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

Abstract

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.

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

“…In another RCT on hypertensive NAFLD patients, losartan plus simvastatin significantly improved ultrasonographic steatosis, visceral adiposity, HOMA and CRP compared with amlodipine plus simvastatin, despite similar BP reduction [76] (ESM Table 4). …”

A Meta-Analysis of Randomized Trials for the Treatment of Nonalcoholic Fatty Liver Disease

“…An HQ RCT (quality score 7) randomized 54 hypertensive NASH patients to 20 months of valsartan or telmisartan (an angiotensin receptor blockers with PPAR-c-modulating activity). 61 Both agents improved steatosis; telmisartan significantly improved ballooning, lobular inflammation, and fibrosis compared with valsartan (Figs. 2-4).…”

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

“…After this pilot study, many animal and in vitro studies confirmed the beneficial efficacy of ARBs against NASH, but clinical studies were very limited. Only one RCT was published in 2009 [98]; however, this RCT was conducted with two treatment groups, and each group of patients was given a different ARB. This RCT reported that both telmisartan and valsartan have beneficial efficacy against NASH, but there was no placebo treatment group [98].…”

“…Only one RCT was published in 2009 [98]; however, this RCT was conducted with two treatment groups, and each group of patients was given a different ARB. This RCT reported that both telmisartan and valsartan have beneficial efficacy against NASH, but there was no placebo treatment group [98]. Thus, it is difficult to assess whether the beneficial efficacy against NASH is specific to ARBs or whether other antihypertensive agents might also have the same effect on NASH.…”