Prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation.

PURPOSE: To evaluate the prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation and the correlations between vitamin deficiencies, nutritional markers, and severity of liver disease. METHODS: This is a single centre retrospective study. Serum vitamin A, D, E, and zinc levels were collected in adult patients being assessed for liver transplantation between January and July 2012. Patient and liver disease demographics, nutritional markers, Child-Pugh score, and MELD-Na score were collected. Fisher's exact test and multiple variable logistic regression was used for statistical analysis. RESULTS: A total of 109 adult patients were assessed for liver transplantation during the 6-month period. The mean patient age was 54 ± 10 years and 66% were males. Mean BMI was 27 ± 6 kg/m2, pre-albumin was 0.10 ± 0.07 g/L, albumin was 33 ± 6 g/L, total bilirubin was 48 ± 61 mmol/L, MELD-Na score was 16 ± 5 (range 6-33), and 15% had hepatocellular carcinoma. The Child-Pugh score was A in 29%, B in 54%, and C in 17%. The causes of liver disease were hepatitis C in 36%, alcohol in 20%, non-alcoholic fatty liver disease in 17%, and other in 27%. The mean vitamin A level was 0.88 ± 0.86 umol/L, D was 69 ± 52 nmol/L, E was 24 ± 17 umol/L, and zinc was 477 ± 145 ug/L. Vitamin A deficiency was prevalent in 77%, D in 63%, E in 37%, and zinc in 84%. On multiple variable analysis, low albumin (OR = 0.78, 95% CI = 0.65-0.94, p = 0.0069) was a predictor of vitamin A deficiency ; cholestatic liver enzyme elevation (OR = 3.53, 95%CI = 1.40-8.89, p = 0.0073) and low albumin (OR = 0.83, 95%CI = 0.73-0.94, p = 0.0032) were predictors of vitamin D deficiency ; low albumin (OR = 0.85, 95% CI = 0.74-0.97, p = 0.015) was a predictor of vitamin E deficiency ; and age (OR = 0.83, 95% CI = 0.72-0.96, p = 0.012), low albumin (OR = 0.59, 95% CI = 0.42-0.84, p = 0.0036), and high MELD-Na (1.43, 95% CI = 1.05-1.94, p = 0.021) were predictors of zinc deficiency. Vitamin A (p = 0.0034), D (p = 0.020), E (p = 0.012), and zinc (p<0.001) deficiency correlated with a higher Child-Pugh. CONCLUSION: Low albumin was a recurrent predictor of fat-soluble vitamin (A, D, and E) and zinc deficiency while other predictors varied depending on the vitamin or mineral. Further studies need to be conducted on fat-soluble vitamin and zinc supplementation in deficient patients with cirrhosis to assess clinical outcomes.

Genetic Predictors of Azathioprine Toxicity and Clinical Response in Patients with Inflammatory Bowel Disease.

BACKGROUND: Thiopurines (Azathioprine (AZA) and 6-Mercaptopurine (6-MP) are considered a well-established therapy for patients with Inflammatory Bowel Disease (IBD) including ulcerative colitis (UC) and Crohn's Disease (CD). However, nearly 20% of patients discontinue thiopurines due to adverse events. Functional polymorphisms of several enzymes involved in the metabolism of thiopurines have been linked with toxicity. The clinical value of variant carriers such as TPMT, ITPA and GSTs in predicting toxicity and adverse events for IBD patients treated with thiopurines remains to be clarified. OBJECTIVES: To determine if variation in TPMT, ITPA and GST genotypes can predict adverse effects such as neutropenia, pancreatitis, liver enzyme elevation, as well as clinical response for patients with IBD treated with thiopurines. METHODS: Patients known to have IBD and treated with AZA or 6MP were enrolled. Adverse effects were calculated and their correlation with TPMT, ITPA and GST genotypes was evaluated. Further, the correlation between clinical response and TPMT, ITPA and GST genotypes were assessed. RESULTS: A total of 53 patients were enrolled. 16/53 patients (28.6%) responded to AZA therapy. 17 patients experienced adverse events with 10 having to discontinue treatment. Three patients (5.4%) developed severe myelosuppression (WBC< 2.0 or neutrophils <1.0). Loss of function TPMT genotype was associated with adverse events (OR 3.64, 95% CI 0.55 - 24.23, p=0.0313). ITPA and GST polymorphisms were not associated with toxicity. GSTM1 deletion was associated with poor clinical response to therapy (OR 3.75, 95% CI 0.940 - 14.97, p=0.1028), however, neither TPMT*3A nor ITPA polymorphisms were associated with clinical response. CONCLUSION: In addition to TPMT for adverse events, genotyping for GSTM1 appears to predict clinical response in IBD patients treated with thiopurines.

Safety and efficacy of tegaserod therapy in patients with irritable bowel syndrome or chronic constipation.

BACKGROUND: Tegaserod, a 5-HT4 agonist, is effective for treating irritable bowel syndrome and chronic constipation. However, sales of this drug were recently suspended due to concerns about a higher rate of cardiovascular events in patients receiving tegaserod over placebo in clinical trials. Our aim was to review patients in our practice prescribed tegaserod to determine if any of them had suffered a cardiovascular event or other significant adverse effects while on this therapy. Additionally, we attempted to determine the efficacy of tegaserod in clinical practice. METHODS: Patients with irritable bowel syndrome or chronic constipation in our practice prescribed tegaserod were identified through a search of billing codes and charts reviews. These patients were contacted and questioned about symptoms of cardiovascular events or other adverse events while on tegaserod. The efficacy of this drug was determined by a symptom scale during and after stopping tegaserod. RESULTS: Sufficient data for analysis was retrieved for 51 of 67 patients prescribed tegaserod. Of these, 37 patients (72.5%) experience no adverse events and 14 patients (27.4%) experienced at least one adverse event, including 6 patients (11.8%) with major adverse events (2 patients (3.9%) with atypical chest pain; 4 patients (7.8%) with syncope; and 2 patients (3.9%) who died. One patient died from advanced pancreatic cancer. The other, who had multiple cardiovascular risk factors as well as a previous myocardial infarction, suffered a cardiac arrest 2 days postoperatively following a below knee amputation, and had actually been off tegaserod for 7 days after hospital admission. Patients graded the severity of both abdominal pain and constipation as worse after stopping therapy compared to during therapy (p<0.0002 and p<0.0001, respectively). CONCLUSIONS: The risk of cardiovascular events during tegaserod therapy may be increased in patients with other risk factors. However, this drug is effective for treating irritable bowel syndrome and chronic constipation, and might be used in a select patient population with severe symptoms but without other risk factors for cardiovascular events.