16 research outputs found
Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib
Background and aims: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. Methods: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. Results: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment
Evaluating the risk-benefit ratio of immunotherapy according to liver-functional reserve in advanced HCC: the dark side of the moon
n
Low-Baseline PD1+ Granulocytes Predict Responses to Atezolizumab–Bevacizumab in Hepatocellular Carcinoma
Simple Summary Immune check point inhibitors (ICPIs) are one of the treatment options for advanced hepatocellular carcinoma (HCC). No biomarker is currently available to upfront select patients to be addressed to one or another drug. We have tested a prospective series of patients with advanced HCC treated with atezolizumab-bevacizumab combination with the aim of identifying biomarkers of response by using a simple cytofluorimetric test on peripheral blood. Due to the relevant role of granulocyte in the immune response, here we have focused on granulocyte immunophenotype by investigating PD1 and PD-L1 expression on their surface by using a simple cytofluorimetric test on peripheral blood. A low baseline PD1+ granulocyte percentage identified patients likely to benefit from atezolizumab-bevacizumab. Our findings warrant to validate this cheap and immediate cytofluorimetric test in larger cohorts, to verify whether the individual accuracy could be informative for the clinical practice. Introduction: Immune check point inhibitors have recently entered the armamentarium of advanced hepatocellular carcinoma (HCC) treatment. Among them, the combination of atezolizumab plus bevacizumab has pushed it a step forward; however, a number of patients still present primary non-responses without any biomarker to predict responses to different options. Here, we aimed to identify a putative baseline biomarker to predict the response to atezolizumab-bevacizumab, by investigating whether baseline PD1+ and PD-L1+ peripheral granulocyte percentages might offer a non-invasive, cheap, and easily feasible assay. Methods: A prospective Italian cohort of 34 patients treated by atezolizumab-bevacizumab was tested to assay the baseline percentage of peripheral granulocytes and their PD1 and PD-L1 expression. The neutrophil to lymphocyte ratio (NLR) was also considered, and all data were compared with the clinical course of patients. Results: A low-baseline PD1+ peripheral granulocyte percentage turned out to predict responder patients (mean +/- SD of PD1+ granulocyte percentage in responders versus non-responders: 9.9 +/- 9.1 vs. 29.2 +/- 17.6; student's t-test, p < 0.01). In line, patients identified by a low PD1+ granulocyte percentage displayed a longer TTP (log-rank test, p < 0.0001). A lower granulocyte percentage on total white blood cells, irrespective of PD1 or PD-L1 expression, is also associated with responses to atezolizumab-bevacizumab (log-rank test, p < 0.05). No predictive value was observed for either the PD-L1+ granulocyte percentage or NLR. Conclusions: A low-baseline PD1+ peripheral granulocyte percentage is associated with responses to atezolizumab-bevacizumab treatment in advanced HCC. These findings encourage evaluating this minimally invasive, cheap, and easy test in further independent cohorts and outlining the relevance of innate immunity in the response to immune-checkpoint inhibitors
Circulating CD8 lymphocytes predict response to atezolizumab–bevacizumab in hepatocellular carcinoma
Due to the lack of biomarkers predictive of response to atezolizumab-bevacizumab, the standard of care for advanced HCC, we analyzed baseline and early on-treatment variation of peripheral lymphocyte populations of 37 prospective patients treated by atezolizumab-bevacizumab and in 15 prospective patients treated by sorafenib or lenvatinib (TKIs). RNAseq analysis followed by RT-PCR validation on patients-derived PBMC was also performed. At first imaging, re-evaluation 13 patients receiving atezolizumab-bevacizumab, showed an objective response, 17 stable disease, while 7 were nonresponders. Baseline CD8+ and CD8+PD-L1+ peripheral lymphocytes were lower in responders versus nonresponders (T-test, p = 0.012 and 0.004, respectively). At 3 weeks, 28 of 30 responders displayed a rise of CD8+PD1+ lymphocytes with a positive mean fold change of 4.35 (±5.6 SD), whereas 6 of 7 nonresponders displayed a negative fold change of 0.89 (±0.84 SD). These changes were not observed in patients treated by TKIs. TRIM56, TRIM16, TRIM64, and Ki67 mRNAs were validated as upregulated in responders versus nonresponders after 3 weeks after treatment start, providing possible evidence of immune activation. Baseline CD8+ and CD8+PD-L1+ peripheral lymphocytes and early changes in CD8+PD1+ lymphocytes predict response to atezolizumab-bevacizumab providing noninvasive markers to complement clinical practice in the very early phases of treatment of HCC patients
Palliative care in patients with hepatocellular carcinoma: Results from a survey among hepatologists and palliative care physicians
Background: Delays and limitations of palliative care in patients with liver transplantation-ineligible end-stage hepatocellular carcinoma according to Barcelona Clinic Liver Cancer staging system may be explained by different perceptions between hepatologists and palliative care physicians in the absence of shared guidelines. Aim: To assess physicians’ attitudes toward palliative care in end-stage hepatocellular carcinoma and to understand what the obstacles are to more effective management and co-shared between palliative care physicians and hepatologists. Design: Members of the Italian Association for the Study of Liver Disease and the Italian Society of Palliative Care were invited to a web-based survey to investigate practical management attitude for patients with liver transplant-ineligible end-stage hepatocellular carcinoma. Participants: Physician members of the of the two associations, representing several hospitals and services in the country. Results: Ninety-seven hepatologists and 70 palliative care physicians completed the survey: >80% regularly follow 1–19 patients; 58% of hepatologists collaborate with palliative care physicians in the management of patients, 55% of palliative care physicians take care of patients without the aid of hepatologists. Management of cirrhosis differed significantly between the two groups in terms of prescription of albumin, esophagogastroduodenoscopy, anti-viral treatment, anticoagulation, indication to paracentesis and management of encephalopathy. Full-dose acetaminophen is widely used among hepatologists, while opioids are commonly used by both categories, at full dosage, regardless of liver function. Conclusions: This survey highlights significant differences in the approach to patients with liver transplantation-ineligible end-stage hepatocellular carcinoma, reinforcing the need for shared guidelines and further studies on palliative care in the setting
Superior bowel preparation quality for colonoscopy with 1L-PEG compared to 2L-PEG and picosulphate: Data from a large real-world retrospective outpatient cohort
Background: Several randomized clinical trials comparing different bowel preparations (BP) have shown similar efficacy; however, there is a lack of real-world studies on this topic. Aims: This study aims to identify the most effective BP regimen in a real-world setting and any predictors of inadequate BP. Methods: A retrospective single-center study was conducted over 14 months at an academic hospital including outpatient colonoscopies in which adult patients did not teach on how to perform BP before colonoscopy. Colonoscopies with 1L-PEG, 2L-PEG and picosulphate mixtures were considered. A multivariable analysis for factors associated to poor BP was fitted. Results: Overall, 1779 patients (51 %F, 60±14) years were included. The 1L-PEG regimen provided a higher rate of BP adequacy at multivariate analysis (adjusted OR 2.30, 95 %CI 1.67-3.16,p < 0.001) and was associated with higher median Boston Bowel Preparation Scale score (p < 0.001), higher rate of right-colon cleansing (p < 0.001) and exam completion (p = 0.04). Furthermore, we identified male sex, history of constipation, active smoking, previous pelvic surgery, concomitant psychiatric/neurological or chronic kidney diseases as predictors of inadequate BP. Conclusions: This is the largest real-world study comparing 1L-PEG to other BP regimens. Our results suggest 1L-PEG provides better BP in a non-controlled setting, improving clinical practice quality and minimizing the need for repeated colonoscopies and saving healthcare resources
Efficacy and safety of lenvatinib in patients with recurrent hepatocellular carcinoma after liver transplantation
Abstract Introduction Lenvatinib is approved for the treatment of patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, clinical outcomes of lenvatinib therapy in patients with post‐liver transplantation (LT) HCC recurrence remain unclear. We investigated the efficacy and safety of lenvatinib in patients with post‐LT HCC recurrence. Methods This multinational, multicenter, retrospective study included 45 patients with recurrent HCC after LT who received lenvatinib at six institutions in three countries (Korea, Italy, and Hong Kong) from June 2017 to October 2021. Results At the time of lenvatinib initiation, 95.6% (n = 43) of patients had Child–Pugh A status, and 35 (77.8%) and 10 (22.2%) participants were classified as having albumin–bilirubin (ALBI) grades 1 and 2, respectively. The objective response rate was 20.0%. With a median follow‐up duration of 12.9 months (95% confidence interval [CI]: 11.2–14.7), the median progression‐free survival and overall survival (OS) were 7.6 (95% CI: 5.3–9.8) months, and 14.5 (95% CI: 0.8–28.2) months, respectively. Patients with ALBI grade 1 showed significantly better OS (52.3 months, [95% CI: not assessable]) than patients with ALBI grade 2 (11.1 months [95% CI: 0.0–30.4 months], p = 0.003). The most common adverse events were hypertension (n = 25, 55.6%), fatigue (n = 17, 37.8%), and anorexia (n = 14, 31.1%). Conclusion Lenvatinib showed consistent efficacy and toxicity profiles in patients with post‐LT HCC recurrence that were comparable to those reported from previous studies among non‐LT HCC patients. The baseline ALBI grade correlated with better OS in post‐LT lenvatinib‐treated patients
Undefined/non-malignant hepatic nodules are associated with early occurrence of HCC in DAA-treated patients with HCV-related cirrhosis
An unexpected early increased incidence, recurrence and clinical aggressiveness of hepatocellular carcinoma (HCC) has been reported in HCV cirrhotic patients after treatment with direct-acting antivirals (DAA), but denied in other studies. To clarify this controversy, we performed a prospective multicenter study on consecutively enrolled cirrhotic patients with or without history of HCC undergoing DAA therapy
SARS-CoV-2 infection in patients with inflammatory bowel disease: comparison between the first and second pandemic waves
Background: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. Methods: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. Results: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007). Conclusion: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves