Angiotensin receptor blockers in the treatment of NASH/NAFLD: Could they be a first-class option?

Georgescu, E

doi:10.1007/s12325-008-0110-2

Cited by 51 publications

(58 citation statements)

References 190 publications

(291 reference statements)

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“…Of course, a reasonable explanation could be the specific PPARγ modulatory activity of this ARB, but also other unique properties of this drug can contribute to this effect. As extensively discussed elsewhere [15] , it seems that various ARBs have different "second-level" pharmacologic effects, unrelated to presence or absence of certain PPAR-modulating activity, as for example candesartan, which shows capacities to decrease liver fibrosis and diminish portal pressure in Child A cirrhotic patients [65] , but do not have significant PPAR-modulating activity. It is subsequently possible that the better clinical results observed for telmisartan are driven through some undisclosed mechanism(s) that further studies will undoubtedly unveil.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, no major studies have been performed to confirm its efficacy in steatohepatitis, although a theoretical and experimental fundament exists [15] . Interestingly, a study by Fujita et al [16] tested the same compounds as we did in this study in a rat model of NASH, providing evidence that telmisartan, but not valsartan, improved both qualitatively and quantitatively hepatic steatosis, inflammation, and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis

Georgescu¹,

Ionescu²,

Niculescu³

et al. 2009

WJG

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159

127

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AIM:To evaluate insulin resistance, cytolysis and nonalcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS:All patients met the NCEP-ATP Ⅲ criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly assigned either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS:At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION:Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis

Georgescu¹,

Ionescu²,

Niculescu³

et al. 2009

WJG

Self Cite

159

127

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“…Ang II may contribute to the pathogenesis of hyperglycemia in NAFLD patients via its regulative effects on adiponectin. ACEIs and ARBs used to be considered potential treatments for NAFLD (31). However, clinical evidence regarding the efficiency of ACEIs and ARBs in NAFLD patients is limited to those with hypertension or T2D.…”

Section: Discussionmentioning

confidence: 99%

An Increased Circulating Angiotensin II Concentration is Associated with Hypoadiponectinemia and Postprandial Hyperglycemia in Men with Nonalcoholic Fatty Liver Disease

Xia

Wang

et al. 2013

Intern. Med.

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Objective Nonalcoholic fatty liver disease (NAFLD) is a condition associated with type 2 diabetes (T2D). Insulin resistance, a common pathogenesis of NAFLD and T2D, is partially caused by alterations in angiotensin II (Ang II) and is accompanied by hypoadiponectinemia. We aimed to investigate whether the circulating Ang II and adiponectin concentrations are related to hyperglycemia in male NAFLD patients. Methods Thirty-five controls and 85 NAFLD patients without prior known T2D were enrolled. All participants were non-smoking men who performed 75-g oral glucose tolerance tests. According to the American Diabetes Association (ADA) criteria, the NAFLD patients were divided into the euglycemia and hyperglycemia groups. The NAFLD patients with hyperglycemia were further divided into the isolated impaired fasting glucose (I-IFG) and postprandial hyperglycemia subgroups. The fasting serum Ang II and adiponectin concentrations were measured. Results Among the 85 NAFLD patients, 40 (47%) had hyperglycemia, including I-IFG (18%) and postprandial hyperglycemia (29%). The serum Ang II concentrations in the euglycemia and hyperglycemia groups were significantly higher than those observed in the control and euglycemia groups, respectively; whereas the serum adiponectin concentrations were significantly lower. The serum Ang II concentrations were significantly higher in the postprandial hyperglycemia subgroup than in the I-IFG subgroup. The serum Ang II and adiponectin concentrations were found to be independent predictors of hyperglycemia in the NAFLD patients. The serum Ang II concentration was significantly associated with the serum adiponectin and 2-hour postprandial glucose concentrations in the NAFLD patients. Conclusion An increased circulating Ang II concentration is associated with hypoadiponectinemia and postprandial hyperglycemia in male NAFLD patients and may be involved in the pathogenesis of T2D in NAFLD patients.

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“…106 Previous studies showed that the renin-angiotensin system may be up-regulated during liver injury contributing to recruitment of inflammatory cells and activation of stellate cells, and that the use of angiotensin-receptor inhibitors attenuated these effects and improved liver enzymes and histology. [107][108][109] Attempts to block RAS overexpression with the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-II receptor blockers (ARBs) thus could be beneficial for patients with NAFLD and NASH.…”

Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin-ii mentioning

confidence: 99%

Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis

Le¹,

Loomba²

2012

Journal of Clinical and Experimental Hepatology

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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations. (J CLIN EXP HEPATOL 2012;2:156-173)

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Angiotensin receptor blockers in the treatment of NASH/NAFLD: Could they be a first-class option?

Cited by 51 publications

References 190 publications

Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis

Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis

An Increased Circulating Angiotensin II Concentration is Associated with Hypoadiponectinemia and Postprandial Hyperglycemia in Men with Nonalcoholic Fatty Liver Disease

Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis

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