Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis

Aliment Pharmacol Ther 2010; 32: 1211–1221Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment.To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH.Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias.Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36–0.77, P  = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24–0.49, P  < 0.001) and ALT (WMD = 16.4, 95% CI 7.7–25.0, P  < 0.001), but not inflammation ( P  = 0.09) or fibrosis ( P  = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078–0.51, P  = 0.008). Metformin failed to improve any pooled outcome.Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79251/1/j.1365-2036.2010.04467.x.pd

Comprehensive surface magnetotransport study of SmB6

After the theoretical prediction that SmB6 is a topological Kondo insulator, there has been an explosion of studies on the SmB6 surface. However, there is not yet an agreement on even the most basic quantities such as the surface carrier density and mobility. In this paper, we carefully revisit Corbino disk magnetotransport studies to find those surface transport parameters. We first show that subsurface cracks exist in the SmB6 crystals, arising both from surface preparation and during the crystal growth. We provide evidence that these hidden subsurface cracks are additional conduction channels, and the large disagreement between earlier surface SmB6 studies may originate from previous interpretations not taking this extra conduction path into account. We provide an update of more reliable magnetotransport data than the previous one (S. Wolgast et al., Phys. Rev. B 92, 115110) and find that the orders-of-magnitude large disagreements in carrier density and mobility come from the surface preparation and the transport geometry rather than the intrinsic sample quality. From this magnetotransport study, we find an updated estimate of the carrier density and mobility of 2.71×1013 (1/cm2) and 104.5 (cm2/Vsec), respectively. We compare our results with other studies of the SmB6 surface. By this comparison, we provide insight into the disagreements and agreements of the previously reported angle-resolved photoemission spectroscopy, scanning tunneling microscopy, and magnetotorque quantum oscillations measurements

Trends, Management and Outcomes of Acute Myocardial Infarction in Chronic Liver Disease

Peer reviewedPostprin

The clinical presentation and prognostic factors for intrahepatic and extrahepatic cholangiocarcinoma in a tertiary care centre

Aliment Pharmacol Ther   31 , 625–633The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined.To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients.Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed.In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months–25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01–1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17–3.08) and stage of disease (HR 1.51, 95%CI 1.16–1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26–0.88). There were no significant differences regarding clinical presentation, disease stage ( P  = 0.98), and survival ( P  = 0.51) between intra- and extrahepatic cholangiocarcinoma.Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79101/1/j.1365-2036.2009.04218.x.pd

Identification of a humanized mouse model for functional testing of immune-mediated biomaterial foreign body response.

Biomedical devices comprise a major component of modern medicine, however immune-mediated fibrosis and rejection can limit their function over time. Here, we describe a humanized mouse model that recapitulates fibrosis following biomaterial implantation. Cellular and cytokine responses to multiple biomaterials were evaluated across different implant sites. Human innate immune macrophages were verified as essential to biomaterial rejection in this model and were capable of cross-talk with mouse fibroblasts for collagen matrix deposition. Cytokine and cytokine receptor array analysis confirmed core signaling in the fibrotic cascade. Foreign body giant cell formation, often unobserved in mice, was also prominent. Last, high-resolution microscopy coupled with multiplexed antibody capture digital profiling analysis supplied spatial resolution of rejection responses. This model enables the study of human immune cell-mediated fibrosis and interactions with implanted biomaterials and devices

Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma

Background & Aims: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC. Methods: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses (58.6%). Results: Provider beliefs about risk of HCC recurrence after DAA therapy varied: 48% responded that DAAs reduce risk, 36% responded that DAAs do not change risk, and 16% responded that DAAs increase risk of HCC recurrence. However, most providers believed DAAs to be beneficial to and reduce mortality of patients with complete response to HCC treatment. Accordingly, nearly all providers (94.9%) reported recommending DAA therapy to patients with early-stage HCC who received curative treatment. However, fewer providers recommended DAA therapy for patients with intermediate (72.9%) or advanced (57.5%) HCC undergoing palliative therapies. Timing of DAA initiation varied among providers based on HCC treatment modality: 49.1% of providers reported they would initiate DAA therapy within 3 months of surgical resection whereas 45.9% and 5.0% would delay DAA initiation for 3–12 months and >1 year post-surgery, respectively. For patients undergoing transarterial chemoembolization (TACE), 42.0% of providers would provide DAAs within 3 months of the procedure, 46.7% would delay DAAs until 3–12 months afterward, and 11.3% would delay DAAs more than 1 year after TACE. Conclusions: Based on a survey sent to hepatology providers, there is variation in provider attitudes and practice patterns regarding use and timing of DAAs for patients with HCC. Further studies are needed to characterize the risks and benefits of DAA therapy in this patient population