Hepatic Adenomatosis

Hepatic adenomatosis is the presence of multiple (usually 10 or more) hepatocellular adenomas in a liver without cirrhosis. It is rare, and mostly in women.

It is linked with oral contraceptives, anabolic androgenic steroids, obesity and metabolic syndrome, glycogen storage disease, and maturity onset diabetes of the young type 3 (HNF1A mutation). It may also appear without identifiable risk factors.

Adenomas may be of different molecular subtypes: HNF1A-inactivated (steatotic, lowest risk), inflammatory (bleeding risk), beta catenin exon 3 mutated (highest risk of malignant change) and sonic hedgehog (bleeding risk). Haemorrhage occurs in up to 20% to 25% of adenomas, mainly those over 5 cm. Malignant transformation is about 4% to 5%, mainly in men and beta catenin subtype.

Pathophysiology.

Oestrogen or androgen exposure and metabolic signalling drive hepatocyte proliferation, while somatic mutations in HNF1A, beta catenin or inflammatory signalling genes define the subtypes.

Often asymptomatic. Abdominal pain, a mass, and acute pain with shock from haemorrhage or rupture. Abnormal liver tests (raised gamma glutamyl transferase and alkaline phosphatase) are common.

Red flags.

• Acute severe abdominal pain with hypotension (rupture).
• Rapid growth or a lesion over 5 cm.
• Raised alpha fetoprotein.
• Pregnancy with a known adenoma.

Magnetic resonance imaging with hepatobiliary or extracellular contrast is the best test, and can often assign the subtype (fat in the HNF1A type; marked T2 signal and persistent enhancement in the inflammatory type). Ultrasound screens; CT is less specific. Biopsy with immunohistochemistry (beta catenin, glutamine synthetase, liver fatty acid binding protein, serum amyloid A, C-reactive protein) is used when imaging is non-diagnostic and management depends on it. Test glucose and HNF1A where relevant, and exclude glycogen storage disease.

Differential diagnosis.

• Focal nodular hyperplasia.
• Hepatocellular carcinoma.
• Metastases.
• Nodular regenerative hyperplasia.
• Hepatic haemangioma.
• Fibrolamellar carcinoma.

Remove risk factors: stop oestrogen containing contraceptives and androgenic steroids, use non-oestrogen contraception (levonorgestrel intrauterine system), and lose weight.

Surveillance with magnetic resonance imaging at 6 months, then yearly, for lesions under 5 cm without high risk features.

Treat lesions over 5 cm (6 months after stopping risk factors if still over 5 cm), those in men, those with beta catenin mutation, rapidly growing lesions and symptomatic lesions: resection or ablation, with liver transplantation for diffuse adenomatosis with severe or complicated disease. Treat bleeding with resuscitation, transfusion at haemoglobin 70 g/L (80 g/L with cardiovascular disease) and transarterial embolisation, with surgery for failure or rupture.

Pregnancy needs counselling: adenomas over 5 cm should be treated before conception, and pregnancy with smaller lesions needs 6-weekly ultrasound.

Monitoring. Magnetic resonance imaging and alpha fetoprotein, liver tests every 6 to 12 months.

Referral and escalation. Hepatobiliary surgery and hepatology; interventional radiology for bleeding; transplant centre for diffuse disease.

Special groups. Pregnancy and glycogen storage disease need specialist planning.