Laura Maiocchi

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.

Forthcoming challenges in the management of direct-acting antiviral agents (DAAs) for hepatitis C

Agents that specifically target the replication cycle of the virus direct-acting antiviral agents (DAAs) by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of C(min)/IC(50) (inhibitory quotient or IQ) can provide a surrogate measure of a drugs ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to DAAs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.

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.

The clinical value of controlled attenuation parameter for the noninvasive assessment of liver steatosis.

Ultrasound is the imaging modality most widely utilized in the general population for diagnostic purposes. Controlled attenuation parameter is a novel noninvasive method for assessing steatosis. Our aim was to investigate whether the clinical value of controlled attenuation parameter in patients referred for abdominal ultrasound examinations is affected by liver fibrosis.

Hepatotoxicity and nelfinavir: a meta-analysis.

BACKGROUND & AIMS The inclusion of protease inhibitors in 3-drug highly active antiretroviral regimens for treating patients who are infected with human immunodeficiency virus-1 has had a significant impact in increasing survival and decreasing morbidity. However, the effectiveness of this class of drugs may be compromised by the occurrence of drug-related hepatotoxicity, which is problematic especially in individuals co-infected with hepatitis viruses. Based on its clinical and pharmacologic profile, especially its unique pattern of resistance, nelfinavir has been used frequently as a first-line protease-inhibitor therapy for human immunodeficiency virus-1-infected patients. The aim of this study was to identify the relative potential for developing hepatotoxicity for nelfinavir vs other protease inhibitors. METHODS An exploratory meta-analysis of liver enzyme level increases was conducted in a combined total of 4268 patients derived from 3 large recently conducted prospective and retrospective clinical trials and a prospective cohort study. RESULTS The results indicate that among 4 commercially available protease inhibitors and a 2-protease inhibitor combination, nelfinavir and indinavir are associated with the lowest rates of occurrence of severe hepatotoxicity (ie, combined estimates of liver enzyme level increases of 2.9% and 3.1%, respectively). The low rate of occurrence of severe hepatotoxicity for nelfinavir was shown even among patients co-infected with hepatitis viruses. CONCLUSIONS In conclusion, these data provide support for the conclusion that differences in the potential for hepatotoxicity do exist among the commercially available protease inhibitors.

Ruling-in and ruling-out significant fibrosis and cirrhosis in patients with chronic hepatitis C using a shear wave measurement method

AIMS To prospectively assess the cutoff values of a point shear wave measurement (SWM) method for ruling-in and ruling-out significant fibrosis and cirrhosis using transient elastography (TE) as the reference standard. METHOD Consecutive patients with chronic hepatitis C were enrolled. Liver stiffness was assessed with the SWM method implemented on the HI VISION Ascendus ultrasound system (Hitachi Ltd, Japan) and with the TE method of the FibroScan® device (Echosens, France). For staging significant fibrosis (F>/=2) and cirrhosis (F=4) we used the TE cutoffs of 7.0 and 12.0 kiloPascal (kPa), respectively. The diagnostic performance of SWM was assessed by calculating the area under the receiver operating characteristic (AUROC) curve. Cutoffs with specificity or sensitivity > 90% were chosen to rule-in or rule-out F>/=2 and F=4. RESULTS 445 individuals [235 males, 210 females; mean age, 61.1 (13.3) years] were studied: 190 (42.7%) individuals had F0-F1 fibrosis stage, 82 (18.4%) F2, 46 (10.3%) F3, and 127 (28.6%) F4 fibrosis stage. For ruling-in F>/=2 the SWM cutoff was 6.78 kPa [sensitivity, 76.9%(70.6-82.4); specificity, 90.3% (85.0-94.3)] and for ruling-out it was 5.55 kPa [sensitivity, 90.6% (85.8-94.1); specificity, 72.2% (64.9-78.6)]. For ruling-in F=4 the SWM cutoff was 9.15 kPa [sensitivity, 83.3% (74.4-90.2); specificity, 90.1% (86.0-93.2)] and for ruling-out it was 8.41 kPa [sensitivity, 90.6% (82.9-95.6); specificity, 82.2% (77.3-86.4)]. AUROCs were 0.92 (0.89-0.94) for F>/=2 and 0.94 (0.91-0.96) for F=4. CONCLUSIONS In clinical practice, the use of a dual cutoff of SWM may increase the confidence in staging liver fibrosis with a non-invasive shear wave elastography technique.

Adherence to quality criteria improves concordance between transient elastography and ElastPQ for liver stiffness assessment—A multicenter retrospective study

BACKGROUND Assessment of liver stiffness provides important diagnostic and prognostic information in patients with chronic liver disease. AIMS To investigate whether the use of quality criteria (i) improves the concordance between transient elastography (TE) and a novel point shear wave elastography technique (ElastPQ®) and (ii) impacts on the performance of ElastPQ® for liver fibrosis staging using TE as the reference standard. METHODS In this multicenter retrospective study, data of patients undergoing liver stiffness measurements (LSM) in five European centers were collected. TE was performed with FibroScan® (Echosens, France) and ElastPQ® with EPIQ® or Affiniti® systems (Philips, The Netherlands). The agreement between TE and ElastPQ® LSMs was assessed with Lins concordance correlation coefficient (CCC). Diagnostic performance of ElastPQ® was assessed by the area under receiver operating characteristic (AUROC) curves. RESULTS Overall, 664 patients were included: mean age: 54.8(13.5) years, main etiologies: viral hepatitis (83.1%) and NAFLD (7.5%). CCC increased significantly when LSMs with ElastPQ® were obtained with IQR/M ≤ 30% (p < 0.001). The diagnostic performance of ElastPQ® for fibrosis staging also increased if LSM values were obtained with IQR/M ≤ 30%. CONCLUSION Quality criteria should be followed when using ElastPQ® for LSM, since the concordance with TE fibrosis staging was better at an ElastPQ® IQR/M ≤ 30.