Antiviral Therapy 2015; 20:193–197 (doi: 10.3851/IMP2819)
Original article Epidemiological and clinical features of hepatitis delta in HBsAg-positive patients by HIV status Laura A Nicolini1,2*, Lucia Taramasso1,2, Irene Schiavetti3, Edoardo G Giannini4, Andrea Beltrame1, Marcello Feasi5, Giovanni Cassola5, Alessandro Grasso6, Valentina Bartolacci7, Laura Sticchi2,8, Antonino Picciotto4, Claudio Viscoli1,2, the Ligurian HBV Study Group Infectious Diseases Department, IRCCS San Martino-IST, Genoa, Italy Department of Health Sciences, University of Genoa, Genoa, Italy 3 Section of Biostatistics, Department of Health Sciences, University of Genoa, Genoa, Italy 4 Gastroenterology Unit, Internal Medicine Department, University of Genoa, Genoa, Italy 5 Infectious Diseases Unit, Galliera Hospital, Genoa, Italy 6 Gastroenterology Unit, San Paolo Hospital, Savona, Italy 7 Infectious Diseases Unit, Santa Maria di Misericordia Hospital, Albenga, Italy 8 Department of Health Sciences, University of Genoa, Hygiene Unit, Genoa, Italy 1 2
*Corresponding author e-mail: [email protected]
Background: The epidemiology of HBV-associated hepatitis has changed in recent years, especially after the introduction of anti-HBV vaccination, with a consequent decrease in the incidence of HDV-associated hepatitis. However, HDV remains of concern in non‑vaccinated people and in immigrants. The aim of this retrospective survey has been to assess prevalence and clinical characteristics of HDV infection in Liguria, a region in Northern Italy, in both HIV‑positive and negative patients. Methods: During the year 2010, 641 patients chronically infected with HBV entered an observational study of HBV infection conducted in eight tertiary care centres belonging to the ‘Ligurian HBV Study Group’. Results: Of 641 patients, 454 (70.8%) were evaluated for HDV serology and 26 (5.7%) were found positive. Among
them, 16 were also HIV-positive and 10 were not. Of the 428 HDV-negative patients, only 313 were tested for HIV and 33 (10.5%) were positive. At the time point of study entry there was no age difference between HIV-positive or negative patients, but HIV‑positive patients were 10 years younger than HIV‑negative (mean age 34.25 ±6.16 versus 41.50 ±8.89 years; P=0.021) at the time point of their first visit in each centre and they were also more frequently intravenous drug users (P=0.009). Despite a similar rate of cirrhosis in the two groups, no HIV‑positive patient received an HDV-active therapy (that is, interferon), versus 4 of 10 HIV-negative patients (P=0.014). Conclusions: HDV infection is still a problem in patients not covered by HBV vaccination. Both HDV and HIV testing were frequently overlooked in our setting.
Introduction HDV is a major cause of chronic viral hepatitis worldwide. As a defective virus lacking the surface protein, HDV uses HBV surface antigen (HBsAg) as an envelope for itself. The prevalence of HBV infection has decreased in recent years worldwide, probably because of the implementation of HBV vaccination, with consequent change in the epidemiology of HDV hepatitis. In Italy, a decrease in acute HDV infection has been reported between 1987 and 2004 from 1.7 to 0.5 per million inhabitants [1]. However, this decline has now stopped, probably because of new ©2015 International Medical Press 1359-6535 (print) 2040-2058 (online)
AVT-14-OA-3205_Nicolini.indd 193
infections among both immigrants and Italian nonvaccinated people [2]. Today, the prevalence of HDV among Italian HBsAg-positive people is 4.2% versus 17% in non-EU citizens [3]. The identification of HBV–HDV-coinfected patients is particularly important because of the well-known risk of rapid progression of the hepatic disease in these patients [4–7]. Moreover, HDV infection is more frequent in HIV– HBV-coinfected versus HIV-negative patients [8], with increased liver-related morbidity and mortality and progression to AIDS [8,9]. 193
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LA Nicolini et al.
The aim of this study has been to evaluate the rate of HIV coinfection among HBV–HDV-infected or noninfected patients and to compare epidemiological and clinical characteristics of HDV-exposed patients with respect to their HIV status.
Methods The ‘Ligurian HBV Study Group’ is a network of eight tertiary referral centres, including Infectious Diseases, Gastroenterology and Internal Medicine divisions, which was created in 2006 to explore epidemiological and clinical features of the HBsAg-positive population in Liguria, an Italian region with 1,572,000 inhabitants. Objectives and data collection procedures have been previously described [10,11]. For the purposes of this study, a cross-sectional analysis had been performed on HBsAgpositive patients seen in the participating centres in 2010; data were retrospectively extrapolated from the existing database. For HDV-immunoglobulin (Ig)G antibody (HDV‑Ab) positive patients, demographic data (age, gender, nationality), potential route of HBV infection, time of first access to a referral centre and other non-infectious risk factors for liver disease (alcohol intake, overweight, diabetes and hyperlipidaemia) were analysed. Hepatitis B e antigen (HBeAg) status and HBV viral load (HBV DNA) were also collected, as well as the presence of HCV and HIV coinfections. In terms of the HBV infection status, every patient was classified as being an inactive carrier or having chronic hepatitis or cirrhosis, based on clinical, biochemical and histological findings. Patients who tested positive for HDV-Ab and carrying HBsAg were considered to be HDV-infected patients, independently of the presence or not of HDV RNA and/or HDV antigen. According to current guidelines, inactive HBV carrier status was defined as the presence of persistently normal liver enzymes and undetectable serum HBV DNA [12]. Previous and current anti-HBV treatments were evaluated.
Statistical analyses c2 test or Fisher exact tests were carried out to compare categorical variables, in particular to assess any association between anti-HIV positive or negative subjects and other categorical clinical characteristics. Fisher’s exact test was used if more than 20% of the expected cell frequencies were less than 5. Differences in the mean ages both at time of first visit and at time of study entry between anti-HIV-positive and negative patients were performed by Student’s t-test. Statistical analysis was computed using Statistical Package for Social Science (SPSS version 20; IBM Corporation, New York, NY, USA). A P
Original article Epidemiological and clinical features of hepatitis delta in HBsAg-positive patients by HIV status Laura A Nicolini1,2*, Lucia Taramasso1,2, Irene Schiavetti3, Edoardo G Giannini4, Andrea Beltrame1, Marcello Feasi5, Giovanni Cassola5, Alessandro Grasso6, Valentina Bartolacci7, Laura Sticchi2,8, Antonino Picciotto4, Claudio Viscoli1,2, the Ligurian HBV Study Group Infectious Diseases Department, IRCCS San Martino-IST, Genoa, Italy Department of Health Sciences, University of Genoa, Genoa, Italy 3 Section of Biostatistics, Department of Health Sciences, University of Genoa, Genoa, Italy 4 Gastroenterology Unit, Internal Medicine Department, University of Genoa, Genoa, Italy 5 Infectious Diseases Unit, Galliera Hospital, Genoa, Italy 6 Gastroenterology Unit, San Paolo Hospital, Savona, Italy 7 Infectious Diseases Unit, Santa Maria di Misericordia Hospital, Albenga, Italy 8 Department of Health Sciences, University of Genoa, Hygiene Unit, Genoa, Italy 1 2
*Corresponding author e-mail: [email protected]
Background: The epidemiology of HBV-associated hepatitis has changed in recent years, especially after the introduction of anti-HBV vaccination, with a consequent decrease in the incidence of HDV-associated hepatitis. However, HDV remains of concern in non‑vaccinated people and in immigrants. The aim of this retrospective survey has been to assess prevalence and clinical characteristics of HDV infection in Liguria, a region in Northern Italy, in both HIV‑positive and negative patients. Methods: During the year 2010, 641 patients chronically infected with HBV entered an observational study of HBV infection conducted in eight tertiary care centres belonging to the ‘Ligurian HBV Study Group’. Results: Of 641 patients, 454 (70.8%) were evaluated for HDV serology and 26 (5.7%) were found positive. Among
them, 16 were also HIV-positive and 10 were not. Of the 428 HDV-negative patients, only 313 were tested for HIV and 33 (10.5%) were positive. At the time point of study entry there was no age difference between HIV-positive or negative patients, but HIV‑positive patients were 10 years younger than HIV‑negative (mean age 34.25 ±6.16 versus 41.50 ±8.89 years; P=0.021) at the time point of their first visit in each centre and they were also more frequently intravenous drug users (P=0.009). Despite a similar rate of cirrhosis in the two groups, no HIV‑positive patient received an HDV-active therapy (that is, interferon), versus 4 of 10 HIV-negative patients (P=0.014). Conclusions: HDV infection is still a problem in patients not covered by HBV vaccination. Both HDV and HIV testing were frequently overlooked in our setting.
Introduction HDV is a major cause of chronic viral hepatitis worldwide. As a defective virus lacking the surface protein, HDV uses HBV surface antigen (HBsAg) as an envelope for itself. The prevalence of HBV infection has decreased in recent years worldwide, probably because of the implementation of HBV vaccination, with consequent change in the epidemiology of HDV hepatitis. In Italy, a decrease in acute HDV infection has been reported between 1987 and 2004 from 1.7 to 0.5 per million inhabitants [1]. However, this decline has now stopped, probably because of new ©2015 International Medical Press 1359-6535 (print) 2040-2058 (online)
AVT-14-OA-3205_Nicolini.indd 193
infections among both immigrants and Italian nonvaccinated people [2]. Today, the prevalence of HDV among Italian HBsAg-positive people is 4.2% versus 17% in non-EU citizens [3]. The identification of HBV–HDV-coinfected patients is particularly important because of the well-known risk of rapid progression of the hepatic disease in these patients [4–7]. Moreover, HDV infection is more frequent in HIV– HBV-coinfected versus HIV-negative patients [8], with increased liver-related morbidity and mortality and progression to AIDS [8,9]. 193
23/04/2015 10:50:45
LA Nicolini et al.
The aim of this study has been to evaluate the rate of HIV coinfection among HBV–HDV-infected or noninfected patients and to compare epidemiological and clinical characteristics of HDV-exposed patients with respect to their HIV status.
Methods The ‘Ligurian HBV Study Group’ is a network of eight tertiary referral centres, including Infectious Diseases, Gastroenterology and Internal Medicine divisions, which was created in 2006 to explore epidemiological and clinical features of the HBsAg-positive population in Liguria, an Italian region with 1,572,000 inhabitants. Objectives and data collection procedures have been previously described [10,11]. For the purposes of this study, a cross-sectional analysis had been performed on HBsAgpositive patients seen in the participating centres in 2010; data were retrospectively extrapolated from the existing database. For HDV-immunoglobulin (Ig)G antibody (HDV‑Ab) positive patients, demographic data (age, gender, nationality), potential route of HBV infection, time of first access to a referral centre and other non-infectious risk factors for liver disease (alcohol intake, overweight, diabetes and hyperlipidaemia) were analysed. Hepatitis B e antigen (HBeAg) status and HBV viral load (HBV DNA) were also collected, as well as the presence of HCV and HIV coinfections. In terms of the HBV infection status, every patient was classified as being an inactive carrier or having chronic hepatitis or cirrhosis, based on clinical, biochemical and histological findings. Patients who tested positive for HDV-Ab and carrying HBsAg were considered to be HDV-infected patients, independently of the presence or not of HDV RNA and/or HDV antigen. According to current guidelines, inactive HBV carrier status was defined as the presence of persistently normal liver enzymes and undetectable serum HBV DNA [12]. Previous and current anti-HBV treatments were evaluated.
Statistical analyses c2 test or Fisher exact tests were carried out to compare categorical variables, in particular to assess any association between anti-HIV positive or negative subjects and other categorical clinical characteristics. Fisher’s exact test was used if more than 20% of the expected cell frequencies were less than 5. Differences in the mean ages both at time of first visit and at time of study entry between anti-HIV-positive and negative patients were performed by Student’s t-test. Statistical analysis was computed using Statistical Package for Social Science (SPSS version 20; IBM Corporation, New York, NY, USA). A P
