Predicting portal thrombosis in cirrhosis: A prospective study of clinical, ultrasonographic and hemostatic factors.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis. METHODS: We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography. RESULTS: Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found. CONCLUSIONS: In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis. LAY SUMMARY: Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.

Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH / Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH

El carcinoma hepatocelular es la neoplasia primaria de hígado más común y una de las causas de muerte más frecuentes en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos años han aparecido novedades importantes en el diagnóstico, estadificación y tratamiento del carcinoma hepatocelular. Por tal motivo, desde la Asociación Española para el Estudio del Hígado se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento (la Sociedad Española de Trasplante Hepático, la Sociedad Española de Radiología Médica, la Sociedad Española de Radiología Vascular e Intervencionista y la Sociedad Española de Oncología Médica). Se ha tomado como documento de referencia las guías de práctica clínica publicadas en 2009 aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos años. La evidencia científica en el tratamiento del carcinoma hepatocelular se ha evaluado de acuerdo con las recomendaciones del National Cancer Institute (www.cancer.gov) y la fuerza de la recomendación se basa en el sistema GRADE (AU)

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system (AU)

[Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH]. / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH.

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.

Intraperitoneal Administration of Autologous Tolerogenic Dendritic Cells for Refractory Crohn's Disease: A Phase I Study.

BACKGROUND AND AIMS: Ex vivo-generated autologous tolerogenic dendritic cells [tolDCs] can restore immune tolerance in experimental colitis. The aim of this study was to determine the safety and tolerability of administration of autologous tolDCs in refractory Crohn's disease [CD] patients. METHODS: A phase-I, single-centre, sequential-cohorts, dose-range study was designed. Stable tolDCs were generated ex vivo from monocytes following a previously developed protocol, and administered by sonography-guided intraperitoneal injection. Six sequential refractory-CD cohorts were established: the first three cohorts received a single intraperitoneal injection of tolDCs at escalating doses [2 x 10(6)/5 x 10(6)/10 x 10(6)]; and the last three cohorts received three biweekly intraperitoneal injections at same escalating doses. Safety was sequentially evaluated. Patients were assessed from week 0 to 12 and followed up for 1-year period for safety. RESULTS: Nine patients were included. No adverse effects were detected during tolDC injection or follow-up. Three patients withdrew from the study due to CD worsening. Crohn's Disease Activity Index [CDAI] decreased from 274 [60] {mean (standard deviation [SD])} to 222 [113] [p = 0.3]; one [11%] patient reached clinical remission [CDAI < 150] and two [22%] clinical response [CDAI decrease ≥ 100]. Crohn's Disease Endoscopic Index of Severity [CDEIS] decreased from 18 [5] to 13 [8] [p = 0.4]; lesions improved markedly in three patients [33%]. Quality of life (inflammatory bowel disease questionnaire [IBDQ]) changed from 125 [27] to 131 [38] [p = 0.7]; remission [IBDQ at Week 12 ≥ 170] was reached in one [11%] case and response [IBDQ score increase ≥ 16] in two [22%]. CONCLUSIONS: Intraperitoneal administration of autologous tolDCs appears safe and feasible in refractory CD patients. Further studies should be developed to test clinical benefit, determine the optimal administration route and dose, and monitor the immune responses; See [www.eudract.ema.europa.eu, EudraCT number 2007-003469-42; www.aemps.gob.es number PEI 08-049].

Lack of arterial hypervascularity at contrast-enhanced ultrasound should not define the priority for diagnostic work-up of nodules <2 cm.

BACKGROUND & AIMS: Current guidelines recommend diagnostic work-up for nodules >1cm detected during screening for hepatocellular carcinoma (HCC). This implies that patients with benign conditions may undergo unnecessary evaluation and those with small nodules may be intervened too early, leading to overdiagnosis. Since increased arterial vascularization is the hallmark of malignancy, its detection by contrast-enhanced ultrasound (CEUS) could become the signal to proceed with diagnosis confirmation. The aim was to assess if HCCs <2 cm without arterial hyperenhancement by baseline CEUS have a benign evolutionary profile, suggesting that diagnosis and invasive treatment could be delayed until detection of an overt malignant profile, associated with increased vascularization. METHODS: We prospectively included 168 cirrhotic patients with a newly detected solitary nodule of 5-20mm by screening ultrasonography. MRI, CEUS and fine needle biopsy (FNB) were performed and if no confident diagnosis was obtained, patients were closely followed to rule out HCC. Final diagnosis was: HCC (n = 119), cholangiocarcinoma (n = 3), neuroendocrine tumour (n = 1) and benign lesions (n = 45). RESULTS: CEUS did not detect contrast hyperenhancement in the arterial phase in 55 cases (34%). Eighteen out of these 55 nodules were diagnosed as HCC. Non-CEUS hyperenhanced HCCs were more frequently well-differentiated than CEUS-hyperenhanced HCCs (p < 0.004). Fourteen patients were treated with ablation and 4 with resection. Ten (55.6%) patients experienced tumour recurrence after treatment, mostly distant, confirming their overt malignant profile. CONCLUSIONS: Absence of contrast hyperenhancement on CEUS during the arterial phase in nodules <2 cm in a cirrhotic liver does not predict a less malignant profile. Accordingly, priority for diagnostic work-up and treatment should not differ according to contrast profiles on CEUS.

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

UNLABELLED: 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.

Percutaneous ethanol injection before liver transplantation in the hepatocellular carcinoma.

BACKGROUND/OBJECTIVES: The study evaluates the outcome of patients who performed orthotopic liver transplantation (LT) as treatment for hepatocellular carcinoma (HCC), with percutaneous ethanol injection (PEI) while on the waiting list, verifying the effectiveness of this treatment in producing tumor necrosis and avoiding dropout and identifying treatment-related complications. MATERIAL AND METHODS: Medical records of 97 patients on the waiting list for LT at Hospital Clinic of Barcelona were examined. Sixty-two (56.3%) patients had been treated with PEI (group 1); 35 (31.8%) had not received any anti-tumor therapy before LT (group 2). RESULTS: Complete necrosis of the tumor was observed in 38/59 (64.3%) patients. The presence of additional nodules in the explant and the diameter of the main tumor of group 1 was significantly lower than in group 2 (p = 0.002). Dropout related to tumor progression occurred in 4.8% and 8.5%, and tumor recurrence in 5% and 6.2% for groups 1 and 2, respectively. Major complications were not evidenced after 421 PEI sessions and there was no tumor implant in the needle traject. CONCLUSIONS: In conclusion, the percutaneous treatment of HCC with PEI is a safe and effective method before the LT.

Diagnóstico y tratamiento del carcinoma hepatocelular / Diagnosis and treatment of hepatocellular carcinoma

No disponible

No disponible

Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma.

This study prospectively evaluates the accuracy of contrast-enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine-needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines.

Early-stage hepatocellular carcinoma: the high accuracy of real-time contrast-enhanced ultrasonography in the assessment of response to percutaneous treatment.

Image-guided tumor ablation has a major role in the therapeutic management of hepatocellular carcinoma and the assessment of the efficacy of percutaneous ablation is crucial for the management of cirrhotic patients. Contrast-enhanced ultrasonography (CEUS) is extremely sensitive in detecting the intratumoral microvasculature in real time, with the same sensitivity in the detection of residual HCC as CT. CEUS has some advantages. It can be used before and during the ablative procedure as a guide for percutaneous needle placement. Moreover, CEUS can be performed almost immediately after ablation to determine whether the tumor has been completely ablated or needs additional treatment that can be performed in the same session, improving the cost-effectiveness of the treatment.

Sonography of Budd-Chiari syndrome.

OBJECTIVE: The purpose of this pictorial essay is to review the color Doppler sonographic features of Budd-Chari syndrome. CONCLUSION: Combining color and spectral data, sonography provides hemodynamic and anatomic information about vessel patency and collateral vessel formation. The diagnosis of Budd-Chari syndrome is based on the involvement of hepatic veins although intrahepatic collateral circulation and dilated caudate veins are also important and frequent signs. Half of the patients will develop regenerative nodules that can simulate hepatocellular carcinoma.

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.

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome.

OBJECTIVE: To determine the prevalence of preclinical vascular disease and associated risk factors in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). METHODS: We consecutively studied 70 SLE patients and 25 primary APS patients without clinical coronary artery disease. The control group included 40 healthy women. Carotid ultrasound was performed and the intima-media wall thickness (IMT) and presence of plaque was investigated in all patients and controls. Traditional vascular risk factors and SLE-disease and treatment related factors were also analysed. RESULTS: SLE patients had a higher prevalence of traditional atherosclerosis risk factors: hypertension (P<0.005) and dyslipidaemia (P<0.05) and higher levels of total cholesterol (P = 0.03), triglycerides (P = 0.004) and apolipoprotein B (P = 0.04). The prevalence of carotid plaque was higher and appeared earlier in SLE patients than in the primary APS patients or controls (P<0.001). The IMT was similar in the three groups. SLE patients with secondary APS had a higher prevalence of carotid plaque than patients with primary APS (37.5% vs 8%, P = 0.03). The presence of plaque in SLE patients was associated with a higher SLICC score (2.40 +/- 1.78 vs 1.02 +/- 1.18, P = 0.002), higher ECLAM score (3.10 +/- 2.32 vs 1.84 +/- 1.59, P = 0.02) and older age (47.3 +/- 8.44 vs 37.38 +/- 11.28, P = 0.003) at the time of carotid ultrasound study. CONCLUSION: Plaque prevalence in patients with primary APS is similar to that of controls and inferior to that of SLE patients with secondary APS. SLE patients have a high prevalence of early carotid atherosclerosis that is associated with cumulative disease damage and disease activity.

A tele-operated mobile ultrasound scanner using a light-weight robot.

This paper presents a new tele-operated robotic chain for real-time ultrasound image acquisition and medical diagnosis. This system has been developed in the frame of the Mobile Tele-Echography Using an Ultralight Robot European Project. A light-weight six degrees-of-freedom serial robot, with a remote center of motion, has been specially designed for this application. It holds and moves a real probe on a distant patient according to the expert gesture and permits an image acquisition using a standard ultrasound device. The combination of mechanical structure choice for the robot and dedicated control law, particularly nearby the singular configuration allows a good path following and a robotized gesture accuracy. The choice of compression techniques for image transmission enables a compromise between flow and quality. These combined approaches, for robotics and image processing, enable the medical specialist to better control the remote ultrasound probe holder system and to receive stable and good quality ultrasound images to make a diagnosis via any type of communication link from terrestrial to satellite. Clinical tests have been performed since April 2003. They used both satellite or Integrated Services Digital Network lines with a theoretical bandwidth of 384 Kb/s. They showed the tele-echography system helped to identify 66% of lesions and 83% of symptomatic pathologies.

Utility of color Doppler ultrasonography predicting tips dysfunction.

OBJECTIVES: Color Doppler ultrasonography (CDUS) has been proposed as an alternative to portal pressure gradient (PPG) measurement to detect transjugular intrahepatic portosystemic shunt (TIPS) dysfunction but with inconsistent results. This study aimed at developing and validating CDUS criteria to assess TIPS dysfunction. METHODS: A total of 117 consecutive follow-up simultaneous CDUS and hemodynamic evaluations in 34 patients with TIPS were analyzed. TIPS dysfunction was defined as a PPG >12 mmHg. A predictive model was obtained with logistic regression and was validated in an independent, prospective sample of 119 consecutive paired CDUS/hemodynamic evaluations in 55 patients. RESULTS: TIPS dysfunction was present in 57 of the 117 studies in the retrospective series. At multivariate analysis, mean maximum flow velocity at the portal vein (mVPmax) and direction of flow in the intrahepatic portal vein branches (FD) were the only independent predictors of TIPS dysfunction. The prediction rule for TIPS dysfunction derived from the model (mVPmax <28 cm/s when flow is hepatofugal or mVPmax <39 cm/s when flow is hepatopetal) had 90% sensitivity, 45% specificity, and negative likelihood ratio of 0.23. This prediction rule was validated both in patients with bare stents and in patients with polytetra fluoroethylene (PTFE)-covered stents, showing an overall 87% sensitivity, 57% specificity, and 0.23 negative likelihood ratio. CONCLUSIONS: The combination of two CDUS parameters correlate with TIPS dysfunction with high sensitivity and low specificity but with a good negative likelihood ratio. TIPS catheterization can be safely avoided in half of the patients using this predictive rule.

Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.

Outcome predictors in patients with hepatocellular carcinoma (HCC) who are treated with percutaneous ablation are ill defined, and it is unknown if successful therapy is associated with improved survival. In our study, 282 cirrhotic patients with early nonsurgical HCC were treated with percutaneous ablation during a 15-year period. Single tumors were seen in 244 patients, and 2 to 3 nodules were seen in 38 patients. Initial complete response was achieved in 192 patients and was independently related to the size of the main tumor (P = .015) and tumor stage (P = .0001) (< or =2 cm, 96%; 2.1-3 cm, 78%; >3 cm, 56%; 2-3 nodules, 46%). At the end of follow-up, 80 patients presented sustained complete response. The 1-, 3-, and 5-year survival rates were 87%, 51%, and 27%, respectively. The independent predictors of survival were Child-Turcotte-Pugh class (P = .0001) and initial complete response (P = .006). Child-Turcotte-Pugh class A patients with initial complete response achieved 42% survival at 5 years; this figure increased to 63% in patients with tumors 2 cm or smaller. In conclusion, our results demonstrate that initial complete response to percutaneous ablation is associated with an improved survival in both Child-Turcotte-Pugh class A and B patients with nonsurgical HCC. Accordingly, initial complete tumor necrosis should be considered a relevant therapeutic target irrespective of tumor size and liver function.

High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation.

Surgical resection and liver transplantation offer a 5-year survival greater than 70% in patients with hepatocellular carcinoma, but the high recurrence rate impairs long-term outcome after resection. Pathological data such as vascular invasion and detection of additional nodules predict recurrence and divide patients into high and low risk profile. Based on this, we proposed salvage liver transplant to resected patients in whom pathology evidenced high recurrence risk even in the absence of proven residual disease. From January 1995 to August 2003 we have evaluated 1,638 patients. Resection was indicated in 77 patients, but only 17 (22%) (all cirrhotics, 14 hepatitis C virus+) were optimal candidates for both resection and transplantation. Of them, 8 exhibited a high risk profile at pathology and were offered transplantation. Among the 8 high risk patients, 7 presented recurrence, compared with only 2 of the 9 at low risk (P = .012). Two of the high risk patients refused transplant and developed multifocal disease during follow-up. The other 6 were enlisted and all but 1 had tumor foci in the explant. Only 1 presented extrahepatic dissemination early after transplant and died 4 months later. The others are free of disease after a median follow-up of 45 months. Two recurrences were detected in low risk patients, 1 of them being transplanted 18 months after surgery. These data in a small series of patients confirm that pathological parameters identify patients at higher risk of recurrence, which allow them to be listed for liver transplantation without proven malignant disease. In conclusion, this policy is clinically effective and could further improve the outcome of resected patients.

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.