Hepatitis delta infection among persons living with HIV in Europe.
Humans
Hepatitis B
/ complications
Cohort Studies
Carcinoma, Hepatocellular
Hepatitis B Surface Antigens
Coinfection
/ epidemiology
Drug Users
Substance Abuse, Intravenous
/ complications
Liver Neoplasms
/ epidemiology
HIV Infections
/ complications
Europe
/ epidemiology
Hepatitis A
/ complications
Hepatitis Delta Virus
/ genetics
Hepatitis D
/ epidemiology
Prevalence
Hepatitis B virus
HCC
HIV
Hepatitis Delta
PLWH
prevalence
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
20
11
2022
received:
08
07
2022
accepted:
04
01
2023
pubmed:
11
1
2023
medline:
22
3
2023
entrez:
10
1
2023
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND AND AIMS
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
Substances chimiques
Hepatitis B Surface Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
819-828Investigateurs
I Abela
(I)
K Aebi-Popp
(K)
A Anagnostopoulos
(A)
M Battegay
(M)
E Bernasconi
(E)
D L Braun
(DL)
H C Bucher
(HC)
A Calmy
(A)
M Cavassini
(M)
A Ciuffi
(A)
G Dollenmaier
(G)
M Egger
(M)
L Elzi
(L)
J Fehr
(J)
J Fellay
(J)
H Furrer
(H)
C A Fux
(CA)
A Hachfeld
(A)
B Hasse
(B)
H H Hirsch
(HH)
M Hoffmann
(M)
I Hösli
(I)
M Huber
(M)
L Kaiser
(L)
O Keiser
(O)
T Klimkait
(T)
R D Kouyos
(RD)
H Kovari
(H)
G Martinetti
(G)
B Martinez de Tejada
(B)
C Marzolini
(C)
K J Metzner
(KJ)
N Müller
(N)
J Nemeth
(J)
D Nicca
(D)
P Paioni
(P)
G Pantaleo
(G)
M Perreau
(M)
A Rauch
(A)
P Schmid
(P)
R Speck
(R)
M Stöckle
(M)
P Tarr
(P)
A Trkola
(A)
G Wandeler
(G)
S Yerly
(S)
A Harxhi
(A)
M Losso
(M)
M Kundro
(M)
B Schmied
(B)
R Zangerle
(R)
I Karpov
(I)
A Vassilenko
(A)
V M Mitsura
(VM)
D Paduto
(D)
N Clumeck
(N)
S De Wit
(S)
M Delforge
(M)
E Florence
(E)
L Vandekerckhove
(L)
V Hadziosmanovic
(V)
J Begovac
(J)
L Machala
(L)
D Jilich
(D)
D Sedlacek
(D)
G Kronborg
(G)
T Benfield
(T)
J Gerstoft
(J)
O Kirk
(O)
C Pedersen
(C)
I S Johansen
(IS)
L Ostergaard
(L)
L Wiese
(L)
L N Nielsen
(LN)
K Zilmer
(K)
Jelena Smidt
(J)
Nakkusosakond Siseklinik
(N)
I Aho
(I)
J-P Viard
(JP)
K Lacombe
(K)
C Pradier
(C)
E Fontas
(E)
C Duvivier
(C)
J Rockstroh
(J)
O Degen
(O)
C Hoffmann
(C)
H J Stellbrink
(HJ)
C Stefan
(C)
J Bogner
(J)
G Fätkenheuer
(G)
N Chkhartishvili
(N)
H Sambatakou
(H)
G Adamis
(G)
N Paissios
(N)
J Szlávik
(J)
M Gottfredsson
(M)
E Devitt
(E)
L Tau
(L)
D Turner
(D)
M Burke
(M)
E Shahar
(E)
L M Wattad
(LM)
H Elinav
(H)
M Haouzi
(M)
D Elbirt
(D)
A D'Arminio Monforte
(A)
G Guaraldi
(G)
R Esposito
(R)
I Mazeu
(I)
C Mussini
(C)
F Mazzotta
(F)
A Gabbuti
(A)
A Lazzarin
(A)
A Castagna
(A)
N Gianotti
(N)
M Galli
(M)
A Ridolfo
(A)
V Uzdaviniene
(V)
R Matulionyte
(R)
T Staub
(T)
R Hemmer
(R)
Marc van der Valk
(M)
J Trajanovska
(J)
D H Reikvam
(DH)
A Maeland
(A)
J Bruun
(J)
B Knysz
(B)
B Szetela
(B)
M Inglot
(M)
E Bakowska
(E)
R Flisiak
(R)
A Grzeszczuk
(A)
M Parczewski
(M)
K Maciejewska
(K)
B Aksak-Was
(B)
M Beniowski
(M)
E Mularska
(E)
E Jablonowska
(E)
J Kamerys
(J)
K Wojcik
(K)
I Mozer-Lisewska
(I)
B Rozplochowski
(B)
A Zagalo
(A)
K Mansinho
(K)
F Maltez
(F)
R Radoi
(R)
C Oprea
(C)
D Gusev
(D)
T Trofimova
(T)
I Khromova
(I)
E Kuzovatova
(E)
E Borodulina
(E)
E Vdoushkina
(E)
J Ranin
(J)
J Tomazic
(J)
J M Miro
(JM)
J M Miró
(JM)
M Laguno
(M)
E Martinez
(E)
F Garcia
(F)
J L Blanco
(JL)
M Martinez-Rebollar
(M)
J Mallolas
(J)
P Callau
(P)
J Rojas
(J)
A Inciarta
(A)
S Moreno
(S)
S Del Campo
(S)
B Clotet
(B)
A Jou
(A)
R Paredes
(R)
J Puig
(J)
J M Llibre
(JM)
J R Santos
(JR)
P Domingo
(P)
M Gutierrez
(M)
G Mateo
(G)
M A Sambeat
(MA)
J M Laporte
(JM)
P Novak
(P)
A Thalme
(A)
A Sönnerborg
(A)
J Brännström
(J)
L Flamholc
(L)
K Kusejko
(K)
D Braun
(D)
M Cavassini
(M)
A Calmy
(A)
H Furrer
(H)
M Battegay
(M)
P Schmid
(P)
A Kuznetsova
(A)
J Mikhalik
(J)
M Sluzhynska
(M)
A Milinkovic
(A)
A M Johnson
(AM)
S Edwards
(S)
A Phillips
(A)
M A Johnson
(MA)
A Mocroft
(A)
C Orkin
(C)
A Winston
(A)
A Clarke
(A)
C Leen
(C)
I Karpov
(I)
M Losso
(M)
J Lundgren
(J)
J Rockstroh
(J)
I Aho
(I)
L D Rasmussen
(LD)
P Novak
(P)
G Wandeler
(G)
C Pradier
(C)
N Chkhartishvili
(N)
R Matulionyte
(R)
C Oprea
(C)
J D Kowalska
(JD)
J Begovac
(J)
J M Miró
(JM)
G Guaraldi
(G)
R Paredes
(R)
G Wandeler
(G)
R Paredes
(R)
L Peters
(L)
L Peters
(L)
J F Larsen
(JF)
B Neesgaard
(B)
N Jaschinski
(N)
O Fursa
(O)
D Raben
(D)
D Kristensen
(D)
A H Fischer
(AH)
S K Jensen
(SK)
T W Elsing
(TW)
M Gardizi
(M)
A Ahmed
(A)
A Mocroft
(A)
A Phillips
(A)
J Reekie
(J)
A Cozzi-Lepri
(A)
A Pelchen-Matthews
(A)
A Roen
(A)
E S Tusch
(ES)
W Bannister
(W)
Informations de copyright
© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.
Références
Stockdale AJ, Kreuels B, Henrion MYR, et al. The global prevalence of hepatitis D virus infection: systematic review and meta-analysis. J Hepatol. 2020;73(3):523-532.
Chen HY, Shen DT, Ji DZ, et al. Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis. Gut. 2019;68(3):512-521.
Kushner T, Serper M, Kaplan DE. Delta hepatitis within the veterans affairs medical system in the United States: prevalence, risk factors, and outcomes. J Hepatol. 2015;63(3):586-592.
Le Gal F, Brichler S, Sahli R, Chevret S, Gordien E. First international external quality assessment for hepatitis delta virus RNA quantification in plasma. Hepatology. 2016;64(5):1483-1494.
Koh C, Heller T, Glenn JS. Pathogenesis of and new therapies for hepatitis D. Gastroenterology. 2019;156(2):461-76 e1.
Wedemeyer H, Heidrich B, Manns MP. Hepatitis D virus infection--not a vanishing disease in Europe! Hepatology. 2007;45(5):1331-1332. author reply 2-3.
Soriano V, Grint D, d'Arminio Monforte A, et al. Hepatitis delta in HIV-infected individuals in Europe. Aids. 2011;25(16):1987-1992.
Honge BL, Jespersen S, Medina C, et al. Hepatitis B and Delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study. PLoS One. 2014;9(6):e99971.
Romeo R, Del Ninno E, Rumi M, et al. A 28-year study of the course of Hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009;136(5):1629-1638.
Fernandez-Montero JV, Vispo E, Barreiro P, et al. Hepatitis delta is a major determinant of liver decompensation events and death in HIV-infected patients. Clin Infect Dis. 2014;58(11):1549-1553.
Beguelin C, Moradpour D, Sahli R, et al. Hepatitis delta-associated mortality in HIV/HBV-coinfected patients. J Hepatol. 2017;66(2):297-303.
Kamal H, Westman G, Falconer K, et al. Long-term study of Hepatitis Delta virus infection at secondary care centers: the impact of viremia on liver-related outcomes. Hepatology. 2020;72(4):1177-1190.
Swiss HIVCS, Schoeni-Affolter F, Ledergerber B, et al. Cohort profile: the Swiss HIV cohort study. Int J Epidemiol. 2010;39(5):1179-1189.
Laut K, Kirk O, Rockstroh J, et al. The EuroSIDA study: 25 years of scientific achievements. HIV Med. 2020;21(2):71-83.
Ferns RB, Nastouli E, Garson JA. Quantitation of hepatitis delta virus using a single-step internally controlled real-time RT-qPCR and a full-length genomic RNA calibration standard. J Virol Methods. 2012;179(1):189-194.
Shen DT, Han PC, Ji DZ, et al. Epidemiology estimates of hepatitis D in individuals co-infected with human immunodeficiency virus and hepatitis B virus, 2002-2018: a systematic review and meta-analysis. J Viral Hepat. 2021;28(7):1057-1067.
Lin HH, Lee SS, Yu ML, et al. Changing hepatitis D virus epidemiology in a hepatitis B virus endemic area with a national vaccination program. Hepatology. 2015;61(6):1870-1879.
Kucirka LM, Farzadegan H, Feld JJ, et al. Prevalence, correlates, and viral dynamics of hepatitis delta among injection drug users. J Infect Dis. 2010;202(6):845-852.
Stroffolini T, Morisco F, Ferrigno L, et al. Acute Delta hepatitis in Italy spanning three decades (1991-2019): evidence for the effectiveness of the hepatitis B vaccination campaign . J Viral Hepat . 2022;29(1):78-86.
Hung CC, Wu SM, Lin PH, et al. Increasing incidence of recent hepatitis D virus infection in HIV-infected patients in an area hyperendemic for hepatitis B virus infection. Clin Infect Dis. 2014;58(11):1625-1633.
Hung CC. Recent trends of hepatitis D virus infection among people living with HIV in Taiwan. 28th Virtual Conference on Retroviruses and Opportunistic Infections; Chicago; 2020.
Su S, Chow EP, Muessig KE, et al. Sustained high prevalence of viral hepatitis and sexually transmissible infections among female sex workers in China: a systematic review and meta-analysis. BMC Infect Dis. 2016;16:2.
Besombes C, Njouom R, Paireau J, et al. The epidemiology of hepatitis delta virus infection in Cameroon. Gut. 2020;69(7):1294-1300.
Sheng WH, Hung CC, Kao JH, et al. Impact of hepatitis D virus infection on the long-term outcomes of patients with hepatitis B virus and HIV coinfection in the era of highly active antiretroviral therapy: a matched cohort study. Clin Infect Dis. 2007;44(7):988-995.
Fattovich G, Giustina G, Christensen E, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep). Gut. 2000;46(3):420-426.
Beguelin C, Friolet N, Moradpour D, et al. Impact of tenofovir on hepatitis delta virus replication in the Swiss human immunodeficiency virus cohort study. Clin Infect Dis. 2017;64(9):1275-1278.
Palom A, Rodriguez-Tajes S, Navascues CA, et al. Long-term clinical outcomes in patients with chronic hepatitis delta: the role of persistent viraemia. Aliment Pharmacol Ther. 2020;51(1):158-166.
Alfaiate D, Clement S, Gomes D, Goossens N, Negro F. Chronic hepatitis D and hepatocellular carcinoma: a systematic review and meta-analysis of observational studies. J Hepatol. 2020;73(3):533-539.
Coghill S, McNamara J, Woods M, Hajkowicz K. Epidemiology and clinical outcomes of hepatitis delta (D) virus infection in Queensland. Australia Int J Infect Dis. 2018;74:123-127.
Cross TJ, Rizzi P, Horner M, et al. The increasing prevalence of hepatitis delta virus (HDV) infection in South London. J Med Virol. 2008;80(2):277-282.