BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance.
OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD.
METHODS: A systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD).
RESULTS: Pooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9).
CONCLUSIONS: Probiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD.
BACKGROUND: PROSPERO registration number CRD42023424290.

BACKGROUND: Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear.
OBJECTIVE: This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials.
METHODS: An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023.
METHODS: The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials.
METHODS: The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: -2.88, 95% CI: -4.72 to -1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: -1.67, 95% CI: -3.12 to -0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: -3.19, 95% CI: -6.00 to -0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: -0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported.
CONCLUSIONS: IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function.
BACKGROUND: PROSPERO registration no. CRD42023396211.

In recent years, an increase in the incidence of liver diseases has been reported all over the world. This study aims to comprehensively summarize and quantitatively analyze the existing evidence concerning the effectiveness of grape-derived products on liver enzymes through a systematic review and meta-analytic approach. PubMed, Scopus, Cochrane Library, and ISI Web of Science were comprehensively searched until January 2024. Articles that reported the effect of grape-derived products on serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were included. Weighted mean differences (WMDs) were pooled using a random-effects model. Nine studies were included in the meta-analysis. The results revealed that grape-derived products did not significantly change the concentrations of ALT (WMD: -2.70 IU/L, 95% CI: -6.14 to 0.75, p = 0.12), and AST (WMD: -1.42 IU/L, 95% CI: -3.54 to 0.70, p = 0.18). However, a significant reduction was observed in serum ALP levels (WMD: -5.49 IU/L, 95% CI: -9.57 to -1.4, p = 0.008). The present findings suggest that grape-derived products positively influence serum ALP levels among adults. However, a more comprehensive decision necessitates additional studies.

BACKGROUND: The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is lifestyle modification; this should accompany any pharmacological intervention. Intermittent fasting (IF) has shown benefits over metabolic and cardiovascular parameters. Non-religious IF includes Time-Restricted Feeding (TRF), Alternate-Day Fasting (ADF), and 5:2 IF interventions.
OBJECTIVE: To evaluate the effects of IF on anthropometric, liver damage, and lipid profile markers in subjects with NAFLD.
METHODS: A bibliographic search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed and Scopus databases.
RESULTS: Five studies involving 470 patients with NAFLD were included. In relation to anthropometric markers, all the articles reported body weight reduction (2.48-7.63%), but only ADF and 5:2 IF reported a body weight reduction >5%; also, all the articles reported fat mass reduction. Concerning hepatic markers, all the articles reported a reduction in hepatic steatosis and alanine aminotransferase activity, but no changes in fat-free mass and high-density lipoprotein cholesterol levels. There were variable results on fibrosis, other liver enzymes, waist circumference and body mass index, as well as the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol.
CONCLUSIONS: Any form of IF could be potentially beneficial for NAFLD treatment and some associated cardiometabolic parameters. However, it is necessary to evaluate the effects and safety of IF in long-term studies involving a higher number of participants with different stages of NAFLD. The effect of IF on NAFLD-associated vascular risk also needs evaluation.

BACKGROUND: Clinical evidence from investigations of the effects of curcumin on liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD) have led to inconsistent results.
OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate the overall effects of curcumin and curcumin plus piperine supplementation on liver enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) in patients with NAFLD.
METHODS: The Scopus, Web of Science, PubMed, and Cochrane Library databases were searched from inception through July 2023, using search terms representing NAFLD and liver enzymes. Articles were screened independently by 2 researchers based on PICOS inclusion criteria.
METHODS: The following data were extracted: first author\'s name, study location, year of publication, mean age, study duration, study design, participants\' sex, number of participants in each group, dose of curcumin supplementation, and ALT, ALP, and AST concentrations. Risk of bias was assessed using the Cochrane Collaboration\'s modified risk-of-bias tool.
METHODS: Fixed- or random-effects meta-analysis was performed to estimate the effects of curcumin on liver enzymes, considering heterogeneity across studies. The I2 and Cochran\'s Q tests were used to assess heterogeneity between studies.
RESULTS: Overall, 15 randomized controlled trials comprising 905 participants were eligible for this meta-analysis. Curcumin supplementation significantly reduced ALT (weighted mean difference [WMD], -4.10, 95%CI, -7.16 to -1.04) and AST (WMD, -3.27; 95%CI, -5.16 to -1.39), but not ALP (WMD, -0.49; 95%CI, -1.79 to 0.82). Curcumin plus piperine supplementation had no significant effect on ALT (WMD, -3.79; 95%CI, -13.30 to 5.72), and AST (WMD, -1.1; 95%CI, -3.32 to 1.09).
CONCLUSIONS: Curcumin supplementation improved AST and ALT levels compared with the control group. However, better-designed randomized controlled trials with larger sample sizes and of higher quality are needed to assess the effects of curcumin on ALP.
BACKGROUND: PROSPERO registration no. CRD42023448231.

OBJECTIVE: Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact of policosanol on liver enzymes remained controversial. The current meta-analysis aims to evaluate the effect of policosanol supplementation on the levels of alanine transaminase (ALT) and aspartate transaminase (AST).
METHODS: The literature was systematically searched for studies published up to November 2023 in PubMed/Medline, Google Scholar, EMBASE, and Scopus. Randomized controlled trial (RCT) studies were included to evaluate the intervention effect of policosanol compared to placebo on ALT and AST. DerSimonian and Laird models were used to calculate effect sizes.
RESULTS: Twenty-three trials including 2535 participants were included in the study. The combination of effect sizes, regarding the random-effects model, demonstrated significant changes in ALT serum levels after intervention (WMD: -1.48 U/L; 95% CI: -2.33 to -0.64; P = 0.001), and AST (WMD: -1.10 U/L; 95% CI: -1.70 to -0.51; P < 0.001). Subgroup analysis of AST and ALT showed that this reduction effect was most often observed at the dose of 20 mg/d. The dose-response analysis represented a non-significant non-linear connection between the dosage and duration of policosanol intervention in ALT and AST serum reduction.
CONCLUSIONS: Policosanol supplementation exerts a beneficial effect on liver enzymes as well as ALT and AST concentrations in adults. However, further long-term and well-designed RCTs with better quality are needed to further assess and confirm these results.

Rice Bran Arabinoxylan Compound (RBAC) results from an enzymatic modification of rice bran, which is reported to have immunomodulatory, anti-oxidant, and anti-inflammatory effects by regulating the production of pro-inflammatory cytokines. The current systematic review and meta-analysis aimed to determine the hepatic adverse effects of RBAC by assessing the effect through liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
In the present study, the Medline (PubMed), Web of Sciences, and Scopus databases were searched for relevant publications from the beginning to October 2022. The meta-analysis was based on the Mixed effect model to generate the mean effect sizes in weighted mean differences (WMD) and the 95% confidence intervals (95%CI). The heterogeneity was assessed using the Cochrane Chi-squared test, and the analysis of Galbraith plots was applied.
Subgroup meta-analysis on five eligible randomized controlled trials (n = 239) showed a significant decrease in serum AST regarding RBAC supplementation in powder form (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170), three months and more supplementation duration (WMD (95%CI) = -3.71 (-5.95, -1.48) U/L; P-value = 0.001, I2 (%) = 29.9; P heterogeneity = 0.240) and studies with a good quality (WMD (95%CI) = -3.52 (-5.62, -1.42) U/L; P-value = 0.001, I2 (%) = 46.9; P heterogeneity = 0.170).
In conclusion, RBAC supplementation seems to not have any hepatic adverse effects and its supplementation as powder or for three months and more may decrease serum AST levels. However, we need further studies to confirm the results.
CRD42022361002, registration time: 29/09/2022.

Chronic hepatitis B (CHB) remains a relatively major public health problem. Simultaneously, an unhealthy lifestyle causes a series of metabolic abnormalities, the most critical of which are metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD). Therefore, it is increasingly common for MS and NAFLD to coexist with CHB. MS is a cluster of metabolic disorders, while NAFLD is always considered as the manifestation of MS in the liver. The aim of this article is to review recent advances to explain the complex relationship among MS, NAFLD, and hepatitis B virus (HBV) infection. MS and NAFLD both have obesity and insulin resistance as central factors and both can lead to adverse hepatic and extrahepatic outcomes. However, there is insufficient evidence to associate NAFLD with all components of MS, and genetically related NAFLD has little association with MS. Incidences of MS and NAFLD are inversely associated with HBV infection. However, the effect of HBV infection on the risk of insulin resistance and dyslipidemia is not well understood. Evidence from both clinical studies and animal experiments suggested that hepatic steatosis inhibits HBV replication. MS and NAFLD may have adverse effects on CHB disease progression and prognosis. Furthermore, in related studies of CHB with normal alanine aminotransferase (ALT), the roles of MS and NAFLD should also be emphasized. In conclusion, there are complicated interactions that are not yet fully defined among MS, NAFLD, and CHB. To control chronic liver disease effectively, the relationship among the three must be clarified.

Studies examining the effect of artichoke on liver enzymes have reported inconsistent results. This systematic review and meta-analysis aimed to assess the effects of artichoke administration on the liver enzymes. PubMed, Embase, the Cochrane Library, and Scopus databases were searched for articles published up to January 2022. Standardized mean difference (Hedges\' g) were analyzed using a random-effects model. Heterogeneity, publication bias, and sensitivity analysis were assessed for the liver enzymes. Pooled analysis of seven randomized controlled trials (RCTs) suggested that the artichoke administration has an effect on both alanine aminotransferase (ALT) (Hedges\' g, -1.08; 95% confidence interval [CI], -1.76 to -0.40; p = 0.002), and aspartate aminotransferase (AST) (Hedges\' g, -1.02; 95% CI, -1.76 to -0.28; p = 0.007). Greater effects on ALT were detected in trials that lasted ≤8 weeks. Also, greater effects on AST were detected in trials using > 500 mg artichoke. Overall, this meta-analysis demonstrated artichoke supplementation decreased ALT and AST.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.