Liver transplantation and hepatocellular carcinoma 2023: a narrative review of management and outcomes.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in the United States. For certain patients, liver transplantation (LT) may be curative. The determination of which patients would benefit most from transplant and have the lowest risk of post-transplant recurrence has evolved as technology and treatments have expanded. We aim to review epidemiological changes in the HCC landscape, selection criteria for transplant, organ allocation, bridge therapies and post-transplant recurrence, and identify points for palliative care involvement. METHODS: Literature review was performed using PubMed MeSH searches in addition to reference list review. Additional information was retrieved from government regulatory and procurement organizations. KEY CONTENT AND FINDINGS: Metabolic and alcohol-associated liver diseases have surpassed hepatitis C as the leading causes of LT over the last decade, and have also risen as the underlying conditions seen in patients with HCC requiring LT. The United Network for Organ Sharing (UNOS) coordinates organ allocation, which includes disease severity, waitlist time, blood type, and distance from donor hospital. It has progressed to incorporate treatment response and alpha-fetoprotein into its listing criteria for patients with HCC, in addition to the well-established Milan Criteria (MC, one tumor <5 cm, ≤3 tumors ≤3 cm). Therapies to bridge patients until LT include locoregional therapies as well as immunotherapy. Dropout on the waitlist is seen up to 20% either due to decompensation or progression of disease. Recurrence of HCC post-transplant remains challenging. Given this, current guidelines recommend early palliative care involvement regardless of transplant listing status for both symptom management and advance care planning. CONCLUSIONS: For patients with HCC with favorable tumor biology, LT can be curative. However, given the symptom burden while awaiting LT and the notable number of patients who are unable to receive a transplant, early palliative care is critical in appropriate management of HCC.

Microbiota transfer following liver surgery involves microbial extracellular vesicle migration that affects liver immunity.

BACKGROUND: Short-term perioperative administration of probiotics was shown to alleviate postoperative complications and promote liver recovery among patients undergoing resection for liver malignancy. The mechanisms by which probiotic bacteria effectively influence the gut microbiome composition during the perioperative time are controversial. Here, we aim to elucidate the short-term direct biological effect of probiotic microbiota-derived vesicles on host liver cells during the perioperative period. METHODS: Probiotic-derived vesicles (pbMVs) were administered postoperatively. pbMVs were isolated and characterized from probiotics, mainly from the bacteria genus Lactobacillus, Bifidobacterium, and Lactococcus. Mice underwent bile duct ligation, sham laparotomy (SHAM), or 70% partial hepatectomy (70%PH). pbMVs were tracked in vivo, and intrahepatic cellular and molecular aspects were analyzed by flow cytometry and qRT-PCR techniques. Liver sinusoidal endothelial cells (LSECs) analysis for Vascular Cell Adhesion Molecule-1(VCAM-1) expression following pbMV stimulation of cultured liver non-parenchymal cells which had been activated by LPS. RESULTS: The administered pbMV rapidly translocated to the liver after surgery. pbMV administrations following surgeries enhanced neutrophil clearance; there was a dramatic decline in the liver neutrophil-to-lymphocyte ratio Ly6G+/CD3+ and an increase in IL6 levels. pbMVs reduced intrahepatic VCAM1 and ICAM2 expression compared with control following SHAM and decrease in IL10 levels following 70%PH. The administration of pbMV improved liver regeneration 72 hours following surgical liver resection with a significant decrease in IL17 expression. pbMVs modulated VCAM-1 on liver sinusoidal endothelial cells in liver cell culture. CONCLUSIONS: Our study findings provide mechanistic insights into the liver-gut axis following surgery and illustrate how probiotic vesicles can reduce adhesion molecule expression and affect immune cell invasion and liver immunity, resulting in improved liver recovery following hepatic surgery.

Resection vs Transplant Listing for Hepatocellular Carcinoma: An Intention-to-Treat Analysis.

BACKGROUND: Liver transplantation (LT) and liver resection (LR) are curative treatment options for patients with hepatocellular carcinoma within the Milan criteria. Severe organ shortage dictates the preference for LR. Our aim was to provide an intention-to-treat retrospective comparison of survival between patients who were placed on waiting lists for LT and those who underwent LR. METHODS: The medical records of patients with hepatocellular carcinoma within the Milan criteria treated by LR or listed for LT between 2007 and 2016 were reviewed. We performed intention-to-treat analyses of overall survival and recurrence. RESULTS: There were 54 patients on the waiting list for LT, and 30 of them underwent LR. Thirteen of the 54 patients (24%) were not transplanted because of disease-related mortality or tumor progression. The median waiting time to transplantation was 304 days. The 90-day mortality was higher in transplanted patients (9.8% vs 3.3%, P = .003). Intention-to-treat survival was similar for the LT and LR groups (5-year survival, 47.8% vs 55%, respectively, P = .185). There was a trend toward improved 5-year disease-free survival for listed patients (56.2% vs 26.3% for patients undergoing LR, P = .15). CONCLUSION: Intention-to-treat survival is similar in patients undergoing LR and those on waiting lists for LT. There is a 24% risk to drop from the transplant list. The higher perioperative mortality among patients undergoing LT is balanced by a higher tumor recurrence rate after LR.