Translating the Role of Vitamin D Supplementation in Chronic Liver Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Vitamin D (VD) deficiency is highly prevalent in Chronic Liver Disease (CLD). Although international societies recommend supplementation in cases of proven deficiency, its impact on CLD remains uncertain. Our aim was to evaluate the effect of VD supplementation in CLD by conducting a systematic review and meta-analysis of Randomized Controlled Trials (RCTs). Methods: We systematically searched three databases on 8th November 2022 (PROSPERO: CRD42022370312). Our primary outcomes involved survival, Controlled Attenuation Parameter (CAP), Liver Stiffness Measurement (LSM), and effects on changes in liver enzymes. Secondary outcomes included lipid profile and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), among others. Pooled Risk Ratio (RR), Mean Difference (MD), and corresponding 95%Confidence Intervals (CI) were calculated using the random-effects model. Findings: Forty-one RCTs were included, comprising 3,562 patients. When comparing the VD group with the control, the overall survival RR was 1.14 (CI: 0.85; 1.54; 4 RCTs) at 6 months and 0.99 (CI: 0.83; 1.17; 4 RCTs) at 12 months. VD supplementation resulted in non-significant lower CAP (3 RCTs, MD: -23.50 dB/m; CI: -81.72, 34.72). The MD for LSM was -0.65 kPa (3 RCTs; CI: 1.98; 0.68). A significant reduction in HOMA-IR was observed in the VD group (12 RCTs; MD: 0.44; CI: -0.87; -0.01). A summary forest plot showed that alanine aminotransferase (20 RCTs; MD: -3.26 IU/L; CI: -6.37, -0.16) and gamma-glutamyl transferase (10 RCTs; MD: 5.15 IU/L; CI: 9.05; -1.25) were significantly reduced in the supplemented patients.Conclusions: Our results showed significant differences for ALT, GGT, and HOMA-IR in the VD group. In addition, there were no differences in survival, CAP, and LSM. Further RCTs with adequate power and appropriate sample size are warranted to clarify these results.

Author(s): Petrana Martinekova1, Mahmoud Obeidat1, Mihaela Topala1, Szilard Vancsa1, Daniel Sandor Veres2, Adam Zolcsak2, Miheller Pal3, Laszlo Foldvari-Nagy4, Peter Banovcin5, Balint Eross1, Peter Hegyi1 and Krisztina Hagymasi3*

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