Liver Transplantation for Hepatitis B in Early Adulthood: Analysis of the United Network for Organ Sharing Database.

BACKGROUND: Chronic hepatitis B virus (HBV) infection has a mild course in most children that may delay initiation of treatment even when indicated. Unfortunately, a small number of cases can progress rapidly to cirrhosis, which may require liver transplantation (LT) in early adulthood. The aim of this study was to assess the characteristics of HBV-positive young adults who received LT and to evaluate post-transplant outcomes including patient and graft survival and differences between pre- and post-implementation of Model for End-stage Liver Disease (MELD) prioritization. METHODS: The United Network for Organ Sharing (UNOS) database review was conducted from 1987 to 2012, and a retrospective analysis was performed on all young adult patients (ages 18-35 years) who underwent LT in the United States with a primary diagnosis of HBV or were seropositive for HBV surface antigen at time of LT. Kaplan-Meier analysis was used to assess patient and graft survival in the pre-MELD and post-MELD eras. Factors associated with survival were identified through the use of Cox regression analysis. RESULTS: A total of 522 HBV-infected subjects were included. Average age at time of transplant was 28.4 ± 5.2 years; 60.9% were male, 48.6% were white, the mean body mass index was 25 ± 5.5 kg/m2, diabetes was present in 3.9%, hepatocellular carcinoma (HCC) was present in 4.4%, and 10.4% were on dialysis prior to LT. Median follow-up after first LT was 48.2 months [12.5, 109]. During this time, 174 (33.3%) patients died with a mean age at the time of death of 31.6 ± 7.8 years, including 144 of 522 (28%) after the first LT, 26 of 74 (35%) after the second LT, and 4 of 12 (33%) after the third LT. The most common cause of death was graft failure (27.6%), followed by infection (16.6%). Overall, only 58% of patients were alive with their first LT at last follow-up. Kaplan-Meier analysis revealed worse patient and graft survival after re-transplantation in comparison to initial LT. Three hundred thirty subjects were transplanted in the pre-MELD era and 192 were transplanted in post-MELD era. Obesity, HCC, shorter ventilation use, shorter cold ischemia time, and non-white donor race were significantly more common in the post-MELD era (all with P < .05). Importantly, 5-year patient and graft survival rates were higher in the post-MELD era compared with the pre-MELD era. CONCLUSIONS: LT in young adults for HBV has poor outcomes and can be associated with premature death. These findings should prompt more aggressive evaluation and treatment for HBV in young patients. Superior outcomes in the post-MELD era compared with the pre-MELD era may be attributed to pre-transplant factors, improved surgical technique, and better treatment options for HBV infection.

Sofosbuvir and Simeprevir for the Treatment of Recurrent Hepatitis C with Fibrosing Cholestatic Hepatitis after Liver Transplantation.

Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT), which frequently results in graft failure and death. Treatment of FCH remains challenging, and the optimal antiviral therapy is yet to be determined. Between November 2013 and early 2015, 62 patients with HCV cirrhosis underwent OLT at our transplant center, of whom, 5 patients developed recurrence HCV in the form of severe FCH and were treated with sofosbuvir and simeprevir (SOF-SMV) for 24 weeks. All patients achieved significant improvement of HCV viral load and had undetectable viral PCR at 6-8 week of treatment. The HCV RNA remained undetectable throughout treatment course. The first two patients achieved SVR at week 12 after completion of the treatment. There were significant histologic and biomarkers improvements after initiation of the treatment. One patient developed refractory pruritus and acute pancreatitis. The second, fourth and fifth patients had very benign treatment courses with no side effects recorded. The third patient was starting the treatment with multiple comorbid conditions. His course was complicated with hepatic artery thrombosis, and later developed sepsis and renal failure. Therefore, it seems that the combination of SOF-SMV is an efficacious oral regimen in OLT recipient with recurrent hepatitis C and FCH. However, safety profile needs to be carefully evaluated.

Treatment of Recurrent Hepatitis C Genotype-4 Post-Liver Transplantation with Sofosbuvir plus Simeprevir.

Hepatitis C virus (HCV) infection remains a leading indication for orthotopic liver transplantation (OLT) worldwide. Recurrence of HCV following OLT is universal. There is scarcity of data on the post-OLT treatment of HCV genotype-4-the predominant genotype in North Africa and the Middle East. Herein, we present three patients who have experienced HCV genotype-4 recurrence post-OLT. All three patients were interferon-naive and were treated with simeprivir (SIM) and sofosbuvir (SOF) combination therapy for 12-24 weeks. The data from this case series show that SIM+SOF are well-tolerated and effective for achieving viral clearance in HCV genotype-4 post-OLT patients. Given the limited nature of a case series, further research must be pursued regarding post-OLT HCV genotype-4 responses to direct-acting anti-viral therapy.

Review article: breath analysis in inflammatory bowel diseases.

BACKGROUND: There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease. AIM: Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD. METHODS: A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed. RESULTS: Mean breath pentane, ethane, propane, 1-octene, 3-methylhexane, 1-decene and NO levels were elevated (P < 0.05 to P < 10(-7)) and mean breath 1-nonene, (E)-2-nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)-2-nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin-1ß showed an inverse relation with clinical disease activity. CONCLUSIONS: Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well-designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD.

Breathprints of childhood obesity: changes in volatile organic compounds in obese children compared with lean controls.

OBJECTIVE: The objective of this study was to investigate changes in volatile organic compounds (VOCs) in exhaled breath in overweight/obese children compared with their lean counterparts. STUDY DESIGN: Single exhaled breath was collected and analyzed per protocol using selective ion flow tube mass spectrometry (SIFT-MS). RESULTS: Sixty overweight/obese children and 55 lean controls were included. Compared with the lean group, the obese group was significantly older (14.1 ± 2.8 vs. 12.1 ± 3.0 years), taller (164.8 ± 10.9 vs. 153.3 ± 17.1 cm) and more likely to be Caucasian (60% vs. 35.2%); P < 0.05 for all. A comparison of the SIFT-MS results of the obese group with the lean group revealed differences in concentration of more than 50 compounds. A panel of four VOCs can identify the presence of overweight/obesity with excellent accuracy. Further analysis revealed that breath isoprene, 1-decene, 1-octene, ammonia and hydrogen sulfide were significantly higher in the obese group compared with the lean group (P value < 0.01 for all). CONCLUSION: Obese children have a unique pattern of exhaled VOCs. Changes in VOCs observed in this study may help to gain insight into pathophysiological processes and pathways leading to the development of childhood obesity.

Metabolomic analysis of breath volatile organic compounds reveals unique breathprints in children with inflammatory bowel disease: a pilot study.

BACKGROUND: Breath testing is becoming an important diagnostic method to evaluate many disease states. In the light of rising healthcare costs, is important to develop a simple non-invasive tool to potentially identify paediatric patients who need endoscopy for suspected inflammatory bowel disease (IBD). AIM: To analyse exhaled volatile organic compounds (VOCs) and investigate the presence of a unique breath patterns to differentiate paediatric patients with (IBD) from healthy controls. METHODS: A cross-sectional, single-centre study included paediatric IBD patients and healthy controls (age range, 5-21 years). The diagnosis of IBD was confirmed by endoscopic, histological and radiographic data. Exhaled breath was collected and analysed using a selective ion flow tube mass spectroscopy (SIFT-MS) to identify new markers or patterns of IBD. RESULTS: One hundred and seventeen patients (62 with IBD and 55 healthy controls) were included in the study. Linear discriminant analysis and principle component analysis of mass scanning ion peak data demonstrated 21 pre-selected VOCs correctly classify patients with IBD or as healthy controls; P < 0.0001. Multivariable logistic regression analysis further showed three specific VOCs (1-octene, 1-decene, (E)-2-nonene) had excellent accuracy for predicting the presence of IBD with an area under the curve (AUC) of 0.96 (95% CI: 0.93-0.99). No significant difference in VOCs was found between patients with Crohn's disease or ulcerative colitis, and no significant correlation was seen with disease activity. CONCLUSION: These pilot data support the hypothesis that a unique breathprint potentially exists for paediatric IBD in the exhaled metabolome.

Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer.

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.

Elevation of the erythrocyte sedimentation rate precedes exacerbation of bleomycin-induced pulmonary toxicity: report of two cases and review of literature.

Bleomycin is included in a number of potentially curative chemotherapy regimens. It is associated with distinct forms of pulmonary toxicity, with interstitial pneumonitis the most common. Early detection of pulmonary toxicity is not always predictable by monitoring serial chest radiographs and pulmonary function tests. Even newer serum markers are not useful indicators of bleomycin-induced pulmonary damage. Two patients developed bleomycin pulmonary toxicity, in both of whom increases in erythrocyte sedimentation rate (ESR) preceded clinical deterioration and radiographic changes. The ESR may have potential significance as a monitoring test in patients receiving bleomycin.