KETOgenic diet therapy in patients with HEPatocellular adenoma: study protocol of a matched interventional cohort study

Abstract

IntroductionHepatocellular adenoma (HCA) is an uncommon, solid and benign liver lesion, mainly occurring in women using oral contraceptives. Patients are advised to stop using oral contraceptives (OC) and, as overweight is frequently observed, dietary restrictions. Metabolic changes are assumed to play a role and it has been suggested that diet may help to reduce tumour size. A low-calorie ketogenic diet (LCKD) has been shown to induce weight loss and multiple metabolic changes, including the reduction of portal insulin concentrations, which downregulates hepatic growth hormone receptors. Weight reduction and an LCKD can potentially reduce the size of HCAs.Methods and analysisWe designed a matched, interventional cohort study to determine the effect of an LCKD on the regression of HCA. The study population consists of female subjects with an HCA, 18–50 years of age, body mass index>25 kg/m2, who are entering a surveillance period including cessation of OC. A historical control group will be matched. The intervention consists of an LCKD (approximately 35 g carbohydrate/1500 kcal/day) for 3 months, followed by a less strict LCKD for 3 months (approximately 60 g carbohydrate/1500 kcal/day). Main study endpoint is the diameter of the HCA after 6 months, as compared with the historic control group. Secondary endpoints include adherence, quality of life, change in physical activity, liver fat content, body weight, body composition and resting energy expenditure.Ethics and disseminationThe medical ethical committee has approved the study protocol, patient information files and consent procedure and other study-related documents and procedures.Trial registration numberNL75014.078.20; Pre-results. https://www.trialregister.nl/trial/9092

Body weight changes and duration of estrogen exposure modulate the evolution of hepatocellular adenomas after contraception discontinuation

“…A prospective interventional study is currently being conducted to assess the effect of a low-calorie ketogenic diet on the evolution of HCA. [27] Moreover, weight gain should be discouraged in patients with HCA and a normal BMI at diagnosis. Our data suggested also that progestin-only-based contraception seems safe in women with residual HCAs even though the current study was not specifically designed to answer this question.…”

“…In addition to estrogen‐based contraception discontinuation, these data suggested that weight loss should be actively encouraged in patients with HCAs who are overweight or obese. A prospective interventional study is currently being conducted to assess the effect of a low‐calorie ketogenic diet on the evolution of HCA 27. Moreover, weight gain should be discouraged in patients with HCA and a normal BMI at diagnosis.…”

Do treats facilitate the interpretation of findings on caloric restriction?

“…We selected 200 email addresses of healthcare professionals from departments associated with the active clinical trials 29–31. The survey was sent twice, on 26 April 2023 and 10 May 2023, and people were given a response window of 6 weeks from 26 April 2023.…”

“…Contents and protocol on this investigational product have been published earlier 6. At the start of the presentation, colleagues were informed about the content of the presentation; an update on the active clinical trials investigating STF 29–31. After this brief introduction, they received information about the current randomised study.…”

“…We hypothesise that providing a treat positively influences the score given by participants who are not familiar with fasting, while not or negatively influencing the participants who are familiar with it. By combining two studies we hope to shed light on the factors that shape the attitudes of medical professionals toward research into fasting, to facilitate successful implementation of potential findings of current research,29–31 and ultimately contribute to evidence-based strategies. In summary, our study explores the effect of treats offered as a treat during presentations about IF and STF, while accounting for the irony of the situation: a calorie-rich brownie versus the information on the potential health benefits of restricting calories.…”