Elsevier

Journal of Hepatology

Volume 50, Issue 1, January 2009, Pages 59-68
Journal of Hepatology

Early detection in routine clinical practice of cirrhosis and oesophageal varices in chronic hepatitis C: Comparison of transient elastography (FibroScan) with standard laboratory tests and non-invasive scores

https://doi.org/10.1016/j.jhep.2008.08.018Get rights and content

Background/Aims

To assess prospectively the accuracy of transient elastography (TE, FibroScan) for the detection of cirrhosis and oesophageal varices (OV) in chronic hepatitis C (CHC), as compared with currently available non-invasive methods (AST/ALT ratio (AAR), APRI, prothrombin index (PI), platelet count (PC), FibroTest (FT) and Lok index).

Methods

All tests were performed the day of liver biopsy (LB), taken as reference, in 298 consecutive CHC patients (cirrhosis: 70; Child-Pugh A: 70; OV: 25).

Results

TE had the best diagnostic accuracy for detection of cirrhosis (AUROCs: TE 0.96 vs. FT 0.82, Lok and APRI 0.80, PC 0.79, PI 0.73, AAR 0.61, respectively; p < 0.0001). Overall, the percentage of saved LB was: TE (cut-off: 12.5 kPa) 90%, PC 82%, FT 79%, PI 77%, AAR 76%, APRI 70%, and Lok 45%, respectively. At a cut-off of 21.5 kPa, TE predicted the presence of OV with 76% sensitivity and 78% specificity and correctly classified 73% of patients vs. AAR 81%, Lok 77%, FT, PI 70%, PC 69%, and APRI 66%, respectively.

Conclusions

TE is currently the most accurate non-invasive method for early detection of cirrhosis in CHC (cut-off: 12.5 kPa), as compared with other available methods, but cannot replace endoscopy for OV screening.

Introduction

Hepatitis C virus infection, with an estimated prevalence of more than 170 million worldwide, is a major public health care problem [1]. Chronic hepatitis C (CHC) is the most common cause of cirrhosis and hepatocellular carcinoma (HCC), and the leading indication for liver transplantation in the United States and many Western countries. In patients with compensated cirrhosis, the annual incidence of decompensation, HCC, and death reach approximately 4%, 3% and 3%, respectively [2], [3]. Early diagnosis of cirrhosis is important in patients with CHC not only because it prompts screening for HCC and oesophageal varices (OV) but also because these patients have the most urgent need for antiviral therapy.

Liver biopsy (LB) is still considered as the gold standard and is recommended in the majority of patients with CHC for fibrosis evaluation and treatment indication [4]. However, its accuracy for the diagnosis of cirrhosis has been questioned, in relation to sampling errors and intra- and inter-observer variability that may lead to understaging [5], [6], [7], [8], [9], [10]. In addition, LB is an invasive and painful procedure [11], [12], with rare but potentially life-threatening complications [13]. Thus, many patients with CHC are reluctant to undergo LB and may be discouraged from starting therapy for this reason.

These limitations have prompted the search for new approaches [14], [15], [16]. Several laboratory tests and scores have been proposed for the non-invasive prediction of cirrhosis in patients with CHC. Among these, prothrombin index (PI) [17], platelet count [18], AST/ALT ratio (AAR) [19], [20], and AST-to-platelet ratio index (APRI) [21] are based on routine laboratory parameters and therefore readily available in clinical practice. Among scores calculated from statistical models, the FibroTest (FT; Biopredictive, Paris, France) is based on a mathematical formula combining five variables (total bilirubin, γGT, haptoglobin, α2-macroglobulin and apoliprotein A1) [22] and the Lok index (combining platelet count, AST/ALT ratio, and international normalized ratio, INR) has been specifically designed for the diagnosis of HCV-cirrhosis [23]. The latest technological advance in the setting of non-invasive diagnosis is the measurement of liver stiffness by means of transient elastography, TE (FibroScan®, Echosens, Paris, France) [24], [25]. TE has been recently demonstrated to be a reliable tool for assessing hepatic fibrosis in patients with CHC [26], [27] with achieving the greatest accuracy for detecting severe fibrosis and cirrhosis [28], [29]. In addition, in patients with cirrhosis, TE may be of prognostic value in predicting OV [30], [31]. However, these different methods have not been compared against each other yet in a single and independent study.

The aim of this prospective study was to assess the accuracy of TE for the detection of cirrhosis and OV in patients with CHC, as compared with standard laboratory tests (AAR, APRI, PI and platelet count) and non-invasive scores (FT and Lok index).

Section snippets

Patients

The study cohort included 333 consecutive patients with CHC who underwent percutaneous LB at our center between June 2003 and April 2007. CHC was defined by detectable serum anti-HCV antibodies and HCV RNA with chronically elevated serum alanine aminotransferase (ALT) levels. Exclusion criteria were: co-infection with hepatitis B virus, HBV (n = 3) or human immunodeficiency virus, HIV (n = 4), other causes of liver disease (n = 6), decompensated liver disease (n = 7), liver transplantation (n = 2),

Patients

The characteristics of the 298 patients at the time of LB are shown in Table 1. There were 171 men and 127 women, and their mean age was 51.7 ± 11.8 years. The mean LB length was 19.5 ± 7.8 mm and the mean number of portal tracts was 14.6 ± 7.5. Biopsy length was greater than 15 mm in 210 patients (69%) and than 25 mm in 75 patients (25%). Cirrhosis (F4) was present in 70 patients (23%). As expected, these patients had lower platelet count, PI and albumin, higher INR and bilirubin levels than patients

Discussion

The results of the present prospective study, comparing seven non-invasive methods to LB, show that TE is currently the most accurate method for detection of cirrhosis in patients with CHC. Diagnostic accuracy of TE for detecting cirrhosis was significantly better than those of all the other tests with an AUROC of 0.96 (95%CI 0.93–0.98). In addition, using more discriminating criteria independent of cirrhosis prevalence, such as the likelihood ratios (LR), which describe how many times more

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    The authors who have taken part in the research of this paper declared that they do not have a relationship with the manufacturers of the device involved either in the past or present and they did not receive funding from the manufacturers to carry out their research.

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