Chronic Hepatitis CNCT00466271
Prediction of Significant Hepatic Fibrosis in HCV Carriers With PNALT by SAPI- A Validation Study
An observational study of Chronic Hepatitis C and Hepatic Fibrosis, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C, Hepatic Fibrosis
- How many people
- 102 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2007to Dec 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HCV carriers with persistently normal ALT levels who will receive percutaneous liver biopsy
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this 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
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.
Read the 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.
- Conditions
- Chronic Hepatitis C, Hepatic Fibrosis
- Keywords
- Chronic hepatitis C, Persistently normal alanine aminotransferase levels, Hepatic fibrosis, Non-invasive diagnosis, Splenic arterial pulsatility index
- Medical subject headings
- Hepatitis C, Chronic, Liver Cirrhosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionNov 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Chen-Hua Liu, MD, Study director, Department of Internal Medicine, National Taiwan Universitys Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466271
- Sponsor's protocol ID
- 200611011R
- Status last verified
- Dec 2008
- First submitted
- 24 Apr 2007
- Last updated
- 23 Dec 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
PubMed 11439948Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels. Hepatology. 2002 Nov;36(5 Suppl 1):S179-84. doi: 10.1053/jhep.2002.36386.
PubMed 12407592EASL International Consensus Conference on Hepatitis C. Paris, 26-28, February 1999, Consensus Statement. European Association for the Study of the Liver. J Hepatol. 1999 May;30(5):956-61. No abstract available.
PubMed 10365827Puoti C, Guido M, Mangia A, Persico M, Prati D; Committee on HCV carriers with normal alanine aminotransferase levels of the Italian Association for the Study of the Liver. Clinical management of HCV carriers with normal aminotransferase levels. Dig Liver Dis. 2003 May;35(5):362-9. doi: 10.1016/s1590-8658(03)00185-3.
PubMed 12846410Gholson CF, Morgan K, Catinis G, Favrot D, Taylor B, Gonzalez E, Balart L. Chronic hepatitis C with normal aminotransferase levels: a clinical histologic study. Am J Gastroenterol. 1997 Oct;92(10):1788-92.
PubMed 9382037Puoti C, Magrini A, Stati T, Rigato P, Montagnese F, Rossi P, Aldegheri L, Resta S. Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels. Hepatology. 1997 Dec;26(6):1393-8. doi: 10.1053/jhep.1997.v26.pm0009397976.
PubMed 9397976Conry-Cantilena C, VanRaden M, Gibble J, Melpolder J, Shakil AO, Viladomiu L, Cheung L, DiBisceglie A, Hoofnagle J, Shih JW, et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med. 1996 Jun 27;334(26):1691-6. doi: 10.1056/NEJM199606273342602.
PubMed 8637513Pradat P, Alberti A, Poynard T, Esteban JI, Weiland O, Marcellin P, Badalamenti S, Trepo C. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology. 2002 Oct;36(4 Pt 1):973-7. doi: 10.1053/jhep.2002.35530.
PubMed 12297846Alberti A, Noventa F, Benvegnu L, Boccato S, Gatta A. Prevalence of liver disease in a population of asymptomatic persons with hepatitis C virus infection. Ann Intern Med. 2002 Dec 17;137(12):961-4. doi: 10.7326/0003-4819-137-12-200212170-00009.
PubMed 12484711Persico M, Persico E, Suozzo R, Conte S, De Seta M, Coppola L, Palmentieri B, Sasso FC, Torella R. Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels. Gastroenterology. 2000 Apr;118(4):760-4. doi: 10.1016/s0016-5085(00)70145-4.
PubMed 10734027Martinot-Peignoux M, Boyer N, Cazals-Hatem D, Pham BN, Gervais A, Le Breton V, Levy S, Degott C, Valla DC, Marcellin P. Prospective study on anti-hepatitis C virus-positive patients with persistently normal serum alanine transaminase with or without detectable serum hepatitis C virus RNA. Hepatology. 2001 Nov;34(5):1000-5. doi: 10.1053/jhep.2001.28458.
PubMed 11679971Mathurin P, Moussalli J, Cadranel JF, Thibault V, Charlotte F, Dumouchel P, Cazier A, Huraux JM, Devergie B, Vidaud M, Opolon P, Poynard T. Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity. Hepatology. 1998 Mar;27(3):868-72. doi: 10.1002/hep.510270333.
PubMed 9500720Jamal MM, Soni A, Quinn PG, Wheeler DE, Arora S, Johnston DE. Clinical features of hepatitis C-infected patients with persistently normal alanine transaminase levels in the Southwestern United States. Hepatology. 1999 Nov;30(5):1307-11. doi: 10.1002/hep.510300526.
PubMed 10534355Okanoue T, Makiyama A, Nakayama M, Sumida Y, Mitsuyoshi H, Nakajima T, Yasui K, Minami M, Itoh Y. A follow-up study to determine the value of liver biopsy and need for antiviral therapy for hepatitis C virus carriers with persistently normal serum aminotransferase. J Hepatol. 2005 Oct;43(4):599-605. doi: 10.1016/j.jhep.2005.04.008.
PubMed 16024129Hui CK, Belaye T, Montegrande K, Wright TL. A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase. J Hepatol. 2003 Apr;38(4):511-7. doi: 10.1016/s0168-8278(03)00004-7.
PubMed 12663245
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of Significant Hepatic Fibrosis in HCV Carriers With Persistently Normal Alanine Aminotransferase Levels by Splenic Arterial Pulsatility Index- A Validation Study
- ClinicalTrials.gov ID
- NCT00466271
- Acronym / sponsor ID
- 200611011R
- Conditions
- Chronic Hepatitis C, Hepatic Fibrosis
- Keywords
- Chronic hepatitis C, Persistently normal alanine aminotransferase levels, Hepatic fibrosis, Non-invasive diagnosis, Splenic arterial pulsatility index
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Apr 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 27 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HCV carriers with persistently normal ALT levels who will receive percutaneous liver biopsy
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (8 listed)
- HBV and HCV co-infection
- HBV and HIV co-infection
- History of heavy alcohol use (> 50 gram/day)
- Autoimmune liver diseases
- Metabolic liver diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2008.
- Background: PubMed 11439948Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. doi: 10.1056/NEJM200107053450107. No abstract available.
- Background: PubMed 12407592Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels. Hepatology. 2002 Nov;36(5 Suppl 1):S179-84. doi: 10.1053/jhep.2002.36386.
- Background: PubMed 10365827EASL International Consensus Conference on Hepatitis C. Paris, 26-28, February 1999, Consensus Statement. European Association for the Study of the Liver. J Hepatol. 1999 May;30(5):956-61. No abstract available.
- Background: PubMed 12846410Puoti C, Guido M, Mangia A, Persico M, Prati D; Committee on HCV carriers with normal alanine aminotransferase levels of the Italian Association for the Study of the Liver. Clinical management of HCV carriers with normal aminotransferase levels. Dig Liver Dis. 2003 May;35(5):362-9. doi: 10.1016/s1590-8658(03)00185-3.
- Background: PubMed 9382037Gholson CF, Morgan K, Catinis G, Favrot D, Taylor B, Gonzalez E, Balart L. Chronic hepatitis C with normal aminotransferase levels: a clinical histologic study. Am J Gastroenterol. 1997 Oct;92(10):1788-92.
- Background: PubMed 9397976Puoti C, Magrini A, Stati T, Rigato P, Montagnese F, Rossi P, Aldegheri L, Resta S. Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels. Hepatology. 1997 Dec;26(6):1393-8. doi: 10.1053/jhep.1997.v26.pm0009397976.
- Background: PubMed 8637513Conry-Cantilena C, VanRaden M, Gibble J, Melpolder J, Shakil AO, Viladomiu L, Cheung L, DiBisceglie A, Hoofnagle J, Shih JW, et al. Routes of infection, viremia, and liver disease in blood donors found to have hepatitis C virus infection. N Engl J Med. 1996 Jun 27;334(26):1691-6. doi: 10.1056/NEJM199606273342602.
- Background: PubMed 12297846Pradat P, Alberti A, Poynard T, Esteban JI, Weiland O, Marcellin P, Badalamenti S, Trepo C. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology. 2002 Oct;36(4 Pt 1):973-7. doi: 10.1053/jhep.2002.35530.
- Background: PubMed 12484711Alberti A, Noventa F, Benvegnu L, Boccato S, Gatta A. Prevalence of liver disease in a population of asymptomatic persons with hepatitis C virus infection. Ann Intern Med. 2002 Dec 17;137(12):961-4. doi: 10.7326/0003-4819-137-12-200212170-00009.
- Background: PubMed 10734027Persico M, Persico E, Suozzo R, Conte S, De Seta M, Coppola L, Palmentieri B, Sasso FC, Torella R. Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels. Gastroenterology. 2000 Apr;118(4):760-4. doi: 10.1016/s0016-5085(00)70145-4.
- Background: PubMed 11679971Martinot-Peignoux M, Boyer N, Cazals-Hatem D, Pham BN, Gervais A, Le Breton V, Levy S, Degott C, Valla DC, Marcellin P. Prospective study on anti-hepatitis C virus-positive patients with persistently normal serum alanine transaminase with or without detectable serum hepatitis C virus RNA. Hepatology. 2001 Nov;34(5):1000-5. doi: 10.1053/jhep.2001.28458.
- Background: PubMed 9500720Mathurin P, Moussalli J, Cadranel JF, Thibault V, Charlotte F, Dumouchel P, Cazier A, Huraux JM, Devergie B, Vidaud M, Opolon P, Poynard T. Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity. Hepatology. 1998 Mar;27(3):868-72. doi: 10.1002/hep.510270333.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chen-Hua Liu, MD study director
Department of Internal Medicine, National Taiwan Universitys Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Hepatitis C and Hepatic Fibrosis, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00466271, which also lists 31 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2008.