Vitamin D Receptor Regulates Liver Regeneration After Partial Hepatectomy in Male Mice.

Vitamin D signals through the vitamin D receptor (VDR) to induce its end-organ effects. Hepatic stellate cells control development of liver fibrosis in response to stressors and vitamin D signaling decreases fibrogenesis. VDR expression in hepatocytes is low in healthy liver, and the role of VDR in hepatocyte proliferation is unclear. Hepatocyte-VDR null mice (hVDR) were used to assess the role of VDR and vitamin D signaling in hepatic regeneration. hVDR mice have impaired liver regeneration and impaired hepatocyte proliferation associated with significant differential changes in bile salts. Notably, mice lacking hepatocyte VDR had significant increases in expression of conjugated bile acids after partial hepatectomy, consistent with failure to normalize hepatic function by the 14-day time point tested. Real-time PCR of hVDR and control livers showed significant changes in expression of cell-cycle genes including cyclins D1 and E1 and cyclin-dependent kinase 2. Gene expression profiling of hepatocytes treated with vitamin D or control showed regulation of groups of genes involved in liver proliferation, hepatitis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death. Together, these studies demonstrate an important functional role for VDR in hepatocytes during liver regeneration. Combined with the known profibrotic effects of impaired VDR signaling in stellate cells, the studies provide a mechanism whereby vitamin D deficiency would both reduce hepatocyte proliferation and permit fibrosis, leading to significant liver compromise.

Nonalcoholic Fatty Liver Disease: Interface Between Primary Care and Hepatology Clinics.

Primary care physicians (PCPs) have the primary role in the diagnosis and management of nonalcoholic fatty liver disease (NAFLD), and in selecting patients for referral to a hepatologist for further evaluation. This study aimed to characterize PCP referrals for patients diagnosed with NAFLD at a major referral hospital, and to determine the severity of liver disease and patient pathway following evaluation in secondary care. New patients seen in the hepatology outpatient clinic (HOC) with a secondary care diagnosis of NAFLD were identified from the HOC scheduling database. PCP referrals for these patients were retrieved from the electronic medical records and reviewed by study clinicians, along with the hepatologists' clinic notes and letters. Over a 14-month period, 234 new PCP referrals received a diagnosis of NAFLD, accounting for 20.4% of the total number of new cases (n = 1,147) seen in the HOC. The 234 referrals were received from 170 individual PCPs at 135 practices. Most patients with NAFLD (88.5%) were referred for investigation of abnormal liver enzymes or other clinical concerns, including abnormal iron studies, hepatomegaly, and abdominal pain. Only 27 (11.5%) referrals included an assessment of liver disease severity. Following evaluation in the liver clinic, 175 patients (74.8%) were found to have a low risk of advanced fibrosis, and most (n = 159; 90.9%) were discharged back to their PCP for ongoing follow-up in primary care. Conclusion: In addition to better access to noninvasive fibrosis tests, educational strategies to enhance awareness and recognition of NAFLD as a cause for many of the initial concerns prompting patient referral might improve risk stratification and increase the appropriateness of PCP referrals.

Vitamin D and the Liver-Correlation or Cause?

Vitamin D is becoming increasingly accepted as an important physiological regulator outside of its classical role in skeletal homeostasis. A growing body of evidence connects vitamin D with hepatic disease. This review summarises the role of vitamin D in liver homeostasis and disease and discusses the therapeutic potential of vitamin D-based treatments to protect against hepatic disease progression and to improve response to treatment. While pre-clinical experimental data is promising, clinical trials around liver diseases have mostly been under-powered, and further studies will be required to clarify whether vitamin D or vitamin D analogues have beneficial effects on liver disease.

Vitamin D in liver disease: Current evidence and potential directions.

Consistent with its multifaceted nature, growing evidence links vitamin D with hepatic disease. In this review, we summarise the roles of vitamin D in different liver pathologies and explore the clinical utility of vitamin D-based treatments in hepatology. We find that the small number of clinical trials coupled with the profound heterogeneity of study protocols limits the strength of evidence needed to ascribe definite clinical value to the hormone in liver disease. Nevertheless, the experimental data is promising and further bench and bedside studies will likely define a clearer role in hepatic therapeutics.