Outcomes in Hepatitis C Positive Liver Transplantation: Timing of Direct-Acting Antiviral Treatment and Impact on Graft Fibrosis

Liver transplantation for hepatitis C virus (HCV)-related disease has the lowest five-year graft survival among all liver transplant recipients. Graft failure due to accelerated fibrosis from unrestrained HCV replication is common. Optimal timing of HCV treatment with direct-acting antiviral agents remains unknown. We compared HCV liver transplant recipients successfully treated for HCV before transplant to those treated within 1 year of transplant to determine if graft fibrosis, measured by Fib-4 scores, differs with timing of treatment. Fib-4 scores less than or equal to 1.45 defined minimal fibrosis and greater than 1.45 defined greater than minimal fibrosis. We identified 117 liver transplant recipients: 52 treated before transplantation and 65 treated within 1 year of transplantation. Overall, 34% of recipients had minimal fibrosis, and the likelihood of having minimal fibrosis following treatment and liver transplantation did not differ by timing of treatment. The odds ratio of having greater than minimal fibrosis was 0.65 (95% CI 0.30, 1.42) among those treated within 1 year after transplantation compared to those treated before transplantation (p-value 0.28). Importantly, nearly 2/3 of these patients had evidence of fibrosis progression one year after sustained virologic response, supporting recommendations for early antiviral-based treatment to prevent accumulation of HCV-related disease.     

Effect of inhibition of inducible nitric oxide synthase (iNOS) on the murine splenic immune response induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans lipopolysaccharide

Animal studies suggest that inducible nitric oxide synthase (iNOS) may be associated with destructive periodontal disease. l- N ⁶-(1-Iminoethyl)-lysine ( l -NIL) has been shown to inhibit iNOS in a selective manner, and hence the aim of the present study was to test the hypothesis that treatment with l -NIL may induce a T-cell helper 1 (Th1)-like immune response by Aggregatibacter ( Actinobacillus ) actinomycetemcomitans lipopolysaccharide (LPS)-stimulated murine spleen cells in vitro . BALB/c mice were either sham-immunized or immunized with A. actinomycetemcomitans LPS. Spleen cells were stimulated with A. actinomycetemcomitans LPS in the presence or absence of l -NIL. Nitric oxide (NO), iNOS activity, specific IgG subclass antibodies, interferon- γ (IFN- γ ), and interleukin-4 (IL-4) levels and cell proliferation were determined. The results showed that treatment with l -NIL suppressed both NO production and iNOS activity but enhanced specific IgG2a, IFN- γ levels, and increased cell proliferation following stimulation with A. actinomycetemcomitans LPS-stimulated cells. The results of the present study suggest that inhibition of iNOS activity by l -NIL may skew the A. actinomycetemcomitans LPS-stimulated murine splenic immune response towards the Th1-like immune profile in vitro .     

Rituximab is associated with improved survival in cardiac allograft patients with antibody‐mediated rejection: a single center review

Antibody‐mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and the optimal treatment of this condition is poorly defined. Rituximab has been used successfully for the treatment for antibody‐mediated diseases; however, its role in AMR is unclear. We review our experience with rituximab in patients with cardiac allograft AMR. We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR from 2001 to 2011. Inclusion criteria were clinical suspicion of rejection with the presence of C4d complement staining on endomyocardial biopsy and the absence of cellular rejection of grade 2R or greater. Patients were divided into Rituximab and NoRituximab groups. The primary endpoint was all‐cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and rehospitalization. Thirty‐three patients met inclusion criteria, of whom 13 received rituximab and 20 did not. Baseline characteristics were similar between groups. Kaplan–Meier curves for a three‐yr follow‐up period demonstrate improved survival in the Rituximab group (p = 0.0089). There were no differences in secondary endpoints. We found that rituximab therapy was associated with improved survival in cardiac allograft AMR. Further prospective, randomized studies in larger patient populations are needed to confirm this finding and to define ideal timing for rituximab administration.     

Massive Hemobilia: A Diagnostic and Therapeutic Challenge

Background

Massive hemobilia is a rare but potentially life-threatening cause of upper gastrointestinal hemorrhage. In this retrospective analysis, we have evaluated the challenges involved in the diagnosis and management of massive hemobilia.

Methods

Between 2001 and 2011, a total of 20 consecutive patients (14 males) who were treated in our department for massive hemobilia were included in the study and their records were retrospectively analyzed.

Results

Causes of hemobilia were blunt liver trauma (n = 9), hepatobiliary intervention (n = 4), post-laparoscopic cholecystectomy hepatic artery pseudoaneurysm (n = 3), hepatobiliary tumors (n = 3), and vascular malformation (n = 1). Melena, abdominal pain, hematemesis, and jaundice were the leading symptoms. All patients had undergone upper GI endoscopy, abdominal ultrasound, and computerized tomography of the abdomen. An angiogram and therapeutic embolization were done in 12 patients and was successful in nine but failed in three, requiring surgery. Surgical procedures performed were right hepatectomy (n = 4), extended right hepatectomy (n = 1), segmentectomy (n = 1), extended cholecystectomy (n = 1), repair of the pseudoaneurysm (n = 3), and right hepatic artery ligation (n = 1).

Conclusion

The successful diagnosis of hemobilia depends on a high index of suspicion for patients with upper GI bleeding and biliary symptoms. Although transarterial embolization is the therapeutic option of choice for massive hemobilia, surgery has a definitive role in patients with hemodynamic instability, after failed embolization, and in patients requiring laparotomy for other reasons.     

Collagen-chitosan polymeric scaffolds for the in vitro culture of human epidermoid carcinoma cells.

A biodegradable polymer scaffold was developed using collagen and chitosan, in the form of interpenetrating polymeric network (IPN), for in vitro culture of human epidermoid carcinoma cells (HEp-2, Cincinnati). Glutaraldehyde was used as cross-linking agent for the development of scaffold. Various types of scaffolds were prepared using different proportionate mixtures of collagen and chitosan solutions in the ratio of 3:7, 4:6, 5:5, 6:4 and 7:3 (collagen:chitosan). These scaffolds were fully characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA). Equilibrium swelling studies were carried out in phosphate buffer of physiological pH (7.4) to study its swelling characteristics at slightly alkaline pH. The scaffold that showed optimum swelling property was selected as the best scaffold for performing in vitro culture studies. In vitro culture studies were carried out using HEp-2 cells, over the selected scaffold and its growth morphology was determined through optical photographs taken at different magnifications at various days of culture. The results of the above studies suggest that the scaffolds prepared from collagen and chitosan can be utilized as a substrate to culture HEp-2 cells and can also be used as an in vitro model to test anticancerous drugs.     

Trends and relationship between chlorophyll-a and sea surface temperature in the central equatorial Indian Ocean

This work presents the trend analysis and relationship between chlorophyll-a (chl-a) concentration and sea surface temperature (SST) in the central equatorial Indian Ocean (CEIO) using Aqua MODIS chl-a Level-3 Standard Mapped Image (SMI) data for a period of 10 years (2002–2012). In order to understand the monsoonal variability of chl-a concentration and SST and to evaluate their relationships over the CEIO, trend analysis of chl-a values was carried out. The area average chl-a concentration in the region shows a weak annual cycle with high concentration during winter (October–December) and low in summer (June). High chl-a concentration (~0.22 mg m^?3) is observed during early winter in the region. Chl-a concentration starts decreasing from March onwards until the onset of summer monsoon. The data reveal low chl-a concentrations during summer period, i.e., from June to September, which is in accordance with several observations, and higher concentrations during October to December. The other reason is that satellite sensor may not capture chl-a variability more accurately because of cloud cover during summer monsoon time. A reasonably significant coefficient of determination (R² = 0.51; significant at p < 0.05 level) between SST and chl-a concentration is recorded. This study clearly suggests that the SST acts as a proxy for variables which cause high chl-a concentration in the CEIO.