EASL-ALEH 2015 Algorithm for the Use of Transient Elastography in Treatment-naive Patients With Hepatitis B

An Independent Validation

Jean Nana; Kristina Skaare; Jean Luc Bosson; Vincent Leroy; Tarik Asselah; Michael Adler; Nathalie Sturm; Jean-Pierre Zarski

Disclosures

J Viral Hepat. 2021;28(8):1169-1176. 

In This Article

Abstract and Introduction

Abstract

Various non-invasive methods have been evaluated in chronic hepatitis B, but none of them have been fully validated for the assessment of liver fibrosis. The issued EASL-ALEH 2015 guidelines provide detailed algorithms based on LSM and ALT serum levels. The aim of our study was to validate the diagnostic accuracy of this algorithm and to better understand discrepancies. Four hundred and thirteen patients from 3 centres were retrospectively included. All included patients were classified for fibrosis stage according to results of a liver biopsy. The overall diagnostic value was expressed with AUROCs given with 95% confidence intervals for the diagnostic targets. For each diagnostic target, optimal cut-offs were determined according to the Youden method. For the population of patients with ALT<N (n = 65), the AUROCs of TE were 0.75 (0.62–0.88) and 0.72 (0.56–0.88) for F ≥ 2 and F ≥ 3 diagnostic targets. Taking the EASL cut-offs, the prevalence of significant fibrosis was 8%, 38% and 67% when LSM was <6kPa, between 6 and 9 kPa or >9 kPa, respectively. For patients with ALT>N but ≤5N (n = 306), AUROCs of transient elastography were 0.79 (0.73–0.84) and 0.84 (0.75–0.92) for F ≥ 2 and F ≥ 3 diagnostic targets. The prevalence of significant fibrosis was, respectively, 15%, 52% and 85% when LSM was <6kPa, between 6 and 12 kPa or >12 kPa. Our study independently validates the EASL-ALEH algorithm based on ALT levels and LSM assessed by transient elastography.

Introduction

Viral hepatitis is a major public health problem. It caused 1.34 million deaths in 2015, a number comparable to deaths caused by tuberculosis and higher than those caused by HIV. Most viral hepatitis deaths in 2015 were due to chronic liver disease (720,000 deaths due to cirrhosis) and primary liver cancer (470,000 deaths due to hepatocellular carcinoma).[1] Approximately one third of the world's population has serological evidence of past or present infection with hepatitis B virus (HBV), and 350–400 million people are chronic HBV surface antigen (HBs Ag) carriers.[2] Globally, an estimated 240 million persons have chronic hepatitis B. This prevalence varies geographically and is highest in Africa and Asia.[3] Chronic viral hepatitis B (CHB) is a prolonged inflammatory disease of the liver that may lead to the progressive development of fibrosis.[4–6] Since fibrosis and its end-point cirrhosis are the main causes of morbidity and mortality, fibrosis assessment is considered as the most relevant information for the evaluation of the severity of the disease and as a useful indicator for prognosis and treatment decision. Since fibrosis is a morphological damage, liver biopsy is considered as the natural gold standard for staging the disease.[7] However, the high prevalence of chronic hepatitis B in addition to the morbidity and the cost generated by this procedure has triggered an intensive search for alternative methods for fibrosis evaluation. A number of non-invasive techniques have been developed which can be used instead of liver biopsy to assess liver disease severity, including serum markers and transient elastography (TE). Various non-invasive methods and scores have been studied to overcome the limitations of liver biopsy, such as invasiveness and sampling errors.[8–16] None of these techniques has been fully validated for the assessment of liver fibrosis during chronic hepatitis B. Recent studies and meta-analysis showed that TE can be performed with good diagnostic accuracy for quantifying liver fibrosis in patients with CHB. Although differences also exist among the cut-off values for different stages of liver fibrosis, the optimal cut-off values for different stages of liver fibrosis for CHB patients are yet to be defined. One reason for the vast difference in the liver stiffness measurement (LSM) cut-off values might be related to the mix of patients with different alanine aminotransferase (ALT) levels in different studies. Recent studies showed that the degree of fibrosis evaluated by TE could be overestimated in the presence of acute hepatitis. In fact, higher ALT level, which reflects more severe hepatic necrotic and inflammation, tends to be associated with higher LSM even among patients with moderately elevated ALT level.[8] This effect has been shown to be independent of the stages of liver fibrosis. Therefore, the LSM cut-off values for various stages of liver fibrosis should be analysed in the context of ALT levels. The most recent guidelines issued by EASL/ALEH stated that TE could be used for evaluating liver fibrosis in hepatitis B and suggested specific cut-offs taking into account ALT serum levels. However, these guidelines have not been prospectively validated. Therefore, the objectives of this study were to evaluate the diagnostic performance of TE in CHB patients and validate the algorithm proposed by EASL/ALEH and to search for the impact of taking into account HBV-DNA for optimizing the model in identifying diagnostic targets.

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