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      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
      Drugs & Diseases > Gastroenterology

      Hepatocellular Adenoma (Hepatic Adenoma) Treatment & Management

      Updated: Dec 03, 2020
      • Author: Michael H Piper, MD; Chief Editor: BS Anand, MD  more...
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      Treatment

      Approach Considerations

      Imaging and follow-up

      Baseline imaging with contrast enhanced magnetic resonance imaging (MRI) is recommended at the initial diagnosis of hepatocellular adenoma (HCA) (hepatic adenoma), to aid in characterization of lesion and possible subtype determination. It is important to recognize the size of the tumor as well as any exophytic protrusion, as these features are associated with an increased risk of hemorrhage. [48, 49]  

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      Medical Care

      For women with hepatocellular adenomas (HCAs) (hepatic adenomas) with a baseline size smaller than 5 cm, rupture and subsequent hemorrhage are rare, and medical management is reasonable with appropriate imaging followup. [103] For tumors with multiple lesions, management is based on the size of the largest lesion, rather than on the number of lesions, as previous studies have not shown a significant increased risk of hemorrhage or malignancy based on number alone. [32]

      For all presumed HCAs, the 2016 European Association for the Study of the Liver (EASL) guidelines recommend repeat contrast-enhanced magnetic resonance imaging (MRI) 6 months from the baseline diagnosis to assess for persistent size of at least 5 cm or for increasing diameter size (≥20%) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid malignant tumors. [20, 104] The RECIST (version 1.1) criteria note that the 20% or greater increase in diameter should also be accompanied by a 5-mm absolute increase in diameter. [104]

      A definition for stable disease is lacking; however, the 2016 EASL guidelines recommend annual imaging if the hepatic adenoma is stable 12 months from the initial diagnosis. Overall, the initial diagnosis would thus involve a baseline imaging study, followed by imaging at 6 and 12 months following baseline, and then annual imaging, if stable. Imaging intervals can be lengthened to every 2 years if the HCA size is stable after 5 years. [105] Ultrasonography is acceptable if the lesion is clearly defined. [20]  The 2014 American College Gastroenterology (ACG) guidelines slightly differ from the EASL's, recommending computed tomography (CT) scanning or MRI at 6-12 month intervals for at least 2 years, followed by annual imaging based on tumor growth and stability. [1, 106]

      General measures

      In women, HCAs smaller than 5 cm are less likely to rupture or progress to hepatocellular carcinoma (HCC). [56] Women should stop using any medications implicated in HCA formation, which most often includes oral contraceptives. This cessation allows for regression in the size of the majority of the tumors, although complete resolution is atypical. [20] Repeat imaging following discontinuation of causative medications should follow in 6-12 months to ensure stability of the hepatic adenoma. Note that the risk of malignant transformation or even possible HCA enlargement remains even after the contraceptive or steroid use has been discontinued. [59, 107, 108]

      Women with HCAs smaller than 5 cm and who have a body mass index (BMI) over 25 kg/m2 should be encouraged to maintain a healthy body weight. [20] If β-catenin activated HCA (β-HCA) is confirmed, curative treatment or resection should be considered regardless of tumor size. [1, 20] Symptomatic HCA should be considered for surgical resection as well. [52]

      In men, resection or curative therapy should be pursued regardless of tumor size, owing to a significant risk of malignant transformation in this population. [26]

      Hemorrhage

      Do not delay adequate resuscitation with intravenous (IV) fluids and blood products if any concern for active hemorrhage of HCA is suspected. Prompt imaging with CT or MRI should be pursued. In cases of hemodynamic instability or hemorrhage not responding to resuscitation as well as lesions with difficult anatomic position, transarterial embolization or other noninvasive procedures can be performed to control bleeding. [109] Hepatic adenomas of 5 cm and larger should be considered for surgical resection due to their propensity for rebleeding. [1, 20, 110]

      Pregnancy

      Given the tendency of HCAs to enlarge and the increased risk of rupture and hemorrhage during pregnancy, close monitoring of these women is required along with a multidisciplinary approach. [111]  The 2016 EASL guidelines recommend close monitoring with ultrasonography every 6-12 weeks to monitor for changes in tumor size. For HCAs smaller than 5 cm without growth or exophytic location, vaginal delivery can be pursued. [20, 111] If the HCA enlarges significantly, embolization can be considered. If the pregnancy is at less than 24 weeks' gestation, surgical intervention can be considered to reduce the maternal and fetal risk of ionizing radiation. [20, 112]

      There are no consensus guidelines for pursuing pregnancy with known hepatic adenoma, especially if it is at least 5 cm. In this setting, discussion regarding surgical resection prior to pregnancy may be most appropriate. A 2020 prospective study that evaluated pregnant women with tumors smaller than 5 cm found minimal maternal risk and no risk to the fetus. [61] The study recommended contrast-enhanced MRI prior to pregnancy to ensure an accurate diagnosis and to differentiate HCA from focal nodular hyperplasia (FNH), as well as serial ultrasonographic examinations during pregnancy to monitor for changes in the size of the lesion. [61]  HCA rupture and hemorrhage during pregnancy requires appropriate hemodynamic resuscitation and noninvasive embolization when appropriate. [113]

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      Surgical Care

      Surgical indications and considerations

      Surgical management of hepatocellular adenoma (HCA) (hepatic adenoma) is indicated regardless of tumor size in men, [26]  as well as with confirmation of β-catenin activated HCA (β-HCA) subtype, [1, 20] symptomatic HCA, [52] and residual lesion following HCA hemorrhage with intervention. [20]  Patients with significantly elevated serum alpha-fetoprotein (AFP) levels should undergo further evaluation and consideration of resection regardless of HCA size due to the concern for underlying hepatocellular carcinoma (HCC).

      Surgical management of HCA is indicated when its diameter is at least 5 cm or has an increasing diameter (≥20%) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid malignant tumors. [20, 104] Increasing diameter should be reevaluated 6-12 months following cessation of causative agents regardless of HCA size. Although a tumor diameter of 5 cm and larger is an indication for surgery, for patients with an HCA of at least 5 cm with steroid exposure, reevaluation in 6-12 months is reasonable based on patient preference, with the understanding that HCC can develop and the diameter can increase regardless of steroid cessation. [20]

      In a multicenter study of 124 patients, Deneve et al reported that factors that predisposed HCAs to rupture were larger tumors and recent hormone use in women. [51] The investigators recommended surgical resection when HCAs approached 4 cm in size or if hormonal therapy was required.

      Cho et al reported their experience with the management and outcomes of 41 patients with hepatic adenomas treated at the University of Pittsburgh between 1988 and 2007, in which surgical resection was preferable to observation if patients' comorbidities and the anatomic location of the tumor were acceptable due to risks of hemorrhage (29%) and malignancy (5%). [50]

      Liver transplantation

      In rare patients with glycogen storage disease (GSD), or other underlying liver disease, liver transplantation may be the only intervention that may remove all lesions and cure the underlying metabolic defect. [114] It is important to monitor these patients closely, as evidence exists showing the chromosomal aberration of simultaneous gain of 6p and loss of 6q could be high risk in the progression from HCA to HCC, regardless of metabolic control. [45] Liver transplantation has also been successfully performed for spontaneous intrapartum rupture of a hepatic adenoma. [115]

      Timing and approach

      With regard to the timing of resection, Klompenhouwer et al have suggested that a 6-month cut-off point in women is too early for assessment of regression of HCAs of 5 cm and larger. [116] Rather, they indicate that in women with typical, non-β-HCAs, regardless of the baseline diameters, the cut-off point may be extended to up to 12 months. [116]

      The majority of tumors can be resected locally or with segmental partial lobectomy. In cases of multiple hepatic adenomas, resection of the largest lesions may be the most appropriate approach. [20, 29]  Data from limited case series show mortality for emergency resection of ruptured HCA is about 5-10%, whereas mortality for elective surgery has been estimated to less than 1%. [54]

      In a retrospective (1989-2013) multi-institutional European study of all patients who had undergone open or laparoscopic hepatectomies for hepatic adenomas to investigate the effects of the surgical approach on postoperative morbidities, Landi et al found that open surgery and laparoscopy showed similar postoperative morbidity rates and severities. [117] However, laparoscopy was associated with significantly less blood loss, a reduced need for transfusion, and a shorter hospital stay. [117]

      Radiofrequency (RF) ablation

      RF ablation can be used effectively in the treatment of hepatic adenoma. [118] However, multiple sessions are often required, and signs of residual adenoma might persist in some patients despite repetitive treatment. RF ablation may be especially beneficial in cases not amenable to surgery or in patients who would require major hepatic resection. Cases not amenable to surgery include those with centrally located lesions or the presence of multiple HCAs in both lobes of the liver.

      In a retrospective, single-arm study of 36 patients with 58 HCAs who underwent 44 procedures with percutaneous thermal ablation, Mironov et al reported a primary efficacy of 88% and a secondary efficacy of 100%, with a major complication rate of 4.5% (postprocedural hemorrhage). [119] At a median follow-up of 1.7 years, there was 100% clinical efficacy with no reports of malignant transformation, adenoma-related hemorrhages, or deaths.

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