Hepatitis delta-associated mortality in HIV/HBV-coinfected patients.

Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC). Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9-18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41-3.84), liver-related death (7.71, 3.13-18.97) and with the occurrence of HCC (9.30, 3.03-28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses. The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC. Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection.

Béguelin C ，Moradpour D ，Sahli R ，Suter-Riniker F ，Lüthi A ，Cavassini M ，Günthard HF ，Battegay M ，Bernasconi E ，Schmid P ，Calmy A ，Braun DL ，Furrer H ，Rauch A ，Wandeler G ，Swiss HIV Cohort Study ... -  《-》

Hepatitis delta infection among persons living with HIV in Europe.

A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes. All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using cumulative incidence plots and cause-specific multivariable Cox regression. Of 2793 HBsAg-positive participants, 1556 (56%) had stored serum available and were included. The prevalence of HDV coinfection was 15.2% (237/1556, 95% confidence interval [CI]: 13.5%-17.1%) and 66% (132/200) of HDV-positive individuals had active HDV replication. Among persons who inject drugs (PWID), the prevalence of HDV coinfection was 50.5% (182/360, 95% CI: 45.3%-55.7%), with similar estimates across Europe, compared to 4.7% (52/1109, 95% CI: 3.5%-5.9%) among other participants. During a median follow-up of 10.8 years (interquartile range 5.6-17.8), 82 (34.6%) HDV-positive and 265 (20.1%) HDV-negative individuals died. 41.5% (34/82) of deaths were liver-related in HDV-positive individuals compared to 17.7% (47/265) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.6; 95% CI 1.2-2.1), liver-related death (2.9, 1.6-5.0) and HCC (6.3, 2.5-16.0). We found a very high prevalence of hepatitis delta among PWID across Europe. Among PLWH who do not inject drugs, the prevalence was similar to that reported from populations without HIV. HDV coinfection was associated with liver-related mortality and HCC incidence.

Béguelin C ，Atkinson A ，Boyd A ，Falconer K ，Kirkby N ，Suter-Riniker F ，Günthard HF ，Rockstroh JK ，Mocroft A ，Rauch A ，Peters L ，Wandeler G ，for EuroSIDA and SHCS ... -  《-》

Prevalence and clinical course of hepatitis delta infection in Greece: a 13-year prospective study.

Hepatitis D virus (HDV) has decreased in Europe, but recent reports indicate a rising trend. We report the epidemiological changes, clinical progress, and effect of treatment on the natural course of HDV infection in Greece during the last 13 years. Prospective data were extracted from the HepNet.Greece Cohort-Study. Since 1997, 4673 chronic HBV (CHB) cases (4527 adults, 146 children) have been followed prospectively. Two thousand one hundred thirty-seven patients were tested for anti-HDV [101 (4.7%) positive]. Anti-HDV testing in Greece decreased significantly (57.0% before 2003, 35.3% thereafter; p<0.001). Anti-HDV prevalence among HBsAg-positives was 4.2%; lower in native Greeks (2.8%) than in immigrants (7.5%) or in children (15.3%; p<0.001). Within 2.3 years of follow-up, HDV occurred in 11/2047 HBsAg-positive patients (2.2 new delta-infected adults and 8.7 children per 1000 HBsAg-positive annually). HDV-positive compared to CHB adults were younger (p=0.035) and had more active and advanced disease at baseline, as indicated by laboratory indices and the higher prevalence of cirrhosis at younger age. During a 4.2-year median observation, significantly more anti-HDV-positive than CHB adults developed a liver-related first event (20.0% vs. 8.5%, p Log-rank=0.014).Treatment was received by 46/90 (51.1%) patients, 40 of them interferon-based. In multivariable analysis, interferon significantly decreased disease progression in HDV-positive patients [HR=0.14 (95% CI: 0.02-0.86; p=0.033)]. In Greece, HDV serology is currently tested in only one-third of HBsAg-positive patients. HDV prevalence is lower in native Greeks compared to immigrants, who may contribute >50% of the HDV infection burden in Greece. Data show that HDV infection is a rapidly progressive disease, but interferon-based treatment may alter its course.

Manesis EK ，Vourli G ，Dalekos G ，Vasiliadis T ，Manolaki N ，Hounta A ，Koutsounas S ，Vafiadis I ，Nikolopoulou G ，Giannoulis G ，Germanidis G ，Papatheodoridis G ，Touloumi G ... -  《-》

Higher rate of hepatitis events in patients with human immunodeficiency virus, hepatitis B, and hepatitis D genotype II infection: a cohort study in a medical center in southern Taiwan.

The epidemiology and impact of hepatitis δ virus (HDV) on hepatic outcomes and virological and immunological responses to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) patients coinfected with hepatitis B virus (HBV) in northern Taiwan have been reported. However, the epidemiology and impact of HDV infection in HIV-HBV coinfection patients in southern Taiwan remains uncertain. In this cohort study, a total of 64 HIV patients coinfected with HBV were identified between January 1, 2009 and May 30, 2012. The seroprevalence of anti-HDV antibodies, HDV genotyping, clinical manifestations and hepatic outcomes were compared between the patients with and without HDV coinfection, and laboratory examinations and hepatic outcomes were recorded. Among the 64 HIV patients coinfected with HBV, seven were seropositive for HDV (10.9%). There were no statistically significant differences in risk factors for acquiring HIV infection. During a median observation period of 27.8 months, the adjusted hazard ratio of HDV and HBV genotype (type B vs. non-type B) on hepatitis flare-ups were 62.132 (p = 0.04) and 0.028 (p = 0.01), respectively. All seven patients had genotype II and were HDV viremic. The phylogenetic tree analysis and clinical history evaluation did not identify any clusters of HDV infection. HDV infection resulted in higher rate of hepatitis flare-ups, but it did not have a statistical significance on HIV progression and immunological response to HAART. Whether higher rate of HDV viremia has worse impact on the hepatic outcomes requires further investigation.

Lee CY ，Tsai HC ，Lee SS ，Wu KS ，Sy CL ，Chen JK ，Chen YS ... -  《-》

Absence of hepatitis delta infection in a large rural HIV cohort in Tanzania.

The epidemiological and clinical determinants of hepatitis delta virus (HDV) infection in Sub-Saharan Africa are ill-defined. The prevalence of HDV infection was determined in HIV/hepatitis B virus (HBV) co-infected individuals in rural Tanzania. All HBV-infected adults under active follow-up in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) were screened for anti-HDV antibodies. For positive samples, a second serological test and nucleic acid amplification were performed. Demographic and clinical characteristics at initiation of antiretroviral therapy (ART) were compared between anti-HDV-negative and -positive patients. Among 222 HIV/HBV co-infected patients on ART, 219 (98.6%) had a stored serum sample available and were included in the study. Median age was 37 years, 55% were female, 46% had World Health Organization stage III/IV HIV disease, and the median CD4 count was 179 cells/μl. The prevalence of anti-HDV positivity was 5.0% (95% confidence interval 2.8-8.9%). There was no significant predictor of anti-HDV positivity. HDV could not be amplified in any of the anti-HDV-positive patients and the second serological test was negative in all of them. No confirmed case of HDV infection was found among over 200 HIV/HBV co-infected patients in Tanzania. As false-positive serology results are common, screening results should be confirmed with a second test.

Winter A ，Letang E ，Vedastus Kalinjuma A ，Kimera N ，Ntamatungiro A ，Glass T ，Moradpour D ，Sahli R ，Le Gal F ，Furrer H ，Wandeler G ，KIULARCO Study Group ... -  《-》