SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Cirrhosis

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Non-alcoholic steatohepatitis (NASH) represents a risk factor for the development of hepatocellular carcinoma (HCC) and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice). Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD)-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h) increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.

Concepts: Triglyceride, Cancer, Fatty acid, Cirrhosis, Fat, Nutrition, Glycerol, Cholesterol

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Evaluation of fibrosis is crucial in the assessment of chronic hepatitis C (CHC). The enhanced liver fibrosis (ELF) is a serological panel including hyaluronic acid (HA), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), and amino-terminal propeptide of type III procollagen (PIIINP) that has shown good results in predicting liver fibrosis in distinct scenarios of chronic liver diseases.

Concepts: Bilirubin, Hepatocellular carcinoma, Alcoholic liver disease, Hepatitis A, Hepatitis B, Hepatitis, Hepatitis C, Cirrhosis

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Abstract Background: Recurrence of hepatitis C virus (HCV) infection after liver transplantation is inevitable and decreases survival. Graft loss due to recurrent HCV occurs in 25% to 30% of patients. The recommended AASLD treatment is PEG-IFN, with or without ribavirin, but some patients might be not eligible for this treatment. An alternative antiviral agent is silibinin (SIL). In vitro silibinin stops replication, probably by inhibiting HCV RNA polymerase. Case Report: We present the cases of 2 patients with severe recurrent HCV infection who received intravenous silibinin (IV SIL) as a “rescue therapy”. In the first patient with cholestatic fibrosing hepatitis, HCV RNA became undetectable. We also noted significant viremia reduction, and improvement in laboratory results and clinical presentation in the second patient. Conclusions: Administration of IV SIL resulted in a rapid decrease of HCV viremia. In post-transplant patients with HCV recurrence who are not eligible for standard antiviral treatment, IV SIL can be considered as an alternative, but further investigations are necessary to establish treatment protocols.

Concepts: Hepatology, Hepatocellular carcinoma, Liver, Organ transplant, Cirrhosis, Hepatitis C virus, Virus, Hepatitis C

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Rifaximin is a non-absorbable antibiotic used to prevent relapses of hepatic encephalopathy which may also be a candidate for prophylaxis of spontaneous bacterial peritonitis (SBP).

Concepts: Hepatorenal syndrome, Hepatic portal vein, Liver, Gastroenterology, Ascites, Cirrhosis, Spontaneous bacterial peritonitis, Hepatic encephalopathy

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Over the last decade, metabolomics has evolved into a mainstream enterprise utilized by many laboratories globally. Like other “omics” data, metabolomics data has the characteristics of a smaller sample size compared to the number of features evaluated. Thus the selection of an optimal subset of features with a supervised classifier is imperative. We extended an existing feature selection algorithm, threshold gradient descent regularization (TGDR), to handle multi-class classification of “omics” data, and proposed two such extensions referred to as multi-TGDR. Both multi-TGDR frameworks were used to analyze a metabolomics dataset that compares the metabolic profiles of hepatocellular carcinoma (HCC) infected with hepatitis B (HBV) or C virus (HCV) with that of cirrhosis induced by HBV/HCV infection; the goal was to improve early-stage diagnosis of HCC.

Concepts: Metabolism, Interferon, Machine learning, Hepatocellular carcinoma, Hepatitis, Cirrhosis, Hepatitis B, Hepatitis C

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Aggressive recurrence of hepatitis C remains problematic post OLT. There are limited data on treatment of HCV infection with telaprevir/boceprevir therapy with peginterferon/ribavirin (PR) post OLT. AIM To review our experience with telaprevir addition to peginterferon/ribavirin in treatment of aggressive hepatitis C in null responders to PR post OLT. Methods: Adult patients with recurrent HCV infection post OLT with null response to peginterferon/ribavirin for 12 weeks (< 2 log reduction) received 4 week lead-in PEG-IFN alfa-2b (1.0 μg/kg/wk) plus RBV (600-1000 mg/day) followed by addition of telaprevir 750 q8. All patients were converted to cyclosporine from tacrolimus. Results: Seven patients (3 M, 4 F), mean age 56 years, were treated. 3 were < 1 year post-OLT, 6 had cirrhosis/1 bridging fibrosis. Three of 7 achieved SVR. All patients required RBV dose reduction, 6/7 required EPO, 5/7 required filgrastim, 2/7 required eltrombopog for platelets <20,000 μl. There were no supra/sub-therapeutic CYA levels encountered, no episodes of renal insufficiency. Conclusions. Conversion to cyclosporine followed by four week peginterferon/ribavirin lead-in with addition of telaprevir can lead to significant clearance rates at week 24 in null responders with advanced fibrosis though high rates of anemia/RBV dose reduction, growth factor, and transfusion requirements were noted. This article is protected by copyright. All rights reserved.

Concepts: All rights reserved, Immune system, Copyright, Hepatocellular carcinoma, Organ transplant, Hepatitis C, Liver, Cirrhosis

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Abstract Background: Accurate prediction of prognosis for cancer patients is important for good clinical decision making in therapeutic and care strategies. The application of prognostic tools and indicators could improve prediction accuracy. Objective: This study aimed to develop a new prognostic scale to predict survival time of advanced cancer patients in China. Methods: We prospectively collected items that we anticipated might influence survival time of advanced cancer patients. Participants were recruited from 12 hospitals in Shanghai, China. We collected data including demographic information, clinical symptoms and signs, and biochemical test results. Log-rank tests, Cox regression, and linear regression were performed to develop a prognostic scale. Results: Three hundred twenty patients with advanced cancer were recruited. Fourteen prognostic factors were included in the prognostic scale: Karnofsky Performance Scale (KPS) score, pain, ascites, hydrothorax, edema, delirium, cachexia, white blood cell (WBC) count, hemoglobin, sodium, total bilirubin, direct bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (ALP) values. The score was calculated by summing the partial scores, ranging from 0 to 30. When using the cutoff points of 7-day, 30-day, 90-day, and 180-day survival time, the scores were calculated as 12, 10, 8, and 6, respectively. Conclusions: We propose a new prognostic scale including KPS, pain, ascites, hydrothorax, edema, delirium, cachexia, WBC count, hemoglobin, sodium, total bilirubin, direct bilirubin, AST, and ALP values, which may help guide physicians in predicting the likely survival time of cancer patients more accurately. More studies are needed to validate this scale in the future.

Concepts: Chemical pathology, Liver, Cirrhosis, Forecasting, Future, Red blood cell, Regression analysis, Liver function tests

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Total tumor volume (TTV), as a better predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, has been explored by our center. Some tumors are not spherical, and calculating their TTV based on one dimension only may overestimate their volume and exclude them from candidacy for transplantation. So, we aimed to study the actual tumor volume (ATV) calculated using the ellipsoid formula and assess its impact on recurrence. HCC patients transplanted between 1990 and 2010 at University of Alberta Hospital were analyzed. Tumor volumes were calculated using both formulas: [(4/3) r(3) ] (r=max. radius) & [(4/3) abc] (a,b,c = the 3 radiuses). A total of 115 patients were included with a mean follow up of 4.99 4.23 years. Five-year recurrence free survival was 79.8%. Univariate analysis for predictors of recurrence included: maximum tumor diameter, ATV, TTV, and AFP400ng/ml. Multivariate analysis showed that ATV & AFP 400 ng/ml were the only predictors of recurrence. Combining both variables provide better predication of recurrence with accuracy that exceeds 80%. Three-dimensional calculation of tumor volume is of critical importance for a small group of patients with ellipsoid tumors where volumes are overestimated with the spheroidal formula and could lead to inappropriate exclusion from transplant. This article is protected by copyright. All rights reserved.

Concepts: Dimension, Liver transplantation, Formula, Cirrhosis, Organ transplant, Sphere, Cancer, Volume

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Although cardiovascular disease is thouht to be common in cirrhosis, there are no systematic investigations on the prevalence of electrocardiographic (ECG) abnormalities in these patients and data on the occurrence of post-transplant cardiac events in comparison with the general population are lacking. We aimed to study the prevalence and predictors of ECG abnormalities in patients with cirrhosis undergoing liver transplantation and to define the risk of cardiac events post-transplant compared to the general population.

Concepts: Hepatic portal vein, Hepatology, Bilirubin, Hepatocellular carcinoma, Disease, Liver transplantation, Liver, Cirrhosis

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Hepatic hemangioma patients with Kasabach-Merritt syndrome have reportedly been cured by liver transplantation. However, liver transplantation as a potential cure for a stable patient without Kasabach-Merritt syndrome remains debatable. We report the case of a 27-year-old female patient with a giant hepatic hemangioma. The hemangioma measured 50 x 40 x 25 cm in size and weighed 15 kg, which is the largest and heaviest hemangioma reported in the literature. The patient showed jaundice, ascites, anemia, and appetite loss; but no disseminated intravascular coagulation was observed through laboratory findings. We successfully operated using a right lobe graft without the middle hepatic vein from a 55-year-old donor. At the long-term follow-up, the patient experienced two acute rejections, which were confirmed by biopsy. However, the patient still survives with good graft function after 50 months.

Concepts: Hemoglobin, Patient, Cancer, Hepatic vein, Cirrhosis, Hepatic portal vein, Disseminated intravascular coagulation, Liver