Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

Brunetto, Maurizia Rossana; Oliveri, Filippo; Coco, B.; Leandro, Gioacchino; Colombatto, P.; Gorin, Juliana Monti; Bonino, Ferruccio

doi:10.1016/s0168-8278(01)00266-5

Cited by 311 publications

(290 citation statements)

References 33 publications

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“…Although all HBeAg-negative patients fulfilled the criteria at the screening visit (HBV DNA Ͼ 1 ϫ 10 5 , ALT Ͼ 1.2), fluctuations in serum HBV DNA and ALT levels were observed in some patients at baseline. 24 Genotype distribution was as follows: eight patients were infected with genotype A, one patient with genotype C, 14 patients with genotype D, and two patients with genotype G. One patient could not be genotyped. Before the start of combination therapy, all patients had a liver biopsy, with a median necroinflammatory score of 2 (range 1-3) and fibrosis score of 1 (range 0-4).…”

Section: Resultsmentioning

confidence: 99%

Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

et al. 2006

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I nfection with hepatitis B virus (HBV) causes acute and chronic hepatitis and is strongly associated with the development of cirrhosis and hepatocellular carcinoma. Immediately after infection of hepatocytes, the viral DNA is transferred to the nucleus, where the viral polymerase is removed, and the double-stranded, open circular DNA is converted to a covalently closed circular DNA molecule (cccDNA). During chronic HBV infection (CH-B), cccDNA accumulates in hepatocyte nuclei, apparently at a level of about 5-50 copies per cell, where it persists as a minichromosome and functions as the template for the transcription of viral genes. 1 The RNA pregenome, in addition to producing capsid and polymerase proteins, becomes encapsidated and is reverse-transcribed. A particularity of the hepadnavirus life cycle is that DNA-containing nucleocapsids can either recycle back to the nucleus to amplify and maintain the pool of cccDNA or become enveloped and secreted into the blood, where new viral particles can spread to other hepatocytes. 2,3 Because cccDNA is the transcriptional template of the virus, it is required for maintenance of HBV infection.Evidence from the woodchuck hepatitis virus system indicated that the pool of cccDNA persisted even when viral production was strongly reduced by the presence of nucleoside analogues. 4,5 Woodchuck studies 6,7 and recent

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Section: Resultsmentioning

confidence: 99%

Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

et al. 2006

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“…Patients who developed elevated serum ALT levels also showed a trend toward having a significant increase in modified HAI score on follow-up liver biopsy compared with that on initial liver biopsy (median 10 [range [8][9][10][11][12][13][14][15][16][17][18] 24 Using the revised serum ALT cutoff limits, 3 of the 51 patients (5.9%) would be predicted to develop elevated serum ALT levels compared with a predicted 9 of 57 patients (15.8%) if the existing normal range were used (P ϭ 0.10).…”

Section: Resultsmentioning

confidence: 99%

“…Although seroconversion of HBeAg to hepatitis B e antibody (anti-HBe) often leads to hepatic inflammation subsiding and an improved prognosis, the identification of precore/core promoter mutations and recognition of HBeAg-negative CHB disease explain the disease progression noted after HBeAg seroconversion. [7][8][9][10] Recent studies have demonstrated a strong link between viral replication, liver injury, and progression to cirrhosis with increased risk of HCC in CHB-infected From the …”

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confidence: 99%

Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase

et al. 2007

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In view of the findings that high hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is associated with increased risk of chronic hepatitis B (CHB)-related complications, disease progression in CHB patients in the immune-tolerant phase is uncertain. We evaluated disease progression in 57 immune-tolerant CHB patients with high HBV DNA. Each subject underwent an initial liver biopsy. In those who remained in the immune-tolerant phase, a follow-up liver biopsy was performed after 5 years of follow-up. Patients who developed elevated serum alanine aminotransferase (ALT) levels were discontinued from the study after a follow-up liver biopsy. Traditionally, serum alanine aminotransferase (ALT) level and HBV serology analysis have been widely used for the assessment of patients with CHB infection. The annual incidence of cirrhosis has been estimated to be 2%-6% for hepatitis B e antigen (HBeAg)-positive CHB patients and 8%-10% for HBeAg-negative CHB patients. 4,5 The higher incidence of cirrhosis among HBeAg-negative patients is related to older age and more advanced liver disease at presentation. 2,4,5 More advanced fibrosis stage at presentation correlates with risk of cirrhosis, and those with milder forms of hepatitis have a longer time to cirrhosis. 6 HBeAg positivity has also been found to be associated with higher hepatic inflammation and an increased risk of HCC. Although seroconversion of HBeAg to hepatitis B e antibody (anti-HBe) often leads to hepatic inflammation subsiding and an improved prognosis, the identification of precore/core promoter mutations and recognition of HBeAg-negative CHB disease explain the disease progression noted after HBeAg seroconversion. [7][8][9][10] Recent studies have demonstrated a strong link between viral replication, liver injury, and progression to cirrhosis with increased risk of HCC in CHB-infected From the

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“…Serum HBV DNA levels are lower than in HBeAg-positive patients but may be very high. In a study of 164 anti-HBe-positive patients who were monitored at monthly intervals for a median period of 21 months, 64% had fluctuating ALT levels, including 44% whose ALT levels were intermittently normal [5].…”

Section: Phases Of Chronic Hbv Infectionmentioning

confidence: 99%

Should chronic HBV infected patients with normal ALT treated: debate

Sarin

Kumar

2008

Hepatol Int

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Alanine aminotransferase (ALT) levels have traditionally been used for treatment decisions in chronic hepatitis B virus (CHBV) infected patients. But recent data have raised doubts on this wisdom, as a significant proportion of CHBV infected patients with normal ALT have high HBVDNA levels and significant liver injury at presentation especially in areas of intermediate to high endemicity. A normal ALT value only identifies patients less likely to respond to current treatments, rather than patients who are not in need of the treatment. Patients with CHBV infection with normal ALT should be considered for treatment based on the HBV DNA levels and histological injury.

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Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

Cited by 311 publications

References 33 publications

Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B

Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase

Should chronic HBV infected patients with normal ALT treated: debate

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