Serum Vitamin D Levels Are Not Predictive of the Progression of Chronic Liver Disease in Hepatitis C Patients with Advanced Fibrosis

In animal models and human cross-sectional studies, vitamin D deficiency has been associated with liver disease progression. Vitamin D supplementation has been suggested as a treatment to prevent disease progression. We sought to evaluate the role of vitamin D levels in predicting chronic liver disease development. We conducted a nested case-control study of vitamin D levels in subjects with (cases) and without (controls) liver histologic progression or clinical decompensation over the course of the HALT-C Trial. Vitamin D levels were measured at 4 points over 45 months. 129 cases and 129 aged-matched controls were included. No difference in baseline vitamin D levels were found between cases and controls. (44.8 ng/mL vs. 44.0 ng/mL, P = 0.74). Vitamin D levels declined in cases and controls over time (P = 0.0005), however, there was no difference in the level of decline (P = 0.37). Among study subjects with diabetes mellitius, baseline vitamin D levels were higher in cases, 49.9 ng/mL, than controls, 36.3 ng/mL. (P = 0.03) In addition, baseline vitamin D levels were higher in black case subjects, 32.7 ng/mL, than in black control subjects, 25.2 ng/mL (P = 0.08) No difference in vitamin D levels was found between patients with and without progression of hepatitis C-associated liver disease over 4 years. Our data do not suggest any role for vitamin D supplementation in patients with advanced chronic hepatitis C and raise the possibility that higher vitamin D levels may be associated with disease progression

Influence of Body Mass Index on Outcome of Pediatric Chronic Hepatitis C Virus Infection

BACKGROUND/AIMS: Evidence demonstrates that obesity is associated with progression of chronic hepatitis C virus (HCV) infection and poor response to interferon therapy among HCV-infected adults. However, this evidence has been confounded by multiple comorbidities present in adult cohorts and the use of single adult doses. METHODS: We performed a retrospective investigation to evaluate the role of body mass index (BMI) in chronic HCV progression and response to therapy in the children. One hundred twenty-three children and teenagers followed at Children's Hospital Boston for HCV infection between 1998 and 2007 were included. Patients' weight and height at the time of liver biopsy or before and after HCV therapy were obtained and body mass index (BMI) calculated. RESULTS: The presence of steatosis was statistically associated with higher mean (±SE) BMI percentiles (72(nd) (± 5.8) vs. 58(th) (± 3.5) percentile) F(1,101)=4.2, p=0.04). Non-responders to treatment had a higher mean (±SE) BMI percentile (70(th) ±7.4) when compared to responders (50(th) ±6.5) in univariate and multivariate analyses (p=0.04, p=0.02 respectively). Using a multivariate model, it was calculated that one standard deviation (one Z score unit) increase in baseline BMI Z score is associated with a 12% decrease in the probability of sustained virologic response (SVR). CONCLUSION: Overweight adversely affects the progression of chronic HCV liver disease and is associated with diminished response to antiviral therapy using weight-based dosing in a cohort with minimal comorbidities

Correlates of adiponectin in hepatitis C-infected children: the importance of body mass index

Adiponectin is a regulator of cytokines that, in turn, play a vital role in inflammatory and immune responses. Adiponectin is therefore likely to have a contributory role in hepatitis C virus (HCV) infection. We sought to characterize adiponectin levels and examine correlates in a pediatric HCV-infected cohort. We performed a cross-sectional study in children (5-17 years of age, n = 86) in the Pediatric Study of Hepatitis C (PEDS-C) trial. Adiponectin levels were univariately correlated with patient demographics, anthropometrics, and viral and histological measures. Multivariate regression models were used to identify the unique (ie, nonconfounded) associations with adiponectin concentrations. Body mass index (BMI) had the highest univariate inverse correlation with log(e) adiponectin (r = -0.5, P < 0.0001). In multivariate analysis, BMI remained inversely correlated with log(e) adiponectin after accounting for age and route of HCV transmission (r = -0.38, P = 0.0003). Steatosis and fibrosis were inversely related to log(e) adiponectin in univariate analysis, but these associations were not statistically significant after multivariate adjustments (P ≥ 0.1827). High BMI among HCV-infected children is associated with lower adiponectin levels. Practitioners should be cognizant of the possible risks of low adiponectin when managing HCV-infected children who are overweight. Further studies are indicated to determine the impact of having low adiponectin on HCV infection in youth

Mean baseline vitamin D (ng/mL) levels by in patients by diabetes status.

<p>Mean baseline vitamin D (ng/mL) levels by in patients by diabetes status.</p

Analysis of vitamin D levels in patients with detectable vitamin D2 at all time points.

<p>This is publication #59 of the HALT-C Trial.</p

Baseline characteristics of diabetic cases and controls in the nested analysis.

<p>Baseline characteristics of diabetic cases and controls in the nested analysis.</p

Baseline characteristics of the cases and controls in the nested analysis.

<p>Baseline characteristics of the cases and controls in the nested analysis.</p

Reduction of Insulin Resistance With Effective Clearance of Hepatitis C Infection: Results From the HALT-C Trial

Hepatitis C virus (HCV) infection is associated with an increased prevalence of diabetes and insulin resistance (IR); whether this is a causal relationship has not been established. We performed a longitudinal study within the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial to evaluate whether suppression of hepatitis C is associated with improvement in IR. Participants had advanced hepatic fibrosis and carried non-3 HCV genotypes (n = 96). Patients underwent 24 weeks of pegylated interferon and ribavirin therapy and were categorized into HCV clearance groups at week 20 on the basis of HCV RNA levels; null responders had <1 log 10 decline (n = 38), partial responders had ≥1 log 10 decline (n = 37) but detectable HCV RNA, and complete responders had no detectable HCV RNA (n = 21). The primary outcome was change (week 20 minus week 0) in IR by using the homeostasis model assessment (HOMA2-IR). Adjusting only for baseline HOMA2-IR, mean HOMA2-IR differences were −2.23 (complete responders), −0.90 (partial responders), and +0.18 (null responders) ( P = .036). The observed differences in mean HOMA2-IR scores were ordered in a linear fashion across response groups ( P = .01). The association between HCV clearance and improvement in HOMA2-IR could not be accounted for by adiponectin or tumor necrosis factor–alpha and was independent of potential confounders including age, gender, ethnicity, body mass index, duration of infection, medications used, and fibrosis. HCV suppression correlates with improvement in IR. These data provide further support for a role of HCV in the development of insulin resistance

Mean vitamin D (ng/mL) levels in cases and controls.

<p>Mean vitamin D (ng/mL) levels in cases and controls.</p

Mean baseline vitamin D (ng/mL) levels by race.

<p>Mean baseline vitamin D (ng/mL) levels by race.</p