Downstaging with atezolizumab-bevacizumab: a case series

Backgrounds/Aims Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown. Methods In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection. Conclusions Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging

Acute-on-Chronic Liver Failure (ACLF): The ‘Kyoto Consensus’-Steps From Asia

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the APASL ACLF Research Consortium (AARC) was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the \u27Golden Therapeutic Window\u27, the \u27transplant window\u27, and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The \u27Kyoto APASL Consensus\u27 presented below carries the final recommendations along with the relevant background information and areas requiring future studies

Impact of Karnofsky performance status on outcomes of patients with severe alcohol-associated hepatitis: a propensity-matched analysis

Background and Aims: Severity scores, including the model for end-stage liver disease (MELD) and discriminant function score, guide the treatment of patients with severe alcohol-associated hepatitis (AH). We aimed to investigate the impact of functional status on outcomes of patients with AH. Methods: Medically managed patients (n = 133) with AH from 1 January 2019 to 31 December 2022 were included in this prospective study. The objectives were to compare the long-term survival, recompensation rates, corticosteroid response, incidence of infections, hepatic encephalopathy (HE) and acute kidney injury (AKI) among propensity score-matched patients with good Karnofsky performance status (KPS) (score >= 50) and poor KPS (score <50) using Kaplan-Meier analysis. Results: Twenty-five patients with good KPS were matched with 25 patients with poor KPS and followed up for a median duration of 10 (0.5-33) months. Survival was 76% (19/25; 95% confidence interval (CI), 54.9-90.6) in patients with good KPS compared to 42.3% (11/25; 95% CI, 23.4-63.1) patients with poor KPS (P = 0.001) at 10 months. The recompensation rate was higher in the good KPS group than in the poor KPS group (68% vs 44%; P = 0.04). A higher proportion of patients in the good KPS group (78.9%) than in the poor KPS group (42.8%; P = 0.03) responded to corticosteroids. Survival was lower among non-responders in the poor KPS group (0% vs 75%; P = 0.01). The proportion of patients who developed infection (36% vs 28%; P = 0.051), HE (36% vs 12%; P = 0.01) and AKI (60% vs 16%; P < 0.001) was higher in patients with poor KPS than in good KPS. Conclusions: KPS is an important determinant of outcomes in patients with AH, including survival, recompensation, response to corticosteroids and complications

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes