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

MARCH 2004

LAMIVUDINE THERAPY

Long-term safety. Anna Lok et al retrospectively reviewed clinical safety data from 998 patients with HBeAg-positive compensated chronic hepatitis B who had received lamivudine therapy for up to 6 years (median, 4 years) and 200 patients who had received placebo for 1 year. Hepatitis flares occurred in 10% of lamivudine-treated patients during the first year of treatment and in 18% to 21% in years 2 to 5. The association between hepatitis flares and the development of lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events and 60 liver-disease-related serious adverse events (SAEs) occurred in 8 (<1%) and 53 (5%) lamivudine-treated patients, respectively. Among 4 deaths, 2 were due to liver-related causes. The proportion of patients with lamivudine-resistant mutations increased from 23% during the first year of treatment to 65% in year 5. Patients who developed lamivudine-resistant mutations had more hepatitis flares than patients without lamivudine-resistant mutations. In addition, the occurrence of hepatic decompensation and liver-disease-related SAEs among patients with lamivudine-resistant strains increased from 0%-2% and 1%-10%, respectively, during the first 4 years to 6% and 20%, respectively, after 4 years. These safety data demonstrate that lamivudine was well tolerated for at least 6 years of treatment by patients with HBeAg-positive compensated chronic hepatitis B. However, patients with long-standing lamivudine-resistant mutations may develop worsening liver disease. (Lok ASF, et al. Gastroenterology 2003;125:1714-1722)

Early therapy for HBV patients undergoing chemotherapy is superior. Reactivation of HBV infection is a serious cause of morbidity and mortality in HBsAg-positive cancer patients undergoing chemotherapy. George Lau and coworkers randomized 30 consecutive patients with malignant lymphoma undergoing intensive chemotherapy to lamivudine 100 mg daily either preemptively 1 week prior to the start of chemotherapy (group 1) or after evidence of HBV reactivation (group 2). Evidence of HBV reactivation was monitored serially at 2-week intervals by a Digene Hybrid Capture II assay for serum HBV DNA. Eight (53%) patients in group 2 and none of the patients in group 1 had HBV reactivation after chemotherapy. The median onset of HBV reactivation was 16 weeks (range, 4-36 weeks) after the initiation of chemotherapy. Seven (87.5%) of the 8 cases of HBV reactivation in the group 2 patients were followed by clinical hepatitis (5 anicteric hepatitis, 1 icteric hepatitis, and 1 hepatic failure). Following lamivudine withdrawal, 3 (13%) of 23 evaluable patients developed HBV-related hepatitis. These results indicated that preemptive lamivudine therapy more effectively prevented the development of hepatitis than deferred lamivudine treatment in HBsAg-positive lymphoma patients undergoing chemotherapy. (Lau GKK, et al. Gastroenterology 2003;125:1742-1749)

PEDIATRIC FULMINANT HEPATIC FAILURE

Follow-up 15 years after universal hepatitis B vaccination. Huey-Ling Chen and colleagues from the Childhood Fulminant Hepatic Failure Study Group in Taiwan studied the role of HBV infection in pediatric fulminant hepatic failure (FHF) after the initiation of a universal HBV vaccination program. Their investigation included 95 children from the age of 1 month to 15 years who were diagnosed with FHF (62 males and 33 females) between 1985 and 1999. HBV infection (HBsAg and/or IgM anti-HBc seropositivity) accounted for 40% (43 cases) of all FHF cases. The average annual incidence of FHF from 1985 to 1999 was 0.053/100,000 in patients of ages 1 - 15 years and 1.29/100,000 in patients of <1year of age. Infants made up 61% (58 cases) of all FHF cases. Furthermore, HBV infection occurred in 57% of infants compared to 27% of children aged 1 - 15 years. The incidence rate ratios of patients <1 year of age to those 1 to 15 years of age for HBV-positive FHF and HBV-negative FHF were 54.2 and 15.2, respectively. Maternal HBsAg was positive in 97% of infants with HBV-positive FHF. Seventy-four percent of all HBV-positive FHF patients and 81% of the infantile HBV-positive patients had been vaccinated. These findings demonstrated that FHF caused by HBV infection was rare in patients >1 year of age within the first 15 years of universal vaccination. However HBV remained a significant cause of FHF in infants. HBV-positive FHF was found predominantly among infants born to HBeAg-negative, HBsAg-carrier mothers. These infants may benefit from the administration of HBIG. (Chen H-L, et al. Hepatology 2004;39: 58-63)

REVIEW

Treatment of chronic hepatitis B in the human immunodeficiency virus (HIV)-infected patient. Martina Nunez et al recently updated the current status regarding treatment of chronic HBV in HIV-coinfected patients. HBV and HIV have similar routes of transmission and up to 80% of HIV-infected patients have serological markers indicating present or past HBV infection. The dramatic increase in survival of HIV patients due to HAART has progressively enlarged the clinical impact of HBV infection. In addition, HIV infection increases the risk of liver-related mortality in HBV patients by up to 12.7 fold. The management of HBV in the presence of HIV needs to address both infections and poses specific problems. For example, treatment of HBV-HIV coinfected patients with anti-HBV drugs is often associated with lower response rates and faster selection of HBV-resistant strains. Furthermore, nucleoside analogues, such as lamivudine, that are active against both HBV and HIV can induce the selection of resistance mutations in the HIV genome. More recently, tenofovir has shown encouraging short-term results and several drugs with combined anti-HIV and anti-HBV are actively under development. Specific recommendations for the treatment of HIV-HBV coinfected patients are discussed further in this review article. (Nunez M, et al. Clinical Infectious Diseases 2003;37;1678-1685)

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