In light of positive efficacy and safety findings from the IMbrave150 trial of 
atezolizumab plus bevacizumab, this novel combination has become the preferred 
first-line standard of care for patients with unresectable hepatocellular 
carcinoma (HCC). Several additional trials are ongoing that combine an immune 
checkpoint inhibitor with another agent such as a multiple kinase inhibitor or 
antiangiogenic agent. Therefore, the range of first-line treatment options for 
unresectable HCC is likely to increase, and healthcare providers need succinct 
information about the use of such combinations, including their efficacy and key 
aspects of their safety profiles. Here, we review efficacy and safety data on 
combination immunotherapies and offer guidance on monitoring and managing 
adverse events, especially those associated with atezolizumab plus bevacizumab. 
Because of their underlying liver disease and high likelihood of portal 
hypertension, patients with unresectable HCC are at particular risk of 
gastrointestinal bleeding, and this risk may be exacerbated by treatments that 
include antiangiogenic agents. Healthcare providers also need to be alert to the 
risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of 
hepatitis B or C virus infection. They should also be aware of the possibility 
of rarer but potentially life-threatening adverse events such as pneumonitis and 
cardiovascular events. Awareness of the risks associated with these therapies 
and knowledge of adverse event monitoring and management will become 
increasingly important as the therapeutic range broadens in unresectable HCC.