L. Aprea

Treatment of chronic hepatitis B in children with prednisone followed by alfa-interferon: a controlled randomized study.

The efficacy and safety of sequential treatment with prednisone and interferon was evaluated in a randomized, controlled study on 43 children with biopsy proven HBsAg/HBeAg/hepatitis B virus-DNA positive, anti-delta negative, chronic hepatitis (34 chronic persistent hepatitis, 9 chronic active hepatitis). Patients received either a 1-month course of prednisone (0.6 to 0.3 mg/kg per day) followed by interferon alfa-2a (3 MU/m2, thrice weekly, for 12 months; 22 patients) or no treatment (21 patients). At the end of the study (20 months), clearance of hepatitis B virus-DNA and HBeAg seroconversion were observed in nine (41%) of the patients treated with prednisone and interferon and in two (9.5%) of the untreated controls (p = 0.020). Two of the treated patients who lost HBeAg, also cleared HBsAg. In the treated group, 13 (59%) patients had stable normal levels of alanine aminotransferase on their last examination. The baseline serum level of hepatitis B virus-DNA was an important predictor of response. In fact, HBeAg clearance was observed in 75% of patients with a baseline hepatitis B virus-DNA level lower than 100 pg/ml and in none with a level above 100 pg/ml. We suggest that combined treatment with prednisone followed by alfa-interferon may be safe and effective in inducing a stable clearance of HBeAg and, in some cases, of HBsAg in children with chronic hepatitis B and with a low level of viral replication. For children with high levels of viral replication, this regimen seems to be ineffective.

Interaction between HDV and HBV infection in HBsAg-chronic carriers

SummaryWe studied the interaction between HBV and HDV infection in 149 consecutive subjects with HBsAg positive chronic hepatitis and in 22 chronic HBsAg healthy carriers. Liver HBcAg was detected in 52 (30.4%) of the 171 subjects. Of these 52, 35 were HBV-DNA and HBeAg positive, 11 HBV-DNA positive only; two HBeAg positive only and four were negative for both HBeAg and HBV-DNA. None of the 119 HBcAg-negative subjects had detectable HBV-DNA in serum. HD-Ag in hepatocytes was detected in 31 of the 171 subjects (18%); it was detectable in none of the 22 HBsAg healthy carriers, in four of the 56 patients with chronic persistent hepatitis (7.2%), in six of the 24 patients with chronic lobular hepatitis (25%), in 16 of the 40 patients with chronic active hepatitis (40%) and in five of the 29 with cirrhosis (17%). A presence of anti-HD in serum in the absence of liver HD-Ag was found in 54 of the 171 subjects (32%). This condition was observed not only in patients with a progressive disease (37.7% of chronic active hepatitis or cirrhosis and 33% of chronic lobular hepatitis), but also in healthy carriers (36%) and in chronic persistent hepatitis patients (21.4%). Liver HBcAg was detected in 6.4% of the 31 HD-Ag-positive patients, in 12.9% of the 54 HD-Ag-negative/anti-HD positive, but in 50% of the 86 with no marker of HDV infection. HDV appears to inhibit HBV genome and such inhibition may persist even when anti-HD is the only HDV marker detectable.ZusammenfassungBei 149 nacheinander eingewiesenen chronischen HBsAg-positiven Patienten mit chronischer Hepatitis und 22 gesunden HBsAg Trägern wurde die Interaktion zwischen der HBV- und HDV-Infektion untersucht. Bei 52 der insgesamt 171 Personen (30,4%) fand sich HBsAg in den Leberzellen. Bei 35 dieser 52 Fälle wurde HBV-DNA und HBeAg nachgewiesen, in 11 Fällen HBV-DNA allein. Bei den 119 HBcAg-negativen Personen waren HBV-DNA in keinem Fall im Serum nachweisbar. Bei 31 der 171 Personen wurden HD-Ag in Hepatozyten entdeckt (18%). Die 22 gesunden HBsAg-Träger waren alle HD-Ag negativ. Von den 56 Patienten mit chronisch persistierender Hepatitis waren vier positiv (7,2%); von den 24 Patienten mit chronischer lobulärer Hepatitis sechs (25%), von den 40 Patienten mit chronisch aktiver Hepatitis 16 (40%) und von den 29 Patienten mit Zirrhose fünf (17%). 54 der 171 Untersuchten (32%) wiesen im Serum anti-HD auf, ohne daß sich HD- Ag in der Leber nachweisen ließ. Dabei handelte es sich nicht nur um Patienten mit progressivem Krankheitsverlauf (37,7% der Patienten mit chronisch aktiver Hepatitis und 33% derer mit chronischer lobulärer Hepatitis) sondern auch um gesunde Träger (36%) und Patienten mit chronisch persistierender Hepatitis (21,4%). Bei 6,4% der 31 HD-Ag positiven Patienten ließ sich HBcAg in der Leber nachweisen; positiv waren auch 12,9% der 54 HD-Ag-Negativ/anti-HD-Positiven und 50% der Personen ohne Marker für eine HDV-Infektion. Offensichtlich hemmt HDV das HBV-Genom; diese Hemmwirkung kann bestehen bleiben, auch wenn anti-HD der einzige nachweisbare Marker für eine durchgemachte HDV-Infektion ist.

Non responders to interferon therapy among chronic hepatitis patients infected with hepatitis C virus

We studied a series of 268 chronic hepatitis C patients (31 chronic persistent hepatitis CPH, 69 mild chronic active hepatitis CAH, 125 severe CAH, and 43 active cirrhosis) enrolled from 1988 to 1991 in different therapeutic protocols using lymphoblastoid or recombinant interferon (IFN) at a dosage of 3 mega units (M.U.), three times a week for 12 months. Of these patients 54.8% showed a complete response (normalization of aminotransferases), 14.2% a partial response (decrease in aminotransferases of over 50%), 27.6% no response, and 3.4% a substantial progressive increase in the liver enzymes during IFN (becoming worse). The prevalence of non responders was lower in CPH (9.7%) than in CAH patients (31.9% in the mild form and 20.8% in the severe), and significantly higher in patients with cirrhosis (53.5%). No correlation was observed between non response and the baseline aminotransferase level or the patients sex. Patients under 35 had a better response to IFN when compared with patients 36-50 years. This is probably due to the higher prevalence of CPH patients with a good response to IFN in the youngest group. No effect was gained in non responders by increasing the dose or shifting from recombinant to lymphoblastoid IFN; three patients were then treated with steroids, but only one benefitted. For 5 of the 9 patients who became worse, steroids were started after discontinuation of IFN therapy, and they induced a favorable response only for the 3 who had developed autoantibodies during IFN treatment.

Effect of prednisone priming followed by alfa-interferon in treatment of children with chronic hepatitis B: an interim analysis of a controlled trial.

A six-month analysis of a controlled trial on the treatment of chronic hepatitis B in children shows that prednisone priming followed by alpha-interferon 2A was effective in 6 of 9 treated patients in reducing HBV replication and disease activity.