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Journal of Clinical and
Translational Research Propranolol as a treatment for HCC

found that propranolol was associated with a decreased
risk of HCC death in patients with cirrhosis; however, a
significant difference in overall survival between patients
who took propranolol and those who did not was not
detected. Another study by Nkontchou et al. found that
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long-term propranolol treatment was associated with a
significant reduction in the incidence of HCC in patients
with HCV-associated cirrhosis. In addition, London and
McGlynn showed that patients who took propranolol for
an average of 3.5 years were significantly less likely to
develop HCC than patients who did not take propranolol,
and the risk of HCC was reduced by about 50% in those
taking propranolol. 54
At present, there are four clinical trials on ClinicalTrials.
gov investigating the effects of propranolol on HCC. At
the time of writing this article, one of these trials was in
phase II, while patient enrollment was still ongoing for the
remainder of the trials. To determine whether propranolol
Figure 2. Schematic mechanism of the effect of propranolol on liver cancer is a safe and effective treatment for HCC, the outcomes
cells. The use of propranolol reduces PD-1 and TIM-3, which increases of these trials will be crucial. The status of these trials
granzyme B and IFN-γ, which ultimately reduces the proliferation and may alter over time; therefore, it is always advisable to
metastasis of cancer cells. consult the ClinicalTrials.gov website for the most recent
Abbreviations: HCC: Hepatocellular carcinoma; IFN-γ: Interferon- information, as summarized in Table 1.
gamma; PD-1: Programmed cell death protein 1; TIM-3: T cell
immunoglobulin and mucin domain-containing protein-3.
7. Comparison of propranolol with other
propranolol can help kill liver cancer cells and boost the HCC prevention strategies
immune response against cancer (Figure 2). 49
7.1. Antiviral therapies
Propranolol has been shown to inhibit the formation
of new blood vessels essential for tumor growth. This The goals of antiviral treatments for persistent HBV
is one potential mechanism for its antitumor activity. infection are to inhibit viral replication, lessen hepatic
Observational studies have yielded promising results; inflammation, and stop the development of cirrhosis
however, randomized controlled trials are required to and HCC. Nucleos(t)ide analogs and IFN are the two
establish the drug’s efficacy and safety profile definitively. main families of antiviral drugs that have shown promise
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This multifaceted mechanism of action makes propranolol a in reducing HBV infection. By inhibiting HBV DNA
compelling adjunct therapy for HBV- and HCV-associated polymerase, nucleos(t)ide analogs such as entecavir
HCC. However, further studies, including randomized (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir
clinical trials, are needed to confirm its efficacy, determine alafenamide provide strong viral suppression while
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optimal dosing, and evaluate its long-term safety in cancer lowering hepatic inflammation and fibrosis. Patients
patients. 42,50 with persistent HBV infection have shown a considerable
decrease in their likelihood of developing HCC while
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6. Clinical studies on propranolol’s efficacy receiving long-term nucleos(t)ide analogs. Nonetheless,
against HBV/HCV-induced HCC there is variation in HCC risk reduction between various
nucleos(t)ide analogs; research indicates that TDF users
Several studies have investigated the effect of propranolol could have a lower incidence of HCC than ETV users.
on HCC. In 2023, a study by Wu et al. showed that However, because these results are observational in nature,
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propranolol reduced the risk of HCC development in they should be interpreted with caution. Furthermore,
patients with cirrhosis by up to 40% and also improved compared to individuals who were not treated, IFN
survival in patients with HCC, with a median survival of treatment has demonstrated a 34 – 41% reduced incidence
20 months in patients who received propranolol compared of HCC, indicating its potential advantages despite
to 12 months in patients who did not receive propranolol, restrictions on patient eligibility and adverse effects.
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but the optimal dose and duration of propranolol Direct-acting antivirals (DAAs), which provide sustained
treatment for HCC remains unknown. Cheng et al. virologic response (SVR) rates of 95% across all genotypes,
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Volume 11 Issue 4 (2025) 23 doi: 10.36922/JCTR025080010