Chronic hepatitis E virus infection in a patient with leukemia and elevated transaminases: a case report

Introduction Acute hepatitis E virus infection may cause mild, self-limiting hepatitis, either as epidemic outbreaks or sporadic cases, the latter of which have been reported in industrialized countries. Chronic infections are uncommon and have been reported in immunosuppressed patients, patients with human immunodeficiency virus infection, and patients with hematological malignancies. Case presentation A 46-year-old Caucasian man was admitted to the gastroenterology clinic with a history of increasing transaminases, persistent exhaustion, and occasional right-side abdominal pain over the course of a 6-month period. B-cell chronic lymphocytic leukemia had been diagnosed several years earlier, and the patient was treated with rituximab, pentostatin, and cyclophosphamide. A diagnostic workup ruled out autoimmune and metabolic liver disease, hepatitis A-C, and herpes virus infection. A physical examination revealed enlarged axillary lymph nodes. The results of an abdominal ultrasound examination were otherwise unremarkable. Hepatitis E virus infection was diagnosed by detection of hepatitis E virus-specific antibodies. Blood samples were positive for hepatitis E virus ribonucleic acid with high viral loads for at least 8 months, demonstrating a rare chronic hepatitis E virus infection. Sequencing and phylogenetic analysis revealed hepatitis E virus genotype 3c with homologies to other European isolates from humans and swine, indicating an autochthonous infection. Conclusions Usually, hepatitis E virus infection appears as an acute infection; rare chronic infections have been reported for transplant patients, patients with human immunodeficiency virus, and patients with hematological malignancies. The chronic nature of hepatitis E infection in our patient was most likely induced by the immunosuppressive B-cell chronic lymphocytic leukemia treatment. The differential diagnosis in patients with unexplained hepatitis should include hepatitis E virus infection, and appropriate laboratory analyses should be considered

Association between expression of the Bone morphogenetic proteins 2 and 7 in the repair of circumscribed cartilage lesions with clinical outcome

<p>Abstract</p> <p>Background</p> <p>Although there is much known about the role of BMPs in cartilage metabolism reliable data about the <it>in vivo </it>regulation in natural and surgically induced cartilage repair are still missing.</p> <p>Methods</p> <p>Lavage fluids of knee joints of 47 patients were collected during surgical therapy. 5 patients had no cartilage lesion and served as a control group, the other 42 patients with circumscribed cartilage defects were treated by microfracturing (19) or by an Autologous Chondrocyte Implantation (23). The concentrations of BMP-2 and BMP-7 were determined by ELISA. The clinical status was evaluated using the IKDC Score prior to and 1 year following the operation.</p> <p>Results</p> <p>High level expression in the control group was found for BMP-2, concentrations of BMP-7 remained below detection levels. No statistical differences could be detected in concentrations of BMP-2 or BMP-7 in the lavage fluids of knees with cartilage lesions compared to the control group. Levels of BMP-7 did not change after surgical cartilage repair, whereas concentrations of BMP-2 statistically significant increased after the intervention (p < 0.001). The clinical outcome following cartilage regenerating surgery increased after 1 year by 29% (p < 0.001). The difference of the IKDC score after 1 year and prior to the operation was used to quantify the degree of improvement following surgery. This difference statistically significant correlated with initial BMP-2 (R = 0.554, p < 0.001) but not BMP-7 (R = 0.031, n.s.) levels in the knee joints.</p> <p>Conclusions</p> <p>BMP-2 seems to play an important role in surgically induced cartilage repair; synovial expression correlates with the clinical outcome.</p

Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients

Background: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Methods: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. Results: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. Conclusions: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT

E6 and E7 from Beta Hpv38 Cooperate with Ultraviolet Light in the Development of Actinic Keratosis-Like Lesions and Squamous Cell Carcinoma in Mice

Cutaneous beta human papillomavirus (HPV) types appear to be involved in the development of non-melanoma skin cancer (NMSC); however, it is not entirely clear whether they play a direct role. We have previously shown that E6 and E7 oncoproteins from the beta HPV type 38 display transforming activities in several experimental models. To evaluate the possible contribution of HPV38 in a proliferative tissue compartment during carcinogenesis, we generated a new transgenic mouse model (Tg) where HPV38 E6 and E7 are expressed in the undifferentiated basal layer of epithelia under the control of the Keratin 14 (K14) promoter. Viral oncogene expression led to increased cellular proliferation in the epidermis of the Tg animals in comparison to the wild-type littermates. Although no spontaneous formation of tumours was observed during the lifespan of the K14 HPV38 E6/E7-Tg mice, they were highly susceptible to 7,12-dimethylbenz(a)anthracene (DMBA)/12-0-tetradecanoylphorbol-13-acetate (TPA) two-stage chemical carcinogenesis. In addition, when animals were exposed to ultraviolet light (UV) irradiation, we observed that accumulation of p21WAF1 and cell-cycle arrest were significantly alleviated in the skin of Tg mice as compared to wild-type controls. Most importantly, chronic UV irradiation of Tg mice induced the development of actinic keratosis-like lesions, which are considered in humans as precursors of squamous cell carcinomas (SCC), and subsequently of SCC in a significant proportion of the animals. In contrast, wild-type animals subjected to identical treatments did not develop any type of skin lesions. Thus, the oncoproteins E6 and E7 from beta HPV38 significantly contribute to SCC development in the skin rendering keratinocytes more susceptible to UV-induced carcinogenesis