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Background The progression of hepatic fibrosis into cirrhosis is a main prognostic factor for survival in people with alcoholic liver disease. The range of cut-off values characterising the stage of hepatic fibrosis seems to be dependent on the aetiology of the liver disease. Aims To determine the diagnostic accuracy of transient elastography (the index test) for diagnosis of fibrosis in alcoholic liver disease when compared with liver biopsy (the reference standard), using the METAVIR scoring system. To establish the optimal cut-off values for the hepatic fibrosis stages. Methods We followed Cochrane Methodology for diagnostic test accuracy reviews. We identified 14 studies. Among the study participants with alcoholic liver disease, 834 provided numerical data for analysis (August 2014). Only half of the studies were monoaetiology studies. We used the bivariate model and estimated the summary sensitivities and summary specificities. Hence, we calculated the summary likelihood ratios ( LRs) to rule in or rule out hepatic fibrosis. We investigated pre-defined sources of heterogeneity. Results Severe fibrosis (F3 or worse): summary (95% CI) sensitivity 0.92(0.89-0.96) and specificity 0.70(0.61-0.79); LR+ 3.1(2.1-4.1), LR− 0.11(95% CI 0.06-0.16). Cirrhosis (F4): summary (95% CI) sensitivity of 0.95(0.87-0.98) and specificity 0.71(0.56-0.82); LR+ 3.3(2.1-5.0); LR− 0.07(0.03-0.19). Conclusions Transient elastography may be used as a diagnostic method to exclude cirrhosis or severe fibrosis when the test is negative. Cut-off values of around 12.5 kPa for cirrhosis may be used in clinical practice, but caution is needed, as the values reported in the review are not yet prospectively validated. [ABSTRACT FROM AUTHOR]

Aliment Pharmacol Ther 2010; 32: 356–367 Background Several liver diseases have been associated with oxidative stress. Accordingly, antioxidants have been suggested as potential therapeutics for various liver diseases. The evidence supporting these suggestions is equivocal. Aim To assess the benefits and harms of antioxidant supplements for patients with liver diseases. Methods We identified trials through electronic and manual searches until August 2009. We included randomized trials comparing antioxidant supplements (beta-carotene, vitamin A, C, E and selenium) vs. placebo or no intervention for autoimmune liver diseases, viral hepatitis, alcoholic liver disease and cirrhosis (any aetiology). Random-effects and fixed-effect meta-analyses were conducted. Results were presented as relative risks (RR), or mean difference (MD), both with 95% confidence intervals (CI). Results Twenty randomized trials with 1225 participants were included. The trials assessed beta-carotene (3 trials), vitamin A (2 trials), vitamin C (9 trials), vitamin E (15 trials) and selenium (8 trials). The majority of the trials had high risk of bias and showed heterogeneity. Overall, the assessed antioxidant supplements had no significant effect on all-cause mortality [relative risk (RR) 0.84, 95% confidence interval (CI) 0.60–1.19, I2 = 0%] or liver-related mortality (RR 0.89, 95% CI 0.39–2.05, I2 = 37%). Stratification according to the type of liver disease assessed did not affect the conclusions. Antioxidant supplements significantly increased the activity of gamma glutamyl transpeptidase (MD 24.21 IU/L, 95% CI 6.67–41.75, I2 = 0%). Conclusions We found no evidence to support or refute antioxidant supplements in patients with liver disease. Antioxidant supplements may increase liver enzymes. [ABSTRACT FROM AUTHOR]

Background The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory. Aim To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers. Methods Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random-effects and fixed-effect models meta-analyses. Results We identified 20 randomized trials (211 818 participants) assessing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83–1.06, I 2 = 54.0%). The heterogeneity seemed to be explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96–1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43–0.80, test of interaction P < 0.0005) and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97–1.07, I 2 = 53.5%) but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02–1.07). Conclusions We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer may be prevented by reducing the development of adenomatous polyps. Aim To assess the benefits and harms of antioxidant supplements in preventing colorectal adenoma. Methods Using the Cochrane Collaboration methodology we reviewed all randomized clinical trials comparing antioxidant supplements with placebo or no intervention. We searched electronic databases and the reference lists until October 2005. Outcome measures were development of colorectal adenoma adverse events. We analysed dichotomous outcomes with fixed- and random-effects model meta-analyses and calculated the relative risk with 95% confidence interval. Results We identified eight randomized trials (17 620 participants). Neither fixed-effect (relative risk: 0.93, 95% CI: 0.81–1.1) nor random-effect model meta-analyses (0.82, 0.60–1.1) showed statistically significant effects of supplementation with β-carotene, vitamins A, C, E and selenium alone or in combination. Antioxidant supplements seemed to increase the development of colorectal adenoma in three low-bias risk trials (1.2, 0.99–1.4) and significantly decrease its development in five high-bias risk trials (0.59, 0.47–0.74). The estimates difference is significant ( P < 0.0001). There was no significant difference between the intervention groups regarding adverse events, including mortality (0.82, 0.47–1.4). Conclusion We found no convincing evidence that antioxidant supplements have significant beneficial effect on primary or secondary prevention of colorectal adenoma. [ABSTRACT FROM AUTHOR]

The authors discuss their response on the comments regarding their article on transient elastography for staging liver fibrosis in alcoholic liver disease. They agree that their article is based on their Cochrane systematic review but stress that including data from the two studies will not influence the results of the meta-analyses. They argue against the comment that the mixed aetiology in the 50% of the included studies is a limitation of their review.

A response by the G. Bjelakovic and colleagues to a letter to the editor on their article "Metaanalysis: antioxidant supplements for liver disease: the Cochrane Hepato-Biliary Group" in the 2010 issue is presented.