ClinicalTrials.gov
ClinicalTrials.gov Menu

The Follow-up Study of Chronic Hepatitis B Patients With Liver Cirrhosis Receiving Anti-HBV Therapy (CTEAM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01957618
Recruitment Status : Enrolling by invitation
First Posted : October 8, 2013
Last Update Posted : October 8, 2013
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:

Hepatitis B virus (HBV) infection is a global health problem, especially in the endemic area like Taiwan, where there are more than 3 million chronic hepatitis B carriers. Patients with chronic HBV infection are at increased risk of developing cirrhosis, which may have disastrous complications, including hepatic decompensation, and hepatocellular carcinoma (HCC). The liver cirrhosis related complications accounts for the 8th leading cause of deaths in Taiwan; whereas, the HCC is the 2nd leading cause of deaths among all cancers. Therefore, it is prudent to develop strategies to prevent or halt the progression of liver cirrhosis.

For HBV patients who have already had cirrhosis, the main treatment objective is to reduce their risk of complications. A large-scale multicenter clinical trial showed that viral suppression using lamivudine in patients with advanced fibrosis effectively decreases the risk of HCC and liver-related complications. This study highlights the importance to treat HBV-related cirrhosis patients; however, several issues remain to be addressed.

The first issue is that this clinical trial only enrolled patients with positive HBeAg or HBV-DNA level >1.4 x105 IU/mL. However, the current recommended threshold for cirrhotic patients to start anti-viral treatment is 2000 IU/mL. Whether anti-HBV therapy benefits cirrhotic patients in this level is still unclear. Second, lamivudine was used in this clinical trial; however, the high resistant rate of lamivudine during treatment probably lowers its protective effect against HCC. Whether a more potent anti-HBV agent with extremely low resistance profile, entecavir, is more beneficial to HBV-related cirrhotic patients is also unclear.

The Bureau of National Health Institute launched the reimbursement program for anti-HBV therapy since 2003 and extended this program to cirrhotic patients with HBV DNA level > 2000 IU/mL for long-term use since Aug, 2010. Taking this advantage, we may explore the above-mentioned clinical questions more easily.

To address these issues, we will first retrospectively collect a cohort of HBV-related cirrhosis patients. All the patients will be enrolled from the time before oral anti-HBV therapy is widely used. We will determine their baseline serum HBV-DNA levels using the stored sera and enrolled those with baseline HBV-DNA levels higher than 2000 IU/mL as our historical controls. Second, we will enroll a retrospective cohort of HBV-related cirrhotic patients from 2008 who had HBV-DNA levels higher than 2000 IU/mL and received indefinite therapy of entecavir. By comparing these two cohorts, we will be able to clarify whether indefinite viral suppression by entecavir is beneficial for the cirrhotic patients.

With comprehensive analysis, we wish to document that re-setting the risk level of HBV DNA from 140,000 IU/mL to 2,000 IU/mL is more beneficial for HBV-related cirrhotic patients and long-term entecavir does lower the risk of HCC further. These lines of evidence will assist in delivering appropriate and more aggressive treatment for these high-risk patients.


Condition or disease
Hepatitis B Virus-Related Hepatocellular Carcinoma

Study Type : Observational
Estimated Enrollment : 1500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Follow-up Study of Chronic Hepatitis B Patients With Liver Cirrhosis Receiving Anti-HBV Therapy
Study Start Date : October 2011
Actual Primary Completion Date : January 2012
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Group/Cohort
Treatment group
liver cirrhosis group who received indefinite anti-viral treatment
Historical control group
Liver cirrhotic patients who were enrolled before 2004 and did not receive treatment during the follow-up



Primary Outcome Measures :
  1. hepatocellular carcinoma [ Time Frame: within a 10-year follow-up. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
from hospitals
Criteria

Inclusion Criteria for treatment group:

  1. Age older than 20 years old.
  2. HBsAg (+) > 6 months
  3. Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL)
  4. Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy(Metavir F4 or Ishak > F5) or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices)
  5. Receiving long-term anti-HBV therapy

Inclusion Criteria for control group:

  1. Age older than 20 years old.
  2. HBsAg (+) > 6 months
  3. Baseline serum HBV DNA ≧ 2000 IU/mL (10,000 copies/mL)
  4. Liver cirrhosis (Child A) before or at enrollment, diagnosed by 1). Liver biopsy(Metavir F4 or Ishak > F5) or 2). Ultrasonographic evidence of cirrhosis with signs of portal hypertension (splenomegaly or presence of esophageal or gastric varices)
  5. without receiving treatment

Exclusion Criteria:

  1. . Co-infection of HCV (anti-HCV (+)) or HIV
  2. . Alcoholism (alcohol consumption > 20 gm/day)
  3. . Serological evidence suggestive of autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease and hemochromatosis
  4. . Liver decompensation (Child-Pugh classification of B or C)
  5. . Evidence of HCC at study entry
  6. . Pregnant women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01957618


Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Jia-Horng Kao, PhD National Taiwan University Hospital

Publications:
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01957618     History of Changes
Other Study ID Numbers: 201110057RC
First Posted: October 8, 2013    Key Record Dates
Last Update Posted: October 8, 2013
Last Verified: October 2013

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Carcinoma, Hepatocellular
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Cirrhosis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Hepadnaviridae Infections
DNA Virus Infections