Immune checkpoint inhibitors for hepatocellular carcinoma

Jensen, Christopher E.; Loaiza‐Bonilla, Arturo; Bonilla-Reyes, Paula A

doi:10.2217/hep-2016-0004

Cited by 5 publications

(2 citation statements)

References 92 publications

(93 reference statements)

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“…Hepatocellular carcinoma (HCC) carries global mortality of over 600,000 cases every year [ 1 ]. The comparatively poorer prognosis of HCC with respect to other malignancies derives from the high proportion of patients presenting with advanced disease, the high rates of recurrence following radical treatment of early-stage tumours and the concomitant presence of liver dysfunction, a factor that often limits aggressive treatment [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

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

Pinato

Kaneko

Saeed

et al. 2020

Cancers

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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 < 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 < 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p > 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.

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Section: Introductionmentioning

confidence: 99%

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

Pinato

Kaneko

Saeed

et al. 2020

Cancers

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“…For HCC, depending on the stage at presentation, treatments range from resection and ablation for the early stage, transarterial chemoembolization for the intermediate stage, and kinase inhibitors and supportive care for advanced stage disease 92 . Numerous ongoing research studies are focused on the development and application of new therapeutic strategies including checkpoint inhibitors and procedures, such as selective internal radiotherapy, which could be used throughout the distinct disease stages 93–95 . For pediatric hepatoblastoma, although early stage tumors can often be cured by surgery alone without chemotherapy, all other stages usually require aggressive cisplatin/doxorubicin-based chemotherapy together with surgical resection and in some cases liver transplantation 96 …”

Section: Hepatitis B and C Virusesmentioning

confidence: 99%

Emerging trends in modeling human liver disease in vitro

Underhill

Khetani

2019

APL Bioengineering

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The liver executes 500+ functions, such as protein synthesis, xenobiotic metabolism, bile production, and metabolism of carbohydrates/fats/proteins. Such functions can be severely degraded by drug-induced liver injury, nonalcoholic fatty liver disease, hepatitis B and viral infections, and hepatocellular carcinoma. These liver diseases, which represent a significant global health burden, are the subject of novel drug discovery by the pharmaceutical industry via the use of in vitro models of the human liver, given significant species-specific differences in disease profiles and drug outcomes. Isolated primary human hepatocytes (PHHs) are a physiologically relevant cell source to construct such models; however, these cells display a rapid decline in the phenotypic function within conventional 2-dimensional monocultures. To address such a limitation, several engineered platforms have been developed such as high-throughput cellular microarrays, micropatterned cocultures, self-assembled spheroids, bioprinted tissues, and perfusion devices; many of these platforms are being used to coculture PHHs with liver nonparenchymal cells to model complex cell cross talk in liver pathophysiology. In this perspective, we focus on the utility of representative platforms for mimicking key features of liver dysfunction in the context of chronic liver diseases and liver cancer. We further discuss pending issues that will need to be addressed in this field moving forward. Collectively, these in vitro liver disease models are being increasingly applied toward the development of new therapeutics that display an optimal balance of safety and efficacy, with a focus on expediting development, reducing high costs, and preventing harm to patients.

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