Maximising Diagnoses of Advanced Fibrosis in Primary Care with Non-Invasive Markers of Liver Fibrosis and Minimising Unnecesary Referals to Secondary Care

Background & aim Liver fibrosis screening in primary care population is a major public health issue. The FIB-4 index is a simple non-invasive fibrosis test combining age, transaminases, platelets count, developed for the diagnosis of advanced fibrosis. The aim of our study was to evaluate the interest of liver fibrosis screening using systematic calculation of FIB-4 in routine blood analysis. Methods Between December 2018 and May 2019, we conducted a prospective screening of liver fibrosis in 134 158 patients during a medical check-up including routine blood analysis. Among these patients, 29 707 had transaminases and platelets counts available and benefited from an automatic calculation of FIB-4. Results were obtained from 21 French clinical laboratories in the Bouches du Rhône region. Results Among the 29 707 patients, 2161 (7.3%) had a high risk of advanced fibrosis (FIB-4>2.67). Individual investigation of patients with FIB-4>2.67 allowed to screen 1268 (1268/2161: 58.7%) patients who were not managed for any liver disease. Conclusions This work demonstrates the interest of FIB-4 for the screening of liver fibrosis in primary care population. Although additional clinical validation study is required to determine the utility and applicability of Fib-4 to daily practice, our study strongly supports this easy-to-implement strategy using a simple Fib-4 measure resulting from the use of available routine test results.

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Liver fibrosis is associated with carotid atherosclerosis in patients with liver biopsy-proven nonalcoholic fatty liver disease

Scientific Reports ◽

10.1038/s41598-021-95581-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Taeang Arai ◽

Masanori Atsukawa ◽

Akihito Tsubota ◽

Keizo Kato ◽

Hiroshi Abe ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Biopsy ◽

Fatty Liver Disease ◽

Carotid Atherosclerosis ◽

Subclinical Atherosclerosis ◽

Scoring Systems ◽

Advanced Fibrosis ◽

Nonalcoholic Fatty Liver ◽

Non Invasive

AbstractNonalcoholic fatty liver disease (NAFLD) is related to subclinical atherosclerosis. However, whether the severity of the disease (or which histopathological component) is associated with subclinical atherosclerosis remains controversial. This study aimed to investigate the association between the histopathological severity of NAFLD and carotid intima-media thickness (CIMT) in Japanese patients with liver biopsy-proven NAFLD. Maximum-CIMT (max-CIMT) was measured as an index of carotid atherosclerosis in 195 biopsy-proven NAFLD patients. A significant association was observed between the severity of fibrosis (but not steatosis, inflammation, and ballooning) and max-CIMT. Older age, male gender, hypertension, and advanced fibrosis were independently linked to max-CIMT ≥ 1.2 mm. The prevalence of max-CIMT ≥ 1.2 mm was significantly higher in the advanced fibrosis group than in the non-advanced fibrosis group (75.4% versus 44.0%; p < 0.01). Non-invasive liver fibrosis markers and scoring systems, including fibrosis-4 index, NAFLD fibrosis score, hyaluronic acid, and Wisteria floribunda agglutinin positive Mac-2-binding protein, demonstrated that the diagnostic performance for max-CIMT ≥ 1.2 mm was similar to that of biopsy-based fibrosis staging. In conclusion, advanced fibrosis is significantly and independently associated with high-risk CIMT. Non-invasive fibrosis markers and scoring systems could help estimate the risk of atherosclerosis progression in patients with NAFLD.

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A209 NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS USING APRI, FIB-4, AND TRANSIENT ELASTOGRAPHY IN CHRONIC HEPATITIS B PATIENTS

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.207 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 239-240

Author(s):

D H Little ◽

S Fischer ◽

S K Fung

Keyword(s):

Chronic Hepatitis ◽

Liver Fibrosis ◽

Hepatitis B ◽

Liver Biopsy ◽

Chronic Hepatitis B ◽

Transient Elastography ◽

Hbv Dna ◽

Advanced Fibrosis ◽

Predictive Values ◽

Non Invasive

Abstract Background Accurate assessment of liver fibrosis is important to identify patients with chronic hepatitis B (CHB) who require antiviral therapy. As liver biopsy is invasive and costly, non-invasive tests of liver fibrosis are increasingly being used. Aims We aimed to evaluate the performance of the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4), and transient elastography (TE) in predicting fibrosis in patients with CHB. Methods We retrospectively analyzed a prospectively enrolled cohort of consecutive adults with CHB who underwent liver biopsy for routine clinical indications (ALT > ULN and HBV DNA > 2,000 IU/ml) from January 2018 to December 2019. Demographic information, routine biochemistry, HBV serology including HBV DNA, abdominal ultrasound, fibrosis stage by liver biopsy and TE data were collected. Positive predictive values (PPV) and negative predictive values (NPV) were calculated using published cut-off values with liver biopsy as the reference standard. Results Fifty-five patients of Asian ethnicity (mean age 46 years, 65% male) were included. Most patients were HBeAg-negative (67%) and treatment-naïve (80%). Eleven (20%) patients had advanced fibrosis (F3-F4 METAVIR) and 4 (7%) patients had cirrhosis (F4). APRI <0.50 had a NPV of 73% for significant fibrosis (F2-F4) and APRI >1.50 had a PPV of 33% for significant. All 4 patients with cirrhosis were misclassified as having no cirrhosis with an APRI <1. FIB-4 <1.45 had a NPV of 90% for advanced fibrosis (F3-F4). No patient, including 11 patients with advanced fibrosis, had a FIB-4 above the cut-off value to detect advanced fibrosis (>3.25). TE data was available for 38 patients. TE <7.25 kPa had a NPV of 78% for significant fibrosis and TE >12.4 kPa had a PPV of 50% for cirrhosis. Conclusions In Asian patients with CHB and a low prevalence of advanced fibrosis or cirrhosis, APRI, FIB-4, and TE performed well in excluding those with advanced fibrosis but were unable to accurately identify those with significant/advanced fibrosis and cirrhosis. Further studies with larger numbers of CHB patients are needed to confirm our results. Funding Agencies None

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Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics

International Journal of Molecular Sciences ◽

10.3390/ijms22147411 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7411

Author(s):

Jingjing Jiao ◽

Jessica I. Sanchez ◽

Erika J. Thompson ◽

Xizeng Mao ◽

Joseph B. McCormick ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Fibrosis ◽

Somatic Mutations ◽

Advanced Fibrosis ◽

Cell Free Dna ◽

Non Invasive ◽

Free Dna ◽

Significant Difference ◽

Advanced Liver Fibrosis

Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.

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The diagnostic conundrum in non-alcoholic fatty liver disease

Exploration of Medicine ◽

10.37349/emed.2020.00018 ◽

2020 ◽

Vol 1 (5) ◽

Author(s):

Valerio Rosato ◽

Mario Masarone ◽

Andrea Aglitti ◽

Marcello Persico

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Biopsy ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Advanced Fibrosis ◽

Alcoholic Fatty Liver ◽

Simple Steatosis ◽

Non Invasive ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver alteration worldwide. It encompasses a spectrum of disorders that range from simple steatosis to a progressive form, defined non-alcoholic steatohepatitis (NASH), that can lead to advanced fibrosis and eventually cirrhosis and hepatocellular carcinoma. On liver histology, NASH is characterized by the concomitant presence of significant fat accumulation and inflammatory reaction with hepatocellular injury. Until now, liver biopsy is still required to differentiate simple steatosis from NASH and evaluate the degree of liver fibrosis. Unfortunately, this technique has well-known limitations, including invasiveness and expensiveness. Moreover, it may be biased by sampling error and intra- or inter-observed variability. Furthermore, due to the increasing prevalence of NAFLD worldwide, to program a systematic screening with liver biopsy is not imaginable. In recent years, different techniques were developed and validated with the aim of non-invasively identifying NASH and assess liver fibrosis degrees. The non-invasive tests range from simple blood-tests analyses to composite scores and complex imaging techniques. Nevertheless, even if they could represent cost-effective strategies for diagnosing NASH, advanced fibrosis and cirrhosis, their accuracy and consequent usefulness are to be discussed. With this aim, in this review the authors summarize the current state of non-invasive assessment of NAFLD. In particular, in addition to the well-established tests, the authors describe the future perspectives in this field, reporting the latest tests based on OMICS, gut-miocrobioma and micro-RNAs. Finally, the authors provide an accurate assessment of how these non-invasive tools perform in clinical practice depending on the clinical context, with the aim of giving the clinicians a useful tool to try to resolve the diagnostic conundrum of NAFLD.

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NAFLD: Diagnostic Algorithms for Regulating Patient Fluxes

Current Pharmaceutical Design ◽

10.2174/1381612827666210127120748 ◽

2021 ◽

Vol 27 ◽

Author(s):

Giada Pallini ◽

Emmanuel A. Tsochatzis

Keyword(s):

Primary Care ◽

Metabolic Syndrome ◽

Secondary Care ◽

Integrated Management ◽

Management Plan ◽

Industrialized Countries ◽

Non Invasive ◽

Testing Strategies ◽

Review Analysis ◽

Efficiency And Effectiveness

: The global prevalence of NAFLD is estimated to be over 25% and it is already the leading cause of chronic liver disease in industrialized countries, as a consequence of the spread of obesity and metabolic syndrome. The prognosis of NAFLD is generally benign in the absence of fibrosis, but liver fibrosis rapidly progresses in 20% of the cases and can lead to cirrhosis and/or HCC. This review analysis focuses on non-invasive fibrosis testing strategies for patients with NAFLD in order to increase the efficiency and effectiveness of diagnosis and care, regulating secondary care referral fluxes. An integrated management plan between primary care and secondary care with a defined algorithm of non-invasive testing to stratify the risk of NAFLD fibrosis is indispensable to increase the early diagnosis of fibrosis but also decrease unnecessary referrals.

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Sa1557 PRAGMATIC USE OF NON-INVASIVE DIAGNOSTIC METHODS OF LIVER FIBROSIS IN NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD). INDUCTIVE-DECISION MODEL FOR PRIMARY CARE ATTENTION IN “REAL LIFE”.

Gastroenterology ◽

10.1016/s0016-5085(20)31568-7 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-348

Author(s):

Angel N. Del Cueto-Aguilera ◽

Diego Garcia-Compean ◽

Alan R. Jimenez Rodriguez ◽

Martin I. Wah-Suarez ◽

Juan Muñoz-Ayala ◽

...

Keyword(s):

Primary Care ◽

Liver Disease ◽

Liver Fibrosis ◽

Fatty Liver Disease ◽

Decision Model ◽

Real Life ◽

Diagnostic Methods ◽

Alcoholic Fatty Liver ◽

Non Invasive ◽

Alcoholic Fatty Liver Disease

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905 Non-Invasive Screening for NAFLD and Advanced Fibrosis in Diabetics in Primary Care Setting by MRI and MRE: A Prospective Pilot Study

Gastroenterology ◽

10.1016/s0016-5085(15)33414-4 ◽

2015 ◽

Vol 148 (4) ◽

pp. S-1000

Author(s):

Iliana Doycheva ◽

Phirum Nguyen ◽

Jeffrey Y. Cui ◽

Heather L. Hofflich ◽

Ricki Bettencourt ◽

...

Keyword(s):

Primary Care ◽

Pilot Study ◽

Care Setting ◽

Primary Care Setting ◽

Advanced Fibrosis ◽

Non Invasive ◽

Prospective Pilot Study

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Is there scope to improve the selection of patients with alcohol-related liver disease for referral to secondary care? A retrospective analysis of primary care referrals to a UK liver centre, incorporating simple blood tests

BMJ Open ◽

10.1136/bmjopen-2020-047786 ◽

2021 ◽

Vol 11 (6) ◽

pp. e047786

Author(s):

Freya Alison Rhodes ◽

Sara Cococcia ◽

Preya Patel ◽

Jasmina Panovska-Griffiths ◽

Sudeep Tanwar ◽

...

Keyword(s):

Primary Care ◽

Liver Disease ◽

Fatty Liver ◽

Retrospective Analysis ◽

Secondary Care ◽

Fatty Liver Disease ◽

Secondary Outcome ◽

Advanced Fibrosis ◽

Blood Tests ◽

Related Liver Disease

ObjectivesTwenty per cent of people with alcohol use disorders develop advanced fibrosis and warrant referral to secondary care. Improving outcomes in alcohol-related liver disease (ArLD) relies on its earlier detection in primary care with non-invasive tests (NIT). We aimed to determine the proportion of alcohol-related referrals who were diagnosed with advanced fibrosis in secondary care, the prevalence of both alcohol and fatty liver disease (‘BAFLD’) and the potential impact of NIT on referral stratification.Design/settingRetrospective analysis of all general practitioner-referrals with suspected ArLD/non-alcoholic fatty liver disease (NAFLD) to a UK hepatology-centre between January 2015 and January 2018.ParticipantsOf 2944 new referrals, 762 (mean age 55.5±13.53 years) met inclusion criteria: 531 NAFLD and 231 ArLD, of which 147 (64%) could be reclassified as ‘BAFLD’.Primary outcome measureProportion of referrals with suspected ArLD/NAFLD with advanced fibrosis as assessed by tertiary centre hepatologists using combinations of FibroScan, imaging, examination and blood tests and liver histology, where indicated.Secondary outcome measuresIncluded impact of body mass index/alcohol consumption on the odds of a diagnosis of advanced fibrosis, and performance of NIT in predicting advanced fibrosis in planned post-hoc analysis of referrals.ResultsAmong ArLD referrals 147/229 (64.2%) had no evidence of advanced fibrosis and were judged ‘unnecessary’. Advanced fibrosis was observed in men drinking ≥50 units per week (U/w) (OR 2.74, 95% CI 1.51 to 5, p=0.001) and ≥35 U/w in women (OR 5.11, 95% CI 1.31 to 20.03, p=0.019). Drinking >14 U/w doubled the likelihood of advanced fibrosis in overweight/obesity (OR 2.11; 95% CI 1.44 to 3.09; p<0.001). Use of fibrosis 4 score could halve unnecessary referrals (OR 0.50; 95% CI 0.32 to 0.79, p=0.003) with false-negative rate of 22%, but was rarely used.ConclusionsThe majority of referrals with suspected ArLD were deemed unnecessary. NIT could improve identification of liver damage in ArLD, BAFLD and NAFLD in primary care. Anecdotal thresholds for harmful drinking (35 U/w in women and 50 U/w in men) were validated. The impact of alcohol on NAFLD highlights the importance of multi-causality in chronic liver disease.

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