- Use of Sofosbuvir-Based Treatment of Chronic Hepatitis C in Liver Transplant Recipients on Hemodialysis. [JOURNAL ARTICLE]
- J Clin Gastroenterol 2016 Aug 19.
The use of direct acting agents has changed the management paradigm of hepatitis C (HCV) in liver transplant (LT) recipients. However, the appropriate antiviral regimen in LT recipients on hemodialysis (HD) remains unclear.We retrospectively evaluated the safety and efficacy of sofosbuvir-based LT recipients on HD followed at the University of California Los Angeles.Twelve LT recipients on HD were treated for recurrent HCV with sofosbuvir-based therapy. Indications for antiviral therapy included fibrosing cholestatic hepatitis, symptomatic cryoglobulinemia, and recurrent HCV. The causes of renal failure included hepatorenal syndrome, acute tubular necrosis and cryoglobulinemia. Of those who were not on dialysis at the time of transplantation, the mean creatinine (±SD) was 1.7 (±0.8) mg/dL. The mean age (±SD) of the cohort was 62.2 (±6.0) years. Most recipients were male (67%) and infected with genotype 1 (83%). Baseline alanine aminotransferase, total bilirubin, hemoglobin and HCV RNA values (±SD) were 53.2 (±59.4) IU/L, 3.2 (±5.5) mg/dL, 10.5 (±1.8) g/dL, and 30,499,500 (±29,655,754) IU/mL. HCV RNA levels were undetectable in all recipients at the end of therapy. The trough mean (±SD) hemoglobin of patients on treatment and on HD was 8.4 (±2.3). The sustained viral response was 58% (7/12), and the overall patient survival was 42%. All the deaths occurred a mean (±SD) after 5.4 (±3.6) months after treatment was completed.All patients achieved viral suppression from therapy, and over half the recipients achieved a sustained virological response. A high mortality underscores the necessity of starting antiviral treatment sooner in LT recipients and the need for larger cohort studies.
- Hyperbilirubinemia Protects against Aging-Associated Inflammation and Metabolic Deterioration. [Journal Article]
- Oxid Med Cell Longev 2016.:6190609.
Mild constitutive hyperbilirubinemia is associated with a reduced risk of cardiovascular diseases, diabetes, and cancer. Since these pathologies are associated with aging, inflammation, and oxidative stress, we investigated whether hyperbilirubinemia interferes with ROS homeostasis in cell cultures and with inflammation, senescence, and mitochondrial dysfunction in aged rats. Human embryonic kidney cells and rat primary fibroblasts showed a dose-dependent decrease in the ratio of oxidized/reduced glutathione, intracellular H2O2 levels, and mitochondrial ROS production, with increasing bilirubin concentrations in the culture media. Compared to their normobilirubinemic siblings, aged hyperbilirubinemic Gunn rats showed significantly smaller amounts of visceral fat, better glucose tolerance, and decreased serum levels of proinflammatory cytokines TNFα, IL-1β, and IL-18. Simultaneously, livers from Gunn rats showed decreased expression of senescence markers and cell cycle inhibitors p21 and p16. Mitochondria from aged Gunn rats showed higher respiration and lower H2O2 production compared to controls. In conclusion, we demonstrated that mildly elevated serum bilirubin is generally associated with attenuation of oxidative stress and with better anthropometric parameters, decreased inflammatory status, increased glucose tolerance, fewer signs of cellular senescence, and enhanced mitochondrial function in aged rats.
- Assessment of Vitamin D status in a group of Egyptian children with non alcoholic fatty liver disease (multicenter study). [Journal Article]
- Nutr Metab (Lond) 2016.:53.
Nonalcoholic fatty liver disease (NAFLD) is one of the health problems with great burden on the liver that may end with liver cirrhosis and hepatocellular carcinoma. The aim of this work was to assess serum vitamin D level in nonalcoholic fatty liver disease children.This cross sectional case control study involved 47 patients with nonalcoholic fatty liver disease selected while recruiting the pediatric hepatology clinics. Their ages ranged from 5-15 years and were compared with 23 healthy age and sex matched children. All involved patients were subjected to careful history taking, clinical examination and for patients and control, anthropometric measures for body mass index (BMI) calculation (plotted on WHO percentile growth charts), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin (total and direct), serum albumin, creatinine, triglycerides, cholesterol, high density lipoprotein (HDL),low density lipoprotein (LDL), fasting blood glucose and fasting insulin (for calculation of insulin resistance), C reactive protein and serum vitamin D all were assayed. NAFLD was detected by ultrasonography and graded as absent, mild, moderate and severe.Ninety-three percent of NAFLD patients were obese. Significant differences were found between patients and control regarding AST, ALT, ALP, GGT, total and direct bilirubin, serum albumin, creatinine, triglycerides, cholesterol, HDL, fasting blood glucose, fasting insulin, the homeostatic model assessment for insulin resistance (HOMA-IR) and serum vitamin D levels. Significant negative correlation was found between serum vitamin D level and grades of steatosis.Serum vitamin D level decreases in children with NAFLD. This low serum vitamin D level is associated with higher stages of steatosis but not with BMI.
- A donor body mass index greater than 30 is not a contraindication for live liver donation. [JOURNAL ARTICLE]
- Am J Transplant 2016 Aug 22.
The increased prevalence of obesity worldwide threatens the pool of living liver donors. While the negative effects of graft steatosis on liver donation and transplantation is well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Therefore, we compared the outcome of LDLT using donors with a BMI<30kg/m(2) vs donors with a BMI ≥30kg/m(2) . Between April 2000-May 2014, 105 patients received a right lobe liver graft from donors with BMI ≥30kg/m(2) , while 364 recipients were transplanted with grafts from donors with BMI<30kg/m(2) . Liver steatosis >10% was excluded in all donors with a BMI>30kg/m(2) by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with a BMI<30 vs. BMI≥30kg/m(2) had similar post-operative complication rate (Dindo-Clavien ≥3b: 2% vs 3%; p=0.71) and length of hospital stay (6 vs 6; p=0.13). Recipient graft function, assessed by post-transplant peak serum bilirubin and INR was identical. Furthermore, no difference was observed in recipient's complications rate (Dindo-Clavien ≥3b: 25% vs 20%; p=0.3) or length of hospital between groups. We conclude that donors with a BMI ≥30kg/m(2) , in the absence of graft steatosis, are not a contraindication to LDLT. This article is protected by copyright. All rights reserved.
- Physiological response, blood chemistry profile and mucus secretion of red sea bream (Pagrus major) fed diets supplemented with Lactobacillus rhamnosus under low salinity stress. [JOURNAL ARTICLE]
- Fish Physiol Biochem 2016 Aug 19.
Environmental stressors caused by inadequate aquaculture management strategies suppress the immune response of fish and make them more susceptible to diseases. Therefore, efforts have been made to relieve stress in fish by using various functional feed additives in the diet, including probiotics. The present work evaluates the effects of Lactobacillus rhamnosus (LR) on physiological stress response, blood chemistry and mucus secretion of red sea bream (Pagrus major) under low salinity stress. Fish were fed four diets supplemented with LR at [0 (LR0), 1 × 10(2) (LR1), 1 × 10(4) (LR2) and 1 × 10(6) (LR3) cells g(-1)] for 56 days. Before stress, blood cortisol, urea nitrogen (BUN) and total bilirubin (T-BIL) showed no significant difference (P > 0.05), whereas plasma glucose and triglyceride (TG) of fish-fed LR2 and LR3 diets were significantly lower (P < 0.05) than those of the other groups. Plasma total cholesterol (T-CHO) of fish-fed LR3 diet was significantly (P < 0.05) lower than that of the other groups. Furthermore, total plasma protein, mucus myeloperoxidase activity and the amount of mucus secretion were significantly enhanced in LR-supplemented groups when compared with the control group (P < 0.05). After the application of the low salinity stress test, plasma cortisol, glucose, T-CHO and TG contents in all groups showed an increased trend significantly (P < 0.01) compared to the fish before the stress challenge. However, plasma total protein and the amount of secreted mucus showed a decreased trend in all groups. On the other hand, BUN, T-BIL and mucus myeloperoxidase activity showed no significant difference after exposure to the low salinity stress (P > 0.05). In addition, the fish that received LR-supplemented diets showed significantly higher tolerance against low salinity stress than the fish-fed LR-free diet (P < 0.05). The physiological status and the detected immune responses, including total plasma protein and mucus myeloperoxidase activity in red sea bream, will provide a more comprehensive outlook of the effects of probiotics to relieve stress in fish.
- Left lobe living donor liver transplantation in adults: What is the safety limit? [JOURNAL ARTICLE]
- Liver Transpl 2016 Aug 19.
Small-for-size syndrome (SFSS) is the most significant cause of graft loss after living donor liver transplantation (LDLT), especially after left lobe (LL) LDLT in adults. The safety limit of applying LL-LDLT in adults without severe SFSS with high-rate lethality needs to be determined.A total of 207 LL-LDLT in adults since September 2005 were evaluated to analyze the risk factors for severe SFSS, defined as serum total bilirubin concentration of ≥ 20.0 mg/dl after LDLT.Although there were no significant differences in cumulative graft survival after LDLT between medium grafts (graft-to-standard volume standard liver volume ratio [GV/SLV] ≥ 40.0%), small grafts (35.0% ≤ GV/SLV < 40.0%), and extra-small grafts (GV/SLV < 35.0%), patients with severe SFSS showed a significantly lower 5-year graft survival rate than those without (42.9% vs. 94.3%, respectively; p<0.01). Multivariate analysis for severe SFSS after LL-LDLT showed that donor age of ≥ 48 years (p=0.01), Model for End-Stage Liver Disease (MELD) score of ≥ 19 (p<0.01), and end portal venous pressure of ≥ 19 mmHg (p=0.04), were the significant and independent factors for severe SFSS after LL-LDLT. Within such the high-risk subgroups of patients with a donor age of ≥ 48 years or MELD score of ≥ 19 before LDLT, operative blood loss volume of ≥ 8.0 L was a risk factor for severe SFSS.LL-LDLT in adults could be indicated and provide acceptable outcomes for the combinations of donors aged < 48 years and recipients with a MELD score of <19. Smaller grafts might yield acceptable outcomes in appropriately selected donor-recipient combinations. This article is protected by copyright. All rights reserved.
- Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use. [JOURNAL ARTICLE]
- Br J Haematol 2016 Aug 19.
Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: (i) SCD baseline and controls, and (ii) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean ± standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32·4 ± 11·6 vs. 22·9 ± 7·6, P = 0·0009). SP in SCD pain was higher than baseline (78·1 ± 43·4 vs. 32·4 ± 11·6, P = 0·004). Haemolysis correlated with increased SP: Hb (r = -0·7, P = 0·0002), reticulocyte count (r = 0·61, P = 0·0016), bilirubin (r = 0·68, P = 0·0216), lactate dehydrogenase (r = 0·62, P = 0·0332), aspartate aminotransferase (r = 0·68, P = 0·003). Patients taking hydroxycarbamide had increased SP (β = 29·2, P = 0·007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment.
- Autoimmune hemolytic anemia after nivolumab treatment in Hodgkin lymphoma responsive to immunosuppressive treatment. A case report. [CASE REPORTS]
- Hematol Oncol 2016 Aug 19.
The patients with refractory Hodgkin lymphoma have a poor prognosis. The nivolumab, an IgG4 monoclonal antibody inhibiting the program death 1 pathway has recently demonstrated its efficacy and its safety in patients with heavily pretreated refractory Hodgkin lymphoma. The side effects of this immunotherapy include autoimmune-like syndromes. A 75-year-old woman with no significant comorbidities was treated by nivolumab (3 mg/kg every 2 wk) as a third-line treatment for refractory Hodgkin lymphoma. A clinical response was observed with the first injection of nivolumab, with a reduction in superficial lymph nodes. After the second injection, the patient presented an authentic autoimmune hemolytic anemia with a profound anemia at 64 g/L and biologic characteristics of hemolysis (elevated unconjugated bilirubin, lactate dehydrogenase, and reticulocytes). The direct antiglobulin test was strongly positive for IgG antibodies, and the indirect antiglobulin test became positive with a very high level of autoantibodies. After 2 injections of nivolumab, the patient underwent a fluodeoxyglucose F 18 positron emission tomography-computed tomography, showing a partial response according to modified Cheson criteria. A treatment with prednisone (2 mg/kg), initiated after transfusion of 2 units of red blood cells, permitted the complete resolution of this autoimmune reaction after 3 months of corticotherapy. The fluodeoxyglucose F 18 positron emission tomography-computed tomography performed at the end of the corticotherapy showed a clear disease progression. Considering the very good response achieved after only 2 injections of nivolumab, the limited therapeutic resources for this old woman, and the complete resolution of the autoimmune hemolytic anemia, nivolumab was reintroduced at the same dose, with close clinical and biological monitoring. She received 6 more injections of nivolumab without recurrence of hemolysis.
- A diagnostic nomogram for delayed hemolytic transfusion reaction in sickle cell disease. [JOURNAL ARTICLE]
- Am J Hematol 2016 Aug 18.
Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso-occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within one week following an index transfusion and repeated within two months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%) and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post-transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. This article is protected by copyright. All rights reserved.
- Short-term effects and adverse events of endoscopically applied radiofrequency ablation appear to be comparable with photodynamic therapy in hilar cholangiocarcinoma. [Journal Article]
- United European Gastroenterol J 2016 Aug; 4(4):570-9.
Radiofrequency ablation (RFA) is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to compare the short-term effects of biliary drainage and adverse events of this technique with the standard of endoscopical treatment of hilar cholangiocarcinoma, photodynamic therapy (PDT).We retrospectively and since December 2012 prospectively investigated the efficacy and adverse events of RFA in patients with hilar cholangiocarcinoma in two tertiary referral centers between November 2011 and January 2013. The approach of the study was prospective, but because of the large amount of retrospectively included patients, the design of the study is overall retrospective. A group of 20 patients treated with PDT between April 2005 and May 2011 served as a historical control.Fourteen patients received 31 biliary RFAs and 20 patients received 36 PDTs. Within the RFA group, a significant decrease (p = 0.046) of the bilirubin level was seen 14 days after the first RFA (3.3 ± 3.9 (mg/dl) versus 2.3 ± 2.6 (mg/dl)). In the PDT group no significant decrease (p = 0.67) of the bilirubin level was obtained (4.1 ± 6.9 (mg/dl) versus 3.5 ± 5.3 (mg/dl)). In the PDT group (13/20, 65%) a significantly higher number of premature stent replacements (<3 months) after the first intervention was noticed in comparison with the RFA group (four of 14, 29%) (p < 0.01). Between the first and fifth procedure, post-interventional adverse events tend to occur more frequently in patients with PDT (eight of 20, 40%) than with RFA (three of 14, 21%) (p = 0.277).Looking at the short-term effects, we conclude that RFA may present a therapeutic alternative to PDT for palliative treatment of malignant biliary obstruction because of its simple feasibility and moderate adverse event rate. To provide a definitive evaluation of the long-term effects and of overall median survival, a controlled trial with PDT must follow.