Luis Bianchi

Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study

BACKGROUND Risk factors for lipodystrophy in patients infected with HIV-1 treated with highly active antiretroviral therapy (HAART) containing HIV-1 protease inhibitors are poorly understood. We aimed to identify the risk factors for lipodystrophy in antiretroviral-naive HIV-1-infected adults on HAART. METHODS Moderate or severe body-fat changes were clinically assessed and categorised as subcutaneous lipoatrophy, central obesity, or both, in all consecutive antiretroviral-naïve HIV-1-infected adults who began HAART with two nucleoside reverse transcriptase inhibitors plus at least one protease inhibitor from October, 1996, to September, 1999. A person-years analysis was used to calculate the incidence of types of lipodystrophy, and Cox proportional hazards models were used to describe the univariate and multivariate factors associated with progression to any lipodystrophy. FINDINGS After a median follow-up of 18 months, 85 (17%) of the 494 patients developed some type of lipodystrophy. The incidences of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and lipodystrophy with central obesity were 11.7 (95% CI 9.2-14.2), 9.2 (7.0-11.4), and 7.7 (5.7-9.7) per 100 patient-years. An increased risk for any lipodystrophy was found among women as compared with men (relative hazard 1.87 [1.07-3.28]), heterosexuals (2.86 [1.50-5.48]), and homosexuals (2.17 [1.07-4.42]) as compared with intravenous drug users, with increasing age (1.33 per 10 years older [1.08-1.62]), and with the duration of exposure to antiretroviral therapy (1.57 per 6 months extra [1.30-1.88]) but not with any individual antiretroviral agent. The factors associated with an increased risk for lipodystrophy with subcutaneous lipoatrophy or lipodystrophy with central obesity were very similar to those associated with any lipodystrophy. The duration of indinavir use may represent an additional contribution for the development of lipodystrophy with central obesity (1.26 per 6 months extra [0.99-1.60]); p=0.064). INTERPRETATION Risk factors associated with development of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and tipodystrophy with central obesity in patients infected with HIV-1 who were receiving HAART containing protease inhibitors are multifactorial and overlapping, and cannot be exclusively ascribed to the duration of exposure to an particular antiretroviral agent.

Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable?

Evaluation of response to treatment is a key aspect in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) are used in most oncology trials, but those criteria evaluate only unidimensional tumor measurements and disregard the extent of necrosis, which is the target of all effective locoregional therapies. Therefore, the European Association for the Study of the Liver (EASL) guidelines recommended that assessment of tumor response should incorporate the reduction in viable tumor burden. The current report provides an assessment of the agreement/concordance between both RECIST and the EASL guidelines for the evaluation of response to therapy.

Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound.

The aim of this study was to describe the imaging features by contrast‐enhanced ultrasound (CEUS) of intrahepatic cholangiocarcinoma (ICC) in cirrhosis patients. We registered the CEUS images of cirrhosis patients with histologically confirmed ICC. In all cases magnetic resonance imaging (MRI) was done to confirm the diagnosis and/or staging purposes. A total of 21 patients met all the criteria to be included in the study. The median nodule size was 32 mm. All nodules showed contrast enhancement at arterial phase; in 10 cases it was homogeneous and in 11 cases peripheral (rim‐like). All nodules displayed washout during the venous phases; it appeared during the first 60 seconds in 10 nodules, between 60‐120 seconds in five cases, and in six cases after 2 minutes. Ten nodules (five larger than 2 cm) displayed homogeneous contrast uptake followed by washout and they correspond to the specific pattern of hepatocellular carcinoma according to the American Association for the Study of Liver Diseases criteria. However, none of these lesions displayed washout on MRI. Conclusion: CEUS should not be used as the sole imaging technique for conclusive hepatocellular carcinoma diagnosis and if the MRI does not display the diagnostic vascular pattern, a confirmatory biopsy is mandatory. Hepatology 2010;51:2020–2029

Evaluation of hepatocellular carcinoma using SonoVue, a second generation ultrasound contrast agent: correlation with cellular differentiation

The appearance of hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound (CEUS) in the vascular phase is described and evaluated as to whether the enhancement pattern correlates with the degree of cellular differentiation. One hundred four HCCs were prospectively evaluated with CEUS using coherent-contrast imaging (CCI) and SonoVue with a low mechanical index (<0.2). The enhancement of HCCs in the vascular phase was analyzed according to the degree of pathological differentiation obtained by fine-needle biopsy. In the arterial phase, all HCCs except for four well differentiated ones (96.2%) showed enhancement (P<0.05). Histological differentiation of hypoechoic lesions in the early portal phase (7 HCCs; 16%) significantly differed from hyperechoic (1 HCC; 1%) or isoechoic lesions (87 HCCs; 83.6%) (P<0.05), with a significant probability of a worse differentiation in hypoechoic lesions. Histological differentiation of isoechoic lesions in the late phase (30 HCCs; 28.8%) significantly differed from hypoechoic lesions (74 HCCs; 71.2%) (P<0.05), with a significant probability of a better differentiation in isoechoic lesions. CEUS using CCI and SonoVue revealed enhancement in the arterial phase in >95% of HCCs, with a few well-differentiated cases not being diagnosed due to the absence of enhancement. Echogenicity in the portal and late phases correlated with cellular differentiation.

Importance of Evaluating All Vascular Phases on Contrast-Enhanced Sonography in the Differentiation of Benign from Malignant Focal Liver Lesions

OBJECTIVE Our objective was to evaluate the accuracy of a blood-pool sonographic contrast agent in the late phase compared with the three vascular phases for differentiation between benign and malignant focal liver lesions. SUBJECTS AND METHODS In 152 patients (105 with chronic liver disease), 152 solid focal liver lesions characterized either by fine-needle biopsy or by dynamic CT or MRI were studied. The final diagnoses were metastasis for 24, hepatocellular carcinoma for 75, focal nodular hyperplasia for 13, regenerating or dysplastic nodule for 14, hemangioma for 22, cholangiocarcinoma for two, and another focal liver lesion for two. Real-time sonography was performed after a bolus injection of 2.4 mL of SonoVue, using a low mechanical index (< 0.2). All lesions were evaluated in the arterial, portal, and late phases; classified as benign or malignant; and correlated with final diagnoses. RESULTS For discrimination between malignant and benign focal liver lesions, evaluation of all vascular phases improved the sensitivity from 78.4% to 98% and the accuracy from 80.9% to 92.7%, compared with evaluation of the late phase alone. The increase in accuracy was higher in patients with chronic liver disease (16.3%) than in those without (2.1%). CONCLUSION Evaluation of SonoVue enhancement in all three vascular phases is superior to evaluation of SonoVue enhancement in the late phase alone, especially in patients with chronic liver disease.

Non-invasive diagnosis of hepatocellular carcinoma ⩽2 cm in cirrhosis. Diagnostic accuracy assessing fat, capsule and signal intensity at dynamic MRI

BACKGROUND & AIMS To prospectively assess the diagnostic accuracy of the incorporation of additional magnetic resonance imaging (MRI) parameters in those based on contrast enhancement pattern for the diagnosis of solitary nodules between 5 and 20mm, detected during surveillance in patients with cirrhosis. METHODS Between November 2003 and January 2010, we prospectively included 159 cirrhotic patients with a newly detected solitary nodule between 5 and 20mm in diameter by screening ultrasonography (US). Hepatic MRI and fine-needle biopsy were performed in all patients. RESULTS Final diagnoses were hepatocellular carcinoma (HCC) (n=103), other malignant lesions (intrahepatic cholangiocarcinoma/metastases) (n=4), and benign lesions (n=52). The specific enhancement pattern (arterial enhancement followed by washout) yielded a sensitivity and specificity of 58.3% and 96.4%, respectively. Peritumoral capsule was present in 43 HCC and in 2 non-HCC lesions. Intralesional fat was detected in 24 nodules; 5 nodules were non-HCC. Finally, the presence of both capsule and fat was observed in 10 cases, all of them HCC (100% specificity), but all of them also displayed the specific enhancement pattern, thus adding no sensitivity or specificity. CONCLUSIONS Conclusive non-invasive diagnosis of HCC in cirrhosis should be based only on the contrast enhancement pattern, while other characteristics at MRI do not increase the diagnostic accuracy.

Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma

Background and aims Conventional pathological analysis fails to achieve sufficient sensitivity and specificity for the diagnosis of hepatocellular carcinoma (HCC) in small nodules. Immunohistochemical staining for glypican 3 (GPC3), heat shock protein 70 (HSP70) and glutamine synthetase (GS) has been suggested to allow a confident diagnosis but no prospective study has established the diagnostic accuracy of this approach. The aim of this study is to assess prospectively the diagnostic accuracy of a panel of markers (GPC3, HSP70, GS) for the diagnosis of HCC in patients with cirrhosis with a small (5–20 mm) nodule detected by ultrasound screening. Methods Sixty patients with cirrhosis with a single nodule 5–20 mm newly detected by ultrasound were included in the study. Contrast-enhanced ultrasound, magnetic resonance and fine needle biopsy of the nodule (gold standard) were performed; the biopsy was repeated in case of diagnostic failures. Three consecutive sections of the first biopsy sample with meaningful material were stained with antibodies against GPC3, HSP70 and GS. Results Forty patients were diagnosed with HCC. The sensitivity and specificity for HCC diagnosis were: GPC3 57.5% and 95%, HSP70 57.5% and 85%, GS 50% and 90%, respectively. The sensitivity and specificity of the different combinations were: GPC3+HSP70 40% and 100%; GPC3+GS 35% and 100%; HSP70+GS 35% and 100%; GPC3+HSP70+GS 25% and 100%. When at least two of the markers were positive (regardless of which), the sensitivity and specificity were 60% and 100%, respectively. Conventional pathological analysis yielded three false negative results, but the addition of this panel only correctly classified one of these cases as HCC. Conclusion These data within a prospective study establish the clinical usefulness of this panel of markers for the diagnosis of early HCC. However, the panel only slightly increases the diagnostic accuracy in an expert setting.

Characterization of focal liver lesions: comparative study of contrast-enhanced ultrasound versus spiral computed tomography

The purpose of this study was to compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with spiral computed tomography (SCT) for the characterization of focal liver lesions (FLL) and to determine the degree of correlation between the two techniques. Seventy-seven FLL (45 hepatocellular carcinomas; 12 metastases; ten hemangiomas; two regenerating/dysplastic nodules; eight focal nodular hyperplasias) detected with ultrasound (US) were prospectively evaluated by CEUS using a second-generation contrast agent and SCT (with an interval of no more than one month between the two techniques). Independent observers made the most probable diagnosis and the results were compared with the final diagnoses (histology n = 59; MRI n = 18). Statistical analysis was performed by the Chi-square and Kappa tests. CEUS provided a correct, specific diagnosis in 69/77 (90%) of the FLL, while SCT did so in 67/77 (87%). The sensitivity, specificity, and diagnostic accuracy for malignancy were 91%, 90%, and 91%, respectively, for CEUS and 88%, 89%, and 88%, respectively, for SCT. No statistically significant difference was found between CEUS and SCT in the characterization of FLL (p > 0.05). In addition, agreement between the two imaging techniques was good (k = 0.75). We conclude that CEUS and SCT provide a similar diagnostic accuracy in the characterization of FLL, with a good degree of correlation between the two techniques.

Sonographic assessment of regional fat in HIV-1-infected people.

The routine clinical assessment of lipodystrophy in HIV-1-infected patients is hindered by the absence of easy and reliable methods to measure regional fat. We used sonography to measure subcutaneous fat thickness at three reference skin points (periumbilical, brachial, and malar) and intra-abdominal fat thickness in HIV-1-infected patients with and without lipodystrophy and in healthy controls. Patients without lipodystrophy had less subcutaneous fat than uninfected controls. Sonographic assessment of subcutaneous malar and brachial fat in patients with lipodystrophy was more sensitive and specific than that of intra-abdominal fat in the diagnosis of abnormal fat distribution.

Early detection of hepatic artery thrombosis after liver transplantation by Doppler ultrasonography: prognostic implications.

We assessed the usefulness of routine Doppler ultrasonography for early detection of hepatic artery thrombosis after orthotopic liver transplantation and repercussions in patient prognosis. Seventeen confirmed cases of early hepatic artery thrombosis initially diagnosed by Doppler ultrasonography (10 of them before clinical indication) were reviewed. All patients underwent Doppler ultrasonographic studies in the first 3 days after orthotopic liver transplantation. Twelve cases of hepatic artery thrombosis (70.6%) were detected by this early Doppler ultrasonography. All 10 unsuspected cases of hepatic artery thrombosis and 5 of the 7 cases diagnosed after clinical indication were treated by revascularization. Grafts were salvaged in 80% of asymptomatic patients and in 42.8% of symptomatic patients. Furthermore, biliary complications were less serious in the first group. In conclusion, Doppler ultrasonography performed routinely in the first 3 days after orthotopic liver transplantation may permit early detection of hepatic artery thrombosis, even before clinical indications. This allows hepatic artery repermeabilization before liver function damage, improving graft rescue and patient prognosis.