Prediction of Significant Hepatic Fibrosis in HCV Carriers With PNALT by SAPI- A Validation Study
Condition: Chronic Hepatitis C; Hepatic Fibrosis
MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Liver Cirrhosis; Fibrosis
Study type: Observational

Summary: 
      The purpose of the study is to validate the diagnostic accuracy and reproducibility of SAPI
      to predict significant hepatic fibrosis in HCV patients with PNALT who are scheduled to
      receive combination therapy with pegylated interferon plus ribavirin and percutaneous liver
      biopsies.
    

Detailed description: 
      Hepatitis C virus (HCV) infection is a major health problem, affecting 170 million persons
      worldwide. Approximately 25-30% of patients with chronic hepatitis C have persistently normal
      alanine aminotransferase (PNALT) levels, and another 40% have ALT levels less than twice the
      upper limit of normal (ULN). PNALT is generally defined as at least three normal ALT levels
      documented at least 2 months apart over a period of 6 months. Although the natural history of
      HCV carriers with PNALT levels remains unclear, most of them may have mild necroinflammation
      with mild or no fibrosis on liver histology, and the rate of disease progression is slower
      than patients with elevated ALT levels. However, some patients with PNALT levels still
      present with advanced fibrosis or even cirrhosis. A recent study has shown that combined
      pegylated interferon alpha plus ribavirin treatment for HCV carriers with PNALT levels can
      achieve comparable sustained virological response (SVR) to those with elevated ALT levels,
      suggesting antiviral therapy could be initiated irrespective of ALT levels. Furthermore,
      patients with initial diagnosis of significant fibrosis on liver biopsies harbor higher risks
      to advanced fibrosis and cirrhosis, and may merit antiviral therapy to stop or delay the
      progression of hepatic fibrosis.

      Currently, liver biopsy is recognized as the gold standard for assessing the grade of
      necroinflammation and stage of fibrosis before the initiation of antiviral therapy. However,
      it is costly and harbors risk of complications. In addition, sampling error due to the
      non-uniform distribution of the parenchymal damage, as well as intra- and inter-observer
      variability is often encountered. A noninvasive tool to evaluate liver disease activity or
      fibrosis stage is helpful, particularly in monitoring HCV carriers over time.

      Studies assessing the usefulness of noninvasive tests to predict hepatic fibrosis were mainly
      performed in patients with elevated ALT levels. In patients with PNALT levels, only three
      studies have addressed the value of Fibroscan, Fibro Test and aspartate aminotransferase
      (AST) to platelet ratio index (APRI). However, Fibro Test is costly and Fibroscan has not
      been widely used. In addition, APRI has not been shown by other cohorts in patients with
      PNALT levels to possess excellent diagnostic accuracy and reproducibility (32). Currently,
      splenic arterial pulsatility index (SAPI) has been shown to have superior diagnostic accuracy
      to various biochemical indices (including APRI, API (age-platelet index), and AAR (AST to ALT
      ratio)) in predicting significant hepatic fibrosis in HCV carriers with PNALT. However, SAPI
      has not been validated in an independently prospective cohort to confirm both the diagnostic
      accuracy and reproducibility. Therefore, our study is aimed to validate the diagnostic
      accuracy and reproducibility of SAPI to predict significant hepatic fibrosis in HCV patients
      with PNALT who are scheduled to receive combination therapy with pegylated interferon plus
      ribavirin and percutaneous liver biopsies.
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        HCV carriers with persistently normal ALT levels who will receive percutaneous liver biopsy
      
Keywords: Chronic hepatitis C; Persistently normal alanine aminotransferase levels; Hepatic fibrosis; Non-invasive diagnosis; Splenic arterial pulsatility index