ACEIs/ARBs prevent hepatocellular carcinoma, cirrhotic complications in NAFLD

Treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) results in a reduced risk of hepatocellular carcinoma (HCC) and cirrhotic complications in patients with nonalcoholic fatty liver disease (NAFLD), particularly among those with chronic kidney disease (CKD), according to a study presented at the virtual Asian Pacific Digestive Disease Week (APDW) 2021.

“Our findings support the use of ACEI/ARB as the preferred antihypertensive in patients with NAFLD,” said lead author Xinrong Zhang, from the Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.

In animal models, ACEIs and ARBs had been shown to inhibit liver fibrogenesis, but data from clinical studies were limited and inconclusive. To address this, researchers from The Chinese University of Hong Kong assessed the impact of ACEI/ARB use on the risk of HCC and cirrhotic complications in patients with NAFLD.

A retrospective, territory-wide cohort study was conducted involving adult NAFLD patients from 1 January 2000 to 31 December 2014 to allow for at least 5 years of follow-up. ACEI/ARB users were characterized as patients who initiated ACEI/ARB treatment at least 6 months before last visit or the primary endpoint of liver-related events, defined as a composite of HCC and cirrhotic complications.

Data from 12,494 NAFLD patients (mean age 54.4±14.5 years, 50.4 percent men) were analysed. More than half of the patients (59.5 percent) received ACEI/ARB. Liver-related events developed in 268 (3.6 percent) users of ACEI/ARB and 173 (3.4 percent) nonusers over a median follow-up of 9.9 years (interquartile range, 5.4–14.2). [APDW 2021, abstract 725-244]

After propensity score weighting, treatment with ACEI/ARB led to a reduction in the risk of liver-related events (weighted subdistribution hazard ratio [SHR], 0.44, 95 percent confidence interval [CI], 0.33–0.59; p<0.001), HCC (weighted SHR, 0.46, 95 percent CI, 0.30–0.72; p<0.001), and cirrhotic complications (weighted SHR, 0.42, 95 percent CI, 0.29–0.61; p<0.001).

Subgroup analysis revealed an association between ACEI/ARB treatment and greater decrease in liver-related events in patients with CKD than in those without (CKD-weighted SHR, 0.12, 95 percent CI, 0.06–0.26; p<0.001; non-CKD–weighted SHR, 0.67, 95 percent CI, 0.49–0.93; p=0.02).

“ACEI/ARB treatment was associated with a lower risk of liver-related events, HCC, and cirrhotic complications in NAFLD patients,” Zhang said. “The greatest benefits were observed in CKD subgroup.”

An earlier study of 191 patients with various stages of CKD found that those treated with ACEIs or ARBs had a significantly lower degree of liver stiffness than those who were not treated with these medications (p=0.005). However, no between-group differences were noted with respect to liver steatosis or fibrosis. [Wien Klin Wochenschr 2015;127:355-362]

A previous study also reported the efficiency of ARBs in hypertension-related nonalcoholic steatohepatitis (NASH), with telmisartan exhibiting a higher efficacy in terms of insulin resistance and histology, potentially due to its specific peroxisome proliferator-activated receptor gamma ligand effect. [World J Gastroenterol 2009;15:942-954]