| Abstract | Cilj istraživanja: Pronaći najbolje dokaze o sigurnosti i učinkovitosti primjene antioksidanasa u pacijenata sa oboljelom jetrom.
Materijal i metode: Na stranici Cochrane Library je pronađen sustavni pregled „Antioxidant supplements for liver diseases“ koji je bio temelj daljnjeg istraživanja. Dalje su pretražene baze podataka MEDLINE (PubMed), DARE i CENTRAL u potrazi za novim randomiziranim kontroliranim pokusima i sustavnim pregledima, a prema kriterijima uključenja i isključenja navedenima u Cochrane sustavnom pregledu. Nakon pretraživanja literature napravljena je RAMSTAR procjena Cochrane sustavnog pregleda i novih pronađenih sustavnih pregleda.
Rezultati: Prema Cochrane sustavnom pregledu nije pronađeno nikakvo uporište za primjenu antioksidans pojedinačno ili u kombinacijama u bolesnika s oštećenjem jetre. Učinci antioksidansa na sve uzroke smrtnosti u studijma s niskim rizikom od pristranosti (RR 0.98,
95% CI 0.64 do 1.49, I2 = 0%) nisu bili značajni. Antioksidansi nisu imali značajan utjecaj na smrtnost povezanu s jetrom (RR 0.89, 95% CI 0.39 do 2.05, I2 = 37%). Također nisu imali značajan utjecaj na morbiditet povezan s jetrom: gastrointestinalna krvarenja (RR 1.18, 95% CI 0.38 do 3.63, I2 = 0%), jetrene encefalopatije (RR 0.90, 95% CI 0.65 do 1.25), sepsa (RR 0.90, 95% CI 0.47 do 1.71), ili na rak jetre (RR 0.36, 95% CI 0.12 do 1.11). Vitamin A i vitamin E nisu pokazali značajno tendenciju porasta jetrenih enzima (RR 5.00, 95% CI 0.66 do 37.85 i RR 2,27, 95% CI 0.48 do 10.67). Dok u pronađenom sustavnom pregledu utvrđeno je da vitamin E pridonosi smanjenju razina ALT (SMD 0.61, 95% CI (0.20 do 1.02)) i AST (0.68, 95% CI (0.07 do 1.29)). U meta-analizi fiksnog učinka, antioksidansi znatno povećavaju aktivnost aspartat aminotransferaze (MD 7.64 IU/L, 95% CI 3.78 do 11.51, I2 = 80%) i gama glutamil transpeptidase (MD 24.21 IU / L, 95% CI 6.67 do 41.75, I2 = 0%), ali nisu imali značajan učinak na alanin aminotransferaze, koncentraciju serumskog albumina i bilirubina. U meta-analizi slučajnog učinka, antioksidansi nisu imali značajan utjecaj na aktivnost aspartat aminotransferaze (MD 3.80 IU/L, 95% CI -6.07 do 13.67). Antioksidansi nisu imali značajan utjecaj na virološki odgovora u bolesnika s kroničnim hepatitisom B ili kroničnim hepatitisom C na kraju liječenja (RR 0.57, 95% CI 0.32 do 1.02; RR 0.85, 95% CI
0.55 do 1.32, I2 = 95%), te nisu imali značajan utjecaj na održivost virološkog odgovora u kroničnom hepatitisu C (RR 0.89, 95% CI 0.54 do 1.45, I2 = 79%). Antioksidansi su imali značajan blagotvoran učinak na kraju liječenja i održivog odgovora (biokemijska i virološki) u bolesnika s kroničnim hepatitisom B (RR 0.55, 95% CI 0.34 do 0.87 i RR 0.55, 95% CI
0.34 do 0.86 ), ali nisu u bolesnika s kroničnim hepatitisom C (RR 0.80, 95% CI 0.39 do
1.65). Cochrane sustavni pregled je prema R-AMSTAR procjeni ocijenjen sa 36 bodova. Pronađen je još jedan sustavni pregled, koji je ocijenjen sa 20 bodova.
Zaključak: Na temelju pregledanih sustavnih pregleda ne postoje uvjerljivi dokazi koji podupiru upotrebu antioksidansa (beta-karotena, vitamina A, vitamina C, vitamina E i selena) u bolesnika s autoimunim, alkoholnim, akutnim i kroničnim hepatitisom B, virusnim hepatitisom C ili cirozom jetre. Potrebna su daljnja istraživanja kako bi se sa sigurnošću potvrdila opravdanost primjene antioksidansa u raznim jetrenim oštećenjima. |
| Abstract (english) | Diploma Thesis Title: Finding evidence of efficacy and safety of antioxidant supplements for liver diseases: systematic review approach.
Objectives: Finding the best available evidence of efficacy and safety of antioxidant supplements for liver diseases.
Material and Methods: „Antioxidant supplements for liver diseases“ systematic review was found by searching the Cochrane Library website. Further, we searched MEDLINE (PubMed), DARE and CENTRAL databases in order to find new randomised controlled trials and systematic reviews, following the same criteria that were used in Cochrane systematic review. After the search for studies was done, we made quality assessment of all systematic reviews using R-AMSTAR tool.
Results: According to the Cochrane systematic review were found no basis for the use of an antioxidant alone or in combination in patients with hepatic impairment. The effects of antioxidants on all-cause mortality in study with low risk of bias (RR 0.98, 95% CI 0.64 to 1.49, I2=0%) were not significant. Antioxidants have no significant effect on mortality associated with liver (RR 0.89, 95% CI 0.39 to 2.05, I2 = 37%). Also, antioxidants have no significant effect on morbidity associated with liver: gastrointestinal bleeding (RR 1.18, 95% CI 3.63 to 0.38, I2 = 0%), hepatic encephalopathy (RR 0.90, 95% CI 0.65 to 1.25), sepsis (RR 0.90, 95% CI 1.71 to 0.47), or liver cancer (RR is 0.36, 95% CI 0.12 to 1.11). Vitamin A and vitamin E showed a non-significant tendency toward elevation of liver function tests (RR 5.00, 95% CI 0.66 to 37.85 and RR 2.27, 95% CI 0.48 to 10.67). While, found systematic review showed that vitamin E contributes to a reduction in ALT levels (SMD 0.61, 95% CI (0.20 to 1.02)) and AST (SMD 0.68, 95% CI (0.07 to 1.29)). In fixed-effect meta-analysis, antioxidant supplements significantly increased the activity of aspartate aminotransferase (MD 7.64 IU/L, 95% CI 3.78 to 11.51, I2 = 80%) and gamma glutamyl transpeptidase (MD 24.21 IU/L, 95% CI 6.67 to 41.75, I2 = 0%) but had no significant effect on alanine aminotransferase, serum concentration of albumin and bilirubin. In random-effects metaanalysis, antioxidant supplements had no significant effect on the activity of aspartate aminotransferase (MD 3.80 IU/L, 95% CI -6.07 to 13.67). The antioxidant supplements had no significant effect on end-of treatment virological response in patients with chronic hepatitis B or chronic hepatitis C (RR 0.57, 95% CI 0.32 to 1.02; RR 0.85, 95% CI 0.55 to 1.32, I2 = 95%), and also had no significant effect on the sustained virological response in patients with chronic hepatitis C (RR 0.89, 95% CI 0.54 to 1.45, I2 = 79%). The antioxidant supplements had significant beneficial effect on the end-of-treatment and sustained response (biochemical and virological) in patients with chronic hepatitis B (RR 0.55, 95% CI 0.34 to 0.87 and RR 0.55, 95% CI 0.34 to 0.86, respectively), but had no significant effect on end-of treatment response in patients with chronic hepatitis C (RR 0.80, 95% CI 0.39 to 1.65). Total RAMSTAR score for Cochrane systematic review was 36. It was found one more systematic review, which is evaluated with 20 points.
Conclusion: Based on the reviewed systematic reviews there are no convincing evidence to support the use of antioxidants (beta-carotene, vitamin A, vitamin C, vitamin E and selenium) in patients with autoimmune, alcoholic, acute and chronic hepatitis B, viral hepatitis C or liver cirrhosis. Further research is needed to safely confirmed the validity of the application of antioxidants in a variety of liver damage. |
