Liver 1994: 14: 175-181 Copyrighf zyxw 0 Munksgaard 1994 zyx LNER Printed in Denmark All rights reserved ISSN 0106-9S43 zyxw Fluctuations in viremia, aminotransferases and IgM antibody to hepatitis B core antiizen in chronic hepatitis B patients with disea& exacerbations Mels GC, Bellati G, Leandro G, Brunetto MR, Vicari 0, Borzio M, Piantino P, Fornaciari G, Scudeller G, Angeli G, Bonino F, Ideo G. Fluctu- ations in viremia, aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations. Liver 1994: 14: 175-181. 0 Munksgaard, 1994 Abstract: We studied the relationships between the serum levels of viremia, aminotransferases and IgM anti-HBc, measured by monthly quantitative assays, in 52 untreated chronic hepatitis B patients (41 anti-HBe+, 11 HBeAg +) followed up for 12-20 months. Forty hepatitis exacerbations were observed in 17/41 anti-HBe+ (41.5%) and in 6/11 HBeAg+ patients (54.5%) (p = NS); all but one were clinically asymptomatic. We analyzed the fluctuations in the serum levels of the three parameters before, during and after the hepatitis exacerbations and found this chronological sequence of events in 96.2% of them: HBV-DNA increase+ALT flare+IgM anti- HBc increase. These results suggest that both antiviral immune reactions and ALT flares were triggered by quantitative variations in viremia. HBV- DNA baseline levels before flares were lower in anti-HBe+ (3.91 1.2 pgiml) than in HBeAg+ patients (35.3 k5.4 pg/ml) (p<O.OOOl) and there was an inverse correlation between basal values and viremia level increases at the time of disease exacerbations zyxwvuts (p < 0.001). This suggests that for a hepatitis exacerbation to occur, low basal viremia needed to increase markedly, while moderate increases in HBV-DNA serum levels were sufficient to trigger ALT flares in patients with elevated basal viremia. In conclusion, asymptomatic hepatitis B exacerbations are frequent in the natural history of chronic HBV infection, and monthly monitoring of HBV- DNA, ALT and IgM anti-HBc appears to be a suitable method to evaluate their frequencies and entities. This method can be a helpful guide for clinical and therapeutic decision-making in the single patient with chronic hepatitis B. Phases of moderate liver disease or temporary re- mission alternate with spontaneous hepatitis ex- acerbations in chronic hepatitis B virus infection (1-19), and the frequency and severity of the ALT flares influence the natural history of the disease (20). Although hepatitis exacerbations may be clin- ically relevant (2, 4, 13, 15), the majority of them are asymptomatic and escape clinical observation if careful biochemical monitoring of the patient is not performed (14, 16, 18). In addition, it is import- ant to differentiate true hepatitis B exacerbations zyxwv Guido Coltoredo Mels, Giorgio Bellati’, Gioacchino Leandro*, Maurizia Rossana Brunetto3, Omar Vicari4, Mauro Borz105, Paolo Piantino3, Giovanni Fornaciari’, Guido Scudellel.4, Giovanni Angeli, Ferruccio Bonino3 and Gaetano Ideo’ Departments of Internal Medicine: Bolognini Hospital, Seriate (BG), ‘Saverio De Bellis Hospital IRCCS, Castellana Grotte (BA), ’Fatebenefratelli Hospital, Milano, ‘Arcispedale S. Maria Nuova, Reggio Emilia. 4Transfusion Center, OOMM Hospital, Bergamo; ’ Hepatology Center “Crespi”, Niguarda Hospital, Milano and 3Laboratory of the Division of Gastroenterology, Molinette Hospital, Torino, Italy Key words: HBV - HBV-DNA - hepatitis B - IgM anti-HBc Ferruccio Bonino MD, Department of Gastroenterology, Molinette Hospital, Corso Bramante 88, 10126 Torino, Italy Received 25 January, accepted for publication 7 December 1993 from ALT flares secondary to other causes (super- infections with non-B hepatotropic viral agents or toxic/iatrogenic injuries). In the past, studies of hepatitis B exacerbations were done in the East (1, 6-11, 13), while in the West attention has been focused on high-risk groups, such as homosexual men (2-4, 14, 15, 18). Serum HBV-DNA and IgM anti-HBc are con- sidered as markers of HBV replication and HBV- induced liver disease and have been proposed as the “gold standard tests” for monitoring HBV in- 175