Vitamin D deficiency in patients with liver cirrhosis.
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PROVIDER: S-EPMC4923814 | BioStudies |
REPOSITORIES: biostudies
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Project description:BACKGROUND:Vitamin D is required to maintain the integrity of the intestinal barrier and inhibits inflammatory signaling pathways. OBJECTIVE:Vitamin D deficiency might be involved in cirrhosis-associated systemic inflammation and risk of hepatic decompensation in patients with liver cirrhosis. METHODS:Outpatients of the Hepatology Unit of the University Hospital Frankfurt with advanced liver fibrosis and cirrhosis were prospectively enrolled. 25-hydroxyvitamin D (25(OH)D3) serum concentrations were quantified and associated with markers of systemic inflammation / intestinal bacterial translocation and hepatic decompensation. RESULTS:A total of 338 patients with advanced liver fibrosis or cirrhosis were included. Of those, 51 patients (15%) were hospitalized due to hepatic decompensation during follow-up. Overall, 72 patients (21%) had severe vitamin D deficiency. However, patients receiving vitamin D supplements had significantly higher 25(OH)D3 serum levels compared to patients without supplements (37 ng/mL vs. 16 ng/ml, P<0.0001). Uni- and multivariate analyses revealed an independent association of severe vitamin D deficiency with the risk of hepatic decompensation during follow-up (multivariate P = 0.012; OR = 3.25, 95% CI = 1.30-8.2), together with MELD score, low hemoglobin concentration, low coffee consumption, and presence of diabetes. Of note, serum levels of C-reactive protein, IL-6 and soluble CD14 were significantly higher in patients with versus without severe vitamin D deficiency, and serum levels of soluble CD14 levels declined in patients with de novo supplementation of vitamin D (median 2.15 vs. 1.87 ng/mL, P = 0.002). CONCLUSIONS:In this prospective cohort study, baseline vitamin D levels were inversely associated with liver-cirrhosis related systemic inflammation and the risk of hepatic decompensation.
| S-EPMC6224127 | BioStudies
Project description:The liver is crucial for 25-hydroxyvitamin D (25(OH)D) metabolism, and vitamin D deficiency is highly prevalent in patients with cirrhosis and predicts adverse outcomes. We aimed to evaluate whether vitamin D supplementation in patients with cirrhosis is effective in increasing 25(OH)D serum concentrations. Secondary outcome measures included liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), and alkaline phosphatase (AP)), albumin, International Normalized Ratio (INR), bilirubin, the liver fibrosis marker hyaluronic acid, and parameters of mineral metabolism including parathyroid hormone (PTH).This is a double-center, double-blind, placebo-controlled study conducted from December 2013 to May 2014 at the Medical University of Graz, and the hospital Hoergas-Enzenbach, Austria. We enrolled 36 consecutive patients with cirrhosis and 25(OH)D concentrations below 30 ng/mL. Study participants were randomly allocated to receive either 2800 International Units of vitamin D3 per day as oily drops (n = 18) or placebo (n = 18) for 8 weeks.Thirty-three study participants (mean (SD) age: 60 (9) years; 21% females; 25(OH)D: 15.6 (7.4) ng/mL) completed the trial. The mean treatment effect (95% CI) for 25(OH)D was 15.2 (8.0 to 22.4) ng/mL (p < 0.001). There was no significant effect on any secondary outcome.In this randomized controlled trial, vitamin D supplementation increases 25(OH)D serum concentrations, even in cirrhotic patients.
| S-EPMC4882691 | BioStudies
Project description:<h4>Objectives</h4>Low levels of vitamin D are associated with a higher mortality in cirrhotic patients, but the role of this deficiency is still unknown. The purpose of this study was to assess the levels of vitamin D in cirrhotic patients with and without bacterial infection.<h4>Methods</h4>25-hydroxy (25-OH) vitamin D was assessed by immunoassay in 88 patients hospitalized in our hepatology unit.<h4>Results</h4>The causes of cirrhosis were mainly alcohol (70%), hepatitis C (10%), or both (9%). Infections (n=38) mainly included bacteriemia (21%), urinary tract infections (24%), and spontaneous bacterial peritonitis (29%). A severe deficiency in vitamin D (<10?ng/ml) was observed in 56.8% of patients. Infections were more frequent in patients with a severe deficiency compared with the others (54 vs. 29%, P=0.02). A severe deficiency in vitamin D was a predictive factor of infection (odds ratio=5.44 (1.35-21.97), P=0.017) independently of the Child-Pugh score (odds ratio=2.09 (1.47-2.97) P=0.00004) and the C-reactive protein level (odds ratio=1.03 (1.002-1.052), P=0.03) in a logistic regression also including the alanine amino transferase (not significant). By a Cox regression analysis, only the presence of an infection was significantly associated with mortality (relative risk=3.24 (1.20-8.76), P=0.02) in a model also associating the Child-Pugh score (not significant) and the presence of a severe deficiency in vitamin D (not significant).<h4>Conclusions</h4>Low levels of 25-OH vitamin D were independently associated with bacterial infections in cirrhotic patients. The impact of 25-OH vitamin D supplementation on the infection rate and death of cirrhotic patients should be assessed in randomized trials.
| S-EPMC4042021 | BioStudies
Project description:An optimal vitamin D status may benefit liver transplantation (LT) patients. Higher levels of 25-hydroxyvitamin D [25(OH)D] mitigate steroid-induced bone loss after LT, correlate with better hepatitis C virus treatment responses, and increase graft survival. This study investigated 25(OH)D levels and assessed strategies for vitamin D deficiency prevention in human immunodeficiency virus (HIV)-positive patients with advanced liver disease who were enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study. 25(OH)D was measured in banked specimens from 154 LT candidates/recipients with the DiaSorin assay; deficiency was defined as a 25(OH)D level?<?20 ng/mL. Information about vitamin D supplement use after LT was obtained from medication logs and via surveys. Logistic regression, Cox regression, and linear repeated measures analyses were performed with SAS software. We found that none of the 17 academic medical centers in the United States routinely recommended vitamin D supplements before LT, and only a minority (4/17) recommended vitamin D supplements to all patients after LT. Seventy-one percent of the 139 patients with pre-LT values had vitamin D deficiency, which was significantly associated with cirrhosis (P?=?0.01) but no other variable. The vitamin D status improved modestly after LT; however, the status was deficient for 40% of the patients 1 year after LT. In a multivariate linear repeated measures model, a higher pre-LT 25(OH)D level (P?<?0.001), specimen collection in the summer (P?<?0.001), a routine vitamin D supplementation strategy after LT (P?<?0.001), and the time elapsing since LT (P?=?0.01) were significantly associated with increases in the post-LT 25(OH)D level; black race was associated with a decreased level (P?=?0.02). In conclusion, the majority of patients awaiting LT were vitamin D deficient, and approximately half were vitamin D deficient after LT. More extensive use of vitamin D supplements, more sun exposure, or both are needed to prevent this deficiency in HIV-positive LT candidates and recipients.
| S-EPMC3946843 | BioStudies
Project description:The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy.To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis.In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured.Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism.ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.
1999-01-01 | S-EPMC1727409 | BioStudies
Project description:<h4>Background</h4>The risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.<h4>Methods</h4>This is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).<h4>Results</h4>The prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).<h4>Conclusion</h4>Using a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.<h4>Trial registration</h4><h4>Ucsd irb</h4>140084.<h4>Funding</h4>National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.
| S-EPMC5490764 | BioStudies
Project description:Morbidly obese patients are at risk for non-alcoholic fatty liver disease (NAFLD) and vitamin D deficiency (VDD). Non-alcoholic steatohepatitis (NASH) is the progressive variant of NAFLD and can advance to fibrosis, cirrhosis, and liver cancer. We aimed to examine prevalence of liver fibrosis and its non-invasive predictors in bariatric patients with VDD (<75 nmol/l).Baseline liver biopsy of a randomized controlled trial was performed in 46 patients with omega loop gastric bypass. Clinical, laboratory, and histological data were examined and tested with univariate and multivariable analysis.In total, 80 % were females, aged 42?(SD 13)?years with BMI 44?(4)?kg/m(2). Twenty-six percent had diabetes mellitus (DM) and 44 % metabolic syndrome (MeS). Seventy-two percent had NASH, 11 % simple steatosis, and 17 % normal liver. In total, 30 % demonstrated significant fibrosis (F???2) with 9 % of advanced (F3) and 4 % cirrhosis (F4). Increased stages of fibrosis were primarily associated with higher levels of HOMA2-insulin resistance (IR), procollagen type I propeptide (P1NP), lower osteocalcin, albumin-corrected calcium, parathyroid hormone, vitamin D, male sex, and higher age. Other independent risk factors for advanced fibrosis were MeS (OR?=?9.3 [0.99-87.5], p?=?0.052) and DM (OR?=?12.8 [1.2-137.4], p?=?0.035). The fibrosis FIB-4 index <10.62 and NAFLD fibrosis score <-26.93 had a negative predictive value of 100 and 96 %, respectively.Liver fibrosis is frequent in morbidly obese patients with concurrent DM and/or MeS. Increased serum levels of IR, P1NP, lower osteocalcin, and VDD are clinically relevant predictors of fibrosis. Consequently, we suggest that patients with preoperative presence of these markers are at increased risk for liver fibrosis and should be monitored closely.
| S-EPMC5018030 | BioStudies
Project description:UNLABELLED:The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P<0.0001). Child-Turcotte-Pugh (CTP) score?7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score?7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. CONCLUSION:Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7.
| S-EPMC3144992 | BioStudies
Project description:We aimed to evaluate the association of plasma biomarkers linked to inflammation (bacterial translocation, inflammatory response, and endothelial dysfunction), coagulopathy, and angiogenesis with the severity of liver cirrhosis (assessed by the Child-Pugh-Turcotte score, CTP) and Child-Pugh B cirrhosis (CTP 7-9) in patients with advanced hepatitis C virus (HCV)-related cirrhosis. We carried out a cross-sectional study in 97 patients with advanced HCV-related cirrhosis (32 HCV-monoinfected and 65 HIV/HCV-coinfected). Plasma biomarkers were measured by ProcartaPlex multiplex immunoassays. The outcome variable was the CTP score and the Child-Pugh B cirrhosis (CTP 7-9). HIV/HCV-coinfected patients and HCV-monoinfected patients with advanced HCV-related cirrhosis had near-equivalent values of plasma biomarkers. Higher values of plasma biomarkers linked to an inflammatory response (IP-10, IL-8, IL-6, and OPG), endothelial dysfunction (sVCAM-1 and sICAM-1), and coagulopathy (D-dimer) were related to higher CTP values. The most significant biomarkers to detect the presence of Child-Pugh B cirrhosis (CTP 7-9) were IP-10 (p-value= 0.008) and IL-6 (p-value=0.002). The AUC-ROC values of IP-10, IL-6, and both biomarkers combined (IP-10+IL-6) were 0.78, 0.88, and 0.96, respectively. In conclusion, HIV infection does not appear to have a significant impact on the analyzed plasma biomarkers in patients with advanced HCV-related cirrhosis. However, plasma biomarkers linked to inflammation (inflammatory response and endothelial dysfunction) were related to the severity of liver cirrhosis (CTP score), mainly IP-10 and IL-6, which discriminated patients with Child-Pugh B concerning Child-Pugh A.
| S-EPMC7316790 | BioStudies
Project description:LESSONS LEARNED:Recruitment of patients with advanced hepatocellular carcinoma and Child-Pugh B for sorafenib treatment and additional pharmacokinetic studies is challenging.Patients with Child-Pugh B liver cirrhosis have high rates of cirrhosis-related adverse events. BACKGROUND:Few data are available on the pharmacokinetics (PK) of sorafenib in patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh B liver cirrhosis. This study aimed to explore the sorafenib PK and its relationship with efficacy and toxicity in these patients. METHODS:Patients with advanced HCC and Child-Pugh B7-8 liver function were prospectively recruited at a tertiary center. Adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were recorded. Patients received a starting dose of 200 b.i.d. with toxicity-adjusted dose escalation to a target dose of 400 mg b.i.d. with PK sampling at fixed time points. RESULTS:Between May 2014 and March 2017, 12 patients were screened, of whom 7 progressed to a terminal stage during the screening (n =?6) or shortly after recruitment (n =?1). The five included patients had median PFS of 3.8 months (range, 1.7-10.8) and OS of 7.4 months (range, 1.7-25.8). Three patients had severe AEs and one patient had a partial response with an OS of 25.8 months. In 2017, the trial was aborted for lack of accrual. CONCLUSION:Because of low accrual, no conclusion can be drawn on the sorafenib PK in patients with advanced HCC and Child-Pugh B liver cirrhosis. The poor survival and frequent cirrhosis-related AEs suggest limited benefit for most of these patients.
| S-EPMC7485346 | BioStudies