Preexposition Prophylaxis With Truvada (Tenofovir/Emtricitabine) as Potential Cause of Celiac Disease-Like Enteropathy.

We present here a case of a 39-year-old patient who presented with celiac-disease-like symptoms and MARSH 3a histology in duodenal biopsies under normal diet. Interestingly, HLA genotyping and celiac-specific serology were negative, primarily leading to exclusion of celiac disease. However, biopsies from a second endoscopy a couple of months later (still under normal diet) showed histologic progression of the disease to MARSH 3b and led to the re-evaluation of the out-of-hospital-obtained histological samples by a pathologist experienced in celiac disease. The second biopsy described previously as MARSH 3b turned out to be non-specific and was therefore re-classified as MARSH 0. After all known causes of duodenal villous atrophy were excluded by a thorough evaluation, a correlation between the first biopsy (MARSH 3a) and Truvada intake could be established. After Truvada discontinuation and under normal diet, normalisation of duodenal mucosa was observed, leading to the assumption that Truvada could lead to celiac-like enteropathy.

Thalidomide in advanced hepatocellular carcinoma as antiangiogenic treatment approach: a phase I/II trial.

BACKGROUND: The high vascularity of hepatocellular carcinoma (HCC) seems to be a potential therapeutic target. We evaluated the efficacy, toxicity, and histologic response to thalidomide in advanced HCC in a single center phase I/II pilot trial. METHODS: Between September 2000 and August 2004 patients with HCC uneligible for any established therapy were enrolled in the study. The initial thalidomide dosage of 100 mg/day was escalated in 100 mg steps weekly up to 300 mg/day based on tolerability. Discontinuation and dose reduction were based on toxicity. Tumor biopsies were scheduled to assess tumor microvessel density and serum levels of angiogenic factors, vascular endothelial growth factor, basic fibroblast growth factor, and endostatin were determined. RESULTS: Twenty-eight patients with histologically proven HCC were entered into this study. The median maximum-tolerated dose of thalidomide was 300 mg/day. Most common toxicities were fatigue (75%), dizziness (64%), nausea (43%), and constipation (39%). Two patients had stable disease for 2.6 and 5.4 months, the remaining 26 patients had disease progression. The median overall survival was 5.1 months. Well preserved liver function was associated with longer overall survival on univariate analysis (P=0.0279). The serum concentrations of vascular endothelial growth factor and endostatin increased significantly (P=0.039 and P=0.024, respectively) after 3 months of thalidomide treatment. No clear differences were observed between the serum basic fibroblast growth factor concentrations at study entry and after 3 months (P=0.983). Microvessel density did not decrease significantly during thalidomide therapy (P=0.109). CONCLUSION: Thalidomide is moderately tolerated and minimally effective in large HCC.

Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha.

BACKGROUND & AIMS: Treatment of chronic hepatitis C with interferon (IFN)-alpha often has hematotoxic effects. We evaluated the effects of acute vs. chronic and standard vs. pegylated IFN-alpha on hematopoiesis. METHODS: We studied hematopoiesis in 46 patients with chronic hepatitis C receiving single high-dose IN-Falpha2b followed by daily dose standard or weekly pegylated IFN before combination antiviral therapy. RESULTS: Single high-dose therapy resulted in a significant drop in hemoglobin (HB), leukocytes, and platelet count. Although platelets, stimulated by a significant increase in thrombopoietin (TPO), and leukocytes recovered quickly, HB remained below baseline for 7 days. Daily standard or weekly pegylated IFN-alpha leads to a more pronounced drop in all 3 lineages with concomitant increases in TPO and erythropoietin (EPO). No difference was observed between standard and pegylated IFN, except for HB, which fell more during pegylated IFN therapy. Consecutive combination antiviral therapy aggravated the anemia but not the drop in leukocytes or thrombocytes. CONCLUSIONS: The drop in all 3 hematopoietic lineages through IFN-alpha treatment, high-dose standard, standard daily dose, or pegylated, is caused by a combination of bone marrow inhibition and probably some other rapid acting mechanisms. Hematopoietic growth factors are increased as a consequence but cannot overcome the bone marrow suppression.