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Background/aims: The place of liver transplantation in hepatitis B viral (HBV)-related diseases remains controversial because of the high rate of reinfection. The aim of this study was to define the determinants of long-term prognosis after transplantation., Methods: Fifty-eight patients were transplanted during the period February 1984-September 1996. Six patients died during the early (< 3 months) posttransplant period from causes unrelated to HBV infection. All 52 long-term (> 3 months) survivors were evaluated in relation to the mode of presentation, viral replication at time of transplantation, absence of hepatocellular cancer at time of transplantation and use of adequate immunoprophylaxis (IP). Adequate immunoprophylaxis, defined as maintenance of anti-HBs levels over 100 mUI/ml, was introduced in December 1989. Intention-to-treat IP analysis compared patients transplanted before and after this date. The median follow-up was 74 months (range 4 to 131). Forty-seven patients (90%) had a minimal follow-up of 3 years., Results: Five-year actuarial survival rates of 58 patients and of 52 long-term survivors were 72 +/- 6% and 80 +/- 6%, respectively. Univariate analysis showed that delta co-infection (n = 25) significantly improved survival (p < 0.001) [96 +/- 4% vs 63 +/- 10% in HBV patients (n = 27) at 5 years] as did absence of hepatocellular cancer (n = 36) (p = 0.020) [89 +/- 5% vs 61 +/- 12% in 16 non-cancer patients]. IP, however, significantly influenced 5-year survival in the HBV-patient group (n = 17) (p = 0.001) [85 +/- 10% vs 30 +/- 14% in 10 patients without IP). Multivariate analysis selected delta co-infection (p = 0.002) and IP (p = 0.01) as the significant determinants of prognosis independently influencing survival. Uni- and multivariate analyses showed that survival without reinfection was significantly influenced by IP (p = 0.002) [73 +/- 8% (n = 31) versus 33 +/- 12% in 15 non-treated patients)., Conclusions: Delta virus co-infection and immunoprophylaxis are the most important prognostic factors after transplantation for postnecrotic HBsAg-positive cirrhosis. Transplantation can be proposed as a therapeutic tool only if life-long adequate adjuvant therapy can be achieved. Under this condition good results can even be obtained if there is viral replication at the time of transplantation.

The mode of contamination, presentation, clinical evolution and liver histology of 10 native Belgian patients with chronic hepatitis B likely due to a peculiar viral strain, the so called precore mutant hepatitis B virus were reviewed. This viral strain first described in Southern European regions is characterized by a mutation of a single base change at nucleotide 1896 in the preterminal codon of the precore region which creates a stop codon that prevents the production of HBeAg. In this setting, abnormal liver biochemistry and active viral replication as evidenced by HBV DNA positivity often coincides with a serological profile similar to that observed in healthy HBsAg carriers. Our data indicate that chronic hepatitis related to such a viral strain may be observed in a native Belgian population. This unusual presentation of chronic hepatitis B should thus be kept in mind when interpreting atypical sero-biochemical features, evaluating the risk of infectivity and the potential benefit of antiviral therapy.

These data clearly show the sensitivity differences and the correlations between the HBV DNA and the DNA polymerase assay. The Abbott HBV DNA is a molecular hybridization test in a liquid phase using a 125I-labelled probe and allowing the detection and the quantitation of HBV DNA in serum samples. This test was found to be 20-200 times more sensitive than the DNA polymerase assay and its sensitivity was evaluated to be about 0.3 pg HBV DNA. It is very easy to use and the results are obtained within 24 hours. In the patients with persistent HBV infection a close correlation between the positivity of the DNA polymerase activity and of the HBV DNA (R = 0.94) was observed. These two markers evolve quite parallel whatever the results obtained in the HBe system or whatever the sample time in a group of patients treated with recombinant interferon.

Twenty nine children (mean age 8.3 years, 18 boys, 11 girls) who had biopsy proved chronic hepatitis B virus infection (HBV) with active viral replication were given a 16 week course of interferon alfa-2b treatment (9 million units (MU)/m2, thrice weekly). Fourteen children (48%) showed persistent loss of HBV-DNA 8 months after the end of treatment; 11 (38%) lost hepatitis B e antigen (HBeAg), and two (7%) hepatitis B surface antigen (HBsAg). Alanine aminotransferase activities returned to normal in 12 children. Those who responded had significantly higher initial transaminase activities than those who did not (p < 0.01) but similar serum HBV-DNA. Results were compared with the natural evolution of the disease in a group of 25 children (mean age 8.3 years) with identical initial mean serum HBV-DNA values, followed up during the same period. Two of these (8%) lost HBeAg and one (4%) HBsAg. The 23 remaining control subjects had no decrease in serum HBV-DNA or in transaminase activities compared with values 1 year earlier. It is concluded that treatment with interferon alfa-2b in children may lead to inhibition of HBV replication similar to that described in adults, and may thus shorten disease evolution. Further studies are necessary to establish the best protocols and to identify those patients who are the most likely to respond to treatment.

Twenty-seven carriers of the hepatitis B surface antigen who underwent liver transplantation in Italy and Belgium for terminal Hepatitis delta virus (HDV) cirrhosis were investigated. In 22 of the patients, HDV infection recurred. Two patients died of coexisting HDV and hepatitis B virus (HBV) reactivation. Four patients who died of unrelated causes were found to have HDV without signs of HBV reactivation. Five patients (18%) cleared both HBV and HDV after transplantation with no evidence of hepatitis (mean follow-up, 29 months). In many surviving patients. HDV infection recurred early without signs of HBV reactivation. Disease returned in the 11 HDV-infected patients in whom HBV also recurred. Histological hepatitis did not recur during an interim of 12-33 months in the 5 HDV-infected patients in whom HBV did not return. The overall medium-term survival in patients with HDV who underwent transplantation was 77.7%. Liver transplantation offers patients with HDV a hope of cure from disease despite a high risk of reinfection. In the transplantation setting. HDV can cause subclinical infections without any apparent assistance from HBV; these infections become symptomatic only if and when HBV reactivates. Thus, HDV may not be in itself pathogenic but requires cooperation from HBV to cause the appearance of the disease.

A boy was born to a mother who was a chronic hepatitis B virus (HBV) carrier. She was hepatitis Be (HBe) antibody positive and HBe antigen and HBV-DNA negative. The boy had not received hepatitis B vaccine and died from fulminant hepatitis at 3 months of age. This case demonstrates the need to vaccinate babies of HBe antibody positive, HBe antigen negative carriers.

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by positivity for hepatitis B e antigen and hepatitis B virus DNA, with increased DNA polymerase levels for more than 6 months, were entered into a prospective trial of low-dose recombinant human alpha-interferon therapy. All patients were treated with 5 million units of recombinant interferon alfa-2b given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNA polymerase levels (p less than or equal to 0.001), which reached normal values in ten (48%). After 10 months' mean follow up, seven patients (33%) were hepatitis B e antigen negative and five (24%) subsequently became positive for antibodies to e antigen. By 27 months, nine patients (43%) were both hepatitis B e antigen negative and e antibody positive. Only one patient became permanently negative for hepatitis B surface antigen. One patient relapsed during the second year of follow up. Side effects necessitated withdrawal of therapy in two patients: one due to worsening thrombocytopenia after two doses of interferon (data omitted from the study results) and one due to a local reaction at the injection sites. Our data indicate that small doses of recombinant interferon alfa-2b given during a 12-week period induce a significant reduction in viral replication and approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B.