Reliability of Liver Stiffness Measurement in NAFLD
Reliability of Liver Stiffness Measurement in NAFLD
Background Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood.
Aim To assess LSM.
Methods Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe.
Results Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut-off for predicting significant fibrosis at biopsy (AUC 0.794); however, this cut-off still failed to rule out F2-F4 fibrosis in 31% (false-negative rate) or rule in F3-F4 in 29% (false-positive rate). Similarly a LSM value >8.75 kPa was the best cut-off for severe fibrosis (F3-F4) (AUC 0.870), with a rate of false-negatives 24% and of false-positives 2%. Body mass index was the major determinant of these diagnostic errors in predicting significant and severe fibrosis both by overestimating or underestimating the stage of fibrosis.
Conclusions In NAFLD patients, even when liver stiffness measurement is feasible, high BMI values negatively affect the diagnostic reliability. Improved performance of transient elastography could be obtained using specifically designed probes.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, with a prevalence of about 20–30%. A relevant proportion of NAFLD patients, particularly those with non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Anthropometric factors and liver necroinflammation are associated with the progression of liver disease over time, even if the severity of fibrosis is the strongest predictor of liver related morbidity and mortality. Along this line, the evaluation of liver fibrosis is crucial for the prognostic evaluation of NAFLD patients, particularly in patients without advanced disease, but at risk of developing cirrhosis, like those with significant or severe fibrosis.
Biopsy, even if invasive, painful and with potentially life-threatening complications, remains the gold standard for the evaluation of liver fibrosis. In the past few years, different non-invasive biochemical and instrumental tools have been used, with contrasting results. In this setting, various number of studies have proposed liver stiffness measurement (LSM) using transient elastography (TE) as a quick, accurate and non-invasive test to assess the stage of fibrosis and portal hypertension in patients with chronic liver disease of different aetiologies. Most of these studies were performed in patients with chronic hepatitis C, whereas limited data are available in subjects with NAFLD. Recent studies on children and adults with NAFLD have shown a good performance of LSM in staging fibrosis. Two of these studies also identified severe steatosis as a factor reducing the reliability of TE, while an insufficient length of the liver biopsy may underestimate the stage of fibrosis more correctly classified by TE. A major limiting factor to the diagnostic performance of TE in NAFLD is obesity, which may hinder the execution of TE especially when using the standard M probe.
We aimed to assess in a cohort of consecutive patients with biopsy-proven NAFLD: (i) the reliability of LSM, (ii) its performance in diagnosing significant and severe fibrosis, and (iii) which factors may affect its diagnostic performance.
Abstract and Introduction
Abstract
Background Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood.
Aim To assess LSM.
Methods Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe.
Results Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut-off for predicting significant fibrosis at biopsy (AUC 0.794); however, this cut-off still failed to rule out F2-F4 fibrosis in 31% (false-negative rate) or rule in F3-F4 in 29% (false-positive rate). Similarly a LSM value >8.75 kPa was the best cut-off for severe fibrosis (F3-F4) (AUC 0.870), with a rate of false-negatives 24% and of false-positives 2%. Body mass index was the major determinant of these diagnostic errors in predicting significant and severe fibrosis both by overestimating or underestimating the stage of fibrosis.
Conclusions In NAFLD patients, even when liver stiffness measurement is feasible, high BMI values negatively affect the diagnostic reliability. Improved performance of transient elastography could be obtained using specifically designed probes.
Introduction
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, with a prevalence of about 20–30%. A relevant proportion of NAFLD patients, particularly those with non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Anthropometric factors and liver necroinflammation are associated with the progression of liver disease over time, even if the severity of fibrosis is the strongest predictor of liver related morbidity and mortality. Along this line, the evaluation of liver fibrosis is crucial for the prognostic evaluation of NAFLD patients, particularly in patients without advanced disease, but at risk of developing cirrhosis, like those with significant or severe fibrosis.
Biopsy, even if invasive, painful and with potentially life-threatening complications, remains the gold standard for the evaluation of liver fibrosis. In the past few years, different non-invasive biochemical and instrumental tools have been used, with contrasting results. In this setting, various number of studies have proposed liver stiffness measurement (LSM) using transient elastography (TE) as a quick, accurate and non-invasive test to assess the stage of fibrosis and portal hypertension in patients with chronic liver disease of different aetiologies. Most of these studies were performed in patients with chronic hepatitis C, whereas limited data are available in subjects with NAFLD. Recent studies on children and adults with NAFLD have shown a good performance of LSM in staging fibrosis. Two of these studies also identified severe steatosis as a factor reducing the reliability of TE, while an insufficient length of the liver biopsy may underestimate the stage of fibrosis more correctly classified by TE. A major limiting factor to the diagnostic performance of TE in NAFLD is obesity, which may hinder the execution of TE especially when using the standard M probe.
We aimed to assess in a cohort of consecutive patients with biopsy-proven NAFLD: (i) the reliability of LSM, (ii) its performance in diagnosing significant and severe fibrosis, and (iii) which factors may affect its diagnostic performance.
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