Niacin regresses collagen content in human hepatic stellate cells from liver transplant donors with fibrotic non-alcoholic steatohepatitis (NASH)

In patients with non-alcoholic steatohepatitis (NASH), the onset of fibrosis is a major predictor of cirrhosis and its deadly complications. There is no approved effective pharmacologic therapy for liver fibrosis. Niacin (in pharmacologic concentrations or dose) reverses hepatic steatosis and steatohepatitis. Niacin's efficacy on human hepatic fibrosis is unknown. We investigated the effect of niacin on reversal of preexisting collagen content, in cultured primary human hepatic stellate cells (HSC) obtained from 7 donor livers (processed for transplantation) selected from 5 deceased patients having histologically diagnosed NASH with fibrosis (F1-F3) and 2 non-NASH-fibrosis subjects (Samsara Sciences, Inc., now LifeNet Health). Pharmacologically relevant concentrations of niacin produced a robust and significant dose and time-dependent regression of pre-existing fibrosis by an average of 47.6% and 60.1% (0.25 and 0.5 mM niacin at 48 h incubation) and 53.5% and 65.0% (0.25 and 0.5 mM niacin at 96 h incubation), respectively. In stellate cells from non-NASH-fibrosis subjects, niacin prevented, and regressed fibrosis induced by liver fibrosis stimulators, transforming growth factor-beta (TGF-beta) and hydrogen peroxide. Niacin significantly inhibited oxidative stress induced by stressors, palmitic acid, or hydrogen peroxide by 52% and 50%, respectively. Translationally, these human HSC data, coupled with emerging in vivo animal data and in vitro human hepatocyte data, suggest that niacin (used clinically for dyslipidemia) could be repurposed as an effective drug for the clinical treatment of patients with NASH-fibrosis or liver cirrhosis. This is in addition to its known efficacy for reversing steatohepatitis and steatosis which can also result in liver cirrhosis.