Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

Hepatocellular Carcinoma (HCC) is the most common liver malignancy and third leading cause of cancer death worldwide. For early- and intermediate-stage disease, liver-directed therapies for locoregional control, or down-staging prior to definitive surgical therapy with hepatic resection or liver transplantation, have been studied broadly, and are the mainstays of current treatment guidelines. As HCC incidence has continued to grow, and with more patients presenting with advanced disease, our current treatment modalities do not suffice, and better therapies are needed to improve disease-specific and overall survival. Until recently, sorafenib was the only systemic therapy utilized, and was associated with dismal results. The advent of immuno-oncology has been of significant interest, and has changed the paradigm of therapy for HCC. Lately, combination regimens including atezolizumab plus bevacizumab; durvalumab plus tremelimumab; and pembrolizumab plus Lenvatinib have shown impressive responses of between 25–35%; this is much higher than responses observed with single agents. Complete responses with checkpoint inhibitor therapy have been observed in advanced-stage HCC patients. These dramatic results have naturally led to several questions. Can or should checkpoint inhibitors, or other immunotherapy combinations, be used routinely before resection or transplant? Is there a synergistic effect of immunotherapy with locoregional therapy, and will pre-treatment increase disease-free survival after surgical intervention? Is it immunologically safe to use these therapies prior to transplantation? Much is still to be learned in terms of the dosing, timing, and overall utility of the use of immune checkpoint inhibitors for pre-transplant care and down-staging. More studies will be needed to understand the management of adverse events while maximizing the therapeutic window of these agents. In this review, we look at the current data on therapy with immune checkpoint inhibitors in advanced HCC, with a focus on pre-transplant treatment prior to liver transplant.