Outcome of chronic anti-HBe positive hepatitis B

Brunetto, M.R.; Oliveri, Filippo; Coco, B.; Colombatto, P.; Gorin, Juliana Monti; Bonino, Ferruccio

doi:10.1016/s1590-8658(00)80702-1

Cited by 18 publications

(25 citation statements)

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“…It has been reported that HBeAg-negative chronic hepatitis B is associated with a high relapse rate and a poor sustained response rate of only 10% to standard IFN therapy [130]. Although precore A1896 stop codon mutant and BCP T1762/A1764 mutant are known to abolish or reduce the production of HBeAg, leading to the development of HBeAg-negative chronic hepatitis B [131,132], the influence of these two common HBV mutants on the response to currently available anti-HBV agents remains largely unknown.…”

Section: Naturally Occurring Mutantsmentioning

confidence: 99%

“…Although precore A1896 stop codon mutant and BCP T1762/A1764 mutant are known to abolish or reduce the production of HBeAg, leading to the development of HBeAg-negative chronic hepatitis B [131,132], the influence of these two common HBV mutants on the response to currently available anti-HBV agents remains largely unknown. Earlier studies showed that precore A1896 stop codon mutant might be associated with the poor response to IFN therapy in patients with HBeAg-negative chronic hepatitis B [130]; however, the results seem controversial [133]. Recently, Erhardt et al performed sequence analysis of several HBV subgenomic regions in 96 HBeAg-positive and HBeAg-negative patients treated with standard interferon [134].…”

Section: Naturally Occurring Mutantsmentioning

confidence: 99%

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Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

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Section: Naturally Occurring Mutantsmentioning

confidence: 99%

Section: Naturally Occurring Mutantsmentioning

confidence: 99%

Role of viral factors in the natural course and therapy of chronic hepatitis B

Kao

2007

Hepatol Int

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“…2-4 Nevertheless, several observations suggest that an undefined amount of free viral genomes may persist into the hepatocytes of these subjects, 5,6 and such episomal HBV forms might be implicated in the reactivation of silent infections that may occur either spontaneously 7-9 or in conditions of immunosuppression, [10][11][12] or, in patients treated with antiviral drugs, after stopping therapy. [13][14][15][16][17] Thus, analysis and quantification of intrahepatic HBV genomes appear to be of biological interest and may provide useful clinical information.The aim of this study was to quantify the intrahepatic HBV DNA in HBsAg-positive patients with either active HBV infection or suppressed viral replication. Our additional purpose was to measure liver HBV DNA in HBsAg-negative cases with ''occult'' HBV infection.…”

mentioning

confidence: 99%

“…[2][3][4] Nevertheless, several observations suggest that an undefined amount of free viral genomes may persist into the hepatocytes of these subjects, 5,6 and such episomal HBV forms might be implicated in the reactivation of silent infections that may occur either spontaneously [7][8][9] or in conditions of immunosuppression, [10][11][12] or, in patients treated with antiviral drugs, after stopping therapy. [13][14][15][16][17] Thus, analysis and quantification of intrahepatic HBV genomes appear to be of biological interest and may provide useful clinical information.…”

mentioning

confidence: 99%

Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection

et al. 2000

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No data are available about the amount of hepatitis B virus (HBV) genomes in liver of patients with chronic HBV infection. The aim of this study was to quantify the intrahepatic HBV DNA in hepatitis B surface antigen (HBsAg)-positive patients with either active or suppressed viral replication and in HBsAg-negative subjects with occult HBV infection. We optimized the Roche ''Amplicor HBV Monitor'' kit for quantifying liver HBV DNA and analyzed hepatic DNA extracts and serum samples from 19 HBs-Ag-positive and 43 HBsAg-negative individuals. Eight of the HBsAg carriers had active HBV replication, and for 3 of them we analyzed samples obtained before and at the end of 1 year of lamivudine treatment. Five hepatitis Delta virus (HDV) coinfected patients and 6 healthy HBsAg carriers had inhibited HBV activity. Among the HBsAg-negative subjects 21 had occult HBV infection and 22 had no evidence of HBV infection. The median of HBV genomes per microgram of liver DNA milliliter of serum was 34,500 to 2,620,000 in patients with active viral replication, 20,000 to 3,900,000 before and 10,000 to 2,800 at the end of therapy in lamivudine-treated individuals, 9,800 to 600 in HDVinfected individuals, and 7,450 to 17,400 in healthy HBsAg carriers. These data indicate that cases with suppressed HBV activity, despite the very low levels of viremia, maintain a relatively high amount of intrahepatic viral genomes. This virus reservoir is likely involved in HBV reactivation, which is usually observed after stopping lamivudine treatment. Finally, the analysis of cases with occult HBV infection showed that the assay we used was able to specifically detect and quantify as few as 100 copies of viral genomes per microgram of liver DNA. (HEPATOLOGY 2000;31: 507-512.)Hepatitis B virus (HBV) is a major health problem worldwide and it is estimated that 350 million individuals are chronically infected with this virus. 1 Chronic HBV infection may be associated with a large spectrum of clinical forms ranging from the status of healthy carrier of hepatitis B surface antigen (HBsAg) to a moderate or severe chronic hepatitis susceptible of evolution to cirrhosis and development of hepatocellular carcinoma (HCC). 1 HBV-induced liver damage is strictly related with virus active replication, which is usually investigated detecting serum viral DNA by direct hybridization techniques. Consequently, HBsAg-positive patients with suppressed viral replication and undetectable levels of viremia have usually low grade or absence of hepatocellular injury. 2-4 Nevertheless, several observations suggest that an undefined amount of free viral genomes may persist into the hepatocytes of these subjects, 5,6 and such episomal HBV forms might be implicated in the reactivation of silent infections that may occur either spontaneously 7-9 or in conditions of immunosuppression, [10][11][12] or, in patients treated with antiviral drugs, after stopping therapy. [13][14][15][16][17] Thus, analysis and quantification of intrahepatic HBV genomes appear to be of biological inter...

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“…After a 6-to 12-month course of IFN-␣ treatment, the rate of HBsAg loss during the initial year may vary from 10% to 16% 7 and reach up to 44%. 23 However, there is no information in patients who respond to a second or third course of treatment and the clinical significance needs to be investigated in the future.…”

Section: Discussionmentioning

confidence: 99%

Pilot study of combination therapy with ribavirin and interferon alfa for the retreatment of chronic hepatitis B e antibody-positive patients

Cotonat¹,

Quiroga²,

López‐Alcorocho³

et al. 2000

Hepatology

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Twenty-four patients with chronic hepatitis B virus (HBV), antibody to hepatitis B e antigen (anti-HBe), HBV DNA positivity, and alanine transaminase (ALT) elevation who failed previous interferon alfa (IFN-␣) therapy were included in a pilot study of combination therapy with ribavirin and IFN-␣. The patients received daily oral ribavirin (1,000-1,200 mg according to body weight) plus 5 million units (MU) IFN-␣2b three times a week for 12 months and were followed-up for 12 months. The median viremia level decreased significantly at the end of treatment (1.2 ؋ 10 3 copies/mL) and follow-up (4.0 ؋ 10 2 copies/mL) compared with the baseline (3.0 ؋ 10 6 copies/mL; P F .05). After 12 months, 8 of 24 (33%) patients had cleared HBV DNA and 12 (50%) had normal ALT levels. At the end of the study virological and biochemical response was 50% and 21%, respectively. Thus, virological and biochemical response sustained in 5 of 24 (21%) patients retreated with ribavirin and IFN-␣; none of them lost hepatitis B surface antigen (HBsAg). Liver histology improved in 2 of 4 sustained responders but in none of the 12 nonresponders with paired biopsies (P ‫؍‬ .05). The response was independent of dose and duration of previous treatment, viral load, or the distribution of HBV precore wild-type/mutant variants. However, sustained responders had significantly higher necroinflammation (P ‫؍‬ .036) and fibrosis (P ‫؍‬ .007) scores. IFN-␣-related side effects were mild and reversible on discontinuation. In 4 (17%) patients who suffered nausea and diarrhea the ribavirin dosage was reduced by 50% after 1 month of therapy and finally discontinued in all of them. No patient had liver disease decompensation. Two phases can be recognized in the natural history of chronic hepatitis B virus (HBV). Initially patients are highly viremic, have detectable hepatitis B e antigen (HBeAg), and HBV DNA is present in a high number of copies. Treatment with interferon alfa (IFN-␣) leads to viral clearance and seroconversion from HBeAg to antibody to hepatitis B e antigen (anti-HBe) in approximately 25% to 40% of these cases, whereas spontaneous disease remission occurs in only 5% of untreated cases. 1 Despite IFN-␣ treatment, a low level of HBV DNA still continues to be detectable by the polymerase chain reaction (PCR) in the serum of patients who have seroconverted to anti-HBe. 2 These anti-HBe-and HBV-DNA (by PCR)-positive patients with abnormal alanine transaminase (ALT) values have progressive liver disease. In addition, they usually have a variant HBV strain with the presence of precore mutants, among which the most frequent is a point mutation from G to A at position 1896. 3 It has been postulated that the existence of this precore mutant is associated with a lower rate of response to IFN-␣ treatment. 4 In several reports, IFN-␣ treatment of anti-HBe-positive chronic hepatitis B patients resulted in the clearance of HBV DNA and normalization of ALT in 20% to 90% of the cases, but the response was transient. [4][5][6][7] More recently, IFN-␤ treatment ...

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Outcome of chronic anti-HBe positive hepatitis B

Cited by 18 publications

References 0 publications

Role of viral factors in the natural course and therapy of chronic hepatitis B

Role of viral factors in the natural course and therapy of chronic hepatitis B

Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection

Pilot study of combination therapy with ribavirin and interferon alfa for the retreatment of chronic hepatitis B e antibody-positive patients

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