Potential conflict of interest: Dr. Lok is a consultant for and received grants from Bristol-Myers Squibb, Gilead, Pharmasset, Schering-Plough, and Roche. She also received grants from GlaxoSmithKline and Novartis.
Article first published online: 8 JUN 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 50, Issue 2, pages 658–659, August 2009
How to Cite
Lok, A. S. (2009), Reply:. Hepatology, 50: 658–659. doi: 10.1002/hep.23115
- Issue published online: 29 JUL 2009
- Article first published online: 8 JUN 2009
- Accepted manuscript online: 8 JUN 2009 12:00AM EST
We are in complete agreement with Drs. Zhao and Miao1 that studies should be conducted to determine if patients with chronic hepatitis B virus (HBV) infection, who are negative for hepatitis B e antigen (HBeAg) and have normal alanine aminotransferase (ALT) will benefit from antiviral therapy. As we pointed out in our article,2 some HBeAg-negative patients with normal ALT have significant liver disease on liver biopsy and some may develop cirrhosis or hepatocellular carcinoma. The risk is related to the duration and severity of liver injury prior to HBeAg seroconversion and the level of HBV replication after HBeAg seroconversion. Thus, in Figure 3 of our article, we qualified our recommendation to monitor for HBeAg-negative patients with normal ALT only if serum HBV DNA is less than 2000 IU/mL (less than 10,000 copies/mL). Furthermore, we recommended that these patients be monitored every 3 months for the first year so patients with fluctuating HBV DNA and/or ALT levels can be identified and treatment can be initiated if necessary.
Although current treatments for hepatitis B are largely safe, we would like to caution that the long-term safety of these treatments remains to be established. On April 20, 2009 Pharmasset Inc. announced the termination of worldwide phase III clinical trials of clevudine following reports of myopathy.3 Clevudine was shown to be safe in previous studies, most of which involved short durations (4-24 weeks) of treatment, and had been approved for use in South Korea. Myopathy was not observed until after patients had been exposed to more than 8-12 months of clevudine.4, 5 Adverse events have also been reported to be associated with other HBV treatments including renal tubular abnormalities and renal impairment in patients receiving adefovir or tenofovir and myopathy and neuropathy in those receiving telbivudine. Although these events are rare, careful balance of the benefits versus risks of treatment is warranted, particularly in patients who have quiescent disease.
- 1A call for attention and trials on HBeAg-negative, ALT-normal chronic hepatitis B virus infection. HEPATOLOGY 2009; doi:10.1002/hep.23110., .
- 2Indications for therapy in hepatitis B. HEPATOLOGY 2009; 49 ( 5 Suppl. ): S129–S137., .
- 3Pharmasset voluntarily halts clinical studies with clevudine in hepatitis B infected patients [press release]. Princeton, NJ: Pharmasset Inc.; April 20, 2009. http://investor.pharmasset.com/releasedetail.cfm?ReleaseID=378789. Accessed June 2009.
- 4Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mitochondrial DNA. HEPATOLOGY 2009; 49: 2080–2086., , , , , , et al.
- 5Clevudine myopathy in patients with chronic hepatitis B. J Hepatol 2009; doi:10.1016/j.jhep.2009.04.019., , , , , , et al.
Anna S. Lok M.D.*, * Division of Gastroenterology, University of Michigan, Ann Arbor, MI.