Abstract
ObjectiveWe developed a predictive model for significant fibrosis in chronic hepatitis B (CHB) based on routinely available clinical parameters.Methods237 treatment-naïve CHB patients [58.4% hepatitis B e antigen (HBeAg)-positive] who had undergone liver biopsy were randomly divided into two cohorts: training group (n = 108) and validation group (n = 129). Liver histology was assessed for fibrosis. All common demographics, viral serology, viral load and liver biochemistry were analyzed.ResultsBased on 12 available clinical parameters (age, sex, HBeAg status, HBV DNA, platelet, albumin, bilirubin, ALT, AST, ALP, GGT and AFP), a model to predict significant liver fibrosis (Ishak fibrosis score ≥3) was derived using the five best parameters (age, ALP, AST, AFP and platelet). Using the formula log(index+1) = 0.025+0.0031(age)+0.1483 log(ALP)+0.004 log(AST)+0.0908 log(AFP+1)−0.028 log(platelet), the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index predicts significant fibrosis with an area under the receiving operating characteristics (AUROC) curve of 0.776 [0.797 for patients with ALT <2×upper limit of normal (ULN)] The negative predictive value to exclude significant fibrosis was 88.4%. This predictive power is superior to other non-invasive models using common parameters, including the AST/platelet/GGT/AFP (APGA) index, AST/platelet ratio index (APRI), and the FIB-4 index (AUROC of 0.757, 0.708 and 0.723 respectively). Using the PAPAS index, 67.5% of liver biopsies for patients being considered for treatment with ALT <2×ULN could be avoided.ConclusionThe PAPAS index can predict and exclude significant fibrosis, and may reduce the need for liver biopsy in CHB patients.
Highlights
Up to 40% of patients with chronic hepatitis B (CHB) would develop cirrhotic complications or hepatocellular carcinoma (HCC) during their lifetime [1]
Liver biopsy is still recommended for certain CHB patients, especially those with an ALT level of,26upper limit of normal (ULN) [5,6]
All patients were positive for hepatitis B surface antigen (HBsAg) for at least 6 months, with a HBV DNA level of more than 2,000 IU/mL, and a serum ALT of less than 10 times the ULN prior to recruitment
Summary
Up to 40% of patients with chronic hepatitis B (CHB) would develop cirrhotic complications or hepatocellular carcinoma (HCC) during their lifetime [1]. While several clinical parameters, including male gender, older age, higher levels of alanine aminotransferase (ALT) and serum HBV DNA have been identified as risk factors for severe liver disease [2,3,4], the golden standard in assessing disease severity remains to be liver biopsy. Liver biopsy is still recommended for certain CHB patients, especially those with an ALT level of ,26upper limit of normal (ULN) [5,6]. Up to 2% of patients develop complications from liver biopsy [7,8]. Others problems like intra-observer variation and sampling error are unavoidable [9,10,11]. There is an increasing demand for developing predictive models of fibrosis based on non-invasive markers
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