Quantitation of hepatitis B viral DNA by solution hybridization: Comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy

Kuhns, Mary C.; McNamara, Anne L.; Perrillo, Robert P.; Cabal, C; Campbell, Carolyn

doi:10.1002/jmv.1890270404

Cited by 74 publications

(31 citation statements)

References 13 publications

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“…Serum HBV-DNA levels were determined with a solution-hybridization assay that incorporates an iodine-125 probe (Abbott Laboratories). 17 The sensitivity of this test is 1.5 pg/mL.…”

Section: Methodsmentioning

confidence: 99%

Efficacy of thymosin ?1 in patients with chronic hepatitis B: A randomized, controlled trial

et al. 1998

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Thymosin ␣ 1 (T␣) is an immune modifier that has been shown in a pilot study to be effective for chronic hepatitis B; this requires confirmation. Ninety-eight patients with clinicopathologically proven chronic hepatitis B were randomly allocated to 3 groups: 1) group A received a 26-week course of T␣ with a 1.6-mg subcutaneous injection two times a week (T 6 group); 2) group B received the same regimen as group A, but T␣ therapy extended for 52 weeks (T 12 group); and 3) group C served as a control group and was followed up for 18 months without specific treatment (T 0 group). The three groups were comparable in clinicohistological features at entry. The complete virological response rate (clearance of serum hepatitis B virus [HBV] DNA and hepatitis B e antigen [HBeAg]) was higher in group A (40.6%) and group B (26.5%) than in group C (9.4%) (group A vs. group C: P ‫؍‬ .004; group B vs. group C: P ‫؍‬ .068) when assessed 18 months after entry, although complete response rates among these three groups were similar when first assessed at the end of therapy. There was a trend for complete virological response to increase or accumulate gradually after the end of T␣ therapy. None of the responders lost hepatitis B surface antigen. Blinded histological assessment showed a significant improvement in treated patients, particularly in lobular necroinflammation and scores excluding fibrosis. No significant side effects were observed. These results suggest that a 26-week course of T␣ therapy is effective and safe in patients with chronic hepatitis B. (HEPATOLOGY 1998;27:1383-1387.)Chronic hepatitis B virus (HBV) infection is a serious problem because of its worldwide distribution and possible adverse sequalae, such as cirrhosis and hepatocellular carcinoma. [1][2][3][4][5] The ultimate goals of therapy for chronic hepatitis B are to prevent progression to cirrhosis and to prevent development of hepatocellular carcinoma. Over the past 20 years, many antiviral or immunomodulatory agents, or both, have been used in patients with chronic HBV infection. 6,7 Among them, interferon alfa (IFN-␣) has been shown to be effective, because 30% to 40% of adult white patients with elevated alanine transaminase (ALT) levels lost hepatitis B e antigen (HBeAg) and HBV DNA when treated with IFN-␣ at a dose of 5 MU daily or 10 MU three times a week for 16 weeks. 8,9 However, the response rate is far from satisfactory, particularly in Asian patients, although corticosteroid priming may enhance the efficacy of interferon therapy. [10][11][12] Thymosin ␣ 1 (T␣) is an immune modifier that has been shown to trigger maturational events in lymphocytes, to augment T-cell function, and to promote reconstitution of immune defects. 13 A small pilot study conducted by Mutchnick et al. 14 showed an 80% complete response associated with clinical, immunological, and histological improvement in patients with chronic hepatitis B. However, a multicenter American study involving 97 patients only showed a marginally significant benefit. 15 Thus, the efficacy of ...

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“…Serum HBV-DNA levels were determined with a solution-hybridization assay that incorporates an iodine-125 probe (Abbott Laboratories). 17 The sensitivity of this test is 1.5 pg/mL.…”

Section: Methodsmentioning

confidence: 99%

Efficacy of thymosin ?1 in patients with chronic hepatitis B: A randomized, controlled trial

et al. 1998

View full text Add to dashboard Cite

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“…The degree of viral replication was assessed by quantification of HBV DNA in the serum using an hybridization technique. Detection of serum HBV DNA has been shown to be a sensitive assay for viraemia, and a reliable marker of active viral replication [12]. Furthermore, it appears to be a valuable technique to detect HBV mutants in patients with anti-HBe antibodies.…”

Section: Disci Ssionmentioning

confidence: 99%

Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B

Pham

Mosnier

Walker

et al. 1994

Clinical and Experimental Immunology

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SUMMARY T lymphocytes have been assumed to play an essential role in tissue injury in patients with chronic hepatitis B. As hepatitis B virus (HBV) is considered as a major factor controlling liver inflammation, we assessed whether a particular T lymphocyte subset could be preferentially detected in the liver in accordance with viral replication. Liver‐derived lymphocytes and peripheral blood lymphocytes were analysed by flow cytometry in 21 patients with histologically confirmed chronic hepatitis B without cirrhosis. Viral replication was quantified by hybridization of serum HBV DNA. Eleven patients exhibited an active viral replication with serum HBV DNA ranging from 10 to 388pg/ml at the time of the liver biopsy, whereas 10 patients had no detectable serum HBV DNA. In patients exhibiting viral replication. CD4+/CD8+ ratios of liver‐derived lymphocytes were significantly higher [P < 005) than those obtained in patients without viral replication. In contrast, the percentage of T cells expressing the γ/δ receptor and that of CD2±/ CD57+ cells were similar in both groups of patients. Furthermore, in patients exhibiting viral replication. CD4+/CD8+ ratios of liver‐derived lymphocytes correlated with serum HBV DNA levels (P<0.0001). No relationship between CD4+ CD8* ratio of liver‐derived and peripheral blood lymphocytes was observed. Our data indicate that, in patients with chronic hepatitis B. the CD4+/CD8+ ratio of liver‐derived lymphocytes correlates with viral replication. This suggests that in situ helper/inducer CD4+ T lymphocytes may positively regulate the cytoxic T cell activity in patients with HBV‐related chronic hepatitis.

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“…Ongoing HBV replication triggers immune responses, causing liver injury. Knowledge of the minimum amount of HBV needed to produce continuous liver damage is important for a better understanding of the natural course of the disease and of the cutoff value for clinical differentiation of HBeAg-negative CHB from the inactive HBsAg carrier state (7)(8)(9)(10)(11)(12). Value of serum HBV DNA levels as determined by the hybridization method is limited, because assay sensitivity is as low as 10 5 to 10 6 copies/mL.…”

Section: Introductionmentioning

confidence: 99%

Serum Hepatitis B Virus (HBV)DNA Levels at Different Stages of Clinical Course in Patients with Chronic HBV Infection in an Endemic Area

et al. 2003

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The aims of this study were to investigate serum hepatitis B virus (HBV) DNA levels at different clinical stages in patients with chronic HBV infection, and to determine the serum HBV DNA level that discriminated HBeAg-negative chronic hepatitis B (CHB) cases from inactive HBsAg carriers. In all, 222 patients, encompassing 68 HBeAg-positive CHB patients (HBeAg-positive, ALT-elevation), 89 HBeAg-negative CHB patients (HBeAg-negative, ALT-elevation), and 65 inactive HBsAg carriers (HBeAg-negative, ALT-normal), were tested. The ALT levels had been tested more than twice during the previous six months, and the serum HBV DNA levels were quantified by a polymerase chain reaction-based assay. The serum HBV DNA levels of the HBeAg-negative patients were significantly lower than those of the HBeAgpositive patients (median 2.7×10 4 vs. 1.6×10 8 copies/mL; p=0.000). In addition, the HBV DNA levels of the HBeAg-negative CHB patients were significantly higher than those of the inactive HBsAg carriers (median 2.2×10 5 vs. 3.2×10 3 copies/ mL; p=0.000). The optimal HBV DNA level for discriminating HBeAg-negative CHB cases from inactive HBsAg carriers was 2.0×10 4 copies/mL. The serum HBV DNA levels were lower than the cutoff value in 72.3% (47/65) of the inactive HBsAg carriers, and in 31.5% (28/89) of the HBeAg-negative CHB patients. The serum HBV DNA levels differed significantly between these two groups. However, the levels in the two groups overlapped extensively, preventing the definition of a differentiation cut-off value.

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Quantitation of hepatitis B viral DNA by solution hybridization: Comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy

Cited by 74 publications

References 13 publications

Efficacy of thymosin ?1 in patients with chronic hepatitis B: A randomized, controlled trial

Efficacy of thymosin ?1 in patients with chronic hepatitis B: A randomized, controlled trial

Flow cytometry CD4+/CD8+ ratio of liver-derived lymphocytes correlates with viral replication in chronic hepatitis B

Serum Hepatitis B Virus (HBV)DNA Levels at Different Stages of Clinical Course in Patients with Chronic HBV Infection in an Endemic Area

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