gt180141
Topics:
Module 4 Gut 24/4/09 09:47:47
Author query sheet
Queries for Author Journal: Gut Paper: gt180141 Title: The proof of your manuscript appears on the following page(s). Please note that this is a galley proof and the layout of the article may change before publication. Please read the manuscript carefully, checking for accuracy, verifying the reference order and double-checking figures and tables. When reviewing your page proof please keep in mind that a professional copyeditor edited your manuscript to comply with the style requirements of the journal. This is not an opportunity to alter, amend or revise your paper; it is intended to be for correction purposes only. During the preparation of your manuscript for publication, the questions listed below have arisen (the query number can also be found in the gutter close to the text it refers to). Please attend to these matters and return the answers to these questions when you return your corrections.
Please note, we will not be able to proceed with your article and publish it in print if these queries have not been addressed. Query Reference
1
Query
Please check that all names and postal and e-mail addresses are correct, and indicate any necessary alterations.
If you are happy with the proof as it stands, please email to confirm this. Changes that do not require a copy of the proof can be sent by email (please be as specific as possible). Email:
[email protected] If you have any changes that cannot be described easily in an email, please mark them clearly on the proof and email a scan of the changes by replying to the eProof email or by fax: +44 (0)1227 831965.
PLEASE RESPOND WITHIN 48 HOURS
0
Gut Month 2009 Vol 000 No 000
gt180141
Topics:
Module 4 Gut 24/4/09 09:47:49
Letter
LETTER
Elastography for the non-invasive assessment of liver disease: limitations and future developments We read the article by Vizzutti et al (Gut 2009;58:157–60) with great interest; however, we are uncertain that the proposed algorithm for the non-invasive assessment of fibrosis evolution in patients with chronic hepatitis C (CHC) infection is the best way to utilise the information provided by transient elastography (TE). The role of non-invasive tests for liver fibrosis is still evolving. Historically, liver biopsy was used to target treatment for patients only with moderate to advanced fibrosis (METAVIR >F2). In the United Kingdom, liver biopsy has not been a requirement to guide antiviral therapy since 2006.1 Therefore, irrespective of fibrosis stage, patients with CHC, and without contra-indications, can be commenced on treatment. In the clinic, many patients with CHC will be in the grey area between METAVIR F1 and F3 with a TE measurement between 6 and 12 kPa. The proposed algorithm suggests these would be the patients requiring liver biopsy. If non-invasive tests are to be used in the manner in which they were conceived these are the patients we do not want to biopsy. A further weakness of the proposed algorithm is that it fails to make any allowance for
Gut Month 2009 Vol 000 No 000
virus genotype or patient age. Given the different sustained virological response (SVR) rates to combination therapy with pegylated interferon and ribavirin as determined by genotype, this is likely to influence how the clinician will utilise non-invasive tests. Given the better SVR rate for genotypes 2 and 3 and the shorter duration of therapy, particularly for those attaining a rapid virological response (RVR), starting treatment is likely to be less contentious than for those patients infected with genotypes 1 and 4, many of whom await the arrival of more efficacious and less toxic therapies. Furthermore, patient age indirectly reflects the duration of infection and, in general, older patients have more fibrosis. It has been shown that SVR is more likely in younger patients treated for CHC infection. Thus, we would contend that genotype and patient age should be incorporated into any algorithm as should factors known to accelerate the natural history of the disease including: co-infection with human immunodeficiency virus (HIV), alcohol excess, obesity, and male gender.2 Patients with a liver stiffness measurement between 6 and 12 kPa are likely to receive treatment and do not need long-term follow-up should SVR be achieved, so why subject these patients to biopsy? The patients at risk are those with advanced fibrosis or cirrhosis. These patients need to be identified for screening for oesophageal varices and hepatocellular carcinoma surveillance. The studies have shown that it is in detecting advanced fibrosis and cirrhosis
that TE has particular utility.3 Furthermore, the use of serial measurements over time for patients declining therapy (particularly patients with genotype 1 or 4) may have more utility than a liver biopsy prone to sampling error and inter and intraobserver variability. Therefore we believe that transient elastography should be used to screen for advanced fibrosis and cirrhosis and liver biopsy (with a minimum core of 2. 5 cm) be used where the result is at odds with the clinical suspicion. The addition of other non-invasive tests to the algorithm may add to the diagnostic accuracy for lesser degrees of fibrosis3 but are unlikely to affect the decision to treat, and thus are probably not necessary. T J S Cross, J D Mitchell, M E Cramp Hepatology Department, Derriford Hospital, Plymouth, UK
;
Correspondence to: Dr T J S Cross, Hepatology Department, Derriford Hospital, Derriford Road, Plymouth PL6 8DH, UK;
[email protected] Competing interests: None.
REFERENCES 1.
2.
3.
NICE. Peginterferon alfa and ribavirin for the treatment of mild chronic hepatitis C. London: National Institute for Health and Clinical Excellence, 2006. Ascione AT, MT. Di Constanzo, GG. Natural history of chronic hepatitis c virus infection. Dig Liver Dis 2007;39(Suppl 1):S4–7. Castera L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343– 50.
1
