Dataset Information

Multidisciplinary lifestyle intervention is associated with improvements in liver damage and in surrogate scores of NAFLD and liver fibrosis in morbidly obese patients.

ABSTRACT:

Purpose

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Particularly morbidly obese patients are at risk of developing progressive liver disease. Nutritional and lifestyle intervention is recommended as the standard of care in NAFLD. However, there is a striking lack of evidence to support the efficacy of lifestyle intervention to treat NAFLD in morbidly obese patients. Here, we aimed to assess the impact of lifestyle intervention on NAFLD in the morbidly obese in a real-world setting.

Methods

136 obese patients were included in an industry-independent, multiprofessional lifestyle intervention program with a lead-in phase of 12 weeks of formula diet and a total of 48 weeks intensive counselling. Body weight and markers of the metabolic syndrome were analyzed. Presence of NAFLD was screened for by use of non-invasive markers of fatty liver, non-alcoholic steatohepatitis and liver fibrosis.

Results

Weight loss goals (i.e. > 5% or > 10% of initial body weight, respectively, depending on baseline BMI) were achieved in 89.7% of subjects in the intention-to-treat analysis and 93.9% in the per-protocol analysis. This was associated with a pronounced improvement in serum ALT values. The percentage of subjects who fulfilled non-invasive criteria for fatty liver dropped from 95.2 to 54.8%. Risk of NASH improved and the number of patients at risk of liver fibrosis declined by 54.1%.

Conclusion

Lifestyle intervention was associated with a marked improvement of serum ALT and an improvement of surrogate scores indicative of NAFLD and, importantly, advanced fibrosis, in a real-world cohort of morbidly obese patients.

SUBMITTER: Bischoff M

PROVIDER: S-EPMC9279260 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is common in both prediabetic patients and healthy overweight individuals, yet it remains understudied. This study investigates the effects of hepatic steatosis on fibrosis and evaluates the major predictors of liver injury in prediabetes and whether this damage is reversible with Mediterranean diet and administration of the nutraceutical silymarin.MethodsFirst, a case-control study was conducted in which 212 patients with prediabetes, not known to have NAFLD, and 126 healthy controls underwent clinical evaluation, transient elastography with measurement of liver stiffness (LS) and controlled attenuation parameter (CAP). Subsequently, the 212 prediabetic patients were enrolled into a prospective randomized interventional study: 104 were allocated to Mediterranean diet alone while 108 followed Mediterranean diet plus supplementation with silymarin (a flavonolignan complex isolated from Silybum marianum and Morus alba). The administered silymarin dose was 210 mg twice daily for 6 months. Clinical and instrumental evaluations were repeated at the end of the 6 month-study period. Prediabetics were genotyped for patatin like phospholipase domain containing 3 (PNPLA3).ResultsIn the case-control study, 29% of prediabetic patients have significant fibrosis defined as LS ≥ 7.9 kPa vs only 3% of controls (p < 0.001). PNPLA3 genotype CG/GG are significantly associated with significant fibrosis LS ≥ 7.9 relative to CC genotype χ2(1) = 76.466, p < 0.001. Binomial regression analysis shows that increase in BMI, ALT and AST are significantly associated with increased likelihood of significant fibrosis (χ2(7) = 191.9, p < .001) prior to intervention. In the randomized interventional study, prediabetics following Mediterranean diet alone (group 1) experienced a significant regression of fibrosis and decrease in ALT, HbA1c, FBS after 6 months (p < 0.001); similar findings were observed in patients following Mediterranean diet plus silymarin regimen (group 2); group 2 had a significant decrease in HbA1c relative to group 1 (95% CI: 37.8-38.6 vs 39.5-40.3, p < 0.001).ConclusionPNPLA3 genotype CG/GG and elevated BMI are the major predictors of significant fibrosis in prediabetic patients prior to intervention in this study. Mediterranean diet either alone or with silymarin treatment for 6 months leads to significant regression of liver damage and improvement of the glycemic profile in prediabetic patients. Yet, as combination treatment of silymarin with Mediterranean diet shows significant reduction of HbA1c when compared to diet alone, this suggests that silymarin may exert an independent anti-glycemic action.

Project description:The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression.Abbreviations: ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson's correlation coefficient (r); rs: Spearman's rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissue.

Project description:IntroductionNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western world and is highly associated with multiple cardiometabolic complications. The Zhejiang University (ZJU) index was first developed to predict NAFLD in Chinese populations, where it was shown to have better predictive value than other currently used indices. The aims of the present study were to 1) determine the diagnostic accuracy of ZJU index in identifying NAFLD in a well-phenotyped cohort of obese middle-aged American women and 2) compare its performance with other non-invasive indices for NAFLD identification.MethodsTo achieve this goal, we performed a retrospective analysis of a prospectively-collected cohort of participants enrolled in a weight loss trial for severe obesity (RENEW, clinicaltrials.gov identifier: NCT00712127). One hundred and seven women between the age of 30 and 55 with obesity class II (BMI 35-39.9 kg/m2) or class III (BMI ≥ 40 kg/m2) were recruited for analyses. Hepatic steatosis was measured using liver/spleen attenuation ratio (L/S ratio) from unenhanced abdominal computed tomography. Beside ZJU index, hepatic steatosis index (HSI), lipid accumulation production index (LAPI), and visceral adiposity index (VAI) were also determined and to compare their performance in predicting NAFLD.ResultsOf 107 obese women in the study, 40 (37.4%) met imaging criteria for NAFLD using cut-off value of L/S ratio < 1.1. The ZJU index was positively correlated with HIS, LAPI, but not VAI. The area under the curve was highest for the ZJU index (AUC = 0.742, 95% CI:0.647-0.837), followed by HSI (AUC = 0.728, 95% CI:0.631-0.825), LAPI (AUC = 0.682, CI:0.583-0.781), and VAI (AUC = 0.621, 95% CI:0.518-0.725), respectively, using the Youden method.ConclusionThe ZJU index is a powerful surrogate marker for NAFLD in severely obese western females and its predictive value was better than that of other commonly used indices for predicting NAFLD. Our study is the first to suggest that the ZJU index could be a promising model for use in western as well as Chinese populations.