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

JULY 2003

ACUTE SELF-LIMITED HBV INFECTION

Long-term outcomes. The long-term implications of acute HBV infection are unknown. Nobukazu Yuki and colleagues investigated outcomes in 14 patients who had been admitted to the Osaka National Hospital between 1990 and 1998 with acute self-limited HBV infection. All patients had seroclearance of HBsAg, and anti-HBs developed in 12 patients. Three patients had low levels of circulating HBV DNA up to 8.9 years after acute HBV infection. Liver biopsies were performed in 9 of the patients at a median of 7.2 years after the onset of HBV infection. HBV DNA (surface and X regions) was detected in the livers of all 9 patients, including 7 patients with negative serum HBV DNA. Qualitative PCR analysis showed an intact direct repeat region indicative of the ccc HBV DNA replicative intermediate in all patients. Liver fibrosis and mild inflammation persisted in 8 of 9 patients; none of the patients had piecemeal or confluent necrosis. These preliminary findings indicate that occult HBV infection persists after acute self-limited hepatitis B and is associated with abnormal liver histology for at least a decade following clinical recovery from acute infection. Further studies are warranted to confirm these provocative findings. (Yuki N, et al. Hepatology 2003;37:1172-1179)

Interferon (IFN) Therapy

A study of individualized therapy. Young-Hwa Chung and associates conducted a controlled trial in which 65 patients with chronic hepatitis B, both HBeAg-positive and HBeAg-negative, with ALT levels more than twice the upper limit of normal were randomized to receive subcutaneous IFN alfa-2b 5 MU/m² 3 times weekly for either 6 months (control arm; n = 35) or for an additional 6 months after HBV DNA became undetectable in serum by hybridization assay (individualized treatment arm; n = 30). Patients were followed for 12 months after the end of IFN therapy. HBV DNA became undetectable in serum (responders) in 16 patients (53%) in the individualized treatment arm and in 18 patients (51%) in the control arm. The mean duration of IFN therapy in patients receiving individualized treatment was 7.2 months (range, 7 to 12 months in responders; 6 months in nonresponders). At the end of follow-up 50% (n = 15) of the individualized-treatment arm patients compared with 29% (n = 10) of controls remained negative for serum HBV DNA (p = 0.01). In addition, serum ALT levels remained normal at the end of follow-up in 47% (n = 14) of patients in the individualized arm versus 26% (n = 9) of patients in the control arm (p <0.01). These results suggest that continuing IFN treatments for 6 months after the achievement of serum HBV DNA negativity by hybridization assay may decrease the viral relapse rate after IFN therapy is stopped. A multivariate analysis to identify predictive and potential confounding factors was not included in this study; thus, further studies are needed. (Chung Y-H, et al. Eur J Gastroenterol Hepatol 2003;15:489-493)

HBV Transmission

Laboratory-based screening of health care workers (HCWs). There have been recent reports of the transmission of HBV to patients during surgery by HBV-infected surgeons and other HCWs whose serum was negative for HBeAg. Corden et al performed a multicenter cross-sectional survey of 211 HCWs who were HBV carriers with negative HBeAg. HBV DNA was detected in 136 carriers (64.5%), with a median serum HBV DNA level of 3.6 log₁₀ copies/mL. Sera from 8 surgeons who transmitted hepatitis B was tested, and the lowest HBV DNA level found was 4 x 10⁴ copies/mL. A wide range of HBV DNA levels was found in the serum of HBeAg-negative HBV carriers. These data were the basis for recommendations contained in a recent Health Service Circular in the United Kingdom defining a serum HBV DNA cut-off level of 10³ copies/mL for fitness to conduct exposure-prone procedures by HCWs who are HBeAg-negative carriers. However, given the wide range (10² to 10⁹ copies/mL) and the frequent fluctuations in HBV DNA levels among HBeAg-negative carriers, recommendations based on HBV DNA level at a single time point of a small number of subjects must be interpreted with caution. (Corden S, et al. J Clin Virol 2003;27:52-58)

OUTCOME OF HBV Therapy

Durability of treatment-induced HBeAg seroconversion. Loss of HBeAg is associated with improved clinical outcomes in chronic HBV patients. HBeAg seroconversion induced by IFN therapy is durable in 80% to 90% of patients; however, reports of the durability of HBeAg seroconversion following lamivudine therapy have been contradictory. van Nunen and coworkers in Rotterdam contacted more than 50 medical centers to request data from patients with HBeAg seroconversion in controlled randomized trials or cohort studies. The authors performed a meta-analysis that included 130 patients from 24 centers in 14 countries with HBeAg seroconversion at the end of antiviral therapy (59 patients after lamivudine, 49 patients after IFN, and 22 patients after combination lamivudine plus IFN). The 3-year cumulative HBeAg relapse rates were 54%, 32%, and 23% for lamivudine, IFN, and combination therapy, respectively (p = 0.01). The relative HBeAg relapse risk of lamivudine compared with IFN therapy was 4.6, and 0.7 for combination therapy compared with IFN. Multivariate Cox regression analysis showed that high pretreatment HBV DNA level, low ALT level, lamivudine therapy, and male sex, but not Asian race, were independent predictive factors for post-treatment relapse. This analysis indicates that the durability of HBeAg seroconversion is lower following lamivudine therapy compared with that following IFN or IFN and lamivudine combination therapy. However, differences in baseline variables were observed among the three treatment groups, and it is not clear if consecutive patients with HBeAg seroconversion in participating centers were included in the analysis. (van Nunen AB, et al. Gut 2003;52:420-424)

HBV Watch is produced through educational grants from and

Hepatology Watch is a registered trademark of Market Development Group

Back to Issues Archive