Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4959
Peer-review started: April 24, 2019
First decision: July 22, 2019
Revised: July 29, 2019
Accepted: August 7, 2019
Article in press: August 7, 2019
Published online: September 7, 2019
In nonalcoholic fatty liver disease (NAFLD), studies demonstrate that the severity of liver fibrosis is the most important determinant of the disease prognosis. Although liver biopsy is considered the gold standard for identifying fibrosis stage, it is an invasive procedure, and liver stiffness measurement (LSM) is widely preformed as a noninvasive means. However, LSM tends to overestimate fibrosis stage in NAFLD.
Controlled attenuation parameter (CAP), provided by LSM device, has been introduced for noninvasive quantification of hepatic steatosis. It also has been suggested that CAP may contribute in enhancing the accuracy of transient elastography measured LSM in patients with NAFLD.
Our aim was to determine the role of CAP values in predicting liver fibrosis stages by LSM.
This retrospective study involves 184 patients with biopsy proven nonalcoholic steatohepatitis (NASH), seen at a tertiary hospital in Seoul, Republic of Korea between 2010 and 2017. These patients had LSM and CAP evaluated within one month before the liver biopsy. Liver stiffness and CAP scores were measured by the FibroScan (Echosens, Paris, France), a medical device, using a standard probe. The patients in whom liver stiffness was measured when aspartate aminotransferase or alanine aminotransferase level was more than fivefold the upper limit of normal were excluded from the analysis due to the possibility of exacerbated LSM values. From 184 patients, 130 patients had 1-year follow-up LSM and analyzed for the changes of LSM after pioglitazone or ursodeoxycholic acid (UDCA) treatment.
Among 184 NASH patients with liver biopsy, histologically assessed steatosis grade (S) was distributed as follows: S1, n = 44 (2.9%); S2, n = 81 (44.0%); S3, n = 59 (32.1%). CAP scores were significantly different between S1 and S2-S3 (P < 0.001). However, no significant difference was found between S2 and S3 (P = 0.075). LSM significantly increased in accordance with the liver biopsy detected fibrosis stage (P < 0.001). After multivariate analysis, CAP value along with pathologically detected fibrosis stages was identified as a significant factor associated with LSM. Since our assessment showed that no reliable cutoff was demonstrated to differentiate S3 from S2 and 76.1% (140/184) of our study patients were either S2 or S3, variations of LSM within the same stage of liver fibrosis was evaluated according to the arbitrary CAP tertiles (lower 223-310, middle 311-339, high 340-400 dB/m). In Kleiner fibrosis stage F0 - 1, LSM values increased at high CAP tertile (P = 0.001), and in F2, at middle and high tertile (P = 0.027). No difference was noticed in F3-4 (P = 0.752) according to CAP tertile. Receiver operating characteristic curves for LSM cutoff in diagnosis of F ≥ 2 identified 8.05 kPa for lower CAP tertile, 9.35 kPa for middle, and 10.55 kPa for high tertile. The patients treated with pioglitozone demonstrated decreased LSM values after 1 year of the treatment (P < 0.001), when that in UDCA treated patients did not show significant changes (P = 0.068). CAP values did not show significant changes after pioglitazone (P = 0.197) or UDCA treatment (P = 0.057). When changes in proportion of significant fibrosis (F ≥ 2) were assessed among pioglitazone or UDCA treated patients reflecting CAP values, pioglitazone treated patients demonstrated decrease in proportion of high LSM.
In conclusion, LSM in NASH may overestimate the liver fibrosis stage particularly in patients with high CAP values. Interpretation of LSM considering simultaneously measured CAP scores may provide more helpful information preventing unnecessary liver biopsy in patients with NAFLD.
In patients with NAFLD with high CAP scores, LSM cutoff that leads to liver biopsy may need to be set higher than in those with other chronic liver diseases. Validation studies for more precise LSM cutoffs should be performed incorporating larger number of patients with biopsy proven NAFLD. With more reliable LSM cutoffs for noninvasive diagnosis of liver fibrosis in NAFLD, clinical studies evaluating efficacies of treatment would be more widely preformed in NAFLD.