Changes in Serum Hepatitis B Virus (HBV) DNA Positivity in Chronic HBV Infection: Results of a Long-Term Follow-Up Study of 138 Patients

Alberti, Alfredo; Pontisso, Patrizia; Fattovich, Giovanna; Schiavon, E; Chemello, Liliana; Bortolotti, Flavia; Tremolada, F.; Realdi, Giuseppe

doi:10.1093/infdis/154.4.562

Cited by 46 publications

(10 citation statements)

References 14 publications

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“…Four such occurrences were detected in this study, and none were associated with abnormal ALT values. These findings corroborate those from previous studies in Asian children with HBV (20) and differ from findings in adults in whom episodes of active virus replication after loss of HBeAg are frequently accompanied by severe abnormalities in liver function tests and liver histological findings (4,16,17,21,22).…”

Section: Discussionsupporting

confidence: 90%

Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children

et al. 1990

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During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 90%

Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children

et al. 1990

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“…We have reported that replication of HCV occurs even in advanced or late stages of liver disease (11). In HBV infection, the replicative level of HBV usually declines with time (19). In contrast, quantitation of circulating HCV RNA revealed that the serum concentration of HCV was higher in patients with CAH, cirrhosis or HCC than in patients with CPH or asymptomatic blood donors.…”

Section: Discussionmentioning

confidence: 98%

Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease

et al. 1993

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We describe a method for quantifying hepatitis C virus RNA in serum. This competitive assay combines reverse transcription and polymerase chain reaction and is based on coamplification of the target RNA with known amounts of synthetic mutated RNA. We tested serum samples from 104 hepatitis C virus carriers (9 asymptomatic blood donors and 95 patients with type C chronic liver disease) to determine the relationship between the replicative level of hepatitis C virus and various stages of the carrier states. The amount of circulating hepatitis C virus RNA ranged from 10(4) to 10(9.5) genomes/ml serum. The titer of hepatitis C virus RNA (logarithmic transformed copy numbers of RNA per milliliter of serum) was lower in asymptomatic blood donors (5.4 +/- 2.0) and in patients with chronic persistent hepatitis (7.3 +/- 1.1) than in patients with chronic active hepatitis (7.9 +/- 0.8), cirrhosis (7.8 +/- 0.7) or hepatocellular carcinoma (7.9 +/- 0.7). The titer of hepatitis C virus RNA was significantly lower in carriers younger than 40 yr old and correlated positively with the logarithmic transformed serum ALT level. Logistic regression showed that age and titer of hepatitis C virus RNA correlated independently with the stages of liver disease. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that elevation of viral replication may play an important role in liver injury and progression of liver disease. This competitive assay is useful in evaluating the state of viral replication in hepatitis C virus infection.

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“…[20][21][22][23][24][25][26][27][28][29] In addition, histological assessments of patients in other studies of lamivudine have shown that liver biopsy features improve significantly during lamivudine-induced suppression of HBV replication. 5,30,31 Further controlled trials of prolonged lamivudine treatment are in progress to define the efficacy and safety of lamivudine therapy and maintenance of virological responses after drug withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

Dienstag¹,

Schiff²,

Mitchell³

et al. 1999

Hepatology

188

128

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In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg); posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%). Therapy was discontinued after HBeAg loss/seroconversion in 7 patients, and Chronic hepatitis B virus (HBV) infection occurs in approximately 5% of the world' s population and is among the top 10 causes of death. Although interferon alfa has been approved as therapy for chronic hepatitis B, such treatment is suboptimal, yielding clinical benefit in a minority of patients. Lamivudine is an oral dideoxynucleoside that inhibits reverse transcription by causing chain termination of nascent viral DNA in human immunodeficiency virus (HIV) and HBV infection. 1 As reported previously, phase-II dose-ranging trials in North American and western European patients with chronic hepatitis B included daily doses of 5 to 600 mg administered for 1 to 6 months. 2-4 Therapy was well tolerated, doses of 100 mg or more suppressed serum HBV DNA levels consistently during therapy, and no significant advantage was identified for doses above 100 mg. 3,4 A sustained response posttreatment, however, defined as the loss of hepatitis B e antigen (HBeAg) and failure of HBV DNA to reappear after discontinuation of therapy, occurred in only 4% to 12% of patients in these dose-ranging studies. In a recently completed placebo-controlled phase-III trial involving 358 Chinese patients, Lai et al. 5 reported that 12 months of lamivudine therapy at a dose of 100 mg/d was associated with histological improvement in 67% of patients and HBeAg seroconversion in 16%, which is significantly better than response rates observed in concurrent placebo controls. This study in Asian patients, however, did not address treatmentstopping criteria; regardless of HBeAg status at the end of 12 months of therapy, all patients were enrolled in a continuingtreatment follow-up study. 5 In the present study, we wished to determine whether prolonged lamivudine therapy in Western patients would be safe and tolerable and result in loss of HBeAg and HBeAg seroconversion in a higher proportion of patients compared with the shorter dosing regimens studied previously. We also sought to determine whether lamivudine therapy could be withdrawn after HBeAg loss or HBeAg seroconversion. Therefore, we undertook an extended-treatment trial in previously Abbreviations: HBV, hepatitis...

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Changes in Serum Hepatitis B Virus (HBV) DNA Positivity in Chronic HBV Infection: Results of a Long-Term Follow-Up Study of 138 Patients

Cited by 46 publications

References 14 publications

Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children

Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children

Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease

Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy

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