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Corresponding authors. Department of Medicine, Atherosclerosis Research Center, Tibor Rubin Veterans Affairs Healthcare System, 5901 E.7th Street, Long Beach, CA 90822, USA.
Corresponding authors. Department of Medicine, Atherosclerosis Research Center, Tibor Rubin Veterans Affairs Healthcare System, 5901 E.7th Street, Long Beach, CA 90822, USA.
New evidence indicates that niacin may treat nonalcoholic fatty liver disease.
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Niacin prevents and reverses hepatic steatosis and inflammation and prevents fibrosis.
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Steatosis significantly decreased in a small clinical trial.
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The mechanisms are oxidative stress reduction and DGAT2 inhibition.
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Randomized clinical trials are needed.
Abstract
Niacin has been widely used clinically for over half a century for dyslipidemia. Recent new evidence indicates that niacin may be useful in the treatment of nonalcoholic fatty liver disease (NAFLD) and its sequential complications including nonalcoholic steatohepatitis and fibrosis. There is an urgent unmet need for a cost-effective solution for this public health problem affecting nearly one in three adults. Niacin inhibits and reverses hepatic steatosis and inflammation in animals and liver cell cultures. It prevents liver fibrosis in animals and decreases collagen in cultured human stellate cells. Its mechanism of action is by oxidative stress reduction and inhibition of diacylglycerol acyltransferase 2 and other possible targets. An uncontrolled clinical trial in 39 hypertriglyceridemic patients with steatosis showed reduction of liver fat by 47% and reductions in liver enzymes and C-reactive protein from the baseline when treated with niacin extended-release for 6 months These hypothesis-generating data indicate a novel repurposed use of niacin for NAFLD. Niacin beneficially affects NAFLD at 3 major stages directly and, by affecting steatosis, it indirectly decreases the cascade effect on inflammation and fibrosis. It offers the advantage potentially of combination with other drugs in development for evolving synergistically more intense and broader efficacy. In select patients, it may benefit frequently associated atherogenic dyslipidemia. A randomized placebo-controlled double-blind parallel trial (with niacin alone or in combination with another drug in development) to assess the safety and efficacy of niacin on steatosis, inflammation, and fibrosis in patients with nonalcoholic steatohepatitis/NAFLD is warranted.
In the United States, it is estimated to affect over a stunning 75 million adults. The disease is characterized by triglyceride accumulation in the liver and often associated with caloric excess. In approximately 25% to 30% of patients with NAFLD, it progresses to a subtype characterized by inflammation (nonalcoholic steatohepatitis [NASH]). Fibrosis (scarring) is a major complication in about 20% of these patients, which clinically leads to cirrhosis, liver failure, transplantation, and liver cancer.
In its early stages (steatosis and steatohepatitis), it is asymptomatic and because of lack of clinically available tests, it is often not diagnosed and therefore underestimated. Worldwide, and in certain countries, its incidence is increasing almost at epidemic levels. It is a major public health problem. There is an urgent need not only for treatment but for prevention of this serious disease.
Mechanisms involved in the progression of steatosis to NASH and its complications are poorly understood. The central feature in NAFLD is an excess of fatty acids in the liver, which result in triglycerides (TG) accumulation (steatosis). The fatty acids originate from 3 sources: de novo lipid synthesis, adipose tissue fatty acid mobilization, and from lipolysis of TG-rich lipoproteins (chylomicrons from dietary fat and very-low-density lipoproteins [VLDL]). In approximately 20% to 25% of patients, oxidative stress and lipid peroxidation result in progressive form of NASH with hepatic inflammation, apoptosis, fibrosis (affecting stellate cells), and cirrhosis.
The disease is silent for decades and the first clinical presentation is related to portal hypertension secondary to cirrhosis (eg, ascites, esophageal hemorrhage, jaundice) or liver failure or hepatocellular carcinoma. The costs to society are huge and early detection and treatment are needed to reduce cost. Currently, lifestyle modification (weight loss, exercise, and dietary modification) is the main treatment. At the time of this writing, there is no FDA-approved pharmacologic therapy for this condition.
This review is based on published peer reviewed work. It is recognized that the volume of current research is relatively small and based on recent discoveries. Thus, it is hypothesis generating. Hopefully, it will lead to more research in an important therapeutic field with a significant unmet need. Niacin stands uniquely apart from most drugs in development, which aim at different therapeutic targets.
Although early, current evidence is significant as it points a direction for future and potentially fruitful research for a cost-effective therapy for NAFLD.
Preclinical evidence
Recent preclinical research discoveries from our laboratory and others have suggested a new use of niacin for the treatment of fatty liver disease. Using in vitro studies in human liver cells and in vivo experimental animal model of NAFLD, niacin was shown to significantly and robustly reduce hepatic fat accumulation and steatosis, inflammation, and fibrosis, the major pathophysiological processes involved in NAFLD and its progression to NASH.
Kashyap ML, Kamanna S, Hoa N, Kamanna V. New Use of Niacin for the Potential Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): Efficacy on Fibrosis. Abstract Presented at the 2018 AASLD Industry Colloquium: Novel targets and therapies in liver disease. Washington DC, January 19-20, 2018.
In human primary hepatocytes and human hepatoblastoma cell line (HepG2 cells), pharmacologically relevant concentrations of niacin markedly reduced fat accumulation induced by palmitic acid.
This inhibitory action of niacin on hepatocyte fat accumulation was associated with inhibition of diacylglycerol acyltransferase 2 (DGAT2), a key committed enzyme in triglyceride synthesis.
showed that the addition of niacin in the diet significantly decreased liver fat content and prevented hepatic steatosis. Furthermore, niacin treatment to rats with preexisting steatosis induced by high-fat diet significantly regressed hepatic steatosis (Fig. 1). Using high-fat diet fed animal NAFLD model, these authors also showed that niacin treatment significantly inhibited hepatic mRNA expression and activity of DGAT2 without affecting fatty acid synthesis and oxidation enzymes.
have shown that niacin also attenuated chronic alcohol-induced fatty liver in rats, thus potentially extending the use of niacin in this disorder.
Figure 1Representative histological images of liver sections stained with H&E showing that niacin causes regression of pre-existing steatosis in high-fat (HF) diet fed rat model of NAFLD. Rats were first fed the HF diet for 6 wk to induce hepatic steatosis. These rats were then treated with niacin (0.5% in the diet) while they continued on HF diet for 6 wk.
Adapted from Ganji SH et al. Am J Physiol Gastronitest Liver Physiol. 306:320-G327, 2014(7).
Oxidative stress with increased reactive oxygen species (ROS) and lipid peroxidation products play a crucial role in hepatic inflammation and progression to NASH.
have recently shown that niacin significantly attenuated hepatocyte ROS production. Niacin was also shown to significantly decrease hepatic lipid peroxidation products in high-fat fed rat model of NAFLD.
In view of increased levels of plasma myeloperoxidase (MPO) and MPO-derived hepatic oxidation products in patients with NASH and its potential contribution in hepatic inflammation,
investigated the effect of niacin on MPO release and activity in human neutrophils, the major cellular source of MPO. The findings indicate that niacin treatment significantly inhibited MPO release and activity in human neutrophils. Using specific inhibitors, these authors also showed that ROS-dependent signaling mediate decreased MPO by niacin.
These studies suggest that niacin, through inhibiting ROS production and ROS-sensitive redox genes, attenuates hepatic inflammation.
Fibrosis
The potential use of niacin as an anti-fibrotic agent has been tested in chronic thioacetamide-induced liver fibrosis in rats and in vitro studies using human liver stellate cells. Arauz et al
have shown that niacin markedly reduced liver fibrosis induced by chronic administration of thioacetamide in rats. Niacin prevented the elevation of liver enzymes. Liver histopathology and hydroxyproline levels were significantly lower in the rats treated with thioacetamide plus niacin compared with thioacetamide only. Niacin demonstrated antioxidant properties by restoring the redox equilibrium (lipid peroxidation and glutathione peroxidase levels). Western blot assays showed decreased expression levels of TGF-β and its downstream inductor connective tissue growth factor (CTGF). In addition, niacin prevented hepatic stellate cell activation by blocking the expression of alpha smooth muscle actin. Zymography assays showed that niacin decreased the activity of matrix metalloproteinases 2 and 9. These authors suggest that niacin, through antioxidant properties and reducing TGF-β expression, prevented hepatic fibrosis in this animal model.
recent studies conducted in our laboratory investigated the direct effect of niacin on stellate cell fibrosis using primary cultures of human hepatic stellate cells isolated from normal (non-NASH) and from NASH patients with fibrosis (cells were obtained from Samsara Sciences, San Diego, CA).
Treating human primary stellate cells from normal subjects with pharmacologically relevant concentrations of niacin markedly inhibited stellate cell fibrosis (collagen type 1 and Sirus Red staining) induced by TGF-β or oxidative stress mediator hydrogen peroxide (H2O2), major physiological stimulators of liver fibrosis.
Kashyap ML, Kamanna S, Hoa N, Kamanna V. New Use of Niacin for the Potential Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): Efficacy on Fibrosis. Abstract Presented at the 2018 AASLD Industry Colloquium: Novel targets and therapies in liver disease. Washington DC, January 19-20, 2018.
Additional studies assessed regression of pre-existing fibrosis in stellate cells from patients with NASH with fibrosis. Stellate cells from patients had significantly increased fibrosis when compared with stellate cells from normal subjects.
Kashyap ML, Kamanna S, Hoa N, Kamanna V. New Use of Niacin for the Potential Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): Efficacy on Fibrosis. Abstract Presented at the 2018 AASLD Industry Colloquium: Novel targets and therapies in liver disease. Washington DC, January 19-20, 2018.
Kashyap ML, Kamanna S, Hoa N, Kamanna V. New Use of Niacin for the Potential Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): Efficacy on Fibrosis. Abstract Presented at the 2018 AASLD Industry Colloquium: Novel targets and therapies in liver disease. Washington DC, January 19-20, 2018.
examined the effect of niacin extended-release (Niacin ER, trade name: Niaspan) on liver fat content in 39 adult patients with hypertriglyceridemia in an uncontrolled clinical trial. All patients were treated with niacin ER, gradually increasing the dose to 2 g/d for a total of 23 weeks. The liver fat content and visceral/subcutaneous fat was measured before and after treatment by proton MR spectroscopy. Mean baseline liver fat content was 12.8%. Patients were also genotyped for DGAT2 rs3060 and rs101899116 polymorphisms. There were significant (P < .001) reductions in liver fat content (−47.2 ± 32.8%) and visceral fat (−6.3 ± 15.8%, P < .05) after niacin treatment. Mean body weight decreased by 1.46% of baseline during the study. Although a limitation of this trial, the liver fat decrease remained statistically significant after adjustment for age, gender, and body weight changes. Of note, statistically significant decreases from the baseline in liver enzymes ALT, GGT, and alkaline phosphatase were observed. The inflammatory marker high sensitivity C-reactive protein (CRP) was also reduced significantly. The DGAT2 variant alleles were associated with a smaller reduction in liver fat content in response to niacin after adjustment for other covariates (P < .01).
This pilot trial indicates that niacin treatment reduces liver fat content in patients with hypertriglyceridemia. The reductions in liver enzymes and CRP are consistent with other reports indicating that niacin reduces oxidative stress and has anti-inflammatory properties that may mitigate nonalcoholic steatohepatitis and fibrosis. The observation that DGAT2 polymorphisms were associated with a lesser liver fat reduction is consistent with the concept that niacin's mechanism of action may, in part involve inhibition of DGAT2.
Based on currently available evidence, niacin appears to affect NAFLD by at least 2 major mechanisms summarized in the following.
Niacin and hepatic triglyceride synthesis inhibition: role of hepatic DGAT2, adipose tissue lipolysis, and de novo lipogenesis
One target site of action is DGAT2, which converts diglyceride to triglyceride. In preclinical research, niacin inhibits DGAT2 mRNA when cultured human hepatocytes are stimulated by free fatty acids
Jin et al. also reported that niacin inhibits de novo lipogenesis (DNL) as it decreased the incorporation of radiolabeled acetate into long chain fatty acids in hepatocyte cultures.
However, the enzyme target for DNL reduction needs further research.
Figure 2 gives an overview of the position of DGAT2 in the major pathway in the synthesis of hepatic TG and subsequent formation of VLDL. There are 3 major sources of fatty acids destined for TG synthesis: (1), DNL from acetate (from glucose) to form long chain fatty acids; (2) endogenous fatty acids mobilized from adipose tissue and (3) lipolysis of TG rich lipoproteins: chylomicrons after a fatty meal and VLDL in fasting state by lipoprotein lipase. Fatty acids are esterified to monoglycerides and diglycerides. DGAT2 converts diglycerides to TG. The TG is then complexed (via microsomal triglyceride transport protein) to apolipoprotein B and other apolipoproteins and lipids to form VLDL (not shown in figure). Excessive fatty acid formation in liver (from glucose or fatty acids) can lead to TG deposited in liver (steatosis) in addition to VLDL formation and secretion resulting in hypertriglyceridemia.
Figure 2Sources of liver fatty acids: site of action of niacin vs ACC inhibitors. ACC, acetyl coenzyme-A carboxylase; DGAT2, diacylglycerol acyltransferase 2; TG, triglycerides.
Consistent with this mechanism of action is a previous older report by Grundy et al who infused radiolabeled glycerol in humans and measured its incorporation into TG by kinetic turnover techniques (reviewed in
). Niacin decreased TG production rate suggesting that the effect was on TG synthesizing organs of which the liver is the major organ. Jin et al. subsequently showed that niacin inhibited the synthesis of TG from radiolabeled precursors (oleic acid and glycerol) in HepG2 cells, which was associated with increased apolipoprotein B degradation thereby lowering circulating TG (reviewed in
). Additional support for this mechanism is that antisense oligonucleotide DGAT2 inhibitor was associated with reduced hepatic TG synthesis, decreased steatosis and increased free fatty acid oxidation in obese mice on high fat diet or leptin deficiency (reviewed in Ref.
The older work of Carlson et al showed that niacin inhibits adipose tissue fatty acid mobilization. This has been the widely held view of niacin's mechanism of action in lowering plasma TG by decreasing the supply of nonesterified fatty acids to the liver (reviewed in
). Although this is another possible mechanism for niacin's action, there are at least 2 reasons why this mechanism may not be important in humans. First, the decline in plasma fatty acids is transient and there is a rebound increase after niacin administration eventually leading to baseline concentrations suggesting that the long-term flux or transport of fatty acids is unaltered. This is supported by the well-known clinical observation that niacin therapy does not result in increase in body weight. By contrast, insulin is a potent inhibitor of adipose tissue lipolysis and its administration may be associated with adiposity and weight gain. Second, niacin appears to act on a receptor, GPR109A (HCAR2), which inhibits fatty acid mobilization. GPR109A agonists developed to act on this receptor do reduce fatty acid mobilization like niacin in humans but do not affect plasma TG or other lipids (reviewed in
). This indicates that this mechanism of action of niacin may not be important in explaining its anti-steatosis effect. In adddition, GPR 109A is not expressed in liver tissue.
By inhibiting TG synthesis from all 3 fatty acid sources, niacin differentiates from other drugs that attempt to decrease steatosis by DNL only. Drugs inhibiting fatty acid synthesis (eg, acetyl coenzyme-A carboxylase [ACC inhibitors]) will decrease de novo fatty acid synthesis, but TG synthesis is not inhibited because fatty acids from adipose tissue mobilization and chylomicron and VLDL lipolysis remain available. Recently reported clinical data on an ACC inhibitor showed an increase in plasma TG levels in patients treated with an ACC inhibitor.
Cellular redox state, with increased NADPH and GSH levels, is a known protective mechanism against cellular oxidative injury in various cell types including hepatocytes. NADPH, in turn, is used as a reducing equivalent to maintain reduced glutathione stores (GSH), which are used to scavenge ROS and protect against oxidative injury. Cellular GSH status modulates the activation of key transcription factors (eg, NF-kB) and NF-kB-responsive inflammatory cytokines gene expression. Activation of NF-kB increases the expression of NADPH oxidase subunits (eg, p47phox subunit), a key oxidase involved in cellular ROS production. Thus, cellular redox state with increased NADPH and intracellular GSH play a crucial role in reducing ROS production through inhibiting NF-kB activation and expression of NADPH oxidase.
Emerging evidence indicates that NADPH oxidase–derived ROS play a vital role in initiating liver stellate cell activation and progression to fibrosis.
Specifically, ROS stimulates the production of stellate cell collagen type 1 resulting in liver fibrosis through mediating intracellular signaling of the fibrogenic actions of TGF-β.
Recent research has shown that niacin markedly reduces oxidative stress and inflammation in several cellular types including human aortic endothelial cells, neutrophils, hepatocytes, and liver stellate cells (6, 8, reviewed in Ref.
). Recent evidence suggests that niacin through increasing cellular redox state (with increased NADPH and GSH levels) reduces cellular oxidative stress and subsequent inflammatory responses in various cell types (reviewed in
). For example, treatment of HepG2 cells with niacin at pharmacologic concentrations for 24 h markedly and significantly increased NADPH levels and significantly increased GSH levels as compared with control. Furthermore, treatment of HepG2 cells with niacin significantly inhibited palmitic acid–induced NADPH oxidase activity, and niacin at 0.5 mM completely blocked palmitic acid–induced NADPH oxidase activity.
Niacin-mediated reduced ROS and lipid peroxidation products, through inhibition of the activation of NF-kB transcription factor, inhibit the activation of hepatic cells (eg, hepatocytes and stellate cells), which in turn reduces hepatic inflammation, TGF-β expression, collagen type-I deposition, and fibrosis.
Based on current evidence, Figure 3 depicts an overview of the mechanism of action of niacin on steatosis, inflammation, and fibrosis with DGAT2 and oxidative stress reduction as the main drivers of its action on NASH-NAFLD.
Figure 3Mechanism of action of niacin on NASH-NAFLD.
Clinical pharmacology of niacin for dyslipidemia and atherosclerosis: successes and failures
In pharmacologic doses, niacin is a broad-spectrum lipid-modifying agent. It reduces all atherogenic lipoproteins and lipids and several inflammatory markers (reviewed in
). As monotherapy, it significantly reduces cardiovascular and stroke events by 27% and 21%, respectively, and slows or reverses occlusive atherosclerosis in combination with LDL-C-lowering agents.
Despite these encouraging properties and positive clinical trials, 2 recent trials with use of niacin in high-risk patients on statin-based therapy (to maintain low LDL-C levels) and with pre-existing atherosclerotic cardiovascular disease (the AIM HIGH and HPS2 THRIVE trials) failed to show additional efficacy (Ref.
and references therein on AIM HIGH study). The results and limitations have been discussed by the authors and others. One major criticism of these trials is that the inclusion criteria were so loose that patients who benefitted were diluted by most patients who did not. For example, in the AIM HIGH trial, a subgroup of 439 patients (of total 3414) with high TG (>200 mg/dL) and very low HDL-C (<32 mg/dL) had a statistically significant (P = .03) 36% reduction in primary end-points of CV events (Ref.
and references therein). In HPS2 THRIVE, extended-release niacin was combined with laropiprant to decrease flushing. This drug could also have confounded the results.
Importantly, the clinical profile of patients recruited for these trials, which had a high prevalence of metabolic syndrome features and type 2 diabetes mellitus would have been expected to have a high prevalence of NAFLD. However, NAFLD was not assessed in these trials.
Niacin formulations: Safety and toxicity
Considerable misconceptions and confusion exist in understanding various formulations that are available. Because crystalline niacin causes flushing and must be taken 3 to 4 times daily, preparations have been developed to mitigate this adverse effect and yet have safety and efficacy. These “timed-release” preparations are labeled “controlled-release”, “slow-release”, “sustained-release”, “prolonged-release”, “long-acting niacin”, etc. They are available without a prescription. Their efficacy data are meager and there are few data on safety. The only prescription niacin formulation approved by the FDA is Niacin ER, which is the generic version of Niaspan. It is extensively studied for efficacy for dyslipidemia and safety has been well documented.
First, the use of niacin for NAFLD/NASH capitalizes on the vast amount of clinical experience in a drug that is readily available. Second, niacin has unique mechanisms of action at an early stage of NAFLD (steatosis), thus preventing and potentially reversing later complications of steatohepatitis, fibrosis, and cirrhosis resulting in devastating consequences, which are synergized further by direct effects on inflammation and fibrosis in preclinical research. Third, NAFLD is often associated with dyslipidemia and atherosclerosis. Niacin thus acts on 2 important diseases concurrently in many patients. Finally, it can be very useful in combination therapy with other drugs in development for potential synergy and augmentation of efficacy and discussed in the following.
Rationale for clinical trial for NASH-NAFLD
The preclinical and the clinical trial data summarized previously and elucidation of niacin's unique mechanism of action on steatosis, inflammation, and fibrosis form a strong rationale for a randomized, placebo-controlled double-blind trial.
Niacin's effects on the earliest stage of steatosis imply that niacin would be expected to reduce the cascade effect of the subsequent complications of NASH and fibrosis. It is noteworthy that niacin, via oxidative stress reduction, ameliorates inflammation and fibrosis. Fibrosis would be reduced not only by stellate cell collagen production, but also indirectly by mitigation of prior pathophysiological stages (inflammation and steatosis) for fibrosis. Thus 2 separate and unique mechanisms potentially impact the clinical manifestation of liver cirrhosis and its serious consequences.
Because niacin's mechanism of action is different from the many drugs in development for NASH-NAFLD, combination of niacin-based therapy could be very synergistic and more potent than either drug alone.
Potential clinical trials
Safety and preliminary efficacy
As indicated earlier, although the efficacy and safety of niacin is established, it is not yet indicated for the treatment of NASH-NAFLD. Because niacin is taken up by liver after absorption, it is possible that lower dose of niacin may achieve efficacy for NAFLD. Thus, its safety, efficacy, and dose need to be tested in a phase 2 randomized placebo-controlled double-blind trial in patients with NAFLD/NASH. Once safety and preliminary efficacy are established, a phase 3 double-blind randomized placebo-controlled trial in patients with NASH is needed to assess the efficacy of niacin on steatosis, inflammation, and fibrosis and other clinical complications.
Combination therapies including niacin: Rationale
Because niacin affects NAFLD at 3 major stages of the disease by its unique mechanisms of action, it offers the option of combinations with other drugs and synergistically resulting in a broad-spectrum enhanced efficacy. It is noteworthy that niacin acts both directly on the 3 major stages of NAFLD and indirectly by decreasing the cascade effect on the later stages of the disease. For example, a drug that inhibits fibrosis would incrementally benefit directly by niacin's antifibrosis action and indirectly by mitigating earlier stages of steatosis and inflammation that lead to fibrosis. Its unique characteristics also allow combinations with other drugs that are in development.
Summary and conclusions
In preclinical research, niacin inhibits and reverses hepatic steatosis, inflammation, and prevents fibrosis by reduction of oxidative stress, and inhibition of DGAT2 and other possible mechanisms. An uncontrolled clinical trial in 39 hypertriglyceridemic patients with steatosis showed a statistically significant reduction of liver fat by 47% and reductions in liver enzymes and CRP from the baseline when treated with Niacin ER for 6 months. Because niacin acts on the 3 major stages of NASH-NAFLD, combination with a drug in development for NASH is likely to result in a broader and more intense efficacy than either drug alone. By acting on the earliest stage of NAFLD, niacin mitigates the cascade effect on the later stages of the disease. Niacin uniquely offers the potential of not only treating NASH but also concurrent dyslipidemia, which very often occur together.
Randomized placebo-controlled double-blind parallel trials to assess the safety and efficacy of niacin in patients with NASH are warranted.
Acknowledgments
The research work cited by the authors (MLK, SG, and VSK) was supported by research grants from Southern California Institute for Research and Education and the Department of Veterans Affairs Healthcare System, Long Beach.
Authors' contributions: Moti Kashyap, MD, FNLA, and Vaijinath Kamanna, PhD, contributed equally. Dr Kashyap was the principal writer and reviewed the overall significant clinical and translational aspects of this review. Drs Kamanna and Ganji reviewed the basic science aspect of this article. Dr Nakra contributed to its applied significance. All authors have approved the final article.
Financial Disclosures
Drs Kashyap has received research grants from AbbVie, Amgen, Amylin, Arisaph, AstraZeneca, Bristol Meyers Squibb, Eli-Lilly, Kos, Merck, Sanofi-Aventis, and Takeda and has been advisor and/or speaker for AbbVie, Amarin, Kos, Bristol Meyers Squibb, and Merck. Dr Kashyap is a Co-chair Publications and Executive Committee Member of the AIM-HIGH Trial sponsored by the NIH and AbbVie. Moti Kashyap, Shobha Kamanna, and Vaijinath Kamanna are inventors of the patent issued by the US Patent Office titled “Indication for use of niacin (nicotinic acid) for treatment and reversal of fatty liver disease (Patent no.: US 9,072,732 B2). Drs Kashyap, Nakra, and Kamanna are principals in Aasta Pharmaceuticals, LLC.
References
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Past, present and future perspectives in nonalcoholic fatty liver disease.
Kashyap ML, Kamanna S, Hoa N, Kamanna V. New Use of Niacin for the Potential Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): Efficacy on Fibrosis. Abstract Presented at the 2018 AASLD Industry Colloquium: Novel targets and therapies in liver disease. Washington DC, January 19-20, 2018.
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