Prediction of Significant Hepatic Fibrosis in HCV Carriers With PNALT by SAPI- A Validation Study
Prediction of Significant Hepatic Fibrosis in HCV Carriers With PNALT by SAPI- A Validation Study
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.
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.
Inclusion Criteria:

 -  Age older than 18 years

 -  HCV RNA and anti-HCV positivity for more than 6 months

 -  4 consecutive normal ALT values (< 40 IU/L for men and < 34 IU/L for women)at 3 months
 apart over a period of 12 months

 Exclusion Criteria:

 -  HBV and HCV co-infection

 -  HBV and HIV co-infection

 -  History of heavy alcohol use (> 50 gram/day)

 -  Autoimmune liver diseases

 -  Metabolic liver diseases

 -  Presence of hepatocellular carcinoma

 -  Bleeding tendency

 -  Decline liver biopsies