June 5, 2013

Fibroscan (ultra-sound hepatic elastography) Review

Provided by NATAP

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Noninvasive assessment of liver fibrosis (and Biopsy)
Hepatology
June 2011

"The use of FibroTest or TE or MRE imaging will be helpful if evidence for cirrhosis or minimal to no fibrosis is predicted by these tests." http://www.natap.org/2011/HCV/061311_02.htm

Ultrasound-based Hepatic Elastography Origins, Limitations, and Applications

Journal of Clinical Gastroenterology October 2010
CLINICAL REVIEW

Eric B. Cohen, MD* and Nezam H. Afdhal, MD

*Yale University School of Medicine, Department of Digestive Diseases Liver Center, Beth Israel Deaconess Medical Center

"In conclusion, there is an urgent need for noninvasive markers to quantify liver fibrosis. Hepatic elastography is a novel tool that exploits the correlation between liver stiffness and liver fibrosis. It is excellent at making the diagnosis of cirrhosis and at excluding fibrosis87; it is not able to discriminate between the intermediate stages of fibrosis. Several intrahepatic processes confound the accuracy of HE to gauge fibrosis, and it remains to be seen how these processes will influence future research efforts. It is conceivable that instead of absolute cutoffs, a range of values will be used for diagnosis. HE can be helpful for treatment and management decisions.2,82,88 The era of HE used as the evaluator of the natural history of disease, both pretransplant and posttransplant, is now underway. More studies are necessary to delineate the most appropriate clinical scenarios for this useful new tool."

"The original manuscript published by Sandrin et al in 2003 evaluated a cohort of chronic hepatitis C patients, all with abnormal aminotransferase levels.

Importantly, liver stiffness correlated well at both F0 and F4 stages of fibrosis. Perhaps not surprisingly, there was poor discriminatory ability between metavir F1 and F2 stages of fibrosis (Fig. 2). These observations mirror the diagnostic ability of other, noninvasive markers of fibrosis, namely serologic panels. It is unclear what accounts for the overlap within intermediate stages, although it suggests that our current staging system is an oversimplified representation of a more fluid spectrum of disease."

"In general, transient elastography is as good as the serologic markers (Fibrotest, Lok Index, APRI, Prothrombin index, AST/ALT ratio, and platelet count) to diagnose the earlier stages of fibrosis (31). Elastography has superior accuracy in the detection of cirrhosis, with an AUROC of 0.96, versus the serologic markers (AUROC from 0.61 to 0.82) (31). A separate study found that combining HE with a serologic marker of fibrosis, such as APRI, significantly enhanced the prediction of fibrosis stage. However, combinations of 3 or 4 tests led to redundancy and increased cost.22.....

.....With respect to liver biopsy, HE correlates very well with established cirrhosis. Although considered the gold standard, biopsy is susceptible to understaging, and there is the potential for a correlative discrepancy when elastography is suggestive of cirrhosis. The quality of the biopsy is therefore important, and fortunately, most studies incorporate the quality of the tissue sample."

Abstract: A reliable, noninvasive marker to help clinicians evaluate hepatic fibrosis is urgently needed. The liver biopsy, an imperfect gold standard, has recognized limitations including sampling error and interobserver variability. Hepatic elastography (HE) is a novel sonographic method for assessing liver stiffness and has excellent accuracy in making the diagnosis of minimal fibrosis and cirrhosis. Several conditions intrinsic to the pathology of the liver compromise the positive predictive value of HE for fibrosis alone including acute hepatitis, obstructive cholestasis, and passive congestion. Technical considerations that hinder the performance of elastography include an advanced body mass index, the presence of ascites and narrow intercostal spaces. Despite these limitations, elastography has a role in staging fibrosis, prognosis of disease outcome, surveillance, and treatment decisions. HE is now being used in lieu of liver biopsy to investigate the natural history of chronic liver diseases. Additional studies are required to better define the appropriate role of HE in clinical practice.

Liver fibrogenesis is the wound-healing response and "final" pathway of chronic liver disease.1 Accurate staging of fibrosis is valuable for prognosis, treatment decisions, and surveillance of disease progression or regression.2,3 Liver biopsy, currently the gold standard4 has several recognized limitations including sampling error and interobserver variability in interpretation and staging.5 Furthermore, the dynamic process of fibrosis resulting from progression and regression is difficult to capture with biopsy alone.6 The hepatology community is actively researching noninvasive methods of fibrosis quantification.

Hepatic elastography (HE), which uses the novel method of transient elastography (TE), has been extensively evaluated in many different forms of liver disease as a tool to measure liver stiffness as a surrogate for fibrosis. However, as it is not widely available in the United States and is awaiting FDA approval, there is considerable uncertainty about elastometry's niche within the day-to-day practice of hepatology.7 Perhaps the most critical question for clinicians, as multiple methods develop for the evaluation of fibrosis, is how to cost effectively and safely incorporate this multimodality approach into clinical care. The aim of this review is 3-fold: (1) to provide background that sets the stage for the emergence of HE as a leading noninvasive marker candidate, (2) to identify the strengths and weaknesses of HE, and (3) to describe how it is being applied to the clinical and research setting.

A NEED FOR NONINVASIVENESS

Our understanding of liver fibrogenesis has led to new insights that liver fibrosis is not a relentless and progressive condition. Gone is the dogma of fibrosis following a single, common pathway. New insights dictate that clinically significant histologic improvement can occur even in a cirrhotic liver.8 Pathways favoring fibrogenesis include stellate cell activation, the process of epithelial-to-mesenchymal transition (EMT) of hepatocytes and cholangiocytes, activation of resident portal fibroblasts and bone marrow-derived fibrocytes.9 There is additional variability within pathways, with the composition of extracellular matrix (ECM) changing over time. At the earliest stages of fibrogenesis, elements such as collagen-type IV, heparin-sulfate proteoglycans, and laminin predominate, whereas the ECM of more established fibrosis is dominated by fibril forming collagens type I and III.9 There is, however, a definite inability to accurately measure fibrogenesis and fibrosis regression in vivo using any of our currently available technologies. To really look at these dynamic changes, we will probably need to advance molecular imaging of the cells involved in liver fibrosis and regression. Thus it is essential to have an accurate method to quantify the amount of fibrosis regardless of stage, underlying pathway or disease etiology. To this end liver biopsy has been the clinician and investigator's gold standard for decades. Beyond its diagnostic capability, liver biopsy is an invaluable tool for clinical prognostication as it relates to the stage of fibrosis. For a clinician, defining the stage of liver fibrosis provides a general estimation of disease chronicity and severity. Clinically relevant outcomes in liver disease are often a result of advanced fibrosis or cirrhosis, with eventual development of portal hypertension and hepatocellular carcinoma. In fact, septal thickness and small nodularity are 2 histologic features independently predictive of clinically significant portal hypertension (HVPG ≥10).10 In addition, HCC occurs primarily in the setting of cirrhosis and one can argue that the major role of biopsy is in diagnosing or excluding advanced fibrosis and cirrhosis so that appropriate screening can be undertaken.

In addition, the fibrosis stage has been used to determine the relative urgency for disease treatment, especially with highly prevalent, indolent conditions such as hepatitis C virus infection and nonalcoholic steatohepatitis. Valid recognition of the extreme ends of the fibrosis spectrum, therefore, would either allow for a cautious, cost-effective delay of treatment or herald imminent treatment and surveillance for the complications of cirrhosis. This paradigm helps define the utility we seek in noninvasive biomarkers. In effect, categorizing an established diagnosis as early or late in its natural history can add efficiency to treatment algorithms and provide important prognostic information for both the patient and clinician.

However, the need for staging disease is also dependant on the outcome of treatment; as treatment becomes more effective the need for staging disease precisely becomes less necessary and the need to exclude cirrhosis more important. For example, in genotype 2 and 3 HCV, biopsy is not necessary as over 80% of patients achieve a sustained virologic response that is independent of disease stage. In such cases, biopsy can be reserved for those that fail to respond.

A biopsy is said to represent 1/50,000 of the liver,11,12 and therefore it is not surprising that sampling error frequently occurs. The actual frequency is an area of debate; 25% to 30% is commonly ascribed, with understaging occurring especially at the lower strata of fibrosis.13,14 In a recent paper by Robert et al,15 the percentage of disagreement between hepatopathologist and community pathologist assessments for staging hepatitis C ranged between 22 and 58% depending on the stage of fibrosis, and was augmented in biopsy samples less than 1.5 cm. In addition to the propensity for sample error and interobserver interpretation, liver biopsy suffers from poor patient acceptance because it is invasive and sometimes painful.16 Furthermore, there is a small but significant risk for serious complications and death,4 even when carried out transjugularly. Toward the future, as more clinical trials of antifibrotics are designed, serial biopsy will unlikely be the sole evaluator of regression, and therefore, noninvasive methods are paramount.

Mehta et al evaluated a critical aspect in the search for the ideal noninvasive marker of fibrosis.17 Assuming a conservative error rate for biopsy staging of 10% to 20%, how is it possible to validate a perfect alternative when it is compared with an imperfect standard? Their model suggested that the area under the ROC curve for a surrogate marker for fibrosis compared with liver biopsy could not exceed 0.9. In effect, biopsy error causes the true validity of surrogate tests to be underestimated. This will in turn lead a clinician to falsely misperceive the test as inaccurate, when in fact it is possible that a perfect surrogate marker could already exist.

The ideal noninvasive marker should have certain characteristics for practical application. For an imaging modality such as elastometry, salient features should include: ability to accurately determine fibrosis stage; reliability unaffected by the underlying disease and conditions intrinsic to hepatopathology; ease of performance and reproducibility. These characteristics are similar to ones earlier described for serologic markers of fibrosis.18 Studies thus far suggest that HE possesses many of the characteristics of an ideal marker, and will be elaborated in this review.

ELASTOGRAPHY AND FIBROSIS STAGING

The evolution of elastography in the field of hepatology took many forms over nearly 2 decades before finding success in HE.19 The methods of static, dynamic and remote elastography were all first attempted without success. The primary reason was the boundary effect, or motion artifact from respiration that interferes with hepatic imaging. Those methods proved more successful with breast19,20 and prostate19 evaluation.

A sentinel study by Yeh et al21 from China, published in Ultrasound and Medical Biology in 2002, laid the foundation for HE when it was shown that liver stiffness positively correlated with fibrosis. Partial hepatectomy specimens were sectioned into blocks and placed on an electronic balance. This balance was connected to a personal computer and acrylic compressor, which was lowered on to the tissue. The compressor then applied intervals of increasing pressure (in kPa), allowing for measurement of the internal displacement of liver tissue. In effect, healthier livers allowed for greater internal displacement whereas cirrhotic livers, stiffer by nature, had less internal displacement.

Interestingly, this correlation was greatest at the ends of the fibrosis spectrum, and suffered from poor discriminatory ability at the middle strata of fibrosis. This dilemma would prove to haunt HE's applicability throughout subsequent clinical investigations.

This technology was initially used in the cheese industry as a way to evaluate the internal stiffness of large blocks of cheese. Echosens (Paris, France) capitalized on the shear elasticity of another soft solid material and developed the now widely used FibroScan unit. The hand-held probe is placed in the intercostal space overlying the right, lateral lobe of the liver. It sends out 2 types of waves. The first, a shear, mechanical wave, propagates through firm tissue quickly, and through healthy tissue more slowly. The second type of wave emitted by the probe is an ultrasound wave. At a depth between 2.5 and 5.5 cm from the skin, successive ultrasound waves reach a propagating shear wave at a given distance apart, depending on the velocity of that initial shear wave (Fig. 1). The distance between the 2 points can then be used to calculate the shear wave velocity, and in turn, through a mathematical model using Young modulus, the stiffness is determined.19 The area of liver surveilled by FibroScan is 100 times that of liver biopsy, and can be expanded by sampling in different intercostal spaces.

The original manuscript published by Sandrin et al in 2003 evaluated a cohort of chronic hepatitis C patients, all with abnormal aminotransferase levels.

Importantly, liver stiffness correlated well at both F0 and F4 stages of fibrosis. Perhaps not surprisingly, there was poor discriminatory ability between metavir F1 and F2 stages of fibrosis (Fig. 2). These observations mirror the diagnostic ability of other, noninvasive markers of fibrosis, namely serologic panels. It is unclear what accounts for the overlap within intermediate stages, although it suggests that our current staging system is an oversimplified representation of a more fluid spectrum of disease. In general, transient elastography is as good as the serologic markers (Fibrotest, Lok Index, APRI, Prothrombin index, AST/ALT ratio, and platelet count) to diagnose the earlier stages of fibrosis (31). Elastography has superior accuracy in the detection of cirrhosis, with an AUROC of 0.96, versus the serologic markers (AUROC from 0.61 to 0.82) (31). A separate study found that combining HE with a serologic marker of fibrosis, such as APRI, significantly enhanced the prediction of fibrosis stage. However, combinations of 3 or 4 tests led to redundancy and increased cost.22

With respect to liver biopsy, HE correlates very well with established cirrhosis. Although considered the gold standard, biopsy is susceptible to understaging, and there is the potential for a correlative discrepancy when elastography is suggestive of cirrhosis. The quality of the biopsy is therefore important, and fortunately, most studies incorporate the quality of the tissue sample.

Transient elastography and biopsy were compared in a group of 100 patients coinfected with HCV and HIV, and diagnostic values were compared by calculating the area under the ROC.23 Liver stiffness was 0.80 (0.72 to 0.89) when discriminating between F 2, 0.93 (0.85 to 1.00) when discriminating between F 3 and 0.99 (0.97 to 1.00) when discriminating between F/=3 was 11 kPa and F4 was 14 kPa.

An analysis of discordance between transient elastography and biopsy was conducted and an association with liver disease related factors was determined.24 Thirty-four percent of 300 patients had discordant findings, the majority of which had histologic stage >/=2 and TE<7.1 kPa (false negative). A smaller group had stage <2 and TE>7.1 kPa (false positive). Importantly, no patient with discordant results had cirrhosis.

As noted above, the intermediate stages of fibrosis do not correlate well with histology. This may be in part owing to the heterogeneous patterns of fibrosis, that is, periportal, pericellular, and perivenular. It is well recognized that conditions such as hepatitis C and nonalcoholic steatohepatitis lead to different patterns, periportal and pericellular, respectively. A published morphometric analysis revealed a higher correlation between liver stiffness measurement and pericellular fibrosis (r=0.43) than periportal (r=0.21) or perivenular fibrosis (r=0.25).25 The variable nature of fibrosis patterns are more likely to play a role in these intermediate stages of fibrosis, compared with established cirrhosis, in which the architectural distortion is homogenous and the underlying etiology more difficult to discern.

A meta-analysis of 9 studies concurred that the ability to differentiate mild from advanced fibrosis was poor, and was partially explained by a lack of uniformity of stiffness cut-offs between the studies.26 The stiffness cut-off level for cirrhosis from 1 study to the next contains greater variability (from 11 kPa to 19 kPa) than cut-off values diagnosing no or minimal fibrosis, (kPa<7). A recent meta-analysis shows that significant fibrosis, stage F2 or higher, begins around 7.2 kPa.27 Thus interpreting stiffness values at opposite ends of the fibrosis spectrum allows some flexibility without compromising discriminatory ability. The underlying liver disease etiology (viral vs. mixed) and biopsy sample size does not influence the ability to distinguish minimal from advanced disease (22). In contrast, cut-off values for intermediate stages of fibrosis are poorly established. There are too few studies to determine the influence of the specific variables such as disease etiology. Subgroup analyses could not be done reliably (22). Therefore, it can be safely concluded that intermediate stiffness values, between 6 kPa and 9 kPa, do not allow for accurate interpretation of fibrosis stage.

The cut-off values are influenced by disease states and not only the underlying disease itself. In several studies, an "active" disease state is more likely to be reflected by increased stiffness values, and this distinction is critical to accurately interpret stiffness values. The most common active disease state in the study of elastography is inflammation, common to disorders such as viral hepatitis and fatty liver disease. The category of acute viral hepatitis and steatohepatitis will be discussed in separate sections. However, in the case of a chronic active disease such as hepatitis C infection, should an elevated alanine aminotransferase level affect cut-off values? Probably not, however, shifting the cut-off threshold based on an elevated ALT value alone has been attempted. In a prospective study of a hepatitis C cohort, Wong et al25 find that patients with similar fibrosis staging by histology but with higher ALT levels tended to have higher liver stiffness measurements. To account for this observation, the investigators increased the diagnostic threshold for stage 0 to 1 disease (6 kPa if ALT is less than the upper limit of normal; 9 kPa if ALT is 1 to 5 times the upper limit of normal) and stage 3 to 4 disease (7.5 kPa if ALT is less than the upper limit of normal; 12 kPa if ALT is 1 to 5 times the upper limit of normal). A second study also suggests that minor ALT elevations can alter TE readings and cause discordance with histologic stage.28 These observations reinforce the excellent predictive value of stiffness measurements at the extreme ends of the fibrosis spectrum. It also suggests that the continuous spectrum of fibrosis may be independent of ALT values and therefore ranges of stiffness levels may be preferable to absolute cutoffs.

Nearly every study conducted since has corroborated HE's excellent predictive values for the diagnosis of cirrhosis when alternative underlying variables are accounted for29-31 (Fig. 3). The question was bound to arise...could HE be even better than liver biopsy at making the diagnosis of cirrhosis? In a validation study by Nahon et al32 on a cohort of alcoholic liver disease patients, 4 patient's biopsies staged as F3 showed corresponding HE values near 75 kPa, otherwise suggestive of F4 cirrhosis. The investigators suggested that HE did not suffer from poor positive predictive value, rather, the biopsy may have been understaged and these 4 participants might have been cirrhotic. Although no conclusive evidence was offered, this point of contention is noteworthy.

An important meta-analysis by Friedrich-Rust et al33 reaffirmed the conclusion that HE is excellent at making the diagnosis of cirrhosis. The important aspect of this study of more than 50 publications, some only in abstract form, was its inclusion of hepatitis C cohorts, nonhepatitis C cohorts, and mixed-diagnosis cohorts. What these investigators found was that the underlying cause of liver disease had no effect on the ability to diagnose cirrhosis (mean AUROC 0.94), and even severe fibrosis, defined as F>/=3 (mean AUROC 0.89). However, there was considerable variability in accurately diagnosing significant fibrosis (F>/=2) especially in studies with smaller sample sizes. It looked as if the underlying cause of liver disease played a role in stiffness values.

CONFOUNDERS OF STIFFNESS MEASUREMENT

On account of increased stiffness caused by more than just fibrosis, it is clear that pathologic conditions intrinsic to hepatopathology must also be taken into account. Fortunately, much but not all of the groundwork for understanding these potential confounders has been conducted and reported. These include studies on steatosis,32,34,35 hepatitis,36-42 cholestasis,43 infiltrative disorders,44-46 passive congestion47 and more. Recognizing the confounding effect of these conditions is critical to the clinician's interpretation of elastometric results.

Steatosis

Yoneda et al35 appraised the effect of bland steatosis on HE accuracy. It was evident from their results that bland steatosis does not have a confounding effect, regardless of severity. This was also concluded in several other studies,19,29 including one that assessed healthy individuals for the presence of bland steatosis.34 However, when the necroinflammatory component was taken into account, as in the case of NASH, hepatic stiffness increased concomitantly.34 This suggests that NASH, but not NAFLD must be considered carefully when interpreting results. Despite the above conclusions, the literature is not unanimous in its dismissal of simple steatosis. 27,48,49

Hepatitis

The effects of hepatitis per se on HE accuracy have been reported, and there is an emerging consensus on how to interpret elevated aminotransferase levels. Magnitude of elevation and acuity of illness are important variables.37,42,50-53 On one extreme of the hepatitis spectrum, flares of acute or chronic disease, the conclusion is foregone: stiffness is increased.52,53 Sagir et al published a report in 2007 on a cohort of participants with chronic hepatitis B who experienced an acute flare of their disease. Alanine aminotransferase levels ranged from as little as 151 to over 5000 IU/L. These initial values corresponded with HE measurements from 14 to 52 kPa, all within the range of advanced fibrosis or cirrhosis.

Other studies confirmed that stiffness values during a flare are higher than states of chronic viral hepatitis or the inactive carrier.54 These cases were followed longitudinally until resolution of the flare, marked by a return to normal ALT levels, and the liver stiffness levels also decreased to single digit values. Histologic comparisons were not the intention of this descriptive phenomenon. Interestingly, there was a 2-week lag time between the resolution of laboratory parameters (ALT and bilirubin) and stiffness. This finding was not corroborated in a separate study,53 but nevertheless serves as a red flag for cautious interpretation of HE results after flares in disease activity.

Acute flares of hepatitis are one thing, elevated levels from chronic disease55 or even coinfection36 could be another. Castera et al56 report that inflammatory activity does not influence HE values in hepatitis C-infected patients and regression analysis data overwhelmingly supports the claim that ALT levels in chronic disease have no correlation to stiffness.

We have reason to believe that in the cellular milieu of the hepatic lobule during injury, there are additional factors unaccounted for that alter the viscoelastic property. In a revealing study by Georges et al,57 where it was earlier shown that the activation of stellate cells and portal fibroblasts results from increasing substrate stiffness, the same hypothesis was tested in an in vivo rat model of injury with carbon tetrachloride. The investigators found that not only did liver stiffness increase progressively with ongoing liver injury, but that the development of fibrosis lagged behind the development of stiffness. Although it is still unclear what causes this prefibrosis change in stiffness, it is likely that the extracellular matrix undergoes significant dynamic changes with acute injury that is irrespective of the amount of fibrosis. This property is probably one reason for any discrepancy of opinion on the topic of hepatitis and HE accuracy.

Sinusoidal Congestion

Yet another factor intrinsic to hepatopathology is sinusoidal congestion. Passive congestive hepatopathy was highlighted as a case report in a patient with chronic hepatitis C and mildly elevated serum aminotransferase levels.47 Before the cardiac transplant and ostensibly as an evaluation of hepatic reserve, the patient was biopsied after HE revealed a level of 44.3 kPa, highly suggestive of cirrhosis. Histology showed dilated sinusoids and perisinusoidal fibrosis, but periportal fibrosis was limited. Eighteen months after cardiac transplantation, with ALT still mildly elevated, repeat HE revealed a level of just 3.8 kPa, and a repeat liver biopsy confirmed early fibrosis. LeBray et al concluded that congestive hepatopathy lowers the positive predictive value of HE. This study also initiated dialogue about additional factors related to a plethoric liver, such as the use of nonselective ß-blockade, postprandial portal hyperemia, and what effect these have on stiffness.

Extrahepatic Cholestasis

Extrahepatic cholestasis is another variable that has been studied.43 In a series of 15 cases of extrahepatic obstruction, serial HE measurements were used in addition to serum markers of cholestasis. In all but 1 case, biliary stenting was carried out for various causes of obstructive jaundice. Preintervention and postintervention bilirubin levels documented successful resolution of the obstruction. Interestingly, in all but 2 cases, the liver stiffness also decreased postintervention. Of note, several more cases showed only a trivial decrease in stiffness values, but the general trend was such that a firm conclusion was possible. Acute biliary obstruction also accounts for falsely elevated measurements of stiffness.

Extrinsic Factors

There are also conditions extrinsic to the liver that may confound, or, in some cases, altogether preclude the gathering of reliable HE data. The presence of ascites, even in small amounts, negates the applicability of elastography. This, fortunately, is a situation that begs the question. These patients will be cirrhotic by virtue of the presence of their ascites. Advanced age has been reported to affect performance and success of data acquisition.58 Narrow intercostal spaces are another recognized element extrinsic to the liver that makes data acquisition difficult.59 A second-generation probe, engineered for such cases, is in development.

Obesity is also a major hindrance to the practical application of elastography. It is another variable that has attracted much international debate and has yet to be fully resolved. To obtain reliable measurements, the operator must gather a total of 10 elastographic values; successful acquisition must occur 60% of the attempts and the interquartile range of all successful measurements should be less than 30% of the median value.39,49 As mentioned earlier, the probe begins measurement just 2.5 cm from its tip, and therefore, a habitus replete with central adiposity becomes problematic. Again, second-generation probes said to overcome the limits of advanced body mass index (BMI) are in development. The French group led by Castera found that with BMI >30 kg/m2, there is a failed rate (zero successful acquisitions) in 3% of cases, and unreliable results (<60% successful acquisitions or IQR >30%) in 15.8% of cases.60 In other manuscripts, BMI cutoffs of 2861,62 and 3063 are also reported. This last example quoted a failed acquisition rate of 25% when BMI is > 30 kg/m2. In sum, the exact cutoff is not established. This may be owed to the fact that BMI does not always correlate with thoracic adiposity/wall thickness. It also remains to be determined whether unsuccessful acquisition of HE data in itself, owing to overweight, can be used for any predictive value. As several serologic panels of fibrosis markers have been previously validated64 and possess acceptable diagnostic accuracy, their combination with failed HE from obesity could also prove useful.

TOWARD THE NATURAL HISTORY OF DISEASE

Although most research efforts thus far attempted to validate HE against liver biopsy, perhaps an equally apropos translation is to validate HE against the hepatic venous portal pressure gradient, or HVPG. After all, most clinical outcomes in end-stage liver disease are tightly correlated with advanced portal pressures, including detection of esophageal varices, first variceal bleed65,66 and development of hepatocellular carcinoma.67 Several studies validated HE as a noninvasive means of diagnosing portal hypertension.38,68,69

The report by Vizzutti et al70 offers an excellent figure depicting this relationship (Fig. 4). Elastography can indeed diagnose earlier stages of portal hypertension, as the major determinant at gradients between 5 and 12 mm Hg is intrahepatic fibrosis. Beyond this 10 to 12-mm Hg threshold, when the sequelae of elevated portal pressures occur with greater frequency, elastography loses its correlative ability and its well-fitted regression line. The investigator's explanation focuses on the physiologic factors extrinsic to the liver that impact HVPG at these advanced gradients. These factors include portosystemic collateral development, splanchnic vasodilatation, and hyperdynamic circulation. The performance of liver stiffness for predicting significant portal hypertension, defined by HVPG>/=10 mm Hg was found to be 92% predictive with a cutoff of 21 kPa.71 This finding was compared with the accuracy of the prothrombin index, a previously validated serologic marker, and found to be superior. Although the data supporting the ability of HE to diagnose portal hypertension is strong,71,72 the overall data supporting its role in evaluating the consequences of portal hypertension remain unconvincing.73

There has been an inevitable, fundamental shift in the focus of HE studies over the past year toward an investigation into the natural history of disease. This comes as the validation studies and limitation studies reinforce similar conclusions with respect to overall efficacy of HE. These studies by and large aim to exploit elastography's ability to diagnose advanced fibrosis or cirrhosis. One such study looked at hepatitis B virus DNA and ALT levels in HbeAg negative patients to predict cirrhosis.74 The percentage of patients with probable or possible cirrhosis increased with increasing ALT levels, and these findings were subdivided into gender and showed the relative increased risk for males to have HE cirrhosis. Furthermore, DNA evaluation showed a positive correlation with possible and probable cirrhosis, with higher rates corresponding to DNA levels greater than log 6. Other studies predicting advanced fibrosis in cohorts with HCV/HIV coinfection and metabolic syndrome have also been conducted75 with HE as a primary diagnostic tool.

As it is now recognized that significant regression of fibrosis can occur, even in cirrhotic livers, there is great interest in clinical pharmacologic trials for antifibrotics, with no lack of candidates. Of the myriad categories there are inhibitors blocking the activation, migration or proliferation of hepatic stellate cells, hepatocyte maintenance and protection, plant-derived drugs, and even commoner agents such as statins and interferons. One of the first trials using HE to evaluate regression of stiffness as a marker of fibrosis was published in 2008 by Vergniol et al.76 These investigators used standard treatment of Peginterferon and Ribavirin in cases of hepatitis C and measured stiffness before and after treatment. Although the no therapy arm showed no change in stiffness values, each of the 3 study arms showed an effect: nonresponders (10.3% decrease in stiffness), responders/relapsers (29.5% decrease) and sustained virologic responders (24.5% decrease). Although there is no evidence of actual regression of fibrosis, and decreased inflammation can be responsible for decreased stiffness, this study nevertheless proved that HE can be successfully employed to monitor regression of fibrosis in such trials. The liver transplant community also eagerly awaits additional trials using HE. To date, only hepatitis C recurrence has been adequately studied.69,77-79 These trials used protocol liver biopsies anywhere from 1 to 2 years posttransplant and showed accuracy for staging of fibrosis, similar to the hepatitis C in a native liver. Acute viral recurrence immediately after transplant and acute cellular rejection has not been adequately studied, and it remains to be seen whether HE can help differentiate one diagnosis from the other in cases of elevated liver tests at early time points in the liver allograft. In essence this would exploit the other factors that are readily measured by elastography, such as flares of hepatitis and prefibrosis changes in stiffness. Utilization of HE in clinical practice for indications other than fibrosis staging has been suggested.80

With all that has been learned from the studies of HE and the liver since the first publication in 2003, it is now important to ask how this technique can impact day-to-day practice in 2010 and beyond. It seems logical that HE could be used to stage fibrosis from chronic hepatitis C infection. With this diagnostic challenge in mind, some investigators argue that many, if not a majority, of liver biopsies can be avoided altogether. This could amount to a substantial decrease in the overall number of liver biopsies, considering that 50% to 60% of all biopsies are ostensibly for staging purposes.

For example, if HE gives a low value, below 6 kPa, no biopsy is required and serial HE measurements are warranted. This approach seems reasonable. Of participants with a score <5.1 kPa, 93% were stage F0 or F1.19 Moreover, a systematic review found excellent accuracy for diagnosing the earliest stages of fibrosis.81 If HE values suggest cirrhosis and the pretest probability is high, again no biopsy is warranted and the patient could receive appropriate cirrhotic management. For values in the gray zone, between 6 and 9 kPa, a clinician can opt to proceed with biopsy only if treatment is not planned, so as to avoid missing false negative results and the opportunity to treat a compensated cirrhotic patient. If treatment is planned, liver biopsy can be avoided.82 A second paper detailing an algorithm for hepatitis C staging and management offers an additional feature. For these intermediate values, a serologic panel can be added to increase the predictive value. The AST: platelet index (APRI) and Forns Index were suggested.83 As these noninvasive markers have AUROC>0.8 in validation studies64 they may be especially useful in combination with HE for treatment decision-making,56,84-86 such as a second opinion to strengthen an argument against biopsy. It is easy to imagine other scenarios in which HE can be used in lieu of biopsy, such as when biopsy is contraindicated, unavailable or not-preferred by the patient; when the clinician does not believe the interpretation of a biopsy; a baseline HE measurement is obtained in patients with biopsy F0 so that future surveillance can be carried out with HE; pregeneral surgery evaluations; and the list goes on.

CONCLUSIONS

In conclusion, there is an urgent need for noninvasive markers to quantify liver fibrosis. Hepatic elastography is a novel tool that exploits the correlation between liver stiffness and liver fibrosis. It is excellent at making the diagnosis of cirrhosis and at excluding fibrosis87; it is not able to discriminate between the intermediate stages of fibrosis. Several intrahepatic processes confound the accuracy of HE to gauge fibrosis, and it remains to be seen how these processes will influence future research efforts. It is conceivable that instead of absolute cutoffs, a range of values will be used for diagnosis. HE can be helpful for treatment and management decisions.2,82,88 The era of HE used as the evaluator of the natural history of disease, both pretransplant and posttransplant, is now underway. More studies are necessary to delineate the most appropriate clinical scenarios for this useful new tool.

Source

EU funds d-LIVER project to help people suffering from liver disease

Published on June 5, 2013 at 3:51 AM

The EU has provided funding for the d-LIVER project, in which researchers from several countries will work on a number of measures to help people suffering from liver disease. The patients will be offered technology that can monitor and manage their condition at home. The project will also construct a system that will help patients within this chronically ill group to undergo artificial liver support treatment when their own livers are compromised or incapable.

Complex organ
The liver is not just a 'rubbish cleaner', but a central, complex organ that is vital for major parts of the body's biochemistry, and is used by our metabolism and for protein synthesis. Because of this complexity, no one has ever managed to create an artificial, synthetic liver. Quite simply, it is too difficult to find a good replacement for all the functions performed by the liver.

When the liver fails, a patient's body becomes poisoned. If the liver failure is acute, it may be only a few hours before it develops into a life-threatening condition that affects all the cells in the body. Not even the brain will be able to function optimally. Many patients suffering from liver failure find that a liver transplant is their only treatment option, but only one in twenty receive this, because of a lack of donors.

Financial burden of treatment
Chronically ill patients need intensive monitoring, treatment and also periodic stays in hospital. They often have a poor quality of life, because it is difficult to have this kind of illness and have a job at the same time.
Special skills are required to monitor patients with liver failure, since they have complex clinical symptoms, including abnormal blood parameter values. Their medical monitoring therefore requires them to have access to specialists. Patient treatment places a high financial burden on society, and this is one of the things that the d-LIVER project aims to improve.

Blood circulated through artificial liver
Instead of an artificial liver within the body, the researchers are now developing an artificial liver unit outside the body. Cells from humans or pigs live and grow in it - and function as real liver cells. The cells grow in a three-dimensional structure in a reactor that functions like an 'incubator'. It ensures that the conditions are right for the liver cells to function properly. The reactor must be able to control temperature and to circulate nutrients and oxygen in the right quantities to all the cells.

The artificial liver will be able to act as an 'auxiliary engine' for a patient, during periods when the patient's own liver cannot manage to function adequately. Blood is recirculated from the patient through the artificial liver - a process that takes several hours. In order to avoid the problem of rejected cells, every single patient needs a bio-reactor. This means that meticulous planning and preparations are required for every patient.
'We envisage that it will be possible for this type of artificial liver to be used for patients with extremely poor liver function, preferably before the patients become so ill that their brain function is affected and they cannot manage to look after themselves,' says Frode Strisland of SINTEF. Patients undergo crisis periods when their liver function is insufficient, resulting in a build-up of waste products in the body. This tends to happen when the patients are suffering from infections or colds - conditions that a healthy liver has plenty of capacity to handle. For liver patients, treatment with an artificial liver can be live-saving until they have recovered, and their own liver capacity becomes sufficient to keep the body going.

'What is very clear is that the new artificial livers will probably have to be operated and maintained in a hospital environment, although the research project will also look at what would be required in order to be able to offer this kind of treatment in a patient's home,' says Strisland.

Prevention is just as important
If we can manage to detect when a liver patient is beginning to have problems, it may be possible to prevent these problems in an early phase, by adjusting their medical treatment. This is cheaper and easier for the health services, and much better for the patient, giving them a chance to avoid the worst crises. For this reason, it is important to pick up on the first signs that a liver is not functioning properly.

It is here - in the preventative part of d-LIVER - that the Norwegian researchers at SINTEF ICT are concentrating their efforts. The idea is to make it possible to supervise patients with liver problems and monitor them at home.
'Monitoring at home should be able to detect patients who are starting to have problems. We think that this may reduce the need for hospital admissions,' says Frode Strisland.

Since the balance of the liver is fundamentally linked to infections and a compromised immune system, the researchers will be developing sensors that patients can wear, that will provide information about physical condition and activity. The project will also create a blood analysis instrument that will measure selected blood parameters on a daily basis. 'This will enable these patients to be monitored significantly better than they are now, when many of them might only get to see a doctor every three months,' says Strisland.

Source: SINTEF

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High serum ferritin not predictive of advanced fibrosis in NAFLD

Provided by Healio

June 5, 2013

ORLANDO, Fla. — Elevated serum ferritin levels were associated with severe liver injury among patients with nonalcoholic fatty liver disease but were not predictive of advanced fibrosis, according to data presented at Digestive Disease Week.

In a multicenter cohort study, researchers assessed data from 1,014 patients with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD). Serum ferritin (SF) levels were collected, with the upper limit of normal (ULN) defined as fewer than 300 mcg/L among men and fewer than 200 mcg/L among women. Three cutoff values for SF were established and compared for predictive value: more than ULN (n=331), more than 1.5 times ULN (n=189) and more than twice ULN (n=103).

Patients with elevated SF were more frequently non-Caucasian, with lower levels of HDL cholesterol and higher levels of AST, ALT, bilirubin and HOMA. NASH was significantly more common among these participants (45.9% of cases vs. 34.8%; P=.003), as was fibrosis of stage 3 or 4 (33.3% vs. 23.5%; P<.001). Multivariate analysis, adjusting for factors including age, sex, race, BMI, ALT levels and diabetes, indicated a significant association between SF and advanced fibrosis using all three cutoffs. Risk increased along with cutoff values.

AUROC analysis indicated low accuracy and sensitivity values, but high specificity, for SF alone at all cutoffs in distinguishing of advanced fibrosis, with an AUROC of 0.55 (0.51-0.59), sensitivity of 41% and specificity of 70% for above ULN; AUROC 0.56 (0.52-0.6), 27% sensitivity and 84% specificity for 1.5 times ULN, and AUROC 0.54 (0.5-0.58), 16% sensitivity and 92% specificity for more than twice ULN (95% CI for all). Adding SF to current noninvasive scoring systems for the prediction of fibrosis did not affect diagnostic accuracy.

“Increased SF is associated with the presence and severity of fibrosis based on multivariate analysis, as shown by previously published studies,” researcher Anna Christina Dela Cruz, MD, digestive diseases and nutrition division of the University of Kentucky Medical Center, said. “However, SF on its own lacks the accuracy to detect the presence and severity of liver fibrosis.”

Disclosure: Researcher Christopher P. Day reported a board membership at Abbott. Researcher Jacob George has served on advisory committees/review panels for Bristol-Myers Squibb, Gilead Sciences, MSD, Novartis Pharmaceuticals and Roche Pharma.

For more information:

Dela Cruz AC. #382: Diagnostic Relevance of Serum Ferritin in Patients with Nonalcoholic Fatty Liver Disease. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.

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NIH Scientists Discover How HIV Kills Immune Cells

prDHHSNIH

National Institute of Allergy and
Infectious Diseases (NIAID)
http://www.niaid.nih.gov

FOR IMMEDIATE RELEASE
Wednesday, June 5, 2013

MEDIA AVAILABILITY

Findings Have Implications for HIV Treatment

WHAT:
Untreated HIV infection destroys a person’s immune system by killing infection-fighting cells, but precisely when and how HIV wreaks this destruction has been a mystery until now. New research by scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, reveals how HIV triggers a signal telling an infected immune cell to die. This finding has implications for preserving the immune systems of HIV-infected individuals. 

HIV replicates inside infection-fighting human immune cells called CD4+ T cells through complex processes that include inserting its genes into cellular DNA. The scientists discovered that during this integration step, a cellular enzyme called DNA-dependent protein kinase (DNA-PK) becomes activated. DNA-PK normally coordinates the repair of simultaneous breaks in both strands of molecules that comprise DNA. As HIV integrates its genes into cellular DNA, single-stranded breaks occur where viral and cellular DNA meet. Nevertheless, the scientists discovered, the DNA breaks during HIV integration surprisingly activate DNA-PK, which then performs an unusually destructive role: eliciting a signal that causes the CD4+ T cell to die. The cells that succumb to this death signal are the very ones mobilized to fight the infection. 

According to the scientists, these new findings suggest that treating HIV-infected individuals with drugs that block early steps of viral replication—up to and including activation of DNA-PK and integration—not only can prevent viral replication, but also may improve CD4+ T cell survival and immune function. The findings also may shed light on how reservoirs of resting HIV-infected cells develop and may aid efforts to eliminate these sites of persistent infection.

ARTICLE:
A Cooper et al. HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature DOI:10.1038/nature12274 (2013). 

WHO:
NIAID Director Anthony S. Fauci, M.D.; Arik A. Cooper, Ph.D., staff scientist in the Virology Laboratory of the NIAID Vaccine Research Center; and Costas Petrovas, Ph.D., staff scientist in the Immunology Laboratory of the NIAID Vaccine Research Center, are available for comment. 

CONTACT:
To schedule interviews, please contact Laura S. Leifman, (301) 402-1663, niaidnews@niaid.nih.gov


NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Are over-the-counter pain medications safe?

Jun 5th, 2013

We depend on over the counter pain medications to help ease headaches, achy joints and raging fevers. Conversely, could the side effects of these medications outweigh the benefits?

Many trusted over-the-counter pain medications contain acetaminophen, ibuprofen and aspirin that can have deadly side effects if taken in excess. Acetaminophen is one of the most popular over-the-counter painkillers but research has shown that it could be your liver’s worst enemy.

Most documented cases of liver damage are from long-term use but new research is challenging even their short-term use. The latest research shows that taking slightly too much acetaminophen over a period of several days can pose serious threats as well.

“Even supposedly safe amounts of acetaminophen — doses close to 4,000 milligrams (mg) per day, the current daily limit — may be quite toxic to the liver in a small number of people,” according to the Harvard Medical School.

Also, you may be getting more acetaminophen than you think. It’s used in more than 600 medications. Initial symptoms of liver toxicity from acetaminophen are often vague — fatigue and nausea — and easily confused with the symptoms associated with the illness attempting to be treated with the drug.

Ibuprofen and NSAIDs warnings

Unlike acetaminophen, overdosing on ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) can put one at a higher risk for cardiovascular diseases and heart attacks. NSAIDs can also damage the kidneys and increase the occurrence of stomach bleeding.

A new study published in the Lancet looked at more than 353 000 records from 639 different clinical trials to assess the risks associated with NSAID use. Researchers found for every 1,000 people taking NSAIDs there would be three additional heart attacks, four more cases of heart failure and one death.

The overall number of heart attacks would increase from 8 per 1,000 to 11 per 1,000 people with the drugs. NSAIDs posed an even greater risk to smokers, individuals that are overweight and physically inactive.

Long-term, high-dose use of NSAIDs such as ibuprofen or diclofenac is ‘equally hazardous’ as the drug Vioxx. Vioxx is a type of NSAID that goes by the generic name Rofecoxib. Vioxx was taken off the market due to its cardiovascular risks.

A similar NSAID study of over 100,000 people found that ibuprofen was associated with a 3 times greater risk of stroke in comparison to the placebo control group.

There is a natural tendency to view over-the-counter medications as being safer than prescription drugs because you don’t need a prescription. However, the user rarely follows the safe maximum dose of over-the-counter medications. This is especially true when people develop a tolerance to the medication, causing them to take more and more.

While taking ibuprofen, make sure to monitor your blood pressure, especially if it tends to run too high. For long-term or chronic pain, you shouldn’t take it for more than 10 days. The latest advice is to try not to take it more than three days per week.

Adverse side effects of aspirin

Just because aspirin is sold over-the-counter doesn’t mean it’s safe. Previous advice for preventing heart attacks and strokes has been simple: take an aspirin every day. However, new research suggests that patients and doctors prescribing them may need to think twice about that advice.

A recent study published in the Journal of the American Medical Association found that taking 300 milligrams or less of aspirin increased bleeding in the stomach and brain by 55 per cent. Researchers looked at more than 186 000 patients taking a daily dose of aspirin and found nearly 2 300 cases of stomach bleeding and nearly 1 300 cases of brain bleeding.

“The results show that the risks of bleeding are much higher than what doctors had previously suspected after several clinical trials and should prompt doctors to carefully consider a patient’s individual health before prescribing aspirin,” according to Dr Antonio Nicolucci, one of the study’s authors.

“When the cardiovascular risk is low, the adverse effects of aspirin overwhelm any benefit,” said Dr Steve Nissen, Chair of Cardiovascular Medicine at the Cleveland Clinic. “Unfortunately, many patients taking aspirin represent the ‘worried well’ rather than individuals with a high risk of coronary artery disease.”

Daily aspirin therapy can be lifesaving or life threatening even to the high-risk cardiovascular patients. Generally people who have uncontrolled high blood pressure and advanced kidney disease are at the greatest risk. Blood pressure should be controlled before any type of aspirin therapy is initiated.

“Aspirin should only be used to prevent a cardiovascular event in association with an overall programme of lifestyle measures including healthy eating, cessation of smoking, control of blood pressure and regular physical activity,” according to a aspirin study in the Medical Journal of Australia.

There is a wide range of adverse reactions that may result from aspirin use including effects on the body as a whole, or on specific body systems, organs and functions. High doses can cause hearing loss and ringing in the ears called tinnitus. Other side effects include nausea, vomiting, stomach pains, fatigue and coincidently headaches.

Aspirin should not be used for fevers in children under age 16 as research has shown it can cause the combination of swelling of the brain and liver damage called Reye’s Syndrome. Reye’s Syndrome is most likely to affect children under 5 but cases are seen in older children as well.

Reye’s Syndrome can kill within days or leave a child with permanent disability. Symptoms can include severe vomiting, drowsiness or loss of consciousness after a viral infection and there is no current treatment. It is not known why only some children and no adults are affected.

People with asthma often cannot take aspirin or NSAIDs medications. This is due to a condition called Samter’s triad — a combination of asthma, aspirin sensitivity, and nasal polyps. Nasal polyps are small growths inside the nasal cavity that can affect breathing.

An aspirin allergy or sensitivity is very common and occurs in about 30 to 40 per cent of those who have asthma. Reactions can range from mild to severe and generally occur within a few hours of taking the medication. The symptoms can include hives, itchy skin, red eyes, swelling of the lips, tongue or face as well as difficulty breathing.

Don’t ignore the risks of over-the-counter painkillers. Always check first with your doctor to determine the pros and cons and ensure the benefits will outweigh their risks. The important thing is to be an active patient and an informed consumer.

Dr Cory Couillard is an international healthcare speaker and columnist for numerous newspapers, magazines, websites and publications throughout the world. He works in collaboration with the World Health Organization’s goals of disease prevention and global healthcare education. Views do not necessarily reflect endorsement.

Email: drcorycouillard@gmail.com

Facebook: Dr Cory Couillard

Twitter: DrCoryCouillard

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A Global View of HCV Infection and Barriers to Treatment

Published in Journal Watch Gastroenterology May 10, 2013

Even with new treatments on the horizon for HCV infection, worldwide issues of access, cost, and gaps in physician knowledge must be addressed.

As we anticipate a new generation of treatments for hepatitis C virus (HCV) infection, it is important to view the global picture of HCV infection. The current companion studies estimate HCV seroprevalence and potential barriers to care worldwide.

To estimate global HCV seroprevalence, Mohd Hanafiah and colleagues conducted a meta-analysis of studies published between 1980 and 2007 that reported the prevalence of hepatitis B, C, and D virus infections. Researchers grouped countries into 21 epidemiologically homogenous regions. Overall, HCV seroprevalence increased from 2.3% to 2.8% from 1990 to 2005 (from >122 million to >185 million). The regions with the highest seroprevalence were North Africa/Middle East, Central Asia, and East Asia (>3.5%). The regions with the lowest seroprevalence were Asia Pacific, Tropical Latin America, and North America (<1.5%).

To understand physicians' perceived barriers to care, knowledge, and opinions, McGowan and colleagues surveyed 697 physicians from 29 countries. Overall, patient-level barriers were the most commonly cited (e.g., fear of side effects, cost of treatment); however, regional variation was noted (e.g., government-related barriers were cited most frequently in the Central/Eastern Europe region). Two thirds of physicians felt that patients did not have adequate access to providers in their communities. Globally, physicians demonstrated gaps in basic knowledge, such as the role of viral kinetics in treatment. Physicians with lower knowledge scores were more likely to perceive greater barriers to treatment versus physicians with higher scores (e.g., physicians in the Middle East/Africa region vs. those in the Nordic region).

Comment: These studies demonstrate that, globally, the seroprevalence of HCV infection is on the rise, especially in parts of the Middle East, Africa, and Asia. These same regions seem to have significant barriers to treatment, mainly at the patient level, such as side effects and cost, according to physicians. But gaps in physician knowledge are also a barrier. Although the coming generations of simpler, better-tolerated, shorter-duration treatments should eliminate some of these barriers, more work is needed to address access to care and cost of treatment, as well as awareness and education — not only for patients, but also providers.

Atif Zaman, MD, MPH

Citation(s):

Mohd Hanafiah K et al. Global epidemiology of hepatitis C virus infection: New estimates of age-specific antibody to HCV seroprevalence. Hepatology 2013 Apr; 57:1333. (http://dx.doi.org/10.1002/hep.26141)

    McGowan CE at al. A global view of hepatitis C: Physician knowledge, opinions, and perceived barriers to care. Hepatology 2013 Apr; 57:1325. (http://dx.doi.org/10.1002/hep.26246)

    Source

    IL Lottery Launches Nation's Only HIV/AIDS Awareness and Prevention Instant Game -- 'Spread the Word'

    PRESS RELEASE June 5, 2013, 1:00 p.m. ET

    Since 2008 game has raised over $4.7 million 


    CHICAGO, June 5, 2013 /PRNewswire/ -- This week the Illinois Lottery, in partnership with the Illinois Department of Public Health and a host of Illinois-based HIV/AIDS advocates, launched Spread the Word -- a lottery game where 100 percent of net proceeds are used for HIV/AIDS education, prevention and support programs that serve Illinoisans living with HIV/AIDS. The Illinois Lottery is the only lottery in the nation with a game whose profits are used exclusively to fund HIV/AIDS prevention and treatment programs.



    (Logo: http://photos.prnewswire.com/prnh/20130528/CG21596LOGO)



    Since 2008, the Illinois Lottery has contributed over $4.7 million to the fight against HIV/AIDS, through previous iterations of this game. The Lottery expects to raise an additional $1 million from the new game for HIV/AIDS prevention and treatment efforts.



    "Spread the Word is a perfect example of what a Lottery is all about," said Michael Jones, Superintendent of the Illinois Lottery. "Lotteries exist to fund important causes. In Illinois, those causes include public schools, roads and bridges, and four special areas determined by the Illinois Legislature: Veterans' programs, MS research, Breast Cancer research, and services that support people with HIV/AIDS. With the new Spread the Word game, anyone who would like to support this cause can buy a $2 Spread the Word instant ticket and have a chance to win up to $20,000 cash. If they play and lose, they know their money will go to fund vital support services for people in Illinois living with HIV/AIDS."



    According to the Illinois Department of Public Health, the agency responsible for administering Spread the Word grants, Illinois ranks seventh nationwide in the diagnosis of HIV infections, and fifth in the estimated number of AIDS cases. In 2011, there were 1,760 new cases of HIV/AIDS diagnosed in Illinois. In Chicago, there are more than 20,000 people living with HIV/AIDS -- three times the national prevalence rate.



    "Knowing your HIV status puts you in greater control. I encourage everyone to utilize the resources available -- many of which are free and confidential -- to get tested," said Illinois Department of Public Health Director Dr. LaMar Hasbrouck. "We're proud that our partnership with the Illinois Lottery through this specialty ticket will continue to provide much-needed resources for people living with HIV/AIDS in Illinois."



    Spread the Word was officially unveiled at the James R. Thompson Center Wednesday, June 5 during the Chicago National HIV Testing Collaborative's "Step Up, Get Tested" campaign. More information on the month-long testing campaign is available at www.stepupgettested.com. The Spread the Word instant game is available at more than 8,100 Illinois Lottery retailers throughout the state. If you don't see Spread the Word displayed at your local retailer, please ask for it.



    About Illinois Lottery: Founded in 1974, the Illinois Lottery has contributed over $17.5 billion to the state Common School Fund to assist K-12 public schools, as well as the Capital Projects Fund. Players must be at least 18 years old. More information is available at www.illinoislottery.com.



    About HIV/AIDS in Illinois



    For more information about HIV/AIDS in Illinois, call the Illinois AIDS/HIV & STD Hotline at 1-800-243-2437 or TTY (hearing impaired use only) 1-800-782-0423. It's free and anonymous (no names). Trained counselors can help to answer your questions and help you to find a testing site that's right for you. They are available seven days a week (9 a.m. to 9 p.m. on weekdays and 10 a.m. to 6 p.m. on weekends). To find the closest free HIV testing site by calling the department's HIV/AIDS and STD Hotline at 1-800-AID-AIDS (1-800-243-2437). IDPH's innovative Text2Survive mobile service also provides free HIV testing locations by texting IL plus ZIP code to 36363. This service is also available in Spanish by texting "CENTRO" plus ZIP code to 36363.



     
    Contact: Mike Lang 217-524-5158
    Chanele Newton 312-368-5814


    SOURCE Illinois Lottery



    /Web site: http://www.illinoislottery.com



    Source

    AHF Launches First 1-minute “INSTI” HIV Testing Program in New York City

    ahf_2011_withname_thumbnail

    June 05, 2013 09:00 AM Eastern Daylight Time 

    AIDS Healthcare Foundation will launch the program at the Brooklyn Pride Festival on Saturday, June 8th, offering free one-minute results HIV tests through two mobile testing units

    1-minute “INSTI” testing will be available on an ongoing basis through AHF’s new Out of the Closet Thrift Store in Brooklyn and through its mobile testing program

    NEW YORK--(BUSINESS WIRE)--On Saturday, June 8th, AIDS Healthcare Foundation (AHF) will make history as the first HIV testing program in New York City to use a revolutionary HIV test that provides results to people in just one minute. The program will be launched at the 17th annual Brooklyn Pride Festival where free testing will be offered out of AHF’s mobile testing unit and the visiting Condom Nation van throughout the festival from 11:00 am to 5:00 pm. Free, confidential 1-minute INSTI testing will be available on an ongoing basis at AHF’s new Out of the Closet Thrift Store in Brooklyn (475 Atlantic Ave.) every Monday-Saturday from 10:00 am to 7:00 pm beginning on Monday, June 10th. AHF is a proud sponsor of this year’s Brooklyn Pride.

     

    What:  

    AHF launches 1-minute HIV testing at Brooklyn Pride Festival

         
    When:  

    SATURDAY, June 8th 11:00 am to 5:00 pm

         
    Where:  

    Brooklyn Pride Festival

        Park Slope on 5th Avenue from 3rd to 9th Streets
        AHF booth will be located at 5th Ave. between 4th and 5th Streets
         
    Who:  

    Michael Camacho, MPH, NYC Regional Director, AIDS Healthcare Foundation

        AHF HIV testing counselors
         
    B-roll:   Mobile testing unit and Condom Nation van offering free INSTI HIV testing
         
    Contacts:  

    Michael Camacho, AHF NYC Regional Director, mobile 646.265.7460

       

    Lori Yeghiayan Friedman, AHF Assoc. Dir. of Communications, mobile 323.377.4312

    Last September, AHF was the first HIV testing program in the United States to use the revolutionary HIV test when it launched a program to offer it at all of its Los Angeles locations last September. AHF now offers the test at many of its locations throughout Florida as well. For more information about AHF’s testing locations in New York and other parts of the U.S., please visit: www.freehivtest.net.

    “With an estimated 15% of people who are HIV-positive unaware of their status, our hope is that the INSTI one-minute test removes a barrier that prevents people from getting tested regularly,” said Michael Camacho, NYC Regional Director for AHF. “Though the 1-minute test has been widely deployed in other countries in Africa and elsewhere over the past four years, it has only been available in the U.S. since last September. Unlike other tests that take 15 to 30 minutes for results, the INSTI™ test produces results in as little as 60 seconds—a revolution for testing in the U.S. – and, now, New York!”

    bioLytical Laboratories’ one-minute HIV test, the INSTI™ Rapid HIV Test, was approved for widespread use in the United States in late July 2012 by the Food and Drug Administration (FDA). At the time, Whitney Engeran-Cordova, Senior Director of AHF’s Public Health Division, said, “The increased availability of the INSTI™ 60-second rapid test in the U.S. … is a game-changer and will allow for large-scale testing events and new ways for point-of-care testing in Emergency Rooms. Most importantly, it will lead to new techniques to reach people.”

    According to a bioLytical statement of the time of FDA approval in July, “The INSTI™ Rapid HIV Antibody Test is the first rapid HIV test to meet the stringent requirements of the updated Clinical Laboratory Improvement Amendments (CLIA) guidelines, which pertain to the complexity of laboratory tests. A CLIA Waived test is categorized as a ‘simple laboratory examination or procedure that has an insignificant risk of an erroneous result,’ meaning the tests can be performed by untrained users at point-of-care (POC) locations across the country.” bioLytical also noted, “The INSTI™ Rapid HIV-1 Antibody Test, the world’s only proven 60-second test for HIV/AIDS, is being made more widely available to the U.S. population. Found to meet the CLIA Waived performance requirements for finger-stick blood samples, INSTI™ can now be used by HIV testers and healthcare providers in a significantly expanded variety of settings.”

    About AIDS Healthcare Foundation

    AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 200,000 individuals in 28 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org, find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare.

    Contacts

    AIDS Healthcare Foundation
    Lori Yeghiayan Friedman
    AHF Assoc. Director of Communications
    Telephone: 323-308-1834
    Mobile: 323-377-4312
    loriy@aidshealth.org
    or
    Michael Camacho, MPH
    NYC Regional Director, AHF
    Mobile: 646-265-7460
    michael.camacho@aidshealth.org

    Source

    Video: Highlights of the International Liver Congress 2013 - Amsterdam, The Netherlands

    Published on Jun 4, 2013
     
     

    Source