APRI-M6 for predicting long-term outcome of chronic hepatitis C patients after interferon-based therapy: More questions than answers
Authors: Tung-Hung Su, Jia-Horng Kao, Ding-Shinn Chen
Journal: Hepatology (2007)

We read with interest the article by Yu et al. in which they claim that aspartate aminotransferase-to-platelet ratio index 6 months after end of treatment (APRI-M6) can accurately predict the long-term outcome of patients subjected to interferon-based therapy.1 Although the application of APRI-M6 seems simple and potentially useful in our daily clinical practice, several issues should be considered before drawing definite conclusions. First, the enrolled population was heterogeneous in both study and control groups. For example, in the study group, one-third of patients received IFN monotherapy and the rest of them received combination therapy of IFN plus ribavirin. It is known that the chronic hepatitis C patients having different treatments vary in terms of compliance, virological response,2 and potential long-term outcome.3 In addition, one-fourth of study patients were excluded for further analysis because of unavailable data. However, the author failed to analyze the reasons of unavailability such as early dropout due to IFN intolerance, poor response, or even early death, which may contribute to the adverse long-term outcomes. The control patients were significantly younger and had less cirrhosis than did the study patients. In addition, their baseline health status and fibrotic stages were also lacking. It is generally conceivable that age and advanced fibrosis are 2 major predictors for the progression of liver disease and response to IFN-based therapy.4 Second, selection bias existed because of the retrospective and prospective study design. Different and unmatched enrollment periods (1985-1999 for the control group and 1992-2002 for the study group) may lead to the incomparable willingness to receive IFN-based therapy because of different treatment standards or information of hepatitis C. Accordingly, unmatched study and control groups had variable follow-up periods that may be problematic in evaluating long-term outcomes. For example, compared to IFN-treated patients with preexisting cirrhosis, untreated controls survived more if the follow-up years were set at 9.5 years (79.8% versus 92.4%) (Appendix 2 and 3). Similarly, the liver-related mortality was also better in untreated controls (10 of 562 patients in 5.15 years of the untreated group versus 14 of 776 patients in 4.75 years of the treated group). Concerning HCC development, it is obvious that more HCC developed in the untreated group than the treated group (54 of 562 patients versus 41 of 776 patients); however, it is hard to explain why HCC patients in the untreated group survived more than those in the treated group at the end of follow-up (48 of 54 patients versus 29 of 41 patients) if all HCC patients were at the same tumor stage and received standard therapies. Third, the limited value of APRI-M6 on patients with cirrhosis and those with SVR for survival discrimination may restrict its application in special patient groups for whom prediction of long-term outcome is important. In clinical practice, we commonly use preexisting fibrosis stage and SVR after antiviral therapy to predict HCC development and survival in both treated and untreated chronic hepatitis C patients.5, 6 Although APRI has been shown to identify patients with chronic hepatitis C who have significant fibrosis and cirrhosis before IFN-based therapy,7 whether reduction of APRI correlates with improvement of fibrosis stage after IFN-based therapy remains unclear. It has been reported that fibrosis stage may not significantly change within 6 months after IFN therapy.8 Thus, APRI-M6 does not seem to be a good indicator for fibrosis regression, and may merely reflect SVR and biochemical response to IFN-based therapy. Taken together, these lines of evidence suggest that APRI-M6 may correlate well with SVR, and SVR itself rather than APRI-M6 can predict long-term outcomes of chronic hepatitis C patients after IFN-based therapy. Therefore, do we really need APRI-M6 in our daily practice? The APRI-M6 may remain useful in patients who refuse liver biopsy or have unknown virological response to antiviral treatment. Does APRI-M6 change our follow-up policy? For low-risk groups (patients without cirrhosis and sustained responders), regular follow-up is recommended because HCC or liver-related death still occurs, albeit rarely. Nevertheless, there are no convincing data to suggest a closer follow-up for high-risk groups (patients with cirrhosis and nonsustained responders) is of benefit. In summary, the existing data indeed point out new directions for the prediction of long-term outcomes of chronic hepatitis C patients after IFN-based therapy by using simple noninvasive tests. However, more studies are needed to clarify the clinical usefulness of serial APRI or other tests.9 Tung-Hung Su M.D. , Jia-Horng Kao M.D., Ph.D.* §, Ding-Shinn Chen M.D. , * Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan, Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan, § Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.