Association of modifiable metabolic risk factors and lifestyle with all-cause mortality in patients with hepatocellular carcinoma.

We aimed to investigate the potential impact of metabolic risk factors and lifestyles on mortality in hepatocellular carcinoma (HCC) patients. From the Korean Central Cancer Registry database (2008-2016), 8,505 HCC patients were included in the analysis. Patients with 2 or more metabolic risk factors (n = 2384, 28.0%) showed significantly worse overall survival (OS, 29 months, 95% confidence interval [CI] 27-33) than patients with 0 (n = 2269 [26.7%]; 41 months, 95% CI 37-47), or 1 (n = 3852 [45.3%]; 42 months; 95% CI 38-46) metabolic risk factor. (P < 0.001) In the multivariable Cox analysis, patients with ≥ 2 metabolic risk factors had significantly elevated risk of overall mortality (adjusted hazards ratio (HR) = 1.14 [95% CI 1.06-1.23], P < 0.001) and HCC-specific mortality (sub-distribution HR = 1.09 [95% CI 1.00-1.09], P = 0.046), compared to those without. Alcohol and smoking were also independent risk factors for worse overall and HCC-specific mortality (all P < 0.05). Metabolic comorbidities were associated with greater risk of mortality in a dose-dependent manner in HCC patients, regardless of tumor stage and liver function. Alcohol intake and smoking significantly increased mortality by themselves and even further with the presence of metabolic risk.

Effect of Direct Acting Antiviral Drugs on the Occurrence and Recurrence of Intra- and Extra-Hepatic Malignancies in Patients with Chronic Hepatitis C Virus Infection.

Introduction: The use of direct-acting antivirals (DAAs) has drastically changed the management of HCV-infected patients by achieving a 95-98% sustained virologic response (SVR) and reducing morbidity and mortality in this population. However, despite their effectiveness, controversy exists concerning the occurrence of oncologic events following DAA therapy. Aims and Methods: A retrospective analysis was conducted on data from the Swiss Hepatitis C Cohort Study, a prospective cohort involving patients with positive HCV viremia upon inclusion, enrolled in various Swiss centers from September 2000 to November 2021. To examine potential differences in the risk of intrahepatic tumor (IHT) occurrence and death among patients treated with direct-acting antivirals (DAAs), untreated patients, and those receiving interferon (IFN)-based therapy, a semiparametric competing risk proportional hazards regression model was used. Results: Among 4082 patients (63.1% male, median age 45 years; genotype 1: 54.1%; cirrhosis: 16.1%), 1026 received exclusive treatment with IFN-based regimens, and 1180 were treated solely with DAAs. Over a median follow-up of 7.8 years (range: 3.8-11.9), 179 patients (4.4%) developed intrahepatic tumors (IHT), and 168 (4.1%) experienced extrahepatic tumors (EHT). The 5-year cumulative incidence of IHT was 1.55% (95% CI 0.96-2.48) for IFN-based therapy, 4.27% (95% CI 2.93-6.2) for DAA and 0.89% (95% CI 0.4-1.99) for untreated patients. There was no statistically significant difference in the risk of developing IHT (HR = 1.34; 95% CI = [0.70; 2.58]; p = 0.380) or death (HR = 0.66; 95% CI = [0.43; 1.03]; p = 0.066) between patients treated with DAAs and those treated with IFN. Conclusions: The DAAs reduced the risk of death and were not associated with an increased risk of extrahepatic tumors (EHT). In the adjusted model, accounting for cirrhosis and high liver stiffness, the DAA treatment was associated with a higher risk of IHT occurrence compared with untreated patients, emphasizing the relevance of implementing standardized hepatocellular carcinoma (HCC) screening post-DAA treatment.

Regional Differences in Clinical Presentation and Prognosis of Patients With Post-Sustained Virologic Response Hepatocellular Carcinoma.

BACKGROUND & AIMS: Widespread use of direct-acting antivirals for hepatitis C virus infection has been paralleled with increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response (post-SVR HCC) worldwide. Few data compare regional differences in the presentation and prognosis of patients with post-SVR HCC. METHODS: We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March 2015 and October 2021 from 30 sites in Europe, North America, South America, the Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. RESULTS: Among 8796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of patients detected by surveillance (range: 59.5%-100%), median maximum tumor diameter (range, 1.8-5.0 cm), and the proportion with multinodular HCC (range, 15.4%-60.8%). The prognosis of patients highly varied by region (hazard ratio range, 1.82-9.92), with the highest survival rates in East Asia, North America, and South America, and the lowest survival rates in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early stage detection (Barcelona Clinic Liver Cancer stage 0/A, 71.0% vs 21.3%; P < .0001) and lower mortality rates (adjusted hazard ratio, 0.29; 95% CI, 0.18-0.46). CONCLUSIONS: Clinical characteristics, including early stage detection, and prognosis of post-SVR HCC differed significantly across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally.

Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma.

Background & Aims: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. Methods: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. Results: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. Conclusions: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. Impact and implications: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy.

Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma.

BACKGROUND & AIMS: Single-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1. METHODS: Overall, 111 tumor samples from patients with aHCC were obtained from 13 centers before systemic therapies. We performed molecular analysis and immune deconvolution using whole-genome expression data (n = 83), mutational analysis (n = 72), and histologic evaluation with an endpoint of objective response. RESULTS: Among 83 patients with transcriptomic data, 28 were treated in frontline, whereas 55 patients were treated after tyrosine kinase inhibitors (TKI) either in second or third line. Responders treated in frontline showed upregulated interferon-γ signaling and major histocompatibility complex II-related antigen presentation. We generated an 11-gene signature (IFNAP), capturing these molecular features, which predicts response and survival in patients treated with anti-PD1 in frontline. The signature was validated in a separate cohort of aHCC and >240 patients with other solid cancer types where it also predicted response and survival. Of note, the same signature was unable to predict response in archival tissue of patients treated with frontline TKIs, highlighting the need for fresh biopsies before immunotherapy. CONCLUSION: Interferon signaling and major histocompatibility complex-related genes are key molecular features of HCCs responding to anti-PD1. A novel 11-gene signature predicts response in frontline aHCC, but not in patients pretreated with TKIs. These results must be confirmed in prospective studies and highlights the need for biopsies before immunotherapy to identify biomarkers of response.

What Is the Role of Body Composition Assessment in HCC Management?

In the last decade, body composition (BC) assessment has emerged as an innovative tool that can offer valuable data concerning nutritional status in addition to the information provided by the classical parameters (i.e., body mass index, albumin). Furthermore, published data have revealed that different types of body composition are associated with different outcomes. For example, abnormalities of skeletal muscle, a common finding in cirrhotic and oncologic patients, are associated with poor outcome (i.e., high morbidity and high mortality). The disposition (visceral/subcutaneous adipose tissue) and radiodensity of adipose tissue proved to also be determinant factors for HCC outcome. Despite all the advantages, BC assessment is not part of the standard pre-therapeutic workup. The main reasons are the high heterogeneity of data, the paucity of prospective studies, the lack of a standard assessment method, and the interpopulation variation of BC. This paper aims to review the available evidence regarding the role of BC as a prognostic tool in the HCC population undergoing various therapies.

Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score.

BACKGROUND & AIMS: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need. METHODS: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). We investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n = 204). RESULTS: Baseline serum alpha-fetoprotein ≥100 ng/ml (hazard ratio [HR] 1.7; p = 0.007) and C-reactive protein ≥1 mg/dl (HR, 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95% CI 19.5-35.8) months), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 (95% CI 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95% CI 4.8-8.1) months; p <0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and ≥1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response. CONCLUSIONS: The CRAFITY score is associated with survival and radiological response in patients receiving PD-(L)1 immunotherapy. The score may help with patient counseling but requires prospective validation. LAY SUMMARY: The immunotherapy-based regimen of atezolizumab plus bevacizumab represents the new standard of care in systemic first-line therapy of hepatocellular carcinoma (HCC). Biomarkers to predict treatment outcome are an unmet need in patients undergoing immunotherapy for HCC. We developed and externally validated a score that predicts outcome in patients with HCC undergoing immunotherapy with immune checkpoint blockers.

Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention.

In many countries worldwide, the burden of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing. Preventive strategies are needed to counteract this trend. In this review, we provide an overview of the evidence on preventive strategies in NAFLD-associated HCC. We consider the impact of lifestyle factors such as weight loss, physical activity, smoking, dietary patterns and food items, including coffee and alcohol, on both HCC and NAFLD/NASH. Furthermore, evidence on chemopreventive treatments, including aspirin, antidiabetic treatments and statins is summarised. The role of adjuvant therapies for tertiary prevention of HCC is briefly reviewed.

Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort.

BACKGROUND AND AIMS: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. METHODS: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients' characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. RESULTS: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%). CONCLUSION: Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease - in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to that reported in the phase 3 trial (CELESTIAL).

Combined treatments in hepatocellular carcinoma: Time to put them in the guidelines?

The time for battling cancer has never been more suitable than nowadays and fortunately against hepatocellular carcinoma (HCC) we do have a far-reaching arsenal. Moreover, because liver cancer comprises a plethora of stages-from very early to advanced disease and with many treatment options-from surgery to immunotherapy trials-it leaves the clinician a wide range of options. The scope of our review is to throw light on combination treatments that seem to be beyond guidelines and to highlight these using evidence-based analysis of the most frequently used combination therapies, discussing their advantages and flaws in comparison to the current standard of care. One particular combination therapy seems to be in the forefront: Transarterial chemoembolization plus ablation for medium-size non-resectable HCC (3-5 cm), which is currently at the frontier between Barcelona Clinic Liver Cancer classification A and B. Not only does it improve the outcome in contrast to each individual therapy, but it also seems to have similar results to surgery. Also, the abundance of immune checkpoint inhibitors that have appeared lately in clinical trials are bringing promising results against HCC. Although the path of combination therapies in HCC is still filled with uncertainty and caveats, in the following years the hepatology and oncology fields could witness an HCC guideline revolution.

High subcutaneous adipose tissue density correlates negatively with survival in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Body composition parameters have been reported to add information, which can lead to tailored treatment and prognostication for oncological patients. Data for patients with hepatocellular carcinoma (HCC) are scarce. We assessed the association between different body composition parameters and overall survival (OS) in two different newly diagnosed HCC populations. METHODS: The area (cm2 ) and density (Hounsfield Units [HU]) of skeletal muscle (SM) and adipose tissue (subcutaneous [SAT], visceral [VAT] and intermuscular [IMAT]) were measured on computed tomography (CT) scans at the level of the third lumbar vertebra (L3) in two cohorts of patients diagnosed in different HCC stages (Bern, Switzerland n = 187 and Newcastle, United Kingdom n = 216). Univariate and multivariate Cox regressions analyses were used to assess the crude and adjusted association of body composition parameters with OS. RESULTS: By univariate analysis, in both cohorts, Bern and Newcastle, high SAT density (hazard ratio [HR]: 1.35; 1.12-1.62, P < .001 and 1.44; 1.27-1.63, P < .001, respectively) and high VAT density (HR: 1.38; 1.1-1.72, P = .005 and HR: 1.53; 1.3-1.81, P < .001, respectively) correlated negatively with survival. After model adjustment for potential baseline confounders (gender, age, diabetes, cirrhosis, MELD score, BCLC stage) in a multivariate analysis, SAT density remained associated with mortality in Bern and Newcastle (Bern: HR: 1.27; 1.04-1.57, P = .022; Newcastle: HR: 1.23; 1.03-1.48, P = .022) and VAT remained associated with mortality in Bern (HR: 1.31; 1.05-1.65, P = .019). CONCLUSIONS: Based on two HCC cohorts, our data show that high SAT density correlates negatively with OS in HCC patients.

Microwave ablation in the treatment of liver tumors. A better tool or simply more power?

It has been a long time since tumor ablation was first tested in patients with liver cancer, especially hepatocellular carcinoma. Since than it has become a first line treatment modality for hepatocellular carcinoma. Over the years, the indications of thermal ablation have expanded to colorectal cancer liver metastases and intrahepatic cholangiocarcinoma as well. Together with the new indication for ablation, new ablation devices have been developed as well. Among them microwave ablation shows potential in replacing radiofrequency ablation as the preferred method of thermal ablation in liver cancer. The debate whether radiofrequency or microwave ablation should be the preferred method of treatment in patients with liver cancer remains open. The main purpose of this review is to offer some answers to the question: Microwave ablation in liver tumors: a better tool or simply more power? Various clinical scenarios will be analyzed including small, medium, and intermediate size hepatocellular carcinoma, colorectal cancer liver metastases and intrahepatic cholangiocarcinoma. Furthermore, the advantages, limitations, and technical considerations of MWA treatment will be provided also.

Prognostic Factors after Percutaneous Radiofrequency Ablation in the Treatment of Hepatocellular Carcinoma. Impact of Incomplete Ablation on Recurrence and Overall Survival Rates.

AIMS: To report on the long-term impact of tumor and non-tumor related parameters on local recurrence, distant recurrence and survival in patients with naïve or recurrent type hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA). METHODS: We performed 240 RFA sessions on 133 patients with 156 HCC nodules developed on a background of liver cirrhosis and analyzed the outcomes. RESULTS: Contrast-enhanced ultrasound performed one month after RFA showed complete ablation in 119 out of 133 (89.65%) patients. With a median follow-up of 46 months, 3-, 5- and 7-year survival rates were 61.7%, 35.7%, and 22.6%, respectively. Previous ethanol injection and histological grade were significantly related to local tumor progression. Child-Pugh class, incomplete ablation, histological grade, previous ethanol injection, alpha-fetoprotein level before the treatment, and local recurrence were all significantly related to distant recurrence. Multivariate analysis demonstrated that age, Child-Pugh class, distant recurrence and multiple incomplete ablations were significantly related to survival. CONCLUSION: Radiofrequency ablation could be locally curative for HCC, resulting in a survival longer than 7 years. Previous ethanol injection and incomplete ablations were strongly associated with poor outcomes.

Contrast enhanced ultrasonography in assessing the treatment response to transarterial chemoembolization in patients with hepatocellular carcinoma.

The last decades have known continuous development of therapeutic strategies in hepatocellular carcinoma (HCC). Unfortunately the disease it still not diagnosed until it is already at an intermediate or even an advanced disease. In these circumstances transarterial chemoembolization (TACE) is considered an effective treatment for HCC. The most important independent prognostic factor of both disease free survival and overall survival is the presence of complete necrosis. Therefore, treatment outcomes are dictated by the proper use of radiological imaging. Current guidelines recommend contrast enhanced computer tomography (CECT) as the standard imaging technique for evaluating the therapeutic response in patients with HCC after TACE. One of the most important disadvantage of CECT is the overestimation of tumor response. As an attempt to overcome this limitation contrast enhanced ultrasound (CEUS) has gained particular attention as an imaging modality in HCC patients after TACE. Of all available imaging modalities, CEUS performs better in the early and very early assessment of TACE especially after lipiodol TACE. As any other imaging techniques CEUS has disadvantages especially in hypovascular tumors or in cases of tumor multiplicity. Not far from now the current limitations of CEUS will be overcome by the new CEUS techniques that are already tested in clinical practice such as dynamic CEUS with quantification, three-dimensional CEUS or fusion techniques.

Prospective comparison between real time contrast enhanced and conventional ultrasound guidance in percutaneous biopsies of liver tumors.

AIMS: The performance of percutaneous echo-guided biopsy in the hepatic tumoral diagnosis is limited (90% sensitivity) by several factors, among which tumor characteristics (type, size, and location) play an important role. Contrast enhanced ultrasound guided percutaneous biopsy (CEUS-PLB) is a new developed technique aimed at increasing the accuracy of percutaneous biopsies. The objective of our study was to evaluate the feasibility and performance of CEUS as a guiding method in performing liver biopsy (PLB). MATERIAL AND METHODS: One hundred and seventy one patients with liver tumors referred to the ultrasound department for LB were prospectively included in the study. PLB was performed with CEUS guidance in 90 patients (46 in patients with and 44 in patients without liver cirrhosis), in the remaining 81 (37 in patients with liver cirrhosis and 44 in patients without) with conventional US guidance. The lesions in the CEUS -PLB group were larger than those in the US-LB group (mean diameter 7.73 cm vs. 6.11 cm, p>0.05). In both groups the lesions were further divided in: a) lesions on cirrhosis; b) poorly visualized tumors; c) large tumors (>6 cm); d) cystic tumors; e) recurrences after ablation; and f) portal vein thrombosis. RESULTS: Real time CEUS-PLB was technically successful in 84 of the 86 procedures (97.6% technical success rate). The rate of successful single puncture attempt in CEUS-PLB (43.02%) was higher than in the US-PLB group (23.4%) (p<0.05). The sensitivity of LB was significantly higher in the CEUS-PLB group than in the conventional US-LB group for all lesions (96.5% vs. 81.48%, p<0.05), for lesions on liver cirrhosis (95.2% vs. 75%, p<0.05), for large (> 6 cm) (97.8% vs. 82%, p<0.05), and for poorly visible lesions (100 vs. 66.6%, p=0.029). The patients with inconclusive pathological results after conventional guided LB were then biopsied with CEUS guidance. In all cases the final diagnosis could be established. One major complication occurred in each group (p>0.05). CONCLUSIONS: Percutaneous LB performed with CEUS guidance is a feasible and safe technique. It significantly improves the overall sensitivity of the procedure especially in patients with large lesions and in those poorly visualized on conventional ultrasound.

Contrast enhanced ultrasound of renal masses. A reappraisal of EFSUMB recommendations and possible emerging applications.

The main imagistic method for characterization of renal lesions is contrast enhanced computed tomography (CECT). Disadvantages of CECT are a contrast-induced nephropathy in patients with renal impairment, allergic reactions and high costs. Contrast-enhanced ultrasound (CEUS) evaluation of hepatic and non-hepatic lesions is a relatively new, but increasingly utilised, diagnostic method. In 2011 the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) updated the Guidelines and Recommendations on the Clinical Practice of CEUS and included in the recommendation the renal pathology. However, there are several possible new indications that have not been discussed (pyelocaliceal masses and renal vein thrombosis) and several issues that remain controversial such as the differentiation of benign and malignant tumours or the differentiation of lymphoma and metastasis. This study aims to review literature data, as well as reveal the latest findings in the field of renal CEUS.

Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

Percutaneous treatment of symptomatic non-parasitic hepatic cysts. Initial experience with single-session sclerotherapy with polidocanol.

AIMS: Hepatic cysts have a prevalence of 2.5-7% and most of them are asymptomatic. However, large cysts may cause complaints; in such cases an appropriate treatment is necessary (open surgery, laparoscopic deroofing, removal of cystic fluid and injection of a sclerosing agent. The aim of this study was to assess the efficacy and safety of a single session technique with polidocanol in the therapy of symptomatic non parasitic hepatic cysts. MATERIAL AND METHODS. The study included 13 patients with symptomatic liver cysts (range 4-10 cm). All patients underwent percutaneous aspiration of the liver cyst under ultrasound guidance followed by instillation of polidocanol (3%, 4-10 ml). The patients were followed up at 1, 3 and 12 months. The disappearance of the cyst or reduction in volume more than 90% was considered successful. If the fluid was accumulated at 1month the procedure was repeated. If after the second injection the fluid accumulation was more than 50% of the initial volume the case was considered a failure and a laparoscopic deroofing was performed. RESULTS: The procedure was successful in 10 patients, 9 after the first instillation and one after the second (76.9%). The mean initial volume of cysts was 228 ml, and the mean reduction in volume at 1, 3 and 12 months was 80.2%, 91.9% and 96.7%. The cyst resolution was gradual with clinically significant cyst reduction achievement within 1 year after therapy. In 3 patients the fluid reaccumulated at the same volume despite 2 instillations. Those 3 cases the procedure was considered failure and the patients were sent to surgery. In 2 patients (one successfully treated and one with treatment failure) bleeding during the first puncture and aspiration appeared and the therapy was postponed for 1 month. There were no significant adverse effects, and all the patients had relief of symptoms after therapy. CONCLUSIONS: This initial experience with percutaneous aspiration and polidocanol sclerosis of hepatic cysts demonstrated that the technique is efficient and safe.

Role of contrast enhanced ultrasound in the assessment of biliary duct disease.

The introduction of microbubble contrast agents (CA), which act as blood pool tracers, has overcome the limitations of conventional B-Mode, colour or power Doppler ultrasound, enabling the display of parenchymal microvasculature. Initially, the use of CA was accepted for hepatic lesions. In the following years, experts have expanded recommendations, as a result of the method's efficiency in extrahepatic applications. In this article we review the methodology and the application of contrast-enhanced ultrasound (CEUS) in the evaluation of biliary pathology. This new imaging tool allows a non invasive differential diagnosis of biliary lesions and a clearer delineation of the tumoral process.