Editorial Board: Emmet B. Keeffe, MD (Chair);

Anna Lok, MD; Brian McMahon, MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD; Bruce Tung, MD

HBV Watch™

Timely Information for Practicing Physicians

 

September 2003

 

Peginterferon (PEG-IFN) a-2A

First report on treatment of chronic hepatitis B.  W.G.E. Cooksley and associates report the results of a phase II study in which 194 patients with chronic hepatitis B were randomized to receive PEG-IFN a-2a 90, 180, or 270 ug/week or IFN a-2a 4.5 MU tiw (13.5 MU/week), for 24 weeks with 24 weeks of follow-up. HBeAg cleared in 25% of patients treated with IFN a-2a compared with 37%, 35%, and 29% of patients treated with PEG-IFN a-2a 90, 180, and 270 ug, respectively.  An assessment of combined response (achievement of HBeAg loss, HBV DNA suppression, and ALT normalization) showed that a greater percentage of patients treated with PEG-IFN achieved combined response (24% vs12%; P = 0.036).  These early data suggest that PEG-IFN may be more effective than conventional IFN in the treatment of chronic hepatitis B.  However, further study is needed to confirm these results, determine the optimal dose, and compare PEG-IFN to the higher doses of conventional IFN in common use (30-35 MU/week).  (Cooksley WGE et al. J Viral Hepatitis 2003;10:298-305)

 

Immunoprophylaxis

Long-term results following liver transplantation.  Immunoprophylaxis with hepatitis B immune globulin (HBIG) is an accepted therapy for the prevention of recurrent HBV infection after liver transplantation in HBV-infected patients without viral replication.  Bruno Roche and colleagues from the Hôpital Paul Brousse (Villejuif, France) report the long-term results of HBIG treatment in 284 HBsAg-positive liver transplantation patients (25 patients received HBIG combined with antiviral therapy).  The 5- and 10-year post-transplantation actuarial rates of recurrence were 24.2% and 25.4%, respectively, and the actuarial 10-year survival rate was 74.4%.  Multivariate analysis identified the following to be predictors of lower HBV recurrence risk: absence of serum HBV DNA before transplantation; acute liver disease; HDV superinfection; and therapy with combination HBIG plus antiviral therapy.  Low-level HBV DNA was detected by PCR in 45.4% of 44 patients without recurrence tested at 10 years of follow-up.  The results show that few recurrences develop after 5 years of follow-up.  However, these findings also demonstrate that despite successful anti-HBs immunoprophylaxis, HBV DNA persists in many patients 10 years after liver transplantation.  Thus, an important message is that antiviral prophylaxis after transplantation should be long-term.  (Roche B et al. Hepatology 2003;38:86-95)

 

Adefovir Dipivoxil (ADV)

Resistance surveillance.  ADV is a nucleotide analogue that has demonstrated in vitro and in vivo activity against wild-type and lamivudine-resistant HBV.  ADV-resistant HBV mutations have not been detected in phase II studies of patients treated for up to 136 weeks.  Christopher Westland and others have recently conducted 2 phase III randomized, double-blind, placebo-controlled studies of ADV treatment in patients with chronic HBV (467 ADV-treated patients and 228 placebo patients).  Tests to monitor for the emergence of ADV-resistant HBV mutations over the first 48 weeks of treatment were included.  Only 4 patients were observed to have an emerging HBV substitution and a ³1 log10 increase in serum HBV DNA levels.  These HBV substitutions remained susceptible to ADV in vitro and all 4 patients had HBV DNA reductions of 3.3 to 5.9 log10 copies/mL by week 48 without rebound.  Thus, in these 2 large trials, no ADV resistance mutations were identified in patients treated with ADV for 48 weeks.  However, Hadziyannis et al (J Hepatol 2003;38:492A) recently reported delayed and infrequent emergence of ADV resistance (2.5%) at week 96.  (Westland CE et al. Hepatology 2003;38:96-103)

 

Genotype and viral response.  Chris Westland et al examined the antiviral efficacy of ADV in 2 multinational phase III studies (n = 694).  Asian patients were infected primarily with genotypes B or C, and Caucasian patients were infected primarily with genotypes A or D.  After 48 weeks of treatment with ADV 10 mg daily, the mean changes in serum HBV DNA levels were similar regardless of HBV genotype (range, -3.4 to -4.2 log10 copies/mL).  A multivariate analysis that adjusted for baseline serum HBV DNA and ALT levels confirmed that there were no differences in antiviral response among genotypes.  In addition, no differences in response were detected based on HBeAg status or race.  These data demonstrate that HBV genotype, HBeAg status, and race do not affect the antiviral response to 48 weeks of ADV therapy.  (Westland C et al. Gastroenterology 2003;125:107-116)

 

HBV Reactivation

Breast cancer patients.  Winnie Yeo and colleagues at the Sir Y. K. Pao Centre for Cancer (Hong Kong, China) prospectively followed 41 HBsAg-positive patients with breast cancer during chemotherapy over an 18-month period.  Seventeen patients (41%) developed HBV reactivation that was frequently associated with either premature termination of chemotherapy or delays in treatment schedules.  (Yeo W et al. J Med Virol 2003;70:553-561)  

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