SciCombinator

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Concept: Cirrhosis

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Since little is known about the prevalence of and factors associated with liver fibrosis in the general population, we aimed to investigate this in a large, well-characterized cohort, by means of transient elastography (TE). This study was part of the Rotterdam Study, a population-based study among individuals ≥45 years. All participants underwent abdominal ultrasound and TE. Liver stiffness measurement (LSM) ≥8.0 kPa was used as cut-off suggesting clinically relevant fibrosis. Of 3041 participants (age 66.0±7.6 years) with reliable LSM, 169 (5.6%) participants had LSM ≥8.0 kPa. Age (OR 2.40, 95%CI 1.72-3.36,p<0.001), ALT (OR 1.24, 95%CI 1.12-1.38,p<0.001), smoking (OR 1.77, 95%CI 1.16-2.70, p=0.008), spleen size (OR 1.23, 95%CI 1.09-1.40,p=0.001), HBsAg or anti-HCV positivity (OR 5.38, 95%CI 1.60-18.0,p=0.006), and combined presence of diabetes mellitus (DM) and steatosis (OR 5.20, 95%CI 3.01-8.98, p<0.001 for combined presence) were associated with LSM ≥ 8.0 kPa in multivariable analyses. The adjusted predicted probability of LSM ≥8.0 kPa increased per age decade, with probabilities ranging from 1.4% (0.9-3.6) in participants aged 50-60 years to 9.9% (6.8-14.5) in participants >80 years. Participants with both DM and steatosis had the highest probabilities of LSM ≥8.0 kPa (overall probability 17.2% (12.5-23.4), this probability did not increase with age (p=0.8).

Concepts: Insulin, Diabetes mellitus, Glucose, Cirrhosis, Cystic fibrosis, Ageing, Spleen, Blaise Pascal

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& Aims: Interferon-free treatment options are rapidly evolving for patients with chronic hepatitis C virus (HCV) genotype 1b (GT1b) infection with cirrhosis and for nonresponders to prior pegylated interferon and ribavirin therapy. We performed a phase 2b, open-label trial of the combination of ombitasvir (a NS5A replication complex inhibitor), paritaprevir, and ritonavir (an NS3/4A protease inhibitor)-an interferon- and ribavirin-free regimen-in difficult-to-treat patients, including prior null responders and patients with cirrhosis.

Concepts: Virus, Cirrhosis, Hepatitis, Hepatocellular carcinoma, Interferon, Hepatitis C, Ribavirin, Hepatitis B

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Most hepatocellular carcinoma (HCC) patients have complications, including cirrhosis and malnutrition. The efficacy of dietary supplementation with oral branched-chain amino acids (BCAAs) in HCC patients undergoing interventions has not been confirmed. Relevant publications on the efficacy and safety of oral BCAA supplementation for HCC patients undergoing anti-HCC interventions through September, 2014 were searched for identification in the PubMed, Embase, Web of Science, and the Cochrane Library databases. The pooled risk ratio (RR) and standardized mean difference (SMD) were used to assess the supplementation effects. A total of 11 eligible studies (974 patients in total) were evaluated and included in our analysis. Oral BCAA supplementation helped to maintain liver reserve with higher serum albumin (SMD = 0.234, 95 % CI: 0.033-0.435, P = 0.022), and lower rates of ascites (RR = 0.545, 95 % CI: 0.316-0.938, P = 0.029) and edema (RR = 0.494, 95 % CI: 0.257-0.952, P = 0.035) than in the control group. BCAA supplementation seemed to be effective in improving mortality, especially in Child-Pugh class B patients, but the efficacy was not confirmed. Apparent effects were not found in improving HCC recurrence, total bilirubin, ALT, or AST. BCAA supplementation was relatively safe without serious adverse events. BCAA supplementation may be clinically applied in improving liver functional reserve for HCC patients and further improving the quality of life.

Concepts: Acid, Ammonia, Cirrhosis, Liver, Branched-chain amino acids

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During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that’s constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing strategies and economies of scale.

Concepts: Cancer, Cirrhosis, Liver, Hepatology, Organ transplant, Liver transplantation, Liver dialysis, Projection

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Autoimmune hepatitis (AIH) is a chronic inflammatory disease characterised by a loss of tolerance towards the hepatocellular epithelium. Liver transplantation (LT) represents the ultimate therapeutic option for a fulminant course or end stage liver disease. The aim of this study was to elucidate the clinical, serological and genetic features on remission, relapse, overall and LT-free survival.

Concepts: Medicine, Epidemiology, Death, Medical terms, Cirrhosis, Gastroenterology, Debut albums

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Several animal studies have shown that statins can inhibit the progression of cirrhosis; however, few clinical studies have been conducted. Previous study has indicated that statins can prevent the progression of hepatic fibrosis in patients with hepatitis C virus (HCV) infection and advanced hepatic fibrosis but data for human not progress to cirrhosis yet is lacking. This study investigated the association between the use of statin and the risk of cirrhosis development in patients with HCV infection.

Concepts: Cirrhosis, Hepatitis C

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Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem and thus discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great clinical significance. For NASH diagnosis, liver biopsy-proven histological examination is the current gold standard, and noninvasive and reliable biomarkers are greatly needed. Recently, we found two glycobiomarkers, fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac2bp), are useful independently for NASH diagnosis. In this study, we confirmed that serum Fuc-Hpt is suitable for the prediction of ballooning hepatocytes and that serum Mac2bp is suitable for the prediction of liver fibrosis severity in 124 biopsy-proven NAFLD patients (training cohort). In addition, we found the combination of serum Fuc-Hpt and Mac2bp levels was an excellent tool for NASH diagnosis. Using receiver operating characteristic (ROC) analyses, area under the ROC curve (AUROC), sensitivity, and specificity of these two glycobiomarker combination was 0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH diagnosis via logistic regression analysis as: Logit (p) = -2.700 + 0.00242 × Fuc-Hpt + 1.225 × Mac2bp. To validate the prediction model, another 382 biopsy-proven NAFLD patients were enrolled (validation cohort). In the validation cohort, the AUROC of this model for NASH diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity, respectively. In addition, we investigated the significance of our developed NASH diagnosis model in ultrasound-diagnosed NAFLD subjects who received medical health check-ups (n=803). Our model also could predict NAFLD disease severity in this larger population.

Concepts: Regression analysis, Cirrhosis, Hepatitis, Receiver operating characteristic, Non-alcoholic fatty liver disease, Fatty liver, Binary classification, Biostatistics

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The relative contributions of inflammatory signalling and sequential oncogenic dysregulation driving liver cancer pathogenesis remain incompletely understood. Lymphotoxin-β receptor (LTβR) signalling is critically involved in hepatitis and liver tumorigenesis. Therefore, we explored the interdependence of inflammatory lymphotoxin signalling and specific oncogenic pathways in the progression of hepatic cancer.

Concepts: Cancer, Oncology, Cirrhosis, Liver, Hepatocellular carcinoma, Hepatitis C, Hepatitis B, Liver transplantation

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The number of persons with chronic hepatitis B virus (HBV) infection in the United States is affected by diminishing numbers of young persons who are susceptible because of universal infant vaccination since 1991, offset by numbers of HBV-infected persons migrating to the United States from endemic countries.

Concepts: United States, Cirrhosis, Hepatitis, Milk, Hepatitis C, Hepatitis B, Hepatitis A

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The epidemiology of the incidence of sexually transmitted hepatitis C virus (HCV) infection in HIV-positive MSM is only partially understood. In the presence of HIV, HCV infection is more likely to become chronic and liver fibrosis progression is accelerated.

Concepts: AIDS, Epidemiology, Infectious disease, Cirrhosis, Hepatitis C, Cytomegalovirus, Sexually transmitted disease, Blood donation