← Back

Liver

Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Medication3 Peptides and SARMs1 Supplements17 Therapies1 Food and drink1 Diets2 Lab markers6

Medication

OrlistatStrong

Liver enzymes in fatty liver disease

Shown to lower liver enzymes in fatty liver disease, ALT by about 9 U/L. Liver fat and scarring were not measured.

The numbers and sources

Effect: In people with metabolic dysfunction-associated steatotic liver disease, orlistat lowered AST by 4.01 U/L (95% CI 1.97 to 6.05), ALT by 8.70 U/L (95% CI 0.90 to 16.51) and GGT by 7.74 U/L (95% CI 0.59 to 14.88) against control. LDL cholesterol fell 5.61 mg/dL, fasting glucose 4.05 mg/dL, HOMA-IR 0.70 and BMI 0.99 kg/m². Blood pressure did not change [6]. A second meta-analysis also found lower ALT, AST, HOMA-IR, BMI, cholesterol, insulin and waist circumference [7].
Population: 6 RCTs [6]; 11 studies with 582 participants [7].
Sources: [6], [7]
Caveats: Both reviews measured blood markers, not liver fat on imaging or scarring on biopsy. The trials were small and likely overlap between the reviews. The abstract of [7] does not say whether all 11 studies were randomized.

RetatrutideGrey marketLimited

Liver fat

One small trial found liver fat fell up to 82% over 24 weeks in adults with fatty liver disease. Liver scarring and outcomes were not measured.

The numbers and sources

Effect: At 24 weeks, liver fat changed by -42.9% on 1 mg, -57.0% on 4 mg, -81.4% on 8 mg and -82.4% on 12 mg, against +0.3% on placebo. Normal liver fat (under 5%) was reached by 86% on 12 mg and 0% on placebo [10].
Population: 98 adults with metabolic dysfunction-associated steatotic liver disease and at least 10% liver fat, a substudy of the phase 2 trial [10].
Sources: [10]
Caveats: A small phase 2 substudy. It measured liver fat, not liver scarring or outcomes.

SemaglutideLimitedVery common

Fatty liver inflammation and scarring (MASH)

One trial found liver inflammation resolved in 63% on semaglutide against 34% on placebo in adults with MASH. Outcomes were biopsy findings, not cirrhosis or liver failure.

The numbers and sources

How common: Very common: more than 1 in 10 people.
Effect: At 72 weeks, steatohepatitis resolved without worsening of fibrosis in 62.9% on semaglutide and 34.3% on placebo (difference 28.7 points, 95% CI 21.1 to 36.2). Fibrosis improved without worsening of steatohepatitis in 36.8% and 22.4% (difference 14.4 points, 95% CI 7.5 to 21.3). Both improved together in 32.7% and 16.1%. Body weight changed by -10.5% and -2.0% [7].
Population: The first 800 of 1,197 adults with biopsy-confirmed MASH and fibrosis stage 2 or 3, randomized 2 to 1 to 2.4 mg weekly or placebo (534 and 266) [7].
Sources: [7]
Caveats: An interim analysis of an ongoing 240-week trial. The outcomes are liver biopsy findings, not cirrhosis, liver failure or death. Funded by Novo Nordisk [7].
Why limited: This rests on one trial, of 1,197 people. Strength counts independent studies that agree, so one trial is limited at any size.

Peptides and SARMs

TesamorelinModerate

Liver fat

Shown to lower liver fat about 3 to 4 points more than placebo in adults with HIV. Liver scarring and outcomes were not measured.

The numbers and sources

Effect: Pooled across RCTs, liver fat percentage fell by 4.28 points against placebo (95% CI -6.31 to -2.24) [5]. Over 6 months, liver fat changed by a median -2.0% (lipid to water) on tesamorelin and +0.9% on placebo, a net effect of -2.9%. Visceral fat fell by 42 cm² more than placebo (95% CI -71 to -14) [7]. In people with HIV and fatty liver disease, liver fat fraction fell 4.1 points more than placebo at 12 months (95% CI -7.6 to -0.7), a 37% relative reduction. Liver fat under 5% was reached by 35% on tesamorelin and 4% on placebo [8].
Population: RCTs in adults with HIV [5]; 50 adults with HIV and abdominal fat accumulation [7]; 61 adults with HIV and a liver fat fraction of 5% or more [8].
Sources: [5], [7], [8]
Caveats: One meta-analysis built on small trials. They measured liver fat, not liver scarring or liver outcomes. The 2019 trial was funded by the NIH [8].

Supplements

Fisetin and quercetin (senolytics)Moderate

Liver enzymes and lipids in fatty liver disease (quercetin alone)

Shown to lower liver enzymes, LDL and triglycerides with quercetin alone in people with fatty liver disease, at very low to moderate certainty.

The numbers and sources

Effect: A 2025 meta-analysis of 7 RCTs (540 patients) with metabolic dysfunction-associated steatotic liver disease found that quercetin lowered ALT, AST, GGT, direct bilirubin and C-reactive protein, lowered total cholesterol, LDL and triglycerides, and raised HDL. BMI, body fat, kidney function and TNF-α did not change [10].
Population: 540 patients with fatty liver disease in 7 RCTs [10].
Sources: [10]
Caveats: GRADE certainty ranged from very low to moderate. Dose, baseline BMI and age may explain heterogeneity. The abstract gives no pooled effect sizes [10]. None of the trials measured senescent cells.

Milk thistleModerate

Fatty liver disease

Shown to lower liver enzymes in fatty liver disease, ALT by about 7 to 12 U/L, with low certainty and no data on deaths.

The numbers and sources

Effect: In 26 trials (2,375 patients), silymarin lowered ALT (pooled difference -12.39, 95% CI -19.69 to -5.08) and AST (-10.97, 95% CI -15.51 to -6.43), lowered total cholesterol, triglycerides and LDL, and improved steatosis on histology (OR 3.25, 95% CI 1.80 to 5.87) [5]. In a 48-week biopsy trial of 99 adults with NASH, a 30% or greater fall in disease activity score occurred in 32.7% on 700 mg three times a day and 26.0% on placebo (p 0.467). Fibrosis fell by 1 point or more in 22.4% against 6.0% (p 0.023) [6]. A 2025 Cochrane review of 17 RCTs (2,069 adults) found silymarin alone against placebo or no treatment may lower ALT by 7.21 U/L (95% CI -10.62 to -3.80, 6 trials, very low certainty). Silymarin complexes did not lower ALT, and no trial reported deaths or quality of life [7]. In a 2025 meta-analysis of 25 studies (2,283 patients), silymarin alone lowered LDL cholesterol (SMD -0.25), while ALT fell when silymarin was combined with diet or lifestyle change [8].
Population: Adults with fatty liver disease [5][7][8]. 99 adults with biopsy-proven NASH in Malaysia [6].
Sources: [5], [6], [7], [8]
Caveats: The meta-analysis authors state that the effects need confirmation [5]. The biopsy trial missed its primary outcome, and its fibrosis finding was secondary [6]. The Cochrane authors rated the evidence low to very low certainty and called benefits and harms unclear [7].

TurmericModerate

Fatty liver and liver enzymes

Shown to lower the liver enzymes ALT and AST slightly in adults with fatty liver disease, but not in people with diabetes or with piperine added.

The numbers and sources

Effect: In 15 RCTs (905 patients with nonalcoholic fatty liver disease), curcumin lowered ALT by 4.10 (95% CI -7.16 to -1.04) and AST by 3.27 (95% CI -5.16 to -1.39), with no change in ALP. Curcumin with piperine did not change ALT or AST significantly [36]. In 10 RCTs in prediabetes and diabetes, ALT and AST did not change significantly and GGT fell 2.35 IU/L [37]. Across 18 RCTs of curcuminoids with piperine, AST fell 2.29 IU and the ALT change was not significant (p 0.053) [18].
Population: Adults with nonalcoholic fatty liver disease [36]; adults with prediabetes or diabetes [37]; adults in curcumin with piperine trials [18].
Sources: [36], [37], [18]
Caveats: These are blood enzymes, not measures of liver fat or fibrosis. Results differed by population and formulation [36][37].

Vitamin EModerate

Fatty liver inflammation (NASH)

Shown to improve liver inflammation in adults with NASH without diabetes, 43% against 19% on placebo in one trial. Results on fibrosis disagree.

The numbers and sources

Effect: After 96 weeks, nonalcoholic steatohepatitis improved in 43% on 800 IU a day and 19% on placebo. Liver enzymes, fat and inflammation fell. Fibrosis scores did not improve [6]. Across 3 placebo-controlled RCTs in steatohepatitis, vitamin E lowered ALT (MD -12.27, 95% CI -16.66 to -7.89) and raised the odds of fibrosis improvement (OR 1.96, 95% CI 1.25 to 3.09). Resolution of steatohepatitis did not differ significantly (OR 1.71, 95% CI 0.69 to 4.27) [7]. Across 16 RCTs in fatty liver disease, vitamin E lowered AST (WMD -5.94 IU/L) and ALT (WMD -7.33 IU/L) [8]. In a Chinese trial, liver histology improved in 29.3% on 300 mg a day and 14.1% on placebo, with gains in steatosis, inflammation and fibrosis stage [9].
Population: 247 adults with nonalcoholic steatohepatitis and without diabetes [6]; adults with steatohepatitis in 2 US trials and 1 Chinese trial [7]; adults with metabolic dysfunction-associated steatotic liver disease [8]; 124 adults without diabetes with biopsy-proven steatohepatitis in China [9].
Sources: [6], [7], [8], [9]
Caveats: The 3-trial review is small and its resolution result was heterogeneous [7]. The first large trial found no fibrosis improvement [6], while the pooled analysis and the Chinese trial did [7][9]. The enzyme review could not judge fibrosis or long-term liver outcomes [8].

Artichoke leafLimited

Liver detox

One small trial found a single dose of artichoke extract raised bile flow over placebo. No study in people measured whether it clears toxins from the liver.

The numbers and sources

Effect: In a randomized, placebo-controlled, double-blind crossover pilot study, 1.92 g of extract given into the duodenum raised bile secretion by 127.3% at 30 minutes, 151.5% at 60 minutes and 94.3% at 120 minutes over baseline. Placebo peaked at 139.5% at 30 minutes and fell below baseline after 3 hours. The authors reported the differences from placebo as significant (p < 0.01), with more bile on extract at 120 and 150 minutes (p < 0.05). No side effects or lab changes were seen [11]. In rats, the extract raised bile flow and bile acid output [12]. In mice given a toxic dose of acetaminophen, the extract lowered ALT, AST and ALP and reduced liver damage on histology [13].
Population: 20 people in a crossover pilot [11]. Wistar rats [12]. 40 male mice [13].
Sources: [11], [12], [13]
Caveats: One single-dose pilot, with the extract given by tube, not by mouth [11]. Bile flow is not a measure of toxin removal. The liver protection findings come from animals given a poison [13].

CholineLimited

Fatty liver and muscle damage when choline intake is low

Limited evidence: most adults on very low choline diets developed fatty liver or muscle damage, which reversed when choline was added back.

The numbers and sources

Effect: On a diet with under 50 mg of choline a day, 77% of men and 80% of postmenopausal women developed fatty liver or muscle damage, against 44% of premenopausal women. Organ function returned when choline was added back. Six men developed signs on 550 mg a day [8]. In people on long-term IV nutrition with low choline, 1 to 4 g a day of IV choline chloride resolved fatty liver within 6 weeks, and it returned in one patient after choline stopped [9].
Population: 57 adults in a depletion study [8]; 4 adults on IV nutrition for about 10 years [9].
Sources: [8], [9]
Caveats: These are depletion and repletion studies, not trials of supplements in people eating normal diets.

Fisetin and quercetin (senolytics)Limited

Liver fibrosis

One small trial found liver fibrosis improved in 47% on dasatinib plus quercetin against 7% on placebo in adults with fibrotic MASH.

The numbers and sources

Effect: Fibrosis improved by at least one stage without MASH worsening in 47% on dasatinib plus quercetin and 7% on placebo (p = 0.02). MASH resolved in 53% against 7% (p = 0.02) [2].
Population: 31 adults with fibrotic MASH, median age 56, 58% with type 2 diabetes. Dasatinib 100 mg and quercetin 1,000 mg a day for 3 days a week, over three 7-week cycles [2].
Sources: [2]
Caveats: One small phase 2 trial with paired liver biopsies.

GlutathioneLimited

Liver function in chronic hepatitis B

One trial without placebo found lower ALT when glutathione was added to entecavir for 3 months in chronic hepatitis B.

The numbers and sources

Effect: In one trial, reduced glutathione added to entecavir for 3 months lowered ALT to 31.11 U/L against 56.90 U/L on entecavir alone, from about 348 U/L in both groups. Fibrosis markers fell more, and HBV DNA was undetectable at 48 weeks in 68.89% against 42.22% [10].
Population: 90 patients with chronic hepatitis B [10].
Sources: [10]
Caveats: One trial without placebo. The abstract does not state the glutathione dose or route [10].

TMGLimited

Liver health

Small trials without placebo found liver enzymes fell at 2 to 8 g a day in adults with fatty liver disease, but not at 1 g.

The numbers and sources

Effect: In three pilot trials, ALT, AST, cytokeratin 18, pro-C3 and a combined liver injury score fell from baseline at 8, 4 and 2 g a day over 12 to 24 weeks, but not at 1 g a day [6].
Population: 70 adults with metabolic dysfunction-associated steatotic liver disease and ALT of 50 U/L or more: 44 randomized to 4 or 8 g a day for 12 weeks, 10 on 1 g and 16 on 2 g a day for 24 weeks [6].
Sources: [6]
Caveats: No placebo group. Results compare each person's levels before and after treatment, and the outcomes are blood markers rather than liver biopsy [6].

Milk thistleModerate

Liver detox

Mixed results: one meta-analysis found silymarin cut liver injury from tuberculosis drugs by two thirds at 4 weeks, while another found no enzyme fall in drug-induced liver injury.

Compared with placebo [12]; control groups the source does not describe [4]

The numbers and sources

Effect: Across 5 placebo-controlled trials (1,198 patients starting tuberculosis drugs), silymarin lowered drug-induced liver injury at week 4 (RR 0.33, 95% CI 0.15 to 0.75) and improved liver function (SMD -0.15, 95% CI -0.24 to -0.07) [12]. In a meta-analysis of 55 trials of liver injury from various causes, silymarin had no significant effect on AST or ALT in the drug-induced liver injury subgroup [4].
Population: 1,198 adults taking tuberculosis drugs in 5 RCTs [12]. Patients with drug-induced liver injury within 55 trials (3,545 patients) [4].
Sources: [12], [4]
Caveats: "Detox" is not a measured outcome. These trials tested protection of the liver from medicines. The protective effect was reported at week 4 [12]. The two reviews asked different questions, prevention in [12] and treatment of existing injury in [4].

TUDCALimited

Liver protection with alcohol, oral steroids or other drugs

Case reports: one person developed drug-induced liver injury while taking TUDCA for protection. In mice, TUDCA eased acetaminophen liver injury, less than standard treatment.

The numbers and sources

Effect: A 2026 case report describes liver injury from fenbendazole in a person also taking TUDCA as an intended liver protectant, the first published report of that combination [8]. In mice given an acetaminophen overdose, TUDCA lowered transaminases, liver cell death and oxidative stress markers, to a lesser extent than N-acetylcysteine, and the two together did better than N-acetylcysteine alone [9].
Population: One person [8]. Mice [9].
Sources: [8], [9]
Caveats: A single case cannot show whether TUDCA changed the course of the injury [8]. The mouse study tested acetaminophen only, with treatment given after the overdose [9]. No study of TUDCA with alcohol or oral steroids in people was located.

SAM-eModerate

Alcoholic liver disease

Not shown to lower death or liver transplant in adults with alcoholic liver disease. One trial's after-the-fact subgroup, excluding the most advanced cases, found fewer.

The numbers and sources

Effect: Across 9 trials (434 patients), SAMe did not significantly change all-cause mortality (RR 0.62, 95% CI 0.30 to 1.26), liver-related mortality (RR 0.68) or death or transplant (RR 0.55, 95% CI 0.27 to 1.09) [7]. In the largest trial, 123 people with alcoholic cirrhosis on 1,200 mg a day for 2 years had death or transplant in 16% against 30% on placebo (p 0.077). Excluding the most advanced cases, rates were 12% against 29% (p 0.025) [8].
Population: Adults with alcoholic liver disease [7]. 123 adults with cirrhosis in Spain [8].
Sources: [7], [8]
Caveats: The pooled analysis rests mostly on one trial [7]. The subgroup result in [8] excluded Child class C patients after the fact.

DandelionUntested

Liver health

Not studied in people. Dandelion has long been used for liver disorders, and in mice on a high-fat diet a leaf extract cut fat build-up in the liver.

No study in people. This rests on animal studies, documented traditional use.

The numbers and sources

Effect: A 2025 review notes that dandelion has historically been used for liver disorders, and found only preclinical studies of its liver effects [4]. In mice fed a high-fat diet, dandelion leaf extract reduced fat in the liver, liver weight, blood triglycerides and cholesterol compared with the high-fat diet alone [5].
Population: A narrative review of animal studies [4]. C57BL/6 mice [5].
Sources: [4], [5]
Caveats: The review states that clinical trials are needed to confirm any effect in people [4]. Fatty liver in diet-fed mice is a model, not a human outcome.

DandelionUntested

Liver detox

Not studied in people. In animals given liver poisons such as alcohol, carbon tetrachloride or paracetamol, dandelion extracts reduced liver damage.

No study in people. This rests on animal studies.

The numbers and sources

Effect: A 2025 review of animal studies reports that dandelion extracts protected against liver damage caused by alcohol, carbon tetrachloride and paracetamol, and points to taraxasterol, which acts on inflammation and oxidative stress pathways [4].
Population: Animal models of toxic liver injury [4].
Sources: [4]
Caveats: Protecting an animal from a large dose of a poison is not the same as clearing everyday toxins in people. No human study was located [4].

SchisandraUntested

Liver health

Not studied in people. In 54 animal studies of liver injury, Schisandra compounds lowered the liver enzymes ALT and AST and markers of inflammation.

No study in people. This rests on animal studies, documented traditional use.

The numbers and sources

Effect: A 2025 meta-analysis of 54 animal studies of liver injury found Schisandra chinensis compounds lowered ALT (SMD -4.74, 95% CI -5.42 to -4.06), AST (SMD -5.10, 95% CI -5.84 to -4.37) and alkaline phosphatase, lowered TNF-α, IL-6 and IL-1β, and raised the antioxidants SOD and glutathione. The review notes more than 2,000 years of use in traditional Chinese medicine [6].
Population: Animal models of liver injury in 54 studies [6].
Sources: [6]
Caveats: Animal studies with very high heterogeneity (I² above 90%), and the effects varied with species, compound, injury model and dose [6]. No trial of Schisandra alone for liver health in people was located.

TUDCAUntested

Fatty liver

Not studied in people. In mouse models of fatty liver, TUDCA reduced weight gain and liver fat and changed bile acid handling and gut bacteria.

No study in people. This rests on animal studies, how it acts in the body.

The numbers and sources

Effect: In mouse models of fatty liver disease, TUDCA reduced obesity and liver fat buildup, improved gut barrier function, raised liver bile acids and lowered fatty acid uptake through FXR and FATP5 [6]. A 2026 review describes TUDCA as easing endoplasmic reticulum stress, inflammation, oxidative stress and liver cell death, and states that high-quality clinical evidence is still limited [7].
Population: Mice with fatty liver disease [6]. Preclinical studies, reviewed [7].
Sources: [6], [7]
Caveats: Animal data. The one human metabolic trial on this page measured insulin sensitivity over 4 weeks, not liver fat [3]. No trial of TUDCA for fatty liver in people was located.

Therapies

Colon hydrotherapyLimitedStudied in men

Antioxidant levels after coffee enemas

One small crossover trial in healthy men found coffee enemas did not raise blood glutathione or lower a marker of oxidative damage over 12 days.

Compared with drinking coffee, and baseline levels in the same men [8]

The numbers and sources

Effect: Neither single nor repeated coffee enemas raised serum glutathione or lowered serum malondialdehyde over 12 days, and the same held for drinking coffee. Total antioxidant capacity fell from baseline by day 12 after coffee enemas [8]. A companion study found caffeine reached about 3.5 times lower blood levels after a 500 mL coffee enema than after drinking 180 mL of coffee with the same caffeine content [9].
Population: 11 healthy Thai men in each crossover study [8][9].
Sources: [8], [9]
Caveats: Small studies in healthy men, not in people with the illnesses coffee enemas are used for.

Food and drink

CoffeeModerate

Cirrhosis and liver cancer

Linked to 44% lower cirrhosis and 35% lower liver cancer for each extra 2 cups a day, in pooled studies rated very low in quality.

Compared with 2 fewer cups a day, in a dose-response model [9][10]

The numbers and sources

Effect: For each extra 2 cups a day, the relative risk of cirrhosis was 0.56 (95% CI 0.44 to 0.68), of alcoholic cirrhosis 0.62 (95% CI 0.51 to 0.73) and of death from cirrhosis 0.55 (95% CI 0.35 to 0.74) [9]. For hepatocellular carcinoma it was 0.65 (95% CI 0.59 to 0.72), 0.71 in cohorts and 0.53 in case-control studies. Caffeinated coffee gave 0.73 (95% CI 0.63 to 0.85) and decaffeinated 0.86 (95% CI 0.74 to 1.00). The link held with or without heavy drinking, obesity, diabetes, smoking or hepatitis B and C [10].
Population: 432,133 participants and 1,990 cirrhosis cases in 9 studies [9]. 2,272,642 participants in 18 cohorts and 1,825 cases in 8 case-control studies [10].
Sources: [9], [10], [2]
Caveats: Heterogeneity was high for cirrhosis (I² 83.3%). The liver cancer review rated its evidence very low under GRADE, citing no randomized trials, possible publication bias and no accepted definition of a cup [10]. The decaffeinated estimate rests on 3 cohorts.

Diets

Keto dietLimited

Liver fat and insulin sensitivity

One trial found that at equal 10% weight loss, liver insulin sensitivity rose two to three times more than on Mediterranean or very-low-fat diets.

Compared with diets that did not restrict carbohydrates to the level of ketosis

The numbers and sources

Effect: Calories were adjusted so every group lost about 10% of body weight. Muscle insulin sensitivity rose about 50% on all three diets. Liver insulin sensitivity rose two to three times more on the very-low-carbohydrate ketogenic diet (p < 0.001), and liver fat, liver fat production, HbA1c and 24-hour glucose and insulin fell most on it. LDL cholesterol, apolipoprotein B and 24-hour triglycerides did not differ between diets [12].
Population: Adults with obesity, prediabetes and fatty liver. The abstract does not give the number randomized [12].
Sources: [12]
Caveats: One small trial. Food was supplied during weight loss, so it measures the diets eaten as written. It does not apply to people without prediabetes and fatty liver.

Juice cleanseLimited

Toxin removal

Limited evidence: a review found a handful of small, flawed studies of commercial detox diets and no randomized trial. None measured toxin removal on a juice cleanse.

Compared with no randomized comparison exists, per the review [2]

The numbers and sources

Effect: A 2015 critical review found that a handful of clinical studies reported that commercial detox diets enhanced liver detoxification and removed persistent organic pollutants, but described them as hampered by flawed methods and small samples. It found no randomized controlled trial of a commercial detox diet in people, and noted that evidence for detoxifying foods such as coriander and nori came mostly from animals [2].
Population: A review of clinical and animal studies of detox diets [2].
Sources: [2]
Caveats: The studies reviewed were of detox programs in general, not juice-only cleanses [2]. No study measuring toxins in the blood or urine before and after a juice cleanse was located.

Lab markers

Gamma-glutamyl transferase (GGT)Strong

Death from any cause

Linked to more deaths from any cause, about 7% higher risk for each 5 U/L in a meta-analysis of general population cohorts.

The numbers and sources

Effect: In a meta-analysis of 19 cohort studies, the relative risk of death from any cause was 1.60 (95% CI 1.42 to 1.80) comparing the top and bottom thirds of baseline GGT, and 1.07 (1.04 to 1.10) per 5 U/L higher, consistent with a linear relationship [7]. A second meta-analysis of 35 prospective studies found GGT was associated with increased all-cause and cardiovascular mortality even at levels inside the reference interval [8]. In 14,950 US adults without viral hepatitis followed for 12 years, GGT above 51 U/L in men or 33 U/L in women went with more deaths from any cause (HR 1.5, 95% CI 1.2 to 1.8), from liver disease (HR 13.0, 95% CI 2.4 to 71.5), from neoplasms (HR 1.5, 95% CI 1.01 to 2.2) and from diabetes (HR 3.3, 95% CI 1.4 to 7.6) [4].
Population: Over 9.24 million participants and 242,953 deaths in 19 cohorts, which also covered other liver enzymes [7]. 571,511 participants and 72,196 deaths in 35 studies [8]. 14,950 adults in the third US National Health and Nutrition Examination Survey [4].
Sources: [7], [8], [4]
Caveats: Observational. Many of the pooled studies did not exclude people with liver disease or heavy alcohol use, which the authors of one meta-analysis say may have obscured the results [8]. Liver disease deaths were 0.13% of the US cohort, so the interval around that estimate is wide [4].

Alanine aminotransferase (ALT)Moderate

Death from liver disease

Linked to more deaths from liver disease, with risk rising from values of 20 U/L upward in one large Korean cohort.

The numbers and sources

Effect: In 142,055 Korean adults followed for 8 years, death from liver disease rose with ALT even inside the usual reference range. Compared with ALT below 20 IU/L, the adjusted relative risk in men was 2.9 (95% CI 2.4 to 3.5) at 20 to 29 IU/L and 9.5 (7.9 to 11.5) at 30 to 39 IU/L. In women it was 3.8 (1.9 to 7.7) and 6.6 (1.5 to 25.6). The cut-off that predicted liver disease in men with the greatest accuracy was 30 IU/L [10]. In 14,950 US adults without viral hepatitis followed for 12 years, ALT above 30 U/L in men or 19 U/L in women went with more deaths from liver disease (HR 8.2, 95% CI 2.1 to 31.9) [11].
Population: 94,533 men and 47,522 women aged 35 to 59 in the Korea Medical Insurance Corporation study [10]. 14,950 adults in the third US National Health and Nutrition Examination Survey, negative for hepatitis B and C markers [11].
Sources: [10], [11]
Caveats: Observational. Deaths were taken from death certificates. Liver disease deaths were 0.13% of the US cohort over 12 years, so the interval around that estimate is wide [11]. The authors of a US study note that results from South Korea would not necessarily apply to countries where different causes of liver disease predominate [6].

Alanine aminotransferase (ALT)Moderate

Type 2 diabetes

Linked to more type 2 diabetes, 16% higher risk per 5 U/L in pooled cohorts, a result the authors said publication bias may explain.

The numbers and sources

Effect: In a meta-analysis of 17 prospective studies, the relative risk of type 2 diabetes was 1.16 (95% CI 1.08 to 1.25) per 5 IU/L higher ALT and 1.26 (1.14 to 1.41) per standard deviation of log ALT, with high heterogeneity (I2 88%). The association became nonsignificant after correction for publication bias [12]. In a Mendelian randomization study, genetically predicted higher ALT was related to more type 2 diabetes (odds ratio 1.45 per standard unit, 95% CI 1.10 to 1.92) [13].
Population: 60,359 participants and 3,890 new cases of type 2 diabetes in 17 studies [12]. Up to 64,094 people with type 2 diabetes and 607,012 controls in the genetic study [13].
Sources: [12], [13]
Caveats: The cohort studies are observational and their pooled result did not survive correction for publication bias [12]. The genetic study's authors read their findings as support for insulin resistance leading to fatty liver, which in turn raises diabetes risk, so ALT may mark that process and not drive it [13].

FerritinModerate

Organ damage in hereditary hemochromatosis

Linked to liver damage in people with the hemochromatosis genotype, where ferritin of 1,000 ng/mL or more marks those at higher risk.

The numbers and sources

Effect: Among people homozygous for the HFE C282Y variant followed for an average of 12 years, documented disease related to iron overload developed in 28.4% of men (95% CI 18.8 to 40.2) and 1.2% of women (95% CI 0.03 to 6.5). Men with the genotype and ferritin of 1,000 ng/mL or more were more likely to report fatigue, use of arthritis medicine and a history of liver disease than men without the variant [11]. A liver society guideline reports that fewer than 2% of people with HFE hemochromatosis and ferritin below 1,000 ng/mL at diagnosis have bridging fibrosis or cirrhosis in the absence of other conditions, a 94% negative predictive value. It also cites a review in which 64% of patients referred with ferritin over 1,000 ng/mL did not have iron overload on biopsy [12].
Population: 203 C282Y homozygotes among 31,192 people of northern European descent aged 40 to 69 [11]. Studies summarized in an Asian Pacific guideline [12].
Sources: [11], [12]
Caveats: Applies to people who carry the genotype. In people referred for a high ferritin without it, most did not have iron overload [12].

Aspartate aminotransferase (AST)Limited

Death from liver disease

One large Korean cohort found deaths from liver disease rose with AST from 20 U/L upward, inside the usual reference range.

The numbers and sources

Effect: In 142,055 Korean adults followed for 8 years, death from liver disease rose with AST even inside the usual reference range. Compared with AST below 20 IU/L, the adjusted relative risk in men was 2.5 (95% CI 2.0 to 3.0) at 20 to 29 IU/L and 8.0 (6.6 to 9.8) at 30 to 39 IU/L. In women it was 3.3 (1.7 to 6.4) and 18.2 (8.1 to 40.4). The cut-off that predicted liver disease in men with the greatest accuracy was 31 IU/L [5].
Population: 94,533 men and 47,522 women aged 35 to 59 in the Korea Medical Insurance Corporation study [5].
Sources: [5]
Caveats: Observational, one cohort in one country, with deaths taken from death certificates. The abstract does not say which side of the cut-off a result of exactly 31 falls on, so it is not placed as a range on this page [5].

Aspartate aminotransferase (AST)Moderate

Type 2 diabetes

Mixed results: 9 pooled cohort studies found no increase in type 2 diabetes with higher AST, while a genetic study found a 25% higher risk.

The numbers and sources

Effect: In a meta-analysis, 9 prospective studies that measured AST gave a relative risk of type 2 diabetes of 1.02 (95% CI 0.99 to 1.04) per standard deviation of log AST, which the authors read as no evidence of increased risk [8]. In a Mendelian randomization study, genetically predicted higher AST was related to more type 2 diabetes (odds ratio 1.25 per standard unit, 95% CI 1.14 to 1.38) [9].
Population: 17 studies with 60,359 participants in the meta-analysis, 9 of which measured AST [8]. Up to 64,094 people with type 2 diabetes and 607,012 controls in the genetic study [9].
Sources: [8], [9]
Caveats: The cohort studies are observational. The genetic study's authors read their findings as support for insulin resistance leading to fatty liver, which in turn raises diabetes risk, so AST may mark that process and not drive it [9].