Ellison Sivertsen (birchsign6)

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide and carries a poor prognosis. Historically, sorafenib was the only available systemic treatment for advanced HCC. However, in recent years, 6 new treatments have been approved by the US Food and Drug Administration (FDA) regorafenib, lenvatinib, cabozantinib, pembrolizumab, ramucirumab, and nivolumab. Data are lacking regarding the most appropriate sequencing pathway for these agents. Our objective was to conduct a comprehensive cost effectiveness analysis (CEA) of different 1st- and 2nd-line treatment pathways for HCC reflecting all new drug approvals, and then use our data to provide guidance for clinicians on which pathway is the most cost-effective. Markov models were used to evaluate the cost effectiveness of 8 different 1st- and 2nd-line treatment sequences. The model allowed for 9 possible states. Cost effectiveness ratios (CER) and incremental CER (ICER) were calculated to compare costs between different pathways and e strategy was 1st-line tyrosine kinase inhibitor therapy followed by 2nd-line immunotherapy. All pathways exceeded a commonly accepted WTP of USD 100-150,000/QALY. Our preliminary results warrant further studies to best inform real-world practices. Dietary restriction (DR) is a preventive strategy for obesity, metabolic syndrome, cardiovascular disease, and diabetes. Although an interconnection between obesity, metabolic syndrome, fatty liver, and hepatocellular carcinoma has been documented, the mechanism and impact of DR on steatosis-derived hepatocarcinogenesis are not fully understood. This study aimed to evaluate whether DR can prevent hepatic tumorigenesis. Male hepatitis C virus core gene transgenic (HCVcpTg) mice that develop spontaneous age-dependent insulin resistance, hepatic steatosis, and ensuing liver tumor development without apparent hepatic fibrosis, were fed with either a control diet ad libitum (control group) or 70% of the same control diet (DR group) for 15 months, and liver phenotypes were investigated. DR significantly reduced the number and volume of liver tumors. DR attenuated hepatic oxidative and endoplasmic reticulum stress and markedly suppressed nuclear factor-κB, signal transducer and activator of transcription 3 (ST persistent 30% reduction of daily food intake is beneficial for preventing steatosis-associated hepatocarcinogenesis caused by HCV core protein. DR suppressed steatosis-associated hepatic tumorigenesis in HCVcpTg mice, mainly due to attenuation of pathways involved in inflammation, cellular stress, cell proliferation, insulin signaling, and senescence. These findings support the notion that persistent 30% reduction of daily food intake is beneficial for preventing steatosis-associated hepatocarcinogenesis caused by HCV core protein. Background liver function in patients with hepatocellular carcinoma (HCC) has improved remarkably with advances in various treatments. Recently, the Child-Pugh classification (CPC) system has been recognized as limited in its ability to assess patients with good hepatic reserve. We compared the albumin-bilirubin (ALBI) grade, which is suitable for a more detailed evaluation of patients with good liver function, with CPC over a 30-year period. A total of 2,347 patients were analyzed. Patients were stratified by year of diagnosis into 6 groups Group A (1990-1994, = 376), Group B (1995-1999, = 434), Group C (2000-2004, = 438), Group D (2005-2009, = 444), Group E (2010-2014, = 392), and Group F (2015-2018, = 263). We compared ALBI grade and CPC across the groups. The prevalence of patients with CPC A at diagnosis increased throughout the study period, reaching nearly 80% in Groups E and F ( < 0.001). By contrast, the percentage of patients with ALBI grade 1 disease remained approximately 50% in Groups E and F ( < 0.001).