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

Musso, Giovanni; Cassader, Maurizio; Rosina, F.; Gambino, Roberto

doi:10.1007/s00125-011-2446-4

Cited by 575 publications

(481 citation statements)

References 132 publications

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“…In a Metaanalysis study about pioglitazone, results showed that pioglitazone did not further improve treatment of any diabetic patient with NASH, fatty liver, and liver histology. However HOMA and transaminases improved over two and three years, respectively (11). In present study a significant decrease was observed in mean fasting blood glucose and serum insulin level in all groups, and also differences in average changes were significant between the groups.…”

Section: Treatment Of Non Alcoholic Fatty Liver Diseasesupporting

confidence: 58%

Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

Haji-Aghamohammadi¹,

Ziaee²,

Oveisi³

et al. 2012

Hepat Mon

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From our research, there are some implications to treat the fatty liver patients for concerning of internal physician in the practice.Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common reasons of enzyme increase in liver. In About 10 percent of patients with NAFLD, the disease progresses toward Non Alcoholic Steatohepatitis (NASH) and about one third of them may progress toward cirrhosis, liver dysfunction, and even hepatocellular carcinoma. Objectives: According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease, the aim of this study was to assess the effects of metformin, pioglitazone, and silymarin on treatment of NAFLD. Patients and Methods: Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo'ali Hospital, Qazvin, Iran, were assigned randomly into three groups (n = 22). First group was treated by pioglitazone 15 mg/d, second group by metformin 500 mg/d, and third group by silymarin 140 mg/d. All patients underwent clinical and biochemical evaluations including weight, fasting blood sugar (FBS), lipid profiles, body mass index (BMI), aspartate aminotransferase (AST ), alanine aminotransferase (ALT), and serum insulin levels in pre-and post-intervention after eight-week follow up. Results: Before the treatment there was no significant difference between three groups with respect to average age, BMI and gender, FBS, lipid profile, AST, ALT, serum insulin level, and Homeostasis Model Assessment (HOMA) index for insulin resistance. After the intervention, a significant reduction was observed in average amount of FBS, lipid profile, ALT, AST, serum insulin level and HOMA index in three groups (P < 0.01). The most reduction in average FBS, TG, serum insulin level, and HOMA index was observed in pioglitazone group, the most reduction in average amount of cholesterol was seen in metformin group, and the most decrease in average amount of AST and ALT occurred in silymarin group. Conclusions: These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD. Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups.

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Section: Treatment Of Non Alcoholic Fatty Liver Diseasesupporting

confidence: 58%

Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

Haji-Aghamohammadi¹,

Ziaee²,

Oveisi³

et al. 2012

Hepat Mon

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“…First, the number of patients is relatively small because the data and safety monitoring board recommended that the study intervention and enrolment be discontinued in light of the higher proportion of adverse events in the ezetimibe group than in the control group. Second, our trial was a 6 month open-label study that resulted in subtle changes in liver pathology compared with previous reports [40]. Indeed, a 6 month duration may be too short a period to expect improvement of fibrosis, which is a slowly ND, not determined progressive process [40].…”

Section: Discussionmentioning

confidence: 94%

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

et al. 2014

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Aims/hypothesis The cholesterol absorption inhibitor ezetimibe has been shown to ameliorate non-alcoholic fatty liver disease (NAFLD) pathology in a single-armed clinical study and in experimental animal models. In this study, we investigated the efficacy of ezetimibe on NAFLD pathology in an open-label randomised controlled clinical trial. Methods We had planned to enrol 80 patients in the trial, as we had estimated that, with this sample size, the study would have 90% power. The study intervention and enrolment were discontinued because of the higher proportion of adverse events (significant elevation in HbA 1c ) in the ezetimibe group than in the control group. Thirty-two patients with NAFLD were enrolled and randomised (allocation by computer program). Ezetimibe (10 mg/day) was given to 17 patients with NAFLD for 6 months. The primary endpoint was change in serum aminotransferase level. Secondary outcomes were change in liver histology (12 control and 16 ezetimibe patients), insulin sensitivity including a hyperinsulinaemic-euglycaemic clamp study (ten control and 13 ezetimibe patients) and hepatic fatty acid composition (six control and nine ezetimibe patients). Hepatic gene expression profiling was completed in 15 patients using an Affymetrix gene chip. Patients and the physician in charge knew to which group the patient had been allocated, but people carrying out measurements or examinations were blinded to group. Results Serum total cholesterol was significantly decreased in the ezetimibe group. The fibrosis stage and ballooning score were also significantly improved with ezetimibe treatment. However, ezetimibe treatment significantly increased HbA 1c and was associated with a significant increase in hepatic longchain fatty acids. Hepatic gene expression analysis showed coordinate downregulation of genes involved in skeletal muscle development and cell adhesion molecules in the ezetimibe treatment group, suggesting a suppression of stellate cell development into myofibroblasts. Genes involved in the L-carnitine pathway were coordinately downregulated by ezetimibe treatment and those in the steroid metabolism pathway upregulated, suggestive of impaired oxidation of long-chain fatty acids. Conclusions/interpretation Ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA 1c in patients with NAFLD. These findings shed light on previously unrecognised actions of ezetimibe that should be examined further in future studies.

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“…In addition to liver-related complications, NAFLD is also an emerging risk factor for diabetes and cardiovascular disease [3]. There is no established treatment for NASH: lifestyleinduced weight loss is effective in less than 50% of individuals and the long-term safety of pioglitazone and vitamin E, suggested as possible therapeutic options by current guidelines [1], is far from being demonstrated; furthermore, there is no established treatment able to reverse hepatic fibrosis, the strongest predictor of future development of cirrhosis [4].…”

mentioning

confidence: 99%

Ezetimibe in the balance: can cholesterol-lowering drugs alone be an effective therapy for NAFLD?

Musso

2014

Diabetologia

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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

Cited by 575 publications

References 132 publications

Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

Ezetimibe in the balance: can cholesterol-lowering drugs alone be an effective therapy for NAFLD?

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