A low‐energy total diet replacement program demonstrates a favorable safety profile and improves liver disease severity in nonalcoholic steatohepatitis

• Published in: Obesity (Silver Spring, Md.) Md.), 2023-07, Vol.31 (7), p.1767-1778
• Main Authors: Koutoukidis, Dimitrios A., Mozes, Ferenc E., Jebb, Susan A., Tomlinson, Jeremy W., Pavlides, Michael, Saffioti, Francesca, Huntriss, Rosemary, Aveyard, Paul, Cobbold, Jeremy F.
• Format: Article
• Language: English
• Subjects: Adult; Alcohol; Biomarkers; Biopsy; Blood pressure; Cardiovascular disease; Diabetes; Diet; Drug therapy; Fibrosis; Gastrointestinal surgery; Humans; Liver - diagnostic imaging; Liver - pathology; Liver Cirrhosis - pathology; Liver diseases; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Non-alcoholic Fatty Liver Disease - diagnostic imaging; Non-alcoholic Fatty Liver Disease - pathology; Obesity; Obesity - pathology; Patient Acuity; Remission (Medicine); Sample size; Weight control
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.23793

Objective Low‐energy diets are used to treat obesity and diabetes, but there are fears that they may worsen liver disease in patients with nonalcoholic steatohepatitis (NASH) and significant‐to‐advanced fibrosis. Methods In this 24‐week single‐arm trial, 16 adults with NASH, fibrosis, and obesity received one‐to‐one remote dietetic support to follow a low‐energy (880 kcal/d) total diet replacement program for 12 weeks and stepped food reintroduction for another 12 weeks. Liver disease severity was blindly evaluated (magnetic resonance imaging proton density fat fraction [MRI‐PDFF], iron‐corrected T1 [cT1], liver stiffness on magnetic resonance elastography [MRE], and liver stiffness on vibration‐controlled transient elastography [VCTE]). Safety signals included liver biochemical markers and adverse events. Results A total of 14 participants (87.5%) completed the intervention. Weight loss was 15% (95% CI: 11.2%–18.6%) at 24 weeks. Compared with baseline, MRI‐PDFF reduced by 13.1% (95% CI: 8.9%–16.7%), cT1 by 159 milliseconds (95% CI: 108–216.5), MRE liver stiffness by 0.4 kPa (95% CI: 0.1–0.8), and VCTE liver stiffness by 3.9 kPa (95% CI: 2.6–7.2) at 24 weeks. The proportions with clinically relevant reductions in MRI‐PDFF (≥30%), cT1 (≥88 milliseconds), MRE liver stiffness (≥19%), and VCTE liver stiffness (≥19%) were 93%, 77%, 57%, and 93%, respectively. Liver biochemical markers improved. There were no serious intervention‐related adverse events. Conclusions The intervention demonstrates high adherence, favorable safety profile, and promising efficacy as a treatment for NASH.