Current therapeutic approaches in childhood chronic hepatitis B infection: a multicenter study.
ABSTRACT The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection.
A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-alpha 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-alpha was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group.
The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 +/- 93 IU/L, 101 +/- 64 IU/L and 92 +/- 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 +/- 111 IU/L, 38 +/- 41 IU/L and 29 +/- 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05).
Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-alpha monotherapy group, no significant difference was found in the complete response ratios of all three groups.
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ABSTRACT: To evaluate the efficacy of two regimens of combined interferon-alpha2a (IFN-alpha2a) and lamivudine (3TC) therapy in childhood chronic hepatitis B. A total of 177 patients received IFN-alpha2a, 9 million units (MU)/m2 for 6 months. In group I (112 patients, 8.7 +/- 3.5 years), 3TC (4 mg/kg/day, max 100 mg) was started simultaneously with IFN-alpha2a, in group II (65 patients, 9.6 +/- 3.8 years) 3TC was started 2 months prior to IFN-alpha2a. 3TC was continued for 6 months after antiHBe seroconversion or stopped at 24 months in nonresponders. Baseline alanine aminotransferase (ALT) was 134.2 +/- 34.1 and 147.0 +/- 45.3; histological activity index (HAI) was 7.4 +/- 2.7 and 7.1 +/- 2.3; and HBV DNA levels were above 2,000 pg/ml in 76% and 66% of patients in groups I and II, respectively (P > 0.005). Complete response was 55.3% and 27.6% in groups I and II, respectively (P < 0.01). AntiHBe seroconversion was higher and earlier, and HBV DNA clearance was earlier in group I (P < 0.05). HBsAg clearance was 12.5% and 4.6% and antiHBs seroconversion was 9.8% and 6.2% in groups I and II, respectively (P > 0.05). Breakthrough occurred in 17.9% and 24.6%; breakthrough times were 15.9 +/- 4.6 and 14.1 +/- 5.1 months; and relapse rates were 6.8% and none in groups I and II, respectively (P > 0.05, P > 0.05, P > 0.05). Responders had higher HAI (HAI > 6) and higher pre-treatment ALT than non-responders. Simultaneous 3TC+IFN-alpha2a yields a higher response and earlier antiHBe seroconversion and viral clearance than consecutive combined therapy. Relapse rate is low. Predictors of response are high basal ALT and high HAI scores. 3TC can be administered for 24 months without any side effect and breakthrough rate is comparable with previous studies.Antiviral therapy 02/2006; 11(2):255-61. · 3.07 Impact Factor
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ABSTRACT: Die Hepatitis B ist die häufigste chronische Virusinfektion der Leber. Sie betrifft zumindest geschätzte 350 Millionen Menschen weltweit und ist die häufigste leberbedingte Todesursache. In der letzten Zeit gab es dramatische Entwicklungen sowohl in der Diagnostik als auch in der Medikamentenentwicklung der chronischen Hepatitis B. Heute ist die chronische Hepatitis B in der überwiegenden Mehrzahl der Patienten eine gut behandelbare Erkrankung und die wichtigste Herausforderung bleibt die rechtzeitige Identifikation der betroffenen Patienten, bevor diese eine fortgeschrittene Lebererkrankungen mit den assoziierten Komplikationen erleiden. Die rasche Entwicklung der medikamentösen Therapie verlangte nach einer Neufassung der Österreichischen Konsensusempfehlungen zur Behandlung der Hepatitis B, welche bisher nach den Versionen von 1994 und 1998 in ihrer dritten Version von 2005 vorlagen. Alle Kapitel des 3. Konsensus-Statements von 2005 wurden überarbeitet, mit Ausnahme des Kapitels über die Leberbiopsie, welches weiterhin in der Version von 2005 Gültigkeit hat. Im Speziellen spielen nun virologische Parameter für Behandlungsentscheidungen eine zentrale Rolle, die HBV-Genotypisierung wird nun für die Wahl des Therapeutikums vermehrt in Betracht gezogen und die orale Erstlinientherapie für die chronische Hepatitis B hat sich verändert. Dieser Konsensus-Bericht beinhaltet die entscheidenden Fortschritte der Behandlung der Hepatitis B und verändert das klinische Management von Patienten mit Hepatitis B in Österreich entscheidend. Hepatitis B is the most common chronic viral infection of the liver. Chronic hepatitis B is estimated to affect at least 350 million people worldwide and is the leading cause of death from liver disease. There have been dramatic developments both in the diagnostic field and in drug treatment of chronic hepatitis B. Today, chronic hepatitis B is a well manageable disease in the vast majority of cases and the main challenge remains the detection of affected patients at an early enough disease stage to prevent end-stage liver disease and its complications. The rapid pace of drug development mandated an update of the Austrian guidelines on the treatment of hepatitis B, which after 1994 and 1998 were now dating back to 2005 in their third version. All chapters from the 3. consensus statement from 2005 were renewed except for the chapter on liver biopsy, which is still valid in its 2005-version. In particular, virologic parameters take now center stage for treatment decisions, HBV-genotyping is now being considered for the choice of treatment, and the oral first line treatment for chronic hepatitis B has been changed. Overall this consensus statement accounts for the major advances in the management of hepatitis B and significantly changes clinical management of patients with hepatitis B in Austria. KeywordsHepatitis B-Liver transplantation-Interferon-Nucleoside-Nucleotide-Lamivudine-Telbivudine-Entecavir-Tenofovir SchlüsselwörterHepatitis B-Lebertransplantation-Interferon-Nucleosid-Nucleotid-Lamivudine-Telbivudine-Entecavir-TenofovirWiener klinische Wochenschrift 01/2010; 122(9):280-302. · 0.81 Impact Factor
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ABSTRACT: The aim of this study is to investigate the immunoregulatory role of interleukin-12 and interferon-gamma in children with chronic hepatitis B who are treated with interferon-alpha therapy. The patients were divided into 2 groups: Group I included 16 children with naive chronic replicative hepatitis B infection, and Group II included 6 children who are inactive hepatitis B virus (HBV) carriers. Group I received interferon-alpha subcutaneously (10 mU/m(2)/dose), 3 times a week during 4 months. Initial serum alanine aminotransferase (ALT) levels, hepatitis B serologic markers, serum interleukin-12 and interferon-gamma levels were measured. In Group I, laboratory tests were re-evaluated in the second and fourth months. Liver biopsy was performed in all patients and samples were used for tissue interleukin-12 level evaluation and histopathological examination. Hepatic activity index (HAI) and serum interferon-gamma were significantly higher in Group I (P < 0.05). Initial tissue interleukin-12 levels in Group I were low but a significant increase was observed at the fourth month (P < 0.05). While responder patients in Group I had marked elevation of tissue interleukin-12 levels, nonresponders did not reveal considerable changes at the fourth month evaluation. A negative correlation was found between serum HBV-DNA copies and interferon-gamma levels prior to therapy (P < 0.01, r: -0.66). The analysis of cytokine levels with serum transaminases demonstrated a positive correlation between the tissue interleukin-12 levels at the fourth month and serum ALT levels at the beginning and second month of the therapy (r: 0.77, P < 0.05 and r: 0.92, P < 0.05, respectively). This is the first study emphasizing the relationship between tissue cytokine levels and therapy success. Understanding the course of chronic hepatits B in the pediatric population will help us to clarify some debates on the treatment.Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research 03/2010; 30(6):433-8. · 1.63 Impact Factor