The prevalence and management of coronary artery disease (CAD) in liver transplantation (LT) candidates are not well characterized. The aims of this study were to evaluate the impact on clinical ...outcomes of a specifically designed protocol for the management of asymptomatic CAD in LT candidates and to investigate noninvasive risk profiles for obstructive and nonobstructive CAD for 202 LT candidates. Those with high baseline cardiovascular risk (CVR; defined by the presence of classic CVR factors and/or decreased ejection fraction) received coronary angiography and significant arterial stenosis and were treated with percutaneous stents. Patients were followed up after LT until death or coronary event (CE). There were 78 patients who received coronary evaluation (62 direct angiography, 14 computed tomography coronary angiography, and 2 both). Of them, 39 (50%) patients had CAD of any severity, and 6 (7.7%) had significant lesions (5 were amenable to be treated with stents, whereas 1 patient had diffuse lesions which contraindicated the LT). Insulin‐dependent diabetes was the only factor related to CAD of any severity (odds ratio, 3.44; 95% confidence interval CI, 1.00‐11.97). A total of 69 patients (46 with coronary evaluation) received LT. The incidence of CEs and overall survival after LT were similar between patients with and without coronary evaluation. Furthermore, no differences occurred between these groups in a multivariate competing risk model (subhazard ratio, 0.84; 95% CI, 0.27‐2.61; P = 0.76). In conclusion, the application of an angiographic screening protocol of CAD in a selected high‐risk Mediterranean population is safe and effective. The short‐ and medium‐term incidence rates of CEs and death after LT in this population are similar to that observed in low‐risk patients.
Objective
Cirrhosis is characterized by the complex interplay among biological, histological and haemodynamic events. Liver and spleen remodelling occur throughout its natural history, but the ...prognostic role of these volumetric changes is unclear. We evaluated the relationship between volumetric changes assessed by multidetector computerised tomography (MDCT) and landmark features of cirrhosis.
Methods
We included consecutive cirrhotic patients who underwent liver transplantation (LT) or hepatocellular carcinoma (HCC) resection in whom dynamic MDCT was available. Different volumetric indices were calculated. Fibrosis was evaluated by the collagen proportional area and Laennec sub‐stages. Correlation and logistic regression analysis were performed to explore associations of volumetric indexes and fibrosis with key prognostic features across the clinical stages of cirrhosis.
Results
185 patients were included (146 LT; 39 HCC); the predominant aetiology was viral hepatitis (51.35%); 65.9% had decompensated disease and 85.08% clinically significant portal hypertension (CSPH). The standardised liver volume and liver‐spleen volume ratio negatively correlated with Model for End‐stage Liver Disease (MELD), albumin and hepatic venous pressure gradient (HVPG) and were significantly lower in decompensated patients. The liver segmental volume ratio (segments I–III/segments IV–VIII) best captured the characteristic features of the compensated phase, showing a positive correlation with HVPG and a good discrimination between patients with and without CSPH and varices. Volumetric changes and fibrosis severity were independently associated with key prognostic events, with no association between these two parameters.
Conclusions
Liver and spleen volumetric indices evolve differently along the natural history of cirrhosis and are associated with key prognostic factors in each phase, regardless of fibrosis severity and portal hypertension.
Hepatocellular carcinoma (HCC) is the most frequent liver primary cancer and represents the sixth malignant neoplasm and the fourth cause of cancer associated deaths worldwide. Despite improvements ...across the last years in therapeutic options, it is still associated with a high mortality. Therefore, HCC represents a major health problem and a challenge for clinicians in terms of management of patient care.
Clinically significant portal hypertension (CSPH) is a landmark in the natural history of cirrhosis, influencing clinical decisions in patients with hepatocellular carcinoma (HCC). Previous small ...series suggested that splanchnic volume measurements may predict portal hypertension. We aimed to evaluate whether volumetry obtained by standard multidetector computerised tomography (MDCT) can predict CSPH in patients with HCC.
We included 175 patients with HCC, referred for hepatic venous pressure gradient (HVPG) evaluation, in whom contemporary MDCT was available. Liver volume, spleen volume (SV) and liver segmental volume ratio (LSVR: volume of the segments I-III/volume of the segments IV-VIII) were calculated semi-automatically from MDCT. Other non-invasive tests (NITs) were also employed.
Volume parameters could be measured in almost 100% of cases with an excellent inter-observer agreement (intraclass correlation coefficient >0.950). SV and LSVR were independently associated with CSPH (HVPG ≥10 mmHg) and did not interact with aetiology. The volume Index (VI), calculated as the product of SV and LSVR, predicted CSPH (AUC 0.83; 95% CI 0.77–0.89). Similar results were observed in an external cohort (n = 23) (AUC 0.87; 95% CI 0.69–1.00). Setting a sensitivity and specificity of 98%, VI could have avoided 35.9% of HVPG measurements. The accuracy of VI was similar to that of other NITs. VI also accurately predicted HVPG greater than 12, 14, 16 and 18 mmHg (AUC 0.81 95% CI 0.74–0.88, 0.84 95% CI 0.77–0.91, 0.85 95% CI 0.77–0.92 and 0.87 95% CI 0.79–0.94, respectively).
Quantification of liver and spleen volumes by MDCT is a simple, accurate and reliable method of CSPH estimation in patients with compensated cirrhosis and HCC.
An increase in portal pressure strongly impacts outcomes after surgery in patients with early hepatocellular carcinoma (HCC). Direct measurement through hepatic vein catheterization remains the reference standard for portal pressure assessment, but its invasiveness limits its application. Therefore, we evaluated the ability of CT scan-based liver and spleen volume measurements to predict portal hypertension in patients with HCC. Our results indicate that the newly described index, based on quantification of liver and spleen volume, accurately predicts portal hypertension. These results suggest that a single imaging test may be used to diagnose and stage HCC, while providing an accurate estimation of portal hypertension, thus helping to stratify surgical risks.
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•The VI predicts the presence of CSPH and severe portal hypertension in patients with compensated cirrhosis and HCC.•The accuracy of the VI for the prediction of CSPH is comparable to that of other widely used and validated NITs.•Visceral volumetric assessment by MDCT is an accessible, affordable, easy-to-perform, and accurate test.•A single imaging test can confirm the diagnosis/stage of HCC and estimate the individual risk of different degrees of portal hypertension.
Background:
Transarterial radioembolization (TARE) is increasingly used in patients with hepatocellular carcinoma (HCC). This treatment can induce or impair portal hypertension, leading to hepatic ...decompensation. TARE also promotes changes in liver and spleen volumes that may modify therapeutic decisions and outcomes after therapy.
Objectives:
We aimed to investigate the impact of TARE on the incidence of decompensation events and its predictive factors.
Design:
In all, 63 consecutive patients treated with TARE between February 2012 and December 2018 were retrospectively included.
Methods:
We assessed clinical (including Barcelona Clinic Liver Cancer stage, portal hypertension assessment, and liver decompensation), laboratory parameters, and liver and spleen volumes before and 6 and 12 weeks after treatment. A multivariate analysis was performed.
Results:
In total, 18 out of 63 (28.6%) patients had liver decompensation (ascites, variceal bleeding, jaundice, or encephalopathy) within the first 3 months after therapy, not associated with tumor progression. Clinically significant portal hypertension (CSPH) and bilobar treatment independently predicted the development of liver decompensation after TARE. A significant volume increase in the non-treated hemi-liver was observed only in patients with unilobar treatment (median volume increase of 20.2% in patients with right lobe TARE; p = 0.007), especially in those without CSPH. Spleen volume also increased after TARE (median volume increase of 16.1%; p = 0.0001) and was associated with worsening liver function scores and decreased platelet count.
Conclusion:
Bilobar TARE and CSPH may be associated with an increased risk of liver decompensation in patients with intermediate or advanced HCC. A careful assessment considering these variables before therapy may optimize candidate selection and improve treatment planning.
PurposeTo evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in combination with a PD-1 inhibitor in patients with unresectable hepatocellular carcinoma (uHCC) and ...liver-only disease ineligible for chemoembolization.Patients and methodsNASIR-HCC is a single-arm, multicenter, open-label, phase 2 trial that recruited from 2017 to 2019 patients who were naïve to immunotherapy and had tumors in the BCLC B2 substage (single or multiple tumors beyond the up-to-7 rule), or unilobar tumors with segmental or lobar portal vein invasion (PVI); no extrahepatic spread; and preserved liver function. Patients received SIRT followed 3 weeks later by nivolumab (240 mg every 2 weeks) for up to 24 doses or until disease progression or unacceptable toxicity. Safety was the primary endpoint. Secondary objectives included objective response rate (ORR), time to progression (TTP), and overall survival (OS).Results42 patients received SIRT (31 BCLC-B2, 11 with PVI) and were followed for a median of 22.2 months. 27 patients discontinued and 1 never received Nivolumab. 41 patients had any-grade adverse events (AE) and 21 had serious AEs (SAE). Treatment-related AEs and SAEs grade 3–4 occurred in 8 and 5 patients, respectively. Using RECIST 1.1 criteria, ORR reported by investigators was 41.5% (95% CI 26.3% to 57.9%). Four patients were downstaged to partial hepatectomy. Median TTP was 8.8 months (95% CI 7.0 to 10.5) and median OS was 20.9 months (95% CI 17.7 to 24.1).ConclusionsThe combination of SIRT and nivolumab has shown an acceptable safety profile and signs of antitumor activity in the treatment of patients with uHCC that were fit for SIRT.Trial registration numberNCT03380130
Objective
Advances in hepatic radioembolization are based on a selective approach with radical intent and the use of multicompartment dosimetric analysis. The objective of this study is to assess the ...utility of voxel-based dosimetry in the quantification of actual absorbed doses in radiation segmentectomy procedures and to establish cutoff values predictive of response.
Methods
Ambispective study in hepatocarcinoma patients treated with radiation segmentectomy. Calculated dosimetric parameters were mean tumor-absorbed dose, maximum tumor AD, minimal tumor AD in 30, 50, and 70% of tumor volume and mean AD in non-tumor liver. The actual absorbed dose (aAD) was calculated on the Y-90-PET/CT image using 3D voxel-based dosimetry software. To assess radiological response, localized mRECIST criteria were used. The objective response rate (ORR) was defined as CR or PR.
Results
Twenty-four HCC patients, BCLC 0 (5), A (17) and B (2) were included. The mean yttrium-90 administered activity was 1.38 GBq in a mean angiosome volume of 206.9 cc and tumor volume 56.01 cc. The mean theoretical AD was 306.3 Gy and aAD 352 Gy. A very low concordance was observed between both parameters (rho_c 0.027). ORR at 3 and 6 m was 84.21% and 92.31%, respectively. Statistically significant relationship was observed between the maximum tumor-absorbed dose and complete radiological response at 3 m (p 0.022).
Conclusion
A segmental approach with radical intention leads to response rates greater than 90%, being the tumor maximum absorbed dose the dosimetric parameter that best predicts radiological response in voxel-based dosimetry.
Background & Aims
Information on safety and efficacy of systemic treatment in patients with hepatocellular carcinoma (HCC) under dialysis are limited due to patient exclusion from clinical trials. ...Thus, we aimed to evaluate the rate, prevalence, tolerability, and outcome of sorafenib in this population.
Methods
We report a multicenter study comprising patients from Latin America and Europe. Patients treated with sorafenib were enrolled; demographics, dose modifications, adverse events (AEs), treatment duration, and outcome of patients undergoing dialysis were recorded.
Results
As of March 2018, 6156 HCC patients were treated in 44 centres and 22 patients were concomitantly under dialysis (0.36%). The median age was 65.5 years, 40.9% had hepatitis C, 75% had Child‐Pugh A, and 85% were Barcelona Clinic Liver Cancer‐C. The median time to first dose modification, treatment duration and overall survival rate were 2.4 months (interquartile ranges IQR, 0.8‐3.8), 10.8 months (IQR, 4.5‐16.9), and 17.5 months (95% CI, 7.2‐24.5), respectively. Seventeen patients required at least 1 dose modification. The main causes of first dose modification were asthenia/worsening of Eastern Cooperative Oncology Group‐Performance Status and diarrhoea. At the time of death or last follow‐up, four patients were still on treatment and 18 had discontinued sorafenib: 14 were due to tumour progression, 2 were sorafenib‐related, and 2 were non‐sorafenib‐related AE.
Conclusions
The outcomes observed in this cohort seem comparable to those in the non‐dialysis population. Thus, to the best of our knowledge, this is the largest and most informative dataset regarding systemic treatment outcomes in HCC patients undergoing dialysis.
Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown.
This study was aimed to evaluate the influence of ...antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension.
Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN alpha2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score.
HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)%13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response 26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05 and in those with a decrease of at least 2 points in the grade of inflammation 35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015. Nine out of 11 patients with baseline HVPG > or = 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11).
AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.
