This course is part of Advanced Certificate Program II: Management of Chronic Hepatitis B, featuring short vignettes focusing on treatment strategies and challenges clinicians face in managing patients with HBV. This course also offers an "Ask the Experts" forum where you can ask the "Faculty of the Month" questions about the postings contained on this website.
This independent CME/CE activity is supported by an educational grant from
Bristol-Myers Squibb.
Adrian M. Di Bisceglie, MD, FACP
Professor of Internal Medicine
Chief of Hepatology
Saint Louis University School
of Medicine
St. Louis, Missouri
Robert G. Gish, MD
Medical Director
Liver Transplant Program
Chief, Division of Hepatology
and Complex GI
California Pacific Medical
Center
San Francisco, California
Michael W. Fried, MD
Professor of Medicine
Director of Hepatology
Division of Gastroenterology
and Hepatology
University of North Carolina
Chapel Hill, North Carolina
W. Ray Kim, MD
Associate Professor of Medicine
Gastroenterology and
Hepatology
Mayo Clinic
Rochester, Minnesota
Kris V. Kowdley, MD
Professor of Medicine
Division of
Gastroenterology/Hepatology
University of Washington
Medical Center
Seattle, Washington
Statement of Accreditation
Projects In Knowledge is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
Credit Designation
Projects In Knowledge designates this educational activity for a maximum of .25 AMA PRA Category 1 CreditTM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
This activity is planned and implemented as an independent CME activity in accordance with the ACCME Essential Areas and Policies.
You can earn up to 3 credits for completing all postings in this 12-part series.
Projects In Knowledge will issue a certificate of participation for each course the participant completes. Please check with your organization and/or society for reciprocity.
This activity has been approved by the American Association of Critical-Care Nurses (AACN) for a maximum of 6.0 contact hours (.5 contact hour for each posting in this 12-part series). Provider #00013784.
The goal of this CME/CE activity is to examine current and emerging strategies for diagnosing and treating patients infected with HBV, and determine how to tailor these strategies to specific patient populations.
This activity is designed for gastroenterologists, hepatologists, and other clinicians who care for patients with hepatitis B infection or those at increased risk for acquiring the infection.
Projects In Knowledge has developed the contract to demonstrate our commitment to providing the highest
quality professional education to clinicians, and to help clinicians set educational goals to challenge and enhance their learning experience.
For more information on the contract, please click here.
The Disclosure Policy of Projects In Knowledge requires that presenters comply with the Standards for Commercial Support. All faculty are required to disclose any personal interest or relationship they or
their spouse/partner have with the supporters of this activity or any commercial interest that is discussed in their presentation. Any discussions of unlabeled/unapproved uses of drugs or devices will also be disclosed.
For complete prescribing information on the products discussed during this CME/CE activity, please see your current Physicians’ Desk Reference (PDR).
Adrian M. Di Bisceglie, MD, FACP, has received grant/research support from Gilead Sciences, Inc, Idenix Pharmaceuticals, Roche Pharmaceuticals, SciClone Pharmaceuticals, and Vertex Pharmaceuticals Inc; is a consultant for Abbott Laboratories, Bristol-Myers Squibb, Chiron Corporation, Metabasis Therapeutics, and SciClone Pharmaceuticals; is on the speakers bureau of Bristol-Myers Squibb, Gilead Sciences, Inc, and Roche Pharmaceuticals; and is a member of advisory boards for Bristol-Myers Squibb, Idenix Pharmaceuticals, Inc, Novartis Pharmaceuticals Corporation, Pharmasset, Roche Pharmaceuticals, and Vertex Pharmaceuticals Incorporated.
Robert G. Gish, MD, has received grant/research support from Bayer Pharmaceuticals Corporation, Bristol-Myers Squibb, Eximias Pharmaceutical Corporation, Gilead Sciences, Inc, Hoffmann-La Roche Inc, Idenix Pharmaceuticals Inc, InterMune Inc, Ortho Biotech Products, LP, Pfizer Inc, Schering-Plough Corporation, SciClone Pharmaceuticals, and Valeant Pharmaceuticals International; is a consultant for Amgen Inc, Anadys Pharmaceuticals, Inc, Bristol-Myers Squibb, Chiron Corporation, Gilead Sciences, Inc, GlaxoSmithKline, HepaHope, Inc, Hoffmann-La Roche Inc, Human Genome Sciences, Idenix Pharmaceuticals Inc, Innogenetics, InterMune Pharmaceuticals, Inc, Metabasis Therapeutics, Inc, Nucleonics, Inc, Ortho Biotech Products, LP, Pharmasset Pharmaceuticals Inc, Schering-Plough Corporation, SciClone Pharmaceuticals, Valeant Pharmaceuticals International, XTL Biopharmaceuticals, and ZymoGenetics, Inc; and is on the speakers bureau of Bristol-Myers Squibb, Eximias Pharmaceutical Corporation, Gilead Sciences, Inc, GlaxoSmithKline, Hoffmann-La Roche Inc, InterMune Inc, Ortho Biotech Products LP, Schering-Plough Corporation, and Valeant Pharmaceuticals International.
Michael W. Fried, MD, has received grant/research support from, is a consultant for, and is a member of advisory boards for GlaxoSmithKline, Idenix Pharmaceuticals Inc, Roche Pharmaceuticals, and Valeant Pharmaceuticals International.
W. Ray Kim, MD, has received grant/research support from Idenix Pharmaceuticals.
Kris V. Kowdley, MD, is on the speakers bureau of Gilead Sciences, Inc, and Hoffmann-La Roche Inc; and is a consultant for Bristol-Myers Squibb and Gilead Sciences, Inc.
Peer Reviewer has no significant relationships to disclose.
Projects In Knowledge's staff members have no significant relationships to disclose.
Conflicts of interest are thoroughly vetted by the Executive Committee of Projects In Knowledge. All conflicts are resolved prior to the beginning of the activity by the Trust In Knowledge peer review process.
The opinions expressed in this activity are those of the faculty and do not necessarily reflect those of Projects In Knowledge.
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Copyright 2007
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This CME/CE activity has reached its termination date and no longer offers continuing education credit. Please note that expired CME/CE activities may not contain the most up-to-date information available.
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LEARNING OBJECTIVE: Evaluate the role of postoperative antiviral therapy in HBV-infected patients following resection for hepatocellular carcinoma in order to reduce the risk of new tumors and tumor recurrence, and to improve the rate of tumor-free survival.
DISCLOSURE: Robert G. Gish, MD
 A 65-year-old African-American man was referred to a gastroenterologist due to an elevated alanine aminotransferase (ALT) level (180 U/mL) and right upper quadrant pain. Additional laboratory testing showed normal liver synthetic tests (normal liver function). The gastroenterologist subsequently evaluated the patient for viral hepatitis and found the patient to be HBsAg and HBeAg positive, with a HBV DNA level of 1 x 107 IU/mL. An anti-HBV regimen was not started due to the patient's lack of interest in treatment.
An initial abdominal ultrasound showed no evidence of hepatocellular carcinoma (HCC). Follow-up liver cancer surveillance, including abdominal ultrasound and alpha-fetoprotein, was scheduled every 6 months.
Eighteen months later, ultrasound testing showed a liver mass. A four-phase computed tomography (CT) scan strongly supported the diagnosis of HCC. Subsequent laboratory data were as follows: serum HBV DNA, 5.0 x 107 IU/mL; alpha-fetoprotein, 12 ng/mL; ALT, 124 U/mL; HBeAg negative; and anti-HBe positive. Despite a normal spleen size of 9 cm, the patient had a platelet count of 130,000 mm3. A liver biopsy demonstrated active liver disease and stage V fibrosis by Ishak staging.
The patient was referred for liver resection. The surgery went well and identified a circumscribed well-differentiated tumor with clean margins. The patient tolerated the procedure well without decompensation.
Decision Point:
Which of the following represents an appropriate rationale for administering anti-HBV therapy postoperatively to this patient relative to the diagnosis of liver cancer?
| a. | To reduce risk of a new primary HCC |
| b. | To reduce risk of HCC recurrence |
| c. | "a" and "b" |
| d. | None of the above; oral anti-HBV is not indicated at this time |
Discussion
(c) The patient's high viral load and stage V fibrosis suggest that anti-HBV treatment should be administered on the basis of continued HBV replication and active disease in the remaining liver tissue.1,2 Thus, treatment was indicated with the first evaluation based on HBV DNA serum levels, and with the second evaluation based on HBV DNA levels and the new diagnosis of liver cancer. Despite successful resection with clean margins, the remaining liver remains at risk of developing primary HCC.3 To date, there is supportive data that primary chemoprevention of HCC can occur using nucleos(t)ide analog therapy.4-6 The data on interferon therapy are also supportive of a primary chemoprevention effect with treatment and suggest that treatment after liver resection also may decrease the chance of recurrent disease.7-9
High HBV DNA levels are associated with tumor recurrence following resection for HCC.10 In a study of 40 patients undergoing liver resection for HCC, the tumor-free survival rate at 3 years was 0% for patients with a high viral load (defined as ≥0.7 mEq/mL) compared with 64% for those with a low viral load (P = .0025).
The 5-year survival after resection has been reported to exceed 50%, although the rates are lower in patients with cirrhosis.11 Recurrence at 5 years occurs in 31% to 56% of patients.12 In addition to high viral load, other predictors of recurrence include multinodular HCC, satellite nodules, poor differentiation of tumor, presence of wild-type HBV, absence of anti-HBe, absence of precore mutant-type HBV, Child score B, low platelet count, and a positive surgical margin.10,12
Kubo et al studied the effects of lamivudine on outcome following curative liver resection for HCC in patients with active HBV replication.13 Patients who received lamivudine (n = 14) had longer postoperative tumor-free survival compared with control patients (n = 10) (P = .0086). Similarly, studies with interferon in patients following curative resection have shown improved tumor-free survival and reduced incidence of recurrence.14,15
Case Continues
The physician decided to start the patient on entecavir at 0.5 mg per day. The patient is currently being followed with laboratory testing and ultrasound scan every 3 months. At 15 months of treatment, the patient's HBV DNA level was undetectable. Ultrasound scans continue to show no recurrent tumor.
References
- Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507-539.
- Keeffe EB, Dieterich DT, Han SH, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. 2006;4:936-962.
- Omata M, Yoshida H. Prevention and treatment of hepatocellular carcinoma. Liver Transpl. 2004;10(2 Suppl 1):S111-S114.
- Lim LY, Kowdley KV. Chemoprevention of hepatocellular carcinoma in chronic hepatitis B with lamivudine? Gastroenterology. 2005;129:2120-2122.
- Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521-1531.
- Yuen MF, Seto WK, Chow DHF, et al. Long-term beneficial outcome of Chinese asymptomatic patients with HBeAg-positive chronic hepatitis B on continuous lamivudine therapy: 7-year experience. Hepatology. 2005;42:583A.
- Lin SM, Sheen IS, Chien RN, Chu CM, Liaw YF. Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection. Hepatology. 1999;29:971-975.
- Lin SM, Tai DI, Chien RN, Sheen IS, Chu CM, Liaw YF. Comparison of long-term effects of lymphoblastoid interferon alpha and recombinant interferon alpha-2a therapy in patients with chronic hepatitis B. J Viral Hepat. 2004;11:349-357.
- Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, Liaw YF. Interferon therapy in HBeAg positive chronic hepatitis reduces cirrhosis and hepatocellular carcinoma. J Hepatol. 2007;46:45-52.
- Kubo S, Hirohashi K, Tanaka H, et al. Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma. Cancer. 2000;88:1016-1024.
- Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208-1236.
- Gish RG. Hepatocellular carcinoma: overcoming challenges in disease management. Clin Gastroenterol Hepatol. 2006;4:252-261.
- Kubo S, Tanaka H, Takemura S, et al. Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus. Hepatol Res. 2007;37:94-100.
- Sun HC, Tang ZY, Wang L, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol. 2006;132:458-465.
- Someya T, Ikeda K, Saitoh S, et al. Interferon lowers tumor recurrence rate after surgical resection or ablation of hepatocellular carcinoma: a pilot study of patients with hepatitis B virus-related cirrhosis. J Gastroenterol. 2006;41:1206-1213.
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Release Date: May 11, 2007.
Termination Date: May 11, 2008.
Estimated time for completion of this activity:
CME: 3 hours (15 minutes for each posting)
CE: 6 hours (30 minutes for each posting)
Posting 12
Posting 11
Posting 10
Posting 9
Posting 8
Posting 7
Posting 6
Posting 5
Posting 4
Posting 3
Posting 2
Posting 1
To receive credit for your participation in this CME/CE activity, please complete the following steps:
1. Participate in this activity by reading any or all of the online postings.
2. Complete the CME/CE Posttest following each posting, selecting the most appropriate response to each question.
3. Complete the CME/CE Evaluation.
4. Instantly access and print out your certificate.*
*Physicians can earn .25 credit for each posting, and nurses can earn .5 credit for each posting in this 12-part series.
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