Liver 2001: 21: 254–259 Copyright C Munksgaard 2001 Printed in Denmark . All rights reserved Liver ISSN 0106-9543 Clearance of hepatitis B surface antigen in chronic carriers of hepatitis delta antibodies Niro GA, Gravinese E, Martini E, Garrubba M, Facciorusso D, Conosci- Grazia Anna Niro 1 , tore P, Di Giorgio G, Rizzetto M, Andriulli A. Clearance of hepatitis B Eleonora Gravinese 1 , surface antigen in chronic carriers of hepatitis delta antibodies. Elisabetta Martini 2 , Liver 2001: 21: 254–259. C Munksgaard, 2001 Maria Garrubba 3 , Domenico Facciorusso 1 , Abstract: Background/Aims: We evaluated the rate of seroclearance of the Pasquale Conoscitore 1 , hepatitis B surface antigen (HBsAg) and its clinical significance in patients Giuseppe Di Giorgio 2 , with chronic hepatitis delta virus (HDV). Methods: Antibody to HDV was Mario Rizzetto 4 and tested in HBsAg-positive subjects admitted to our Hospital from 1991 to Angelo Andriulli 1 1995. In 1997, a biochemical and virologic study was performed in the sur- viving anti-HD-positive patients who had not undergone transplantation. 1 Division of Gastroenterology, 2 Blood Bank and As a control, a cohort of 106 HBsAg-positive, anti-HD-negative patients 3 Central Laboratory, Casa Sollievo della Sofferenza Hospital, S. Giovanni Rotondo and was studied. Results: One hundred and forty-one subjects were originally 4 Department of Gastroenterology, San Giovanni positive for anti-HD. After 4 years of follow-up, six of the 60 patients who Battista Hospital, Turin, Italy underwent re-evaluation (10%) had cleared the HBsAg: three of the six pa- tients had minimal changes at the initial liver histology and normal ALT, whereas in the remaining three patients with chronic active hepatitis ALT Key words: chronic hepatitis – HBV – HDV normalized during the observation. Anti-HD persisted in five of the six pa- Grazia A. Niro, Divisione di Gastroenterologia, tients. Only one patient had raised anti-HBs. In contrast, three of 106 HBsAg Ospedale Casa Sollievo della Sofferenza, Viale carriers without HDV infection (2.8%) cleared the HBsAg within the same Cappuccini – 71013 San Giovanni Rotondo (FG), time and seroconverted to anti-HBs (pΩ0.002). Conclusion: HBsAg clearance Italy. Tel: 39 882 410798. Fax: 39 882 411879 e-mail: nirograzia/tiscalinet.it is increased over the years in HDV patients compared to ordinary HBsAg carriers, and is often associated with improvement of HDV disease without Received 13 October 2000, accepted 5 March seroconversion to anti-HBs. 2001 The association of hepatitis delta virus (HDV) with hepatitis B virus (HBV) infection is supported by a multitude of clinical and virologic studies (1– 3). In keeping with this association, patients with chronic HDV infection have, as a rule, HBV sur- face antigen (HBsAg) in serum. Spontaneous sero- clearance of HBsAg has been documented in HDV-infected patients (4–6); however, no system- atic long-term follow-up studies have been carried out in chronic HDV patients to evaluate whether and at what rate spontaneous HBsAg elimination occurs, the profile of residual HDV markers, and its significance after the clearance of the HBV. In this study we report the pattern of spon- taneous HBsAg seroclearance in a cohort of HDV- infected patients followed up for a mean period of 4 years. Patients and methods Patients All HBsAg carriers, identified at the Blood Bank 254 or attending as in- or out-patients at the various services of the Hospital Casa Sollievo della Soffer- enza in the years 1991–1995, underwent routine screening for anti-HD. HBsAg carriers with anti- HD, for whom demographic and clinical data were available, were included in this study. Their orig- inal clinical and serologic features and the features of those for whom a 1–6-year follow-up was avail- able were evaluated and compared with the fea- tures of a cohort of HBsAg carriers without anti- HD recruited in the Division of Gastroenterology of the Hospital. We also included in this study patients treated with interferon (IFN) who had not responded to therapy, on the assumption that the natural his- tory of their disease was not modified by the in- effective antiviral therapy. The very few patients who responded to therapy were not considered; there were two cases of sustained responders (6.2% of the 32 treated) in the anti-HD-positive group and two cases (4.9% of the 41 treated) in the HBsAg-positive group without anti-HD.