Martina Gambato

Background: Abnormalities in body composition are common in patients with hepatocellular carcinoma (HCC); however, their impact across different treatment modalities remains poorly understood. We systematically reviewed the prognostic value of body composition in patients with HCC, stratified by curative, locoregional, and systemic therapies. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, the Cochrane Library, and Web of Science (January 2015–March 2025) for studies reporting associations between CT/MRI or bioelectrical impedance analysis (BIA)-assessed body composition and outcomes in HCC. Results: Ninety-two studies were included (35 curative, 10 locoregional, 39 systemic, 8 mixed). Sarcopenia prevalence ranged from 6.4% to 62.8% (median study-level prevalence 38%–50% depending on treatment stratum). Sarcopenia independently predicted worse overall survival across all strata: curative (HR 1.52–3.76), locoregional (HR 1.72–2.51), and systemic therapies (HR 1.34–2.20). Sarcopenic obesity conferred the highest risk in the curative setting (HR up to 3.15). In systemic therapy, myosteatosis independently predicted mortality (HR 1.45–2.01), whereas visceral adiposity was protective (HR 0.56–0.66). In a random-effects meta-analysis of 44 studies, sarcopenia was associated with a pooled HR of 1.85 (95% CI 1.75–1.94; I ² =0%), with consistent effects across curative (HR 1.86), locoregional (HR 2.10), and systemic strata (HR 1.71). Sarcopenia also predicted recurrence after curative treatment (pooled HR 1.71, 95% CI 1.61–1.82; k =14). Conclusions: Sarcopenia predicts mortality in HCC, independently of treatment modality. Visceral adiposity appears detrimental after curative treatment but may be paradoxically protective during systemic therapy. Body composition should be integrated into clinical decision-making in HCC, though a clear consensus on measurement standardization is needed.

Background: Frailty and sarcopenia are associated with mortality in cirrhosis. However, most data come from North American cohorts in the outpatient setting. We aimed to assess the impact of frailty and sarcopenia in a prospective cohort of inpatients with cirrhosis. Methods: All patients with decompensated cirrhosis admitted to our unit between October 2021 and March 2023 were prospectively screened for recruitment. Frailty was assessed using the liver frailty index, while sarcopenia was assessed via skeletal muscle index on CT scans performed during hospitalization, respectively. All patients were followed for transplant-free survival as the primary outcome. Results: We included 127 patients (median age 59 y; 68.5% male; median MELD score: 22; 70% with Child–Pugh C cirrhosis). At inclusion, 48.8% of patients were frail, and 60% were sarcopenic. Compared with robust and non-sarcopenic individuals, those with frailty and sarcopenia required ICU care more frequently during hospitalization. Moreover, frailty was associated with a longer hospital stay (15 [9–27] vs. 6.5 [4–15]; p =0.001). During a median follow-up of 96 days (IQR 37–384), 39.4% patients died. Frailty and sarcopenia were associated with a higher mortality (60% vs. 20% and 58% vs. 38%, respectively; p p p =0.003) was an independent predictor of reduced transplant-free survival. Conclusions: Frailty emerges as the strongest, independent predictor of early mortality in cirrhosis patients with acute decompensation. Thus, its assessment via the liver frailty index should be performed to improve risk stratification and clinical management.

Background/Objectives: Despite advances in hepatocellular carcinoma (HCC) management, prognosis remains poor. Advanced-stage diagnosis often excludes curative treatments, and current biomarkers (e.g., alpha-fetoprotein [AFP]) have limited utility in early detection. Liquid biopsy has emerged as a promising cancer detection tool, with circulating cell-free DNA (ccfDNA) showing significant diagnostic potential. This proof-of-concept study aimed to investigate the potential role of tumor fraction (TF) within ccfDNA as a biomarker in HCC patients. Methods: A total of sixty patients were recruited, including thirteen with chronic liver disease (CLD), twenty-four with cirrhosis, and twenty-three with HCC. Plasma samples were collected, and ccfDNA was extracted for shallow whole genome sequencing (sWGS) analysis. The TF was calculated by focusing on somatic copy number alterations (SCNAs) within the ccfDNA. Results: Among patients with CLD and cirrhosis (n = 37), ctDNA was undetectable in all but one cirrhotic patient who exhibited a significant tumor fraction (TF) of 17% and subsequently developed HCC. Conversely, five out of twenty-three HCC patients (21.7%) displayed detectable ctDNA with TF levels ranging from 3.0% to 32.6%. Patients with detectable ctDNA were characterized by more aggressive oncological features, including a higher number of nodules (p = 0.005), advanced-stage disease (60% BCLC C, p = 0.010), and poorer response to therapy (80% PD, p = 0.001). Moreover, the overall survival (OS) was significantly reduced in patients with detectable ctDNA (median OS: 17 months; CI 95% 4.5–26.5) compared to those without (median OS: 24.0 months; CI 95% 7.0–66.0; log-rank p = 0.002). Conclusions: Our results suggest that the analysis of TF by sWGS is a promising non-invasive tool for the identification of HCC with aggressive clinical behavior, whereas it is not sensitive enough for early HCC detection. This molecular assay can improve prognostic stratification in HCC patients.

Background: Hepatitis B virus (HBV) remains a leading etiology for liver transplantation (LT). In a large cohort of HBsAg-positive patients, this study evaluates long-term patient and graft survival after LT over the past 30 years while analyzing trends and outcomes following waiting list (WL) inclusion over the last 15 years. Methods: HBsAg-positive patients who underwent transplantation between 1991 and 2020 and were waitlisted from 2006 to 2020 at Padua Hospital were included in the analysis. Patients were stratified according to hepatitis delta virus (HDV) coinfection, transplant indication (decompensated cirrhosis vs. hepatocellular carcinoma (HCC)), and WL inclusion period. Results: Among 321 HBsAg-positive LT recipients (31.5% HDV-coinfected, 46.4% HCC), 1-year and 5-year patient/graft survival rates were 87.6%/86.7% and 82.6%/82.2%, respectively. From 2006 to 2020, 284 HBsAg-positive patients were waitlisted (32.6% HDV-coinfected), with a significantly higher prevalence of HCC compared to non-HBV patients (p = 0.008). High-barrier nucleos(t)ide analogues (hbNUCs) significantly reduced mortality (p = 0.041) and improved survival post-WL inclusion (p = 0.007). Survival rates were consistent regardless of LT indication, HDV coinfection, or WL inclusion period. Post-transplant prophylaxis predominantly involved immunoglobulins (HBIG) + NUCs, resulting in only two cases of HBV reactivation, both clinically inconsequential. Conclusions: Over the past 30 years, HBV has remained a consistent indication for LT at our center. Thanks to hbNUCs, WL outcomes have improved and HCC has become the main indication for LT.

Introduction: Psychosocial pre-transplant evaluation in patients undergoing liver transplantation (LT) could help identify those patients at higher risk of pharmacological non-adherence, organ rejection, and mortality. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated tool for assessing LT candidates’ psychosocial well-being. Data on the ability of the SIPAT evaluation to predict post-transplant outcomes are sparse. Material and Methods: clinical and psychosocial data from a sample of 134 candidates for LT were analyzed. Moreover, the association between pre-transplant psychosocial evaluation and post-transplant clinical outcomes, including organ rejection, mortality, and immunosuppressant drug adherence, was calculated. Results: At the pre-transplant evaluation, patients who showed high SIPAT scores (77, 57%) also had more liver disease assessed by model for end-stage liver disease (MELD; F = 5.04; p < 0.05), alcoholic etiology (F = 35.80; p < 0.001), encephalopathy (F = 5.02; p < 0.05), and portal hypertension (F = 7.45; p < 0.01). Of the 51 transplant patients, those who had a high pre-transplant SIPAT score showed lower post-transplant immunosuppressive adherence, linked to more frequent immunological events. Conclusions: Patients with an alcoholic etiology of liver disease and more severe liver dysfunction are likelier to not adhere to medical prescriptions following transplantation. Current data suggests that this specific group of patients could benefit from early psychological pre-habilitation before undergoing liver transplantation.

Bacterial infections are a common complication in patients with decompensated liver cirrhosis. The complex landscape of cirrhosis, characterized by immune paralysis and an exhausted response to exogenous triggers, explains the higher prevalence of such infections, particularly in advanced disease stages. In clinical practice, the onset of a bacterial infection can lead to further deterioration of hepatic and extra-hepatic function, potentially resulting in acute decompensation or acute-on-chronic liver failure. This has significant clinical implications, particularly for patients awaiting a transplant. In this review, we will discuss the latest evidence on the diagnosis and therapy of bacterial infections in patients with decompensated cirrhosis. Additionally, we will analyze the impact of bacterial infections in the context of liver transplantation, discussing debated topics such as the timing of transplantation in patients with infections, potential implications for prioritization, effects on post-operative recovery, grafts, and patient survival.

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.

Background: Primary sclerosing cholangitis (PSC), comprising 5–15% of European liver transplantation (LT) cases, poses a significant challenge due to the risk of post-transplant disease recurrence (rPSC). This single-center study aimed to determine the rPSC rate and long-term post-LT outcomes in PSC patients and to identify potentially modifiable risk factors of rPSC. Methods: All PSC patients receiving LT at Padua Hospital from 1993 to 2021 were included. Recipient data were collected pre-LT, at LT, and during the follow-up. Donor and LT features were recorded. The rPSC rate was assessed according to Mayo Clinic criteria. Patient and graft survival were reported. Results: Thirty-three patients were included. The main indication of LT was decompensated cirrhosis (70%). Nine patients (27%) developed rPSC during a median follow-up of 59 months (45–72). A longer cold ischemia time (p = 0.026), donor female gender (p = 0.049), inflammatory bowel disease reactivation (IBD) post LT (p = 0.005) and hepaticojejunostomy (p = 0.019) were associated with a higher risk of rPSC. Graft and patient survival at 1, 5 and 10 years post LT, 94%, 86%, 74% and 97%, 89%, 77% respectively, were not affected by rPSC development. Conclusion: Specific donor and surgical features might increase the risk of rPSC. Identifying predictive factors for rPSC to prevent graft loss is challenging but could lead to a more personalized organ allocation and follow-up in PSC transplanted patients. IBD reactivation might have a pathogenic role in rPSC. In our single-center experience, rPSC did not affect patient and graft survival.