Prognostic Significance of Severe Vitamin D Deficiency in Patients with Primary Sclerosing Cholangitis

Ebadi, Maryam; Rider, Elora; Tsai, Catherine; Wang, Sarah; Lytvyak, Ellina; Mason, Andrew L.; Montano‐Loza, Aldo J.

doi:10.3390/nu15030576

Cited by 3 publications

(2 citation statements)

References 39 publications

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“…It is known that the liver plays a pivotal role in the activation of vitamin D [ 58 ], and vitamin D regulates bone mineralization and absorption to maintain BMD [ 59 ]. However, patients with PSC are prone to severe vitamin D deficiency [ 60 , 61 ], suggesting that osteoporosis induced by PSC may be a type of hepatic osteodystrophy related to abnormal liver vitamin D metabolism. In addition, the liver is a central hub for lipid metabolism, and high blood lipid levels can induce the accumulation of lipids in cartilage, leading to osteoarthritis [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Lu,

Li,

et al. 2024

J Transl Med

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Background Chronic liver diseases constitute a major global public health burden, posing a substantial threat to patients’ daily lives and even survival due to the potential development of musculoskeletal disorders. Although the relationship between chronic liver diseases and musculoskeletal disorders has received extensive attention, their causal relationship has not been comprehensively and systematically investigated. Methods This study aimed to assess the causal relationships between viral hepatitis, primary biliary cholangitis, primary sclerosing cholangitis (PSC), liver cirrhosis, and hepatocellular carcinoma (HCC) with osteoporosis, osteoarthritis, and sarcopenia through bidirectional Mendelian randomization (MR) research. The traits related to osteoporosis and osteoarthritis included both overall and site-specific phenotypes, and the traits linked to sarcopenia involved indicators of muscle mass and function. Random-effect inverse-variance weighted (IVW), weighted median, MR-Egger, and Causal Analysis Using the Summary Effect Estimates were used to evaluate causal effects, with IVW being the main analysis method. To enhance robustness, sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, MR-PRESSO global test, funnel plots, leave-one-out analyses, and latent causal variable model. Results The forward MR analysis indicated that PSC can reduce forearm bone mineral density (beta = − 0.0454, 95% CI − 0.0798 to − 0.0110; P = 0.0098) and increase the risk of overall osteoarthritis (OR = 1.012, 95% CI 1.002–1.022; P = 0.0247), while HCC can decrease grip strength (beta = − 0.0053, 95% CI − 0.008 to − 0.0025; P = 0.0002). The reverse MR analysis did not find significant causal effects of musculoskeletal disorders on chronic liver diseases. Additionally, no heterogeneity or pleiotropy was detected. Conclusions These findings corroborate the causal effects of PSC on osteoporosis and osteoarthritis, as well as the causal impact of HCC on sarcopenia. Thus, the implementation of comprehensive preventive measures is imperative for PSC and HCC patients to mitigate the risk of musculoskeletal disorders, ultimately improving their quality of life.

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Section: Discussionmentioning

confidence: 99%

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Lu,

Li,

et al. 2024

J Transl Med

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“…This may cause detrimental effects on the patient’s overall health, including impaired bone mass acquisition, rickets, and immune, cardiovascular, and respiratory system dysfunction [ 9 ]. Several previous studies reported that the severity of vitamin D deficiency in patients with cholestasis was associated with poor clinical outcomes, including incomplete response to ursodeoxycholic acid, cirrhosis development, liver-related mortality, and the need for liver transplantation [ 18 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of Optimal Vitamin D Dosage in Children with Cholestasis

Chongthavornvasana,

Lertudomphonwanit,

Mahachoklertwattana

et al. 2023

BMC Pediatr

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Background Vitamin D deficiency in patients with cholestasis is due to impaired intestinal vitamin D absorption, which results from decreased intestinal bile acid concentration. Patients with cholestasis usually do not achieve optimal vitamin D status when a treatment regimen for children without cholestasis is used. However, data on high-dose vitamin D treatment in patients with cholestasis are limited. Methods This study is a prospective study that included pediatric patients with cholestasis (serum direct bilirubin > 1 mg/dL) who had vitamin D deficiency (serum 25-hydroxyvitamin D, 25-OHD, < 20 ng/mL). In Phase 1, single-day oral loading of 300,000 IU (or 600,000 IU if weight ≥ 20 kg) of vitamin D2 was administered, followed by an additional loading if serum 25-OHD < 30 ng/mL, and 4-week continuation of treatment using a vitamin D2 dose calculated based on the increment of 25-OHD after first loading. In Phase 2, oral vitamin D2 (200,000 IU/day) was administered for 12 days, followed by 400,000 IU/day of vitamin D2 orally for another 8 weeks if serum 25-OHD < 30 ng/mL. Results Phase 1: Seven patients were enrolled. Three out of seven patients had a moderate increase in serum 25-OHD after loading (up to 20.3–27.2 ng/mL). These patients had conditions with partially preserved bile flow. The remaining four patients, who had biliary atresia with failed or no Kasai operation, had low increments of serum 25-OHD. Phase 2: Eleven patients were enrolled. Eight out of 11 patients had a moderate increase in serum 25-OHD after 200,000 IU/day of vitamin D2 for 12 days. Serum 25-OHD continued increasing after administering 400,000 IU/day of vitamin D2 for another 8 weeks, with maximal serum 25-OHD of 15.7–22.8 ng/mL. Conclusion Very high doses of vitamin D2 (200,000 and 400,000 IU/day) partly overcame poor intestinal vitamin D absorption and resulted in moderate increases in serum 25-OHD in pediatric patients with cholestasis, particularly when cholestasis was caused by uncorrectable bile duct obstruction.

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The Role of 1,25(OH)<sub>2</sub>D<sub>3</sub> on GCDC-Induced Apoptosis in HiBECs by Stabilising Mitochondrial DNA

李

2024

ACM

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Prognostic Significance of Severe Vitamin D Deficiency in Patients with Primary Sclerosing Cholangitis

Cited by 3 publications

References 39 publications

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Genetic evidence of the causal relationship between chronic liver diseases and musculoskeletal disorders

Determination of Optimal Vitamin D Dosage in Children with Cholestasis

The Role of 1,25(OH)<sub>2</sub>D<sub>3</sub> on GCDC-Induced Apoptosis in HiBECs by Stabilising Mitochondrial DNA

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