A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C

Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment‐naive CHC patients who underwent liver biopsy over a 25‐month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score ≥ 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut‐off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.

[1]  J. Ludwig,et al.  The long‐term pathological evolution of chronic hepatitis C , 1996, Hepatology.

[2]  S. Bhatia The Spleen , 1929, The Indian medical gazette.

[3]  P. Bedossa,et al.  Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus , 1997, Journal of viral hepatitis.

[4]  E. Schiff,et al.  Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection , 2002, American Journal of Gastroenterology.

[5]  S. Tanase,et al.  Plasma clearance of intravenously injected aspartate aminotransferase isozymes: Evidence for preferential uptake by sinusoidal liver cells , 1985, Hepatology.

[6]  V. de Lédinghen,et al.  Daily or three times per week interferon alpha-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C not responding to previous interferon alone. , 2002, Journal of hepatology.

[7]  S. Govindarajan,et al.  Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. , 1997, The American journal of gastroenterology.

[8]  Llorenç Quintó,et al.  Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model , 2002, Hepatology.

[9]  H. Margolis,et al.  Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease , 1998 .

[10]  R. Ohno,et al.  Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis , 1999, American Journal of Gastroenterology.

[11]  F. Degos,et al.  Practices of Liver Biopsy in France: Results of a Prospective Nationwide Survey , 2000, Hepatology.

[12]  W D Carey,et al.  The role of liver biopsy in chronic hepatitis C , 2001, Hepatology.

[13]  H. Kumada,et al.  [Chronic hepatitis B]. , 2001, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.

[14]  Vivek Kaul,et al.  Development and validation of a model to diagnose cirrhosis in patients with hepatitis C , 2002, American Journal of Gastroenterology.

[15]  M McCarthy,et al.  Hepatology , 1999, Rapid Medicine.

[16]  A P Dhillon,et al.  Interobserver study of liver histopathology using the Ishak score in patients with chronic hepatitis C virus infection. , 1999, Liver.

[17]  L. Serfaty,et al.  Diagnostic accuracy of hyaluronan and type III procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. , 1996, Clinical chemistry.

[18]  T. Hassanein,et al.  Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection , 2001, American Journal of Gastroenterology.

[19]  P. Bedossa,et al.  Intraobserver and Interobserver Variations in Liver Biopsy Interpretation in Patients with Chronic Hepatitis C , 1994 .

[20]  R. Levine,et al.  AST/ALT Ratio ≥1 Is Not Diagnostic of Cirrhosis in Patients with Chronic Hepatitis C , 1998, Digestive Diseases and Sciences.

[21]  L. Adinolfi,et al.  Hepatic fibrosis plays a central role in the pathogenesis of thrombocytopenia in patients with chronic viral hepatitis , 2001, British journal of haematology.

[22]  B. Bacon,et al.  Combination of interferon and ribavirin in chronic hepatitis C: Re‐treatment of nonresponders to interferon , 2001, Hepatology.

[23]  J. Dienstag,et al.  The role of liver biopsy in chronic hepatitis C , 2002, Hepatology.

[24]  R. Aster Pooling of platelets in the spleen: role in the pathogenesis of "hypersplenic" thrombocytopenia. , 1966, The Journal of clinical investigation.

[25]  B. McMahon,et al.  Chronic hepatitis B , 2001, Hepatology.

[26]  Frank Scholle,et al.  Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. , 2002, Gastroenterology.

[27]  F. Gordon,et al.  AST/ALT Ratio Predicts Cirrhosis in Patients With Chronic Hepatitis C Virus Infection , 1998, American Journal of Gastroenterology.

[28]  M. Ngu,et al.  Aspartate aminotransferase : alanine aminotransferase ratio in chronic hepatitis C infection: Is it a useful predictor of cirrhosis? , 2000, Journal of gastroenterology and hepatology.

[29]  E. Schiff,et al.  Measurement of serum hyaluronic acid in patients with chronic hepatitis C and its relationship to liver histology , 2000, Journal of gastroenterology and hepatology.

[30]  K. Ishak,et al.  Histological grading and staging of chronic hepatitis. , 1995 .

[31]  R. Jalan,et al.  UK guidelines on the management of variceal haemorrhage in cirrhotic patients , 2000, Gut.

[32]  J. George Biochemical markers of hepatic fibrogenesis: Single measurements are not reliable enough to replace liver biopsy , 2000, Journal of gastroenterology and hepatology.

[33]  M. Alter,et al.  Prevention of spread of hepatitis C , 2002, Hepatology.

[34]  T. Poynard,et al.  Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study , 2001, The Lancet.

[35]  B. Lacour,et al.  Serum Activity of Mitochondrial Aspartate Aminotransferase: A Sensitive Marker of Alcoholism With or Without Alcoholic Hepatitis , 1984, Hepatology.

[36]  Samer S El-Kamary,et al.  Role of liver biopsy in management of chronic hepatitis C: A systematic review , 2002, Hepatology.

[37]  C. Palmer,et al.  Importance of age in chronic hepatitis C virus infection , 1997, Journal of viral hepatitis.

[38]  J. Hoofnagle,et al.  Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. , 1988, Gastroenterology.

[39]  B. Walker,et al.  Hepatitis C virus infection. , 2001, The New England journal of medicine.

[40]  T. Berg,et al.  Randomized, placebo‐controlled, double‐blind trial with interferon‐α with and without amantadine sulphate in primary interferon‐α nonresponders with chronic hepatitis C , 2001, Journal of viral hepatitis.

[41]  O. Cummings,et al.  Need for validation of clinical decision aids: use of the AST/ALT ratio in predicting cirrhosis in chronic hepatitis C , 2000, American Journal of Gastroenterology.

[42]  R. Fontana,et al.  Noninvasive monitoring of patients with chronic hepatitis C , 2002, Hepatology.