Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive. METHODS: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3). RESULTS: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct. CONCLUSION: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging. CLINICALTRIALS: gov number, NCT03318380.

Screening for hepatocellular carcinoma among adults with HIV/HBV co-infection in Zambia: a pilot study.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). An HCC screening initiative was piloted in an established cohort of individuals co-infected with human immunodeficiency virus (HIV) and HBV on antiretroviral therapy (ART) at two outpatient clinics in Lusaka, Zambia. METHODS: All patients underwent abdominal ultrasound (AUS) and transient elastography. RESULTS: Among 279 patients co-infected with HIV/HBV, 165 (59.1%) were men, median age was 34 years [interquartile range (IQR) 28-39 years] and median CD4 count was 246 cells/µL (IQR 112-355 cells/µL) at ART initiation. While 102 (55.7%) individuals had elevated transaminases, 114 (59.7%) had HBV levels >2000 IU/mL and 59 (24.6%) had significant fibrosis. At their first AUS measurement, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) had periportal fibrosis. Five patients had a liver lesion >1 cm, an indication for confirmatory imaging. CONCLUSIONS: In one of the first HCC screening initiatives in SSA, 2% of patients co-infected with HIV/HBV had significant liver lesions, and one-quarter had findings suggestive of schistosomiasis-induced liver damage.

Liver segmental volume and attenuation ratio (LSVAR) on portal venous CT scans improves the detection of clinically significant liver fibrosis compared to liver segmental volume ratio (LSVR).

BACKGROUND: The aim of this proof-of-concept study was to show that the liver segmental volume and attenuation ratio (LSVAR) improves the detection of significant liver fibrosis on portal venous CT scans by adding the liver vein to cava attenuation (LVCA) to the liver segmental volume ratio (LSVR). MATERIAL AND METHODS: Patients who underwent portal venous phase abdominal CT scans and MR elastography (reference standard) within 3 months between 02/2016 and 05/2017 were included. The LSVAR was calculated on portal venous CT scans as LSVR*LVCA, while the LSVR represented the volume ratio between Couinaud segments I-III and IV-VIII, and the LVCA represented the density of the liver veins compared to the density in the vena cava. The LSVAR and LSVR were compared between patients with and without significantly elevated liver stiffness (based on a cutoff value of 3.5 kPa) using the Mann-Whitney U test and ROC curve analysis. RESULTS: The LSVR and LSVAR allowed significant differentiation between patients with (n = 19) and without (n = 122) significantly elevated liver stiffness (p < 0.001). However, the LSVAR showed a higher area under the curve (AUC = 0.96) than the LSVR (AUC = 0.74). The optimal cutoff value was 0.34 for the LSVR, which detected clinically increased liver stiffness with a sensitivity of 53% and a specificity of 88%. With a cutoff value of 0.67 for the LSVAR, the sensitivity increased to 95% while maintaining a specificity of 89%. CONCLUSION: The LSVAR improves the detection of significant liver fibrosis on portal venous CT scans compared to the LSVR.

Liver MR relaxometry at 3T - segmental normal T1 and T2* values in patients without focal or diffuse liver disease and in patients with increased liver fat and elevated liver stiffness.

Magnetic resonance (MR) T1 and T2* mapping allows quantification of liver relaxation times for non-invasive characterization of diffuse liver disease. We hypothesized that liver relaxation times are not only influenced by liver fibrosis, inflammation and fat, but also by air in liver segments adjacent to the lung - especially in MR imaging at 3T. A total of 161 study participants were recruited, while 6 patients had to be excluded due to claustrophobia or technically uninterpretable MR elastography. Resulting study population consisted of 12 healthy volunteers and 143 patients who prospectively underwent multiparametric MR imaging at 3T. Of those 143 patients, 79 had normal liver stiffness in MR elastography (shear modulus <2.8 kPa, indicating absence of fibrosis) and normal proton density fat fraction (PDFF < 10%, indicating absence of steatosis), defined as reference population. T1 relaxation times in these patients were significantly shorter in liver segments adjacent to the lung than in those not adjacent to the lung (p < 0.001, mean of differences 33 ms). In liver segments not adjacent to the lung, T1 allowed to differentiate significantly between the reference population and patients with steatosis and/or fibrosis (p ≤ 0.011), while there was no significant difference of T1 between the reference population and healthy volunteers. In conclusion, we propose to measure T1 relaxation times in liver segments not adjacent to the lung. Otherwise, we recommend taking into account slightly shorter T1 values in liver segments adjacent to the lung.

Cuantificación de la fibrosis hepática mediante biomarcadores de imagen / Imaging biomarkers in liver fibrosis

La creciente prevalencia y la morbimortalidad de las enfermedades crónicas del hígado justifican la necesidad de identificar precozmente la fibrosis. El grado de fibrosis hepática determina el pronóstico y sus opciones terapéuticas. Actualmente, la biopsia hepática representa el patrón de referencia para la estadificación de la fibrosis. Sin embargo, sus limitaciones y complicaciones han forzado el desarrollo de distintos métodos incruentos para la cuantificación de la fibrosis in vivo. Por su precisión y fiabilidad, destacan las mediciones de biomarcadores derivados de la ecografía y la resonancia magnética. Este artículo realiza una revisión de las distintas técnicas actualmente empleadas en la evaluación de la fibrosis hepática, su rendimiento diagnóstico, su aplicabilidad y su uso clínico. Para interpretar correctamente sus resultados en el contexto clínico apropiado, es necesario comprender estas técnicas de imagen y sus parámetros de calidad, la estandarización y la validación de sus unidades, y las medidas de control de los problemas metodológicos (AU)

There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers’ measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems (AU)

Imaging biomarkers in liver fibrosis. / Cuantificación de la fibrosis hepática mediante biomarcadores de imagen.

There is a need for early identification of patients with chronic liver diseases due to their increasing prevalence and morbidity-mortality. The degree of liver fibrosis determines the prognosis and therapeutic options in this population. Liver biopsy represents the reference standard for fibrosis staging. However, given its limitations and complications, different non-invasive methods have been developed recently for the in vivo quantification of fibrosis. Due to their precision and reliability, biomarkers' measurements derived from Ultrasound and Magnetic Resonance stand out. This article reviews the different acquisition techniques and image processing methods currently used in the evaluation of liver fibrosis, focusing on their diagnostic performance, applicability and clinical value. In order to properly interpret their results in the appropriate clinical context, it seems necessary to understand the techniques and their quality parameters, the standardization and validation of the measurement units and the quality control of the methodological problems.

Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado / Vascular diseases of the liver. Clinical Guidelines from the Catalan Society of Digestology and the Spanish Association for the Study of the Liver

Las enfermedades vasculares hepáticas, a pesar de su relativamente baja prevalencia, representan un problema de salud importante en el campo de las enfermedades hepáticas. Una característica común a muchas de estas enfermedades es que pueden causar hipertensión portal, con la elevada morbimortalidad que ello conlleva. Con frecuencia estas enfermedades se diagnostican en pacientes jóvenes y el retraso en su diagnóstico y/o un tratamiento inadecuado pueden reducir de forma importante la esperanza de vida. El presente artículo revisa la evidencia actual en el síndrome de Budd-Chiari, la trombosis venosa portal en pacientes no cirróticos, la hipertensión portal idiopática, el síndrome de obstrucción sinusoidal, las malformaciones vasculares hepáticas en la telangiectasia hemorrágica hereditaria, la trombosis portal en la cirrosis, otras patologías vasculares menos frecuentes como las fístulas arterioportales, así como un apartado sobre el diagnóstico por imagen de las enfermedades vasculares hepáticas y su tratamiento desde el punto de vista hematológico (estudio de la diátesis trombótica y tratamiento anticoagulante). Las recomendaciones se han realizado de acuerdo a los estudios publicados extraídos de Pubmed. La calidad de la evidencia y la intensidad de las recomendaciones fueron graduadas de acuerdo al sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). Cuando no existían evidencias suficientes, las recomendaciones se basaron en la opinión del comité que redactó la guía.

Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.

Age dependency of regional impedance indices regardless of clinical stage in patients with cirrhosis of the liver.

PURPOSE: To prospectively assess if ageing itself induces modifications of the impedance indices (resistance and pulsatility indexes) of hepatic, splenic, superior mesenteric and renal arteries in patients with liver cirrhosis. MATERIALS AND METHODS: 78 consecutive patients with cirrhosis (41 males, 37 females, Child-Pugh score 7 [range 5 - 12]) were studied by colour-Doppler ultrasound. The resistance index (RI) and pulsatility index (PI) were determined in the main hepatic artery, intraparenchymal branches of hepatic, splenic, and renal arteries, and superior mesenteric artery; clinical data were simultaneously collected. Logistic regression analysis was performed to assess the relative impact of age, severity of liver disease and other relevant variables on the increase of impedance indices. Linear regression analysis was used to identify a coefficient to adjust RIs and PIs to age. RESULTS: Resistance and pulsatility indices of all the vessels studied except of the superior mesenteric artery showed a direct correlation with age (e. g. splenic artery RI: R = 0.520, p < 0.0001), and correlated most strongly with Child-Pugh score (e. g. right renal artery PI: R = 0.462, p < 0.0001). Age was associated independently with increased PI and RI in hepatic, splenic and renal arterial districts. In these vessels, the RI threshold of normality can be adjusted to the decade of age adding a correction of 0.03. CONCLUSION: Ageing itself induces an increase of hepatic, splenic and renal impedance indices in cirrhotic patients. The threshold of normality for these indices in cirrhosis should be adjusted according to the patients' age.

"Torsade de pointes" during amiodarone infusion in a cirrhotic woman with a prolonged QT interval.

We describe an interesting case of a woman with decompensated cirrhosis, ischaemic heart disease and prolonged QT interval, who developed a new-onset atrial fibrillation. During amiodarone infusion a torsade de pointes occurred, which was immediately converted to sinus rhythm by synchronized cardioversion. A new episode of atrial fibrillation was treated with infusion of a beta-blocker (metoprolol) that restored sinus rhythm and normalized the QT interval. Delayed repolarization, frequently observed in ischaemic heart disease, cirrhosis and pro-arrhythmic drugs administration, represents the background for the development of torsade de pointes. Our report underlines that the potential harmfulness of a prolonged QT interval in cirrhotic patients is currently not perceived in its entirety, so that various categories of drugs affecting ventricular repolarization are rather thoughtlessly used in clinical practice without monitoring the QT interval. Thus, amiodarone should be avoided, if possible, or used with extreme care in arrhythmic patients with advanced liver disease. Moreover, beta-blockers may be considered the first-line treatment for rate-control during supraventricular tachyarrhythmias in cirrhotic patients with delayed repolarization.

Prevention of recurrent variceal bleeding.

Patients surviving a first episode of variceal bleeding have a risk of over 60% of experiencing recurrent haemorrhages within 1 year from the index episode. Because of this, all patients surviving a variceal bleeding should receive active treatments for the prevention of rebleeding. beta-Blockers+/-isosorbide-5-mononitrate and band ligation are effective in preventing recurrent bleeding and both can be used. Combination of beta-blockers+/-isosorbide-5-mononitrate and band ligation may be the best treatment to prevent rebleeding but more studies are needed to confirm this issue. In patients with recurrent variceal bleeding despite appropriate medical and endoscopic treatment, transjugular intrahepatic porto-systemic shunt is highly effective in controlling bleeding. The efficacy is not significantly different from that of shunt surgery (distal splenorenal shunt or 8mm H-graft shunt), especially since the introduction of polytetrafluoroethylene-covered stents. Therefore, in this situation, transjugular intrahepatic porto-systemic shunt using polytetrafluoroethylene stents should be the treatment of choice.

New abdominal collaterals at ultrasound: a clue of progression of portal hypertension.

BACKGROUND: Abdominal ultrasound can detect non-invasively the presence of abdominal portal-systemic collaterals in patients with liver cirrhosis. Abdominal portal-systemic collaterals may be protective from the formation and growth of oesophageal varices, but available data are inconclusive. AIM: We aimed at investigating the relationship between abdominal portal-systemic collaterals and variceal formation and growth. METHODS: We studied 126 cirrhotic patients without (n=43) or with small (n=83) oesophageal varices who entered a protocol of serial ultrasonographic and endoscopic examinations for a median of 55 months. Presence and kind of abdominal portal-systemic collaterals was recorded on first ultrasonography and on each control thereafter. RESULTS: At inclusion, abdominal portal-systemic collaterals were found in 19/43 patients without varices and in 23/83 patients with small varices (NS). There was no difference in variceal formation and growth between patients with and without abdominal portal-systemic collaterals at inclusion. However, patients developing new abdominal portal-systemic collaterals during follow-up had a significantly higher rate of variceal formation (56.2% vs. 22.2%; p=0.024) and growth (52.9% vs. 30.6%; p=0.041) compared with patients with unchanged ultrasonography. CONCLUSIONS: Abdominal collaterals are not protective from the formation or growth of oesophageal varices. Conversely, new abdominal portal-systemic collaterals emergence is a non-invasive clue of formation and progression of varices. Therefore, endoscopy is probably indicated whenever new abdominal portal-systemic collaterals are detected in cirrhotic patients.

Octreotide in the outpatient therapy of cirrhotic chylous ascites: a case report.

Chylous ascites is a rare complication of liver cirrhosis associated with a poor short-term prognosis. We report the case of an 80-year-old male cirrhotic patient with refractory chylous ascites associated with portal hypertension. He was treated with total parenteral nutrition but chylous ascites relapsed at suspension. Patient was put on long-term subcutaneous octreotide (100 microg t.i.d.) as an outpatient. The treatment was well tolerated and led to clinical improvement, markedly reducing the need of total paracentesis and the amount of ascites. Octreotide was stopped after 6 months, and massive ascites did not relapse. After 1 year the patient was alive, with no need of paracentesis. Octreotide therapy should be considered in patients with cirrhosis and chylous ascites to simplify the outpatient management of the disease.

Splanchnic haemodynamics in non-alcoholic fatty liver disease: effect of a dietary/pharmacological treatment. A pilot study.

BACKGROUND: Previous studies demonstrated that in experimental animals fatty liver is associated with reduced hepatic blood flow and that metformin reverses steatosis, while no data were reported in humans. AIMS: To evaluate the clinical relevance of echo-Doppler measurements and the effects of therapy in non-alcoholic fatty liver disease. PATIENTS: Twenty patients with biopsy proven non-alcoholic fatty liver disease. METHODS: Abdominal echo-Doppler examination was performed at enrolment and, in 11 patients, after 6 months of dietary/pharmacological therapy (metformin 500 mg three times a day). RESULTS: Non-alcoholic fatty liver disease was characterised by hepatomegaly, bright echotexture and posterior attenuation. Mean portal blood velocity and flow were low-normal. Brightness and posterior attenuation significantly correlated with fat score in liver biopsies as well as with the hepatic veins spectrum. After therapy, echotexture improved and liver volume significantly decreased. Portal blood velocity and flow significantly increased, intrahepatic arterial indexes decreased and the spectrum of hepatic veins improved. CONCLUSIONS: Fatty liver is associated with an impaired hepatic blood flow characterised by increased intrahepatic resistances. Vascular changes are reversed by treatment and can be measured by echo-Doppler which may be useful to evaluate the natural course of non-alcoholic fatty liver disease, and to monitor the putative beneficial effects of therapy.

Splanchnic haemodynamics in patients with coeliac disease: effects of a gluten-free diet.

BACKGROUND: Coeliac disease is characterized by structural and functional changes in the small bowel which may also result in haemodynamic changes. AIMS: To establish whether splanchnic haemodynamics can be modified by a gluten-free diet. PATIENTS: Ten coeliac patients and 10 paired healthy subjects. METHODS: Echo-Doppler measurements were made of splanchnic vessels both fasting and after a standard meal before and after 9 months of a gluten-free diet. RESULTS: In comparison to controls, coeliac patients had higher superior mesenteric artery blood velocity and flow, with lower resistance indexes and higher portal vein velocity and flow, particularly 3 h after a meal. Postprandial hyperaemia was reduced and delayed in time. Intrasplenic resistance indexes were also significantly lower both fasting and after a meal. After 9 months of a gluten-free diet, no significant differences were observed between coeliac patients and controls, both fasting and after a meal. CONCLUSIONS: Splanchnic haemodynamics is significantly changed in coeliac patients, mainly after a meal. On treatment with a gluten-free diet, both fasting and postprandial haemodynamics became normal.