Immunotherapy in Hepatocellular Cancer Patients with Mild to Severe Liver Dysfunction: Adjunctive Role of the ALBI Grade

Abstract

<jats:p>Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied 341 patients treated with programmed-death pathway inhibitors (n = 290, 85%). Pre-treatment ALBI independently predicted for OS, with median OS of 22.5, 9.6, and 4.6 months across grades (p &lt; 0.001). ALBI was superior to CTP in predicting 90-days mortality with area under the curve values of 0.65 (95% CI 0.57–0.74) versus 0.63 (95% CI 0.54–0.72). ALBI grade at ICI cessation independently predicted for PIOS (p &lt; 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p &gt; 0.05). ALBI grade identifies a subset of patients with prolonged survival prior to and after ICI therapy, lending itself as an optimal stratifying biomarker to optimise sequencing of systemic therapies in advanced HCC.</jats:p>

Albumin-to-alkaline phosphatase ratio as a predictor of tumor recurrence and prognosis in patients with early-stage hepatocellular carcinoma undergoing radiofrequency ablation as initial therapy

“…In HCC, the ALBI grade is superior to the CP grade in terms of assessing liver function reserve [26]. In addition, recent studies have demonstrated that the ALBI grade is associated with higher levels of AFP and more advanced tumor stage, which is correlated with malignant biological behavior and poor prognosis [32], similar to the association of AAPR in HCC. Moreover, HCC patients without cirrhosis, in whom HCC is presumably attributed to the direct carcinogenic effect of HBV infection, tend to harbor larger-sized or poorly differentiated tumors, contributing to the unfavorable prognosis of early-stage HCC [33,34].…”

NASH limits anti-tumour surveillance in immunotherapy-treated HCC

“…A multi-institutional dataset that included 427 patients with HCC treated with immune checkpoint inhibitors between 2017 and 2019 in 11 tertiary-care referral centres specialized in the treatment of HCC was analysed. Clinical outcomes of this patient cohort have been reported elsewhere 67,68 . Inclusion criteria were: 1) diagnosis of HCC made by histopathology or imaging criteria according to American Association for the Study of Liver Disease and European Association for the Study of the Liver guidelines; 2) systemic therapy with immune checkpoint inhibitors for HCC that was not amenable to curative or loco-regional therapy following local multidisciplinary tumour board review; 3) measurable disease according to RECIST v1.1 criteria at commencement of treatment with immune checkpoint inhibitors.…”

Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy

“…Given this study enrolled patients treated with ICI as part of routine clinical practice, our sample included patients with Child-Pugh B cirrhosis, largely excluded from clinical trials of ICI in HCC. While impaired liver function is a key prognostic determinant in HCC, 20 this was unrelated to the provision of CT and supplementary analyses inclusive of Child-Pugh A patients only were concordant with main study outcomes (online supplemental figures S3-4). We could not ascertain the relationship between CT and comorbidities other than liver dysfunction, an aspect worth exploring in prospective studies.…”