Additionally, we excluded the following studies: in vitro, in vivo, and ex-vivo studies, case reports, observational studies, quasi-experimental studies, and controlled clinical trials. 22, 24 The intestinal mucosa serves as a defense barrier that helps prevent the entrance and the systemic . doi: 10.1136/bmjopen-2017-017995, 28. Lifestyle and dietary interventions in the management of nonalcoholic fatty liver disease. A meta analysis of probiotic treatment and IBS[17] included 20 trials with 23 probiotic treatments. Probiotics and synbiotics may improve liver aminotransferases levels in non-alcoholic fatty liver disease patients. Furthermore, improved intestinal epithelium function and decreased BT and endotoxemia following probiotic treatment have been observed in experimental animals and humans[26]. Nat Rev Gastroenterol Hepatol. However, the use of existing meta-analyses is the main limitation of the umbrella review. Common liver enzymes include: If your liver is injured, it releases enzymes into your bloodstream (most commonly ALT or AST). Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN. Gram-negative BO, increased permeability, and impaired immunity all contribute to increased BT, and there is a strong correlation between the rate of BT and the severity of cirrhosis. Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, Guarner F, Isolauri E, Pannemans D, et al. R. Apicella ASL Napoli 3 Sud, Italy. In alcoholic liver disease, bowel liver interactions are well described, and relationships include increased gut permeability, endotoxemia, and TNF- production[32]. Accessed Jan. 17, 2020. This study[19] used probiotic treatment (6 mo, commercial product of unspecified lactobacilli) in 44 post operational patients. Considering the inclusion criteria, ten articles were included in the umbrella meta-analysis. However, due to the high heterogeneity of the results and the small number of studies included in each subgroup, the outcomes of the present study should be interpreted with caution. Oxford: Oxford University Press (2008). Probiotics and Elevated liver enzymes - a phase IV clinical - eHealthMe Beyond that, microbial therapies reduced circulating GGT according to other evidence-based meta-analyses (25, 27, 31). Here, commensal-loaded dendritic cells induce a local immune response with the activation of specific B-cells to produce secretory IgA against these commensals[8,10]. Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Mascian R, Forgione A, Gabrieli ML, Perotti G, et al. Koutnikova H, Genser B, Monteiro-Sepulveda M, Faurie J-M, Rizkalla S, Schrezenmeir J, et al. Thoma C, Day CP, Trenell MI. doi: 10.1007/s10620-016-4153-y, 11. Am J Gastroenterol. To date, no generalisation can be made from health effects of one probiotic strain to another one and this remains a serious problem within the probiotic research field and its applications. (2021) 11:e634. We do not endorse non-Cleveland Clinic products or services. In a probiotic intervention trial in cirrhotic patients[38] (mainly caused by hepatitis virus B and C; HBV and HCV) patients received two different probiotic capsules [bifidobacteria + L. acidophilus + Enterococcus or Bacillus subtilis (B. subtilis) + Enterococcus faecium (E. faecium)], two capsules per day for 14 d. In both probiotic groups, bifidobacteria counts increased with treatment, while faecal pH and ammonia levels in faeces and blood decreased. The duration of studies ranged between 8 and 20 weeks. Recently, microbiome-targeted treatments (MTTs) are a proposed way to influence the gut microbiome. Received: 27 December 2021; Accepted: 02 May 2022;Published: 23 May 2022. No remarkable heterogeneity was observed between studies (I2 = 0.0%, p = 0.591). Lavekar AS, Raje DV, Manohar T, Lavekar AA. Mayo Clinic offers appointments in Arizona, Florida and Minnesota and at Mayo Clinic Health System locations. Transaminitis: Symptoms, Causes, and Treatment - Healthline Most often, elevated liver enzymes are temporary and resolve on their own without treatment. In liver health, the main benefits of probiotics might occur through preventing the production and/or uptake of lipopolysaccharides in the gut, and therefore reducing levels of low-grade inflammation. Salminen et al[51] investigated the severity and outcome of lactobacillus bacteraemia in 89 patients, and report mortality of 26% 1 mo after illness onset, but only in patients with severe underlying comorbidities. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609680/). The intestinal barrier is seen as the first line of defence against pathogens and food allergens entering the intestinal tract, and probiotics have been intensely studied for their involvement in maintaining this barrier. doi: 10.2217/fmb.15.13, 44. Probiotics as an effective therapeutic approach in alleviating depression symptoms: an umbrella meta-analysis. information is beneficial, we may combine your email and website usage information with Also, probiotic consumption had beneficial effect on reducing GGT level without any significant heterogeneity (39, 40). Even though most studies showed hepatic enzymes as biomarkers for liver function, there is still no comprehensive agreement on counting on the enzyme levels in order to indicate liver function. 1. Angulo P. Obesity and nonalcoholic fatty liver disease. Elevated Liver Enzymes in Patients with COVID-19: Look, but - Springer Treatment of nonalcoholic steatohepatitis with probiotics. (2016) 64:7384. Liver function parameters [alanine aminotransferase (ALT) and aspartate aminotransferase] were significantly improved by probiotics compared to standard treatment, but remained below levels found in healthy controls. Furthermore, bacteriocins (small antimicrobial proteins secreted by some probiotics) are another cause for this trait (52). Supplementary Table 1 | Electronic search strategy. In rats, genotoxic effects of food carcinogens, such as heterocyclic amines, on the colonocytes and hepatocytes were counteracted by the use of different probiotics[43,44]. This study showed that probiotics were associated with improved global IBS symptoms [risk ratio (RR) = 0.77] and with decreased abdominal pain (RR = 0.78). Overall the use of probiotics is very promising, although data are very variable (type of surgery, type of infection, and type of probiotic treatment). Osman N, Adawi D, Ahrn S, Jeppsson B, Molin G. Endotoxin- and D-galactosamine-induced liver injury improved by the administration of Lactobacillus, Bifidobacterium and blueberry. Petrof EO, Claud EC, Sun J, Abramova T, Guo Y, Waypa TS, He SM, Nakagawa Y, Chang EB. Frontiers | Effect of Probiotics on Liver Enzymes in Patients With Non The most common causes of elevated transaminase levels are nonalcoholic fatty liver disease and alcoholic liver disease. This content does not have an English version. If there was any evidence of publication bias or small-study effect, trim and fill analysis was carried out accordingly. Our analysis revealed a significant reduction in GGT levels by probiotics intervention. Elevated liver enzymes Causes - Mayo Clinic (2013) 19:6911. doi: 10.3748/wjg.v19.i40.6911, 31. Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Sensitivity analysis was used to identify the dependency of the overall effect size on a special study. Within the large intestine, bacterial intervention might cause modulation of the microbial fermentation activity and direct action on the colonic epithelium to alter (suppress) innate immunity. More than 10,000 microbiomes live in a synergetic relationship with the intestinal tract and have different effects on the hosts health and disease condition (1315). Kohli R. Theres more under the nonalcoholic fatty liver disease umbrella than an elevated alanine aminotransferase level. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. Cirrhosis is the most severe form, responsible for most liver specific morbidity and mortality[23]. Increasing liver toxicity and cardiovascular risk. Salminen MK, Tynkkynen S, Rautelin H, Saxelin M, Vaara M, Ruutu P, Sarna S, Valtonen V, Jrvinen A. Lactobacillus bacteremia during a rapid increase in probiotic use of Lactobacillus rhamnosus GG in Finland. government site. They found that lactobacilli, bifidobacteria, and enterococci were reduced in alcoholics and the numbers were restored in the probiotic treatment group. Probiotics might alter the intestinal microbiota and hence limit intestinal bacteria overgrowth (IBO) and the production of lipopolysaccharides (LPS). World J Gastroenterol WJG. Many things can cause elevated liver enzymes, which is . doi: 10.1016/j.jpeds.2013.12.026, 64. doi: 10.1093/nutrit/nuy031, 32. Your doctor determines the cause by reviewing your medications, your signs and symptoms and, in some cases, other tests and procedures. Though the most common patterns of liver enzyme abnormalities in patients with SARS-CoV-2 include elevated aminotransferases, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) typically 1-2 times the upper limit of normal . Lactobacilli might counteract BT by (1) promoting growth of anaerobes and Gram-positive bacteria while inhibiting gram-negative bacteria, or (2) increasing SCFA while decreasing pH, inducing growth factors and proliferation of microflora, and inhibiting adherence and invasion of pathogens. Sign up for free, and stay up to date on research advancements, health tips and current health topics, like COVID-19, plus expertise on managing health. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Subgroup analysis indicated that probiotics supplementation with an intervention duration 16 weeks and a sample size of < 300 contributes to a more significant effect in lowering AST (Table 3). This matters because if the inflammation continues unabated for long enough, you could develop scarring in the liver, known as fibrosis. doi: 10.1093/ptj/83.8.713, 38. doi: 10.1194/jlr.R036012, 20. Some evidence from a mouse model of colitis [interleukin (IL)-10 deficient mice] suggests that probiotic lactobacilli and the VSL#3 mix reduced bacterial translocation (BT) and intestinal permeability in the colon[14,15]. How and why to lower your liver enzymes - Medical News Today Buss C, Valle-Tovo C, Miozzo S, de Mattos AA. Systematic review with meta-analysis: the effects of probiotics in nonalcoholic fatty liver disease. Implicating a disrupted intestinal microbiome in the progression of NAFLD/NASH. Furthermore, alcoholics have altered microflora with decreased numbers of bifidobacteria and lactobacilli. Host physiology, age, drugs like antibiotics, diet, and environmental factors can influence the gut microbial ecosystem (44). Elevated liver enzymes - Mayo Clinic Le Yu MY, Wang L. The effect of omega-3 unsaturated fatty acids on non-alcoholic fatty liver disease: a systematic review and meta-analysis of RCTs. doi: 10.1002/jrsm.1092, 29. Probiotics have ameliorating effects on ALT, AST, and GGT levels in patients with NAFLD. (2003) 83:71321. (2014) 109:32534. J Lipid Res. In rats, Lactobacillus GG has been shown to reduce alcohol induced gut leakiness and steatohepatitis[33]. Figure 1 presented the flow diagram of the study selection process. Probiotics are believed to be important for liver health via specific biological processes as follows: (1) increment in insulin sensitivity; (2) decreasing the absorption of glucose and LDL cholesterol; (3) modification of gut dysbiosis and inducing the production of short-chain fatty acids; (4) decrement in endotoxin concentrations; (5) reducing the oxidative stress status and inflammatory markers; (6) diminishing total cholesterol levels and (7) trapping of bile acids substances (4851). (2015) 56:21824. E. coli levels were not altered. Through a cascade of signalling events, probiotics enhance production and secretion of anti-inflammatory cytokines, including interleukin-10 and transforming growth factor-, by a subset of immune cells, referred to as T regulatory cells. Shoaf K, Mulvey GL, Armstrong GD, Hutkins RW. Non-alcoholic steatohepatitis (NASH) is an intermediate state where lobular inflammation occurs. Work with your doctor or other health care professional for an accurate diagnosis. No placebo was included in the control group. (2019) 9:e017995. Ouwehand AC. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Microbial metabolites: critical regulators in NAFLD. Effect on short-chain production affecting glucose and lipid metabolism. (2018) 68:28095. Adv Pharm Bull. Accessed Jan. 17, 2020. No use, distribution or reproduction is permitted which does not comply with these terms. (2014) 164:6846. Moreover, visual inspection of the funnel plot indicated an asymmetric distribution of studies (Figure 2B). Infect Immun. tumor necrosis factor (TNF)-]. Make your tax-deductible gift and be a part of the cutting-edge research and care that's changing medicine. Histopathological changes are very similar to alcoholic liver disease, and there might be a common pathway of development. Many of the probiotic strains used today have been isolated from the human gut flora, and it is therefore more a reintroduction of organisms rather than a novel concept. This umbrella review used systematic methods with robust search strategies of various databases and independent study selection and extraction methods, which systematically summarized the current evidence regarding the effects of probiotics supplementation on serum levels of ALT, AST, and GGT. Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, et al. A recent meta analysis summarised the safety of probiotics in pregnancy and concluded no effect of lactobacillus and bifidobacterium species on incidence of caesarean section, birth weight, or gestational age[49]. The role of liver fat and insulin resistance as determinants of plasma aminotransferase elevation in nonalcoholic fatty liver disease. (2018) 71:11323. (2016) 375:236979. (2011) 343:d5928. Keywords: non-alcoholic fatty liver disease, probiotics, liver enzyme, umbrella meta-analysis, systematic review Go to: Introduction Figure 1. Clin Sci. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Yu JS, Youn GS, Choi J, Kim CH, Kim BY, Yang SJ, et al. Euroasian J Hepato Gastroenterol. Martin FP, Wang Y, Sprenger N, Yap IK, Lundstedt T, Lek P, Rezzi S, Ramadan Z, van Bladeren P, Fay LB, et al. However, bacteremia might be a potential hazard in these vulnerable patients. This procedure uses restriction in stomach size and intestinal malabsorption as measures for achieving substantial weight loss. Safety of probiotics: translocation and infection. Probiotics/symbiotics have also been used to prevent postoperative infections in patients undergoing abdominal surgery (biliary cancer, liver transplantation, and pancreaticoduodenectomy). This hypothesis is further supported by evidence that intestinal BO exacerbates fatty liver disease in rodents and humans, and that obese patients with NASH have increased prevalence of BO. (https://www.aafp.org/afp/2017/1201/p709.html), (https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/elevated-liver-enzymes-hepatitis/). Interestingly, recent studies indicated that gut dysbiosis is related to higher fecal concentrations of some metabolites (2-butanone and 4-methyl-2-pentanone) which lead to hepatocellular toxicity (47). information highlighted below and resubmit the form. This aggravates insulin resistance and leads to oxidative stress (increased production of reactive oxygen by hepatocytes and liver macrophages) and organelle dysfunctions, which kill hepatocytes and promote accumulation of inflammatory cells in the liver and the development of NASH[24]. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. 36. Kirpich IA, Solovieva NV, Leikhter SN, Shidakova NA, Lebedeva OV, Sidorov PI, Bazhukova TA, Soloviev AG, Barve SS, McClain CJ, et al. In a double blind placebo controlled (sucrose capsule) intervention Lata et al[36] studied the effect of probiotic E. coli Nissle in cirrhotic patients (n = 39, 34 with alcoholic cirrhosis). 1998-2023 Mayo Foundation for Medical Education and Research (MFMER). P-value < 0.05 was considered as significance level. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. doi: 10.1080/10715760410001694026, 57. (2017) 65:e114. Probiotic actions most relevant to liver disease are modification of intestinal barrier function and prevention of BT. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Last updated on March 7, 2022. J Pediatr. They May Cause Unpleasant Digestive Symptoms While most people do not experience side effects, the most commonly reported reaction to bacteria-based probiotic supplements is a temporary. Common causes for elevated liver enzymes include: Certain medications, such as cholesterol-lowering drugs (statins) and acetaminophen. Assessing the quality of randomized trials: reliability of the Jadad scale. In vitro, L. rhamnosus GG is able to bind mycotoxins known to interfere with intestinal mucosal barrier. A proof-of-concept study. This article explains elevated liver enzymes, including potential symptoms, causes, and treatments. Vajro P. Transaminases and pediatric nonalcoholic fatty liver disease diagnosis. Probiotic intervention also changed the proteolytic activity and bacterial metabolism of AA and SCFA in the gut[53]. (2020) 11:567654. doi: 10.3389/fmicb.2020.567654, 62. Probiotics and surface-layer proteins competitively exclude microbial pathogens from mucosal surfaces. Higgins JP, Altman DG, Gtzsche PC, Jni P, Moher D, Oxman AD, et al. Peer reviewers: Xiaofa Qin, MD, PhD, Department of Surgery, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, United States; Yasuji Arase, MD, Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon minato-ku, Tokyo 105-8470, Japan, S- Editor Tian L L- Editor Stewart GJ E- Editor Zheng XM, National Library of Medicine Probiotics have ameliorating effects on ALT, AST, and GGT levels in patients with NAFLD. Approach to the patient with abnormal liver and biochemical function tests. The AMSTAR questionnaire contains 11 items that asks reviewers to answer Yes, No, Cant answer or Not applicable. The maximum score is 11. Adhesion of probiotics to enterocytes and enhancement of barrier function (secretion of B-defensins and mucus, TJ proteins) have also been shown for specific strains in vitro. How Probiotics Relieve Damaged Livers, Liver Disease, & Cirrhosis Johnson-Henry KC, Donato KA, Shen-Tu G, Gordanpour M, Sherman PM. Major infections were pneumonia, urinary tract infection, wound infection, intra-abdominal abscess, and cholangitis. Future Microbiol. Commensals, unlike pathogens, are efficiently killed by intestinal macrophages, therefore avoiding an inflammatory response in the mucosa[10]. American Journal of Gastroenterology. It can be attributed to numerous roots, including environmental parameters, metabolic, genetic, and gut microbial factors (41). Arch Med Res. doi: 10.1038/s41575-020-0269-9, 45. Even though the findings suggest that probiotics supplementation may be efficacious for controlling NAFLD, it must be stated that, the effects of probiotics on liver enzymes (ALT & AST) were heterogeneous. Askarpour M, Djafarian K, Ghaedi E, Sadeghi O, Sheikhi A, Shab-Bidar S. Effect of L-carnitine supplementation on liver enzymes: a systematic review and meta-analysis of randomized controlled trials. Manco M, Alisi A, Nobili V. Risk of severe liver disease in NAFLD with normal ALT levels: a pediatric report. Malaguarnera M, Vacante M, Antic T, Giordano M, Chisari G, Acquaviva R, et al. The meta-analysis was done using Stata, version 16 (Stata Corporation, College Station, TX, US). Publication bias was identified by visual inspection of the funnel plot. . A meta-analysis of randomized controlled trials. Interestingly, the authors reported no effect of probiotics in HCV patients. If we combine this information with your protected Get useful, helpful and relevant health + wellness information. doi: 10.15171/apb.2018.005, 49. English-language articles were included in this study. Front Endocrinol. The integration of multicompartment metabolic data using hierarchical principal component analysis showed that probiotic lactobacilli induce changes in hepatic influx and efflux of fatty acids, increased enterohepatic recycling of bile acids and dietary fats, lowered plasma LP, and stimulated glycolysis. In a mouse model of high-fat feeding and NAFLD, an association was shown between the metabolism of choline by microbiota and the host. (http://www.clinlabnavigator.com/most-common-causes-of-elevated-liver-enzymes.html), (https://www.hepmag.com/basics/hepatitis-a-basics/symptoms-hepatitis-a), (https://www.merckmanuals.com/home/liver-and-gallbladder-disorders/diagnosis-of-liver,-gallbladder,-and-biliary-disorders/liver-blood-tests), (https://www.merckmanuals.com/home/liver-and-gallbladder-disorders/manifestations-of-liver-disease/overview-of-liver-disease/), (https://www.hepatitis.va.gov/basics/liver-enzymes.asp), (https://medlineplus.gov/lab-tests/alt-blood-test/), (https://pubmed.ncbi.nlm.nih.gov/27824421/). Xiao M-W, Lin S-X, Shen Z-H, Luo W-W, Wang X-Y. reduced endotoxin, which stimulates pro-inflammatory cytokines (TNF-, IL-1, 6)[22]. doi: 10.1016/s1665-2681(19)31246-3, 18. Low-FODMAP diets are often recommended until SIBO is treated. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Silvia Wilson Gratz, Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Aberdeen AB21 9SN, United Kingdom, Hannu Mykkanen, School of Public Health and Clinical Nutrition, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland, Hani S El-Nezami, Food and Health Research Centre, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland; School of Biological Sciences, University of Hong Kong, S5-13 Kadoorie Biological Sciences Building, Pokfulam, Hong Kong, China. Researchers at the Yale Liver Center found that patients with COVID-19 presented with abnormal liver tests at much higher rates than suggested by earlier studies. A familiar over-the-counter medication that can cause liver damage from an overdose is acetaminophen ( Tylenol ). Liong MT. Indian J Endocrinol Metab. Probiotics supplementation significantly reduced AST level according to the meta-analysis of nine studies (Figure 3A). Bethesda, MD 20894, Web Policies Probiotics and gut health: A special focus on liver diseases Elevated Liver Enzymes: Symptoms, Causes, and Treatment - Verywell Health NAFLD is the most common form of liver disease in the US; its incidence is rising together with rising problems of obesity and Type II diabetes. Table 2. These calculations suggest that up to 1014 cfu/d of lactobacilli and bifidobacteria, a dose way beyond the usual intake of 109-1011 cfu/d, are acceptable for human consumption. doi: 10.1016/j.jhep.2011.06.010, 12. Huang Z, Mu C, Chen Y, Zhu Z, Chen C, Lan L, et al. Araya J, Rodrigo R, Videla LA, Thielemann L, Orellana M, Pettinelli P, et al. The methodological quality of meta-analyses was evaluated by two reviewers (VM and SSA) independently using the AMSTAR questionnaire (28). The results may depend on what assessments to choose from each preliminary study and how to report them in the meta-analysis. (2012) 57:54553. Ma X, Hua J, Li Z. Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells. Probiotic therapy, on the other hand, has been suggested to counteract the development of NAFLD on various different levels. So in fact these criteria may not be reliable for the diagnosis of NAFLD. Cannon JP, Lee TA, Bolanos JT, Danziger LH. Hepatology. According to the studied variables, the distribution of identified articles was ten articles for ALT, nine for AST, and three for GGT. Sheth AA, Garcia-Tsao G. Probiotics and liver disease. Conclusively, further studies need to be conducted for a definite presumption. Alanine aminotransferase (ALT) is an enzyme found inside liver cells. PD contributed to the final revision of the manuscript. (2013) 368:16479. NAFLD has a strong relationship with metabolic syndromes like obesity, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension (1, 58). Cani PD, Delzenne NM. What High ALT Levels Mean and How to Lower Them - Healthline doi: 10.2174/1570161115666170622074007, 3. (2004) 38:5359. (2018) 76:82239. PASSCLAIM--gut health and immunity. Hepatology. The beneficial impacts of probiotics as new promising therapeutic agents for patients with NAFLD have been summarized in this studies. More common causes of elevated liver enzymes include: Other possible causes of elevated liver enzymes include: Causes shown here are commonly associated with this symptom. The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Overall, Probiotics could be recommended as an adjuvant therapeutic method for the management of NAFLD. Role of probiotics in the treatment of nonalcoholic fatty liver disease: a meta-analysis. 2 Occasionally, elevated liver enzymes require additional tests to find out what's going on. Microbes in gastrointestinal health and disease. For more definite results, we aimed to investigate the effects of probiotics supplementation on serum levels of alanine transaminase (ALT), AST, and GGT in an umbrella meta-analysis study.
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