Hepatitis B virus surface antigen seroconversion after pegylated interferon-alpha treatment in an HIV-infected individual with chronic hepatitis B

Abstract

Worldwide, approximately 36 million people live with the human immunodeficiency virus (HIV) and 370 million with the hepatitis B virus (HBV). The prevalence of chronic hepatitis B (CHB) infection in individuals with HIV varies between 5 and 20%, with higher levels found in areas in which CHB is endemic, such as countries in Africa and Asia [1]. Coinfection with HBV and HIV is common due to overlapping routes of transmission and is accompanied by an increased risk for liver-related morbidity and mortality [2]. Indeed, liver disease has emerged as one of the most important causes of morbidity and mortality among HIV-positive individuals after the introduction of highly active antiretroviral therapy (HAART), mainly in patients coinfected with either HBV or hepatitis C virus (HCV) [3]. HBV treatment is based on pegylated interferon-alpha (INF-a) or nucleos(t)ide polymerase inhibitors. While the former treatment has a finite duration and may be associated with durable response in terms of HBV control after its discontinuation, the latter requires life-long treatment to achieve chronic viral suppression. We report the case of a 42-year-old homosexual man presenting with positive HIV-1 serology at first observation in July 1995. His medial history was negative for HBV or HCV infection; he was a smoker, his body mass index was 30 kg/m, and he was diagnosed to have CDC stage A2 HIV. Due to high CD4 counts (range 410–1,352/lL) he was never prescribed antiretrovirals during the subsequent follow-up. In July 2002 the laboratory tests showed elevated liver enzymes, with alanine aminotransferase (ALT) at 527 IU/ml and aspartate aminotransferase (AST) at 204 IU/mL; the other biochemical liver function test values were normal. He was positive for hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg), and antibodies to hepatitis B core antigen (anti-HBc) and negative for anti-hepatitis Be antibody (anti-HBe); HBV DNA was 200,000 IU/mL. Antibodies for HCV and hepatitis A virus (HAV) were negative. HIV infection was still well controlled, with plasma HIV-1 RNA at 1,960 copies/mL and a CD4 ? cell count of 626/lL (24%). The subsequent laboratory tests showed a normalization of liver enzymes and the persistence of HBsAg (Fig. 1). The HBsAg level were not quantified. In September 2005, because of the persistence of HBsAg and elevated ALT, therapy with pegylated INF-a2a 180 lg weekly was initiated and continued until April 2006 (28 weeks). At treatment initiation, plasma HBV DNA was 2.5 million IU/mL, his CD4 ? lymphocyte count was 1,352/lL (53%), and HIV-1 RNA was 8,560 copies/mL. After 19 weeks of treatment, the patient seroconverted from HBeAg to anti-HBe; at the 22th week, HBV DNA became undetectable (detection limit 60 IU/mL). During the entire follow-up period the patient did not require antiretroviral treatment. In April 2009, we observed HBsAg clearance (last positive HBsAg tested in February 2008) and the appearance of anti-HBs (74.6 mLU/mL), the last negative determination of which had been performed in February 2007. This result was confirmed in five subsequent controls, with last result obtained in April 2011 showing normal liver enzymes, negative HBsAg and HBeAg, HBV DNA \12 IU/mL, and positive anti-HBc, anti-HBe, and anti-HBs at 33 mIU/mL (Fig. 1). The lower probability of spontaneous loss of HBeAg or HBsAg in HIV/HBV-coinfected patients is due to impaired host innate and adaptive immunity [4]. In this patient with persistently high CD4 counts and an HBeAg-positive CHB, B. Rossetti (&) C. Bianco A. De Luca Second Division of Infectious Diseases, Policlinico Le Scotte, University of Siena, Viale Bracci 16, 53100 Siena, Italy e-mail: barbararossetti@libero.it