Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C

Background & Aims

In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign – bright liver echo pattern (BLEP) – on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC.

Methods

Patients (n = 618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe.

Results

Male gender (p = 0.04), steatosis as continuous variable (p <0.001), severity of necroinflammation (p = 0.02) and stage of fibrosis (p <0.001) were associated with LSM by multivariate linear regression analysis. Among patients within the same fibrosis stages (F0–F2 and F3–F4; F0–F3 and F4), mean LSM values, expressed in kPa, were significantly higher in subjects with moderate-severe steatosis (⩾20% at liver biopsy) compared with those without, as well as in patients with BLEP on US compared with their counterpart. In subjects without severe fibrosis (F0–F2) and without cirrhosis (F0–F3), a higher rate of false-positive LSM results was observed in patients with steatosis ⩾20% compared with those without (F0–F2: 35.3% vs. 17.9%; F0–F3: 38.9% vs. 16.6%), and in patients with BLEP on US (F0–F2: 28.0% vs. 18.3%; F0–F3: 29.7% vs. 17.8%) compared with their counterpart.

Conclusions

In patients with G1 CHC, the presence of moderate-severe steatosis, detected by histology or by US, should always be taken into account in order to avoid overestimations of liver fibrosis assessed by TE.

Introduction

The prognosis of patients with chronic liver diseases is critically decided by the amount of liver fibrosis that accumulates over the years as a consequence of several mechanisms of liver injury, with the ultimate occurrence of cirrhosis and its complications [1], [2]. Liver biopsy is regarded as the gold standard procedure to assess presence and severity of all liver diseases, including chronic hepatitis C (CHC). However, it is an invasive procedure carrying a certain risk of complications, and its accuracy is affected by concerns related to inter- and/or intra-observer discrepancies [3], and by other factors such as length and width of biopsy sample, sampling errors, and inconsistency in defining histological features due to the variety of the several available scoring systems [4], [5]. Furthermore, new therapeutic strategies against HCV infection at high efficacy and with an excellent profile of tolerability will be available in the near future; consequently, the need for histological staging will decrease, and non-invasive techniques for evaluation and monitoring of patients with CHC, particularly transient elastography (TE) [6] and ultrasonography (US) [7], will play an increasingly relevant role.

The use of TE to estimate liver fibrosis has been repeatedly validated in different settings [8], including CHC [9], [10], [11]. Independently of the underlying etiology, TE showed overall a good accuracy in diagnosing severe fibrosis and cirrhosis [8], [12], [13], even if its performance seems to be affected by several factors, such as alanine aminotransferase flares and severe liver necroinflammation [14], [15], [16], recent food intake [17], hepatic congestion [18], extrahepatic cholestasis [19], high body mass index (BMI) [20], [21] and insulin resistance [22]. Conversely, there are controversial data about the influence of liver steatosis on LSM values and TE performance, especially in patients with CHC. Indeed, even if a lower interobserver agreement for LSM was observed in patients with liver steatosis compared with their counterpart [23], several studies showed no impact of steatosis on liver stiffness [10], [24], others demonstrated increased LSM values in presence of high degrees of steatosis [25], [26], [27], whereas steatosis >33% was associated with lower LSM values in NAFLD patients with severe fibrosis [28].

The aim of the present study was to assess the impact of liver steatosis, detected by histology and US, on LSM values and on accuracy of TE for fibrosis diagnosis in a cohort of consecutive biopsy-proven patients with genotype 1 (G1) CHC.