Very low-calorie ketogenic diet for patients with liver disease

The Role of Very Low Calorie Ketogenic Diet (VLCKD) in Patients Affected by Non-Alcoholic Steatohepatitis (NASH) With Significant Fibrosis (KETONASH)

This study is testing whether a very low-calorie ketogenic diet can improve liver health and help with weight management in people with liver disease compared to a standard low-calorie Mediterranean diet.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Bologna (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Bologna)
• Trial ID: NCT06308757 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a histological diagnosis of NASH and significant liver fibrosis, stable weight, and a BMI between 30-40 kg/m2.

Not a fit: Patients with a BMI below 30 or above 40, those with cirrhosis, or other significant chronic liver diseases will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a novel dietary intervention to improve liver health and manage obesity in patients with NASH.

How similar studies have performed: Other studies have shown promising results with dietary interventions in liver disease, but the specific approach of VLCKD in this context is relatively novel.

Eligibility criteria

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 this trial is running

Bologna

• 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

Conditions NASH; NAFLD; Obesity; Liver Fibrosis; vlckd; diet; ketogenic diet