Liver fibrosis assessment by transient elastography in hepatitis C patients with normal alanine aminotransferase

We read with interest the paper by Foucher et al (Gut 2006;55: 403–8) where the authors assessed the accuracy of transient elastography for the detection of cirrhosis. Its use in assessing the severity of chronic liver disease in other clinical scenarios warrants further evaluation. According to large population studies, the prevalence of chronic hepatitis C virus (HCV) infected patients who have persistently normal serum alanine aminotransferase (PN‐ALT) levels is most likely 30–50%.¹ A major problem is defining whether or not these patients will suffer a progressive disease; additionally, although no consensus exists regarding who must be treated and when antiviral therapy should be initiated, positive decisions have been reinforced by recent results of a large clinical trial indicating that pegylated interferon plus ribavirin combination therapy is effective and safe in these patients with PN‐ALT.²

In a recent review, the schedule of antiviral combination treatment of patients with chronic hepatitis C and normal aminotransferases was described, and indications for antiviral therapy in some cases was decided on the basis of histological findings¹; hence liver biopsy seems to be key in this decision and a patient must be treated if there is significant fibrosis (⩾OR = F2). However, although liver biopsy remains the “gold standard” for assessment of hepatic fibrosis, it represents an invasive procedure with some risks and limitations, as noted by Foucher et al, and is not well accepted by all patients. Non‐invasive methods such as Fibrotest, Forns' index (FI), and APRI have been designed to assess liver fibrosis.³

Fibroscan (FS), a new transient elastography technique to measure liver stiffness or elasticity,⁴,⁵ has provided some optimism as an alternative method for staging liver disease. Stiffness non‐significantly correlates with fibrosis stage and is a promising and reproducible method for the detection of cirrhosis, independent of the operator.⁵ Our aim was to use FS to assess hepatic fibrosis in patients infected by HCV with PN‐ALT, comparing the accuracy of FS to that previously described for biomarkers.

We analysed prospectively 28 chronically infected HCV patients (18 females) with PN‐ALT (at least three determinations yearly), assessing hepatic fibrosis by FS. Concordance and correlation between FS, FI, and APRI were also evaluated. Almost all consecutive patients were asymptomatic and none had the well known complications of advanced liver disease or cirrhosis.⁶ Patient characteristics (mean (SD)) were as follow: age 44.3 (10) years, body mass index 24.1 (2.8) kg/m², platelets count 249.6 (58)/mm³, serum cholesterol 190.5 (26) mg/dl, serum aspartate aminotransferase 25 (5) IU/l, serum ALT 27.7 (6.7) IU/l, and serum gamma glutamyl transferase 23.2 (21) IU/l. Results of the study were as follow: 26 (92.8%) patients had HCV genotype 1. Mean value for FS was 6.35 (3.3) kPa, indicating absence or mild stage fibrosis (<8.5 kPa); as expected, mean values for FI (3.35 (1.4)) and APRI (0.27 (0.09)) also reflected minimal or no fibrosis (<4.5 and <0.5, respectively). These provocative findings show that this cohort of PN‐ALT chronically infected HCV patients had a low stage of fibrosis, based on three non‐invasive methods. A previous study has compared and validated these methods in chronic hepatitis C patients with elevated ALT.⁷

Liver biopsy has been used as the “gold standard” for assessment of hepatic fibrosis. It has been used for staging liver damage in chronic viral hepatitis and for decision analysis as to the need for treatment in patients with chronic hepatitis C. The limitations of biopsy, such as patient acceptability, sampling error, or diagnostic inaccuracy, and the remote risk of complications, have led clinical investigators to study alternative methods of staging chronic viral hepatitis.⁴,⁸ Measurement of serum biological markers is the most widely used procedure for estimation of liver fibrosis⁸; combining serum biomarkers with FS may increase the accuracy of these non‐invasive methods, suggesting that it may be valid to circumvent the limitations of hepatic histology.⁷,⁸ FS is an objective and safe technique, enthusiastically accepted by patients. Hence periodic examinations can be performed as a follow up protocol for assessment of hepatic fibrosis progression or improvement. Moreover, it is a precise method for detection of cirrhosis and is a promising method of predicting complications of cirrhosis.

Accordingly, our data suggest that therapeutic management of PN‐ALT patients could be established according to fibrosis stage detected by successive FS examinations. Those PN‐ALT patients with evidence of fibrosis by FS would need to start early antiviral treatment. Although less effective in obese subjects, transient elastography may be very useful for the diagnosis and therapeutic management of PN‐ALT chronically HCV infected patients, questioning the need for biopsy.⁷,⁸ Further studies are warranted to evaluate the diagnostic accuracy for staging hepatic fibrosis, the natural history of disease, and the optimum response to combination antiviral therapy. Additionally, it has been demonstrated that combining FS measurements with biomarkers may increase the diagnostic accuracy of both tests.⁷,⁸

In conclusion, repeated stiffness assessment appears to be a good and safe alternative method of indicating antiviral combination therapy in PN‐ALT patients reluctant to undergo liver biopsy.