Evaluation of Transient Elastography for Fibrosis Assessment Compared With Large Biopsies in Chronic Hepatitis B and C

Claudia Verveer; Pieter E. Zondervan; Fibo J. W. ten Kate; Bettina E. Hansen; Harry L. A. Janssen; Robert J. de Knegt

Disclosures

Liver International. 2012;32(4):622-628. 

In This Article

Abstract and Introduction

Abstract

Background Fibrosis determines prognosis and management in patients with chronic hepatitis B and C (CHB and CHC). Transient elastography (TE) is a promising non-invasive method to assess fibrosis. We prospectively studied the performance of TE compared to histology and also whether there are differences between CHB and CHC. Only large biopsies (≥25 mm) were used.
Methods We included 241 patients with CHB (n = 125) and CHC (n = 116), of whom we acquired 257 liver biopsies, all preceded by elastography. We correlated liver stiffness with fibrosis stage according to the METAVIR system, inflammation (Histology Activity Index), steatosis and iron. The impact of gender, age, body mass index, alcohol, alanine aminotransferase levels, platelet count, viral load and genotype on liver stiffness was evaluated.
Results The AUROC's for F ≥ 2 were 0.85 for CHB and 0.76 for CHC. AUROC's for F ≥ 3 were 0.91 for CHB and 0.87 for CHC and 0.90 and 0.91 for F4 for CHB and CHC respectively. For F ≥ 2 the cut-off value was 6.0 kPa for CHB and 5.0 kPa for CHC. The cut-off values for ≥F3 were 9.0 and 8.0 kPa for CHB and CHC, respectively, and 13.0 kPa for F4 in both CHB and CHC patients. Besides inflammation, all other remaining factors do not influence liver stiffness.
Conclusion For the diagnosis of fibrosis stages F ≤ 2 TE is suboptimal, and inflammation may induce higher values. For stages F ≥ 3 TE performance is good and equal in both CHB and CHC patients.

Introduction

The treatment of chronic viral hepatitis B (CHB) and hepatitis C (CHC) is directed towards improving life quality, survival and preventing the development of cirrhosis, complicated by hepatic failure and hepatocellular carcinoma (HCC).[1–6] Both conditions have a high mortality. As a result of many therapeutic options in both CHB and CHC, it is one of the greatest challenges to select the patients who benefit most from therapy. One of the parameters, which is used in the treatment criteria, is the stage of liver fibrosis, which can be estimated by histological analysis of the liver according to the fibrosis staging systems METAVIR,[7,8] Ishak[9] and others.[10,11] Currently, the presence of stage ≥F2 is a strong indicator for starting antiviral treatment[12–15]

Although the liver biopsy is regarded as the best standard for evaluation of fibrosis,[16] biopsy size and unequal distribution of fibrosis in the liver may influence its performance, resulting in an under- or overestimation of fibrosis stage with a possible negative impact on prognosis and indication for antiviral therapy. A biopsy with a smaller length has a larger sample size variability as well as intra- and interobserver variability.[17–19] Larger biopsies therefore increase the performance of fibrosis classification, but this is not feasible in clinical practice, for it may increase risk for complications. Studies suggest 25 mm as the optimal biopsy length for correct classification of the fibrosis stage.[18,20] It is well known that because of invasiveness and associated complications[4,21–24] liver biopsies are poorly tolerated by patients.

Transient elastography (TE) is a technique based on the combination of ultrasound and low-frequency waves for measurement of liver stiffness, as an indirect parameter for fibrosis, in a rapid and safe manner. The initial TE evaluation studies in CHC patients proved this technique to be an accurate tool for detecting severe fibrosis and cirrhosis.[25–29] However, there was considerable overlap present between liver stiffness measurements in patients with stages F1 and F2, resulting in a less discriminative power in the lower stages of fibrosis. Finally, the performance for the detection of stage ≥F2 was not optimal. These studies were limited by an imbalanced distribution of fibrosis, with an overrepresentation of stages F1 and F2, but only few F0. Also, the histology specimens were suboptimal and did not meet the criteria for optimal length.[18,20] Currently, there are only few publications on the performance of TE in CHB patients.[30–33]

The natural course of CHB is different from CHC and much more influenced by viral potency and immunological host factors. Where CHC has a more or less continuous progressive course, CHB often displays episodes of inflammation, characterized by a rise in ALT. Histological inflammation is likely to influence liver stiffness,[34,35] but also other factors contribute to liver stiffness.[36–38]

We evaluated the performance of TE in CHB and CHC patients by comparing histology, in large biopsies according to the advised international standards, and studied the impact of inflammation in a cohort of 257 paired measurements in 241 CHB and CHC patients. We evaluated the differences between the CHB and CHC patients regarding performance of TE. In addition, we tested the influence of patient and disease-related factors such as viral genotype, viral load, steatosis, iron, age, gender, weight, body mass index (BMI) and use of alcohol.

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