Hepatitis B Virus-Related Hepatocellular Carcinoma Clinical Trial
— CTEAMOfficial title:
The Follow-up Study of Chronic Hepatitis B Patients With Liver Cirrhosis Receiving Anti-HBV Therapy
| Verified date | October 2013 |
| Source | National Taiwan University Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Taiwan : Food and Drug Administration |
| Study type | Observational |
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.
| Status | Enrolling by invitation |
| Enrollment | 1500 |
| Est. completion date | December 2021 |
| Est. primary completion date | January 2012 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 20 Years and older |
| Eligibility |
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 |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| Taiwan | National Taiwan University Hospital | Taipei |
| Lead Sponsor | Collaborator |
|---|---|
| National Taiwan University Hospital |
Taiwan,
Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | hepatocellular carcinoma | within a 10-year follow-up. | No |