Vincent Mallet

FIB-4: a simple, inexpensive and accurate marker of fibrosis in HCV-infected patients.

We read with interest the article by Sterling et al.1 The authors derived from the AIDS Pegasys Ribavirin International Coinfection Trial (APRICOT)2 an index (FIB-4) to predict liver fibrosis in patients with HIV and hepatitis C virus (HCV) coinfection. The variables entered in the FIB-4 are as simple as age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet (PLT) count. Using the following formula, age [yr] AST [U/L])/((PLT [109/ L]) (ALT [U/L])1/2), the authors show that the FIB-4 index can accurately differentiate nil-moderate fibrosis (Ishak 0-3) from bridging fibrosis and cirrhosis (Ishak 4-6) in HIV/HCV coinfected patients with a cutoff 1.45 or 3.25, respectively. We wondered whether the FIB-4 index could also discriminate nil-moderate fibrosis (Ishak 0-3 or Metavir 0-2) from bridging fibrosis and cirrhosis (Ishak 4-6 or Metavir 3-4) in HCV-mono-infected patients. We explored the accuracy of the FIB-4 index in a series of 919 liver biopsies performed in 848 patients at our center. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4 in the Metavir classification) with an area under the receiver operating characteristic (AUROC) curve of 0.85 [95% confidence interval (CI) 0.82-0.89]. A FIB-4 index 1.45 had a negative predictive value of 95.2% to exclude extensive fibrosis (F3-F4) with a sensitivity of 80.4%. A FIB-4 index 3.25 had a positive predictive value of 81.2% and a specificity of 98.3%. The FIB-4 efficiently identified cirrhosis with an AUROC of 0.91 (95% CI 0.86-0.93). Using these cutoffs, 69.2% of the 919 biopsies with FIB-4 values outside 1.45-3.25 were correctly classified. The FIB-4 index was concordant (kappa 0.537, P .01) with the FibroTest (Biopredictive SAS, Paris, France), the most evaluated commercially-available noninvasive marker of liver fibrosis.3 A FIB-4 index 1.45 was concordant in 92.1% of the cases with the FibroTest (fibrosis score 0.56) to exclude severe fibrosis (Ishak 4-6 or Metavir F3-F4) in a series of 824 FibroTests performed in 595 patients. The post-hoc review of the files of the patients with a FIB-4/FibroTest discordance concluded, in two thirds of the cases, in a FibroTest failure (low haptoglobin, Gilbert disease, data capture failure, or unexplained). With an index 3.25, the FIB-4 was concordant with the FibroTest in 70.4% of the cases (fibrosis score 0.7). The discordances in this subgroup were explained in three quarters of the cases as a FIB-4 failure (very young age, unexplained thrombocytosis). In conclusion, a FIB-4 index beyond 1.45-3.25 is accurate to differentiate nil-moderate (F0-F2) from severe (F3-F4) liver fibrosis in HCV mono-infected patients. In these ranges, the FIB-4 index could replace advantageously expensive and/or invasive methods to assess liver fibrosis, especially in endemic countries were these techniques are barely available.

Improving anti-hepatitis C virus therapy.

The estimated prevalence of hepatitis C virus (HCV) infection is 2%, representing 123 million infected individuals worldwide. HCV infection burdens public health in relation to hepatic (cirrhosis and its complications in 20% of patients) and extrahepatic (vasculitis) complications, and lessens quality of life. Major progress has been made in the last two decades for the diagnosis and treatment of HCV, including more appropriate screening strategies for HCV infection (improved sensitivity of serological and virological tests); a better evaluation of the impact of chronic HCV infection on the liver (semi-quantitative scoring systems of necro-inflammation and fibrosis on liver biopsy, non-invasive evaluation of fibrosis with biochemical markers and elastometry); and improved therapeutic regimens. This progress provides a better definition of who to treat (clinical impact or significant fibrosis); how to treat; tailoring therapies for doses and durations of the pegylated interferon plus ribavirin combination according to virological (mainly genotype and early viral kinetics, but also baseline viral load) and hosts factors (fibrosis, immune status, weight); and how to monitor efficacy and tolerance of therapy. The progress has now resulted in a 50% rate of complete HCV eradication, ranging 45 – 90% according to the genotype and especially in those patients with early viral response. New therapies, specifically HCV protease or polymerase inhibitors, in combination with pegylated interferon, or more potent and less toxic new formulations of interferons or ribavirin, will increase these encouraging results in the future.