Very low-calorie ketogenic diet for patients with liver disease

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

The KETONASH study evaluates the effects of a very low-calorie ketogenic diet (VLCKD) compared to a standard low-calorie Mediterranean diet in patients with non-alcoholic steatohepatitis (NASH) and significant liver fibrosis. This multicenter, open-label, randomized controlled trial will enroll patients with a histological diagnosis of NASH and significant hepatic fibrosis. Participants will be randomly assigned to either the VLCKD or the standard low-calorie diet for an initial 4-month intervention phase, followed by an 8-month weight maintenance phase, with support from a multidisciplinary team. The study aims to assess the impact of these dietary interventions on liver health and weight management.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Patients aged ≥18 years with histological diagnosis of NASH with evidence of fibrosis (defined according to NASH CRN) obtained no more than 6 months before enrollment;
* Stable weight for more than 6 months with BMI between 30-40 kg/m2;
* Patients in whom it is safe and feasible to proceed with liver biopsy and who consent to undergo liver biopsy after 12 months of enrollment to assess the effect of dietary treatment;
* Obtained informed consent.

Exclusion Criteria:

* BMI \<30 or BMI \>40
* Presence of evolved chronic liver disease into cirrhosis (histological F4 or elastometric LSM \>14 kPa)
* Type 1 diabetes mellitus
* Model for End-stage Liver Disease (MELD) score \>12, AST or ALT ≥5× ULN, HbA1c \>9.5%, INR ≥1.4, creatinine \>1.5 mg/dl, platelets \<100,000/mm3, and total bilirubin \>1.5 mg/dl.
* Concurrent presence of any other known chronic liver disease beyond MAFLD/NAFLD, such as alcoholic liver disease, viral (HCV/HBV), cholestatic-autoimmune (PBC/PSC/AIH), Wilson's disease, hemochromatosis, drug-induced liver injury (DILI), or the presence or suspicion of hepatocellular carcinoma (HCC);
* Average alcohol consumption exceeding 4/2 units/day (males/females) in the preceding 6 months and a history of excessive alcohol consumption in the last 5 years;
* Previous or planned liver transplant, bariatric surgery, ileal resection, or biliary diversion;
* History of acute cholecystitis and biliary obstructions (cholangitis);
* Recent (in the last 12 months) or concurrent use of agents known to cause hepatic steatosis (long-term systemic corticosteroids \[\>10 days\], amiodarone, methotrexate, tamoxifen, tetracyclines, high-dose estrogens, valproic acid);
* Recent (in the last 3 months) change in the dose/regimen or introduction of Vitamin E (at doses ≥400 IU/day), ursodeoxycholic acid (UDCA), betaine, S-adenosyl methionine, silymarin, or pentoxifylline;
* Presence of psychiatric disorders and/or diagnosis of any eating disorder;
* Life expectancy \<6 months.

Where it's running

• IRCCS Azienda Ospedaliero-Universitaria di Bologna
  Bologna, Italy Recruiting

Study contacts

• Principal investigator: Fabio Piscaglia — University of Bologna
• Study coordinator: Fabio Piscaglia, MD, PhD, Professor
• Email: fabio.piscaglia@unibo.it
• Phone: 0512142214

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.