Clinical trial NCT00466271: Prediction of Significant Hepatic Fibrosis in HCV Carriers With PNALT by SAPI- A Validation Study
Official title: Prediction of Significant Hepatic Fibrosis in HCV Carriers With Persistently Normal Alanine Aminotransferase Levels by Splenic Arterial Pulsatility Index- A Validation Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis C
Hepatic Fibrosis
Keywords: Chronic hepatitis C
Persistently normal alanine aminotransferase levels
Hepatic fibrosis
Non-invasive diagnosis
Splenic arterial pulsatility index
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2007-04-27
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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

Brief 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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Department of Internal Medicine, National Taiwan Universitys Hospital
name: Chen-Hua Liu, MD
role: STUDY_DIRECTOR
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