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- A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration. [JOURNAL ARTICLE]
- Gut 2014 Aug 20.
The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression.We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100 000/mm(3)), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years).In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001).A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.
- Percutaneous Treatment of Biliary Complications in Pediatric Patients After Liver Transplantation. [JOURNAL ARTICLE]
- Rofo 2014 Aug 20.
Purpose: Evaluation of the efficiency and safety of the percutaneous treatment of biliary complications in pediatric liver transplant recipients. Methods: We conducted a retrospective analysis of children who underwent biliary percutaneous interventions after pediatric liver transplantation (PLT) over a 4-year period. Kind of biliary complication, interval between liver transplantation and intervention, status of the vessels, procedural interventional management, technical and clinical success, course of cholestasis, PTBD-related complications and patient survival were analyzed. Results: 23 percutaneous transhepatic biliary drainages (PTBD) were placed in 16 children due to 18 biliary complications. The drains were customized individually by shortening and cutting additional holes. PTBD placement was performed with technical and clinical success in all children. 4 children received PTBD to bridge the time to retransplantation and surgical revision. One child received PTBD for successful treatment of anastomotic leakage. Long-term dilation of biliary stenoses was performed in 13 children using PTBD. One of these 13 patients showed recurrent stenosis during a median follow-up of 295 days. Bilirubin values decreased significantly after PTBD placement for biliary stenosis. One patient suffered from bacteremia after PTBD replacement. Conclusion: PTBD treatment for biliary complications after PLT is effective and safe. Key points: Various biliary complications after PLT can be successfully treated by PTBD. For this purpose, a highly individualized approach with catheter modification is mandatory. Citation Format: • Uller W, Wohlgemuth WA, Hammer S et al. Percutaneous Treatment of Biliary Complications in Pediatric Patients After Liver Transplantation. Fortschr Röntgenstr 2014; DOI: 10.1055/s-0034-1366656.
- Haematological and biochemical characteristics of the splenic effluent blood in schistosomal patients undergoing splenectomy. [JOURNAL ARTICLE]
- Rev Col Bras Cir 2014 Jun; 41(3):176-180.
To assess hematological and biochemical features of splenic effluent blood and their influence on the rise of hematological values after splenectomy.we studied 20 patients undergoing surgical treatment for schistosomatic portal hypertension. We collected blood samples for CBC, coagulation, bilirubin and albumin in the splenic vein (perioperative) and peripheral blood (immediately pre and postoperative periods).the splenic blood showed higher values of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as reduction of laboratory coagulation parameters in relation to peripheral blood collected preoperatively. In the postoperative peripheral blood there was an increase in the overall leukocytes and in their neutrophil component, and decreased levels of basophils, eosinophils and lymphocytes. The other postoperative variables of complete blood count and coagulation tests were not different compared with the splenic blood. The albumin values were lower postoperatively when compared to preoperative and splenic blood. There were higher values of direct bilirubin in the postoperative period when compared with the preoperative and splenic blood. Postoperative indirect bilirubin was lower compared to its value in the splenic blood.hematological and biochemical values of splenic effluent blood are higher than those found in peripheral blood in the presence of schistosomal splenomegaly. However, the splenic blood effluent is not sufficient to raise the blood levels found after splenectomy.
- Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats. [Journal Article]
- Iran J Basic Med Sci 2014 Jun; 17(6):460-4.
Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats.Thirty male Sprague-Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks.GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase and glutathione peroxidase activities and albumin level (P<0.05). Administration of GSP significantly ameliorated structural changes induced in liver of diabetic rats.GSP have protective effects against hepatic tissue injury due to antioxidant properties.
- Plasma estrone sulfate, clinical biochemistry, and milk yield of dairy cows carrying a fetus from a bull or its clone. [JOURNAL ARTICLE]
- Theriogenology 2014 Jul 23.
The aim of this article was to compare plasma estrone sulfate (E1SO4), clinical biochemistry, and milk yield of dairy cows carrying a female fetus from a bull (BULL) or from its clone (CLONE), evaluating also the relationship between the former variables and the birth weight of the newborn. Sixteen recipient dairy Friesian heifers (10 BULL and 7 CLONE) received a female embryo, obtained by in vitro embryo production and sexing by polymerase chain reaction with the semen of the BULL or the CLONE. Blood samples on all cows were obtained before feed distribution in the morning from jugular vein from 4 weeks before to 4 weeks after calving, to be analyzed for metabolic profile. The samples from late gestation were also analyzed for E1SO4 concentration. To separately assess the effect of calf birth weight (CBW), data were categorized as follows: low (<39 kg; BWT-A), mid (39-46 kg; BWT-B), and high (>46 kg; BWT-C). The plasma concentrations of β-hydroxybutyric acid (BHB, P = 0.019), Na (P = 0.002), Cl (P = 0.026), strong cation-anion balance (P = 0.020), total bilirubin (P = 0.054), and α1-globulin (P = 0.044) were higher in prepartum BULL recipients than those in CLONE, whereas BHB (P = 0.021) and Mg (P = 0.090) were higher in postpartum BULL recipients, while no differences were recorded in the remaining postpartum parameters. The CBW class had significant interaction with week of gestation on antepartum plasma estrone sulfate (P = 0.021), whereas CBW per se affected antepartum plasma BHB (P = 0.021), and nonesterified fatty acids (NEFA; P = 0.011) being higher in BWT-C which also had the lower NEFA concentration during postpartum. Milk yield was unaffected by the sire used, both for quantitative and qualitative aspects. Cows carrying heavier fetus (BWT-C) had a different lactation affected by month compared with the other 2 CBW groups. From these results, there were no differences between BULL and CLONE recipients. Estrone sulfate, BHB, and NEFA may be used to predict CBW and provide different nutritional management during gestation.
- Omentin changes following bariatric surgery and predictive links with biomarkers for risk of cardiovascular disease. [JOURNAL ARTICLE]
- Cardiovasc Diabetol 2014 Aug 21; 13(1):124.
BackgroundAlthough no receptor has yet been identified, changes in circulating levels of the adipokine designated as Omentin have been demonstrated in obesity and related comorbidities such as cardiovascular disease, insulin resistance, metabolic syndrome and chronic inflammation.MethodsChanges in Omentin levels at 1 and 5 days and 6 and 12 months in response to biliopancreatic diversion with duodenal switch bariatric surgery were evaluated, specifically to investigate if changes preceded gain of insulin sensitivity.ResultsPre-operative plasma Omentin was not different between men (n¿=¿18) vs women (n¿=¿48), or diabetic status but correlated with body mass index (BMI). Altogether, Omentin increased as early as 24-h post-surgery, with changes maintained up to 1-year. Fifty-nine percent of subjects increased Omentin >10% by 24-H following surgery (OmentinINC p¿<¿0.0001), while 18% of subjects decreased (OmentinDEC p¿<¿0.0001), with changes maintained throughout one-year. These two groups had comparable age, sex distribution, diabetes, BMI, waist circumference and fat mass, however OmentinDEC had elevated levels of cardiovascular risk markers; homocysteine (p¿=¿0.019), NT-proBNP (p¿=¿0.006) and total bilirubin (p¿=¿0.0001) while red blood cell (RBC) count was lower (p¿=¿0.0005) over the one-year period. Omentin levels at 1-DAY also correlated with immune parameters (white blood cell count, % neutrophil, % monocytes, % lymphocytes).ConclusionOmentinDEC at 1 day following surgery may be a marker of cardiovascular ¿at-risk¿ group before weight loss or insulin sensitivity restoration.
- Haematological and biochemical reference intervals for free-ranging brown bears ( [JOURNAL ARTICLE]
- BMC Vet Res 2014 Aug 21; 10(1):183.
BackgroundEstablishment of haematological and biochemical reference intervals is important to assess health of animals on individual and population level. Reference intervals for 13 haematological and 34 biochemical variables were established based on 88 apparently healthy free-ranging brown bears (39 males and 49 females) in Sweden. The animals were chemically immobilised by darting from a helicopter with a combination of medetomidine, tiletamine and zolazepam in April and May 2006¿2012 in the county of Dalarna, Sweden. Venous blood samples were collected during anaesthesia for radio collaring and marking for ecological studies. For each of the variables, the reference interval was described based on the 95% confidence interval, and differences due to host characteristics sex and age were included if detected. To our knowledge, this is the first report of reference intervals for free-ranging brown bears in Sweden.ResultsThe following variables were not affected by host characteristics: red blood cell, white blood cell, monocyte and platelet count, alanine transaminase, amylase, bilirubin, free fatty acids, glucose, calcium, chloride, potassium, and cortisol. Age differences were seen for the majority of the haematological variables, whereas sex influenced only mean corpuscular haemoglobin concentration, aspartate aminotransferase, lipase, lactate dehydrogenase, β-globulin, bile acids, triglycerides and sodium.ConclusionsThe biochemical and haematological reference intervals provided and the differences due to host factors age and gender can be useful for evaluation of health status in free-ranging European brown bears.
- The usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis. [JOURNAL ARTICLE]
- Indian J Gastroenterol 2014 Aug 21.
Liver stiffness measurement (LSM) is used for the assessment of liver fibrosis. However, there is limited data in Indian patients.The aim of this study was to find the correlation of LSM, aspartate transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver biopsy (LB), and predictors of discordance between LB and LSM.One hundred and eighty-five consecutive patients who underwent liver biopsy and transient elastography (TE) were enrolled. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) was used to evaluate the accuracy of transient elastography and APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4).Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was unsuccessful in ten patients (5 %) because of small intercostal space (n = 3) and obesity (n = 7). Fibrosis is significantly correlated with LSM (r = 0.901, p = 0.001) and APRI (r = 0.736, p = 0.001). There was a significant difference in median LSM value in patients with no fibrosis (F0) in comparison to patients having mild fibrosis [mild portal fibrosis (F1) + fibrosis with few septa (F2)] (4.5 vs. 7.5 kPa, p = 0.001) and advanced fibrosis [bridging fibrosis that is spreading and connecting to other areas that contain fibrosis (F3) + cirrhosis or advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p = 0.001). Similarly, there was a significant difference in mean APRI value in patients with F0 in comparison to patients having mild fibrosis (F1 + F2) (0.55 ± 0.31 vs. 1.09 ± 0.81, p = 0.001) and advanced fibrosis (F3 + F4) (2.3 ± 1.3, p = 0.001). AUROC for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI) 0.963-0.999) for TE and 0.865 (95 % CI 0.810-0.920) for APRI. Optimal TE value was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively. On multivariate analysis, total bilirubin and histological activity index (HAI) were identified as an independent predictor of TE inaccuracy.LSM is a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of discordance between LB and LSM.
- Importance of branched-chain amino acids in patients with liver cirrhosis and advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy. [JOURNAL ARTICLE]
- Cancer Chemother Pharmacol 2014 Aug 20.
The aim of this retrospective cohort study was to clarify the effect of a branched-chain amino acids (BCAA) on the liver function and the prognosis of Child-Pugh class (C-P) A and B liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) undergoing hepatic arterial infusion chemotherapy (HAIC).Ninety-two adult Japanese patients with LC and aHCC underwent HAIC. They were in C-P A or B, and they showed multiple partial responses or stable disease. We excluded 11 patients classified as C-P C and 47 patients who showed no response. The patients were divided into an HAIC group receiving HAIC alone (n = 43) and a BCAA group treated with HAIC plus BCAA (n = 49). HAIC was delivered via the proper hepatic artery. The BCAA group also received oral administration of BCAA.In the BCAA group, serum albumin increased significantly after HAIC, while there were no significant changes in serum total bilirubin, serum aminotransferases, prothrombin time, ascites, and hepatic encephalopathy. The C-P score decreased significantly after HAIC compared with before HAIC in C-P B patients, although there was no significant change in C-P A patients. Survival of the BCAA group was significantly longer than that of the HAIC group, with the median survival time being 426 versus 272 days for C-P B patients, although there was no significant difference for C-P A patients.Branched-chain amino acids might improve the survival and C-P score by increasing serum albumin in C-P B patients with aHCC receiving HAIC.
- Treatment of pegylated-interferon alfa-2a in chronic hepatitis B patients demonstrating a spontaneous decline in HBV DNA after acute exacerbation. [JOURNAL ARTICLE]
- Antivir Ther 2014 Aug 20.
Acute exacerbation (AE) in chronic hepatitis B (CHB) is usually followed by a spontaneous decline in HBV-DNA levels. The subsequent treatment is controversial. In this study, we evaluated the efficacy and safety of pegylated-interferon alfa-2a (PEG-IFNα2a) for such CHB patients.Seventy-four HBeAg-positive patients with a spontaneous HBV-DNA decline (by >2 log(10) IU•mL(-1), compared to baseline levels before antiviral treatment) after AE (alanine aminotransferase ALT: 10-30-fold the upper limit of normal ULN, total bilirubin TBIL: 2-20 mg•mL(-1), prothrombin time activity >60%) were included. Twenty-two patients (group A) received PEG-IFNα2a treatment (180 µg•kg(-1)•week(-1), when ALT was <10ULN and TBIL <2 mg•mL(-1)) for 48 weeks, with 48 weeks of treatment-free follow-up. Twenty-one patients (group B) selected continual entecavir therapy. Thirty-one patients (group C, control group) received routine liver-protective drugs.At week 96, virological response rates were 90.5%, 100%, and 48%, and ALT normalization rates were 81%, 95%, and 40% for groups A, B, and C, respectively. HBeAg seroconversion rates were 71.4%, 45%, and 32% in groups A, B, and C, respectively. A high HBsAg loss rate was observed in PEG-IFNα2a-treated patients, while no entecavir-treated patients achieved HBsAg loss. Group A patients suffered from typical pegylated-interferon therapy-related adverse events. No severe adverse event was observed in any groups.PEG-IFNα2a is effective and safe for treating CHB patients demonstrating a spontaneous decline in HBV DNA after AE, and yields an increased likelihood of HBsAg loss.