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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Antiviral therapy in the palliative setting of HCC (BCLC-B and -C)
Maria Reig1, Giuseppe Cabibbo2
1Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, IMDiM, Hospital Clínic de Barcelona, IDIBAPS, Universidad de Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
Insights
Direct-acting antivirals (DAAs) impact in advanced liver cancer (BCLC-B/C hepatocellular carcinoma) is unclear. Patient-specific decisions are crucial, weighing DAA risks against benefits for optimal treatment.
Area of Science:
- Hepatology
- Oncology
- Viral Hepatitis Treatment
Background:
- Direct-acting antivirals (DAAs) are effective for viral hepatitis but understudied in advanced liver cancer (BCLC-B/C hepatocellular carcinoma).
- Patients with HCC are often excluded from DAA trials, limiting understanding of their benefits and risks in this population.
- Active HCC at DAA initiation predicts treatment failure, with potential for worsened cirrhosis complications.
Purpose of the Study:
- To evaluate the impact and risks of DAAs in patients with BCLC-B/C stage hepatocellular carcinoma.
- To discuss the concept of "the point of no return" regarding DAA treatment in HCC patients.
- To propose decision-making tools for optimizing DAA use in individual HCC patient profiles.
Main Methods:
- Systematic review of current data on DAA usage in BCLC-B/C HCC patients.
- Analysis of factors influencing DAA effectiveness, including HCC status and liver function.
- Discussion of shared decision-making principles for DAA therapy in this cohort.
Main Results:
- DAA effectiveness is less defined in HCC patients, with active cancer potentially leading to treatment failure.
- Reversal of liver dysfunction may lag behind cancer progression, diminishing DAA benefits.
- The impact of DAAs on HCC recurrence remains controversial.
Conclusions:
- DAA treatment decisions for BCLC-B/C HCC patients must be individualized, considering potential risks and benefits.
- Shared decision-making is essential, informing patients about the complex interplay between DAA therapy, liver function, and cancer progression.
- Treatment prioritization should consider liver transplantation options and HCC stage alongside liver dysfunction.
Abstract:
The potential impact of direct-acting antivirals (DAAs) in patients with Barcelona Clinic Liver Cancer (BCLC)-B/C stage hepatocellular carcinoma (HCC) is understudied. Patients with HCC have been systematically excluded from randomised controlled trials evaluating the effectiveness of DAAs. Thus, the benefits of DAAs in patients with HCC are less well defined. The presence of active HCC before the initiation of DAA treatment is reported to be a predictor of DAA failure, and studies in patients without HCC have demonstrated that improvements in cirrhosis complications were lower or absent after DAA failure. Even if viral eradication is achieved using DAAs, reversal of liver function impairment may take longer than the development of end-stage cancer status. Additionally, the impact of DAAs on HCC recurrence is still a controversial topic. Thus, the decision of whether to use DAAs should be made on a patient-by-patient basis, and each patient should be informed of all the potential risks and benefits associated with their usage. This document summarises the current data on the usage of DAAs in BCLC-B/C patients, discusses the concept of "the point of no return" in the setting of DAAs, and proposes tools for deciding the best option for each patient profile. If liver function improvement overlaps with symptomatic HCC progression, the benefits of DAAs could be minimised, worsened, or fully counterbalanced. If the BCLC stage is defined using only liver dysfunction, the decision to prioritise DAA treatment should be based on the option (or lack thereof) of liver transplantation and/or the HCC stage. We propose applying a shared decision-making approach, informing each patient of all the potential risks and benefits of the proposed medical intervention.
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