraconazole during the 6‐month follow‐up. The two patients with haematogenous cryptococcosis did not relapse after the 6‐month follow‐up.

Quantification of HIV-1 proviral DNA in patients with undetectable plasma viremia over long-term highly active antiretroviral therapy

OBJECTIVES To assess the prognostic role of proviral DNA in peripheral blood mononuclear cells (PBMC) of patients with undetectable viremia over long-term highly active antiretroviral therapy (HAART). METHODS Eighty-two human immunodeficiency virus (HIV)-1-infected patients, free of acquired immunodeficiency syndrome (AIDS), received zidovudine plus lamivudine plus indinavir. Levels of plasma HIV-RNA, and PBMC proviral DNA and RNA unspliced (US) transcripts were evaluated by using competitive polymerase chain reaction (cPCR) assays, every 3 months over 1 year. RESULTS Among patients with undetectable viremia at baseline, 13 of 18 with CD4 cell count 350/mm3 or less and 12 of 16 with CD4 between 351 and 700/mm3, constantly maintained undetectable RNA levels; in these patients, a mean proviral DNA decrease of 0.67 6 0.7 and 1.03 6 0.53 log (P < 0.001), respectively, a significant decrease of RNA-US transcripts (P < 0.001), and significant correlations between decreases of proviral DNA and RNA-US transcripts (P = 0.008 and P < 0.001, respectively) were observed. CONCLUSIONS Proviral DNA quantitation permits the continued monitoring of HAART in patients with undetectable viremia.

HAART (zidovudina, lamivudina, indinavir): analisi dei costi in una popolazione di pazienti HIV positivi con conta linfocitaria CD4+ < 200/mmc

SummaryObjective To analyze the cost of a population of HIV patients with less than 200 CD4 cell count treated with HAART (highly active antiretroviral therapy). Design Retrospective study Setting IRCCS Policlinico S. Matteo Pavia, Italy, University of Pavia, Italy. Patients and participants 181 HIV positive patients with less than 200 CD4 cell count observed from January 1996 until December 1997. Main outcome measures Hospitalization, days of stay, AIDS definig events, deaths, direct cost, assessed during two years follow-up. Results During follow-up hospitalizations decreased from 154 to 118, while hospital stays dropped from 3429 to 2832 days, with the decrease beginning at the start of the 2nd four-month period of 1997. There was a reduction in terms of time of AIDS defining events (ADE) compared to those of 1996; in 1997 there was a 70% decrease in new diagnoses. Likewise, for deaths, there was a constant decrease in 1997 when compared to 1996 where there was a peak in the third four-month period. Total costs of our patient cohort were similar for 1996 and 1997, with a shift occurring from hospitalization costs to anti-retroviral therapy costs. Conclusion Our data indicate that patients with CD4 < 200/mmc, that is that population carrying the greatest health costs, does not result in relevant added costs when HAART is used (plus 10% on pro-capite for year bases) but, rather, creates a shift from one type of cost to another.

Daily interferon regimen for chronic hepatitis C. A prospective randomised study

AbstractObjective: To compare the safety and efficacy of two regimens of lymphoblastoid interferon, 3MU daily for 12 months vs 6MU three times weekly for 12 months, for the treatment of patients with chronic hepatitis C. Design: This was a prospective, randomised, nonblind study. Setting: The study was conducted in outpatients attending the University Hospital in Pavia, Italy, between 1997 and 1998. Patients: 100 treatment-naive outpatients with chronic hepatitis C genotype 1b participated in the study. Main Outcome Measures: We measured serum hepatitis C virus (HCV) RNA levels, serum alanine aminotransferase (ALT), histological activity index score and fibrosis stage. Patients were classified as follows: primary responders (PR) when ALT normalised and HCV-RNA became negative during treatment; nonresponders (NR) if ALT remained elevated and HCV-RNA remained positive during treatment; sustained responders (SR) when HCV-RNA became persistently negative and ALT became normalised during treatment and for at least 6 months after treatment; relapsers (R) were PR whose ALT returned to abnormal values and HCV-RNA became positive again after the end of treatment. Results: 50 patients received 3MU daily, of whom 42 (84%) were PR and eight (16%) were NR. Of the 42 PR, 23 (54.7%) were SR and 19 (45.3%) were R. 50 patients received 6MU three times weekly, of whom 21 (42%) were PR and 29 (58%) were NR. Of the 21 PR, five (23.8%) were SR and 16 (76.2%) were R. Adverse effects were comparable in the two groups and were never serious enough to require withdrawal of therapy. Conclusion: These findings support the choice of a 3MU daily regimen of lymphoblastoid interferon for the treatment of patients with chronic HCV infection and provide corroborative evidence in support of molecular virological data suggesting a relatively rapid viral turnover in this clinical setting.

Costo efficacia di peginterferone α-2a + ribavirina verso peginterferone α-2b + ribavirina nel trattamento dell'epatite cronica di tipo C in pazienti non pretrattati

SummaryIntroductionThe objective of this study was to evaluate the cost-effectiveness of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin as initial therapy for patients with Chronic Hepatitis C (CHC).MethodsWe used a pre-existent Markov model of disease progression in which two cohorts of patients received peginterferon α-2a plus ribavirin or peginterferon α-2b plus ribavirin for 48 weeks and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The sustained virological responses (SVR) with peginterferon α-2a plus ribavirin and peginterferon α-2b plus ribavirin, were taken from two different publications. Utilities and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs in 2005 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was conducted from the perspective of the Italian National Health Service.ResultsFor the two cohorts expected life-years with peginterferon α-2a plus ribavirin versus peginterferon α-2a plus ribavirin were respectively 30.85 and 30.15 years. Quality-adjusted life years for peginterferon α-2a plus ribavirina were 17.69, and for peginterferon α-2b plus ribavirin were 17.08. The expected cost was €18,272 with peginterferon α-2a plus ribavirin and €18,549 with peginterferon α-2b plus ribavirin.ConclusionThis economic evaluation suggests that peginterferon α-2a plus ribavirin is a dominant strategy versus peginterferon α-2b plus ribavirin for treatment of adults with CHC, under some assumptions regarding treatment effectiveness and model structure.