Role of Liver Biopsy and Serum Markers of Liver Fibrosis in Non-alcoholic Fatty Liver Disease

2007 ◽  
Vol 11 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Leon A. Adams ◽  
Paul Angulo
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Serum Markers ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Cytokeratin-18 and hyaluronic acid levels predict liver fibrosis in children with non-alcoholic fatty liver disease.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Dariusz M Lebensztejn ◽  
Aldona Wierzbicka ◽  
Piotr Socha ◽  
Maciej Pronicki ◽  
Elżbieta Skiba ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Serum Markers ◽  
Cytokeratin 18 ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

There is a need to replace liver biopsy with non-invasive markers that predict the degree of liver fibrosis in fatty liver disease related to obesity. Therefore, we studied four potential serum markers of liver fibrosis and compared them with histopathological findings in liver biopsy in children with non-alcoholic fatty liver disease (NAFLD). We determined fasting serum level of hyaluronic acid (HA), laminin, YKL-40 and cytokeratin-18 M30 in 52 children (age range 4-19, mean 12 years, 80 % of them were overweight or obese) with biopsy-verified NAFLD. Viral hepatitis, autoimmune and metabolic liver diseases (Wilson's disease, alpha-1-antitrypsin deficiency, cystic fibrosis) were excluded. Fibrosis stage was assessed in a blinded fashion by one pathologist according to Kleiner. Receiver operating characteristics (ROC) analysis was used to calculate the power of the assays to detect liver fibrosis (AccuROC, Canada). Liver fibrosis was diagnosed in 19 children (37 %). The levels of HA and CK18M30 were significantly higher in children with fibrosis compared to children without fibrosis (p=0.04 and 0.05 respectively). The ability of serum HA (cut-off 19.1 ng/ml, Se=84 %, Sp=55 %, PPV=52 %, NPV=86 %) and CK18M30 (cut-off 210 u/l, Se=79 %, Sp=60 %, PPV=56 %, NPV=82 %) to differentiate children with fibrosis from those without fibrosis was significant (AUC=0.672 and 0.666, respectively). The combination of both markers was superior (AUC=0.73, p=0.002). Laminin and YKL-40 levels did not allow a useful prediction. Cytokeratin-18 and hyaluronic acid are suitable serum markers predicting liver fibrosis in children with NAFLD. Studying these markers may identify patients at risk of disease progression.

scholarly journals Short-Term Western Diet Aggravates Non-Alcoholic Fatty Liver Disease (NAFLD) With Portal Hypertension in TGR(mREN2)27 Rats

2020 ◽  
Vol 21 (9) ◽  
pp. 3308 ◽  
Author(s):  
Carla Cremonese ◽  
Robert Schierwagen ◽  
Frank Erhard Uschner ◽  
Sandra Torres ◽  
Olaf Tyc ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Western Diet ◽  
Suitable Model ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.

scholarly journals The diagnostic conundrum in non-alcoholic fatty liver disease

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.

scholarly journals Non-alcoholic fatty liver disease - a look at diagnostic prospects

2021 ◽  
pp. 62-67
Author(s):  
Ya. A. Krasner ◽  
M. F. Osipenko ◽  
N. V. Litvinova ◽  
E. A. Bikbulatova ◽  
S. I. Holin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Diagnostic Criteria ◽  
Fatty Liver Disease ◽  
Diagnostic Value ◽  
Serum Markers ◽  
Diagnostic Methods ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

This article observes the main trends in the diagnosis of non-alcoholic hepatic steatosis, which have been observed in world practice recently. From a practical point of view, one of the most significant events was the introduction of a new term “metabolically associated fatty liver disease” (MAFLD), which partly replaced the previously used term “primary non-alcoholic fatty liver disease”. The new nomenclature induces clear diagnostic criteria for MAFLD, and this disease has ceased to be a diagnosis of exclusion, as a result. In the near future, the practical aspects of the application of this nomenclature and new diagnostic criteria are to be evaluated. The second important trend is the increasing role of direct serum markers of liver fibrosis in the diagnosis and prognosis of MAFLD. Thus, collagen type 3 propeptide (PRO-C3), as well as M2BPGi (Mac2 Binding Proteine Glycosylation isomer), look very promising, since research data have demonstrated a higher diagnostic value of these markers in comparison with indirect fibrosis indices, which are most often used in clinical practice. In addition, the search continues for new direct serum markers of fibrosis, which would be more sensitive for detecting liver fibrosis of stages 1-2. In general, one should expect a gradual replacement by serological markers of fibrosis of technically more complex and expensive diagnostic methods, such as magnetic resonance elastography and fibroelastometry.

scholarly journals Liver Fibrosis in Non-alcoholic Fatty Liver Disease: From Liver Biopsy to Non-invasive Biomarkers in Diagnosis and Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Leen J. M. Heyens ◽  
Dana Busschots ◽  
Ger H. Koek ◽  
Geert Robaeys ◽  
Sven Francque
Keyword(s):  
At Risk ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Diagnostic Tools ◽  
Alcoholic Fatty Liver ◽  
Non Invasive ◽  
Alcoholic Fatty Liver Disease

An increasing percentage of people have or are at risk to develop non-alcoholic fatty liver disease (NAFLD) worldwide. NAFLD comprises different stadia going from isolated steatosis to non-alcoholic steatohepatitis (NASH). NASH is a chronic state of liver inflammation that leads to the transformation of hepatic stellate cells to myofibroblasts. These cells produce extra-cellular matrix that results in liver fibrosis. In a normal situation, fibrogenesis is a wound healing process that preserves tissue integrity. However, sustained and progressive fibrosis can become pathogenic. This process takes many years and is often asymptomatic. Therefore, patients usually present themselves with end-stage liver disease e.g., liver cirrhosis, decompensated liver disease or even hepatocellular carcinoma. Fibrosis has also been identified as the most important predictor of prognosis in patients with NAFLD. Currently, only a minority of patients with liver fibrosis are identified to be at risk and hence referred for treatment. This is not only because the disease is largely asymptomatic, but also due to the fact that currently liver biopsy is still the golden standard for accurate detection of liver fibrosis. However, performing a liver biopsy harbors some risks and requires resources and expertise, hence is not applicable in every clinical setting and is unsuitable for screening. Consequently, different non-invasive diagnostic tools, mainly based on analysis of blood or other specimens or based on imaging have been developed or are in development. In this review, we will first give an overview of the pathogenic mechanisms of the evolution from isolated steatosis to fibrosis. This serves as the basis for the subsequent discussion of the current and future diagnostic biomarkers and anti-fibrotic drugs.

scholarly journals A prospective 5-year study on the use of transient elastography to monitor the improvement of non-alcoholic fatty liver disease following bariatric surgery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shirley Yuk-Wah Liu ◽  
Vincent Wai-Sun Wong ◽  
Simon Kin-Hung Wong ◽  
Grace Lai-Hung Wong ◽  
Carol Man-sze Lai ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Monitoring Tool ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractLiver stiffness measurement (LSM) by transient elastography (TE) is a non-invasive assessment for diagnosing and staging liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Evidence on its role as a longitudinal monitoring tool is lacking. This study aims to evaluate the role of TE in monitoring NAFLD improvement following bariatric surgery. This study prospectively recruited 101 morbidly obese patients undergoing laparoscopic bariatric surgery for intraoperative liver biopsy. Thirty-seven patients of the cohort received perioperative TE. Postoperative anthropometric, biochemical and LSM data were collected annually for 5 years. In 101 patients receiving liver biopsy (mean age 40.0 ± 10.3 years, mean body-mass-index (BMI) 40.0 ± 5.7 kg/m2), NASH and liver fibrosis were diagnosed in 42 (41.6%) and 48 (47.5%) patients respectively. There were 29 (28.7%) stage 1, 11 (10.9%) stage 2, 7 (6.9%) stage 3, and 1 (1.0%) stage 4 fibrosis. In 37 patients receiving TE (mean age 38.9 ± 10.8 years, mean BMI 41.1 ± 5.6 kg/m2), the percentages of total weight loss were 21.1 ± 7.6% at 1 year, 19.7 ± 8.3% at 3 years, and 17.1 ± 7.0% at 5 years after surgery. The mean LSM reduced significantly from 9.8 ± 4.6 kPa at baseline to 6.9 ± 3.4 kPa at 1 year, 7.3 ± 3.0 kPa at 3 years, and 6.8 ± 2.6 kPa at 5 years (P = 0.002). Using pre-defined LSM cut-offs, the rates of significant fibrosis, advanced fibrosis and cirrhosis being ruled out at 5 years improved from baseline values of 43.7 to 87.5% (P < 0.001), 56.8 to 91.7% (P < 0.001), and 64.9 to 91.7% (P < 0.001), respectively. TE was a useful monitoring tool in demonstrating the improvement of liver fibrosis following bariatric surgery.

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