Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine.
(9/743)
Lamivudine is a nucleoside analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Patients coinfected with HIV and HBV may have hepatitis flares when lamivudine therapy is discontinued or when resistance of HBV to lamivudine emerges. This retrospective, descriptive study conducted in three tertiary care medical centers describes patients coinfected with HIV type 1 and HBV who presented with a spectrum of clinical and subclinical hepatitic responses to lamivudine withdrawal or resistance. One patient had fulminant hepatic failure and a second patient had subclinical hepatitis when lamivudine therapy was discontinued and a more efficacious antiretroviral regimen was substituted. Three patients had flares of hepatitis after 13 to 18 months of lamivudine therapy. Lamivudine withdrawal or emergence of lamivudine-resistant mutants in patients coinfected with HIV and HBV may result in severe hepatitis. Clinicians caring for patients with coinfection with HIV and HBV should be aware of the possibility that a hepatitis B flare may occur in previously asymptomatic carrier patients. (+info)
Analysis of the precore and core promoter DNA sequence in liver tissues from patients with hepatocellular carcinoma.
(10/743)
To investigate the role of mutant hepatitis B virus (HBV) in the development of hepatocellular carcinoma (HCC), 20 patients with HCC were studied for precore and core promoter mutations in tumorous and nontumorous tissues. The precore and core promoter region was amplified and analyzed by direct sequencing. Among the 20 tumorous and nontumorous tissues, precore mutant HBV was found in 12 (60%) and 18 (90%), respectively. Of the 12 tumorous tissues with precore mutant, nine tissues had a single mutation (1896) and one tissue had another single mutation (1899). The remaining two tissues had a double mutation (1896 and 1899). A single mutation (1896) and a single mutation (1899) were found in 11 and two of the 18 nontumorous tissues with precore mutant, respectively. Among 20 tumorous and nontumorous tissues, HBV with a C to T mutation at nucleotide (nt) 1846 was detected in six and eight, respectively, and was associated with the virus carrying a mutation (1896 or 1899) except in two tumorous tissues. Mutations at nt 1762 and 1764 in core promoter were observed in 16 (80%) tumorous tissues and 18 (90%) nontumorous tissues. Mutations in the precore and core promoter region were found frequently in nontumorous tissue and in tumorous tissue (18/20 and 12/20 in precore region, 18/20 and 16/20 in core promoter respectively). The high prevalence of precore and core promoter mutations in liver tissue from patients with HCC suggests that these mutations may contribute to the development of HCC. (+info)
Prevalence of hepatitis B virus marker positivity and evolution of hepatitis B virus profile, during chemotherapy, in patients with solid tumours.
(11/743)
To prospectively evaluate the prevalence of hepatitis B virus (HBV) positivity and study the evolution of HBV profile during cancer chemotherapy, serum HBV markers and liver biochemistry were determined in 1008 of 1402 (72%) cancer patients admitted in our Unit and in all 920 (91 %) who received chemotherapy. We found that 54 (5.3%) were HBsAg carriers while 443 (44%) had at least one HBV marker positive. Of the latter, 405 (91%) were HBcAb+ve, 321 (72%) HBsAb+ve and 212 (48%) HBeAb+ve. No patient was HBeAg+ve. Among 920 chemotherapy receivers, 374 (41%) were HBcAb+ve, 280 (30%) HBsAb+ve and 178 (19%) HBeAb+ve. Fifty (5.4%) were HBsAg carriers (versus 0.6% in Greek blood donors). All 50 were systematically screened for HBsAg and HBsAb status throughout chemotherapy, during follow-up or until their death, and liver biochemistry was performed before each chemotherapy course. Stable antigenaemia was observed in 43/50 (86%) while 7/50 (14%) developed clinical and/or biochemical hepatitis. Six of these seven developed serum anti-HBs antibodies with an associated decrease of serum HBsAg titres. We conclude that reactivation of HBV infection during chemotherapy is not rare (14%), while disappearance of HBs antigenaemia is neither a frequent nor usually a permanent phenomenon. (+info)
Lamivudine as initial treatment for chronic hepatitis B in the United States.
(12/743)
BACKGROUND AND METHODS: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). RESULTS: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sustained normalization of serum alanine aminotransferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. CONCLUSIONS: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were generally sustained after treatment. (+info)
Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine.
(13/743)
Hepatitis B viremia and emergence of hepatitis B virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study of extended lamivudine therapy. Within 12 weeks, all patients exhibited a marked virologic response to lamivudine: >99% reduction (median 5 log decrease) in serum HBV DNA levels. Virus remained at >104 genomes/mL in 11 patients and decreased to <104 genomes/mL in the remaining 12 patients. In 10 patients, detectable YMDD variants emerged during the course of treatment. Six patients, including 3 with YMDD variants, experienced hepatitis B e antigen seroconversion while on lamivudine therapy or soon after its discontinuation. No patients with HBV DNA levels >104 genomes/mL seroconverted. Thus, patients who respond to lamivudine therapy with dramatic reductions in viral DNA level (to <104 genomes/mL) appear more likely to seroconvert than patients who do not achieve this level of HBV clearance. (+info)
In vivo regulation of hepatitis B virus replication by peroxisome proliferators.
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The role of the peroxisome proliferator-activated receptor alpha (PPARalpha) in regulating hepatitis B virus (HBV) transcription and replication in vivo was investigated in an HBV transgenic mouse model. Treatment of HBV transgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and steady-state levels of HBV RNAs in the livers of these mice. In male mice, this increase in transcription was associated with a 2- to 3-fold increase in replication intermediates, whereas in female mice it was associated with a 7- to 14-fold increase in replication intermediates. The observed increases in transcription and replication were dependent on PPARalpha. HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV transcripts and replication intermediates as untreated HBV transgenic mice expressing PPARalpha but failed to demonstrate alterations in either RNA or DNA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumstances, result in relatively large increases in HBV replication in HBV transgenic mice. (+info)
Replication of hepatitis B virus in first-degree relatives of patients with hepatocellular carcinoma.
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Hepatocellular carcinoma (HCC) may occur in family clusters. No genetic mechanism has been identified as responsible for this familial tendency. We suspected that a longer hepatitis B virus (HBV) replication phase might be the reason for a higher risk of HCC in families with this disease. We performed liver biochemical tests, test for viral hepatitis markers and hepatitis B e antigen (HBeAg), and liver ultrasonography in relatives of patients with HCC. A total of 1,885 first-degree relatives from 688 families participated in this study. Seven hundred fifty-two relatives were found to be carriers of hepatitis B surface antigen (HBsAg) and 675 of them were tested for HBeAg. The prevalence of HBeAg was 27.4% in relatives of those with HCC and 20% in asymptomatic HBsAg carriers. The HBeAg prevalence rate was higher in relatives of those with HCC > or = 40 years old than in asymptomatic HBsAg carriers. Moreover, HBeAg was more likely to persist in men than in women > or = 40 years old. We conclude that families with HCC showed a prolonged HBV replication phase that may be one of the cofactors for a familial tendency for HCC. (+info)
Risk of hepatitis B transmission after amniocentesis in chronic hepatitis B carriers.
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OBJECTIVE: To measure the risk of perinatal transmission of HBV in chronic carriers who undergo amniocentesis. METHODS: This was a prospective, longitudinal study from 1990 to 1995 of women who were HBV carriers and underwent amniocentesis. The infants of these women were followed from birth to one year of age. Maternal data examined included HBV antigen and antibody status, liver function tests (LFTs) and the amniocentesis report. RESULTS: Twenty-eight women were identified. Two of 28 neonates were stillborn unrelated to hepatitis. Five infants were lost to follow-up leaving 21 mother-child pairs to evaluate. All 21 women were chronic HBV carriers at the time of amniocentesis for delivery. No mother had abnormal LFTs, and only one of 21 women was positive for hepatitis B e antigen (HBeAg). Thirteen amniocenteses were for advanced maternal age, and four were for abnormal maternal serum alphafetoprotein (MSAFP) screening. None of the amniocenteses were recorded as bloody, and the placenta was anterior in 6 of 21 procedures. None of the 21 infants (95% CI: 0-16.8%) were positive for HbsAg during the first month of life or at 12 months of age. All infants received HBV vaccine and HBIG immunoprophylaxis. CONCLUSION: The risk of transmission of HBV to the fetus after amniocentesis in women who are HBV carriers is low. Immunoprophylaxis in these infants was successful. (+info)