Role of the Very Low Calorie Ketogenic Diet (VLCKD) in Patients With Non-Alcoholic Steatohepatitis (NASH) With Fibrosis

Prior treatment

• 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);
• Previous or planned liver transplant, bariatric surgery, ileal resection, or biliary diversion;
• 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);

Other illness

• Presence of evolved chronic liver disease into cirrhosis (histological F4 or elastometric LSM \>14 kPa)
• Type 1 diabetes mellitus
• 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;
• History of acute cholecystitis and biliary obstructions (cholangitis);
• Presence of psychiatric disorders and/or diagnosis of any eating disorder;

Lab values

• 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.

Other

• BMI \<30 or BMI \>40
• 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;
• Life expectancy \<6 months.

• 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.