Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials.
Summary of "Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials."
AIMS/
HYPOTHESIS:
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liver-related complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardio-metabolic risk in NAFLD.
METHODS:
Publications through November 2011 were systematically reviewed by two authors. Outcomes evaluated though standard methods were: histological/radiological/biochemical features of NAFLD, variables of glucose metabolism and cardiovascular risk factors. Seventy-eight randomised trials were included (38 in NASH, 40 in NAFLD): 41% assessed post-treatment histology, 71% assessed glucose metabolism and 88% assessed cardiovascular risk factors. Lifestyle intervention, thiazolidinediones, metformin and antioxidants were most extensively evaluated.
RESULTS:
Lifestyle-induced weight loss was safe and improved cardio-metabolic risk profile; a weight loss ≥7% improved histological disease activity, but was achieved by <50% patients. Statins and polyunsaturated fatty acids improved steatosis, but their effects on liver histology are unknown. Thiazolidinediones improved histological disease activity, glucose, lipid and inflammatory variables and delayed fibrosis progression. Pioglitazone also improved blood pressure. Weight gain (up to 4.8%) was common. Antioxidants yielded mixed histological results: vitamin E improved histological disease activity when administered for 2 years, but increased insulin resistance and plasma triacylglycerols. CONCLUSIONS/
INTERPRETATION:
Weight loss is safe, and improves liver histology and cardio-metabolic profile. For patients not responding to lifestyle intervention, pioglitazone improves histological disease activity, slows fibrosis progression and extensively ameliorates cardio-metabolic endpoints. Further randomised controlled trials (RCTs) of adequate size and duration will assess long-term safety and efficacy of proposed treatments on clinical outcomes.
Affiliation
Gradenigo Hospital, C.so Regina Margherita 8, 10132, Turin, Italy, giovanni_musso@yahoo.it.
Journal Details
This article was published in the following journal.
Name: Diabetologia
ISSN: 1432-0428
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22278337
- DOI: http://dx.doi.org/10.1007/s00125-011-2446-4
Medical and Biotech [MESH] Definitions
Glucose Clamp Technique
Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.
Glucose Transporter Type 2
A glucose transport facilitator that is expressed primarily in PANCREATIC BETA CELLS; LIVER; and KIDNEYS. It may function as a GLUCOSE sensor to regulate INSULIN release and glucose HOMEOSTASIS.
Glycogen Storage Disease Type I
An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.
Glucose-6-phosphate
An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)
Glucose Metabolism Disorders
Pathological conditions in which the BLOOD GLUCOSE cannot be maintained within the normal range, such as in HYPOGLYCEMIA and HYPERGLYCEMIA. Etiology of these disorders varies. Plasma glucose concentration is critical to survival for it is the predominant fuel for the CENTRAL NERVOUS SYSTEM.
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