Biomedical subjects

Monika van Zonneveld

Publications and source records attributed to Monika van Zonneveld.

7 recordsLinked to original sources

PubMed2006

Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: relation to treatment response.

In chronic hepatitis B, it is difficult to predict an early therapeutic response. We investigated the viral decline during therapy with pegylated interferon alpha-2b (PEG-IFN) with or without lamivudine in 266 HBeAg-positive chronic hepatitis B patients. In patients treated with PEG-IFN and lamivudine, a uniform biphasic viral decline pattern was found during therapy and there were no marked differences in viral load between those who lost HBeAg at the end of follow-up (response) or not. In contrast, those treated with PEG-IFN monotherapy exhibited different viral decline patterns. A delayed decline of at least two log from baseline HBV DNA after week 4 but before week 32 was associated with the highest response rate (63%). In comparison, response was 52% for patients with an early decline (week 0-4), 38% for a late decline (week 32-52), 27% for a posttreatment decline (week 52-78) and 11% for patients with no substantial decline. The HBsAg loss was 22% in the delayed decline pattern compared to 4% for those with early decline and none for other decline patterns. In conclusion, different patterns of decline in viral load during treatment with PEG-IFN monotherapy were associated with different rates of HBeAg and HBsAg loss at the end of follow-up. Since there was a considerable response, even in patients with a late or posttreatment decline pattern, prediction of response based on viral decline during the first months of therapy was difficult.

Adult↗

PubMed2006

Peg-interferon improves liver histology in patients with HBeAg-positive chronic hepatitis B: no additional benefit of combination with lamivudine.

BACKGROUND: The effect of pegylated interferon or its combination with lamivudine on liver histology of patients with chronic hepatitis B (CHB) is unknown. In a double-blinded, randomized, multi-center study we assessed histological changes in 110 hepatitis B e-antigen (HBeAg)-positive CHB patients treated for 52 weeks with Pegylated interferon alpha-2b (PEG-IFN) in combination with either lamivudine or placebo. Liver biopsies were taken before and at the end of treatment. All biopsies were blinded and scored according to the Ishak system. RESULTS: Necroinflammatory score improved (defined as a decrease of at least two points) in 25 patients (48%) of the PEG-IFN/lamivudine combination therapy group and in 31 patients (53%) of the PEG-IFN monotherapy group. The fibrosis score improved (decrease of at least 1 point) in 17 patients (33%) of the combination therapy group vs. 13 patients (22%) of the PEG-IFN monotherapy group (P=0.23). Responders (n=42), defined as serum HBeAg negative at the end of therapy, showed a larger decline in necroinflammatory score than non-responders (mean decline 2.3 and 1.2 points, respectively, P=0.02). Among patients receiving PEG-IFN monotherapy necroinflammation improved more frequently in responders (78% of responders vs. 43% of non-responders, P=0.01) and in patients who showed normalization of ALT (76% of patients with normal ALT vs. 40% of patients with abnormal ALT, P=0.01). Fibrosis score in the PEG-IFN monotherapy group improved more often in responders (39%) than in non-responders (15%, P=0.04). In the PEG-IFN/lamivudine combination therapy group, we found no significant association between virological and biochemical endpoints and histological improvement. CONCLUSIONS: Treatment with PEG-IFN therapy improves liver necroinflammation in HBeAg-positive CHB patients, particularly in responders to therapy. PEG-IFN also improves fibrosis in responders. Addition of lamivudine to PEG-IFN did not further improve the histological outcome.

Adult↗

PubMed2006

Treatment with Peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype.

BACKGROUND AND AIMS: Hepatitis B surface antigen (HBsAg) loss is the hallmark of a complete response to antiviral therapy for chronic hepatitis B. In this study, we investigated the frequency of HBsAg loss after treatment with pegylated (Peg)-interferon alpha-2b. METHODS: In a multicenter randomized controlled trial, 266 HBeAg-positive patients were treated for 52 wks with Peg-interferon alpha-2b (100 microg/wk) in combination with either lamivudine (100 mg/day) or placebo. Posttreatment follow-up was 26 wks. RESULTS: At the end of follow-up, 95 (36%) of the 266 patients exhibited HBeAg loss, 18 (7%) HBsAg loss, and 16 (6%) HBsAg seroconversion. Addition of lamivudine did not enhance HBeAg loss, HBsAg loss, or development of anti-HBs. All 18 patients who showed HBsAg loss had normal ALT; 11 (61%) of these patients were also hepatitis B virus (HBV) DNA negative (<400 copies/mL) at the end of follow-up. Loss of HBsAg differed according to HBV genotype: 14% for genotype A, 9% for genotype B, 3% for genotype C, and 2% for genotype D (A vs D: p = 0.006). CONCLUSIONS: One year of Peg-interferon alpha-2b for HBeAg-positive patients led to HBsAg loss in 7%. Our study indicates that treatment with Peg-interferon alpha-2b is the best therapy to achieve HBsAg clearance in patients with genotype A.

Adult↗

PubMed2004

Hepatitis B.

Explore the source record for details and available documents.

Antiviral Agents↗

PubMed2004

Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B.

Data on the long-term effects of interferon alfa (IFN) treatment on disease progression and mortality in patients with chronic hepatitis B (CHB) are limited. To evaluate factors that influence clinical outcome and survival, we performed a follow-up study on 165 hepatitis B e antigen (HBeAg) positive CHB patients treated with IFN between 1978 and 2002. The median IFN dose was 30 megaunits (MU)/week (range, 2-70 MU/week), and the median duration of therapy was 16 weeks (range, 1-92 weeks). Response to treatment was defined as HBeAg loss within 12 months after the end of IFN therapy. Median follow-up was 8.8 years (range, 0.3-24 years). Fifty-four patients (33%) responded to IFN treatment. Relapse (HBeAg reactivation) occurred in 7 of the 54 (13%) responders. Fifty-two percent of the responders lost hepatitis B surface antigen (HBsAg) as compared with 9% of the nonresponders (P <.001). Liver histology showed a decreased necroinflammatory activity and less progression of fibrosis in responders. Twenty-six patients died during follow-up. Hepatocellular carcinoma (HCC) was found in 8 patients, 6 of whom were nonresponders. Of the two responders who developed HCC, one patient had relapsed after discontinuation of therapy. Multivariate analysis showed significantly improved survival (relative risk (RR) of death 0.28, 95% CI 0.10-0.78) and reduced risk of developing HCC (RR 0.084, 95% CI 0.09-0.75) in responders. In conclusion, response to IFN therapy results in a prolonged clinical remission with an increased rate of HBsAg seroconversion and improved liver histology. Our results indicate that after correction for baseline factors, response to IFN therapy increases survival and reduces the risk of developing HCC.

Adolescent↗

PubMed2004

Polyarteritis nodosa associated with hepatitis B virus infection. The role of antiviral treatment and mutations in the hepatitis B virus genome.

Polyarteritis nodosa (PAN) is a systemic inflammatory disease causing vasculitis of medium sized and small arteries. Circulating immune complexes containing viral proteins have been implicated in the pathogenesis of hepatitis B virus (HBV) related PAN and several immunosuppressive and antiviral regimens have been used with varying success. In our hospital seven HBV positive patients with a confirmed diagnosis of PAN could be identified between 1984 and 2001. Most patients had an acute HBV infection and all patients were treated with prednisone. A combination of prednisone and antiviral therapy with alpha-interferon (IFN) was used only in the last four patients. HBV DNA was isolated from serum samples obtained before treatment from the four IFN treated patients and amplified by using the polymerase chain reaction technique. None of the patients without, but two of four with antiviral therapy exhibited HBsAg seroconversion. In three out of four patients HBV DNA decreased rapidly after starting IFN therapy. Clinical remission of PAN was observed in three of the four treated patients, but in none of the three patients who were not receiving antiviral medication. Analysis of the HBV genome revealed no mutations that could be associated with PAN. In one patient a stop codon in the pre-core region and a double mutation A1762T-G1764A were found during antiviral therapy. We did not find HBV heterogeneity predisposing to the development of PAN. In our group of patients it appeared that clinical remission of PAN was primarily related to spontaneous or therapy induced loss of HBV DNA replication. The combined administration of a priming steroid course and IFN appears to be an improvement over prednisone monotherapy and should be considered for every patient with HBV related PAN. The efficacy of new generation nucleoside analogues should be further elucidated in future studies.

Adult↗

PubMedDate not supplied

Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.

BACKGROUND: Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. METHODS: 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. FINDINGS: 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). INTERPRETATION: Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.

Adult↗