Serum vitamins and homocysteine levels in autoimmune liver disease: A systematic review and meta-analysis

Abstract

Objective: Vitamins and homocysteine (Hcy) are involved in liver metabolism and related to the pathogenesis of autoimmune liver disease (AILD), but consensus is lacking. This study aims to systematically summarize relevant evidence to clarify the association of serum vitamins and Hcy levels with AILD.

Methods: The English and Chinese literature was searched until August 29, 2023. Studies were included if they were observational studies of investigating serum vitamins and Hcy levels in patients with AILD and their healthy comparisons. Quality assessment was performed by using the Newcastle-Ottawa Scale, and a meta-analysis was conducted using ReviewManager 5.3. The protocol was registered in the international prospective register of systematic reviews (PROSPERO), with registration number CRD42023455367.

Results: A total of 25 case-control studies comprising 3487 patients (1673 patients and 1814 healthy controls) were included for analysis. There were 548 autoimmune hepatitis (AIH) cases, 1106 primary biliary cholangitis (PBC) cases, and 19 primary sclerosing cholangitis (PSC) cases. We found that serum A and E were decreased in both AIH and PBC/PSC; but vitamin C was reduced only in patients with PBC, not AIH. In addition, decreased content of 25(OH)D3 was found in both AIH and PBC. However, levels of 25(OH)D did not differ between the patients and controls, and were independent of disease types and the country. Only one study that met the inclusion criteria reported vitamin B6, B9, B12, and Hcy changes, and found that vitamin B6 and B9 were significantly decreased in patients with PBC, while serum vitamin B12 and Hcy levels were significantly elevated in them. One eligible study each confirmed a reduction in plasma vitamin K1 and 1,25(OH)2D3 in patients with PBC.

Conclusion: Most vitamins are deficient in AILD, so appropriate vitamin supplementation should be necessary. Further studies with larger sample sizes are needed to validate these findings.

Keywords: autoimmune hepatitis; autoimmune liver disease; meta‐analysis; primary biliary cholangitis; vitamins.

Figure 1

PRISMA flow diagram of the study selection process.

Figure 2

Forest plot of the meta‐analysis on serum vitamin A levels in patients with autoimmune liver disease (AILD). AIH, autoimmune hepatitis; CI, confidence interval; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; SD, standard deviation.

Figure 3

Forest plot of the meta‐analysis on serum vitamin C levels in patients with autoimmune liver disease (AILD). CI, confidence interval; SD, standard deviation.

Figure 4

Forest plot of the meta‐analysis on serum vitamin 25(OH)D levels in patients with autoimmune liver disease (AILD). AIH, autoimmune hepatitis; CI, confidence interval; PBC, primary biliary cholangitis; SD, standard deviation.

Figure 5

Forest plot of the meta‐analysis on serum vitamin 25(OH)D3 levels in patients with autoimmune liver disease (AILD). AIH, autoimmune hepatitis; CI, confidence interval; PBC, primary biliary cholangitis; SD, standard deviation.

Figure 6

Forest plot of the meta‐analysis on serum vitamin E levels in patients with autoimmune liver disease (AILD). AIH, autoimmune hepatitis; CI, confidence interval; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; SD, standard deviation.

Figure 7

Sensitivity analysis of the meta‐analysis on vitamins levels in patients with autoimmune liver disease (AILD): (A) vitamin A; (B) vitamin C; (C) vitamin 25(OH)D; (D) vitamin 25(OH)D3; (E) vitamin E.

Figure 8

Funnel plot of 10 included studies in this meta‐analysis for serum vitamin 25(OH) D levels in patients with autoimmune liver disease (AILD). AIH, autoimmune hepatitis; PBC, primary biliary cholangitis; SMD, standardized mean difference.