Study Results Suggest Waiting Longer Before Resecting Hepatocellular Adenomas

May 17, 2017
Shannon Connelly

Current guidelines recommend waiting 6 months before resecting a large hepatocellular adenoma to prevent a transformation to a malignant tumor; however, a recent study suggests that waiting longer could benefit some patients.

The retrospective cohort study included 194 patients diagnosed with hepatocellular adenoma >5 cm between 1999 to 2015. The results showed significantly higher body mass index (31.6 vs 28.5 kg/m;P= .029), smaller baseline diameter of the adenoma (60% vs 25%;P<.001), and multiple lesions (85% vs 64%;P<.001) in the patients who did not undergo treatment for hepatocellular adenoma. In the surveillance group, 61 hepatocellular adenomas (71%) showed regression to ≤5 cm after a median time of 85 weeks (95% CI, 59-111).

Lead study author Anne Julia Klompenhouwer, MD, and colleagues concluded that a 6-month cut-off point for consideration of resection for tumors ≤5 cm may lead to overtreatment. They recommended the cut-off point should be prolonged for females with typical, non β-catenin-mutated hepatocellular adenoma to ≥12 months, irrespective of baseline diameter. Additionally, it might be justifiable to wait up to 24 months for hepatocellular adenomas of >7 cm size, assuming the risk of complications does not increase.

In an interview withTargeted Oncologyduring the 2017 International Liver Congress, hosted by the European Association for the Study of the Liver (EASL), Klompenhouwer, Department of Surgery at Erasmus Medical Center in Rotterdam, The Netherlands, discussed the risk factors associated with developing hepatocellular adenoma and the key takeaways from this research.

TARGETED ONCOLOGY:What are the risk factors for developing hepatocellular adenomas?


Hepatocellular adenomas are benign liver tumors, but the difficulty with these tumors are that they can be complicated by a few things. The complications can include hemorrhage, which is mostly associated with larger size, and malignant transformation, which is very rare, but it's also associated with size and a few molecular subtypes. Risk factors for the development of adenomas are [gender]—females have them more often, and the use of oral contraceptive pills and obesity [can increase chances].

TARGETED ONCOLOGY:Can you discuss the objective of your study?


The aim of the study is focused on when to decide to resect large liver adenomas, because you want to avoid the complications. That is why we often say adenomas larger than 5 cm should be resected, but the most important question is when to do that. We see a lot of adenomas become smaller after you withdraw oral contraceptives or if a patient loses a lot of weight. It's always a question of when to do the surgery or when to wait. We tried to determine how long we should wait and see the natural course of the adenomas, because the guidelines say you should wait for 6 months and if it's still larger than 5 cm, you should perform a resection.

What we did was a retrospective cohort study in a large cohort of patients. We had about 100 patients with adenomas that we didn't treat and we decided to see how long it took to regress. We saw that the median time for the adenomas to become smaller than 5 cm was about 1.5 years. We say that you should definitely wait longer than 6 months to see if they progress.

TARGETED ONCOLOGY:What do you hope people attending this meeting are going to take away from this research?


I think it's important, especially for adenomas, to determine, first of all, the risk of complications because you have a few subtypes that have a higher risk of complications. Especially in the more benign ones, which are the steatotic subtypes and the inflammatory subtypes. It's justified to wait a little longer and you can spare patients a large liver surgery if you wait a few months longer to see what the natural course of the tumor is.

TARGETED ONCOLOGY:How has detection of adenomas evolved over the years?


For the adenomas, especially for the last few decades, there has been a French study group that did a lot of research on the different subtypes. If you asked them 15 years ago, we thought adenomas was just 1 entity. Now we see there are so many more factors and different molecular classifications. There is still a lot of research going on there, especially in trying to determine which patients are at risk for a malignant transformation. I think it's important that we try to see which patients have a high risk so we can treat them, and to be able to say that in other patients it's essentially benign and we don't have to do anything.

TARGETED ONCOLOGY:Do you think there is potential to identify this high-risk group in the next 5-10 years?

Klompenhouwer: I think the molecular classification is very important, especially because now we can classify them by radiology and immunohistochemistry, but I think the most important 1 is still the molecular classification in the diagnostics, we should expand that a little bit more still.

We have a lot of clinical research still going on in liver adenomas. I think we have a very large cohort in which we can easily study a few things. I think it's very important that we should collaborate with other centers that do a lot of pathology research, because the link between the clinic and pathology is essential here.


Klompenhouwer AJ, Br&ouml;ker MEE, Thomeer MGJ, et al. Resection of larger hepatocellular adenomas: when is it justified? Presented at: 2017 International Liver Congress; April 19-23, 2017; Amsterdam, Netherlands. Abstract THU-082.