Phenotypes of Metabolic Dysfunction-Associated Steatotic Liver Disease-Associated Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) typically develops as a consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis, has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) also can develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not elucidated completely, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardiometabolic risk factors and the molecular targets that could be tackled effectively. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and health care burden, the mechanistic data promoting MASLD, metabolic dysfunction-associated steatohepatitis, and MASLD-HCC. Its natural history, prognosis, and treatment are addressed specifically, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies also are discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.

Ultra Deep Sequencing of Circulating Cell-Free DNA as a Potential Tool for Hepatocellular Carcinoma Management.

BACKGROUND: Cell-free DNA (cfDNA) concentrations have been described to be inversely correlated with prognosis in cancer. Mutations in HCC-associated driver genes in cfDNA have been reported, but their relation with patient's outcome has not been described. Our aim was to elucidate whether mutations found in cfDNA could be representative from those present in HCC tissue, providing the rationale to use the cfDNA to monitor HCC. METHODS: Tumoral tissue, paired nontumor adjacent tissue and blood samples were collected from 30 HCC patients undergoing curative therapies. Deep sequencing targeting HCC driver genes was performed. RESULTS: Patients with more than 2 ng/µL of cfDNA at diagnosis had higher mortality (mean OS 24.6 vs. 31.87 months, p = 0.01) (AUC = 0.782). Subjects who died during follow-up, had a significantly higher number of mutated genes (p = 0.015) and number of mutations (p = 0.015) on cfDNA. Number of mutated genes (p = 0.001), detected mutations (p = 0.001) in cfDNA and ratio (number of mutations/cfDNA) (p = 0.003) were significantly associated with recurrence. However, patients with a ratio (number of mutations/cfDNA) above 6 (long-rank p = 0.0003) presented a higher risk of recurrence than those with a ratio under 6. Detection of more than four mutations in cfDNA correlated with higher risk of death (long-rank p = 0.042). CONCLUSIONS: In summary, cfDNA and detection of prevalent HCC mutations could have prognostic implications in early-stage HCC patients.

Clinical characteristics and prognosis of heart failure in elderly patients.

OBJECTIVES: The aim of this study was to assess prevalence, clinical characteristics, and prognosis in elderly patients with heart failure with preserved ejection fraction (HFPEF) compared to patients with heart failure with reduced ejection fraction (HFREF) who were followed in an internal medicine unit. METHODS: In this retrospective observational study, the sample consisted of 301 patients followed in an internal medicine referral unit between January 2007 and December 2010. All patients were checked to determine their vital status on 31 December 2012. Survival was analyzed using Kaplan-Meier curves, and compared using the log-rank test. RESULTS: Of the 301 patients, 165 (54.8%) were women. In the 263 cases (87.4%) who underwent echocardiographic assessment, 190 (72.2%) had HFPEF and 73 (27.8%) had HFREF. Mean age was similar in the two groups (80.1 and 79.9 years; p=0.905), with a predominance of women in the HFPEF group (60.5% women, 42.5% men; p=0.025). The main etiology was hypertensive heart disease in the HFPEF group. Regarding treatment, more beta-blockers were administered in the HFREF group. No statistically significant differences were observed between the groups in terms of cardiovascular risk factors, comorbidities, NYHA functional class, or mortality. CONCLUSION: Clinical characteristics were similar for both HFPEF and HFREF patients. Women were predominant in the HFPEF group, as was hypertensive etiology. No significant differences in mortality were observed between the groups.