Search

Hepatic Fibrosis, the progressive deposition of collagen in the extracellular matrix of the liver, is a fundamental alteration of liver parenchyma in many chronic liver diseases. It impairs liver function, may lead to cirrhosis and hepatocellular carcinoma, and constitutes an important cause of morbidity, mortality, and health care costs (1–4). Early diagnosis is important to initiate treatment and halt progression. Biopsy is the current gold standard for diagnosis, but it is expensive and invasive—factors that limit utility in longitudinal assessments (5–16). The limitations of biopsy for longitudinal assessment have impeded progress in clinical care and research of diffuse liver diseases associated with hepatic fibrosis. There is a need to develop noninvasive imaging techniques that can safely diagnose fibrosis. Conventional ultrasound, computed tomography, and magnetic resonance imaging (MRI) can assess gross liver morphology, or contour, to confirm cirrhosis in patients with advanced liver disease, but such an assessment is insensitive to the early stages of fibrosis and cirrhosis (6,17–19). An alternative imaging-based approach to evaluate hepatic fibrosis is to assess internal liver architecture, or texture. Texture can be defined as a complex visual pattern within an image that consists of simpler subpatterns with characteristic features (20). These features can be assessed objectively by quantitative texture analysis (TA). Quantitative TA has been used to noninvasively classify the liver in a dichotomous fashion as normal or cirrhotic on unenhanced MR images (21,22). In a study with 13 healthy volunteers and 5 cirrhotic patients, quantitative TA of high spatial resolution T2-weighted images provided 100% sensitivity and specificity for discrimination between normal volunteers and cirrhotic patients (21). In another study of 43 cirrhotic patients and 10 normal volunteers, quantitative TA on unenhanced T2-weighted MR images classified patients as cirrhotic or normal with a misclassification rate of 8% (22). Both studies used a publicly available, free software program (MaZda, v. 3.20, Instytut Elektroniki Politechnika, Lodza, Poland) to compute TA parameters from liver images and to generate multivariate predictive models from the parameters (23–25). Because double contrast-enhanced MRI shows fibrosis with greater clarity than unenhanced imaging (26–30), we hypothesized that quantitative TA of double contrast-enhanced MRI may permit accurate dichotomous classification of fibrosis in clinical patients with a spectrum of fibrosis severity, not just discrimination between healthy volunteers versus patients with cirrhosis. The purpose of this pilot, retrospective study was to demonstrate proof of concept that noninvasive quantitative TA on double contrast-enhanced MR liver images can classify liver fibrosis dichotomously in clinical patients, using histology as the reference standard. We used the same software program used in prior studies (MaZda) to compute TA parameters and applied statistical techniques to develop classification models based on the TA parameters.

Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-alpha and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support.

Objectives Hyperamylasemia (HA) is often reported in patients with acute liver failure (ALF). Direct toxic effects of acetaminophen on the pancreas have been postulated, but the occurrence of HA in other etiologies raises the question of whether multiorgan failure is part of the pathogenesis of HA in this setting. Our main aim was to describe and analyze the incidence, clinical characteristics, and outcomes of HA in ALF of different etiologies. Methods Patients enrolled in the Acute Liver Failure Study Group registry with an admission amylase value available were included. For the purpose of this analysis, HA was defined as > or =3x upper limits of normal. Patients were classified as having acetaminophen (APAP)- or non-APAP-induced ALF, and by amylase group: normal ( 345). Significant variables identified by univariate analysis were added to a multiple linear regression model. The primary outcome was overall survival. Results In total, 622 eligible patients were identified in the database, including 287 (46%) with APAP-induced ALF; 76 (12%) patients met the criteria for HA. Among patients with HA, 7 (9%) had documented clinical pancreatitis. The incidence of HA was similar among APAP (13%) and non-APAP (12%) patients. Although HA was associated with renal failure and greater Model for End-stage Liver Disease scores for both groups, HA was not an independent predictor of mortality in multivariate analysis. Conclusions Although not an independent predictor of mortality, HA in ALF was present in all etiologies and was associated with diminished overall survival. HA appeared to be related to renal dysfunction in both groups and multiorgan failure in non-APAP ALF.

Although clinicians recognize the importance of adherence to HCV therapy, little research has been conducted to determine actual adherence rates or predictors of adherence in this population. Adherence is a challenge in the HCV-infected individual because of the complexities of the drug regimen, side effects from the medication, frequency of clinical monitoring, variable response to therapy, and potential complications. However, because of the time-limited nature of the current medication therapies, multidisciplinary and multifactoral interventional strategies may be designed to positively influence adherence rates and, ultimately, treatment outcomes in this patient population.

In this study, we investigated the use of ion exchange processes using a chelating resin, Diaion CRB02 for the removal of boron from the bittern solution left after the extraction of sodium sulfate and sodium chloride from the water of Lake Qarun, located in Egypt. The effects of parameters such as the initial boron concentration and the pH value on the breakthrough volume were studied using boric acid as the synthetic simulant of the bittern solution. The breakthrough capacity was shown to be directly proportional to the height of the resin bed and inversely proportional to the initial boron concentration and the feed flow rate. In addition, the optimum pH for boron removal was found to be 10. An electrically assisted process, which had been found to be effective for a strongly acidic cation exchange resin, was also applied to the ion exchange by taking the electric current as a parameter. However, no remarkable effect was observed, which may result from the difference in the function group between an ion exchange resin using electrostatic attractive force and a chelating resin using complex formation.

© 2014, Journal of NeuroVirology, Inc. Treatment of hepatitis C virus (HCV) with pegylated interferon and ribavirin (IFN/RBV) can be associated with neuropsychiatric side effects, which may necessitate dose reductions or treatment discontinuation. This study aimed to characterize the time course and predictors of cognitive and affective/mood symptoms after IFN/RBV treatment initiation. Forty individuals enrolled in a longitudinal project underwent comprehensive cognitive, medical, and psychiatric assessment at baseline and 10 weeks, 6 months, 12 months, and 18 months after treatment initiation. Analyses were conducted to determine the prevalence of neurocognitive impairment over time; explicate the relationship between neurocognitive impairment, neuropsychiatric symptoms, and liver disease at each time point; and identify predictors of neurocognitive decline as well as cognitive effects of viral clearance. By 10 weeks after initiating IFN/RBV, the prevalence of neurocognitive impairment rose from 22.5 to 47.4 % (p < 0.05). Infection with genotype 1 and premorbid depression were associated with more severe declines (p < 0.05). After 18 months, 42.5 % remained neurocognitively impaired, independent of viral clearance, severity of liver disease, and current depressive symptoms. Undetectable viral load was not associated with improvement 18 months after initiating treatment (p > 0.10). Results of the current study indicate that IFN/RBV treatment-emergent neurocognitive declines are significant, prevalent, and may persist long after treatment cessation. Clinicians should monitor cognition throughout the course of treatment for HCV, noting that early declines may indicate individuals at elevated risk for persistent neurocognitive impairment. Longer-term studies are needed to determine whether lasting declines may remit over longer intervals or with newer direct acting agents.

Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp 2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. In conclusion, conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.

Serum concentrations of the actin scavenger Gc-globulin may provide prognostic information in acute liver failure (ALF). The fraction of Gc-globulin not bound to actin is postulated to represent a better marker than total Gc-globulin but has been difficult to measure. We tested a new rapid assay for actin-free Gc-globulin to determine its prognostic value when compared with the King's College Hospital (KCH) criteria in a large number of patients with ALF. A total of 252 patients with varying etiologies from the U.S. ALF Study Group registry were included; the first 178 patients constituted the learning set, and the last 74 patients served as the validation set. Actin-free Gc-globulin was determined with a commercial enzyme-linked immunosorbent assay kit. The median (range) actin-free Gc-globulin level at admission for the learning set was significantly reduced compared with controls (47 [0-183] mg/L vs. 204 [101-365] mg/L, respectively, P < 0.001). Gc-globulin levels were significantly higher in spontaneous survivors than in patients who died or were transplanted (53 [0-129] mg/L vs. 37 [0-183] mg/L, P = 0.002). A receiver operating characteristic curve analysis showed that a 40 mg/L cutoff level carried the best prognostic information, yielding positive and negative predictive values of 68% and 67%, respectively, in the validation set. The corresponding figures for the KCH criteria were 72% and 64%. A new enzyme-linked immunosorbent assay for actin-free Gc-globulin provides the same (but not optimal) prognostic information as KCH criteria in a single measurement at admission.

Effects of the combination of PEG-interferon alpha-2B and ribavirin on the inflammation and fibrosis scores of patients with chronic hepatitis C infection who were virologic non-responders to interferon alpha-2B and ribavirin