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Aetiology determines optimal liver stiffness cutoff in chronic liver diseases

Tristan Manalac
05 Jan 2019

Optimal cutoff values for liver stiffness measurement (LSM) should be determined according to the aetiology of the chronic liver disease (CLD), according to a new Singapore study.

“This is the first multicentre, quality-controlled, biopsy-paired study of TE performed in Singapore. Our study demonstrated an optimal LSM of 13 kPa for the diagnosis of liver cirrhosis in the overall study cohort with mixed aetiologies,” said researchers, adding that the corresponding cutoff value for fibrosis was 9 kPa.

A total of 322 CLD patients (mean age 49.4±12.3 years; 55.6 percent male) who underwent liver biopsy and LSM were enrolled in the current study. Almost half (45 percent) of the participants had no or mild (METAVIR stage F0 and F1) fibrosis, while 41 percent and 14 percent had moderate fibrosis (F2 and F3) and cirrhosis (F4), respectively. [Singapore Med J 2018;doi:10.11622/smedj.2018156]

The median LSM value in the study cohort was 9.7 kPa and was significantly correlated with fibrosis (Spearman’s rank correlation coefficient, 0.52; p<0.001). That is, the mean LSM in those with METAVIR stages F0 and F1 were 8.5±0.9 and 8.8±0.5 kPa, respectively. Corresponding mean values for stages F2, F3 and F4 were 13.9±1.5, 15.0±1.3 and 29.1±3.3 kPa.

Transient elastography (TE) was used in the assessment of significant liver fibrosis (METAVIR F2) and returned an area under the receiver operating characteristic curve (AUROC) of 0.775 (95 percent CI, 0.724–0.826; p<0.001).

The above curve identified an optimal LSM cutoff value of 9 kPa, yielding a sensitivity of 76.7 percent and a specificity of 68.4 percent, as well as an overall correct classification rate of 72.7 percent. The positive (PPV) and negative (NPV) predictive values were 74.9 percent and 69.9 percent, respectively.

In comparison, the AUROC for using TE to diagnose cirrhosis (METAVIR F4) was 0.810 (0.738–0.882; p<0.001). At the optimal cutoff LSM value of 13 kPa, the sensitivity, specificity, PPV, NPV and overall correct classification rates were 70.5 percent, 78.7 percent, 35.3 percent, 94.2 percent and 77.6 percent, respectively.

However, subsequent analyses showed that optimal LSM cutoff values varied according to disease aetiology. For instance, in patients with chronic hepatitis B, cutoff values of 9 and 12 kPa values for significant fibrosis and cirrhosis led to the correct classification in 70.5 percent and 77.6 percent of cases, respectively.

In comparison, the optimal cutoff values for nonalcoholic steatohepatitis were 11 and 15 kPa for significant fibrosis and cirrhosis, respectively, leading to the correct classification of 83.3 percent in both scenarios. Corresponding values were 13 and 24 kPa for primary biliary cirrhosis, and 11 and 34 kPa for autoimmune hepatitis.

“In conclusion, the overall cut-off LSM values of 9 kPa and 13 kPa provide reasonable accuracy for the prediction of significant fibrosis and cirrhosis, respectively, in the Singapore population. However, the selection of an optimal cut-off LSM value for clinical use should be based on disease-specific cut-off values that vary among different aetiologies of chronic liver disease,” said researchers.

“We hope that the results of this prospective, multicentre study in a high-quality cohort will help to standardize the interpretation of TE in Singapore,” they added.

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