Polyclonal and monoclonal B lymphocytes response in HCV-infected patients treated with direct-acting antiviral agents

Hepatitis C virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinaemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all-cause mortality. In this study, we used flow cytometry to evaluate the effect of interferon-free antiviral treatment on peripheral blood lymphocytes in HCV-infected patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes was performed at baseline and at the end of treatment. In HCV-infected patients with lymphoproliferative disorders, we evaluated immunoglobulin (Ig) light chain \u3ba/\u3bb ratio variations as a measure of monoclonal B-cell response to antiviral therapy. Healthy volunteers were enrolled as controls. A total of 29 patients were included, nine with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29 of 29 patients. We observed a significant reduction in the B-cell compartment (39% global reduction) in eight of nine HCV-infected patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV-infected patients without lymphoproliferative disorders (9% global reduction). Among HCV-infected patients with lymphoproliferative disorders, three showed an improvement/normalization of the immunoglobulin light chain ratio, whereas in the remaining six patients monoclonal B cells persisted to be clonally restricted even 1\ua0year after the end of treatment. Our data show that DAAs treatment can be effective in reducing the frequency of pathological B cells in the peripheral blood of HCV-infected patients affected by HCV-associated lymphoproliferative disorders; however, monoclonal populations can persist after viral eradication

Maternal HIV status and infant feeding practices among Ugandan women

practices, a questionnaire was administered to women attending the follow-up clinics for child vaccination. Among the mothers who were still breastfeeding at the time of interview (N=838), 61.4% of the HIV-infected women had planned to breastfeed for a maximum of 6 months, compared with 12.1% of the HIV-uninfected women (p<0.001). Among the women who were not breastfeeding at the time of interview (N=108), 82.5% of the HIV-infected women had stopped breastfeeding within 3 months, compared with 23.5% of the HIV-uninfected women (p<0.001). Only 2.1% of HIV-infected women seen up to 14 weeks postnatally practised mixed feeding, compared with 23.6% of HIV-uninfected women (p<0.001). After 6 months, however, 30% of the HIV-infected women and 55% of the HIV-uninfected mothers were using mixed feeding, with no significant differences. Programmes for the prevention of motherto-child transmission of HIV should re-enforce counselling activities to address the issue of early weaning by HIV-infected women, and to support safe breastfeeding up to 6 months

Liver transplantation for non-alcoholic fatty liver disease: indications and post-transplant management

Non-alcoholic fatty liver disease (NAFLD) is currently the fastest growing indication to liver transplantation (LT) in Western Countries, both for end stage liver disease and hepatocellular carcinoma. NAFLD/non-alcoholic steatohepatitis (NASH) is often expression of a systemic metabolic syndrome; therefore, NAFLD/NASH patients require a multidisciplinary approach for a proper pre-surgical evaluation, which is important to achieve a post-transplant outcome comparable to that of other indications to LT. NAFLD/NASH patients are also at higher risk of post-transplant cardiovascular events, diabetes, dyslipidemia, obesity, renal impairment and recurrent NASH. Lifestyle modifications, included diet and physical activity, are key to improve survival and quality of life after transplantation. A tailored immunosuppressive regimen may be proposed in selected patients. Development of new drugs for the treatment of recurrent NASH is awaited

Influence of sex in alcohol‐related liver disease: Pre‐clinical and clinical settings

Alcohol-related liver disease (ArLD) is a major cause of chronic liver disease globally. Traditionally, ArLD was mostly a concern in men rather than in women; however, such a sex gap is rapidly narrowing due to increasing chronic alcohol consumption among women. Female sex is more vulnerable to the harmful effects of alcohol with a higher risk of progression to cirrhosis and development of associated complications. The relative risk of cirrhosis and liver-related mortality is significantly higher in women than in men. Our review endeavors to summarize the current knowledge on sex differences in alcohol metabolism, pathogenesis of ArLD, disease progression, indication for liver transplant and pharmacological treatments of ArLD, and provide evidence in support of a sex-specific management of these patients

The Role of [18F]F-Choline PET/CT in the Initial Management and Outcome Prediction of Prostate Cancer: A Real-World Experience from a Multidisciplinary Approach

Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56&ndash;86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy

Evolution of Liver Transplantation Indications: Expanding Horizons

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients’ management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases

Thromboelastometry hypercoagulable profiles and portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma

BACKGROUND: Cirrhotic patients with hepatocellular carcinoma (HCC) exhibit hypercoagulability. AIM: We investigated whether thromboelastometry can detect hypercoagulability in these patients and the association with portal vein thrombosis (PVT). METHODS: At baseline, cirrhotic patients with and without HCC underwent thromboelastometry. PVT onset was recorded over a 12-month follow-up period. RESULTS: Seventy-six patients (41 with and 35 without HCC) were included. Vital tumor volume (VTV) was\u2009 >5cm3 in 18 patients. Fibrinogen was higher in HCC patients with VTV>5cm3 as compared to those with VTV 645cm3 and those without HCC. Mean platelet count was significantly increased in HCC patients compared with non-HCC. At baseline thromboelastometry, HCC patients showed shorter CTF and higher MCF than non-HCC. PVT incidence was 24,4% and 11.4% in patients with (10/41) and without (4/35) HCC, respectively. Among HCC, 50% of PVT occurred in Child A patients. In HCC, FIBTEM MCF>25mm was associated with a 5-fold increased PVT risk [RR: 4.8 (2-11.3); p=0.0001]. Cox multivariate analysis confirmed HCC and increased MCF (FIBTEM) to be independently associated with increased PVT risk. CONCLUSIONS: Hypercoagulability in HCC which can be detected by thromboelastometry is associated with increased risk of PVT even in Child A patients. The clinical implication of these findings deserves further investigation

COVID-19 and pregnancy, childbirth, and breastfeeding: the interim guidance of the Italian National Institute of Health

This summary is based on the 2nd edition of the "Interim guidance on pregnancy, childbirth, breastfeeding and care of infants (0-2 years) in response to the COVID-19 emergency. Update of the INIH COVID-19 Report n. 45/2020", published on 5 February 2021.

The impact of sarcopenia on the outcome of patients with cirrhosis with and without hepatocellular carcinoma who undergo liver transplantation

Background: The impact of sarcopenia on the outcome of patients with cirrhosis who undergo liver transplantation (LT) has been analysed in heterogeneous cohorts with mixed results. We sought to determine the prevalence and the impact of pre-LT sarcopenia on morbidity and mortality after LT in a cohort of patients with cirrhosis with and without hepatocellular carcinoma (HCC).Methods: Patients with cirrhosis who underwent LT between 2010 and 2016 at Padua University Hospital were retrospectively evaluated. Using image software analysis, cross-sectional area of skeletal muscle at 3rd lumbar vertebra was measured and skeletal muscle index (SMI) was calculated. Sarcopenia was defined by SMI &lt; 50 cm2/m2 in males and &lt; 39 cm2/m2 in females, respectively. Primary outcome was post-LT survival. Secondary outcomes included hospitalization length and post-LT complications.Results: 197 patients were included, of whom, 122 (62%) had sarcopenia. Demographics and severity of cirrhosis were comparable in patients with vs. without sarcopenia. Overall survival was similar between the groups. When survival analysis was adjusted for severity of liver disease, sarcopenia was associated with a significantly reduced survival in decompensated (80% vs. 91%, 1-year post-LT; P = 0.04) but not in compensated (93% vs. 90%, 1-year post-LT; P = 0.7) patients. In patients with HCC, sarcopenia was associated with a trend towards lower survival but only in those with HCC beyond Milan criteria. Among secondary outcomes, bacterial infections were more frequent in patients with vs. without sarcopenia (50% vs. 35%; P = 0.02), whereas hospitalization length and other complications were comparable between the groups.Conclusion: Sarcopenia is a common finding in patients awaiting LT and, in those with decompensated cirrhosis, it is associated with reduced survival after transplantation