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Lamivudine and alpha interferon combination treatment versus alpha interferon treatment in children with chronic hepatitis B infection
Category 6: Viral hepatitis: clinical aspects ~'-~
(p < 0.001). After 6 months of posttreatment follow up, 1 of the antiHBe seroconverted patients and all of the patients with sole HBV-DNA negativity (HBeAg still positive) in the IFN-Lam group but none in the IFN group had relapsed. Prolongation of lamivudine therapy after completion of the 6 months combination treatment can improve the results especially in children with HBV-DNA negativity associated with HBeAg persistence.
QUANTITATIVE HBV-DNA TESTING AS AN EARLY PREDICTOR OF THE MAINTENANCE OF RESPONSE DURING LAMIVUDINE THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B
M. Buff, J.F. Sanchez-Avila, M. Cotrina, R. Jardi, F. Rodrfguez-Ftias, X. Costa, R. Esteban, J. Guardia. Liver and Biochemistry Departments,
Hospital Vall d'Hebron, Barcelona, Spain The safety and efficacy of lamivudine (LAM) in chronic hepatitis B (CHB) is well proven, however, the appropiate duration of therapy in anti-HBe positive patients is still to be defined. The major drawback with lamivudine treatment is the emergence of YMDD variants. It has been suggested that high pretreatment HBV-DNA levels could predict the emergence of HBV variants. Aim: To evaluate whether measuring quantitative HBV-DNA at month 3 of lamivudine treatment is useful in predicting response to therapy and the emergence of YMDD variants in patients with CHB. Patients a n d Methods: 35 patients with elevated serum ALT levels (median: 133 UI) and HBV-DNA +, (15 HBeAg + and 20 anti-HBe +), were treated with LAM 100 mg/day for > 1 year (range: 12-24 months). Biochemical and serological markers, bDNA, quantitative HBV-DNA (LLD < 1000 cop/mi) and YMDD were analyzed at baseline, 3 and 12 months of treatment. Results: At one year a virological response (HBV-DNA negative) was observed in 26/35 (74%) of cases and YMDD variants were detected in 15/34 (44%). HBV-DNA profiles of virological response and YMDD variants emergence are shown in these figures. ~
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Quantitative HBV-DNA < 1000 copies/ml at 3 months of LAM had a sensitivity of 73% and a specificity of 88% in the early prediction of virological response and a sensitivity of 60% and a specificity of 73% in the prediction of the emergence of YMDD variants. Conclusion: Quantitative HBV-DNA at 3 months is useful in making an early prediction of the maintenance of response and the emergence of YMDD variants in CHB patients treated with lamivudine for more than 1 year.
- ~
161
LAMIVUDINE AND ALPHA INTERFERON COMBINATION TREATMENT VERSUS ALPHA INTERFERON TREATMENT IN CHILDREN WITH CHRONIC HEPATITIS B INFECTION
B. Elkabes, O.D. Suoglu, S. Sokucu, G. Saner. Pediatric
Gastroenterology and Hepatology, Istanbul University Istanbul; School of Medicine Pediatric Gastroenterology and Hepatology Department, Turkey Alpha interferon (IFN) and lamivudine (Lam), the two drugs having different mechanisms of action, should have an additive effect against HBV. We compared combination therapy with standart dose IFN monotherapy in 75 naive Turkısh pediatric patients with chronic hepatitis B (age range 3-17 years). Chronic hepatitis B was diagnosed by HBeAg and HBV-DNA positivity with histological activity on liver biopsy. The children were assigned to receive subcutaneous alpha IFN (5 million U/m2/thrice weekly) either alone (IFN group: 55 patients) or together with oral Lam 3-4 mg/kg/day (IFN-Lam group: 20 patients) for six months. At the end of the treatment period, HBeAg seroconversion and HBV-DNA negativization rates were 60% (12/20) and 90% (18/20) vs 38% (21/55) and 40% (22/55) in IFN-Lam and IFN groups respectively
-~-~
HINESE MEDICINAL HERBS FOR CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW
J. Liu, H. Mclntosh, H. Lin. Copenhagen Trial Unit, Copenhagen
University Hospital, Copenhagen; Supported by The Danish Medical Research Council and The 1991 Pharmacy Foundation, Denmark; NHS Centre for Reviews and Dissemination, University of York, UK; Department of Epidemiology, Third Military Medical University, China Objectives: To assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis B. Methods: A systematic review on randomised trials comparing Chinese herbs versus placebo, no intervention, non-specific treatment, or interferon for chronic hepatitis B at >3 months follow-up. Methodological quality of trials was assessed by allocation concealment and Jadad-scale (Jadad 1996). Main Outcomes: Mortality, liver cirrhosis/cancer, viral response, liver biochemistry, and adverse events. Results: Nine trials (n -- 936) were included, of which only one trial had high quality. There was funnel plot asymmetry (intercept 3.37; P = 0.047). Fuzheng Jiedu Tang showed effect on clearance of serum HBsAg (relative risk 5.19; 95% CI 1.24-21.79), HBeAg (10.85; 3.56-33.06), and HBV DNA (8.50; 1.23-58.85). Polyporus umbellatus polysaccharide showed effect on clearance of serum HBeAg (3.06; 1.13-8.29) and HBV DNA (4.14; 1.0-17.19); Phyllanthus amarus showed effect on clearance of serum HBeAg (3.35; 1.49-7.56). Phyllanthus compound and kurorinone versus interferon showed no difference on clearance of HBeAg and HBV DNA and on ALT normalisation. Conclusions: Treatment with Chinese herbs for chronic hepatitis B is not recommended due to the publication bias and low quality of the trials. Rigorous randomised, double blind, placebo-controlled trials are needed.
~
MEDICINAL HERBS VERSUS MEDICINAL HERBS FOR CHRONIC HEPATITIS B VIRUS INFECTION: A SYSTEMATIC REVIEW
J. Liu, H. Lin, C. Ghiud. Copenhagen Trial Unit, Copenhagen
University Hospital, Copenhagen; Supported by The Danish Medical Research Council and The 1991, Pharmacy Foundation, Denmark; Department of Epidemiology, Third Military Medical University, China Objectives: To assess efficacy and safety, of medicinal herbs compared with other herbs for chronic hepatitis B virus (HBV) infection. Methods: Systematic review of randomised trials. Electronic databases and Chinese literature were searched. Methodological quality of trials was evaluated using allocation concealment and double blinding. Main Outcomes: Mortality, liver cirrhosis/cancer, viral markers, liver biochemistry, quality of life, and adverse events. Results: 49 RCTs (6972 patients) testing 54 herbal medicines were included and 47 had low methodological quality. Phyllanthus preparations showed better effect than other herbs on clearance of serum HBsAg (relative risk 2.32; 95% CI 1.25-4.32), HBeAg (3.10; 2.18--4.41), and HBV DNA (2.87; 1.96-4.21). Polyporus umbellatus polysaccharide was better than other herbs regarding antiviral activity and liver biochemistry. Among other herbs showing antiviral activity, Yiganning was better than oleanolic acid, Fuzheng Qudu better than Gansu, Matrine better than
(p < 0.001). After 6 months of posttreatment follow up, 1 of the antiHBe seroconverted patients and all of the patients with sole HBV-DNA negativity (HBeAg still positive) in the IFN-Lam group but none in the IFN group had relapsed. Prolongation of lamivudine therapy after completion of the 6 months combination treatment can improve the results especially in children with HBV-DNA negativity associated with HBeAg persistence.
QUANTITATIVE HBV-DNA TESTING AS AN EARLY PREDICTOR OF THE MAINTENANCE OF RESPONSE DURING LAMIVUDINE THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B
M. Buff, J.F. Sanchez-Avila, M. Cotrina, R. Jardi, F. Rodrfguez-Ftias, X. Costa, R. Esteban, J. Guardia. Liver and Biochemistry Departments,
Hospital Vall d'Hebron, Barcelona, Spain The safety and efficacy of lamivudine (LAM) in chronic hepatitis B (CHB) is well proven, however, the appropiate duration of therapy in anti-HBe positive patients is still to be defined. The major drawback with lamivudine treatment is the emergence of YMDD variants. It has been suggested that high pretreatment HBV-DNA levels could predict the emergence of HBV variants. Aim: To evaluate whether measuring quantitative HBV-DNA at month 3 of lamivudine treatment is useful in predicting response to therapy and the emergence of YMDD variants in patients with CHB. Patients a n d Methods: 35 patients with elevated serum ALT levels (median: 133 UI) and HBV-DNA +, (15 HBeAg + and 20 anti-HBe +), were treated with LAM 100 mg/day for > 1 year (range: 12-24 months). Biochemical and serological markers, bDNA, quantitative HBV-DNA (LLD < 1000 cop/mi) and YMDD were analyzed at baseline, 3 and 12 months of treatment. Results: At one year a virological response (HBV-DNA negative) was observed in 26/35 (74%) of cases and YMDD variants were detected in 15/34 (44%). HBV-DNA profiles of virological response and YMDD variants emergence are shown in these figures. ~
. ~ ~Vo~A p~m~- , ~ 1
D,^. t
\J.-
a
~
.e • N''wxanv"'b'm"t"~" I
~
Din,, I \ \ o P - t~ll \'~ ¢'
blo~
,l"
n2~
]i
t
1 ~ ~" . blmlllu
•"
,l:~"
Quantitative HBV-DNA < 1000 copies/ml at 3 months of LAM had a sensitivity of 73% and a specificity of 88% in the early prediction of virological response and a sensitivity of 60% and a specificity of 73% in the prediction of the emergence of YMDD variants. Conclusion: Quantitative HBV-DNA at 3 months is useful in making an early prediction of the maintenance of response and the emergence of YMDD variants in CHB patients treated with lamivudine for more than 1 year.
- ~
161
LAMIVUDINE AND ALPHA INTERFERON COMBINATION TREATMENT VERSUS ALPHA INTERFERON TREATMENT IN CHILDREN WITH CHRONIC HEPATITIS B INFECTION
B. Elkabes, O.D. Suoglu, S. Sokucu, G. Saner. Pediatric
Gastroenterology and Hepatology, Istanbul University Istanbul; School of Medicine Pediatric Gastroenterology and Hepatology Department, Turkey Alpha interferon (IFN) and lamivudine (Lam), the two drugs having different mechanisms of action, should have an additive effect against HBV. We compared combination therapy with standart dose IFN monotherapy in 75 naive Turkısh pediatric patients with chronic hepatitis B (age range 3-17 years). Chronic hepatitis B was diagnosed by HBeAg and HBV-DNA positivity with histological activity on liver biopsy. The children were assigned to receive subcutaneous alpha IFN (5 million U/m2/thrice weekly) either alone (IFN group: 55 patients) or together with oral Lam 3-4 mg/kg/day (IFN-Lam group: 20 patients) for six months. At the end of the treatment period, HBeAg seroconversion and HBV-DNA negativization rates were 60% (12/20) and 90% (18/20) vs 38% (21/55) and 40% (22/55) in IFN-Lam and IFN groups respectively
-~-~
HINESE MEDICINAL HERBS FOR CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW
J. Liu, H. Mclntosh, H. Lin. Copenhagen Trial Unit, Copenhagen
University Hospital, Copenhagen; Supported by The Danish Medical Research Council and The 1991 Pharmacy Foundation, Denmark; NHS Centre for Reviews and Dissemination, University of York, UK; Department of Epidemiology, Third Military Medical University, China Objectives: To assess the efficacy and safety of Chinese medicinal herbs for chronic hepatitis B. Methods: A systematic review on randomised trials comparing Chinese herbs versus placebo, no intervention, non-specific treatment, or interferon for chronic hepatitis B at >3 months follow-up. Methodological quality of trials was assessed by allocation concealment and Jadad-scale (Jadad 1996). Main Outcomes: Mortality, liver cirrhosis/cancer, viral response, liver biochemistry, and adverse events. Results: Nine trials (n -- 936) were included, of which only one trial had high quality. There was funnel plot asymmetry (intercept 3.37; P = 0.047). Fuzheng Jiedu Tang showed effect on clearance of serum HBsAg (relative risk 5.19; 95% CI 1.24-21.79), HBeAg (10.85; 3.56-33.06), and HBV DNA (8.50; 1.23-58.85). Polyporus umbellatus polysaccharide showed effect on clearance of serum HBeAg (3.06; 1.13-8.29) and HBV DNA (4.14; 1.0-17.19); Phyllanthus amarus showed effect on clearance of serum HBeAg (3.35; 1.49-7.56). Phyllanthus compound and kurorinone versus interferon showed no difference on clearance of HBeAg and HBV DNA and on ALT normalisation. Conclusions: Treatment with Chinese herbs for chronic hepatitis B is not recommended due to the publication bias and low quality of the trials. Rigorous randomised, double blind, placebo-controlled trials are needed.
~
MEDICINAL HERBS VERSUS MEDICINAL HERBS FOR CHRONIC HEPATITIS B VIRUS INFECTION: A SYSTEMATIC REVIEW
J. Liu, H. Lin, C. Ghiud. Copenhagen Trial Unit, Copenhagen
University Hospital, Copenhagen; Supported by The Danish Medical Research Council and The 1991, Pharmacy Foundation, Denmark; Department of Epidemiology, Third Military Medical University, China Objectives: To assess efficacy and safety, of medicinal herbs compared with other herbs for chronic hepatitis B virus (HBV) infection. Methods: Systematic review of randomised trials. Electronic databases and Chinese literature were searched. Methodological quality of trials was evaluated using allocation concealment and double blinding. Main Outcomes: Mortality, liver cirrhosis/cancer, viral markers, liver biochemistry, quality of life, and adverse events. Results: 49 RCTs (6972 patients) testing 54 herbal medicines were included and 47 had low methodological quality. Phyllanthus preparations showed better effect than other herbs on clearance of serum HBsAg (relative risk 2.32; 95% CI 1.25-4.32), HBeAg (3.10; 2.18--4.41), and HBV DNA (2.87; 1.96-4.21). Polyporus umbellatus polysaccharide was better than other herbs regarding antiviral activity and liver biochemistry. Among other herbs showing antiviral activity, Yiganning was better than oleanolic acid, Fuzheng Qudu better than Gansu, Matrine better than