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

Abstract

Aim: To evaluate insulin resistance, cytolysis and non-alcoholic 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.

Figure 1

Primary parameters of the biochemical study. Comparative dynamics for ALT and HOMA-IR from V1 to V6 in the study groups. A: ALT variation from V1 to V6; B: HOMA-IR variation from V1 to V6. ALT: Alanine-aminotransferase; HOMA-IR: Homeostasis model assessment index for insulin-resistance; V1 to V6: Number of scheduled visit; T: Telmisartan study group; V: Valsartan study group; NS: Not statistically significant.

Figure 2

Derivate parameters of the biochemical study. Comparisons (box-and whisker means) of the averaged decreases per month for ALT, HOMA-IR, TC and TG in the two study groups. A: Mean monthly decrease for ALT; B: Mean monthly decrease of HOMA-IR; C: Mean monthly decrease of triglycerides; D: Mean monthly decrease of total cholesterol. ALT: Alanine-aminotransferase; HOMA-IR: homeostasis model assessment index for insulin-resistance; TG: triglycerides; TC: total cholesterol; T: Telmisartan study group; V: Valsartan study group; NS: Not statistically significant.

Figure 3

Histology study. Comparisons of averaged decreases for NAS and its components and for the fibrosis scores between V1 and V6 among the study groups. A: Comparison between the values of NAS components at V6 vs V1; B: Mean NAS decrease in groups T and V; C: Comparison between the values of NAS and respectively fibrosis scores at V6 vs V1; D: Mean decrease of fibrosis scores in groups T and V. St: Steatosis; LI: Lobular inflammation; B: Ballooning; NAS: NASH activity score; V1: Index data at visit 1; V6: End-of-treatment data; NS: Not statistically significant.