Are statins able to improve liver disease?

The lowdown: Probably safe to use in patients with liver disease and potentially beneficial, but avoid in decompensated cirrhosis. Randomized controlled trials are needed.

Statins, the Swiss Army knife of pharmacotherapy ?

Statins are interesting drugs that are indicated for patients with heart disease and certain patients who do not have heart disease now, but who are nevertheless at increased risk for developing cardiovascular disease in the future. While the main mechanism of risk reduction is believed to be related to their LDL-cholesterol lowering effect, other factors may also be important (“pleiotropic effects”) [i]. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of proinflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis.

Statins can hurt your liver …

The pleiotropy of statins is a subject of intense investigation in most other areas of medicine.  It is well known that statins can cause liver injury, but perhaps paradoxically, there is mounting evidence that statins may be beneficial in liver disease.

… and statins can heal your liver

The to-date largest meta-analysis of observational trials published in June 2017 including 259,453 patients concluded that statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with chronic liver disease[ii].

Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis.

The authors of an accompanying editorial agree that there is now mounting observational evidence of a beneficial effect, a limited number of randomized controlled trials demonstrating benefit, and studies supporting biologic plausibility of hepatic protection but stop short of endorsing statins in patients with liver disease[iii]. They caution against using statins in patients with decompensated cirrhosis.

Others are not so cautious and would like to see it used more often in patients with NAFLD/NASH (non-alcoholic fatty liver disease/non-alcoholic steatohepatitis), because these patients would also benefit from the cardiovascular risk reduction that statins impart [iv]

 

[i] Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circulation research. 2017 Jan 6;120(1):229-43.

[ii]  Kamal S, Khan MA, Seth A, Cholankeril G, Gupta D, Singh U, Kamal F, Howden CW, Stave C, Nair S, Satapathy SK. Beneficial effects of statins on the rates of hepatic fibrosis, hepatic decompensation, and mortality in chronic liver disease: a systematic review and meta-analysis. The American journal of gastroenterology. 2017 Oct;112(10):1495.

[iii] Price JC, Tien PC. Statins and Liver Disease: Is it Time to Recommend Statins to Prevent Liver Disease Progression?. The American journal of gastroenterology. 2017 Oct;112(10):1506.

[iv] Athyros VG, Boutari C, Stavropoulos K, Anagnostis P, Imprialos KP, Doumas M, Karagiannis A. Statins: an under-appreciated asset for the prevention and the treatment of NAFLD or NASH and the related cardiovascular risk. Current vascular pharmacology. 2018 May 1;16(3):246-53.

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