DOES HEPATITIS D IN HBV/HIV CO-INFECTED PATIENTS AFFECT LIVER FUNCTION?

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DOES HEPATITIS D IN HBV/HIV CO-INFECTED PATIENTS AFFECT LIVER FUNCTION? *Joanna Kozłowska, **Joanna Kubicka, *Joanna Jabłońska, *Tomasz Mikuła, **Ewa Siwak, ***Tomasz Dyda, *Alicja Wiercińska-Drapało *Hepatology and AIDS Department, Medical University of Warsaw; Warsaw s Hospital for Infectious Diseases **Outpatient Clinic, Warsaw s Hospital for Infectious Diseases ***Molecular Diagnostics Laboratory, Warsaw s Hospital for Infectious Diseases 1st Central and Eastern European Meeting on Viral Hepatitis and Co-infection with HIV 22-23 June 2015, Warsaw, Poland

BACKGROUND - HDV prevalence among HIV/HBV patients in Europe 14.5% 1 - HDV associated with a higher rate of death and liver decompensation events in HIV-infected patients 1,2 - HDV infection has no impact on HIV progression 1,3 and vice versa 4 - Viral interference between hepatitis B, C and D in HIV-positive patients HDV inhibits HBV replication 1,5 HDV inhibits HCV replication 5 reciprocal inhibition between HBV and HCV 6 1. Soriano et al. 2011, AIDS. 2. Fernandez-Montero et al. 2014, Clin Infect Dis. 3. Lee et al. 2015, J MicrobiolImmunol Infect. 4. Nicolini et al. 2015, Antivir Ther. 5. Boyd et al. 2010 J Viral Hepat. 6. Morsica et al. 2009, J Acquir Immune Defic Syndr

BACKGROUND ART regimens (including drugs active against HBV) could have beneficial effect on the clinical course of hepatitis D in HIV-positive patients Onali et al. 2014, Antivir Ther. Soriano et al. 2014, AIDS.

AIM OF THE STUDY The aim of the study was to determine the influence of HDV infection on the severity of liver disease in HIV/HBV co-infected patients

METHODS The study group included 65 HIV/HBV co-infected patients Serum HDV IgG antibodies were tested with EIA test (Dia.Pro) HDV RNA was measured using HDV Real-TM Sacace Biotech test Biochemical, serological, virological and immunological examination was also carried out along with abdominal ultrasound

STUDY GROUP Age, mean years (range) 41 (20-56) Gender, M/F 60 / 5 Transmission route, IDU / MSM / Hx 15 / 33 / 10 HCV infection (%) 30 (46%) HBeAg, pos (%) 21 (32%) CD4, mean cells/ul (SD) 455 (182) ARV treated at analysis (%) 58 (89%)

RESULTS HDV IgG were detected in 15/65 (23%) patients with HIV/HBV co-infection HDV RNA was detected in 9/15 of HDV ab-positive patients and in one HDV ab-negative patient, who was IDU (15% of patients with HIV/HBV co-infection) 13/16 HIV/HBV/HDV co-infected patients had prior history of intravenous drug use

RESULTS All ARV treated patients had low or undetectable levels of HBV DNA No significant relationship was established between HDV infection and HBeAg positivity, CD4 cell count or immunological or virological response on ARV treatment.

RESULTS Among 16 patients with HIV/HBV/HDV co-infection 15 (94%) were also infected with HCV Among 49 remaining (non-infected with HDV) 15 (31%) were HCV positive

RESULTS Taking into account a minimum of 5 results of the given parameter for HDV-positive and HDV-negative patients, statistically significant differences were observed for the following parameters (in red):

RESULTS LIVER PARAMETERS Median Q25 Q75 neg vs pos ALAT all 40 28,5 59 HDV neg 37 28 55 HDV pos 56 43 82 p<0,05 AST all 35 26 52 HDV neg 32 25 43 HDV pos 52 38 78 p<0,05 ALP all 94 78 115 HDV neg 90 78 107 HDV pos 96 74 115 ns GGTP all 42 28 71 HDV neg 35 23 67 HDV pos 61 46,5 115 p<0,05

RESULTS Median Q25 Q75 neg vs pos Cholesterol all 4,52 3,92 5,17 HDV neg 4,43 3,95 5,1 HDV pos 4,41 3,7 4,98 ns Hemoglobin all 14,6 13,5 15,5 HDV neg 15 13,9 15,8 HDV pos 14,5 13,2 15,6 p<0,05 Platelet count all 189 158 220 HDV neg 196 172 231 HDV pos 163 113,5 206,5 p<0,05 Prothrombin time all 98,2 93 104 HDV neg 97 93 105 HDV pos 97 90,8 103 ns

RESULTS Cirrhosis was found in 4 HDV-antibodies-positive patients, but HDV-RNA was not detected in 2 of them Cirrhosis was not found in any of HDV-antibodiesnegative patients, along with 8/10 HDV-RNA-positive patients also cirrhosis-free. These are preliminary data, observation is continued

CONCLUSIONS HDV infection is common in Polish HIV/HBV co-infected patients with a history of IDU Advanced liver dysfunction in HIV/HBV/HDV co-infected patients is not as frequent as expected - it needs further observation Assessment of the impact of HDV infection on liver disease progression in HIV/HBV co-infection is complicated by concomitant HCV infection