Introduction Meta-analyses conducted so far on the association between diabetes mellitus (DM) and the tuberculosis (TB) development risk did not sufficiently take confounders into account in their estimates. The objective of this systematic review was to determine whether DM is associated with an increased risk of developing TB with a sensitivity analyses incorporating a wider range of confounders including age, gender, alcohol consumption, smoke exposure, and other comorbidities. Methods Pubmed, Embase, Web of Science and Global Index Medicus were queried from inception until October 2020. Without any restriction to time of study, geographical location, and DM and TB diagnosis approaches, all observational studies that presented data for associations between DM and TB were included. Studies with no abstract or complete text, duplicates, and studies with wrong designs (review, case report, case series, comment on an article, and editorial) or populations were excluded. The odds ratios (OR) and their 95% confidence intervals were estimated by a random-effect model. Results The electronic and manual searches yielded 12,796 articles of which 47 were used in our study (23 case control, 14 cross-sectional and 10 cohort studies) involving 503,760 cases (DM or TB patients) and 3,596,845 controls. The size of the combined effect of TB risk in the presence of DM was OR = 2.3, 95% CI = [2.0–2.7], I2 = 94.2%. This statistically significant association was maintained in cohort (OR = 2.0, CI 95% = [1.5–2.4], I2 = 94.3%), case control (OR = 2.4, CI 95% = [2.0–2.9], I2 = 93.0%) and cross-sectional studies (OR = 2.5, CI 95% = [1.8–3.5], I2 = 95.2%). The association between DM and TB was also maintained in the sensitivity analysis including only studies with similar proportions of confounders between cases and controls. The substantial heterogeneity observed was mainly explained by the differences between geographic regions. Conclusions DM is associated with an increased risk of developing latent and active TB. To further explore the role of DM in the development of TB, more investigations of the biological mechanisms by which DM increases the risk of TB are needed. Review registration PROSPERO, CRD42021216815.

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Introduction Africa denotes unique facies for hepatocellular carcinoma (HCC) characterized by a conjunction of low sensitization, restricted access to diagnosis and treatment and associated with the highest incidence and mortality in the world. We investigated whether hepatitis B (HBV), C (HCV) and D (VHD) viruses were etiological agents of HCC in Africa. Methods Relevant articles were searched in PubMed, Web of Science, African Index Medicus, and African Journal Online databases, as well as manual searches in relevant reviews and included articles. Analytical studies from Africa evaluating the association between HCC development and HBV, HCV, and HDV were included. Relevant studies were selected, data extracted, and the risk of bias assessed independently by at least 2 investigators. The association was estimated using odds ratios (OR) and their 95% confidence interval (95% CI) determined by a random-effects model. Sources of heterogeneity were determined by subgroup analyses. Results A total of 36 case-control studies were included. With controls having non-hepatic disease, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBeAg (OR = 19.9; 95% CI = [3.7–105.2]), HBsAg (OR = 9.9; 95%) CI = [6.2–15.6]) and DNA (OR = 8.9; 95% CI = [5.9–13.4]); HCV (Anti-HCV (OR = 9.4; 95% CI = [6.3–14.0]) and RNA (OR = 16.5; 95% CI = [7.8–34.6]); HDV (Anti-VHD, (OR = 25.8; 95% CI = [5.9–112.2]); and HBV/HCV coinfections (HBV DNA/HCV RNA (OR = 22.5; 95% CI = [1.3–387.8]). With apparently healthy controls, the overall results suggested a significantly increased risk of HCC in patients with HBV (HBsAg, (OR = 8.9; 95% CI = [6.0–13.0]); HCV (Anti-HCV, (OR = 7.7; 95% CI = [5.6–10.6]); and HBV/HCV coinfections (HBsAg/Anti-HCV (OR = 7.8; 95% CI = [4.4–13.6]) Substantial heterogeneity and the absence of publication bias were recorded for these results. Conclusions In Africa, HBV/HCV coinfections and HBV, HCV, and HDV infections are associated with an increased risk of developing HCC. The implementation of large-scale longitudinal and prospective studies including healthy participants to search for early biomarkers of the risk of progression to HCC is urgently needed.