Perspective:Advances in liver transplantation for hepatocellular carcinoma-A prototype for transplant oncology

In his 1969 book,Experience in Hepatic Transplantation,Thomas E Starzl wrote:“the unequivocal indication for the operation of liver replacement was originally considered to be primary hepatic malignancy which could not be treated with conventional techniques of subtotal liver resection”[1].Thus,it was not surprising that many cases in the early reported series of orthotopic liver transplantation(OLT)were for malignant indications[2-4].

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Combination of transarterial radioembolization with atezolizumab and bevacizumab for intermediate and advanced staged hepatocellular carcinoma:A preliminary report of safety and feasibility

Purpose:The IMbrave150 PhaseⅢtrial demonstrated superiority of atezolizumab and bevacizumab(Atezo/Bev)over sorafenib for unresectable hepatocellular carcinoma(HCC).The present study aims to evaluate the feasibility of TARE in combination with Atezo/Bev for treatment of intermediate and advanced staged HCC.Methods:Retrospective review at a single institution was performed between May 2021 and December 2022.Patients who received TARE using yttrium-90(Y90)with concomitant or sequential Atezo/Bev systemic treatment were included.The following outcomes were retrieved:overall survival(OS),radiologic tumor response,progression-free survival,technical adverse events related to TARE,and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0.Results:Ten consecutive patients with intermediate(n=4)and advanced stage HCC(n=6)were treated with TARE and sequential/concomitant Atezo/Bev.Tumor control was achieved in all TARE-treated target lesions(100%).Overall disease progression occurred in 4 patients with PFS of 78.8%and 66.7%at 6-and 12-months,respectively.Two patients died at follow-up,with 6-month and 12-month OS rates of 90.0%and 77.1%,respectively.Three(75%)patients with intermediate stage disease were downstaged into Milan criteria.One patient developed grade 3 transaminitis and hypoglobulinemia,while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis.Conclusion:This study demonstrates initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC.Further prospective studies with larger sample size are warranted.

Acute portal vein thrombosis after liver transplant presenting with subtle ultrasound abnormalities:A case report and literature review

BACKGROUND Portal vein thrombosis(PVT) after liver transplantation(LT) is an uncommon complication with potential for significant morbidity and mortality that transplant providers should be cognizant of.Recognizing subtle changes in postoperative ultrasounds that could herald but do not definitively diagnose PVT is paramount.CASE SUMMARY A 30-year-old female with a history of alcohol-related cirrhosis presented with painless jaundice and received a deceased donor orthotopic liver transplant.On the first two days post-operatively,her liver Doppler ultrasounds showed a patent portal vein,increased hepatic arterial diastolic flows,and reduced hepatic arterial resistive indices.She was asymptomatic with improving labs.On postoperative day three,her resistive indices declined further,and computed tomography of the abdomen revealed a large extra-hepatic PVT.The patient then underwent emergent percutaneous venography with tissue plasminogen activator administration,angioplasty,and stent placement.Aspirin was started to prevent stent thrombosis.Follow-up ultrasounds showed a patent portal vein and improved hepatic arterial resistive indices.Her graft function improved to normal by discharge.Although decreased hepatic artery resistive indices and increased diastolic flows on ultrasound are often associated with hepatic arterial stenosis post-LT,PVT can also cause these findings.CONCLUSION Reduced hepatic arterial resistive indices on ultrasound can signify PVT post-LT,and thrombolysis,angioplasty,and stent placement are efficacious treatments.

Liver Transplantation Services During the Time of COVID-19

The coronavirus disease 2019(COVID-19)is associated with high morbidity and mortality,prompting overwhelmed hospital systems to reallocate resources to those stricken with the disease.In response,many liver transplantation programs unexpectedly came to an abrupt halt,significantly affecting the lives of living donors and recipients around the world.As the risk-benefit scale of liver transplantation has changed in the era of COVID-19,it is prudent to understand the impact of COVID-19 on those with underlying liver disease and those in need of a liver transplant.In this review,we discuss recommendations put forth by hepatology and transplant societies,summarize results from emerging studies,and propose strategies to appropriately risk stratify patients prior to transplantation.