KETOgenic diet therapy in patients with HEPatocellular adenoma

Hepatocellular adenoma (HCA) is an uncommon, solid and benign liver lesion.
Typically, it is a solitary lesion found in women within their reproductive
years and it is strongly associated with the use of oral contraceptive
medication (OC). Development of HCA is also associated with obesity and
metabolic syndrome. More recently, studies have shown a rising incidence of HCA
diagnosis, current prevalence is estimated to be between 0.001 and 0.004%. HCA
consists off several subtypes: inflammatory, steatotic, β-catenin mutation
associated and unspecified. A higher BMI is associated with inflammatory HCA,
which is also associated with multiple lesions. Steatotic HCA more often
consist of single lesions.

Management of HCA requires a multidisciplinary approach. For female patients,
it depends on the associated symptoms, lesion size and location. All female
patients are advised to stop using OC and maintain a healthy body weight. Women
with a HCA can be included in a surveillance period for 6 months, after which a
contrast-enhanced magnetic resonance imaging (MRI) is performed. The aim is to
predict if larger lesions (>5cm) will regress, thus avoiding unnecessary
surgery. Treatment modalities to further enhance the regression and avoid
surgery are an interesting research possibility. As overweight is frequently
observed in women with liver adenoma, metabolic changes are assumed to play a
role and diet may help to reduce tumor size.

Dietary restriction, defined as reduced intake of food without malnutrition,
may be effective. It*s associated with metabolic changes, extended life span,
lower risk of age associated diseases, improved fitness and increased
resistance to acute stress. In combination with a ketogenic diet, it also
reduces portal insulin concentrations, which down-regulate hepatic growth
hormone receptors and reduces IGF-I synthesis. A recent study also shows the
beneficial effect of eucaloric very-low-carbohydrate diet on disease control of
acromegaly patients. Dietary restriction can be performed in different regimens
such as short-term fasting or up to 30% reduced daily calorie intake. To
explore the potential efficacy of dietary restriction, we aim to investigate
whether the beneficial effects of a ketogenic diet with slight caloric
restriction might increase the regression of HCA. This will further strengthen
the treatment modality of close observation and avoid surgical resection.

to determine the effect of dietary restriction and the ketogenic diet on the
regression of hepatocellular adenoma after 6 months.

A single-centre pilot study

Diet:
Month 1-3: Low carbohydrate, ketogenic diet containing approximately 1500 kcal,
35grams of carbohydrate and 0.8 g/kg of protein /day
Month 4-6: Moderate carbohydrate, ketogenic diet containing approximately 1500
kcal, 60grams of carbohydrate and 0.8 g/kg of protein /day

The extent of the burden of our study is considered low. Dietary restriction
and the ketogenic diet have been proven feasible and safe in previous studies.
For this study, three extra blood samples by 3 venous punctures are taken. No
extra visits to the hospital or imaging studies are needed in order to obtain
all the information required for this study. Several standardized
questionnaires are asked to be filled in during and after the diet. Mentioned
questionnaires take about 5-10 minutes to complete. No other risks concerning
the dietary intervention are to be expected.