Showing posts with label noninvasive tests for fibrosis. Show all posts
Showing posts with label noninvasive tests for fibrosis. Show all posts

Thursday, October 11, 2018

FibroScan after endoscopy found undiagnosed NAFLD, NASH

FibroScan after endoscopy found undiagnosed NAFLD, NASH
October 11, 2018

PHILADELPHIA — FibroScan screening for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis could significantly improve patient diagnosis and care, as data presented at the American College of Gastroenterology Annual Meeting showed that FibroScan found a significant number of undiagnosed cases.
Read the article:

Meeting Coverage

Wednesday, October 10, 2018

Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma

Nature Research Journal - Scientific Reports
Current noninvasive liver reserve models do not predict histological fibrosis severity in hepatocellular carcinoma 
Shu-Yein Ho , Po-Hong Liu, Teh-Ia Huo

...No study to date has specifically evaluated the relationship and accuracy between noninvasive liver reserve models and the severity of liver fibrosis in HCC. We aimed to investigate the correlation of the currently used noninvasive liver function models and histological fibrosis in HCC patients undergoing surgical resection...

Abstract
The Ishak scoring system has been used to stage liver fibrosis. Ten noninvasive liver reserve models were proposed to assess the severity of liver fibrosis, but their performance in hepatocellular carcinoma (HCC) is unknown. We aimed to evaluate the correlation between these models and severity of fibrosis in patients with HCC. A total 464 patients with HCC undergoing surgical resection were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent factors associated with advanced fibrosis (Ishak score 4 or higher). There were no significant correlations between all noninvasive models and severity of fibrosis in HCC (p for trend all >0.1). In subgroup analysis, cirrhosis discriminant index (CDS) and Lok’s index in hepatitis B-, and fibrosis index based on 4 factors (FIB-4), CDS and Lok’s index in hepatitis C-associated HCC, best correlated with the severity of liver fibrosis. Low platelet count, prolonged prothrombin time, hepatitis C and multiple tumors were independently associated with advanced fibrosis. Among the 10 models, CDS was the best model to predict cirrhosis. Currently used noninvasive liver reserve models do not well correlate with severity of histological fibrosis in HCC. New noninvasive models are required to improve the predictive accuracy of liver fibrosis in HCC.

Read the full-text article:

Friday, September 14, 2018

Chronic Hepatitis C Patients with Obesity: Do we Need two Operators for Accurate Evaluation of Liver Stiffness?

In Case You Missed It

September - October, 2018
Vol. 17 Issue 5 

Gamal E. Shiha, Shahira El-Etreby, Mounir Bahgat, Magdy Hamed, Mohamed El Sherbini, Elsayed A. Ghoneem, Khaled Zalata, Reham E. Soliman, Mohamed A. ElBasiouny, Nabiel NH Mikhail Page 795-801

Full-Text

Abstract
Introduction and aim. 
Transient elastography is gaining popularity as a non-invasive method for predicting liver fibrosis, but inter observer agreement and factors influencing reproducibility have not been adequately assessed. Material and methods. This cross-sectional study was conducted at Specialized Medical Hospital and the Egyptian Liver Foundation, Mansoura, Egypt. The inclusion criteria were: age older than 18 years and chronic infection by hepatitis C. The exclusion criteria were the presence of ascites, pacemaker or pregnancy. Three hundred and fifty-six patients participated in the study. Therefore, 356 pairs of exams were done by two operators on the same day. Results. The overall inter observer agreement ICC was 0.921. The correlation the two operators was excellent (Spearman's value q = 0.808, p < 0.001). Inter-observer reliability values were κ = 0.557 (p < 0.001). A not negligible discordance of fibrosis staging between operators was observed (87 cases, 24.4%). Discordance of at least one stage and for two or more stages of fibrosis occurred in 60 (16.9%) and 27 cases (7.6%) respectively. Obesity (BMI ≥ 30 kg/m2) is the main factor associated with discordance (p = 0.002). Conclusion. Although liver stiffness measurement has had an excellent correlation between the two operators, TE presented an inter-observer variability that may not be negligible.

Thursday, August 30, 2018

Current status of imaging in nonalcoholic fatty liver disease

Patients with non-alcoholic fatty liver disease (NAFLD) are at risk of steatohepatitis and progressive liver fibrosis culminating in cirrhosis, typically over a period of decades. Early diagnosis and risk stratification are essential for effective management. Current imaging methods such as ultrasound, computed tomography, and magnetic resonance elastography have demonstrated their values to serve as noninvasive imaging biomarkers to evaluate NAFLD progression, but they are still relatively limited in the detection of inflammation, which is more important than steatosis in terms of its high risk for fibrosis, cirrhosis, and hepatocellular carcinoma.

Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2018; 10(8): 530-542
Published online Aug 27, 2018. doi: 10.4254/wjh.v10.i8.530 

Current status of imaging in nonalcoholic fatty liver disease
Qian Li, Manish Dhyani, Joseph R Grajo, Claude Sirlin, Anthony E Samir 

Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic liver injury and progressive fibrosis in a significant minority. Effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard; however, non-invasive imaging methods are rapidly evolving and may replace biopsy in some circumstances. These methods include well-established techniques, such as conventional ultrasonography, computed tomography, and magnetic resonance imaging and newer imaging technologies, such as ultrasound elastography, quantitative ultrasound techniques, magnetic resonance elastography, and magnetic resonance-based fat quantitation techniques. The aim of this article is to review the current status of imaging methods for NAFLD risk stratification and management, including their diagnostic accuracy, limitations, and practical applicability.

Friday, August 3, 2018

Long–term effect of liver fibrosis after SVR in patients with HCV

Journal of Viral Hepatitis, July 27, 2018 

Cirrhosis, High Age and High Body Mass Index Are Risk Factors for Persisting Advanced Fibrosis After Sustained Virological Response in Chronic Hepatitis C
M. Hedenstierna; A. Nangarhari; A. El-Sabini; O. Weiland; S. Aleman
J Viral Hepat. 2018;25(7):802-810.

The aim of this study was to investigate the long–term effect of achieved SVR on liver fibrosis, measured as liver stiffness with transient elastography, in a cohort with pretreatment advanced chronic HCV infection. We also aimed to identify risk factors associated with persisting fibrosis.

Abbreviations
BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; FU, follow-up; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LSM, liver stiffness measurement; OR, odds ratio; SVR, sustained virological response.

Discussion Only
View Complete article: https://www.medscape.com/viewarticle/898758_1
The long–term effect of achieved SVR on liver fibrosis in patients with HCV–induced advanced fibrosis has not been extensively investigated. To study this, fibrosis in our patients was assessed by LSM during long–term follow–up over more than 5–10 years. Our study shows that the vast majority of our 269 patients with pretreatment advanced fibrosis or cirrhosis improved their fibrosis during long–term follow–up after SVR. A minority, however, continued to have advanced fibrosis even after more than 5–10 years of follow–up. In this subset of patients, a point of no return for advanced liver fibrosis might have been reached, where improvement is not possible. Other possible explanations are contributing cofactors such as liver steatosis with inflammation and alcohol use as driving forces to maintain or even progress liver fibrosis. In this study, we identified pretreatment cirrhosis, high age and high BMI as the main risk factors for lack of improvement. The proportion of patients who maintained advanced fibrosis decreased among patients with longer follow–up time, indicating that fibrosis regression is a slow process that continues over time.

Several studies with varying follow–up times have compared pre– and post–treatment fibrosis stages.[10,19–27] Studies based on liver biopsies have all shown that fibrosis and also cirrhosis can improve after achievement of SVR in a majority of patients, but also that fibrosis will persist or progress after SVR in a subset of 1%–14%, confirming the results in our study.[19–23] In a large study including more than 3000 biopsied patients with a mean follow–up time of 20 months, a low baseline fibrosis stage, age below 40 and BMI below 27 were all factors strongly associated with lack of significant fibrosis at follow–up in patients with SVR.[19] The risk factors identified to be associated with persisting fibrosis found were the same as in our long–term study.

More recent studies have investigated fibrosis regression after SVR with LSM and biochemical markers. The diagnostic accuracy of these methods to detect persisting cirrhosis after SVR, however, has been questioned.[10,24] In a study comparing LSM with follow–up biopsies 61 months after achieved SVR, the sensitivity of LSM to detect cirrhosis after SVR was only 61% when standard pretreatment cut–offs were used.[10] On the other hand, the specificity for diagnosing cirrhosis with LSM after treatment reached 95%. As LSM measures both fibrosis and inflammation, rapid early improvement of liver stiffness after SVR could be explained by a reduction in liver inflammation, and not by fibrosis regression. This could suggest that patients with pretreatment cirrhosis defined by LSM, including some with severe inflammation and less advanced fibrosis, would have lower liver stiffness at follow–up than patients with biopsy–proven cirrhosis. Surprisingly, in our study, we observed the opposite. The difference was not significant, but could be explained by the fact that patients with cirrhosis defined by LSM had shorter follow–up times. This supports our conclusion that cirrhosis regression is a process that continues over time. Recently published studies with repeated LSM up to 2 years after achieved SVR have shown a rapid initial improvement of liver stiffness, but also a continued slower reduction, better reflecting true fibrosis regression.[25–27] The follow–up times in these studies were relatively short, but the findings support the results generated in our study. Another possible explanation for the initial rapid and later slower improvement of liver stiffness levels after SVR could be the remaining presence of nodular architecture in the liver, despite decreased amount of fibrosis.[21] Nodules are the hallmark for a histopathological definition of cirrhosis.[5] This implies that the persisting advanced fibrosis in our study, measured by LSM, probably is accurate, while we might have misclassified the stage of fibrosis in some of the cirrhotic patients that still had nodular architecture.

Although this study was not designed to assess the correlation between LSM and the risk to develop HCC, there were patients in our study with improved fibrosis who later developed HCC up to 15 years after SVR. This finding supports that surveillance for HCC should continue even in patients where cirrhosis has regressed after achieved SVR. The duration for such surveillance needs to be further studied. We have earlier found that diabetes and the presence of pretreatment cirrhosis were risk factors for the development of HCC after SVR had been achieved.[13] No direct correlation between diabetes mellitus and persisting advanced fibrosis was noted in this study. On the other hand, high BMI, known to be associated with diabetes, was found to be a risk factor for persisting advanced fibrosis.

There are several limitations to this study. It had a cross–sectional and retrospective design and lacked sequential LSMs for the included patients. However, in a preliminary prospective study on LSM data collected at 6–month intervals after SVR in 100 patients with F3–F4 fibrosis at baseline, 31% had persisting advanced fibrosis, similar to the results in our study.[28] Furthermore, in our study, a third of the eligible patients were excluded or lost to follow–up, which could introduce a selection bias. Baseline characteristics for the nonincluded patients were, however, comparable to the studied patients, reducing this bias. The clinical outcome was worse in the excluded group with higher occurrence of HCC and death, but the causes of death were not liver related in a majority of the cases.

Assessment of fibrosis after SVR with transient elastography and not liver histology may have caused us to underestimate the extent of advanced fibrosis at follow–up. However, the identified patients with maintained advanced fibrosis are probably correctly classified. As all our patients were treated with IFN–based regimens, we do not know if our findings are relevant for patients treated with IFN–free regimens. One recently published study, however, showed a statistically similar median change in LSM levels 24 weeks after the end of treatment in patients with SVR after IFN–containing and IFN–free regimens.[25]

To conclude, we found that the liver fibrosis after achievement of SVR improved in the vast majority of our patients after long–term follow–up. Our data indicate that fibrosis regression is an ongoing long–term process over years. Risk factors for lack of such improvement during follow–up were pretreatment cirrhosis, older age and high body mass index. Lifestyle intervention to decrease weight in obese persons and treatment before establishment of cirrhosis at a younger age should therefore be recommended to avoid persistence of advanced fibrosis after SVR.

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Abstract and Introduction
Patients and Methods
Results
Discussion

Saturday, May 26, 2018

Weekend Video: HCV From Screening to Cure - Hosted By Ira M. Jacobson, MD.

Good day folks, the following video presentation; "HCV From Screening to Cure: A Closer Look at Changing At-Risk Populations and an Evolving Treatment Landscape" with Ira M. Jacobson, MD., and provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education, is now available for your viewing pleasure.

In this learning activity the good doctor will discuss screening strategies, stigma, patient-related barriers to treatment, hepatitis C testing for identifying current infection, and tests used to stage fibrosis. Also discussed is treatment for HCV patients with cirrhosis, as well as treatment adherence, duration, treatment according to HCV genotype, ending with "How Much Care Do The Cured Need?"

Although the learning activity is aimed at HCV specialists, this short patient-friendly presentation is beneficial for anyone considering HCV testing and treatment.



PeerView CME
Published on May 25, 2018
Released April 30, 2018
Ira M. Jacobson, MD, discusses hepatitis C virus in this CME/CE activity titled "HCV From Screening to Cure: A Closer Look at Changing At-Risk Populations and an Evolving Treatment Landscape." For the full presentation and infographics, complete CME/CE information, and to apply for credit, please visit us at http://www.peerview.com/FNC865. CME/CE credit will be available until April 29, 2019.

This CME/CE activity is jointly provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education.

Wednesday, April 4, 2018

Experiences of liver health related uncertainty among people who inject drugs living with hepatitis C

Experiences of liver health related uncertainty and self-reported stress among people who inject drugs living with hepatitis C virus: a qualitative study
Stelliana Goutzamanis, Joseph S. Doyle, Alexander Thompson, Paul Dietze, Margaret Hellard,
Peter Higgs and on behalf of the TAP study group

BMC Infectious Diseases
https://doi.org/10.1186/s12879-018-3057-1
Received: 4 August 2017
Accepted: 21 March 2018
Published: 2 April 2018

Abstract
Background
People who inject drugs (PWID) are most at risk of hepatitis C virus infection in Australia. The introduction of transient elastography (TE) (measuring hepatitis fibrosis) and direct acting antiviral medications will likely alter the experience of living with hepatitis C. We aimed to explore positive and negative influences on wellbeing and stress among PWID with hepatitis C.

Methods
The Treatment and Prevention (TAP) study examines the feasibility of treating hepatitis C mono-infected PWID in community settings. Semi-structured interviews were conducted with 16 purposively recruited TAP participants. Participants were aware of their hepatitis C seropositive status and had received fibrosis assessment (measured by TE) prior to interview. Questions were open-ended, focusing on the impact of health status on wellbeing and self-reported stress. Interviews were voice recorded, transcribed verbatim and thematically analysed, guided by Mishel’s (1988) theory of Uncertainty in Illness.

Results
In line with Mishel’s theory of Uncertainty in Illness all participants reported hepatitis C-related uncertainty, particularly mis-information or a lack of knowledge surrounding liver health and the meaning of TE results. Those with greater fibrosis experienced an extra layer of prognostic uncertainty. Experiences of uncertainty were a key motivation to seek treatment, which was seen as a way to regain some stability in life. Treatment completion alleviated hepatitis C-related stress, and promoted feelings of empowerment and confidence in addressing other life challenges.

Conclusion
TE scores seemingly provide some certainty. However, when paired with limited knowledge, particularly among people with severe fibrosis, TE may be a source of uncertainty and increased personal stress. This suggests the need for simple education programs and resources on liver health to minimise stress.

Excerpt:
--Noninvasive tests for fibrosis
Recently, the therapeutic landscape of hepatitis C has drastically changed. Non-invasive fibrosis assessment tools, such as transient elastography (TE) (an ultrasound like device which determines liver stiffness by measuring wave velocity [9]) and highly effective interferon-free direct acting antiviral (DAA) medications are now considered standard of care [10, 11]. These advances have made the elimination of hepatitis C as a public health threat a real possibility, particularly in Australia, where DAAs are widely accessible and heavily subsidised [12, 13]. However, such advances may also alter the individual experience of living with hepatitis C....

-Throughout the trial, research nurses experienced in hepatitis C and working with PWID provided participants with information and explanation of TE results.
Most participants had been diagnosed with hepatitis C many years prior to interview as having “non A, non B” hepatitis or when “Hep C wasn’t even invented”, but had only recently been told their level of fibrosis through the TAP study. Throughout the trial, research nurses experienced in hepatitis C and working with PWID provided participants with information and explanation of TE results. Many participants also received consultation regarding their hepatitis C from other healthcare providers, outside of the TAP study. Despite the consultation with research nurses following their liver assessment; most participants either did not understand or missed key information regarding their TE results, which ignited feelings of stress.

Participant:
I didn’t know anything about it, [doctors] were like: ‘liver cancer and liver all these things’ and I got really freaked out. (Score: P15, low-level fibrosis)

Approximately half the participants were unclear about the true meaning of TE results, implications of the result and how to manage their fibrosis. Participants were often left feeling frustrated or perplexed when their perceptions of liver health or treatment options did not align with their doctors’, particularly with their liver specialists:

Participant:
What I understood from [the liver specialist] is that a third is damaged. Well I’m like; ‘can’t you cut a third off?’ Just get rid of that broken bit, it’s simple for me! Then I don’t need to live with the stress. And they’re like; ‘it doesn’t work like that’. That doesn’t make sense to me. (Score: P1, high-level fibrosis)

Read the full article: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-018-3057-1

Tuesday, February 13, 2018

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with HCV

Capacity of non-invasive hepatic fibrosis algorithms to replace transient elastography to exclude cirrhosis in people with hepatitis C virus infection: A multi-centre observational study
Melissa Louise Kelly ,Stephen M. Riordan,Rohan Bopage,Andrew R. Lloyd,Jeffrey John Post

Published: February 13, 2018
https://doi.org/10.1371/journal.pone.0192763

View Full Text Online

Abstract
Introduction
Achievement of the 2030 World Health Organisation (WHO) global hepatitis C virus (HCV) elimination targets will be underpinned by scale-up of testing and use of direct-acting antiviral treatments. In Australia, despite publically-funded testing and treatment, less than 15% of patients were treated in the first year of treatment access, highlighting the need for greater efficiency of health service delivery. To this end, non-invasive fibrosis algorithms were examined to reduce reliance on transient elastography (TE) which is currently utilised for the assessment of cirrhosis in most Australian clinical settings.

Materials and methods
This retrospective and prospective study, with derivation and validation cohorts, examined consecutive patients in a tertiary referral centre, a sexual health clinic, and a prison-based hepatitis program. The negative predictive value (NPV) of seven non-invasive algorithms were measured using published and newly derived cut-offs. The number of TEs avoided for each algorithm, or combination of algorithms, was determined.

Results
The 850 patients included 780 (92%) with HCV mono-infection, and 70 (8%) co-infected with HIV or hepatitis B. The mono-infected cohort included 612 men (79%), with an overall prevalence of cirrhosis of 16% (125/780). An ‘APRI’ algorithm cut-off of 1.0 had a 94% NPV (95%CI: 91–96%). Newly derived cut-offs of ‘APRI’ (0.49), ‘FIB-4’ (0.93) and ‘GUCI’ (0.5) algorithms each had NPVs of 99% (95%CI: 97–100%), allowing avoidance of TE in 40% (315/780), 40% (310/780) and 40% (298/749) respectively. When used in combination, NPV was retained and TE avoidance reached 54% (405/749), regardless of gender or co-infection.

Conclusions
Non-invasive algorithms can reliably exclude cirrhosis in many patients, allowing improved efficiency of HCV assessment services in Australia and worldwide.

Wednesday, January 31, 2018

Non-invasive assessments for liver fibrosis – the crystal ball we long for

Solicited Review
J Gastroenterol Hepatol. 2018 Jan 30. doi: 10.1111/jgh.14103. [Epub ahead of print]

Non-invasive assessments for liver fibrosis - the crystal ball we long for.
Wong GL

Accepted manuscript online: 30 January 2018

Full Text Article
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Abstract
Non-invasive assessment of liver fibrosis has been one of the most rapidly advancing fields in hepatology in the last decade. Progressive liver fibrosis results in cirrhosis, hepatocellular carcinoma (HCC) and various liver-related complications in essentially all chronic liver diseases. Assessment of liver fibrosis allows clinicians to determine the prognosis, need of treatment, disease progression and response to treatment in patients with chronic liver disease. Liver biopsy has been the gold standard in last few decades and most adopted diagnostic tool in clinical trials. Nonetheless, it is impractical to apply the test in a large number of patients or to do it serially. Hence, various non-invasive assessments have been developed and adopted in some international management guidelines. Liver stiffness measurement (LSM) with transient elastography one of the most widely validated non-invasive assessments for liver fibrosis. It is an accurate and reproducible method to predict advanced fibrosis in chronic hepatitis B. Using transient elastography, it is possible to perform repeated liver fibrosis assessments on a large number of asymptomatic patients. The key challenge of his tool is the confounding effect of alanine aminotransferase (ALT) level, such that decrease in LSM may only reflect ALT normalization, hence not accurate enough to indicate regression of liver fibrosis. This may be partially handled by combining LSM with a serum-based formula which is independent of ALT such as the Forns index and Enhanced Liver Fibrosis test. A LSM-based HCC risk score (LSM-HCC score) is useful to prioritize patients for HCC surveillance.

Wednesday, January 3, 2018

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Friday, December 29, 2017

Non-invasive tests for NAFLD are unreliable in South Asians

Non-invasive tests for NAFLD are unreliable in South Asians
Last Updated: 2017-12-27
By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Blood-test-based non-invasive tests for non-alcoholic fatty liver disease (NAFLD) are unreliable alternatives to liver biopsy in South Asians, new research suggests.

Non-invasive liver tests (NILTs) include those based on biomarkers or on clinical and laboratory data such as NAFLD fibrosis score (NFS); Fibrosis-4 (Fib-4); BMI, AST/ALT ratio, diabetes (BARD); aspartate transaminase (AST)-to-platelet ratio index (APRI); and the AST/alanine transaminase (ALT) ratio, researchers note in Frontline Gastroenterology, online November 16.

Dr. Syn cautioned, "Because the sensitivity of these commonly used tests is lower in patients of South Asian ethnicity, it suggests that a significant number of South Asian patients may be inappropriately reassured that they do not have advanced disease. As with any clinical test, there is a danger that, if a test is applied or interpreted inappropriately, wrong decisions can be made and harm may ultimately come to a patient."


Liver Research
Non-invasive markers of liver fibrosis in fatty liver disease are unreliable in people of South Asian descent
Sampath De Silva1, Wenhao Li1, Polychronis Kemos1, James H Brindley1, Jibran Mecci1, Salma Samsuddin1, Joanne Chin-Aleong2, Roger M Feakins2, Graham R Foster1, Wing-Kin Syn1,3,4, William Alazawi1

Abstract
Objective
Liver biopsy is the most accurate method for determining stage and grade of injury in non-alcoholic fatty liver disease (NAFLD). Given risks and limitations of biopsy, non-invasive tests such as NAFLD fibrosis score, aspartate transaminase (AST) to platelet ratio index, Fib-4, AST/alanine transaminase ratio and BARD are used. Prevalence and severity of NAFLD and metabolic syndrome vary by ethnicity, yet tests have been developed in largely white populations. We tested our hypothesis that non-invasive tests that include metabolic parameters are less accurate in South Asian compared with white patients.

Full Text Article

Thursday, October 26, 2017

Primary Care Screening for Fatty Liver Disease Debated

Medscape Conference Coverage from

Primary Care Screening for Fatty Liver Disease Debated
Damian McNamara
October 23, 2017

"We are well aware that more than 50% of patients with fatty livers have normal ATL values," he pointed out. And interoperator variability and "poor predictive ability for diagnosis of fibrosis and steatosis" limit the utility of ultrasonography, which is also commonly used to evaluate patients for liver disease. Liver biopsies are more accurate, but they are invasive, he added.

For their study, Dr Hassanein and his colleagues implemented a 16-week transient elastography screening program at a primary care clinic in Chula Vista, California. They offered screening to 1298 consecutive patients, and ended up with 958 evaluable scans.

Operators used a hand-held FibroScan probe, from Echosens, to assess liver stiffness, an indication of fibrosis, and a controlled attenuation parameter (CAP) score to detect steatosis.

Read the article (LINK)

Tuesday, October 24, 2017

Liver Meeting 2017 - VIDEO: Fibrosis biomarkers show promise to replace liver biopsy

VIDEO: Fibrosis biomarkers show promise to replace liver biopsy

This noninvasive diagnostic method could replace liver biopsy, the current standard used to diagnose patients with NASH.
Read the article at GI & Hepatology News

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Saturday, October 14, 2017

Noninvasive Assessment of Fibrosis Regression in Hepatitis C Virus Sustained Virologic Responders

Gastroenterology & Hepatology
October 2017 - Volume 13, Issue 10
Gastroenterology & Hepatology (G&H) is a monthly peer-reviewed journal reaching nearly 18,000 gastroenterologists and hepatologists. G&H provides editorial content encompassing a wide array of topics relevant and useful to the fields of gastroenterology and hepatology, both separately and together. Content is directed by the strong input of today’s top thought leaders in gastroenterology and hepatology, including feature-length review articles and monthly columns consisting of engaging interviews with experts on current issues in inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), hepatology, and endoscopy. G&H also publishes industry-supported meeting highlights, clinical roundtable monographs, and clinical review supplements. The journal and all affiliated supplements are included in the National Library of Medicine’s PubMed/MEDLINE index as well as EMBASE.

Noninvasive Assessment of Fibrosis Regression in Hepatitis C Virus Sustained Virologic Responders
Hirsh D. Trivedi, MD, Steven C. Lin, MD, and Daryl T. Y. Lau, MD, MSc, MPH

Link

Keywords
Hepatitis C virus, fibrosis, noninvasive serum fibrosis markers, vibration-controlled transient elastography, magnetic resonance elastography

Abstract:
The emergence of direct-acting antiviral (DAA) therapies and noninvasive measures of liver fibrosis has streamlined the management of patients with chronic hepatitis C virus (HCV) infection. DAA therapy is associated with a significantly higher rate of sustained virologic response (SVR) compared to interferon-based therapies. Concomitantly, validated noninvasive measures of fibrosis allow evaluation of patients for therapy without an invasive liver biopsy. Noninvasive measures of fibrosis can be classified as serologic tests or imaging modalities. Several serologic tests have shown robust reliability and clinical applicability. Similarly, imaging modalities such as vibration-controlled transient elastography and magnetic resonance elastography can be used to assess liver stiffness and correlate with fibrosis. Combinations of serologic and imaging tests further improve accuracy compared to an individual modality. The availability of noninvasive fibrosis measures coupled with high SVR rates has shifted the paradigm in the management of HCV infection in the DAA era. Although these noninvasive tests are valuable in evaluating hepatic fibrosis prior to HCV therapy, use of these measures in monitoring fibrosis regression after HCV eradication is currently limited. Furthermore, for patients with pretreatment cirrhosis, the association between fibrosis regression after successful therapy and the risk of hepatocellular carcinoma (HCC) over time is unclear. There are no guidelines on long-term fibrosis monitoring and HCC surveillance after SVR is achieved. This article summarizes the current data on the applications of noninvasive methods to measure hepatic fibrosis and portal hypertension in HCV. In addition, a road map is provided for monitoring patients with advanced fibrosis after HCV eradication.

Continue to article online, or download PDF

Thursday, October 12, 2017

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement
Tag-Adeen M, Sabra AM, Akazawa Y, Ohnita K, Nakao K
     
Received 25 May 2017
Accepted for publication 18 July 2017
Published 6 October 2017 Volume 2017:9 Pages 45—53
DOI https://doi.org/10.2147/HMER.S142600

Background: Liver fibrosis is the most important prognostic factor in chronic hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV prevalence with genotype-4 predominance. The aim of this study was to investigate the degree of liver stiffness measurement (LSM) improvement after successful HCV eradication.

Patients and methods: The study included 84 chronic HCV Egyptian patients, and was conducted at Qena University Hospital from November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan® before starting direct acting antiviral (DAA) treatment and after achieving sustained virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified into F0–F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after achieving SVR-24 was compared with that before starting therapy in each fibrosis group (F0-F4), p-value <0.05 was statistically significant.

Results: Following DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean age: 54.2±7.6 years, and mean body mass index: 28.6±2.2 kg/m2. Mean baseline LSM dropped from 15.6±10.8 to 12.1±8.7 kPa post-SVR; the maximum change of −5.8 occurred in F4 versus −2.79, −1.28 and +0.08 in F3, F2 and F0–F1 respectively (p<0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%) regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic despite achieving SVR-24 (p<0.0001). Patients who achieved LSM improvement (n=64) have had significantly higher baseline aspartate transferase (AST) and alanine transaminase (ALT). Also, those patients showed significant improvement in AST, AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving SVR; 91% showed AST improvement (p=0.01) and APRI improvement (p=0.01) and 81% showed Fib-4 improvement (p=0.04). Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement.

Conclusion: Successful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended.

Link

Recommended Reading

Saturday, August 19, 2017

Podcast - Listen to Mark Sulkowski MD discuss improving HCV patient care

Mark S. Sulkowski, MD - Emerging Issues and Challenges for Improving HCV Patient Care: Expert Perspectives on the Importance of Interdisciplinary Collaboration
Released Aug 16, 2017

Podcast
Listen to Mark Sulkowski, MD, Ira M. Jacobson, MD, and Trang M. Vu, MD, discuss HCV screening, testing, linkage to care, noninvasive tests for fibrosis, drug and alcohol use, treatment regimens in patients with cirrhosis, adherence to therapy and cure.

Although this patient friendly podcast and slideshow is aimed at clinicians, taking part in the program is beneficial for anyone who may consider being tested for HCV or have been diagnosed and thinking about treatment.

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Mark S. Sulkowski, MD - Emerging Issues and Challenges for Improving HCV Patient Care: Expert Perspectives on the Importance of Interdisciplinary Collaboration


Friday, June 30, 2017

Pangenotypic regimens and the next generation hepatitis C virus therapy

The latest issue of Clinical Liver Disease
Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD). CLD publishes easy to read reviews on relevant topics for clinicians diagnosing and managing patients with liver disease. Each article is accompanied by a podcast audio version, and a video interview with the author to help emphasize the key teaching points for a clinical audience.

Issue Publication: June 2017
Volume 9, Issue 6 Pages 131 - 149, June 2017

Reviews
Hepatitis C
Guest Edited by Andrew Muir, MD
Pangenotypic regimens and the next generation hepatitis C virus therapy (pages 131–133)
Nancy S. Reau
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.635
Three new antiviral therapies for viral hepatitis C are anticipated in the next several months: GP, glecaprevir (protease inhibitor [PI])/pibrentasvir (NS5A inhibitor); SOF/VEL/VOX, sofosbuvir (NS5B inhibitor)/velpatasvir (NS5A)/voxilaprevir (NS3); and MK3, grazoprevir (NS3) + MK-3682 (NS5B) + NS5A inhibitor (elbasvir or Ruzasvir).

Each is a pangenotypic all-oral fixed dose combination (FDC) with high potency and efficacy against common NS3 and NS5A polymorphisms. Multiple safety and efficacy abstracts were presented at the 67th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in November 2016. In this article, I will address why we need new therapies as well as what is still unaddressed in the arsenal against hepatitis C.
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Noninvasive Diagnosis of Liver Fibrosis in Children and Adults
Guest Edited by Naim Alkhouri, MD and Jean Molleston, MD
Putting it all together: Noninvasive diagnosis of fibrosis in nonalcoholic fatty liver disease in adults and children (pages 134–137)
Naim Alkhouri
Multiple noninvasive tests have been developed and validated in the adult NAFLD population to predict the stage of fibrosis.[6] These tests are being widely used by gastroenterologists and hepatologists to risk-stratify patients with NAFLD without the need for liver biopsy. These tests can be divided into one of three categories: simple fibrosis scores that can be calculated from readily available clinical variables, complex fibrosis scores that rely on measuring serum biomarkers of fibrosis and extracellular matrix turnover, and imaging studies that are based on measuring liver stiffness as an indirect way to determine fibrosis stage.
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.636
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Antifibrotic therapies in liver disease: Ready for primetime? (pages 138–140)
David A. Rudnick
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.641
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LT in the High MELD Era: Perioperative Management of the Critically Ill Patient
Guest Edited by Julie Heimbach, MD and Michael Schilsky, MD
Transplantation for acute alcoholic hepatitis (pages 141–143)
Patrizia Burra and Giacomo Germani
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.629
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The Practice of Hepatology in a Non-Traditional Setting
Guest Edited by Mitchell Shiffman, MD
Contrasting the academic and nonacademic hepatology practice settings (pages 144–146)
Alexander T. Lalos and Coleman I. Smith
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.638
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Developing clinical research in a clinical hepatology practice (pages 147–149)
Oren K. Fix, Terri Spinelli and Kris V. Kowdley
Version of Record online: 29 JUN 2017 | DOI: 10.1002/cld.639
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Begin here.....

Wednesday, May 17, 2017

Liver fibrosis staging with a new 2D-shear wave elastography using comb-push technique: Applicability, reproducibility, and diagnostic performance

Liver fibrosis staging with a new 2D-shear wave elastography using comb-push technique: Applicability, reproducibility, and diagnostic performance
Sang Min Lee, Jeong Min Lee , Hyo-Jin Kang, Hyung Kung Yang, Jeong Hee Yoon, Won Chang, Su Joa An, Kyoung Bun Lee, Seung Yon Baek

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Published: May 16, 2017
https://doi.org/10.1371/journal.pone.0177264

Abstract
Objective
To evaluate the applicability, reproducibility, and diagnostic performance of a new 2D-shear wave elastography (SWE) using the comb-push technique (2D CP-SWE) for detection of hepatic fibrosis, using histopathology as the reference standard.

Materials and methods
This prospective study was approved by the institutional review board, and informed consent was obtained from all patients. The liver stiffness (LS) measurements were obtained from 140 patients, using the new 2D-SWE, which uses comb-push excitation to produce shear waves and a time-aligned sequential tracking method to detect shear wave signals. The applicability rate of 2D CP-SWE was estimated, and factors associated with its applicability were identified. Intraobserver reproducibility was evaluated in the 105 patients with histopathologic diagnosis, and interobserver reproducibility was assessed in 20 patients. Diagnostic performance of the 2D CP-SWE for hepatic fibrosis was evaluated by receiver operating characteristic (ROC) curve analysis.

Results
The applicability rate of 2D CP-SWE was 90.8% (109 of 120). There was a significant difference in age, presence or absence of ascites, and the distance from the transducer to the Glisson capsule between the patients with applicable LS measurements and patients with unreliable measurement or technical failure. The intraclass correlation of interobserver agreement was 0.87, and the value for the intraobserver agreement was 0.95. The area under the ROC curve of LS values for stage F2 fibrosis or greater, stage F3 or greater, and stage F4 fibrosis was 0.874 (95% confidence interval [CI]: 0.794–0.930), 0.905 (95% CI: 0.832–0.954), and 0.894 (95% CI: 0.819–0.946), respectively.

Conclusion
2D CP-SWE can be employed as a reliable method for assessing hepatic fibrosis with a reasonably good diagnostic performance, and its applicability might be influenced by age, ascites, and the distance between the transducer and Glisson capsule.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177264

Tuesday, April 4, 2017

Noninvasive tests for fibrosis - Editorial: combining elastography with blood test for fibrosis assessment in chronic hepatitis C

Invited Editorial

Editorial: combining elastography with blood test for fibrosis assessment in chronic hepatitis C Authors H. D. Trivedi, M. Lai

First published: 3 April 2017
DOI: 10.1111/apt.14011

Editorial: combining elastography with blood test for brosis assessment in chronic hepatitis C 
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The imprecision and invasive nature of the liver biopsy has led to the development of several validated non-invasive fibrosis markers, which have decreased the need for liver biopsy in chronic hepatitis C patients. In the realm of highly effective oral therapies, management is affected by the presence or absence of severe fibrosis, which would warrant surveillance screening for hepatocellular carcinoma and oesophageal varices. Vibration controlled transient elastography (VCTE) is a validated non-invasive modality that is widely used with an AUROC of 0.90 for detecting advanced fibrosis.[1] The limitation of VCTE is its potential overestimation of fibrosis, particularly in those with obesity or increased necroinflammatory activity.[2, 3] In contrast, serologic markers have historically led to underestimation of fibrosis levels.[4, 5] Combination of VCTE with other markers have shown favorable results[1] and have been proposed by national guidelines.[6, 7]

Calés et al. evaluated the performance of a serologic test (FibroMeterV2G) with VCTE (Fibroscan) as two separate constitutive tests, as well as a single combined test (FibroMeterVCTE2G), for the detection of severe fibrosis in hepatitis C patients.[8] They found increased accuracy with the combination test, compared to individual tests alone, especially when there was concordance between the tests, validating the recommendation of using combined tests. The authors conclude that if the constitutive tests are concordant, then the diagnosis can be accepted, and if discordant, FibroMeterVCTE2G should be pursued. However, in cases (3.2%) of strict discordance, the FibroMeterVCTE2G is unreliable for detecting severe fibrosis (accuracy of 44%) and requires alternative measures for fibrosis (i.e. liver biopsy). The authors projected a reduction in the liver biopsy rates from 28% to 1% with the use of this diagnostic algorithm.

This study validates EASL-ALEH and AASLD-IDSA recommendations to combine biomarkers with VCTE and shows the combined test to have improved accuracy, especially when there is concordance, eliminating the need for an invasive liver biopsy in the majority of patients. However, the claim that the liver biopsy rate is reduced from 28% to 1% should be taken with some caution as the authors did not provide the invalid and failure rate of VCTE, one of major components in their combination test. Although VCTE has revolutionised the non-invasive measurement of fibrosis, unreliable results and failure to obtain results have been reported in 3% and 16% of cases, respectively, mostly due to obesity and operator experience.[3] It would be important to see how the combined test performs in the United States population, which has a higher mean body mass index than this study cohort from France. While the accuracy of the FibroMeterVCTE2G is excellent, it still leaves 8% of patients misclassified, making it important that the clinician still thoroughly evaluates the patient's clinical, radiologic and laboratory data. The role of this combination test in monitoring the progression or regression of fibrosis, as well as its applicability to other chronic liver disease is an important avenue for research.

Wednesday, March 1, 2017

Developing a new algorithm to diagnose advanced liver fibrosis: A lift or a nudge in the right direction?

Developing a new algorithm to diagnose advanced liver fibrosis: A lift or a nudge in the right direction?
Leon A. Adams, Richard K. Sterlinga
DOI: http://dx.doi.org/10.1016/j.jhep.2017.02.011

Publication stage: In Press Accepted Manuscript
Published online: February 17, 2017

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Accurate identification of liver disease severity and fibrosis stage is paramount in the management of those with chronic liver disease. In the past, this was often done by liver biopsy. However, due to it’s invasiveness and risks of bleeding, pain, and sampling error, non-invasive assessment of liver disease has gained increasing attention over the last decade. Non-invasive tests can be divided into serum tests and imaging tests. Although standard “liver function” tests, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are inaccurate when used alone, several models have been developed that use them in combination with other markers of advanced liver disease, such as platelet count. Of those models that utilize routine, readily available tests, the AST-Platelet Ratio Index (APRI) and FIB-4 have gained the most attention[[1], [2]]. Both APRI and FIB-4 have high specificity and negative predictive value’s (NPV) for advanced fibrosis or cirrhosis[[1], [2]]. However, both have only moderate positive predictive values (PPV) and many patients fall in between the upper and lower cut-offs giving an indeterminate result. More complex serum panels have been developed including Fibrosure/Fibrotest[3] and Fibrometer[4], which may offer additional accuracy compared to APRI or FIB-4 but have extra cost. In addition, the alternative non-invasive imaging tests, such as vibration controlled transient elastrography (VCTE)[5] or magnetic resonance elastrography (MRE)[6] are generally only available in specialized centers, leaving many with chronic liver disease inadequately assessed. Because one serum or imaging test alone does not provide 100% sensitivity and specificity, there has been an attempt to combine tests, either performed together or sequentially[[4], [7], [8], [9], [10], [11], [12], [13], [14], [15]]. Thus, the rationale for the study by Boursier and colleagues published in the current issue of the Journal of Hepatology was to develop such a test as part of an algorithm to more accurately and easily identify advanced liver disease[16].

To that goal, the study aimed to develop and validate a stepwise algorithm that could be easily used by all providers to facilitate detection of advanced fibrosis in those with chronic liver disease. The cohort studied consisted of 3754 subjects with chronic liver disease who had undergone liver biopsy and VCTE, who were divided 2:1 into a derivation and validation set. They initially evaluated the utility of both APRI and FIB-4 as an initial screening test. Because FIB-4 outperformed APRI (higher sensitivity), they used it to compare to their new “first line test” which included age, gender, gamma-GT (GGT), AST, platelet count, and prothrombin time (PT). Each of these variables was assigned a number (0-4 depending on the variable and cut off) in the “easy LIver Fibrosis Test (eLIFT), with a score of at least 8 providing 80% sensitivity for advanced fibrosis. In a core group of 1946 subjects, they found that while FIB-4 and eLIFT had similar sensitivity (77-78%), eLIFT had higher specificity (91%), NPV (79%), and PPV (91%) with fewer false positive results than FIB-4, especially in those over age 60. They concluded that eLIFT was better than FIB-4 as a general screening test.

Subsequently, they determined what should be the “second line test” by comparing APRI, FIB-4, liver stiffness by VCTE, and Fibrometer (with or without VCTE) and found that FibrometerVCTE had the highest number of biopsies avoided (81%). A new algorithm was proposed with eLIFT as the initial screening test followed by FibrometerVCTE in those with an eLIFT score ≥ 8 for confirmation. Using this two-step strategy, 46% of patients (33% with eLIFT score <8 and 14% with eLIFT ≥ 8 but FibrometerVCTE <0.384) would not need to see a specialist thus avoiding liver biopsy or additional testing. This two-step approach found that 34% had advanced fibrosis (eLIFT >8 and FibrometerVCTE ≥ 0.715) leaving only 19% with an indeterminate result that might go on to liver biopsy. This combined strategy worked better than FIB-4 or FibrometerVCTE alone in identifying those with advanced fibrosis. Finally, they followed 1275 patients longitudinally (median follow-up 2.9 years) to determine if the eLIFT-FibrometerVCTE strategy could predict liver-related and all-cause mortality. Although eLIFT and FIB-4 had similar performance for all-cause mortality, FibrometerVCTE had the best performance for predicting liver-related mortality.

This study has several strengths; the large patient population enabled comparison of several methods of fibrosis assessment and detected relatively small differences in test performance. Furthermore, the proposed algorithm was accurate across a wide spectrum liver disease increasing applicability and attractiveness to implement in the community. In addition, eLIFT and FibrometerVCTE were demonstrated to be prognostic of liver related outcomes, re-enforcing the appropriateness to use them as tests to guide patient management. Nevertheless, the eLIFT test utilizes some serum tests that may not be routinely ordered by community physicians, such as prothrombin time, which in itself may suffer inter-laboratory variability. In addition, the use of AST and GGT in the eLIFT algorithm, resulted in a reduction in specificity in the setting of alcoholic liver disease. Nevertheless, this was resolved when combined with the FibrometerVCTE. The FibrometerVCTE was developed using the M probe, which provides higher values than the XL probe and has a lower success rate in obesity, limiting applicability in this population. For these reasons, independent validation will be important to confirm the accuracy of the eLIFT-FMVCTE algorithm. Lastly, the study population was not identified from the general population, and so caution should be exercised in trying to extrapolate this algorithm to screen for fibrosis in the general population.

Combining non-invasive algorithms is an attractive way of increasing diagnostic accuracy for liver fibrosis, however uncertainty exists on the best way to combine tests and which tests to use. For example, tests may be used concurrently with discordant results leading to a diagnostic biopsy. Alternatively two modalities may be combined into one diagnostic formula, or thirdly, tests may be used sequentially, with the first being a screening test and the second used following an indeterminate screen or as a confirmatory test for a positive screening test. The approach by Boursier utilizes a combination of firstly, a two-step approach using eLIFT as a screening test and FibrometerVCTE as the confirmatory test, which in itself combines VCTE and a serum test[16]. Thus, this approach requires three non-invasive tests to be performed, adding to the complexity and cost.

In addition to the current study, a range of alternative combination strategies have been examined (outlined in Table 1), primarily among patients with chronic hepatitis C (CHC)[[7], [8], [9], [14], [15], [16], [17], [18], [19]]. These have included the SAFE algorithm which sequentially combines APRI and Fibrotest[8], sequential APRI and Hepascore[13], concurrent Fibrotest and Fibroscan[14] and combining Fibrometer and Fibroscan into one diagnostic model[15]. In non-alcoholic fatty liver disease, concurrent Fibroscan and NAFLD Fibrosis Score and sequential FIB4 and BARD have been proposed[[7], [12]], whilst in chronic hepatitis B, a combination of concurrent ALT with Fibroscan followed by the Enhanced Liver Fibrosis Score or the Forns index has been examined[[9], [10]] Overall, these studies demonstrate an increase in diagnostic accuracy and higher predictive values with multiple non-invasive tests compared with single tests, particularly for the determination of moderate degrees of fibrosis (e.g. METAVIR F2+).

Table 1Cross-sectional studies (n>200) examining the accuracy of combination non-invasive fibrosis tests in the prediction of advanced fibrosis or cirrhosis.
AuthornLiver DiseaseOutcomeAlgorithmsDiagnostic AccuracySensitivitySpecificityNPVPPV
Boursier 2009332MixedCirrhosisAPRI → Fibrotest80%44%93%81%71%
Fibrotest + Fibroscan94%89%96%96%90%
Fibrometer / Fibroscan91%75%97%91%91%
Sebastiani 20092035HCVCirrhosisAPRI → Fibrotest92%90%93%56%99%
Castera 2010302HCVCirrhosisAPRI → Fibrotest89%86%90%94%78%
Fibrotest + Fibroscan96%89%98%96%95%
Sebastiani 20121013HCVCirrhosisAPRI → Fibrotest91%82%92%98%57%
APRI + Fibrotest.94%73%97%96%73%
Boursier 20121785HCVCirrhosisAPRI → Fibrotest89%61%93%95%56%
Fibrotest + Fibroscan94%86%95%98%76%
Fibrometer / Fibroscan87%----
Crisan 2012446HCVAdvanced fibrosisAPRI + FIB4 + Fibrometer89%84%91%94%76%
APRI + FIB4 + Fibrotest85%88%83%95%68%
APRI + FIB4 + Fibroscan86%62%100%59%100%
Wong 2014323HBVAdvanced fibrosisFibroscan + ELF-65-66%86-92%79-80%76-85%
Petta 2014321NAFLDAdvanced fibrosisFibroscan + FIB4-42-85%97-100%91-98%71-100%
Fibroscan + NFS-25-83%100%93-99%100%
FIB4 + NFS-14-35%100%88-91%100%
Boursier 20171946MixedAdvanced fibrosiseLIFT → Fibrometer/Fibroscan-78%91%79%91%

Fibroscan available in 729 patients. Mixed liver disease included patients with liver disease realted to alcohol, hepatitis c virus (HCV), hepatitis B virus (HBV), non-alcoholic fatty liver disease (NAFLD) and other causes. “→” indicates sequentially performed tests, “+” indicates concurrent tests, “/” indicates combined tests into one formula, ELF=Enhanced Liver Fibrosis score, APRI= AST to platelet ratio index.

Determining the optimal combination of tests is difficult as studies have been performed in different diseases, used different cut-offs and aimed to predict different stages of fibrosis. Notably, the only independent prospective multi-center evaluation of a range of non-invasive fibrosis tests including Fibrotest, Fibrometer, Hepascore, APRI and Fibroscan, found no difference in percentage of well-classified patients or biopsies avoided between synchronous combinations of the above tests, for the prediction of cirrhosis in patients with CHC[11]. However, other studies have found the combination of Fibroscan and a serum test (Fibrotest) is more accurate than the combination of two sequential serum tests incorporated into the SAFE algorithm (APRI and Fibrotest)[[14], [15]]. Using a serum based test in combination with elastography is an appealing strategy as they assess different pathophysiological properties associated with fibrosis, and thus this is currently suggested by EASL Guidelines[20]. However, the requirement for a concurrent Fibroscan limits the applicability of this strategy into the community. The ideal algorithm to screen the general population should be a combination of an inexpensive, accessible and highly sensitive test to minimize missed diagnoses, followed by a highly specific test to confirm the diagnosis. To this end, the eLIFT cut-off of eight was chosen to aim for 80% sensitivity, which translated to up to one third of patients with advanced fibrosis being missed but only 3-4% of cirrhotics. One option to minimize false negative cases would be to lower the eLIFT threshold, however this would be at the cost of a greater false positive rate and needless referral for further assessment. Other potential screening tests include FIB4 and APRI in combination given their wide-spread availability and low cost followed by elastrography in those with discordant or increased results above the lower threshold.

Because one test is often inadequate to answer both questions: which patient has minimal liver disease (F0-1) and secondly, which patient has advanced fibrosis (F3-4), it is clear that non-invasive fibrosis markers should not be used in isolation but incorporated into clinical acumen, imaging and other biochemical tests. Overall accuracy and predictive values are improved if two non-invasive fibrosis assessments are used. A sensitive, easy to perform screening test is required for community practitioners (e.g. serum test). More expensive and accurate confirmatory tests such as complex serum models or elastography, can then be done in the hepatology clinic. Currently, further independent comparisons are required to determine the optimal algorithms, however this will also be influenced by factors such including expense and availability. Of equal importance however, is the need to change the paradigm of liver disease assessment in the community to include fibrosis algorithms rather than relying on standard liver enzymes. Until then the current study is a nudge in the right direction.

http://www.journal-of-hepatology.eu/article/S0168-8278(17)30106-X/fulltext