Pterostilbene: The Blueberry Stilbene and What Human Trials Found
Pterostilbene is a small plant molecule from the stilbene family, the same family as resveratrol. It turns up in a few kinds of blueberries, in grapes and in the heartwood of the Indian kino tree, and it is sold as a supplement on its own and paired with nicotinamide riboside, a form of vitamin B3. The most-quoted fact about it, that far more of it reaches the bloodstream than resveratrol, comes from a rat study. This page sets out what is known: how much is in food, what that rat study measured, what the small number of human trials found (including a rise in cholesterol), which results come only from animals and cells, and how much remains unknown.
Table of Contents
- A Close Chemical Relative of Resveratrol
- Where Pterostilbene Is Found in Food and Plants
- Absorption Measured in Rats
- The 2014 Blood Pressure and Cholesterol Trial
- What the Safety Reports Found
- Other Human Studies of Pterostilbene
- Supplements That Pair It With Nicotinamide Riboside
- Findings in Animals and Cells
- The Sirtuin Label and the Evidence Behind It
- What Is Not Known
- Key Research Papers
- Connections
- Featured Videos
A Close Chemical Relative of Resveratrol
Resveratrol and pterostilbene share the same skeleton: two ring-shaped halves joined by a short bridge. Chemists name resveratrol 3,5,4′-trihydroxy-trans-stilbene, meaning it carries three hydroxyl groups (an oxygen bonded to a hydrogen) at three positions on its rings. Pterostilbene is 3,5-dimethoxy-4′-hydroxy-trans-stilbene. Two of those three hydroxyl groups are capped with a methyl group, which turns them into methoxy groups. That is why researchers call pterostilbene the “dimethylether analog” or “dimethylated” form of resveratrol.
The change looks minor on paper, but it matters in the body. Hydroxyl groups are where the liver and gut attach sulfate and glucuronic acid tags so that a molecule can be cleared quickly. Resveratrol is known for exactly this problem: after it is swallowed, only low levels of the original molecule appear in the blood, because it is converted to those tagged forms so fast. With two of its three hydroxyl groups capped, pterostilbene offers fewer attachment points, and it is also more fat-soluble. Researchers expected both features to let more of it reach the bloodstream intact, and a rat study (below) was designed to test that idea.
The amount of stilbenes in a fruit is not fixed. The muscadine grape study described below found that stilbene levels differ between cultivars and from year to year, which its authors tie to changing environmental conditions and the stresses a vine meets in a given season.
Where Pterostilbene Is Found in Food and Plants
Blueberries and their relatives. The most-cited measurement comes from a 2004 study by Rimando and colleagues, who used gas chromatography with mass spectrometry to analyze berries from 10 species of the Vaccinium genus collected in Mississippi, North Carolina, Oregon and Canada. Resveratrol turned up widely, at levels between 7 and 5,884 nanograms per gram of dry sample, with lingonberry the highest and comparable to grapes (6,471 nanograms per gram of dry sample). Pterostilbene was much more limited. The study reported it in two cultivars of rabbiteye blueberry (Vaccinium ashei) and in deerberry (Vaccinium stamineum), at 99 to 520 nanograms per gram of dry sample. Those figures are for freeze-dried berry material, not fresh fruit, and the abstract does not report pterostilbene in the other species tested.
The practical point is that pterostilbene is present in blueberries in trace amounts, measured in billionths of a gram per gram, and only in some kinds. The quantities used in human supplement trials (milligrams a day, see below) are far larger than these trace amounts. The Blueberries page covers the much larger amounts of anthocyanins and other compounds the fruit does provide.
Grapes. Muscadine grapes have been studied for their stilbene content. A study by Kambiranda and colleagues followed berries from 42 muscadine cultivars over three years (2013, 2014 and 2015) and measured four stilbenoids together: trans-piceid, trans-resveratrol, epsilon-viniferins and trans-pterostilbene. The combined total ranged from 1.73 micrograms per gram of fresh weight in the lowest cultivar to 270.20 micrograms per gram in the highest, and certain cultivars produced consistent levels year after year. The abstract reports the four compounds as a combined total, so it does not show how much of that was pterostilbene. More on grapes as a food is on the Grapes page.
The Indian kino tree. The word “pterostilbene” comes from Pterocarpus, a genus of tropical trees. A 1997 study identified pterostilbene as one of three important phenolic constituents of the heartwood of Pterocarpus marsupium, the Indian kino tree, along with marsupsin and pterosupin. Extracts of this heartwood are the source material for several of the human studies described below.
Absorption Measured in Rats
The study behind the common statement that pterostilbene is “80% bioavailable” was a rat study, published in 2011 by Kapetanovic and colleagues at the United States National Cancer Institute. Rats received resveratrol or pterostilbene by stomach tube every day for 14 consecutive days, at doses chosen to deliver the same number of molecules of each compound (50 or 150 milligrams per kilogram of body weight per day for resveratrol, 56 or 168 milligrams per kilogram per day for pterostilbene). Two further groups received a single dose into a vein, which allowed the researchers to calculate what share of the swallowed dose reached the circulation.
- In these rats, resveratrol was about 20% bioavailable and pterostilbene about 80%.
- After oral dosing, blood levels of pterostilbene and its sulfate form were markedly higher than blood levels of resveratrol and resveratrol sulfate.
- One measure went the other way: blood levels of resveratrol glucuronide were higher than those of pterostilbene glucuronide, though that gap was smaller than the gaps for the parent compounds.
The authors concluded that equal-molecule doses of pterostilbene may have greater biological activity in the body than resveratrol. That conclusion is about rats given large doses by tube. The abstract contains no human measurements, and the 80% figure is not a human bioavailability figure. No study read for this page measured the share of a swallowed pterostilbene dose that reaches the blood in people.
One human study did look at blood levels. In a 2005 study of healthy volunteers who took 450 milligrams of a Pterocarpus marsupium extract, pterostilbene levels in the blood rose, but they stayed about five-fold lower than the concentration that had blocked an inflammatory messenger in human blood cells in the laboratory. That study is described in more detail in the section on other human studies.
The 2014 Blood Pressure and Cholesterol Trial
The main human trial of pterostilbene taken on its own was run at the University of Mississippi and published by Riche and colleagues in 2014. It was a prospective, randomized, double-blind, placebo-controlled study, registered as NCT01267227, that enrolled 80 adults with a total cholesterol of at least 200 milligrams per deciliter and/or a low-density lipoprotein (LDL) cholesterol of at least 100 milligrams per deciliter. Participants were divided into four groups for 6 to 8 weeks:
- pterostilbene 125 milligrams twice daily (the high dose);
- pterostilbene 50 milligrams twice daily;
- pterostilbene 50 milligrams plus grape extract 100 milligrams twice daily;
- a matching placebo twice daily.
The trial measured blood lipids, blood pressure and weight. Its findings ran in two directions.
Blood pressure fell. On the high dose, systolic blood pressure (the upper number) fell by 7.8 mmHg and diastolic blood pressure (the lower number) by 7.3 mmHg, and both changes were statistically significant.
Low-density lipoprotein cholesterol rose. Pterostilbene taken alone raised low-density lipoprotein cholesterol by 17.1 milligrams per deciliter (P = 0.001). This rise was not seen in the group that took pterostilbene with grape extract (P = 0.47). People who were already taking a cholesterol medication at the start appeared to have a smaller rise.
Weight changed slightly. Among the 51 participants who were not on cholesterol medication, pterostilbene was followed by a minor drop in body mass index of 0.62 kilograms per square meter.
The authors summarized their result in one line: pterostilbene increases low-density lipoprotein cholesterol and reduces blood pressure in adults. The trial was small and short, it enrolled people who already had raised cholesterol, and it measured blood markers rather than heart attacks or strokes, so it cannot show what either change means over years.
What the Safety Reports Found
The same Mississippi trial published its safety findings separately, a year earlier, in 2013. That report describes the same 80 participants with high cholesterol, split equally across the same four groups for 6 to 8 weeks. Safety was tracked with blood tests and with what participants reported themselves.
- 91.3% of participants completed the trial.
- The average age was 54 years; 71% were women and 70% were Caucasian.
- Blood tests showed no adverse drug reactions on liver, kidney or blood-sugar markers.
- There were no statistically significant self-reported or major adverse drug reactions.
The authors concluded that pterostilbene is generally safe for use in humans up to 250 milligrams a day. That conclusion is bounded by the trial itself: 80 people, at most 8 weeks, and doses no higher than the high-dose group received. The safety report’s abstract does not mention the rise in low-density lipoprotein cholesterol that the efficacy paper later reported from the same trial.
Two other small trials of pterostilbene alone, described in the next section, also reported no adverse events: the 2005 kino-tree extract study, and a 2025 pilot study in healthy men that ran for 12 weeks.
Other Human Studies of Pterostilbene
A PubMed search for clinical trials of pterostilbene turns up few studies of the compound on its own. Besides the Mississippi trial, two stand out.
The 2005 kino-tree extract study. Hougee and colleagues first tested a Pterocarpus marsupium extract in the laboratory. In human blood cells stimulated to make the inflammatory messenger prostaglandin E2, the extract, pure pterostilbene and pure resveratrol all reduced its production; the half-maximal concentration was 1.0 micromolar for pterostilbene and 3.2 micromolar for resveratrol. In whole-blood tests the extract acted on the COX-2 enzyme and not on COX-1. The researchers then gave healthy volunteers 450 milligrams of the extract by mouth. It did not lower prostaglandin E2 production in their blood tested afterwards. Blood pterostilbene went up, but to levels about five-fold below the concentration that had worked in the laboratory. No changes in safety measures and no extract-related adverse events were seen. The authors described a dose-finding study as the next step.
The 2025 microRNA pilot study. A double-blind, placebo-controlled trial by Otsuka and colleagues in Japan gave 30 healthy men pterostilbene at 10 or 100 milligrams a day, or a placebo, for 12 weeks. The main measurements were blood chemistry and blood levels of microRNAs, short strands of genetic material that help switch genes up or down. Two microRNAs, miR-34a and miR-193b, rose very sharply in some participants from week 4 onward, which the authors read as a sign that some people may respond and others not. No adverse events were reported, and the study physician found no abnormalities. This was a pilot study of a laboratory marker; it did not measure any health outcome.
Beyond these, most human research involving pterostilbene has tested it in combination with nicotinamide riboside, described next. In those trials the two ingredients are always given together, so they cannot show what pterostilbene does by itself.
Supplements That Pair It With Nicotinamide Riboside
Pterostilbene is also sold in a two-ingredient capsule with nicotinamide riboside, a vitamin B3 compound that the body uses to make nicotinamide adenine dinucleotide (NAD+), a molecule every cell uses to turn food into energy. The 2020 kidney study below explains the pairing: earlier laboratory and animal work pointed to raising nicotinamide adenine dinucleotide and boosting sirtuin enzymes as two strategies, and the authors describe pterostilbene as a sirtuin activator. Researchers abbreviate the combination as NRPT. Several of these trials include authors employed by the company that markets the combination, and the 2017 paper states that the company funded that trial. The site’s pages on nicotinamide adenine dinucleotide boosters and nicotinamide adenine dinucleotide and nicotinamide mononucleotide cover the vitamin side in depth.
- Healthy older adults, 2017. A randomized, double-blind, placebo-controlled trial of 120 healthy adults aged 60 to 80 compared placebo, the recommended dose and a double dose, taken daily for eight weeks. Blood nicotinamide adenine dinucleotide rose by about 40% on the recommended dose and about 90% on the double dose after 4 weeks, compared with placebo and baseline, and stayed raised through week 8. No serious adverse events were reported. The trial measured a blood level, not a health outcome.
- Acute kidney injury, 2020. In 24 hospitalized patients with acute kidney injury, escalating doses (from 250 milligrams of nicotinamide riboside with 50 milligrams of pterostilbene up to 1,000 milligrams with 200 milligrams, twice a day for 2 days) were compared with placebo. Kidney injury alone cut blood nicotinamide adenine dinucleotide by 50% at 48 hours in the placebo patients. Across all doses together, the combination raised it by 37% at 48 hours. Safety blood tests, including kidney and liver tests, were unchanged, and 3 of the 20 treated patients reported minor stomach or bowel side effects. The study was built to test safety and blood levels, not recovery of the kidneys.
- Muscle injury in older adults, 2022. In a Danish trial, 32 people aged 55 to 80 took 1,000 milligrams of nicotinamide riboside and 200 milligrams of pterostilbene daily, or a placebo. Two weeks in, the researchers injured a thigh muscle with electrically driven exercise and took biopsies over the next 30 days. The combination was safe but did not improve the recruitment of muscle stem cells or any other measure of muscle recovery. This is a clear null result.
- Fatty liver, 2023. A 6-month randomized, double-blind, placebo-controlled trial enrolled 111 adults with non-alcoholic fatty liver disease. The primary goal, a fall in liver fat compared with placebo, was not met. Among the secondary results, the liver enzymes alanine aminotransferase and gamma-glutamyltransferase fell over time on the recommended dose, and so did a fat-derived molecule called ceramide 14:0. The double dose did not produce these changes. The authors described the result as holding promise for markers of liver inflammation. More on the condition is on the fatty liver disease page.
- Menopause symptoms, 2026. An open-label pilot trial gave 40 women over 35 the recommended dose (250 milligrams of nicotinamide riboside and 50 milligrams of pterostilbene) daily for 7 days. The 32 women who reported menopause-transition symptoms described less frequent and less severe bloating, hot flashes and poor sleep compared with their own baseline, and a urine hormone ratio (estradiol to estrone) rose. Everyone knew what they were taking and there was no placebo group, so the design cannot separate the supplement’s effect from expectation.
Taken together, these trials show that the combination raises blood nicotinamide adenine dinucleotide and was well tolerated over periods of 2 days to 6 months. They do not show which ingredient caused any change, and the one trial with a hard functional endpoint (muscle recovery) found nothing.
Findings in Animals and Cells
Much of what is written about pterostilbene comes from animal and laboratory studies. The results below are real findings, but each was measured in rodents or in cells, and none has been repeated as a clinical outcome in people.
- Memory in aged rats (2008). In 19-month-old rats, a diet containing 0.004% or 0.016% pterostilbene reversed age-related declines in learning tasks and in dopamine release in the brain. In these rats, working memory tracked the amount of pterostilbene measured in the hippocampus, a memory centre of the brain.
- Memory in a mouse model of accelerated aging (2012). In SAMP8 mice, a strain used as a model of aging and Alzheimer’s-type changes, two months of a pterostilbene diet improved performance in a water-maze memory test, while the same dose of resveratrol did not. Markers of cellular stress, inflammation and Alzheimer’s-type pathology also improved in these mice on pterostilbene only.
- Colon pre-cancer in rats (2007). In rats given a chemical that causes colon cancer, a diet with 40 parts per million of pterostilbene for 8 weeks reduced aberrant crypt foci, the earliest visible pre-cancerous changes in the colon, by 57%, and clusters of them by 29%. The same study confirmed one of the effects (lower iNOS, an inflammation enzyme) in human colon cancer cells grown in the laboratory.
- Prostate pre-cancer in mice (2022). In two strains of mice engineered to develop prostatic intraepithelial neoplasia (a pre-cancerous prostate change), a pterostilbene-supplemented diet led to fewer and less severe lesions, with lower markers of cell growth, new blood vessel formation and inflammation.
- Blood sugar in diabetic rats (1997). In rats made diabetic with the chemical streptozotocin, pterostilbene and marsupsin from the kino-tree heartwood, injected into the abdomen, lowered blood glucose, and the authors described the effect as comparable to metformin. Injection bypasses the gut, so this says nothing about pterostilbene taken by mouth.
- Brain immune cells in a dish (2013). In mouse microglia, the immune cells of the brain, pterostilbene, resveratrol and two blueberry anthocyanins each reduced inflammatory signals after the cells were exposed to a bacterial toxin. The researchers noted that much higher concentrations of the single compounds were needed than those found in blueberries: one anthocyanin worked at 20 micromolar on its own, while a blueberry extract that contained only 2.6 micromolar of it already had an effect. They concluded that the berry’s effect may not be due to any one compound.
The 2005 kino-tree study is a useful reminder of the gap between these results and people: the anti-inflammatory effect it found in the laboratory was not seen when volunteers took the extract, because their blood levels did not reach the laboratory concentration.
The Sirtuin Label and the Evidence Behind It
Pterostilbene is often described as a “sirtuin activator,” and some trial authors use the same label; the 2020 kidney study called it a potent sirtuin activator found in blueberries. Sirtuins are a family of enzymes involved in how cells respond to stress and nutrient supply, and the background, including the long dispute over whether resveratrol activates them directly, is on the Sirtuin Activators page.
The evidence for pterostilbene specifically is thin. In the 2012 SAMP8 mouse study, which found memory benefits on pterostilbene, neither pterostilbene nor resveratrol increased sirtuin 1 expression or the downstream markers of sirtuin 1 activation. The authors instead linked the benefit to higher expression of a different regulator, peroxisome proliferator-activated receptor alpha, and to pterostilbene’s greater fat-solubility. None of the human trials read for this page measured sirtuin activity directly. The combination trials measured nicotinamide adenine dinucleotide, which comes from the nicotinamide riboside half of the capsule.
What Is Not Known
- How well people absorb it. The 80% figure is from rats given large doses. No study read for this page measured oral bioavailability in humans.
- Long-term safety. Among the studies read for this page, the longest trial of pterostilbene alone ran 12 weeks and the longest combination trial ran 6 months. There is no safety data on use over years.
- What the cholesterol rise means. The 17.1 milligrams per deciliter rise in low-density lipoprotein cholesterol came from one small trial. Why it happened, why grape extract and cholesterol medication appeared to blunt it, and whether it persists are all unexplored in the abstracts read for this page.
- Hard outcomes. No trial has measured heart attacks, strokes, dementia, cancer or survival in people taking pterostilbene.
- Which ingredient does what. In the nicotinamide riboside combination trials, the two ingredients are never tested apart, so any result cannot be credited to pterostilbene.
- Whether food amounts matter. Blueberries carry trace amounts, and the 2004 study reported pterostilbene in only some kinds. The 2013 cell study found that single compounds needed much higher concentrations than those present in blueberry extract to have an effect.
- Specific groups. No safety data on pregnancy, breastfeeding or children turned up in the studies read, and none of the abstracts addressed interactions with medicines beyond the observation that cholesterol medication appeared to blunt the cholesterol rise.
The overall picture: a compound with striking results in rats and mice, a modest drop in blood pressure alongside a rise in low-density lipoprotein cholesterol in its one controlled efficacy trial, a short safety record with no adverse findings, and a set of combination trials whose main measured change, a rise in nicotinamide adenine dinucleotide, belongs to the other ingredient.
Key Research Papers
- Riche DM, Riche KD, Blackshear CT, McEwen CL, Sherman JJ, Wofford MR, Griswold ME. Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial. Evid Based Complement Alternat Med. 2014;2014:459165. PubMed PMID: 25057276
- Riche DM, McEwen CL, Riche KD, Sherman JJ, Wofford MR, Deschamp D, Griswold M. Analysis of safety from a human clinical trial with pterostilbene. J Toxicol. 2013;2013:463595. PubMed PMID: 23431291
- Kapetanovic IM, Muzzio M, Huang Z, Thompson TN, McCormick DL. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother Pharmacol. 2011;68(3):593-601. PubMed PMID: 21116625
- Rimando AM, Kalt W, Magee JB, Dewey J, Ballington JR. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem. 2004;52(15):4713-9. PubMed PMID: 15264904
- Kambiranda DM, Basha SM, Stringer SJ, Obuya JO, Snowden JJ. Multi-year Quantitative Evaluation of Stilbenoids Levels Among Selected Muscadine Grape Cultivars. Molecules. 2019;24(5):981. PubMed PMID: 30862045
- Manickam M, Ramanathan M, Jahromi MA, Chansouria JP, Ray AB. Antihyperglycemic activity of phenolics from Pterocarpus marsupium. J Nat Prod. 1997;60(6):609-10. PubMed PMID: 9214733
- Hougee S, Faber J, Sanders A, de Jong RB, van den Berg WB, Garssen J, Hoijer MA, Smit HF. Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers. Planta Med. 2005;71(5):387-92. PubMed PMID: 15931573
- Otsuka K, Kuriki D, Kamachi K, Tanaka A, Matsuoka R. Analysis of the Effects of Short-Term Pterostilbene Intake on Healthy Participants: A Pilot Study. J Nutr Sci Vitaminol (Tokyo). 2025;71(1):70-80. PubMed PMID: 40024751
- Dellinger RW, Santos SR, Morris M, Evans M, Alminana D, Guarente L, Marcotulli E. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD(+) levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis. 2017;3:17. PubMed PMID: 29184669
- Simic P, Vela Parada XF, Parikh SM, Dellinger R, Guarente LP, Rhee EP. Nicotinamide riboside with pterostilbene (NRPT) increases NAD(+) in patients with acute kidney injury (AKI): a randomized, double-blind, placebo-controlled, stepwise safety study of escalating doses of NRPT in patients with AKI. BMC Nephrol. 2020;21(1):342. PubMed PMID: 32791973
- Jensen JB, Dollerup OL, Møller AB, Billeskov TB, Dalbram E, Chubanava S, Damgaard MV, Dellinger RW, Trošt K, Moritz T, Ringgaard S, Møller N, Treebak JT, Farup J, Jessen N. A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals. JCI Insight. 2022;7(19):e158314. PubMed PMID: 35998039
- Dellinger RW, Holmes HE, Hu-Seliger T, Butt RW, Harrison SA, Mozaffarian D, Chen O, Guarente L. Nicotinamide riboside and pterostilbene reduces markers of hepatic inflammation in NAFLD: A double-blind, placebo-controlled clinical trial. Hepatology. 2023;78(3):863-877. PubMed PMID: 36082508
- Holmes HE, Srivastava K, Scalici JM, Dhuguru J, Shea AE, Migaud ME, Dellinger RW. Nicotinamide riboside and pterostilbene reduces frequency and severity of undesirable symptoms of the menopause transition: an open-label, pilot clinical trial. Front Aging. 2026;7:1773667. PubMed PMID: 42211736
- Joseph JA, Fisher DR, Cheng V, Rimando AM, Shukitt-Hale B. Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging. J Agric Food Chem. 2008;56(22):10544-51. PubMed PMID: 18954071
- Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt-Hale B, Smith MA, Joseph JA, Casadesus G. Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease. Neurobiol Aging. 2012;33(9):2062-71. PubMed PMID: 21982274
- Suh N, Paul S, Hao X, Simi B, Xiao H, Rimando AM, Reddy BS. Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats. Clin Cancer Res. 2007;13(1):350-5. PubMed PMID: 17200374
- Hemani R, Patel I, Inamdar N, Campanelli G, Donovan V, Kumar A, Levenson AS. Dietary Pterostilbene for MTA1-Targeted Interception in High-Risk Premalignant Prostate Cancer. Cancer Prev Res (Phila). 2022;15(2):87-100. PubMed PMID: 34675064
- Carey AN, Fisher DR, Rimando AM, Gomes SM, Bielinski DF, Shukitt-Hale B. Stilbenes and anthocyanins reduce stress signaling in BV-2 mouse microglia. J Agric Food Chem. 2013;61(25):5979-86. PubMed PMID: 23731018
PubMed Topic Searches
Connections
- Other Polyphenols — the parent category
- Resveratrol — the parent stilbene and its human trials
- Sirtuin Activators for Longevity — the sirtuin debate in full
- Blueberries — the whole fruit and its anthocyanins
- Grapes — the other stilbene-bearing fruit
- Nicotinamide Adenine Dinucleotide Boosters — nicotinamide riboside and nicotinamide mononucleotide
- Nicotinamide Adenine Dinucleotide and Nicotinamide Mononucleotide — the cellular energy molecule
- Fatty Liver Disease — the condition in the 2023 combination trial